JP6580567B2 - Systems and methods for deploying and / or characterizing intragastric devices - Google Patents

Description

Incorporation by reference of related applications

  Any priority claim identified in the application data sheet, or any amendment thereto, is incorporated herein by reference under 37 CFR 1.57. This application is a priority over US Provisional Patent Application No. 61 / 911,958, filed December 4, 2013, and US Provisional Patent Application No. 62 / 062,081, filed October 9, 2014. Insist on the right. Each of the above applications is hereby incorporated by reference in its entirety, and each expressly forms part of this specification.

Field

  Devices and methods for treating obesity are provided. More particularly, there are provided intragastric devices and methods for making, deploying, inflating, placing, tracking, monitoring, deflating and retrieving them.

background

  Obesity is a major health problem in developed countries. Obesity creates a higher risk of developing high blood pressure, diabetes and many other serious health problems. In the United States, the complications of being overweight or obese affect nearly 1 in 3 American adults, with annual medical costs exceeding $ 80 billion, including indirect costs such as lost wages, Total annual economic costs are estimated to exceed $ 120 billion. Except for rare pathologies, weight gain is directly correlated with overeating.

  Non-invasive ways to lose weight include increasing metabolic activity that burns calories and / or modifying caloric intake, using pharmacological interventions to reduce appetite, or It can be reduced. Other methods include surgery to reduce stomach volume, binding to limit the size of the fistula, and intragastric devices that reduce appetite by occupying the stomach space.

  The intragastric volume occupancy device gives the patient a feeling of fullness even after eating only a small amount of food. Thus, while a person is satisfied with fullness, caloric intake is reduced. Currently available volume occupancy devices have many disadvantages. For example, complicated gastric procedures are required to insert several devices.

  U.S. Pat. No. 4,133,315, the entire contents of which are hereby incorporated by reference, discloses an apparatus for reducing obesity that includes an inflatable elastomeric bag and tube combination. The bag can be inserted into the patient's stomach by swallowing. The end of the tube attached distal to the bag is placed in the patient's mouth. The second tube snakes through the nasal cavity and enters the patient's mouth. The tube ends located in the patient's mouth are connected to form a continuous tube for fluid communication from the patient's nose to the bag. Alternatively, the bag can be implanted by stomach treatment. In order to reduce appetite, the bag is inflated through the tube to the desired degree before the patient eats. After the patient eats, the bag is deflated. Throughout the procedure, the tube extends out of the patient's nose or abdominal cavity.

  US Pat. Nos. 5,259,399, 5,234,454 and 6,454,785, the entire contents of which are hereby incorporated by reference, describe stomach contents for weight control that must be surgically implanted. A product occupancy device is disclosed.

  U.S. Pat. Nos. 4,416,267, 4,485,805, 4,607,618, 4,694,827, 4,723,547, the entire contents of which are hereby incorporated by reference. Nos. 4,739,758 and 4,899,747 and EP 246,999 relate to intragastric volume occupancy devices for weight control that can be inserted endoscopically. Of these, U.S. Pat. Nos. 4,416,267, 4,694,827, 4,739,758, and 4,899,747, the entire contents of which are hereby incorporated by reference, are desired It relates to a balloon whose surface has been formed in a certain way to achieve the goal. In U.S. Pat. Nos. 4,416,267 and 4,694,827, the entire contents of which are hereby incorporated by reference, the balloon is expanded to facilitate the passage of solids and fluids through the gastric lumen. It is shaped into a torus shape with a central opening. The balloon of US Pat. No. 4,694,827, the entire contents of which are hereby incorporated by reference, has a plurality of smooth surface convex protrusions. The protrusion mitigates the detrimental effects resulting from excessive contact with the gastric mucosa by reducing the amount of surface area in contact with the stomach wall. The process also defines a balloon and stomach wall channel through which solids and fluids can pass. The balloon of US Pat. No. 4,739,758, the entire contents of which are hereby incorporated by reference, has a blister at its outer edge that prevents it from being tightly secured to the cardia or pylorus.

  The balloons of U.S. Pat. Nos. 4,899,747 and 4,694,827, the entire contents of which are hereby incorporated by reference, can be inserted by pushing the inflated balloon to release the tube below the gastric tube Install. US Pat. No. 4,723,547, the entire contents of which are hereby incorporated by reference, discloses a specially adapted insertion catheter for positioning the balloon. In US Pat. No. 4,739,758, the entire contents of which are hereby incorporated by reference, the infusion tube performs balloon insertion. In U.S. Pat. No. 4,485,805, the entire contents of which are hereby incorporated by reference, the balloon is inserted into a finger sack and attached by threading the distal end of a conventional gastric tube, below the patient's throat. insert. The balloon of EP 246,999 is inserted using a gastrocamera with integrated forceps.

  U.S. Pat. Nos. 4,416,267, 4,485,805, 4,694,827, 4,739,758, and 4,899,747, the entire contents of which are hereby incorporated by reference. And European Patent No. 246,999, a balloon is inflated with fluid from a tube extending downwardly from the patient's mouth. Also, in these patents, the balloon contains a self-sealing hole (US Pat. No. 4,694,827, the entire contents of which are hereby incorporated by reference), an injection site (US Pat. No. 4, the entire contents of which are hereby incorporated by reference). , 416, 267 and 4,899, 747), self-sealing filling valves (US Pat. No. 4,485,805, the entire contents of which are hereby incorporated by reference), self-closing valves (the entire contents by reference) European Patent No. 246,999) incorporated herein or a duckbill valve (US Pat. No. 4,739,758, the entire contents of which are hereby incorporated by reference). US Pat. No. 4,723,547, the entire contents of which are hereby incorporated by reference, uses a long and thick plug and fills the balloon by inserting a needle attached to an air source through the plug.

  US Pat. No. 4,607,618, the entire contents of which are hereby incorporated by reference, describes a collapsible instrument formed from semi-rigid skeleton members that are joined to form a collapsible hollow structure. The instrument is not inflatable. It is inserted endoscopically into the stomach using a specially adapted bougie with a draining rod that releases the folded instrument. Once released, the instrument returns to its larger relaxed size and shape.

  US Pat. No. 5,129,915, the entire contents of which are hereby incorporated by reference, relates to an intragastric balloon that is intended to be swallowed and automatically expands under the effect of temperature. Three methods are discussed where the gastric balloon can be inflated by temperature changes. A composition comprising a solid acid and a non-toxic carbonate or bicarbonate is separated from the water by a coating of chocolate, cocoa paste or cocoa butter that melts at body temperature. Alternatively, citric acid and alkali bicarbonate coated with non-toxic vegetable or animal fats that melt at body temperature and placed in the presence of water can produce the same results. Finally, the solid acid and non-toxic carbonate or bicarbonate are isolated from the water with an isolation pouch of low strength synthetic material that is sufficient to break just prior to swallowing the bladder. The destruction of the isolated pouch causes the acid, carbonate or bicarbonate and water to mix, and the balloon immediately begins to expand. The disadvantage of thermal induction of inflation is that it cannot provide the degree of inflation timing control and reproducibility that is desirable in a safe self-inflating intragastric balloon.

  After swallowing, food and oral medication typically reach the patient's stomach in less than a minute. Food stays in the stomach for an average of 1-3 hours. However, residence time is highly variable and depends on factors such as patient starvation or supply. Thus, the proper timing of inflation of the intragastric balloon is a factor in the successful deployment of various aspects of the intragastric device. The timing is chosen to avoid premature dilation in the esophagus that can result in esophageal obstruction or delayed dilation that can result in intestinal obstruction.

  The method for verifying that the intragastric device is in the stomach is useful in that it does not rely only on timing after administration of the intragastric device. The verification of the arrangement can be performed using X-ray imaging. After the patient swallows the encapsulated balloon, the encapsulated balloon visualized by the radiopaque marker can be X-rayed to ensure that the balloon is in the stomach after swallowing . X-ray imaging techniques include x-ray or fluoroscopy techniques that use radiation to provide a real-time image of the balloon. However, radiation can be harmful to the body when prolonged or administered at high doses. Fluoroscopy typically uses low doses of radiation, but repeated use can pose a risk of damage to the patient. Furthermore, there is a risk of accidental administration of very high doses to the patient.

  Electromagnetic based systems and methods offer advantages over, for example, radiography. An electromagnetic force generally refers to a magnetic field corresponding to an electric current. An electric current can be induced in the conductive material by the presence of a magnetic field. The magnetic field can also be induced by the presence of an electric current that runs through the conductive material. Electromagnetic forces are used in many different contexts, which provide advantages when used in the context of placing and characterizing intragastric devices.

  Voltage based systems and methods also provide advantages over, for example, radiography. A voltage is created when the potential at one point is different from the potential at another point. Voltage is used in many different contexts, which provide advantages when used in contexts where a gastric device is placed and characterized.

  US Pat. No. 8,858,432, the entire contents of which are hereby incorporated by reference, discloses an ingestible marker that includes a signal generation circuit. The ingestible event marker system includes an ingestible event marker (IEM) and a personal signal receiver. The IEM includes an identifier such as a physiologically acceptable carrier that is activated upon contact with a physiological site within the body's target, such as a gastrointestinal internal target site. The personal signal receiver is configured, for example, to associate with a physiological location within or on the body and to receive IEM signals. In use, the IEM transmits a signal that is received by a personal signal receiver.

  US Pat. No. 8,836,513, the entire contents of which are hereby incorporated by reference, describes a system having the product that indicates that the ingestible product has been consumed. The system includes conductor elements, electronic components, and partial power sources in the form of dissimilar materials. Upon contact with the conductive fluid, an electrical potential is created to complete the power source and start up the system. Electronic components control the conductivity between dissimilar materials, resulting in a unique current signature. The system may be associated with food and communicate data regarding the intake of food material to the receiver.

  US Pat. No. 8,847,766, the entire contents of which are hereby incorporated by reference, describes a system for physical delivery of pharmacological agents. The system includes an identifier that transmits a conduction signal and a consumable electrode formed from dissimilar material. The electrodes are configured to generate a voltage for energizing the identifier and to transmit a conduction signal to the body when the first and second electrodes are in contact with bodily fluids.

  Ultrasound-based systems and methods also provide advantages over, for example, radiology. Ultrasound is a sound pressure wave that periodically vibrates at a frequency greater than the upper limit of the human audible range. Thus, ultrasound is separated from “normal” (audible) sound based on differences in physical properties, the only fact that humans cannot hear. This limit varies from person to person, which is about 20 kilohertz (20,000 hertz) in healthy young adults. Ultrasonic devices operate at frequencies from 20 kHz to several gigahertz.

  An ultrasonic device can be used to detect an object and measure the distance. Ultrasonic imaging (sonography) is used in both veterinary and human medicine. In non-destructive inspection of products and structures, ultrasound is used to detect invisible flaws. Industrially, ultrasound is used for cleaning and mixing and to facilitate chemical processes. Animals such as bats and porpoises use ultrasound to find food and obstacles.

  Ultrasonic is an application of ultrasound. Ultrasound can be used for medical imaging, detection, measurement and cleaning. At higher power levels, Ultrasonic is useful for changing the chemical properties of materials.

  Medical Sonography (Ultrasonography) visualizes muscles, tendons, and many internal organs, and uses ultrasound-based medical imaging to capture their size, structure, and any lesions along with real-time tomographic images Technology. Ultrasound has been used by radiologists and sonographers to image the human body for at least 50 years and has become a widely used diagnostic tool. This technique is relatively inexpensive and transportable, especially when compared to other techniques such as magnetic resonance imaging (MRI) and computed tomography (CT). Ultrasound is also used to visualize the fetus during daily and emergency maternity checkups. Such a diagnostic application used during pregnancy is called obstetric ultrasonography. As currently applied in the medical community, it is known that properly performed ultrasound does not pose a risk to the patient. Sonography does not use ionizing radiation and the power level used for imaging is too low to cause harmful heating or pressure effects in the tissue.

  Ultrasound is also increasingly used in trauma and first aid cases, and emergency ultrasound has become a necessity for many EMT response teams. Furthermore, ultrasound is used in remote diagnostic cases where remote consultation is required, such as scientific experiments in space or mobile sports team diagnostics. Ultrasound is also useful in detecting pelvic abnormalities, including abdominal (transabdominal) ultrasonography, vaginal (transvaginal or intravaginal) ultrasonography in women, and also the rectum (transrectal) in men. A) a technique known as ultrasonography may be included.

  Ultrasound is used in many different contexts, which offer advantages when used in contexts where a gastric device is placed and characterized.

  Medical diagnostic imaging is used to diagnose a number of diseases. The oldest method, X-ray contrast agent technology, delivers high resolution images in a short examination time; however, it has the disadvantage of exposing the patient to X-rays. Ultrasound imaging is a method of image acquisition that works without the use of radiation. When using said ultrasound imaging, the ultrasound signal is sent via an ultrasound transducer to the object to be inspected and the corresponding control device receives the reflected ultrasound signal for imaging. Process the received signal.

  US Pat. No. 8,535,230, the entire contents of which are incorporated herein by reference, describes an ultrasound device that includes an ultrasound transducer on a robotic arm for tracking an object as it moves. However, such a system is not compatible with tracking devices in the body.

  US Pat. No. 8,105,247, the entire contents of which are hereby incorporated by reference, describes the use of an ultrasonic transceiver to measure the size of a gastric strap device. However, the system is intended for a fixed gastric tying device and is not directly applicable to placing and characterizing a transgastric device that transforms, rotates and deforms.

Overview

There remains a need for devices and methods for placing and characterizing intragastric balloon devices that avoid exposure to radiation in vivo.

  Disclosed is a floating or tethered gastric volume occupying device or a device that maintains volume and / or internal pressure within a predetermined range for an extended period of time or undergoes a predetermined adjustment in volume and / or internal pressure for an extended period of time Is done. Maintaining a predetermined volume and / or internal pressure minimizes stress on the device resulting in failure in structural integrity and prevents premature and / or uncontrolled expansion or other device failure it can. By undergoing a predetermined adjustment in volume and / or internal pressure over time, a preselected volume profile can be obtained to accommodate changes in stomach size over the course of treatment with the device. The device may be self-expanding (also referred to as self-expanding) or inflating (also referred to as tethered manual expansion).

  Volume occupying devices and methods for manufacturing, deploying, inflating, tracking, placing, deflating, and retrieving such devices are provided. The devices and methods of the preferred embodiments can be used to treat overweight and obese individuals. The method using the device of the preferred embodiment does not require the use of an invasive procedure; rather, the patient simply swallows the device attached to or not attached to the catheter. Once in the patient's stomach, the device is expanded to a preselected volume using a preselected fluid, such as a gas, liquid, vapor or mixture thereof. Thus, the use of one fluid, such as a “gas”, eg, an initial charge gas, to describe the various aspects herein does not preclude the use of other fluids as well. Further, a “fluid” such as an initial fill fluid is a solid, liquid contained in, mixed with, carried in, or otherwise entrained in a fluid such as a gas or liquid. , Vapor or gas phase material or materials. The fluid may include one substance, or a mixture of different substances, and may be or include salt water, a physiologically acceptable fluid or substance, etc., as further described herein. The walls of the device are preselected for the diffusion characteristics of that particular fluid, eg, gas. Once in the in vivo environment, the gas in the device diffuses through the device wall and the gas diffuses from the in vivo environment into the device. Taking into account the diffusion properties of the gas from the in vivo environment into the device, the volume of the device and / or the internal pressure can be reduced by pre-selecting the device walls and the gas initially used to expand the device. It can be kept within a preselected range or it can follow a preselected profile of volume and / or pressure change. After a predetermined time, the device can be removed using endoscopic means, or the device is reduced in volume or contracted to pass through the remainder of the patient's gastrointestinal tract.

  After the device is swallowed by the patient, inflation can be achieved through the use of a removable catheter that initially remains in the fluid in contact with the device. Alternatively, in a self-expanding process, for example, once the device has reached the stomach, by gas generation in the device by reaction of gas generating components contained within the device upon swallowing, or by use of a removable catheter Expansion can be achieved by the introduction of one or more components during the gas production process.

  The volume occupancy subcomponent of the device can be formed by injection, blowing or rotational molding of a flexible gas impermeable biocompatible material such as, for example, polyurethane, nylon or polyethylene terephthalate. Materials that can be used to control the gas permeability / impermeability of the volume occupancy sub-part include, but are not limited to, silicon oxide (SiOx), gold, if desired to reduce permeability Or any precious metal, saran, insulation protective coating, etc. are mentioned. If necessary, the volume-occupying subcomponent may be further coated with one or more gas barrier compounds, or Mylar polyester film coating or Kelvalite, metallized to enhance the gas impermeability of the device walls. It can be formed from silver or aluminum as a surface to provide a gas impermeable barrier.

  In a further aspect, the device uses a delivery state that packages the device so that the device can be swallowed while minimizing patient discomfort. In the delivered state, the device can be packaged in a capsule. Alternatively, the device can be coated with a material that can operate to confine the device and facilitate swallowing. Various techniques can also be used to facilitate swallowing of the device, including, for example, wetting, temperature treatment, lubrication, and treatment with agents such as anesthetics.

  The device can be used by a physician to determine the position and / or orientation and / or condition of the device within the patient's body using electromagnetic, magnetic, voltage, pH, and / or acoustic (eg, ultrasonic) methods. Includes a tracking or visualization component or multiple components that can be determined. A tracking or visualization part is a balloon or part thereof or a part therein, or an additional part added to or attached to the balloon or part thereof or part therein, or an additional part having a characteristic indicating the location of the balloon. May be.

  In some embodiments, the tracking subcomponent may include a material that emits electromagnetic energy. A complementary electromagnetic energy sensor that is responsive to the electromagnetic properties of the device can be used to track and position the device. Using such techniques, as the device moves through the body, certain device-specific features such as, but not limited to, the location, orientation, size or condition of the device while it remains in the patient's body. Information and details can also be obtained. An extracorporeal electromagnetic response sensor is an electromagnetic energy that is relayed by an internal device in which energy is reflected by, created by, or otherwise transmitted to an intragastric device or a material or object in or on the intragastric device. Information can be detected and processed. This information can then be interpreted while remaining in the body to identify the location, orientation, size and other attributes of the device. The electromagnetic system provides a simple, non-invasive and less harmful method of tracking, positioning and characterizing intragastric devices.

  In some embodiments, the tracking subcomponent may include a material that is responsive to ultrasonic or other acoustic energy. The device can be tracked and positioned with a complementary ultrasonic energy sensor that is responsive to the acoustic properties of the device. Using such techniques, as the device moves through the body, certain device-specific features such as, but not limited to, the location, orientation, size or condition of the device while it remains in the patient's body. Information and details can also be obtained. An extracorporeal acoustically responsive sensor is a sound that is relayed by an internal device in which energy is reflected by, created by, or otherwise transmitted to an intragastric device or a material or object in or on the intragastric device. Information about energy can be detected and processed. This information can then be interpreted while remaining in the body to identify the location, orientation, size and other attributes of the device. The ultrasound system provides a simple, non-invasive and less harmful method of tracking, positioning and characterizing intragastric devices.

  In some embodiments, the electromagnetic system or part thereof can be combined with the acoustic system or part thereof. The system or a combination of parts thereof can be implemented to further enhance the placement and / or characterization of the intragastric device in vivo.

  Using such techniques, as the device moves through the body, certain device-specific features such as, but not limited to, the location, orientation, size or condition of the device while it remains in the patient's body. Information and details can also be obtained. Magnetic responsive sensors, such as extracorporeal sensors, can detect and relay information regarding the magnetic field of the intragastric device. This information can then be interpreted while remaining in the body to identify the location, orientation, size and other attributes of the device. Magnetic field detection systems provide a simple, non-invasive and less harmful method of tracking, positioning and characterizing intragastric devices.

  In a first aspect, an electromagnetic system for placing an intragastric device in a body, wherein the electromagnetic field generator is configured to generate an electromagnetic field; configured to couple with the system, an in vivo intragastric environment A swallowable electromagnetic sensor further configured to generate an electric current when exposed to an electromagnetic field in; and an initial filling fluid in the intragastric volume occupying device when the intragastric device is in an in vivo intragastric environment A system is provided that includes a valve system that includes a swallowable catheter configured to releasably couple with an intragastric device.

  In an embodiment of the first aspect, the electromagnetic sensor is configured to couple with a swallowable catheter.

  In an embodiment of the first aspect, the electromagnetic sensor is configured to couple with the distal end of the swallowable catheter.

  In an embodiment of the first aspect, the electromagnetic sensor is configured to couple with an intragastric device.

  In an embodiment of the first aspect, the system further includes at least one external reference sensor configured to generate a current when placed outside the body and exposed to a magnetic field.

  In an embodiment of the first aspect, the system further includes three external reference sensors configured to generate a current when placed outside the body and exposed to a magnetic field.

  In an embodiment of the first aspect, the system further includes a sensor interface unit configured to electrically communicate with the electromagnetic sensor and the at least one external reference sensor.

  In an embodiment of the first aspect, the system further includes a system control unit configured to be in electrical communication with the sensor interface unit and the electromagnetic field generator.

  In an embodiment of the first aspect, the system further includes a computer configured to display an identifier that is in electrical communication with the system control unit and that indicates the location of the electromagnetic sensor in the body.

  In an embodiment of the first aspect, the system further comprises at least one external reference sensor configured to generate an electrical current when placed outside the body and exposed to a magnetic field, wherein the computer is at least one external reference sensor Is further configured to display at least one second identifier indicative of the location of.

  In an embodiment of the first aspect, the computer is further configured to display a trace that indicates a path propagated by the electromagnetic sensor in the body.

  In an embodiment of the first aspect, the system further includes an intragastric device, wherein the intragastric device is a balloon.

In an embodiment of the first aspect, the system further comprises an initial fill fluid such that the intragastric device is permeable to CO ₂ greater than 10 cc / m ² / day under conditions of the in vivo gastric environment. The rate and amount of diffusion of CO ₂ from the in vivo gastric environment through the polymer wall to the lumen of the intragastric device is at least partially determined by the initial filling fluid It is controlled by the concentration of inert gas in it.

In an embodiment of the first aspect, the polymer wall comprises a CO ₂ barrier material comprising an ethylene vinyl alcohol layer.

In an embodiment of the first aspect, the polymer wall comprises a two layer CO ₂ barrier material comprising a nylon layer and a polyethylene layer.

In an embodiment of the first aspect, the polymer wall comprises a three layer CO ₂ barrier material comprising a nylon layer, a polyvinylidene chloride layer, and a polyethylene layer.

In an embodiment of the first aspect, the polymer wall comprises a three layer CO ₂ barrier material comprising a nylon layer, an ethylene vinyl alcohol layer, and a polyethylene layer.

In an embodiment of the first aspect, the initial fill fluid consists essentially of gaseous N _2.

In an embodiment of the first aspect, the initial fill fluid consists essentially of gas N ₂ and gas CO ₂ .

In an embodiment of the first aspect, the initial fill fluid consists essentially of gas N ₂ and gas CO ₂ , and the gas N ₂ is over-concentrated with respect to gas CO ₂ in the initial charge fluid.

In an embodiment of the first aspect, the initial fill fluid comprises one or more SF ₆ in liquid form, vapor form, or gaseous form.

In an embodiment of the first aspect, the initial fill fluid includes gas N ₂ and gas SF ₆ .

In an embodiment of the first aspect, the polymer wall is configured to be permeable to CO ₂ in excess of 50 cc / m ² / day under conditions of the in vivo gastric environment.

  In a second aspect, a method for electromagnetically placing an intragastric device in a patient's body, wherein the electromagnetic field is generated using an electromagnetic field generator placed outside the patient's body; releasably with a catheter A swallowing intragastric device comprising an uninflated intragastric balloon coupled with an electromagnetic sensor coupled to generate an electric current in the presence of an electromagnetic field generated by a magnetic field generator Introducing into the body; sensing the current induced in the electromagnetic sensor by the electromagnetic field; and locating the uninflated intragastric balloon within the patient based on sensing the current induced in the electromagnetic sensor To provide a method.

  In an embodiment of the second aspect, the location of the uninflated intragastric balloon within the patient is the patient's stomach.

In an embodiment of the second aspect, the method is inflated, comprising a polymer wall configured to have a CO ₂ permeability of greater than 10 cc / m ² / day under conditions of an in vivo gastric environment. Introducing an initial filling fluid into the lumen of the non-gastric balloon via a catheter; and exposing the inflated gastric balloon to an in vivo gastric environment for a useful life of at least 30 days, the polymer The rate and amount of CO ₂ diffusion from the in vivo gastric environment through the wall into the balloon lumen is controlled, at least in part, by the concentration of inert gas in the initial fill fluid.

In an embodiment of the second aspect, the polymer wall comprises a three layer CO ₂ barrier material comprising a nylon layer, a polyvinylidene chloride layer, and a polyethylene layer.

In an embodiment of the second aspect, the polymer wall comprises a three layer CO ₂ barrier material comprising a nylon layer, an ethylene vinyl alcohol layer, and a polyethylene layer.

In an embodiment of the second aspect, the polymer wall comprises a two layer CO ₂ barrier material comprising a nylon layer and a polyethylene layer.

In an embodiment of the second aspect, the polymer wall comprises a CO ₂ barrier material comprising an ethylene vinyl alcohol layer.

In an embodiment of the second aspect, the initial fill fluid consists essentially of gaseous N _2.

In an embodiment of the second aspect, the first gas consists essentially of gas N ₂ and gas CO ₂ .

In an embodiment of the second aspect, the first gas consists essentially of gas N ₂ and gas CO ₂ , and the gas N ₂ is over-concentrated with respect to the gas CO ₂ in the first gas.

In an embodiment of the second aspect, the first gas comprises one or more SF ₆ in liquid form, vapor form, or gaseous form.

In the embodiment of the second aspect, the first gas includes gas N ₂ and gas SF ₆ .

In an embodiment of the second aspect, the polymer wall is configured to be permeable to CO ₂ in excess of 50 cc / m ² / day under conditions of the in vivo gastric environment.

  In an embodiment of the second aspect, ascertaining the position of the uninflated intragastric balloon within the patient based on sensing of the current induced in the electromagnetic sensor, an identifier indicating the position of the electromagnetic sensor is displayed on the computer. Including displaying.

  In an embodiment of the second aspect, the method places at least one external reference sensor configured to generate an electric current when exposed to an electromagnetic field outside the patient's body; and at least one external reference by the electromagnetic field Further comprising sensing a current induced in the sensor.

  In an embodiment of the second aspect, identifying the position of the uninflated intragastric balloon within the patient based on sensing of current induced in the electromagnetic sensor indicates at least one external reference sensor position. Displaying one second identifier on the computer.

  In an embodiment of the second aspect, the electromagnetic sensor is coupled to the catheter.

  In an embodiment of the second aspect, the electromagnetic sensor is coupled to the intragastric device.

  In a third aspect, a magnetic system for placing an intragastric device in the body, wherein the magnetic field sensor is configured to sense a magnetic field; configured to couple with the system and in an in vivo intragastric environment A swallowable magnetic marker further configured to generate a local magnetic field; and configured to introduce an initial filling fluid into the intragastric volume occupancy device when the intragastric device is in an in vivo intragastric environment A valve system is provided that includes a valve system that includes a swallowable catheter configured to releasably couple with an intragastric device.

  In an embodiment of the third aspect, the magnetic marker is configured to couple with a swallowable catheter.

  In an embodiment of the third aspect, the magnetic marker is configured to couple with the distal end of the swallowable catheter.

  In an embodiment of the third aspect, the magnetic marker is configured to couple with an intragastric device.

  In an embodiment of the third aspect, the system further comprises at least one external reference sensor placed outside the body and configured to sense a local magnetic field.

  In an embodiment of the third aspect, the system further includes a sensor interface unit configured to be in electrical communication with the magnetic marker.

  In an embodiment of the third aspect, the system further includes a system control unit configured to be in electrical communication with the sensor interface unit and the magnetic field sensor.

  In an embodiment of the third aspect, the system further includes a computer configured to display an identifier that is in electrical communication with the system control unit and that indicates the location of the magnetic marker in the body.

  In an embodiment of the third aspect, the computer is further configured to display a trace that indicates a path propagated by the magnetic marker in the body.

  In an embodiment of the third aspect, the system further comprises an intragastric device, wherein the intragastric device is a balloon.

In an embodiment of the third aspect, the system further comprises an initial fill fluid such that the intragastric device is permeable to CO ₂ greater than 10 cc / m ² / day under conditions of in vivo gastric environment. The rate and amount of diffusion of CO ₂ from the in vivo gastric environment through the polymer wall to the lumen of the intragastric device is at least partially determined by the initial filling fluid It is controlled by the concentration of inert gas in it.

In an embodiment of the third aspect, the polymer wall comprises a CO ₂ barrier material comprising an ethylene vinyl alcohol layer.

In an embodiment of the third aspect, the polymer wall comprises a two layer CO ₂ barrier material comprising a nylon layer and a polyethylene layer.

In an embodiment of the third aspect, the polymer wall comprises a three layer CO ₂ barrier material comprising a nylon layer, a polyvinylidene chloride layer, and a polyethylene layer.

In an embodiment of the third aspect, the polymer wall comprises a three layer CO ₂ barrier material comprising a nylon layer, an ethylene vinyl alcohol layer, and a polyethylene layer.

In an embodiment of the third aspect, the initial fill fluid consists essentially of gaseous N _2.

In an embodiment of the third aspect, the initial fill fluid consists essentially of gas N ₂ and gas CO ₂ .

In an embodiment of the third aspect, the initial fill fluid consists essentially of gas N ₂ and gas CO ₂ , and the gas N ₂ is over-concentrated with respect to gas CO ₂ in the initial charge fluid.

In an embodiment of the third aspect, the initial fill fluid comprises one or more SF ₆ in liquid form, vapor form, or gaseous form.

In an embodiment of the third aspect, the initial fill fluid includes gas N ₂ and gas SF ₆ .

In an embodiment of the third aspect, the polymer wall is configured to be permeable to CO ₂ in excess of 50 cc / m ² / day under conditions of the in vivo gastric environment.

  In a fourth aspect, a method for magnetically placing an intragastric device in a patient's body, releasably coupled to a catheter and coupled to a magnetic marker configured to be sensed by a magnetic field sensor. Introducing an intragastric device including an uninflated intragastric balloon into the patient's body by swallowing; sensing a magnetic field using a magnetic field sensor; and inflation within the patient based on sensing of the magnetic field A method is provided that includes locating a non-gastric balloon.

  In an embodiment of the fourth aspect, the location of the uninflated intragastric balloon within the patient is the patient's stomach.

In an embodiment of the fourth aspect, the method is inflated, comprising a polymer wall configured to have a CO ₂ permeability of greater than 10 cc / m ² / day under conditions of an in vivo gastric environment. Introducing an initial filling fluid into the lumen of the non-gastric balloon via a catheter; and exposing the inflated gastric balloon to an in vivo gastric environment for a useful life of at least 30 days, the polymer The rate and amount of CO ₂ diffusion from the in vivo gastric environment through the wall into the balloon lumen is controlled, at least in part, by the concentration of inert gas in the initial fill fluid.

In an embodiment of the fourth aspect, the polymer wall comprises a three layer CO ₂ barrier material comprising a nylon layer, a polyvinylidene chloride layer, and a polyethylene layer.

In an embodiment of the fourth aspect, the polymer wall comprises a three layer CO ₂ barrier material comprising a nylon layer, an ethylene vinyl alcohol layer, and a polyethylene layer.

In an embodiment of the fourth aspect, the polymer wall comprises a two layer CO ₂ barrier material comprising a nylon layer and a polyethylene layer.

In an embodiment of the fourth aspect, the polymer wall comprises a CO ₂ barrier material comprising an ethylene vinyl alcohol layer.

In an embodiment of the fourth aspect, the initial fill fluid consists essentially of gaseous N _2.

In an embodiment of the fourth aspect, the first gas consists essentially of gas N ₂ and gas CO ₂ .

In an embodiment of the fourth aspect, the initial fill fluid consists essentially of gas N ₂ and gas CO ₂ , and the gas N ₂ is over-concentrated with respect to gas CO ₂ in the initial charge fluid.

In an embodiment of the fourth aspect, the initial fill fluid comprises one or more SF ₆ in liquid form, vapor form, or gaseous form.

In an embodiment of the fourth aspect, the initial fill fluid includes gas N ₂ and gas SF ₆ .

In an embodiment of the fourth aspect, the polymer wall is configured to be permeable to CO ₂ in excess of 50 cc / m ² / day under conditions of the in vivo gastric environment.

  In an embodiment of the fourth aspect, identifying the position of the uninflated intragastric balloon within the patient based on sensing of the magnetic field generated by the magnetic marker causes an identifier indicating the position of the magnetic marker to be displayed on the computer Including that.

  In an embodiment of the fourth aspect, the magnetic marker is coupled to the catheter.

  In an embodiment of the fourth aspect, the electromagnetic sensor is coupled to the intragastric device.

  In a fifth aspect, a power generation system for placing an intragastric device in a body, the swallowing configured to be coupled to the system and further configured to generate a voltage in an in vivo intragastric environment A possible power generation sensor; and a valve system configured to introduce an initial filling fluid into the intragastric volume occupying device when the intragastric device is in an in vivo intragastric environment, releasable with the intragastric device A system is provided that includes a valve system that includes a swallowable catheter that is configured to couple to.

  In an embodiment of the fifth aspect, the power generation sensor is configured to couple with a swallowable catheter.

  In an embodiment of the fifth aspect, the power generation sensor is configured to couple with the distal end of the swallowable catheter.

  In an embodiment of the fifth aspect, the power generation sensor is configured to couple with an intragastric device.

  In an embodiment of the fifth aspect, the system further includes at least one receiver placed outside the body and configured to receive a signal associated with the voltage generated by the power generation sensor.

  In an embodiment of the fifth aspect, the system further includes a sensor interface unit configured to be in electrical communication with the power generation sensor.

  In an embodiment of the fifth aspect, the system further includes a system control unit configured to be in electrical communication with the sensor interface unit and the power generation sensor.

  In an embodiment of the fifth aspect, the system further includes a computer configured to display an identifier that is in electrical communication with the system control unit and that indicates a location of the power generation sensor within the body.

  In an embodiment of the fifth aspect, the system further comprises an intragastric device, wherein the intragastric device is a balloon.

In an embodiment of the fifth aspect, the system further comprises an initial fill fluid such that the intragastric device is permeable to CO ₂ greater than 10 cc / m ² / day under conditions of in vivo gastric environment. The rate and amount of diffusion of CO ₂ from the in vivo gastric environment through the polymer wall to the lumen of the intragastric device is at least partially determined by the initial filling fluid It is controlled by the concentration of inert gas in it.

In an embodiment of the fifth aspect, the polymer wall comprises a CO ₂ barrier material comprising an ethylene vinyl alcohol layer.

In an embodiment of the fifth aspect, the polymer wall comprises a two layer CO ₂ barrier material comprising a nylon layer and a polyethylene layer.

In an embodiment of the fifth aspect, the polymer wall comprises a three layer CO ₂ barrier material comprising a nylon layer, an ethylene vinyl alcohol layer, and a polyethylene layer.

In an embodiment of the fifth aspect, the polymer wall comprises a three layer CO ₂ barrier material comprising a nylon layer, a polyvinylidene chloride layer, and a polyethylene layer.

In an embodiment of the fifth aspect, the initial fill fluid consists essentially of gaseous N _2.

In an embodiment of the fifth aspect, the initial fill fluid consists essentially of gas N ₂ and gas CO ₂ .

In an embodiment of the fifth aspect, the initial fill fluid consists essentially of gas N ₂ and gas CO ₂ , and the gas N ₂ is over-concentrated with respect to gas CO ₂ in the initial charge fluid.

In an embodiment of the fifth aspect, the initial fill fluid comprises one or more SF ₆ in liquid form, vapor form, or gaseous form.

In an embodiment of the fifth aspect, the initial fill fluid includes gas N ₂ and gas SF ₆ .

In an embodiment of the fifth aspect, the polymer wall is configured to have a permeability to CO ₂ of greater than 50 cc / m ² / day under conditions of the in vivo gastric environment.

  In a sixth aspect, a method for power generating placement of an intragastric device in a patient's body, releasably coupled to a catheter and configured to generate a voltage in the presence of an intragastric environment. Introducing an intragastric device that includes an uninflated intragastric balloon coupled with a power generation sensor into the patient's body by swallowing; generating a voltage using a power generation sensor that responds to contact with the gastric environment And determining the position of an uninflated intragastric balloon within the patient based on sensing the generated voltage.

  In an embodiment of the sixth aspect, the location of the uninflated intragastric balloon within the patient is the patient's stomach.

In an embodiment of the sixth aspect, the method is inflated, comprising a polymer wall configured to have a CO ₂ permeability of greater than 10 cc / m ² / day under conditions of in vivo gastric environment. Introducing an initial filling fluid into the lumen of the non-gastric balloon via a catheter; and exposing the inflated gastric balloon to an in vivo gastric environment for a useful life of at least 30 days, the polymer The rate and amount of CO ₂ diffusion from the in vivo gastric environment through the wall into the balloon lumen is controlled, at least in part, by the concentration of inert gas in the initial fill fluid.

In an embodiment of the sixth aspect, the polymer wall comprises a three layer CO ₂ barrier material comprising a nylon layer, a polyvinylidene chloride layer, and a polyethylene layer.

In an embodiment of the sixth aspect, the polymer wall comprises a three layer CO ₂ barrier material comprising a nylon layer, an ethylene vinyl alcohol layer, and a polyethylene layer.

In an embodiment of the sixth aspect, the polymer wall comprises a two layer CO ₂ barrier material comprising a nylon layer and a polyethylene layer.

In an embodiment of the sixth aspect, the polymer wall comprises a CO ₂ barrier material comprising an ethylene vinyl alcohol layer.

In an embodiment of the sixth aspect, the initial fill fluid consists essentially of gas N ₂ and gas CO ₂ .

In an embodiment of the sixth aspect, the initial fill fluid consists essentially of gaseous N _2.

In an embodiment of the sixth aspect, the first gas consists essentially of gas N ₂ and gas CO ₂ , and the gas N ₂ is over-concentrated with respect to gas CO ₂ in the initial fill fluid.

In an embodiment of the sixth aspect, the initial fill fluid comprises one or more SF ₆ in liquid form, vapor form, or gaseous form.

In an embodiment of the sixth aspect, the initial fill fluid includes gas N ₂ and gas SF ₆ .

In an embodiment of the sixth aspect, the polymer wall is configured to have a permeability to CO ₂ of greater than 50 cc / m ² / day under conditions of the in vivo gastric environment.

  In an embodiment of the sixth aspect, the power generation sensor is coupled to the catheter.

  In an embodiment of the sixth aspect, the power generation sensor is coupled to the intragastric device.

  In a seventh aspect, a pH-based system for placing an intragastric device in the body configured to be coupled to the system so as to sense the pH level of fluid in an in vivo gastric environment. A swallowable pH sensor further configured; and a valve system configured to introduce an initial filling fluid into the intragastric volume occupying device when the intragastric device is in an in vivo intragastric environment, comprising: A system is provided that includes a valve system that includes a swallowable catheter configured to releasably couple with an inner device.

  In an embodiment of the seventh aspect, the pH sensor is configured to couple with a swallowable catheter.

  In an embodiment of the seventh aspect, the pH sensor is configured to couple with the distal end of the swallowable catheter.

  In an embodiment of the seventh aspect, the pH sensor is configured to couple with an intragastric device.

  In an embodiment of the seventh aspect, the system further comprises at least one receiver placed outside the body and configured to receive a signal associated with the pH level sensed by the pH sensor.

  In an embodiment of the seventh aspect, the system further includes a sensor interface unit configured to be in electrical communication with the pH sensor.

  In an embodiment of the seventh aspect, the system further includes a system control unit configured to be in electrical communication with the sensor interface unit and the pH sensor.

  In an embodiment of the seventh aspect, the system further comprises a computer configured to display an identifier that is in electrical communication with the system control unit and that indicates the location of the pH sensor in the body.

  In an embodiment of the seventh aspect, the system further comprises an intragastric device, wherein the intragastric device is a balloon.

In an embodiment of the seventh aspect, the system further comprises an initial fill fluid such that the intragastric device is permeable to CO ₂ greater than 10 cc / m ² / day under conditions of in vivo gastric environment. The rate and amount of diffusion of CO ₂ from the in vivo gastric environment through the polymer wall to the lumen of the intragastric device is at least partially determined by the initial filling fluid It is controlled by the concentration of inert gas in it.

In an embodiment of the seventh aspect, the polymer wall comprises a CO ₂ barrier material comprising an ethylene vinyl alcohol layer.

In an embodiment of the seventh aspect, the polymer wall comprises a two layer CO ₂ barrier material comprising a nylon layer and a polyethylene layer.

In an embodiment of the seventh aspect, the polymer wall comprises a three layer CO ₂ barrier material comprising a nylon layer, a polyvinylidene chloride layer, and a polyethylene layer.

In an embodiment of the seventh aspect, the polymer wall comprises a three layer CO ₂ barrier material comprising a nylon layer, an ethylene vinyl alcohol layer, and a polyethylene layer.

In an embodiment of the seventh aspect, the initial fill fluid consists essentially of gaseous N _2.

In an embodiment of the seventh aspect, the initial fill fluid consists essentially of gas N ₂ and gas CO ₂ .

In an embodiment of the seventh aspect, the initial fill fluid consists essentially of gas N ₂ and gas CO ₂ , and the gas N ₂ is over-concentrated with respect to gas CO ₂ in the initial charge fluid.

In an embodiment of the seventh aspect, the initial fill fluid comprises one or more SF ₆ in liquid form, vapor form, or gaseous form.

In an embodiment of the seventh aspect, the initial fill fluid includes gas N ₂ and gas SF ₆ .

In an embodiment of the seventh aspect, the polymer wall is configured to be permeable to CO ₂ in excess of 50 cc / m ² / day under conditions of the in vivo gastric environment.

  In an eighth aspect, a method for placing an intragastric device in a patient's body based on sensing the pH level of the fluid in the body, releasably coupled to the catheter, and fluid in the intragastric environment in the body Introducing an intragastric device into the patient by swallowing an intragastric device coupled with a pH sensor configured to sense the pH level of the patient; A method is provided that includes sensing a pH level of a fluid responsive to sensor contact; and locating an uninflated intragastric balloon within the patient based on sensing the pH level.

  In an embodiment of the eighth aspect, the location of the uninflated intragastric balloon within the patient is the patient's stomach.

In an embodiment of the eighth aspect, the method is inflated, comprising a polymer wall configured to have a CO ₂ permeability of greater than 10 cc / m ² / day under conditions of in vivo gastric environment. Introducing an initial filling fluid into the lumen of the non-gastric balloon via a catheter; and exposing the inflated gastric balloon to an in vivo gastric environment for a useful life of at least 30 days, the polymer The rate and amount of CO ₂ diffusion from the in vivo gastric environment through the wall into the balloon lumen is controlled, at least in part, by the concentration of inert gas in the initial fill fluid.

In an embodiment of the eighth aspect, the polymer wall comprises a three layer CO ₂ barrier material comprising a nylon layer, a polyvinylidene chloride layer, and a polyethylene layer.

In an embodiment of the eighth aspect, the polymer wall comprises a three layer CO ₂ barrier material comprising a nylon layer, an ethylene vinyl alcohol layer, and a polyethylene layer.

In an embodiment of the eighth aspect, the polymer wall comprises a two layer CO ₂ barrier material comprising a nylon layer and a polyethylene layer.

In an embodiment of the eighth aspect, the polymer wall comprises a CO ₂ barrier material comprising an ethylene vinyl alcohol layer.

In an embodiment of the eighth aspect, the initial fill fluid consists essentially of gaseous N _2.

In an embodiment of the eighth aspect, the initial fill fluid consists essentially of gas N ₂ and gas CO ₂ .

In an embodiment of the eighth aspect, the initial fill fluid consists essentially of gas N ₂ and gas CO ₂ , wherein gas N ₂ is over-concentrated with respect to gas CO ₂ in the first gas.

In an embodiment of the eighth aspect, the initial fill fluid comprises one or more SF ₆ in liquid form, vapor form, or gaseous form.

In an embodiment of the eighth aspect, the initial fill fluid includes gas N ₂ and gas SF ₆ .

In an embodiment of the eighth aspect, the polymer wall is configured to have a permeability to CO ₂ greater than 50 cc / m ² / day under conditions of the in vivo gastric environment.

  In an embodiment of the eighth aspect, the pH sensor is coupled to the catheter.

  In an embodiment of the eighth aspect, the pH sensor is coupled to the intragastric device.

  In a ninth aspect, an acoustic system for placing an intragastric device in the body, wherein the acoustic signal generator is configured to generate an acoustic signal; A swallowable acoustic marker that is further configured to generate an acoustic response in an in vivo intragastric environment; and, if the intragastric device is in an in vivo intragastric environment, There is provided a valve system configured to introduce an initial fill fluid into the valve system including a swallowable catheter configured to releasably couple with an intragastric device.

  In an embodiment of the ninth aspect, the acoustic marker is configured to couple with a swallowable catheter.

  In an embodiment of the ninth aspect, the acoustic marker is configured to couple with a distal end of a swallowable catheter.

  In an embodiment of the ninth aspect, the acoustic marker is configured to couple with an intragastric device.

  In an embodiment of the ninth aspect, the system further includes at least one external acoustic sensor placed outside the body and configured to sense the acoustic response of the acoustic marker.

  In an embodiment of the ninth aspect, the system further includes a sensor interface unit configured to be in electrical communication with the acoustic marker and the acoustic sensor.

  In an embodiment of the ninth aspect, the system further includes a system control unit configured to be in electrical communication with the sensor interface unit.

  In an embodiment of the ninth aspect, the system further includes a computer in electrical communication with the system control unit and the acoustic sensor and configured to display an identifier indicating the location of the acoustic marker in the body.

  In an embodiment of the ninth aspect, the computer is further configured to display an indication of a path propagated by the magnetic marker in the body.

  In an embodiment of the ninth aspect, the system further comprises an intragastric device, wherein the intragastric device is a balloon.

In an embodiment of the ninth aspect, the system further comprises an initial fill fluid such that the intragastric device is permeable to CO ₂ greater than 10 cc / m ² / day under conditions of the in vivo gastric environment. The rate and amount of diffusion of CO ₂ from the in vivo gastric environment through the polymer wall to the lumen of the intragastric device is at least partially determined by the initial filling fluid It is controlled by the concentration of inert gas in it.

In an embodiment of the ninth aspect, the polymer wall comprises a CO ₂ barrier material comprising an ethylene vinyl alcohol layer.

In an embodiment of the ninth aspect, the polymer wall comprises a two layer CO ₂ barrier material comprising a nylon layer and a polyethylene layer.

In an embodiment of the ninth aspect, the polymer wall comprises a three layer CO ₂ barrier material comprising a nylon layer, a polyvinylidene chloride layer, and a polyethylene layer.

In an embodiment of the ninth aspect, the polymer wall comprises a three layer CO ₂ barrier material comprising a nylon layer, an ethylene vinyl alcohol layer, and a polyethylene layer.

In an embodiment of the ninth aspect, the initial fill fluid is comprised of N ₂ per se.

In an embodiment of the ninth aspect, the initial fill fluid consists essentially of gas N ₂ and gas CO ₂ .

In an embodiment of the ninth aspect, the initial fill fluid consists essentially of gas N ₂ and gas CO ₂ , and the gas N ₂ is over-concentrated with respect to gas CO ₂ in the initial charge fluid.

In an embodiment of the ninth aspect, the initial fill fluid comprises one or more SF ₆ in liquid form, vapor form, or gaseous form.

In an embodiment of the ninth aspect, the initial fill fluid comprises N ₂ and SF ₆ .

In an embodiment of the ninth aspect, the polymer wall is configured to be permeable to CO ₂ in excess of 50 cc / m ² / day under conditions of the in vivo gastric environment.

  In an embodiment of the ninth aspect, the acoustic signal is an ultrasound signal.

  In a tenth aspect, a method for acoustically placing an intragastric device in a patient's body, wherein the intragastric device is releasably coupled to a catheter and generates an acoustic response in response to an acoustic signal. Introducing an intragastric device including an uninflated intragastric balloon coupled to an acoustic marker configured into the patient's body by swallowing; generating an acoustic signal; and responding to the acoustic signal Providing a position of an uninflated intragastric balloon within the patient based on the generated acoustic response.

  In an embodiment of the tenth aspect, the location of the uninflated intragastric balloon within the patient is the patient's stomach.

In an embodiment of the tenth aspect, the method is inflated, comprising a polymer wall configured to have a CO ₂ permeability of greater than 10 cc / m ² / day under conditions of an in vivo gastric environment. Introducing an initial filling fluid into the lumen of the non-gastric balloon via a catheter; and exposing the inflated gastric balloon to an in vivo gastric environment for a useful life of at least 30 days, the polymer The rate and amount of CO ₂ diffusion from the in vivo gastric environment through the wall into the balloon lumen is controlled, at least in part, by the concentration of inert gas in the initial fill fluid.

In an embodiment of the tenth aspect, the polymer wall comprises a three layer CO ₂ barrier material comprising a nylon layer, a polyvinylidene chloride layer, and a polyethylene layer.

In an embodiment of the tenth aspect, the polymer wall comprises a three layer CO ₂ barrier material comprising a nylon layer, an ethylene vinyl alcohol layer, and a polyethylene layer.

In an embodiment of the tenth aspect, the polymer wall comprises a two layer CO ₂ barrier material comprising a nylon layer and a polyethylene layer.

In an embodiment of the tenth aspect, the polymer wall comprises a CO ₂ barrier material comprising an ethylene vinyl alcohol layer.

In an embodiment of the tenth aspect, the initial fill fluid consists essentially of gaseous N _2.

In an embodiment of the tenth aspect, the first gas consists essentially of N ₂ and CO ₂ .

In an embodiment of the tenth aspect, the initial fill fluid consists essentially of gas N ₂ and gas CO ₂ , wherein gas N ₂ is over-concentrated with respect to gas CO ₂ in the first gas.

In an embodiment of the tenth aspect, the initial fill fluid comprises one or more SF ₆ in liquid form, vapor form, or gaseous form.

In an embodiment of the tenth aspect, the initial fill fluid includes gas N ₂ and gas SF ₆ .

In an embodiment of the tenth aspect, the polymer wall is configured to have a permeability to CO ₂ greater than 50 cc / m ² / day under conditions of the in vivo gastric environment.

  In an embodiment of the tenth aspect, ascertaining the position of the uninflated intragastric balloon within the patient based on sensing of the acoustic response includes causing an identifier indicating the position of the acoustic marker to be displayed on the computer.

  In an embodiment of the tenth aspect, the acoustic marker is coupled to the catheter.

  In an embodiment of the tenth aspect, the acoustic marker is coupled to the intragastric device.

  In an embodiment of the tenth aspect, the acoustic sensor is an ultrasonic sensor and the acoustic marker is an ultrasonic marker.

  In an eleventh aspect, a system substantially as described in the specification and / or drawings is provided.

  In a twelfth aspect, a method substantially as described in the specification and / or drawings is provided.

  Any of the above embodiments can be combined with other embodiments or other aspects and related embodiments. For example, any of the methods of the second aspect can be used in connection with the system of the first aspect, and any of the methods of the fourth aspect are used in connection with the system of the third aspect. Any of the methods of the sixth aspect can be used in conjunction with the system of the fifth aspect, and any of the methods of the eighth aspect can be associated with the system of the seventh aspect. Any of the methods of the tenth aspect can be used in connection with the system of the ninth aspect, etc. Similarly, any embodiment of either side can be used in combination with one or more other embodiments of any side. Further, any or all embodiments can use a gas phase or liquid phase material as the “fluid”. Thus, the description of “gas” in any embodiment is not meant to limit it to a gaseous material and may include liquid phase materials as well, as described in more detail herein. Good.

FIG. 1 represents an embodiment of an electromagnetic tracking system for positioning a sensor. FIG. 2 represents an embodiment of an electromagnetic tracking system that uses a sensor to place an intragastric device. FIG. 3A represents an embodiment of an electromagnetic tracking system that uses sensors to place an intragastric device within a human patient. 3B is a rear view of the patient of FIG. 3A showing aspects of the external reference sensor for an anatomical viewpoint. FIG. 4 represents an embodiment of an electromagnetic tracking system on a support that uses a sensor to place an intragastric device in the body of a human patient. FIG. 5 represents an embodiment of a display that can be used with the system of FIGS. FIG. 6 depicts an electromagnetic field generator and corresponding magnetic field envelope embodiment that can be used with the system of FIGS. FIG. 7 represents an aspect of a control panel on a system control unit that can be implemented with the system of FIGS. FIG. 8 represents an embodiment of a sensor control unit that can be implemented with the system of FIGS. FIG. 9 depicts an embodiment of a catheter with an integrated sensor that can be used with the system of FIGS. FIG. 10A represents another embodiment of a catheter and sensor that can be used with the system of FIGS. FIG. 10B represents an embodiment of an electromagnetic sensor that can be implemented with the catheter of FIG. 10A. FIG. 10C depicts an embodiment of a voltage sensor that can be implemented with the catheter of FIG. 10A. FIG. 11 depicts an embodiment of an external reference sensor that can be used as an anatomical reference marker with the system of FIGS. FIG. 12 depicts a jumper cable embodiment that can be used with the system of FIGS. FIG. 13 is a plan view of a detector embodiment illustrating one possible arrangement of magnetic sensors. FIG. 14 illustrates the generation of a magnetic field strength vector using the magnetic sensor configuration of FIG. 3 to determine the position of the magnet. FIG. 15A is a functional block diagram of an exemplary aspect of a system configured to determine the position of a magnet. FIG. 15B is a functional block diagram illustrating the operation of the system of FIG. 15A to present the position of the magnet with a conventional imaging system. FIG. 15C illustrates an embodiment of the system of FIG. 15A for monitoring the position of the detector system. FIG. 16 illustrates a number of magnetic sensors arranged in a predetermined area to form a sensor array. FIG. 17A illustrates the use of the system of FIG. 15C to select a location to be a patient landmark. FIG. 17B illustrates the display of the selected position and the position of the magnet. FIG. 18A is a flowchart used by the system of FIG. 15A for determining the position of a magnet. FIG. 18B is a flowchart illustrating an automatic calibration function of the system of FIG. 15A. FIG. 19A illustrates one aspect of the visual display used by the detector of FIG. FIG. 19B is an alternative embodiment of the indicator used in the detector of FIG. FIG. 19C is yet another alternative embodiment of the display used in the detector of FIG. FIG. 19D is yet another alternative embodiment of the detector display of FIG. 13 with a depth meter indicating the distance of the magnet from the detector. FIG. 20 illustrates the position of a plurality of magnets secured to the distal end of a medical tube placed in the body of a human patient. FIG. 21 illustrates the generation of a magnetic field strength vector using any magnetic sensor configuration to determine the position of multiple magnets. FIG. 22 illustrates the orientation of two magnets on a single tube for detecting the rotation angle of the tube. FIG. 23 depicts one embodiment of a balloon that incorporates an electromagnetic, magnetic or magnetizable pellet in the enclosed volume of the intragastric balloon. The pellet may be unfixed or attached to the wall of the intragastric balloon. FIG. 24 depicts one embodiment of a balloon incorporating an electromagnetic, magnetic or magnetizable button attached to the opposite side of the intragastric balloon. FIG. 25A represents a cross section of a valve system including a septum plug, head unit, ring stop, tube septum, and electromagnetic or magnetized retaining ring. FIG. 25B is a top view of the valve system represented by a cross-section along line 1D-1D in FIG. 25A. FIG. 25C is a top view of the valve system of FIGS. 25A and 25B incorporated into the wall of an intragastric balloon. FIG. 26 represents a gel cap 1400 containing the intragastric balloon of FIGS. 25A-C in an uninflated form. A gel cap containing an uninflated balloon is a dual catheter system comprising a 2FR tube and a 4FR tube through a press-fit connection structure incorporating electromagnetic, magnetic, or magnetized components by a valve system of an intragastric balloon Engage with. FIG. 27 represents an embodiment of a system for otherwise characterizing an intragastric device using ultrasound. FIG. 28 depicts an embodiment of a system for otherwise characterizing an intragastric device using ultrasound. FIG. 29 represents an embodiment of an intragastric device for use in the system of FIGS. 27-28, the device having an inflatable compartment, a solid substrate and an internal coil having a placement tab. FIG. 30A represents an embodiment of an ultrasonic sensing mechanism using induction, showing an inner coil and an outer coil placed concentrically and coaxially with each other. FIG. 30B represents another aspect of an ultrasonic sensing mechanism using induction, showing an inner coil and an outer coil placed in a coaxial non-concentric arrangement with respect to each other. FIG. 31A illustrates an embodiment of a coil holder that can use the concentric, coaxial inductive sensing mechanism of FIG. 30A. FIG. 31B illustrates an embodiment of a coil holder that can use the non-concentric, coaxial inductive sensing mechanism of FIG. 30B. FIG. 32 represents an embodiment of an ultrasound method for characterizing an intragastric device or a marker thereon. FIG. 33A is a top view of an embodiment of a system for device verification using a gastric magnetic sensitivity phantom. FIG. 33B is a side view of the system of FIG. 33A. FIG. 34 is a side view of another embodiment of a system for device verification using a gastric magnetically sensitive phantom showing the operation of an adjustable external coil. FIG. 35 is a graph showing a display of frequency data measured by the system of FIGS. FIG. 36 is a flowchart illustrating aspects of a method for determining the size of the gastric lumen using the system of FIGS. FIG. 37 represents an embodiment of a system for characterizing an intragastric device, where the system is placed in a device that causes the system to measure the size and composition of the marker and / or device using time-of-flight ultrasound technology. It has two ultrasonic modules. FIG. 38 is a graph showing a display of data measured by the system of FIG. FIG. 39 represents an aspect of a pulse timing diagram representing time of flight using the Ultrasonic module. FIG. 40 illustrates a graphical representation of data collected with the disclosed ultrasonic and guidance systems. FIG. 41 depicts an illustration of an identifier aspect that can be used in a power generation based intragastric placement system. FIG. 42 provides details of certain implementations of electronic circuitry of various aspects of a power generation sensor that can be used in a power generation based intragastric placement system. FIG. 43 illustrates an ingestible event marker (IEM) integrated circuit (IC) power generation device configuration aspect according to an aspect. FIG. 44 is a schematic diagram illustrating aspects of design for an IEM IC. FIG. 45 illustrates aspects of a transmission sequence for a “0010” bit pattern according to an aspect of the power generation sensor. FIG. 46 illustrates waveform aspects for 20 kHz transmission of sequence “10101” according to an aspect of the power generation sensor. FIG. 47 illustrates an example of a waveform of 10 kHz transmission of the sequence “10101” according to an embodiment of the power generation sensor. FIG. 48 is a state diagram illustrating the operation of an aspect of an IEM IC according to an aspect of a power generation sensor. FIG. 49 illustrates an embodiment of an IEM chip configuration in which two separate electrodes are used for the battery and signal transmission, respectively, in the power generation sensor. FIG. 50 illustrates an exemplary chip configuration that minimizes circuit latch-up according to one embodiment of the power generation sensor. FIG. 51 illustrates a layout aspect for an IEM chip that minimizes latch-up at the IEM. FIG. 52 is an exploded view of an embodiment of an IEM that can be used with a power generation sensor. FIG. 53 is a diagram illustrating an embodiment of a signal receiver that can be incorporated into a power generation sensor. FIG. 54 is a diagram of an embodiment of a signal receiver that can be incorporated into a power generation sensor. FIG. 55A provides additional information regarding various aspects of the external receiver embodiment according to the power generation sensor embodiment. FIG. 55B provides additional information regarding various aspects of the external receiver embodiment according to the power generation sensor embodiment. FIG. 56 is a side view of an embodiment of an intragastric balloon capsule attached to a delivery / inflation catheter with the balloon having a power generation sensor therein. FIG. 57 is a side view of an embodiment of an intragastric balloon system having an anode with a pH coating and a cathode. FIG. 58 represents an embodiment of a series battery that can be incorporated into a power generation sensor placement system. FIG. 59 represents another embodiment of a series battery that can be incorporated into a power generation sensor placement system. FIG. 60 shows an embodiment of a planar or interdigitated battery for an on-chip battery having two cathodes and one anode that can be incorporated into a power generation sensor placement system. FIG. 61 shows an aspect of a large plate configuration for an on-chip battery that can be incorporated into a power generation sensor placement system. FIG. 62 shows an embodiment of a 3d configuration of an on-chip battery with three anodes bridged on top of the cathode that can be incorporated into a power generation sensor placement system. FIG. 63 is a perspective view of a 3d configuration of an on-chip battery that can be incorporated into a power generation sensor placement system. FIG. 64 represents another aspect of an on-chip battery that can be incorporated into a power generation sensor placement system. FIG. 65 represents another aspect of an on-chip battery that can be incorporated into a power generation sensor placement system. FIG. 66 represents another embodiment of an on-chip battery using wafer bonding that can be incorporated into a power generation sensor placement system. FIG. 67 illustrates the use in a patient of an embodiment of a power generation configuration system with event markers. FIG. 68 illustrates the use in a patient of an embodiment of a power generation arrangement system having an anode and a cathode. FIG. 69A represents an aspect of the present disclosure with an integrated controller and display and separate controller unit options, demonstrated during patient use. FIG. 69B represents an aspect of the present disclosure with a wireless external controller used near the patient. FIG. 69C depicts a side view of an embodiment of the pH sensor of the present disclosure disposed over an intragastric device within a cross section of the stomach. FIG. 70A is a schematic side view of a human having a pH monitor that can be incorporated into an intragastric device in the esophagus. FIG. 70B is a schematic diagram of one embodiment of an electrical circuit for the pH monitor of FIG. 70A. FIG. 70C is a schematic diagram of an embodiment of a pH monitor circuit where the circuit also includes a microprocessor. FIG. 71A is a side view of the proximal end cross section of an embodiment of an intragastric tube showing its chemical property indicating element for pH level detection. 71B is a cross-sectional view of an alternative embodiment of the intragastric tube of FIG. 71A taken along section lines 44-44 of FIG. 71A. FIG. 71C is a side view of the proximal end cross section of a further embodiment of an intragastric tube showing its chemical property display medium for pH level detection in a first exemplary configuration. FIG. 71D is a side view of the proximal end cross-section of a further embodiment of an intragastric tube showing its chemical property display medium for pH level detection in a second exemplary configuration. 71E is a cross-sectional view of an alternative embodiment of the intragastric tube of FIG. 71C taken along section line 47-47 of FIG. 71C. 71F is a cross-sectional view of an alternative embodiment of the intragastric tube of FIG. 71D taken along section line 48-48 of FIG. 71D. FIG. 71G is a side view of a further embodiment of an intragastric tube showing its chemical property display medium for pH level detection in a third exemplary configuration. FIG. 71H is a side view of a further alternative embodiment of an intragastric tube showing its chemical property display medium for pH level detection in a fourth exemplary configuration. FIG. 72 shows an embodiment of an intragastric device having a pH sensor vertically connected with a space filler. FIG. 73A is a schematic illustration of a capsule device that can be incorporated into an intragastric device to detect pH levels. FIG. 73B is a schematic diagram of a system that can be incorporated into an intragastric device for measuring pH, having two capsules connected to each other. FIG. 74 illustrates an embodiment of a capsule system with one or more pH sensors for incorporation into an intragastric device having two hard capsule-like units and a soft flexible tube connecting the capsule units. FIG. 75 is a flowchart of an embodiment of a method for using a pH sensor with an intragastric device to determine the position, orientation and / or status of the intragastric device. This method can be used in other systems including electromagnetic, magnetic, power generation and ultrasound systems. FIG. 76 is a perspective view of a suitcase aspect of the intragastric placement system of the present disclosure. FIG. 77 is a perspective view of the backpack aspect of the intragastric placement system of the present disclosure. FIG. 78 provides experimental data of pressure over time in various intragastric balloons for various concentrations of SF ₆ and / or N ₂ as the filling gas. Line A has a wall comprising a polyethylene layer and a nylon layer (PE / Nylon), refers to the first balloon filled with 100% SF _6. Line B refers to a second balloon having a wall comprising a polyethylene layer and a nylon layer (PE / Nylon) and filled with 100% SF ₆ . Line C refers to a balloon having a wall comprising a polyethylene layer and a nylon layer (PE / Nylon) and filled with 75% SF ₆ /25% N ₂ . Line D refers to a balloon having a wall comprising a polyethylene layer and a nylon layer (PE / Nylon) and filled with 50% SF ₆ /50% N ₂ . Line E refers to a balloon having a wall comprising a polyethylene layer and a nylon layer (PE / Nylon) and filled with 25% SF ₆ /75% N ₂ . Line F has a wall comprising a polyethylene layer and a nylon layer (PE / Nylon), it refers to a balloon filled with _{18~20% SF 6 / 78~80% N} 2. Line G refers to a balloon with a wall containing a layer of ethylene vinyl alcohol (EVOH) and filled with 100% N ₂ . Line H refers to a balloon with a wall containing a 3.5 mil polyethylene layer and a nylon layer (PE / Nylon) and filled with 100% N ₂ .

Detailed description

  The following description and examples illustrate preferred embodiments of the invention in detail. Those skilled in the art will recognize that there are several variations and modifications of this invention that are encompassed by the scope of this invention. Accordingly, the description of preferred embodiments should not be viewed as limiting the scope of the invention.

  The term “degradable” as used herein is a broad term and given its ordinary and customary meaning to those skilled in the art (and is not limited to a special or customized meaning) A process in which the structural integrity of the balloon is impaired (eg, by chemical, mechanical, or other means (eg, light, radiation, heat, etc.), such as, but not limited to, contraction Point to. Degradation processes may include corrosion, dissolution, separation, digestion, disintegration, stripping, grinding, and other such processes. Degradation within a predetermined time frame after ingestion or within a predetermined time frame is particularly preferred.

The term “CO ₂ barrier material” as used herein is a broad term and given its ordinary and customary meaning to those skilled in the art (and is not limited to a special or customized meaning). Not), but not limited to, refers to a material that is permeable to 10 cc / m ² / day or less of CO ₂ under simulated in vivo conditions (100% humidity and 37 ° C. body temperature). As used herein, the term “in vivo conditions” refers to both actual in vivo conditions, such as in vivo intragastric conditions, and simulated in vivo conditions. The permeability of a material to CO ₂ can vary depending on the conditions under which it is measured.

  The term “swallowable” as used herein is a broad term and is given its ordinary and customary meaning to those skilled in the art (and is not limited to a special or customized meaning) Refers to, but not limited to, ingestion of the balloon by the patient such that the external capsule and its components are delivered to the stomach by normal peristaltic movement. While the preferred embodiment systems are swallowable, they are also configured by ingestion by methods other than swallowing. The swallowability of the system is guided, at least in part, by the external container size for self-expanding systems and catheters and the external container size for manual inflation systems. For self-expanding systems, the outer capsule is sufficient to contain the inner container and its components, the amount of activating agent to be injected prior to administration, the balloon size, and the balloon material thickness. is there. The system is preferably of a size that is less than the average diameter of the normal esophagus.

  Described herein is a system for an orally ingestible device that magnetically, electromagnetically and / or ultrasonically locates, tracks, and / or otherwise senses a device or device state . In preferred embodiments, the device can traverse the gastrointestinal tract. The device can be useful, for example, as an intragastric volume occupancy device. The device overcomes one or more of the above problems and drawbacks found in current gastric volume occupancy devices. In certain embodiments, specific devices are described, but it will be understood that the materials and methods may be applied to other devices.

  In order to more clearly explain the subject matter of the preferred embodiment, different embodiments of the same sub-part are described under a single related heading subheading. This organization is not intended to limit the manner in which different subpart aspects can be combined in accordance with the present invention. Any sub-section or sections that discuss various subcomponents for use in the magnetic, electromagnetic and ultrasonic systems disclosed herein under their respective subheading sections, or various tracking and visualization subcomponents. Can be discussed in any other section.

Swallowable intragastric balloon system A swallowable, self-expanding or inflatable intragastric balloon system according to selected preferred embodiments comprises the following parts: self-sealing for the addition of fluid to the balloon lumen or inner container A type valve system (“valve system”), a balloon in a deflated and compressed state (“balloon”) and an outer capsule, container, or coating (“outer container”) containing the balloon. For self-inflating balloons, an inner capsule or other container (“inner container”) containing one or more CO ₂ generating components is present inside the lumen of the balloon. The system may also include various components (“delivery components”) to facilitate delivery of the balloon to the mouth and / or through the esophagus.

  For inflatable balloons, an inflation fluid source, a catheter, and a tube (“inflation assembly”) are provided for inflating the balloon after ingestion or placement into the stomach. In a self-expanding balloon configuration, the valve is preferably attached to the inner surface of the balloon by gluing or other means (eg, welding), and the self-sealing valve provides liquid activation agent to the balloon lumen. An inoculation spacer is provided to prevent puncture of the balloon and inner container wall by a needle or other means for infusion. In an inflatable balloon configuration, a valve is provided that provides releasable attachment of the tube to the balloon. Preferably, the self-sealing valve system attached to the balloon in an inflatable configuration (eg, on its inner surface) is “universal” or compatible with a swallowable catheter or a physician-assisted catheter To do. The valve system serves to allow balloon inflation using a small catheter containing a needle assembly and also provides a mechanism for removal of the catheter after inflation is complete.

The outer container preferably includes a balloon in a compressed state (eg, folded and rolled) and preferably has sufficient space to allow activation liquid to be injected into the balloon in a self-expanding balloon configuration. Where the liquid activator initiates separation, corrosion, decomposition, and / or dissolution of the inner container and generation of CO ₂ upon contact with the expansion agent contained in the inner container, and then CO ₂ gas Pressure causes separation, corrosion, decomposition, and / or dissolution of the outer container. In an inflatable balloon configuration, it is sufficient for the outer container to include a balloon in a compressed state.

  Selected components of the preferred embodiment swallowable intragastric balloon system include: a silicon head containing a radiopaque ring, a trimmed 30D silicon septum, a Nylon 6 inoculation spacer, a compressed balloon, an internal container (self-expanding type Case), and an external container as a component of the system in an unassembled form. A fully assembled outer container has an aligned vent or tube connection port (if inflatable) with a septum for puncture to inject liquid activator (if self-expanding) May be included. As discussed further below, particularly preferred system components have the attributes described herein; however, in certain embodiments, it is possible to use a system that uses components and / or valves with other attributes. it can.

  The device according to the preferred embodiment is intended for deployment without having to rely on ingestion and invasive methods by the patient. Accordingly, it is desirable that the device of the preferred embodiment be operable to be compatible with a compact delivery state that the patient can swallow while minimizing discomfort. Once in the stomach, it is desirable for the device to assume a substantially larger deployed state. To achieve the transition from the delivery state to the deployed state, the device is subjected to inflation.

In order to initiate expansion in the inner container self-expanding configuration, the expansion sub-part may require external input such as an activation agent. Preferably, the activated agent is injected using a syringe having a needle having a gauge diameter of 25-32. The length of the needle is preferably about 0.25 inches (0.6 cm) to 1 inch (2.54 cm) long and within 30 seconds, but by not physically damaging the inner container, Create a flow rate that allows delivery of the full volume of expansion agent in a manner / flow / flow that causes premature CO ₂ production and expansion. The activating agent is preferably pure water or a solution containing anhydrous citric acid at a concentration of up to 50% at 20 ° C., or its equivalent at a solution temperature that varies based on the solubility of the anhydrous citric acid. Preferably, the system is configured to have an occupable void in the central lumen of the balloon when in compressed form in an outer container of about 0.3 ml to about 4.5 ml, and a corresponding volume of activating agent. Can be injected into the gap.

In one embodiment, prior to folding, the partition wall / inoculation spacer is to enter directly on the tip of the capsule, the floating inner container containing a swelling agent for the CO ₂ generation, preferably a self-sealing valve system Align vertically. The balloon contains an inner container. A self-sealing valve system is adhesively bonded to the interior of the balloon wall and provides an inverted configuration balloon by inversion through a patch-sealed hole. The upper quarter of the balloon wall is folded over the inner capsule, and the fold with the capsule is creased similar to the fold formed in the second step of making the paper airplane, and then folded to the left or right. Next, about 3/4 of the lower side of the sphere is folded in a bellows shape using no more than two folds and folded on the capsule. The left half is then folded over the right half of the capsule or vice versa so that the wings touch. It is then rolled until the material makes a tight wrapper. The device is then placed inside the outer container.

  In a self-expanding configuration, the balloon is folded to form a pocket around the inner capsule and the liquid injected through the self-sealing valve system is contained in an area of less than 10% of the total surface area of the balloon Secure. If no inner capsule is provided, there is no need to provide a pocket in the inflatable configuration. The balloon is folded so that the total number of folds is minimized to minimize the possibility of damage to external materials or obstacles to barrier properties. The total number of folds is preferably less than 10 times. Wrap the balloon material as much as possible to minimize the number of folds required to fit the balloon into the outer container. This is done to prevent damage to the luminal material. Also, the self-sealing bulb is preferably constructed off the center of the balloon to minimize the number of times that layer is folded on top of each other.

In a self-expanding configuration, the material that forms the wall of the balloon is processed and folded to localize the initiator injected into the balloon so that the initiator is maintained near the reactants in the inner container. To maximize reaction efficiency. Once the reaction has begun and the outer container has separated, the balloon is folded so that the balloon expands in a manner that creates the maximum surface area possible and inhibits the balloon from easily passing through the pyloric sphincter. The ratio of reactant to activating agent in the inflating agent is such that any residual fluid inside the balloon lumen is acidic and has a pH of less than 6, allowing leakage or breakage of the balloon that allows gastric acid entry. It is chosen not to cause further CO ₂ production and the resulting unintentional re-expansion.

In self-expanding configurations, while minimizing sufficient space and / or capacity to hold the internal container, shaped to provide a good surface area availability for reaction for CO ₂ generation, a swelling agent Compress, form or otherwise hold. Preferably, the inner container is about 0.748 inches (1.9 cm) to 1.06 inches (2.7 cm) long (longest dimension) and about 0.239 inches (0.6 cm) to about 0.00. It has a diameter or width of 376 inches (1 cm). The volume of the inner container is preferably from about 0.41 ml to about 1.37 ml. The inner container is preferably in the form of a standard push-type gelatin capsule, but gelatin tape can be used in place of the push-type capsule. The container is preferably for containing an expanding agent; however, additional sealing or other encapsulations can be used to control the timing of expansion. Gelatin is particularly preferred for use as an internal container; however, other materials such as cellulose may be suitable for use. In order to minimize the internal volume of the system, it is generally preferred to include only a single internal container; however, in certain embodiments, more than one internal container can be advantageously used. The timing of self-inflation is normal esophageal transit time and normal gastric emptying time for large food particles so that the balloon does not expand to a size that can block the esophageal passage or prematurely pass through the pyloric sphincter. Selected based on Also, timing is controlled by compressing the balloon so that the activating agent is substantially localized in the balloon adjacent to the inner capsule, creating an efficient CO ₂ self-inflation method. The inflation of the balloon is initiated by the liquid activator, causing the inner container to break down, such that the inflating agent in the inner container comes into contact with the liquid activator, thereby initiating the gas generation reaction.

An inner container for a self-expanding balloon is contained within the balloon lumen and includes a CO ₂ generator for balloon self-inflation. The CO ₂ generator includes a swelling agent mixture housed in a container. Preferably, about 10% to about 80% of the total swelling agent used comprises powdered citric acid and the remainder comprises powdered sodium bicarbonate. CO ₂ during the formation reaction completion, the balloon is to achieve expanded in the expansion pressure on it said nominal provide sufficient swelling agent. Preferably, a total of about 0.28 to 4 grams of inflation agent mixture is used, depending on the size of the balloon to be inflated; preferably 1.15 to produce 300 cm ³ of CO ₂ at nominal pressure. Up to grams of sodium bicarbonate is used, the rest being powdered citric acid.

Outer container Preferably, the balloon is provided in a contracted and folded state in a capsule or the like that holds, contains or covers the structure (“outer container”). Preferably, the outer container is in the form of a standard push-type gelatin capsule, the push-type is for containing a deflated / folded balloon; however, in certain embodiments, a gelatin wrap is provided. It can be used advantageously. Gelatin is particularly preferred for use as an external container; however, other materials such as cellulose, collagen, etc. may be suitable for use. Preferably, the outer container is about 0.95 inches (2.4 cm) to 2.5 inches (6.3 cm) long (longest dimension) and about 0.35 inches (0.9 cm) to about 0.00. It has a diameter or width of 9 inches (2.4 cm). The volume of the inner container is preferably from about 1.2 ml to about 8.25 ml. In a self-expanding configuration, the outer container preferably reacts at each end, preferably with any gas created for the exposure of the expanding agent to condensation or other environmental humidity present during processing. One or more holes, slits, passages or as a vent to prevent premature separation and degradation of the inner container 30 seconds before inoculation with the liquid activator, which may have undesirable effects on efficiency Configured with other outlets. Such outlets can also facilitate dissolution of the outer container to prepare a balloon for inflation in an inflatable configuration. The process of disassembling (eg, separating, dissolving, or otherwise opening) the outer capsule is facilitated by an increase in pressure caused by balloon inflation (self-inflation or inflation through a catheter). The outer capsule can be immersed in water for a short time to soften the material but not to release the balloon before swallowing in order to minimize the time difference between swallowing and balloon inflation. In the inflatable configuration, the catheter needle housing allows the needle to be inserted into the self-sealing valve while maintaining the balloon housed therein to facilitate pushing or swallowing the balloon assembly. The outer container is provided with a hole for receiving an inflation tube needle assembly, the diameter of which is mechanically compatible with the diameter of the outer container hole. In a preferred embodiment, the outer container is a capsule. The distal half of the capsule can be flared to prevent wear of the balloon material by the tip of the capsule when the compressed balloon is inserted into the capsule. The capsule may also include two parts that include a folded balloon that is held together with the gel band and allows for faster separation of the capsule so that swelling can occur more quickly. The external capsule breaks down (eg, separates, dissolves or otherwise opens) for contact with ingested fluid (eg, water uptake), preferably with the balloon / catheter tube in place. However, in order not to cause discomfort to the patient, it decomposes within 5 minutes or less, more preferably within 2 minutes or less.

  In a preferred embodiment, the device is adapted to a standard size gelatin capsule. The capsule can be formed from a material having a known degradation rate so that the device is not released from the capsule or otherwise deployed prior to entry into the stomach. For example, the encapsulant may include one or more polysaccharides and / or one or more polyhydric alcohols.

  Alternatively, the device in its delivery state can be coated in a substance that traps the device in its delivery state while also facilitating swallowing. The coating can be applied by dipping, sputtering, vapor deposition, or spraying processes that can be performed at ambient or positive pressure.

  In certain preferred embodiments, the encapsulated or coated device is lubricated or otherwise processed to facilitate swallowing. For example, the encapsulated or coated device can be wetted, heated, or cooled prior to swallowing by the patient. Alternatively, the encapsulated or coated device can be immersed in a viscous material that serves to lubricate the passage of the device through the esophagus. Examples of possible coatings may be any material having lubricating and / or hydrophilic properties, such as glycerin, polyvinylpyrrolidone (PVP), petrolatum, aloe, silicon based materials (eg Dow 360) and tetrafluoro Ethylene (TFE) is mentioned. The coating can also be applied by a sputtering, vapor deposition or spray process.

  In a further embodiment, the coating or capsule is impregnated with or treated with one or more local anesthetics or analgesics to facilitate swallowing. Such anesthetics may include aminoamide group anesthetics such as articaine, lidocaine and trimecine, and aminoester group anesthetics such as benzocaine, procaine and tetracaine. Such analgesics may include chloracetic.

  In certain embodiments, the capsule is metered for a particular purpose so that it is administered and travels down the esophagus and / or is properly oriented when it is in the stomach. Can do. The component to be metered may include a polymeric material or an expanded reactant.

To avoid premature inflation while swallowing and prevent passage through the pyloric sphincter during swallowing, ensure self-inflation timing to ensure sufficient inflation once in the stomach A mechanism to control the swallowable self-expanding intragastric device is provided. Normal esophageal transit time for large food particles has been demonstrated to be 4-8 seconds and gastric emptying of large food particles through the pylorus does not occur for at least 15-20 minutes. The outer container preferably has a deflated / folded balloon that separates, dissolves, degrades, erodes and / or otherwise separates in 60 seconds or more, not less than 15 minutes after inoculation with the liquid activator. Configured to begin to spread. The inner container preferably delays the initial CO ₂ production chemistry so that sufficient CO ₂ is not available earlier than 30 seconds after inoculation with the liquid activator, but the balloon is allowed to begin to inflate, At least 10% of the occupable volume of the balloon is filled within 30 minutes, at least 60% of the occupable volume of the balloon is filled within 12 hours, and at least 90% of the occupable volume of the balloon is within 24 hours as it is filled, chemically to allow production of sufficient CO _2, mechanically, or composed of a combination thereof. This timing allows the medical professional to inject the activated drug into an external container, hand the device to the patient, and swallow the patient by normal peristaltic means. This timing also prevents objects over 7 mm in diameter from passing easily, so that the balloon is inflated to a size sufficient to make it difficult to drain the stomach contents of the balloon, thereby introducing the uninflated balloon into the duodenum. Prohibit potential passage.

Delivery Part In certain embodiments, it may be advantageous for administration of the device to deliver the device to the mouth in an optimal orientation, or to facilitate its passage through the esophagus. The delivery means allows the administrator of the device to inject one or more inflation agents or inflation gases into the device as part of administering the device to the patient. In a preferred embodiment, such infusion can be accomplished in the same mechanical action of the administrator used to release the device from the delivery means to the mouth or esophagus. For example, the delivery means may include a plunger, a reservoir containing a fluid, and an injection needle. The administrator injects the liquid contained in the reservoir into the device by pushing the plunger and continuously or nearly simultaneously pushing the needle into the device. Subsequent application of force to the plunger pushes the device from the delivery means to the desired location within the patient. In addition, the delivery means may also include subparts that administer an anesthetic or lubricant to the patient's mouth or esophagus to facilitate swallowability of the device.

The volume-occupying subcomponent ("balloon") of the balloon preferred embodiment is generally formed from a flexible material that forms a wall defining an outer surface and an inner cavity. Various of the above subparts can be incorporated into the wall or internal cavity of the volume occupying subpart. The volume occupancy sub-part may vary in size and shape depending on the patient's internal dimensions and the desired result. The volume occupancy subcomponent can be engineered to be semi-compliant so that the volume occupancy subcomponent can stretch or expand with increasing pressure and / or temperature. Alternatively, in some embodiments, a compliant wall that has little resistance to increased volume may be desirable.

  In certain embodiments, spherical volume occupancy subparts are preferred. Alternatively, the volume-occupiing sub-part may be constructed and metered to be a donut with a hole in the center so that it, like the check valve, faces in the stomach so that it covers all or part of the pyloric sphincter Can be molded. The central hole in the volume occupancy sub-part then serves as the initial passage for stomach contents to enter the small intestine, restricting the passage of food out of the stomach and reducing gastric emptying. Can be induced. Depending on the degree to which gastric emptying is desired to be reduced, volume-occupied subparts with different sized donut holes can be manufactured. Delivery, expansion and contraction of the volume occupancy subpart can be achieved by any of the methods described above.

  In order to minimize its compressed volume as the device moves through the patient's esophagus, it is advantageous that the wall of the volume occupancy subcomponent is strong and thin. In one particular embodiment, a volume occupied subpart wall material having a biaxial orientation that imparts a high modulus value to the volume occupied subpart is produced.

  In one aspect, the volume occupying subcomponent is constructed from a polymeric material such as polyurethane, polyethylene terephthalate, polyethylene naphthalate, polyvinyl chloride (PVC), Nylon 6, Nylon 12, or polyether block amide (PEBA). The volume occupying subcomponent can be coated with one or more layers of material that modify (increase, decrease, or change) gas barrier properties, such as thermoplastic materials.

  Preferably, the gas barrier material has a low permeability to carbon dioxide or other fluid that can be used to expand the volume occupancy subcomponent. The barrier layer should have good adhesion to the base material. Preferred barrier coating materials include biocompatible poly (hydroxyaminoether), polyethylene naphthalate, polyvinylidene chloride (PVDC), saran, ethylene vinyl alcohol copolymer, polyvinyl acetate, silicon oxide (SiOx), acrylonitrile copolymer or terephthalate. And copolymers of acids and isophthalic acid with ethylene glycol and at least one diol. Alternative gas barrier materials include polyamine-polyepoxides. These materials are generally obtained as solvents or aqueous thermosetting compositions and are generally spray coated onto the preform and then heat cured to form the finished barrier coating. Alternative gas barrier materials that can be applied as a coating on the volume occupancy subcomponent include metals such as silver or aluminum. Other materials that can be used to improve the gas impermeability of the volume occupancy subcomponent include, but are not limited to, gold or any precious metal, such as listed in Tables 1a-b , PET coated with saran, and insulating protective coating.

  In certain preferred embodiments, the volume occupancy subcomponent is injected, blown or rotationally molded. A gas barrier coating can be applied immediately after such molding or after a curing period if not already applied in the composite wall.

  In another aspect, the gastric volume occupancy subcomponent is formed using Mylar polyester film coating, silver, aluminum or Kelberite as the metallized surface to improve the gas impermeability of the volume occupancy subcomponent. Let

  In the event that the wall of the volume-occupying sub-part is composed of multiple layers of material, certain materials or methods may be used to connect, attach or hold such multiple layers together May be necessary. Such materials include solvents or ether adhesives. Such multiple layers can also be thermally bonded together. Once such layers are attached together to form (for example) a sheet of material to be made into volume occupied subparts, they can be sealed together for making into volume occupied subparts (e.g. It may also be necessary to apply additional processing steps to such materials (by applying a certain degree of heat and pressure). Thus, it may be advantageous to include certain materials that seal as an additional layer in the volume-occupying subcomponent. For example, a volume-occupied subcomponent composed of a combination of PET and SiOx layers that imparts favorable mechanical properties and gas impermeability to the volume-occupied subcomponent can be sealed in such a volume-occupied subcomponent. It can be sealed by including a layer.

  According to another aspect of the preferred embodiment, the functions of the volume occupancy subcomponent and the contraction component are combined in part or in whole. For example, the volume occupancy subcomponent can be formed from a material that degrades in the stomach over a desired time. Once the disassembly process forms a volume occupancy subpart wall break, the volume occupancy subpart contracts, continues to disassemble, and passes through the remaining gastrointestinal tract.

  Preferably, an automated process is used that takes a fully constructed volume occupancy sub-part, evacuates all air in the internal cavity, and folds or compresses the volume occupant sub-part to the desired delivery state. For example, the exhaust of air from the volume occupancy subcomponent can be activated by reduced pressure or mechanical pressure (eg, rotating the volume occupancy subcomponent). In certain embodiments, it is desirable to minimize the number of folds that are created in the volume occupancy subpart when in the delivery state.

  The contraction and / or expansion of the volume occupancy subcomponent can be achieved by one or more injection sites in the wall of the volume occupancy subcomponent. For example, two self-sealing injection sites can be incorporated on the opposite side of the volume occupancy subcomponent. The volume occupancy subpart can be placed in a fixture that uses two small gauge needles to exhaust air from the volume occupancy subpart.

  In one embodiment, the self-sealing injection site can be further used to insert the chemical element of the expansion sub-part inside the volume-occupying sub-part. After injection of the chemical element into the volume occupancy subpart, the volume occupancy subpart can be discharged using the same needle.

  It may be desirable to package the volume occupancy subpart in a delivery state, for example, under negative vacuum or positive external pressure.

  The volume-occupied subpart wall materials can also be engineered so that once they are first punctured or ruptured, they are relatively easy to tear from the point of such puncture or rupture. Such an initial rupture or puncture can then increase the range and speed up and / or maximize the contraction process so that such characteristics can be used, for example, if the volume occupied subpart shrinks, It may be advantageous if initiated by rupture or puncture of

  It is also possible to coat the volume occupying subpart with a lubricious material that facilitates its passage out of the body after its contraction. Examples of possible coatings may be any material having lubricating and / or hydrophilic properties, such as glycerin, polyvinylpyrrolidone (PVP), petrolatum, aloe, silicon based materials (eg Dow 360) and tetrafluoro Ethylene (TFE) is mentioned. The coating can also be applied by dipping, sputtering, vapor deposition or spraying processes, which can be performed at ambient or positive pressure.

The balloon composite wall material may be of a structure and composition similar to that described in US Patent Application Publication No. 2010-0100116-A1, the entire contents of which are hereby incorporated by reference. The material can be, for example, N ₂ , Ar, O ₂ , CO ₂ , or mixtures thereof, or the atmosphere (N ₂ , O ₂ , Ar, CO ₂ , Ne, CH ₄ , He, Kr, which simulates gastric spatial concentrations. , H ₂ , and a mixture of Xe), preferably in a compressed or uncompressed gas form. In certain embodiments, the balloon can retain fluid (gas) and maintain an acceptable volume for up to 6 months, preferably at least 1 to 3 months after inflation. Particularly preferred fill gases include nonpolar polymeric gases that can be compressed for delivery.

  Before placing in the outer container, the balloon is deflated and folded. In the inverted configuration in the deflated state, the balloon is flat and has inverted seams that extend around the outer periphery of the balloon. A self-sealing valve system is attached to the inner wall of the lumen near the center of the deflated balloon and the inner container is placed adjacent to the self-sealing valve system. The balloon wall is then folded. As part of the balloon design, a self-sealing valve system is “centered” to minimize the number of folds (eg, double or triple) required to fit the balloon into the outer container. Manufactures it in such a way that it is set off. For example, the self-sealing valve system is advantageously placed 1 / 2r ± 1 / 4r from the center of the balloon, where r is the radius of the balloon along the line extending from the center of the balloon through the septum Can do.

  In a preferred embodiment, the self-sealing balloon is completely sealed around 360 degrees. In a self-expanding configuration that uses the injection of an inflating agent with a needle syringe, there is preferably no external opening or opening to the central lumen. In the inflatable configuration, a valve structure (protruding, implanted, or flush with the surface of the balloon) is provided for providing inflation fluid to the central lumen. The balloon may have a “non-inverted”, “inverted” or “overlapping” configuration. In the “non-inverted” configuration, the seam or joint and, if any, the seam allowance is outside the inflated balloon. In the “overlapping” configuration, layers are optionally stacked using one or more folds and secured together with joints, seams, adhesives, etc. to obtain a smooth outer surface. In the “inverted” configuration, the balloon has a smooth outer surface with seams, joints, adhesive beads, etc. inside the inflated balloon. Create a balloon with an inverted configuration, such as a balloon that does not have an external seam allowance (no wall material between the end of the balloon and the joints, seams, or other features that join the sides together) To do so, the two balloon halves are joined together in several ways (eg, glued using glue or heat, etc. based on the balloon material used). One of the balloon halves includes an opening that allows the balloon to ride over itself after bonding the two halves and has a balloon seam inside. The created aperture is preferably annular, but may be any similar shape, and the diameter of the aperture preferably does not exceed 3.8 cm; however, in certain embodiments, a larger diameter Is also acceptable. A patch of material is glued (by gluing, heat welding, etc., based on the material used) to cover the opening of the original balloon half. The reversal holes created in this way, which are subsequently spliced, are small enough so that the forces acting during inflation do not damage the material used to maintain fluid in the balloon.

The preferred shape for the inflated balloon in the final assembly is an ellipsoid, preferably a spheroid or oblate, with a nominal radius of 1 inch (2.5 cm) to 3 inches (7.6 cm), 0.25 inch (0.6 cm) nominal height and 3 inches (7.6 cm), (at 37 ° C. and the internal nominal pressure and / or complete expansion) 90cm ³ ~350cm ³ volume, 0psi (0Pa) ~15psi (103421Pa ) Internal nominal pressure (at 37 ° C.), as well as a weight of less than 15 g. The self-inflating balloon is configured for self-inflation with CO ₂ and is configured to retain 75% or more of the original nominal volume for at least 25 days, preferably at least 90 days when staying in the stomach. Is done. An inflatable balloon delivers an appropriate mixture of gases to deliver a preselected volume profile (including one or more volume increase periods, volume decrease periods, or steady state volume periods) over a preselected time. Configured for expansion to use.

  In certain embodiments where a stable volume over the useful life of the device is preferred, the balloon is configured to maintain a volume that is at least 90% to 110% of its original nominal volume. In other embodiments, it is desirable for the balloon to increase and / or decrease volume over its useful life (eg, in a linear fashion, in a step-wise fashion, or in another non-linear fashion). In other embodiments, the balloon maintains 75% to 125% volume, or 75% to 150% of its original nominal volume.

  The intragastric device may be a single buoyant device or a tethered device. In some aspects, providing a plurality of devices (2, 3, 4, 5, 6 or more), for example, floating or moored together, similar to a bunch of grapes. desirable. Individual devices can be inflated simultaneously using one inflation system connected to all devices, or a separate inflation system can be provided for each device.

Valve System In a preferred embodiment, a self-sealing valve system is provided that contains a self-sealing septum housed in a metallic concentric cylinder. In the inflatable configuration, the self-sealing valve system is preferably adhered to the underside of the balloon material so that only a portion of the valve protrudes slightly outside the balloon surface to ensure a smooth surface. The valve system for the inflatable configuration can use the same self-sealing septum designed for the self-expanding configuration. The partition wall is preferably made of a material having a durometer of 20 Shore A to 60 Shore D. The septum is inserted or otherwise fabricated into a smaller cylinder of a concentric metallic holding structure, which is preferably cylindrical. The smaller cylinder within the larger cylinder controls the alignment of the catheter needle sleeve / needle assembly with the septum and provides a stiff barrier (needle stop mechanism) that prevents the catheter needle from penetrating the balloon material. Provides compression such that the septum reseals after expansion and subsequent needle removal.

  The concentric valve system also provides radiopacity during implantation, preferably titanium, gold, stainless steel, MP35N (non-magnetic, nickel-cobalt-chromium-molybdenum alloy) and the like. Non-metallic polymeric materials such as acrylic, epoxy, polycarbonate, nylon, polyethylene, PEEK, ABS, or PVC or any thermoplastic elastomer made to be visible under x-ray (eg embedded with barium) Alternatively, thermoplastic polyurethane can also be used.

  The septum is preferably conical so that the compressive force is maximized for self-sealing after expansion. Self-sealing septum allows air to be evacuated from the balloon for processing / compression and insertion into an external container, allowing penetration with an inflation agent syringe needle (self-expanding configuration) or an inflation catheter needle (expanding configuration) Thereafter, subsequent removal of the inflation agent syringe needle or removal of the inflation catheter and removal of the catheter needle, which significantly restricts gas leakage to the exterior of the balloon during the inflation process and needle removal / catheter removal, is enabled. The septum is inserted into the valve using a mechanical adaptation mechanism that provides compression. An additional ring can be placed at the distal end of the inner cylinder to provide further compression ensuring that the septum material is sufficiently dense to reseal itself. The ring is preferably metallic in nature, but may be acrylic, epoxy, or a non-metallic polymeric material such as a thermoplastic elastomer or thermoplastic polyurethane. The ring material is preferably the same material as the cylinder, titanium, but may be gold, stainless steel, MP35N, or the like.

  In the inflated configuration, the larger outer cylinder of the concentric valve housing contains a slightly harder durometer material (50 Shore A or higher) than the inner cylinder, but is preferably also silicon. The purpose of using a stiffer durometer material is to ensure a seal when connected to the needle sleeve for expansion. Silicon located in the outer ring of the concentric valve is bonded from the inner surface to the balloon. It provides a small annular lip of this same material that fills the entire outer cylinder and extends slightly to the outer surface of the balloon, slightly larger than the diameter of the inner cylinder. The lip is compatible with a bell-shaped needle sleeve, enhances the connection of the valve to the catheter, provides a seal to withstand the applied inflation pressure, and increases catheter tension. This silicone lip preferably does not protrude beyond the balloon surface beyond 2 mm, ensuring that the balloon surface remains relatively smooth and does not cause mucosal wear or ulceration. It is designed to provide a compressive force against the needle sleeve of the catheter for inflation and removal so that when connected to the needle sleeve of the inflation catheter, the connection force during the inflation process can withstand up to 35 PSI . The sealing force is then broken during removal using a hydrostatic pressure that is greater than 40 PSI and less than 200 PSI to break the connection force. Additional machines, preferably made from the same material as the concentric valve, include two additional retaining rings in the valve system to further enhance the metal-valve silicon seal and ensure proper mechanical fit. It is intended to provide mechanical support and to interrupt the sliding of the silicon material (causing an increase in tension) from the hard (metallic) valve system.

  The valve structure for the inflatable configuration uses a mechanical adaptation mechanism to provide the function of a self-sealing valve for catheter inflation and subsequent catheter removal; however, using a primer and / or adhesive Thus, further support in maintaining the assembly can be provided. The configuration can be modified by modifying the surfaces of the metal parts to make them more tacky or more slippery to provide the desired mechanical / interference fit. The interference fit between the valve and the catheter can be modified to change the pressure requirements for inflation and / or removal. Further assemblies are metallic in silicon so that mechanical support and tensile strength and additional support rings to ensure the force required to sustain the assembly during catheter inflation and removal can be omitted. It may include overmolding the part or concentric system.

  The total valve diameter in the inflatable configuration is designed to be compatible with small catheter systems that do not exceed a diameter of 8 French (2.7 mm, 0.105 inches). To facilitate swallowing, the total diameter does not exceed 1 inch (2.54 cm) and is preferably less than 0.5 inch (1.27 cm). Additional valves can be added as needed; however, in general, a single valve should be used to keep the volume of the deflated / folded balloon (and thus the dimensions of the outer container) as small as possible. It is preferable to use it. The valve system is preferably attached to the inner surface of the balloon so that a shear force greater than 9 lbs (40 N) is required to remove the valve system.

In a self-expanding configuration, the valve system can be attached to the balloon (eg, on its internal surface) without using openings, openings, or other conduits in the balloon wall. The valve system can use a septum having a durometer of 20 Shore A to 60 Shore D. Higher durometers, such as valves having 40 Shore D to 70 Shore D or higher, can be inserted into the holding structure or otherwise fabricated. The retaining structure can be made from any suitable non-metallic polymer material such as silicone, rubber, soft plastic or acrylic, epoxy, thermoplastic elastomer or thermoplastic polyurethane. Preferably, it is metallic or non-metallic, but is radiopaque (eg, barium), visible under x-rays, or magnetic or magnetizable, and is detectable by sensing magnetic fields. Good structures such as rings can be embedded in the holding structure. Using the mechanical fitting mechanism of two structures of different durometers, one softener (bulk) with a large diameter can be inserted into the snug, and the more rigid durometer structures are A compressive force is created at the opening once opened to allow CO ₂ retention and reduce susceptibility to CO ₂ gas leakage. A metallic ring for radiopacity also serves to create a compressive force on the septum. The self-sealing septum allows air to be exhausted from the balloon for processing / compression and insertion into the outer container, and an inflating agent is injected into the outer container to initiate inflation. If desired, additional septa can be provided; however, generally a single septum is used to keep the volume of the deflated / folded balloon (and thus the outer capsule) as small as possible. Is preferred. The valve system is preferably attached to the inner surface of the balloon so that a shear force greater than 9 lbs (40 N) is required to remove the valve system. Similar to the wedge-shaped septum, the silicon head and opaque ring of a self-sealing valve system can be used.

In a self-expanding configuration, the needle penetrates the self-sealing valve for injection of liquid activator into the lumen of the balloon and through the deflated / folded balloon wall and other locations In order to prevent the pressure in the balloon lumen from being unable to be maintained, an inoculation spacer is preferably incorporated. The inoculation spacer also prevents the liquid activator from penetrating the inner container or the folded balloon material, thereby allowing the activator to react in a suitable manner for CO ₂ production according to the above criteria. It also makes it easy to focus on properly mixing things. The inoculation spacer is generally in the form of a tube or cylinder. The inoculation spacer is preferably attached to the inner container and / or self-sealing valve using an adhesive or other securing means; however, in certain embodiments, the inoculation spacer may be “floating” The position can be maintained by folding or rotating the balloon wall. The inoculation spacer may comprise any suitable material that can be passed after separation, corrosion, degradation, digestion, and / or dissolution of the outer container; however, preferred materials include a minimum Shore D durometer of 40 or more. Non-metallic materials, any metallic material, or a combination thereof. In a preferred embodiment, a needle stopper with a cup (inoculation spacer) can be used.

In certain preferred embodiments of the inflation assembly , the volume occupancy subcomponent is filled with fluid using a tube and then removed from the volume occupancy subcomponent and pulled away. One end of the volume-occupying sub-part has a port connected to a tube of sufficient length that, if unrolled, can span the entire length of the esophagus, from the mouth to the stomach. The tube is pulled away from the volume occupancy subpart and is connected to the volume occupancy subpart having a self-sealing valve or septum that can self-seal once the volume occupancy subpart has expanded. A doctor or other medical professional secures one end of the tube as the patient swallows the device. Once the device stays in the stomach, the doctor uses the tube to form a vapor or gas at temperatures of air, nitrogen, SF ₆ , other gases, vapors, saline solutions, pure water, and in vivo, respectively. A fluid, such as a liquid or vapor (eg, SF ₆ ), under external ambient conditions (eg, room temperature) is transmitted into the volume occupancy subcomponent, thereby expanding it. The fluid is an aqueous fluid, eg, water, a physiologically acceptable fluid, such as water, salt water, or water containing one or more additives (eg, electrolytes, nutrients, fragrances, colorants, sodium chloride, glucose, etc.). A variety of other fluids, or similarly non-fluid materials, including or may be included. After the volume occupancy subpart is fully inflated, the tube can be released and withdrawn from the patient's body.

  The tube can be released in several ways. For example, the tube can be removed by applying a gentle force to the tube or pulling it strongly. Alternatively, the tube can be removed by activating a remote release, such as a magnetic or electrical release. Furthermore, the tube can be released from the volume occupying subcomponent by the automatic discharge mechanism. Such a discharge mechanism can be actuated by the internal pressure of the expanded volume occupancy subcomponent. For example, the drainage mechanism may be sensitive to certain pressures beyond those that open and release the tube at the same time as it opens. This aspect provides the desirable features by combining the release of the tube with a safety valve that helps to avoid accidental overexpansion of the volume-occupying subcomponent in the patient's stomach.

  This automatic release feature also provides the benefit that the expansion process of the device can be monitored and controlled more closely. Current technology allows for a self-expanding gastric volume occupancy subcomponent that begins to expand, typically within a 4-minute time frame, after injecting an activator such as citric acid. In this approach, the volume occupancy subcomponent may in some instances begin to swell before staying in the stomach (eg, in the esophagus) or exhibiting gastric dumping syndrome or rapid gastric emptying. In, the volume occupancy subcomponent may arrive at the small intestine prior to the time at which expansion occurs. Thus, in certain aspects, it may be desirable to instruct the volume occupancy subcomponent to be inflated once it has been determined that the volume occupancy subcomponent is staying in the correct position.

  In certain embodiments, the volume occupancy subcomponent expands gradually over time or in several stages, or the volume occupancy subcomponent maintains a volume and / or internal pressure within a preselected range. It can also be advantageous. For example, if the gas escapes the volume occupancy sub-part before the desired contraction time, it may be beneficial to re-inflate the device and keep it in its expanded state.

  In certain embodiments, an intragastric balloon system that is manually inflated by a small catheter can be used. This system preferably retains “swallowability”. The balloon for delivery is in a compressed state and is preferably attached to a flexible small catheter having a diameter of 4 French (1.35 mm) or less. The catheter binds or wraps itself to deliver a portion of the catheter with the encapsulated balloon so that the patient can swallow both the catheter and balloon for delivery to the stomach Designed. The balloon may contain a self-sealing valve system for catheter attachment and balloon inflation once it reaches the gastric lumen. The proximal end of the catheter may be just outside the patient's mouth and may allow connection to an inflation fluid container that can contain the preferred inflation fluid (gas or liquid). After inflation, the catheter can be removed from the balloon valve and pulled back through the mouth. This method allows the intragastric balloon to maintain its swallowability, but allows inflation by a fluid source or mixture of fluid sources through the catheter. Alternatively, a more rigid pusher system can be used where the balloon valve is compatible with a swallowable flexible catheter or pusher rigid catheter assembly.

  The dilatation catheter (swallowing type or pusher type supported by the administrator) described herein is configured to deliver the balloon device orally and without using any additional means. The administration procedure does not require conscious sedation or other similar sedation procedures, or endoscopic means for delivery. However, other types of devices can be used with endoscopic means for visualization or adapted so that the balloon device can be delivered nasogastric as well.

  In operation, the proximal end of the inflation catheter is connected to a valve or connector that allows connection to an inflation source or disconnection source, which is preferably a Y arm connector or an inflation valve. The connector material may be made of polycarbonate or the like and can be connected to a single or multiple lumen catheter tube. The distal end of the dilatation catheter is connected to a universal balloon valve of a balloon that is compressed and contained in a gelatin capsule or compressed using a gelatin band. The catheter tube preferably has a diameter of 1 French (0.33 mm) to 6 French (2 mm). The catheter preferably extends through the mouth (connected to an inflation connector or valve) and is long enough to traverse down the esophagus toward at least the middle of the stomach, approximately 50-60 cm. To help identify where the end of the tube is located, a measurement scale can be added to the tube or catheter. Based on the different pH between the two anatomical sources, the tube can contain a pH sensor that determines the position difference between the esophagus (pH 5-7) and the stomach (pH 1-4), thereby controlling the timing of inflation It can be initiated or derived from the expected pressure in a constrained space (ie, the esophagus) and a less constrained space (ie, the stomach). The tube may also contain nitinol with adjustable transmission to body temperature, taking into account the timing of swallowing. The tube can also be connected to a series of enclosed or compressed balloons on a single catheter. Each can be inflated and released separately. The number of balloons released may be adjustable for patient needs and desired weight loss. In certain embodiments, an intragastric balloon or catheter is placed or tracked in the body by sensing the magnetic field of the magnetized component of both or one device, as discussed in detail below.

  In certain embodiments, a catheter having a balloon at the distal end (inflated with air) is used to hold the balloon temporarily and firmly in place. A small deflated balloon catheter is placed through the head of a gastric balloon (eg, an “in-balloon balloon”) and then inflated with air during delivery to hold the capsule and balloon firmly in place and remove from the catheter. It is possible to prevent the balloon from dropping off spontaneously. The balloon catheter may include a dual channel (by gas or liquid) that can also inflate larger gastric balloons. Once the gastric balloon is inflated satisfactorily, the small air balloon catheter can be deflated and withdrawn from the valve (the valve self-sealing) and withdrawn from the body, leaving the inflated gastric balloon in the stomach.

  In other embodiments, the catheter is coated to enhance swallowability or to be impregnated or treated with one or more local anesthetics or analgesics to facilitate swallowing. Such anesthetics may include aminoamide group anesthetics such as articaine, lidocaine and trimecine, and aminoester group anesthetics such as benzocaine, procaine and tetracaine. Such analgesics may include chloracetic.

Dual lumen catheter In a preferred embodiment, a swallowable dual lumen catheter is provided. The dual lumen catheter has two lumens with a full assembly diameter of 5 French (1.67 mm) or less, preferably 4 French (1.35 mm) or less. The internal lumen preferably does not exceed 3 French (1 mm) and functions as an inflation tube, and the external lumen preferably does not exceed 5 French (1.67 mm) and functions as a disconnected tube; internal and external lumens Do not exceed a diameter of 2 French (0.66 mm) and 4 French (1.35 mm), respectively. The catheter assembly is connected at the distal end to a needle assembly and at a proximal end to a dual port inflation connector, described in more detail below. Because the tube crosses the gastrointestinal tract and enters the gastric lumen, the tube used by the catheter assembly is flexible for swallowability, is torsion resistant, can withstand body temperature, and is resistant to acids And biocompatible. The tube material is preferably soft and flexible to manage the applied pressure, and has a moderate tensile strength and a significant amount of hoop strength. The lumen is preferably round, coaxial, and buoyant to provide flexibility. The dual lumen assembly also preferably does not require an adhesive or glue. Alternative lumen configurations may include two D-type lumens or a combination of D-type and round lumens and can be used in the final catheter assembly in a stiffer configuration. Preferred materials for the tube include a heat resistant polyethylene tube such as PEBAX® or a heat resistant polyurethane tube such as PELLETHANE ™, PEEK or Nylon. In addition, the tube was made of polylactic acid (PLA), poly-L-aspartic acid (PLAA), polylactic acid / glycolic acid (PLG), polycaprolactone (PCL), DL-lactide-co-ε-caprolactone (DL-PLCL). Where the tube can be released after swollen and removed and swallowed as usual.

  At the distal end of the catheter assembly, an inner lumen or inflation tube is attached to the needle assembly and is used to place a balloon, preferably located at one tip of a balloon housed inside a gelatin capsule as an outer container Puncture the self-sealing valve. The outer lumen is connected to the needle sleeve and provides the connection force between the catheter assembly and the balloon and provides tensile strength to withstand balloon inflation pressures, for example, pressures up to 10 psi or more while maintaining the assembly together. The needle sleeve is configured to mechanically couple with the balloon valve assembly. The needle is preferably made of metal, preferably stainless steel or the like, and has a maximum size of 25 gauge (0.455 mm), preferably 30 gauge (0.255 mm) or more for expansion timing purposes. The needle sleeve is preferably a soft material such as nylon or may be polycarbonate, polyethylene, PEEK, ABS or PVC. The needle sleeve covers the entire length of the needle so that the body is protected from the needle and the needle can only penetrate the balloon septum. Preferably, the needle sleeve is flat or extends out slightly beyond the length of the needle. The needle is inserted into the balloon septum prior to swallowing and maintains a holding force of about 0.33 lb (0.15 kg) when bonded to the balloon bulb silicone area. The needle sleeve is preferably slightly bell-shaped, or when inserted into the silicon area of the valve, a key and keyhole mechanism is created to increase the tensile strength of the assembly and enhance the seal for expansion Such an annular relief or lip.

  At the proximal end, the catheter assembly is preferably connected to a Y adapter assembly made from polycarbonate. The Y adapter is “keyed” so that the inflation gas and connecting fluid are properly connected to the catheter assembly and descend into the correct lumen.

  Prior to inflation, splicing lumen priming can be used with the liquid. For example, before balloon inflation, the outer lumen is first flushed with 2 cc of water, salt water, DI water, and the like. The inflation source container is then attached to a connector that leads to the internal lumen. The inflation source vessel operates on the assumption of ideal gas laws and pressure decay models. For a given compressed gas formulation, the device is designed to equalize by inflating the balloon using a starting pressure that is higher than the resulting final pressure of the balloon. The starting pressure and volume will depend on the gas formulation selected and the length and starting temperature (typically ambient temperature) and final temperature (typically body temperature) of the catheter.

  After inflation, the balloon is removed from the catheter assembly using hydraulic pressure. A syringe filled with water, DI water, or preferably saline is attached to the female end of the Y assembly. The syringe contains 2 cc of liquid, and when the syringe plunger is pushed in, sufficient water pressure is applied so that the needle is ejected from the balloon valve.

To further increase swallowing comfort by further reducing the diameter of the single lumen catheter dilatation catheter, a single lumen catheter not exceeding 2 French (0.66 mm) in diameter can be used.

  The needle / needle sleeve assembly is similar in design to that of the dual lumen catheter described herein. However, for a single lumen system, the distal end of the catheter lumen connects only to the needle sleeve and there is no second catheter inside. Instead, a single thread attached to the needle hub runs coaxially with the length of the catheter, assisting in tensile strength for removal and overall flexibility.

  The needle sleeve is slightly bell-shaped, or when inserted into the silicon area of the valve, a key and keyhole mechanism is created to increase the tensile strength of the assembly and enhance the seal for expansion. This happens by chance during the inflation process because it contains a single annular relief or lip, which is a single lumen assembly and the lip increases the force required to remove the needle from the valve. Does not happen.

  The proximal end of the catheter is connected to a three-way valve and uses an exclusion method for balloon inflation and removal. The distal end of the catheter contains a needle sleeve made from nylon or other similar source. The needle is metallic and is preferably stainless steel.

  Because the tube crosses the gastrointestinal tract and enters the gastric lumen, the tube used by the catheter assembly is flexible for swallowability, is torsion resistant, can withstand body temperature, and is resistant to acids And biocompatible. The tube material is preferably soft and flexible, preferably coaxial and resistant to necking or backing or twisting. For single lumen systems, the catheter tube is preferably made from PEBAX®, but may include bioabsorbable materials such as PLA, PLAA, PLG, PCL, DL-PLCL, where After the tube is inflated and removed, it can be released and swallowed as usual. The wire inside the catheter tube attached to the needle is preferably a nylon monofilament, but Kelvar or Nitinol wire or other suitable material can also be used.

  To inflate the balloon, the distal end of the catheter is attached to a balloon capsule with a needle protruding through a self-sealing valve. The container is swallowed and a portion of the dilatation catheter remains outside the mouth. The inflation source container is connected to a proximal 3-way valve where the port for inflation gas is selected by removing the other port. Inflation fluid (preferably compressed nitrogen gas or a mixture of gases) descends through a single catheter lumen, whereby the inflation gas is ballooned from the path of least resistance, or more specifically from the needle lumen. Select the path to go to. The balloon is preferably inflated within less than 3 minutes.

  To remove and remove the needle from the balloon valve, 2cc or other suitable volume of water or other liquid is injected into the catheter at high pressure. Because water has a high surface tension and viscosity, it blocks the needle passage and breaks the fit between the needle sleeve and the balloon valve by transferring pressure to the exterior of the needle sleeve.

  If it is desirable to place a substance inside the balloon, such as water or acid or any alternative liquid, this can be done by injecting the liquid using a lower pressure.

Small rigid body dilatation catheter In certain embodiments, a rigid body dilatation catheter can be used and can be placed orally or nasally. This system may be 1 French (0.33 mm) to 10 French (3.3 mm) in diameter, preferably 8 French (2.7 mm). To enhance indentability, larger diameters are typically preferred, and wall thickness also contributes to indentability and torsion resistance. The length of the tube may be about 50-60 cm. As discussed above, a measurement graduation can be added to the tube to identify the location where the end of the tube is located, or a pH or pressure sensor on the catheter can be used to detect the position of the balloon.

  This system for inflation / removal is similar to the dual lumen system described above, but uses a larger needle sleeve to accommodate larger diameter tubes. Materials that can be used in the lumen include, for example, expanded polytetrafluoroethylene (EPTFE) for the outer lumen and polyetheretherketone (PEEK) for the inner lumen. A strain relief device can be added to the distal and proximal ends to also enhance pushability. In order to ensure that the catheter bypasses the larynx and enters the esophagus, it is particularly preferred to have a strain relief at the distal end, eg, 1-8 inches, preferably 6 inches. The proximal end may have a strain relief as well, for example to ensure Y arm fit. A preferred material for strain relief is polyolefin. The method for inflation / removal is the same method as the dual lumen configuration where the outer lumen connects to the needle sleeve and the inner lumen connects to the needle. As part of the procedure, for smooth passage of the device, the patient can swallow water or other suitable liquid to expand the esophageal tissue. An anesthetic can also be administered in the back of the patient's throat to paralyze the throat and reduce pharyngeal reflexes.

  The tube can also be connected to a series of enclosed or compressed balloons on a single catheter to administer a total volume of up to 1000 cc or more as needed. Each can be inflated and released separately. The number of balloons released may be adjustable for patient needs and desired weight loss.

  In addition, a catheter similar to the balloon catheter used in angioplasty called “over-the-wire” or rapid exchange catheter can be used to administer the gastric balloon. If the patient attempts to swallow the catheter but cannot do so, a stiff or doctor-assisted catheter can be bypassed through the flexible catheter and the balloon can be pushed down in the same manner as the doctor-assisted catheter. it can. Different materials can be used to provide varying degrees of flexibility, or one material made with different diameters over length to vary the degree of hardness can be used. .

  Both the swallowable self-expanding balloon construction method and the swallowable inflation tube construction method eliminate the need for an endoscope to contain the balloon and make the balloon administration process less invasive. This also makes the total amount put into the patient “titratable” or adjustable. If balloons are put in for 30 days, patients can report over time that they lose fullness without eating. To compensate, another balloon can easily be placed without sedation and without an endoscope. When attempting to endoscopically remove a non-shrinkable balloon, the physician can use the vision to remove the balloon at the end of its useful life while holding the balloon with the remaining useful life in the patient's stomach. It is desirable to paint the balloon composite wall differently using different colors so as to have a visual marker.

  Furthermore, when the balloon is punctured by an endoscope, it folds more efficiently on its own, and due to its shape, hardness, and / or wall material thickness, esophageal perforation by the balloon and / or other The balloon wall can be marked at about 180 ° from the self-sealing valve on the balloon wall to facilitate removal of the thin wall structure without causing damage.

Inflation fluid container An inflation fluid container is used to control the amount or volume of fluid contained within the balloon. This may be, for example, in the form of a canister of PVC, stainless steel, or other suitable material. The container may also be in the form of a syringe. The material used is preferably a fluid in gaseous form, for example compressed or uncompressed N ₂ , Ar, O ₂ , CO ₂ , or mixtures thereof, or compressed or uncompressed atmosphere (N ₂ , O ₂ , Ar, CO ₂ , a mixture of Ne, CH ₄ , He, Kr, H ₂ , and Xe). The balloon composite wall material and corresponding diffusion gradient and gas permeability are used to select a fluid for inflation of the intragastric balloon to provide the desired volume profile over time for the inflated balloon. The inflation fluid container material is selected to ensure that there is no or minimal fluid diffusion or leakage prior to connecting it to the Y-arm connector or valve of the inflation catheter. The inflation fluid container preferably includes a pressure gauge and a connector. It may also contain a smart chip that informs the medical professional whether the inflation was successful or whether the balloon should be removed due to a system error.

In order to maintain the “swallowability” of the balloon and ensure patient comfort during the procedure, it is preferable to minimize the amount of time the catheter is placed into the mouth / esophagus. The timing of inflation can be selected to minimize the time at a given location. The outer container-catheter assembly takes about 4-8 seconds to reach the stomach once swallowed. Once in the stomach, the inflation source container can be attached to a valve or port of the catheter system. The timing of inflation can be controlled by selecting the catheter length, catheter tube diameter, starting temperature, and starting pressure. The ideal gas law for Nitrogen and Boyle's law (P ₁ V ₁ = P ₂ V ₂ ) are used to derive the amount of starting volume / pressure and the temperature of the expansion source container to match that of the body Can be controlled inside. It is desirable to have a post-swallow inflation time of less than 5 minutes, preferably 2-3 minutes, prior to balloon removal and catheter removal. Use of input to induce balloon inflation (preferably less than 3 minutes) includes: inflation container volume, inflation fluid type (preferably compressed gas or compressed gas mixture), starting pressure, catheter length and diameter And the desired final volume and pressure of the balloon. Thus, due to the difference in diameter, the 2 French catheter system requires a higher starting pressure to achieve the same target balloon volume and pressure in the same time frame, assuming the use of the same compressed gas formulation. In general, it will be appreciated that starting from a higher pressure at the same flow rate / volume can reduce the expansion time.

The inflation source container provides feedback to the end user based on the pressure damping system. If there is an expected starting pressure and an expected final pressure indicating whether the balloon is properly inflated, viewing with an endoscope is not necessary. Each scenario of expected pressure output may have its own tolerances to reduce the possibility of false positives, and the inflation fluid container relates to balloon inflation and removal conditions based on these tolerances. Feedback can be provided. If there is an expected final pressure based on a fixed volume balloon, this is derived based on the ideal gas law. If the pressure remains high and does not decay as expected, this may indicate a fault in the system (eg, the balloon container did not dissolve, for example, because the tube is twisted or the catheter system has other faults) , The balloon is dilated in the esophagus). For example, for a successful attenuation using only nitrogen as the inflation fluid, the starting pressure to inflate the balloon to 250 cc is 22 PSI and 1.7 psi (0.120 kg / cm ² ) for nylon-based materials. Provide at least one visual, audible, or tactile notification to indicate successful balloon inflation, or else whether inflation was successful, or pressure curve and predetermined pressure tolerance and expectation A math chip can be added to the inflation source container that transmits a notification to the medical professional or administrator of whether there is an error in the system based on the set of inflation timings to be performed.

  The degree of restraint experienced by reading the gauge output (eg, the capsule is dissolved, but the balloon is in the esophagus or duodenum, or the balloon is in the stomach and the capsule is not dissolved) Another method for detection is at least two reservoirs (one large and one small), together with one or more valves that allow the selection of the release of gas into the second reservoir or the balloon itself, and at least Using an expansion canister with two gauges. With respect to the two reservoirs, the larger reservoir may contain the total amount of fluid required to fill the balloon. Initially, a small amount of fluid can be released from the larger reservoir to the smaller reservoir to determine the position of the balloon and its responsiveness for complete inflation. If a small amount of fluid in the smaller reservoir is released into the balloon catheter and the feedback on the gauge of the smaller reservoir indicates that the pressure is high, this means that the balloon is still contained in the capsule and Indicates that it is not ready. If the gauge reads back a moderate pressure level (eg, 1-4 psi), this indicates that the balloon is in a constrained space such as the esophagus or duodenum and should not be inflated. If the balloon catheter feedback read on the gauge is about 1 psi, this indicates that the balloon is in the stomach and ready for inflation. If the feedback is 0 psi, this indicates that there is a leak in the balloon valve catheter system and the device should be retrieved. Once the balloon is detected in the intragastric space, the larger reservoir is opened and the balloon is inflated to its desired pressure.

  Alternatively, the balloon can be filled based on the starting pressure by using a spring mechanism, an intra-balloon balloon mechanism, or other pressure source. These mechanisms can potentially provide a more predictable / consistent pressure decay curve, and again may have an associated predetermined tolerance for end-user feedback.

The material selected for the composite wall of the composite wall balloon can be optimized and maintained without significant diffusion of the original inflation gas, or once the balloon has entered the stomach, It can also be partially or fully inflated through the wall of the balloon, allowing diffusion of gases in the internal environment, such as CO ₂ , O ₂ , argon, or N ₂ . A fluid (liquid or gas) is added to the interior of the balloon using the dilatation catheter described herein to change the diffusion direction of the balloon composite wall when it reaches rest based on the internal and external environment You can also.

A gastric balloon that is inflated by nitrogen, CO ₂ gas, a single fluid (gas) or a mixture of gases is resistant to barrier properties (fluid retention), pH and humidity conditions in the gastric environment or in the central lumen of the balloon. A composite wall is used that provides the properties to impart, as well as the kinetic power of the stomach, wear of the balloon wall in vivo, and structural properties that resist damage during balloon manufacture and folding. Certain materials used in the balloon material can withstand a hostile gastric environment designed to destroy foreign bodies (eg, food particles). Some variables encompassed by the gastric environment are as follows: 1.5-5 gastric fluid pH at varying frequency and cycle time based on gastric feeding conditions; temperature of about 37 ° C; 90-100 % Relative humidity; gastric space gas content entry; and 0-4 psi steady gastric external pressure. External pressure applied by gastric movement can also cause wear on the surface of the balloon. The interior of the balloon lumen may contain moisture from the solution injected into the balloon due to the timing of self-contraction or moisture that has moved across the membrane due to the external humidity environment. In addition to these environmental stresses, the wall material meets biocompatibility requirements, and the full thickness of the wall (barrier material) is compressed inside a container that can be swallowed ("outer container") without significant damage or retention. And built to be thin enough to be put in. The outer container is small enough to get over the esophagus (having a diameter of about 2.5 cm). The wall or barrier material is also thermoformable and sealable for balloon construction, due to the initial inflation pressure as well as the pressure due to the ingress of gas molecules from the gastric lumen until the gas environment of the system reaches a quiescent state. Maintain a bond strength that may contain an internal gas pressure of up to 10 psi produced. Film properties that are evaluated to determine suitability for use in balloon composite walls include pH resistance, water vapor transmission rate, gas barrier properties, mechanical strength / wear properties, temperature resistance, formability, bending cracking. (Gelbo) resistance, surface energy (wetting) extensibility, and heat bonding ability.

The various layers in the composite wall confer one or more desirable properties to the balloon (eg, CO ₂ retention, resistance to moisture, resistance to acidic environments, wettability for processing, and structural strength). be able to. A list of polymer resins and coatings that can be combined in a multilayer preform system (“composite wall”) is provided in Tables 1a-b. These films can be adhesively bonded together, extruded at the same time, or bonded by a bonding layer, or a combination thereof to achieve the desired combination of properties for a composite wall, as discussed below. Obtainable. The material identified as a film coating in Tables 1a-b is provided as a coating applied to a base polymer film, such as PET, Nylon, or other structural layer.

  Table 1a. Film resin

  Table 1b. Film coating

Fluid Retention Layer In a preferred embodiment, a mixed polymer resin with multiple layers is used to maintain the shape and volume of the inflated balloon by retaining the inflation fluid for the intended duration of use. Certain barrier films widely used in the food packaging and plastic bottle industries can be advantageously used for this purpose in the composite wall of the balloon. Preferably, the barrier material has low permeability to carbon dioxide (or other gas, liquid, or fluid that is alternatively or additionally used to expand the volume occupancy subcomponent). These barrier layers preferably have good adhesion to the base material. Preferred barrier coating materials and films include polyamides, polyimides such as polyethylene terephthalate (PET), linear low density polyethylene (LLDPE), ethylene vinyl alcohol (EVOH), Nylon (PA) and Nylon-6 (PA-6) (PI), liquid crystal polymer (LCP), high density polyethylene (HDPE), polypropylene (PP), biocompatible poly (hydroxyaminoether), polyethylene naphthalate, polyvinylidene chloride (PVDC), saran, ethylene vinyl alcohol copolymer, polyvinyl acetate, silicon oxide (SiOx), silicon dioxide (SiO _2), aluminum oxide (Al ₂ O _3), polyvinyl alcohol (PVOH), nanopolymers (e.g., nanoclay), polyimide thermoset Film, EVALCA EVAL EF-XL, Hostafan GN, Hostafan RHBY, RHB MI, Techbarrier HX (SiOx coated PET), Triad Silver (silver metallized PET), Oxyshield 2454, Bicor 84 AOH, acrylonitrile, acrylonitrile Mention may be made of copolymers of terephthalic acid and isophthalic acid with ethylene glycol and at least one diol. Alternative gas barrier materials include polyamine-polyepoxides. These materials are typically provided as solvent-based or aqueous-based thermosetting compositions and are typically spray coated onto the preform and then thermally cured to form the finished barrier coating. Let Alternative gas barrier materials that can be applied as a coating to the volume-occupying subcomponent include metals such as silver or aluminum. Other materials that can be used to improve the gas impermeability of the volume occupancy subcomponent include, but are not limited to, gold or any precious metal, PET coated with saran, and an insulating protective coating. Can be mentioned.

  One method used in the packaging industry to retard the diffusion of inflation fluid is to thicken the material. In order to allow the balloon to be folded to the desired delivery container size for swallowing by the patient, the total thickness of the composite wall should preferably not exceed 0.004 inches (0.010 cm), so that the material is thicker. It is generally not preferred to do so.

  Multilayer polymer films that can withstand the gastric environment over the life of the balloon include linear low density polyethylene (LLDPE) adhesively bonded to Nylon 12 film. Alternatively, additional film layers with barrier properties such as PVDC can be added to the composite wall.

  The layers providing gas barrier properties are preferably positioned as internal layers in the composite wall, as they are not mechanically much stronger than resins considered “structural” such as Nylon.

Layers such as structural layer polyurethane, Nylon, or polyethylene terephthalate (PET) may be added to the composite wall for structural purposes, and the pH resistance of such layers to withstand the acidic environment of the stomach or central lumen of the balloon Preferably as the outermost layer (proximal to the intragastric environment or proximal to the central lumen of the balloon). Additionally or alternatively, other layers can be included such as, but not limited to, those described in the subsections of “Layer Chemistry” below.

Layer chemistry
Polyethylene terephthalate (PET)
Polyethylene terephthalate is a thermoplastic polymer resin of the polyester family. Polyethylene terephthalate can exist as an amorphous (transparent) material or as a semi-crystalline material. Semi-crystalline materials may appear transparent (less than 500 nm spherulite) or opaque and white (spherulite up to several μm in size) depending on their crystal structure and spherulite size. The monomer (bis-β-hydroxyterephthalate) is esterified by reaction between terephthalic acid and ethylene glycol using water as a by-product, or ethylene glycol and dimethyl terephthalate using methanol as a by-product. Can be synthesized by a transesterification reaction between The polymerization is by a polycondensation reaction between the monomer and ethylene glycol as a by-product (performed immediately after esterification / transesterification) (ethylene glycol is directly recycled in production). Some of the trade names for PET products are Dacron, Diolen, Tergal, Terylene, and Trevira fibers, Cleartuf, Eastman PET and Polyclear bottle resins, Hostaphan, Melinex, and Mylar films, and Arnite, Erletyte, x Injection modeling resin.

  PET consists of polymerized units of ethylene terephthalate monomer with C10H8O4 repeat units. Depending on its thickness, PET may be semi-rigid to rigid and is very lightweight. It creates a good gas and considerable humidity barrier, as well as a good barrier to alcohols and solvents. It is strong and impact resistant. It is colorless in nature and has high transparency.

  When produced as a thin film (biaxially stretched PET film, also known by one of its trade names, “Mylar”), a thin film of metal is evaporated on it to reduce its permeability It can be aluminized on PET by making it reflective and opaque (MPET). These properties are useful in many applications such as flexible food packaging. When filled with glass particles or fibers, it becomes significantly harder and more durable. This glass-filled plastic in a semi-crystalline formulation is sold under the trade names Rynite, Arnite, Hostadur, and Crastin.

  One of the most important features of PET is its intrinsic viscosity. The intrinsic viscosity of a material, measured in deciliters per gram (dl / g), depends on the length of its polymer chain. The longer the chain, the harder the material and hence the higher the intrinsic viscosity. The average chain length of a particular batch of resin can be controlled during the polymerization. For use in composite walls, an intrinsic viscosity of about 0.65 dl / g to 0.84 dl / g is preferred.

  In addition to pure (homopolymer) PET, PET modified by copolymerization is also available. In some cases, the modified properties of the copolymer are more desirable for certain applications. For example, cyclohexanedimethanol (CHDM) can be added to the polymer backbone instead of ethylene glycol. Because this component is much larger than the ethylene glycol it replaces (6 additional carbon atoms), it is not compatible with neighboring chains in the way that an ethylene glycol unit can. This hinders crystallization and lowers the melting point of the polymer. Such PET is commonly known as PETG (Eastman Chemical and SK Chemicals are just two manufacturers). PETG is a transparent amorphous thermoplastic that can be injection molded or sheet extruded. It can be colored during processing. Another common polymerization modifier is isophthalic acid which replaces some of the 1,4- (para) linked terephthalate units. 1,2- (ortho-) or 1,3- (meta-) bonds create angles in the chain and also inhibit crystallinity. Such copolymers are advantageous for certain molding applications such as thermoforming. On the other hand, in other applications where mechanical and dimensional stability are important, crystallization is important. For PET bottles, the use of a small amount of CHDM or other comonomer may be useful: if only a small amount of comonomer is used, crystallization is slowed but not totally inhibited. As a result, the bottle is obtainable by stretch blow molding (“SBM”) and is sufficiently transparent and crystalline to be a sufficient barrier to aromas and gases, such as carbon dioxide in carbonated beverages.

  Crystallization occurs when the polymer chain folds itself in a repeating symmetrical pattern. Long polymer chains tend to become tangled on their own, preventing full crystallization except in the most carefully controlled environment. For commercial products, crystallization of 60% is the upper limit except for polyester fibers.

  PET is a crystalline resin in its natural state. A clear product can be produced by rapidly cooling the molten polymer to form an amorphous solid. Like glass, amorphous PET forms when its molecules are not given enough time to align themselves in a regular manner as the melt is cooled. At room temperature, the molecules solidify in-situ, but if enough thermal energy is returned to them, they begin to move again and the crystals nucleate and grow. This procedure is known as solid state crystallization.

  Like many materials, PET tends to produce many small crystallites when crystallized from an amorphous solid, rather than forming one large single crystal. Because light intersects the boundary between the crystallites and the amorphous regions between them, the light tends to scatter. This scattering means that crystalline PET is often opaque and white. Fiber pulling is one of the few industrial processes that produces a nearly single crystalline product.

  Comonomers such as CHDM or isophthalic acid reduce the melting point of PET and reduce crystallinity (especially important when using materials for bottle manufacture). Thus, the resin can be formed plastically at lower temperatures and / or with less force. This helps to prevent degradation that reduces the acetaldehyde content of the final product at an acceptable (ie, unperceivable) level. Another way to improve the stability of the polymer is by using stabilizers, mainly antioxidants such as phosphites. Recently, stabilization at the molecular level of materials using nanostructured chemical substances has also been considered.

Non-reinforced PET has the following properties: Bulk density 0.800-0.931 g / cc; density 1.10-1.20 g / cc at 285-285 ° C., 1.25-1. Apparent bulk density 0.000850 g / cc; water absorption 0.0500-0.800%; moisture absorption at equilibrium 0.200-0.300%; water absorption at saturation 0.400-0. 500%; particle size 2500 μm; water vapor transmission rate 0.490 to 6.00 g / m ² / day; oxygen transmission rate 5.10 to 23.0 cc-mm / m ² -24 hr-atm; viscosity measurement 0.550 to 0.980; viscosity test 74.0-86.0 cm ³ / g; thickness 250-254 microns; linear molding shrinkage 0.00100-0.0200 cm / cm; linear molding shrinkage, lateral direction 0.00200-0. 0110cm cm; Rockwell hardness M80.0 to 95.0; Rockwell hardness R105 to 120 105 to 120; Steel ball indentation hardness 160 to 170 MPa; Maximum tensile strength 22.0 to 207 MPa; Film tensile yield strength, MD 55. 0-59.0 MPa; film tensile yield strength, TD 53.0-57.0 MPa; film break elongation, MD 40.0-600%; film break elongation, TD 200-600%; film yield elongation, MD 4.00 ~ 6.00%; film yield elongation, TD 4.00 to 6.00%; tensile yield strength 47.0 to 90.0 MPa; breaking elongation 1.50 to 600%; yield elongation 3.50 to 30.0% Elastic modulus 1.83 to 14.0 GPa; flexural modulus 1.90 to 15.2 GPa; bending yield strength 55.0 to 240 MPa; compressive yield strength 20.0 123MPa; unnotched Izod impact strength 2.67J / cm-NB; unnotched low Izod impact strength (ISO) 160~181kJ / m ^2; notch has low Izod impact strength (ISO) 3.10~4.20kJ / m ² ; Charpy impact strength without notch 3.00 J / cm ² -NB; Low temperature Charpy impact strength with notch 0.270 to 0.500 J / cm ² ; Charpy impact strength with notch 0.200 to 1.40 J / cm ² ; Temperature − Impact test at 40 ° C. 0.800 to 8.20 J; coefficient of friction 0.190 to 0.250; total tear strength 15.0 to 120 N; Elmendorf tear strength, MD 3.14 to 4.00 g / micron; Elmendorf tear Strength, TD 3.24-5.20 g / micron; drop 1.08-2.00 g / micron; Taber wear mg / 1000 cycle; film tensile strength at break, MD 13.8 to 60.0 MPa; film tensile strength at break, TD 39.0 to 48.0 MPa; Izod impact strength with notch at −40 ° C. 0.270 to 0.630 J / Cm; Izod impact strength with notch 0.139 to 100 J / cm; Izod impact strength with notch (ISO) 2.00 to 10.0 kJ / m ² ; Electrical resistance 5.00e + 6 to 1.00e + 16 ohm-cm; Surface resistance 1.00e + 14-1.00e + 16 ohm; dielectric constant 2.40-3.90; dielectric strength 15.7-60.0 kV / mm; dissipation factor 0.00100-0.0250; arc resistance 80.0-181 sec; Comparative tracking index 175 to 600 V; heat of fusion 56.0 to 65.0 J / g; CTE, linear 25.0 to 92.0 μ CTE, linear, cross flow 48.0-80.0 μm / m- ° C; specific heat capacity 1.10-1.20 J / g- ° C; 1.30-2. 30 J / g- ° C; thermal conductivity 0.190-0.290 W / m-K; melting point 200-250 ° C; maximum use temperature, 100-225 ° C in air; shrinkage temperature at 0.46 MPa (66 psi) 66. 0-245 °; shrinkage temperature at 1.8 MPa (264 psi) 60.0-240 ° C .; Vicat softening temperature 74.0-85.0 ° C .; minimum service temperature, air-20.0 ° C .; glass temperature 70.0 UL RTI, electricity 75.0 to 175 ° C .; haze 0.300 to 10.0%; gloss 108 to 166%; visible light transmittance 67.0 to 99.0%; Gardner color number − 3.00-85.0; processing temperature 120-295 ° C; molding temperature Degree of 10.0 to 163 ° C; Drying temperature 70.0 to 160 ° C; Drying time 3.00 to 8.00 hours; Humidity content 0.0100 to 0.400%; Injection pressure 68.9 to 120 MPa; Back pressure 8 0.00-18.0 MPa.

  Polyethylene terephthalate film is available from Mitsubishi Polyster Film of Wiesbaden, Germany under the trade name Hostaphan®. Hostaphan® GN is a glass transparent biaxially stretched film made from polyethylene terephthalate (PET), with its high transparency and surface gloss and its low haze, with its excellent mechanical strength and dimensional stability. Features. Hostaphan® GN is chemically treated on one or both sides for improved slip and processability and for improved adhesion of coatings, printing inks or metallic layers. Hostaphan® RHBY has a structure optimized to provide barrier properties previously unattainable for oxygen, water vapor and other gases and fragrances after vacuum coating using aluminum, Al2O3 or SiOx. It is a biaxially stretched film made from polyethylene terephthalate (PET).

Linear low density polyethylene (LLDPE)
Linear low density polyethylene (LLDPE) is a substantially linear polymer (polyethylene) having a significant number of short branches, typically made by copolymerization of ethylene and long chain olefins. . Linear low density polyethylene is structurally different from conventional low density polyethylene because there are no long chain branches. The linearity of LLDPE arises from different manufacturing processes of LLDPE and LDPE. In general, LLDPE is produced at lower temperatures and pressures by copolymerization of ethylene with higher alpha olefins such as butene, hexene, or octene. The copolymerization process produces LLDPE polymers with significantly different rheological properties with a narrower molecular weight distribution and linear structure than conventional LDPE.

  The production of LLDPE is initiated by a transition metal catalyst, in particular a Ziegler or Philips type catalyst. The actual polymerization process can be carried out in a solution phase or gas phase reactor. Normally, octene is a copolymer in the solution phase, butene and hexene are copolymerized with ethylene in a gas phase reactor. The LLDPE resin produced in the gas phase reactor is in granular form and can be sold as granules or processed into pellets. LLDPE has higher tensile strength and higher impact and puncture resistance than LDPE. It is very flexible and stretches under stress. It can be used to make thinner films with better environmental stress crack resistance. It has good resistance to chemicals and UV radiation. It has good electrical properties. However, it is not as easy to process as LDPE, it has less gloss and has a narrow range for heat sealing.

  LDPE and LLDPE have unique theoretical or melt flow properties. LLDPE is less shear sensitive due to its narrow molecular weight distribution and shorter chain branching. During a shearing process such as extrusion, LLDPE remains more viscous than comparable melt index LDPE and is therefore difficult to process. The lower shear sensitivity of LLDPE allows for faster stress relaxation of the polymer chain during extrusion and therefore its physical properties are susceptible to changes in blow-up ratio. In melt elongation, LLDPE has a lower viscosity at all strain rates. This means that it does not strain harden as it does when LDPE is stretched. As the deformation rate of polyethylene increases, LDPE shows a dramatic increase in viscosity due to chain entanglement. This phenomenon is not observed for LLDPE due to the lack of long chain branching in LLDPE, and the chains can “pass through” upon stretching without becoming tangled. This feature is important for film applications because LLDPE films can be easily downgauge while maintaining high strength and toughness.

Properties of film grade LLDPE include: density 0.902-0.960 g / cc; humidity vapor transmission rate 0.240-0.470 cc-mm / m ² -24 hr-atm; water vapor transmission rate 6 0.000 to 8.00 g / m ² / day; oxygen permeation rate 0.720 to 236 cc-mm / m ² -24 hr-atm; oxygen permeation rate 3500 to 5000 cc / m ² / day; viscosity at 190 to 190 ° C. 37000-79000 cP at a shear rate of 300-5000 l / s; 37000-79000 cP at a shear rate of 300-5000 l / s; thickness 12.7-76.2 μm; melt flow 0.200-40.0 g / 10 min; base Resin melting index 0.700 to 3.50 g / 10 min; anti-block level 3500 to 9000 pm; slip level 0.000 to 1700 ppm; maximum tensile strength 9.80 to 26.2 MPa; film tensile yield strength, MD 7.38 to 74.0 MPa; film tensile yield strength, TD 6.90 to 77.0 MPa; film Elongation at break, MD 80.0-1460%; Film elongation at break, TD 460-1710%; Film yield elongation, MD 435-640%; Film yield elongation, TD 670-890%; Tensile yield strength 9.70-22. 1 MPa; elongation at break 8.00 to 1000%; modulus 0.0110 to 0.413 GPa; secant modulus, MD 0.0103 to 0.717 GPa; secant modulus, TD 0.0106 to 0.869 GPa; impact strength 48.0 To 65.0; impact test 0.452 to 5.00 J; coefficient of friction 0.100 to 2.00; coefficient of static friction 0. Elmendorf tear strength, MD 25.0-1080 g2; Elmendorf tear strength TD 180-1470 g; Elmendorf tear strength, MD 0.0750-20.9 g / micron; Elmendorf tear strength, TD 0.275-37 8 g / micron; Drop 1.57-42.5 g / micron; Drop test 30.0-1350 g; Seal strength 1800-2400 g / 25 min; Film tensile breaking strength, MD 9.65-82.7 MPa; Film tensile Breaking strength, TD 7.24-55.1 MPa; heat sealing strength starting temperature 72.0-100 ° C .; melting point 120-128 ° C .; crystallization temperature 104-115 ° C .; Vicat softening temperature 93.0-123 ° C .; 700 to 80.0%; Gloss 3.00 to 140%; Processing temperature 90.0 to 310 ° C; Opening 0.0810~0.254cm; blow-up ratio (BUR) 1.50~4.00.

Ethylene vinyl alcohol (EVOH)
Ethylene vinyl alcohol is a regular copolymer of ethylene and vinyl alcohol. Since the latter monomer exists primarily as its acetaldehyde tautomer, the copolymer is prepared by polymerization of ethylene and vinyl acetate followed by hydrolysis. Plastic resins are generally used in food applications and in plastic gasoline tanks for automobiles. Its main purpose is primarily to provide barrier properties as an oxygen barrier for improved food packaging shelf life and as a hydrocarbon barrier for fuel tanks. EVOH is typically coextruded or laminated as a thin layer between cardboard, foil, or other plastic. EVOH copolymers are defined by the mole percent ethylene content: lower ethylene content grades have higher barrier properties; higher ethylene content grades have lower temperatures for extrusion.

  Ethylene vinyl alcohol (EVOH) is one of the most common transparent high barrier films used today. It is applied as a separate layer in coextrusion. EVOH provides excellent oxygen barrier properties (0.006-0.12 cc-mil / 100 in2-day). The barrier provided by a particular EVOH film has several factors: mole percent (the barrier decreases as the mole percent of ethylene increases); crystallinity (the barrier properties improve as crystallinity increases); Thickness (for all films, the barrier increases as the thickness increases); temperature (the barrier decreases as the temperature increases); humidity (at high humidity levels, the barrier provided by EVOH decreases rapidly) (It is the humidity level at the EVOH interface rather than the ambient humidity that is important). In addition to providing an excellent oxygen barrier, EVOH is also an excellent odor and aroma barrier. It has the additional advantage of being thermoforming, making it popular for 3D applications.

EVALCA EVAL® EF-XL ethylene vinyl alcohol copolymer film has the following properties: humidity vapor transmission rate 0.600 cc-mm / m ² -24 hr-atm 40 ° C., 90% RH; oxygen transmission rate 0.00400 cc- mm / m ² -24 hr-atm 20 ° C .; 65% RH (permeability increases significantly at higher humidity content); thickness 15.2 microns; film break elongation, MD 100% 10% / min; ASTM D638 film Elongation at break, TD 100% 10% / min; ASTM D638 secant modulus, MD 3.50 GPa; Young's modulus, ASTM D638, 10% / min; secant modulus, TD 3.50 GPa; Young's modulus, ASTM D638, 10% / min Elmendorf tear strength MD 260g; ASTM D638 Herme Dorf tear strength TD 330 g; ASTM D638 Elmendorf tear strength, MD 17.0 g / micron; ASTM D638 Elmendorf tear strength, TD 21.7 g / micron; ASTM D638 film tensile strength at break, MD 205 MPa 10% / min; ASTM D638 film tensile Breaking strength, TD 195 MPa 10% / min; surface resistance 2.70e + 15 ohm; dielectric constant 5.00; dissipation factor 0.220; specific heat capacity 2.40 J / g- ° C .; thermal conductivity 0.340 W / m-K; Melting point 181 ° C. DSC; haze 0.500% 65% RH; gloss 95.0% 65% RH. EVAL® ethylene vinyl alcohol film is available from Kuraray America, Inc. of Houston, TX. Is available from

Nylon nylon is a generic name for a family of synthetic polymers commonly known as polyamides. Nylon is a thermoplastic silk-like material. There are two common methods of making nylon for fiber applications. In one approach, molecules having acid (COOH) groups on each terminus are reacted with molecules containing amine (NH2) groups on each terminus. The resulting nylon is named based on the number of carbon atoms separating the two acid groups and the two amines. These are formed into intermediate molecular weight monomers and then reacted to form long polymer chains.

  Solid nylon is used for machine parts such as machine screws, gears and other low to medium stress parts previously cast with metal. Engineering grade nylon is processed by extrusion, casting, and injection molding. Solid nylon is used in the comb. Type 6/6 nylon 101 is the most common commercial grade nylon and nylon 6 is the most common commercial grade molded nylon. Nylon is available in glass filled variants that increase structural strength and impact strength and stiffness, and molybdenum sulfide filled variants that increase lubricity.

  Aramids are another type of polyamide with a completely different chain structure that contains aromatic groups in the main chain. Such polymers make excellent bulletproof fibers.

  Nylon is a condensation copolymer formed by reacting equal amounts of diamine and dicarboxylic acid, and peptide bonds are formed at both ends of each monomer in a process similar to polypeptide biopolymers. The numerical subscripts specify the number of carbons provided by the monomer, diamine first and dice second. The most common variant is nylon 6-6, which refers to the fact that diamine (hexamethylenediamine) and diacid (adipic acid) each supply 6 carbons to the polymer chain. As with other regular copolymers such as polyester and polyurethane, the “repeat unit” consists of one of each monomer, which alternate in the chain. Since each monomer in this copolymer has the same reactive group on both ends, the direction of the amide bond is reversed between the monomers, unlike the natural polyamide protein, which has an overall orientation. In the laboratory, nylon 6-6 can also be made using adipic acid chloride instead of adipic acid. It is difficult to make the ratio quite correct, and deviations can lead to chain termination with a molecular weight of less than 10,000 daltons desired. To overcome this problem, it is possible to neutralize each other with exactly 1: 1 ratio of acid and base to form a crystalline solid “nylon salt” at room temperature. Upon heating to 285 ° C, the salt reacts to form a nylon polymer. Above 20,000 daltons, it is impossible to spin the chain into yarn, so to counteract this, some acetic acid is added to react with the free amine end groups during polymer stretching to reduce the molecular weight. Limit. In fact, especially for nylon 6,6, the monomers are often combined in an aqueous solution. The water used to make this solution is evaporated under controlled conditions, and increasing concentrations of “salt” are polymerized to the final molecular weight.

  Homopolymer nylon 6, or polycaprolactam, is not a condensation polymer, but is formed by ring-opening polymerization (or made by polymerizing aminocaproic acid). The peptide bond within caprolactam is broken using the active groups exposed on each side that are incorporated into the two new bonds as the monomer becomes part of the polymer backbone. In this case, all amide bonds are in the same direction, but the properties of nylon 6 are that of nylon 6,6 except for the melting point (N6 is lower) and some fiber properties in products such as carpets and fabrics. Sometimes things are indistinguishable. Nylon 9 is also present.

  Nylon 5,10 made from pentamethylenediamine and sebacic acid has excellent properties but is more expensive to make. According to this nomenclature, “Nylon 6,12” (N-6,12) or “PA-6,12” is a copolymer of 6C diamine and 12C diacid. The same applies to N-5, 10 N-6, 11; N-10, 12 and the like. Other nylons include copolymerized dicarboxylic acid / diamine products that are not based on the monomers listed above. For example, some aromatic nylons are polymerized using the addition of a diacid, such as terephthalic acid (Kevlar) or isophthalic acid (Nomex), more commonly associated with polyesters. There are copolymers of N-6,6 / N6; copolymers of N-6,6 / N-6 / N-12, and the like. Nylon is believed to be limited to unbranched linear chains due to the manner in which the polyamide is formed. However, “star” branched nylons can be produced by condensation of dicarboxylic acids with polyamides having three or more amino groups.

  Above its melting point, Tm, thermoplastics such as nylon are amorphous solids or viscous fluids and the chains are close to random coils. Below Tm, amorphous regions alternate with regions that are layered crystals. Amorphous regions contribute to elasticity, and crystalline regions contribute to strength and stiffness. Planar amide (—CO—NH—) groups are very polar and therefore nylon forms multiple hydrogen bonds between adjacent chains. Since the nylon skeleton is regular and symmetric, nylon has high crystallinity and often produces excellent fibers, especially when all amide bonds are in the trans configuration. The amount of crystallinity depends on the details of formation as well as the type of nylon. At first glance, it can never be quenched from the melt as a completely amorphous solid.

  Nylon 6,6 may have multiple parallel chains aligned with neighboring peptide bonds in a coordinated separation of exactly 6 and 4 carbons of considerable length so that the carbonyl oxygen and amide hydrogen are Side by side, interchain hydrogen bonds can be formed repeatedly without interruption. Nylon 5,10 may have coordinated runs of 5 and 8 carbons. Thus, parallel (not antiparallel) chains are similar to those found in natural silk fibroin and β-keratin (a protein with a continuous —CO—NH— group that separates only the a-carbons of amino acids) in feathers. Can be involved in stretched, unbroken, multi-chain β-fold sheets that are strong and robust supramolecular structures. Nylon 6 forms an uninterrupted H-bond sheet with mixed orientation, but the β-sheet wrinkles are somewhat different. The three-dimensional configuration of each alkane hydrocarbon chain depends on the rotation of a single bonded carbon atom around a 109.47 ° tetrahedral bond.

  Block nylon tends to be less crystalline except near the surface due to shear stress during formation. Nylon is clear and colorless or milky, but easily dried. Multi-chain nylon cords and ropes are slippery and easy to unwind. This end can be melted and fused with a heat source such as a flame or electrode to prevent this.

  When dried, polyamide is a good electrical insulator. However, polyamide is hygroscopic. The absorption of water changes some material properties such as its electrical resistance. Nylon is less absorbent than wool or cotton.

  Nylon can be used as a matrix material in composites with reinforcing fibers such as glass or carbon fibers, which is denser than pure nylon. Such thermoplastic composites (25% glass fiber) are often used in automotive parts adjacent to the engine, such as the intake manifold, and the good heat resistance of such materials makes them feasible against metal Make it a competitor.

  All nylons are particularly susceptible to hydrolysis by strong acids and are essentially the inverse reaction of the synthetic reaction shown above. The molecular weight of such attacked nylon products decreases rapidly and rapidly cracks in the affected zone. Lower grade nylons (such as nylon 6) are more affected than higher grades such as nylon 12. This means that the nylon part cannot be used in contact with sulfuric acid, such as the electrolyte used in lead-acid batteries. When molded, the hot water can also degrade the polymer, so the nylon must be dried to prevent hydrolysis in the molding machine barrel.

Polyimide (PI)
Polyimide is a polymer of imide monomers. Thermosetting polyimides are commercially available as uncured resins, preserved shapes, thin sheets, laminates and mechanical parts. Thermoplastic polyimides are very often called pseudo-thermoplastic materials. There are two general types of polyimide. One type, a so-called linear polyimide, is made by combining imides in a long chain. Aromatic heterocyclic polyimides are another common type. Examples of polyimide films include Apical, Kapton, UPILEX, VTEC PI, Norton TH and Kaptrex. Polyimide moieties and shapes include VTEC PI, Meldin, Vespel, and typical monomers include pyromellitic dianhydride and 4,4′-oxydianiline.

  Thermosetting polyimides are known for thermal stability, good chemical resistance, excellent mechanical properties, and characteristic orange / yellow color. Polyimides combined with graphite or glass reinforcing fibers have a flexural strength of up to 50,000 psi and a flexural modulus of 3,000,000 psi. Thermoset polyimides exhibit very low creep and high tensile strength. These properties are maintained during continuous use up to temperatures of 232 ° C and for short deviations as high as 482 ° C. Molded polyimide parts and laminates have very good heat resistance. Typical operating temperatures for such parts and laminates range from low temperatures to temperatures exceeding 260 ° C. Polyimides are also inherently resistant to flame combustion and usually do not need to be mixed with flame retardants. Many carry VTM-0 UL ratings. The polyimide laminate has a bending strength half-life of 400 hours at 249 ° C.

  Typical polyimide parts are not affected by commonly used solvents and oils such as hydrocarbons, esters, ethers, alcohols and freons. They are also resistant to weak acids but are not recommended for use in environments containing alkali or inorganic acids. Some polyimides such as CPI and CORIN XLS are solvent soluble and exhibit high optical clarity. The dissolution properties are useful for their spraying and low temperature curing applications.

  Polyimide materials are lightweight, flexible, heat resistant and chemical resistant. They are therefore used in the electronics industry as insulating films on magnetic wires, for flexible cables, and for medical tubing. For example, in a laptop computer, the cable connecting the main logic board to the display (which must be bent each time the laptop is opened or closed) is often polyimide based with copper conductors. The semiconductor industry uses polyimide as a high temperature adhesive; it is also used as a mechanical stress buffer. Several polyimides can be used like photoresist; both “positive” and “negative” type photoresist-like polyimides exist on the market.

Thermosetting film polyimide has the following properties: density 1.40 to 1.67 g / cc; water absorption 1.40 to 3.00%; moisture absorption at equilibrium 0.400 to 1.80%; Hygroscopicity 1.20-2.50%; humidity vapor transmission rate 2.40-17.5 cc-mm / m ² -24 hr-atm; oxygen transmission rate 9.90 cc-mm / m ² -24 hr-atm; thickness 22 Film tensile yield strength, MD 49.0-255 MPa; Film tensile yield strength, TD 100-160 MPa; Film break elongation, MD 10.0-85.0%; Film yield elongation, MD 40.0 Film yield elongation, TD 45.0-55.0%; tensile yield strength 73.3-160 MPa; yield elongation 10.0-45.0%; Poisson's ratio 0.340; secant modulus 2. 28 to 5.20 GPa; secant modulus, MD 1.76 to 9.12 GPa; impact test 0.686 to 1.56 J; friction coefficient 0.400 to 0.480; static friction coefficient 0.630; tear strength test 20-430; peel strength 0.240 kN / m; Elmendorf tear strength MD 8.20-270 g; film tensile strength at break, MD 98.1-736 MPa; electrical resistance 1.00 e + 10-2.30 e + 17 ohm-cm; temperature 200 ° C. 1.00e + 15 to 1.00e + 16 ohm-cm; surface resistance 10000 to 1.00e + 17 ohm; 1.00e + 15 to 1.00e + 15 ohm at 200 ° C .; dielectric constant 2.70 to 4.00; dielectric at 200 ° C. Strength 48.0-272 kV / mm; dissipation factor 0.00130-0.0100; CTE, linear, 12.0-20 0 μm / m- ° C .; 32.0 to 40.0 μm / m- ° C. at a temperature of 100 to 300 ° C .; specific heat capacity 1.09 to 1.13 J / g- ° C .; thermal conductivity 0.120 to 0.289 W / m -K; Maximum use temperature, air, 180-400 ° C; Minimum use temperature, air, -269 ° C; Glass temperature 360-500 ° C; Oxygen index 37.0-66.0%; Shrinkage 0.0100-0. 200%; having a refractive index of 1.70.

Liquid crystal polymer (LCP)
Liquid crystal polymers (LCP) are a class of aromatic polyester polymers. They are extremely non-reactive and inert and are very resistant to fire. Liquid crystallinity in the polymer can occur by dissolving the polymer in a solvent (lyotropic liquid crystal polymer) or by heating the polymer above its glass or melting transition point (thermotropic liquid crystal polymer). The liquid crystal polymer exists in a molten / liquid or solid form. In liquid form, liquid crystal polymers have applications primarily in liquid crystal displays (LCDs). In solid form, the main example of a lyotropic LCP is a commercial aramid known as Kevlar. The chemical structure of this aramid consists of a linearly substituted aromatic ring linked by an amide group. Similarly, several series of thermotropic LCPs have been produced trademarked by several companies (eg, Vectra). A number of LCPs produced in the 1980s showed order in the melt phase similar to that exhibited by non-polymeric liquid crystals. Processing of LCP from the liquid crystal phase (or mesophase) results in fibers and injection materials that have high mechanical properties as a result of self-strengthening properties derived from macromolecular orientation in the mesophase. Today, LCP can be melt processed on conventional equipment at high speeds due to excellent reproduction of mold details.

  Liquid crystal polymers, a unique class of partially crystalline aromatic polyesters based on p-hydroxybenzoic acid and related monomers, can form regions of highly ordered structure while in the liquid phase. However, the degree of order is somewhat lower than regular solid crystals. Typically, LCP has high mechanical strength at high temperatures, extreme chemical resistance, inherent flame retardancy, and good weather resistance. Liquid crystal polymers are in various forms from easily sinterable high temperatures to injection moldable compounds. LCP can be welded, but the wire produced from welding is a weakness of the resulting product. LCP has a high Z-axis thermal expansion coefficient.

  LCP is exceptionally inactive. They resist stress cracking in the presence of many high temperature chemicals such as aromatic or halogenated hydrocarbons, strong acids, bases, ketones, and other aggressive industrial materials. Hydrolysis stability in boiling water is excellent. The environment that degrades the polymer is hot steam, concentrated sulfuric acid, and boiling corrosive materials. Because of its various properties, LCP is useful for electrical and mechanical parts, food containers, and any other application that requires chemical inertness and high strength.

High density polyethylene (HDPE)
High density polyethylene (HDPE) or polyethylene high density (PEHD) is a polyethylene thermoplastic made from petroleum. HDPE has few branches and can provide stronger intermolecular force and tensile strength than low density polyethylene. It is also harder and more opaque and can withstand somewhat higher temperatures (120 ° C for short time, 110 ° C for continuous). High density polyethylene, unlike polypropylene, cannot withstand the normally required autoclave conditions. The lack of branching is ensured by the selection of an appropriate catalyst (eg, Ziegler-Natta catalyst) and reaction conditions. HDPE contains chemical elements, carbon and hydrogen. Hollow goods produced by blow molding are the most common application areas for HDPE.

Polypropylene (PP)
Polypropylene or polypropene (PP) is made by the chemical industry and is used in packaging, textile products (eg, ropes, thermal underwear and carpets), stationery, plastic parts and various types of reusable containers, laboratory equipment, loudspeakers It is a thermoplastic polymer used in a wide range of applications such as automotive parts and polymer bills. Further polymers are made from monomeric propylene, which is rugged and very resistant to many chemical solvents, bases and acids.

  Many commercial polypropylenes are isotactic and have intermediate levels of crystallinity between low density polyethylene (LDPE) and high density polyethylene (HDPE); their Young's modulus is also intermediate. PP is usually robust and flexible, especially when copolymerized with ethylene. This makes it possible to use polypropylene as an engineering plastic that competes with materials such as ABS. Polypropylene is reasonably economical and can be translucent if not colored, but not as easily as polystyrene, acrylic or certain other plastics. It is often opaque and / or colored with pigments. Polypropylene has good resistance to fatigue.

  Polypropylene has a melting point of about 160 ° C. (320 ° F.) as determined by differential scanning calorimetry (DSC). MFR (melt flow rate) or MFI (melt flow index) is a measure of the molecular weight of PP. This helps to determine how easily the molten raw material flows during processing. The higher the MFR, the easier the PP will fill the plastic mold during the injection molding or blow molding manufacturing process. However, as the melt flow increases, some physical properties such as impact strength decrease.

  There are three general types of PP: homopolymers, random copolymers and block copolymers. The comonomer used is typically ethylene. Ethylene-propylene rubber or EPDM added to the PP homopolymer increases its low temperature impact strength. Randomly polymerized ethylene monomer added to the PP homopolymer reduces the crystallinity of the polymer and makes the polymer more transparent.

  Polypropylene is susceptible to chain degradation from exposure to UV radiation, such as that present in sunlight. For external applications, it is necessary to use UV absorbing additives. Carbon black also provides some protection from UV attacks. Polymers can also be oxidized at high temperatures, which is a common problem during molding operations. Antioxidants are usually added to prevent polymer degradation.

  The relative orientation of each methyl group compared to the methyl groups on neighboring monomers is relative to the ability of the final polymer to form crystals because each methyl group takes up space and constrains the skeletal bending. Has a powerful effect.

  Like many other vinyl polymers, useful polypropylene cannot be made by radical polymerization due to the higher reactivity of allyl hydrogen during polymerization (resulting in dimerization). Furthermore, the material that can result from such a process may have randomly placed methyl groups, so-called atactic PP. The lack of long-range order prevents crystallization of such materials, giving amorphous materials that have only very low strength and special qualities suitable for niche end use.

  Ziegler-Natta catalysts limit the incoming monomers to a specific orientation and can only add them to the polymer chain if they are pointing to the right. Many commercially available polypropylenes are made using such Ziegler-Natta catalysts that produce many isotactic polypropylenes. Although methyl groups are consistently on one side, such molecules tend to wind in a helical shape; these helices then form crystals next to each other, and many of that in commercial polypropylene Give the desired properties.

  An engineered more precisely made Kaminsky catalyst was produced that provided a much higher level of control. Based on metallocene molecules, these catalysts use organic groups to control the monomer added, and a suitable choice of catalyst is isotactic, syndiotactic, or atactic polypropylene, or even a combination thereof Can be generated. Apart from this qualitative control, they allow a better quantitative control and show a much higher proportion of the desired stereoregularity than the previous Ziegler-Natta technology. They can also result in a narrower molecular weight distribution than traditional Ziegler-Natta catalysts, further improving the properties.

  To produce rubbery polypropylene, a catalyst can be made that has isotactic polypropylene but has organic groups that affect the stereoregularity held in place by relatively weak bonds. After the catalyst has produced a short length of polymer that can be crystallized, the choice of catalyst is used so that light of the appropriate frequency is used to break this weak bond and the remaining length of the chain is atactic. Remove sex. The result is an almost amorphous material with small crystals embedded in it. Each chain has one end in the crystal, but many of its lengths have soft amorphous masses, so the crystalline region serves the same purpose as vulcanization.

  Polypropylene melt processing can be achieved by extrusion and molding. Common extrusion methods include the production of meltblown and spunbond fibers, forming long rolls for future conversion to various useful products such as face masks, filters, diapers and wipes. The most common shaping technique is injection molding, which is used for parts such as cups, cutlery, vials, caps, containers, household items and automotive parts such as batteries. Related techniques of blow molding and injection stretch blow molding, including both extrusion and molding, are also used.

  Many end-use applications for PP are often possible due to the ability to tailor grades and additives with specific molecular properties during their manufacture. For example, an antistatic additive can be added to help make the PP surface resistant to dust and dirt. Many physical finishing techniques, such as machining, can also be used for PP. Surface treatment can be applied to PP parts to promote adhesion of printing inks and paints.

  Since polypropylene is resistant to fatigue, many plastic hinges, such as those on flip top bottles, are made from this material. However, chain molecules are directed across the hinge to maximize strength. An ultra-thin sheet of polypropylene is used as the dielectric in certain high performance pulse and low loss RF capacitors.

  A high purity piping system is constructed using polypropylene. Stronger, more rigid piping systems intended for use in drinking piping systems, hot water circulation heating and cooling, and reclaimed water applications are also produced using polypropylene. This material may be selected for its resistance to erosion and chemical leaching, its resistance to many forms of physical damage, including impact and freezing, and its ability to be joined by thermal fusion rather than gluing. Many.

  Because polypropylene can withstand the heat in autoclaves, many plastic products for medical or experimental use can be made from polypropylene. Also, due to its heat resistance, it can be used as a consumer grade kettle manufacturing material. The food containers made from it do not melt in the dishwasher and do not melt during industrial hot-fill processing. For this reason, many plastic tabs for dairy products are polypropylene (both are heat resistant materials) sealed with aluminum foil. When the product is cooled, the tab is often provided with a lid made from a low heat resistant material such as LDPE or polystyrene. Such containers provide a good example of the coefficient difference, as the elastic (softer, more flexible) feel of LDPE is readily apparent for the same thickness of PP. Rugged, translucent, reusable plastic containers made in various shapes and sizes for consumers from various companies such as Rubbermaid and Sterlite are commonly made from polypropylene, but with lids Often made from LDPE, which is somewhat more flexible, they can snap the container to close the container. Polypropylene can also be made into disposable bottles to contain liquid, powdered or similar consumer products, but HDPE and polyethylene terephthalate are also commonly used to make bottles. It is done. Plastic buckets, car batteries, trash cans, cooler containers, dishes and pitchers are often made from polypropylene or HDPE, both having a rather similar appearance, feel, and properties at ambient temperature.

  Polypropylene is the primary polymer used in nonwovens, and more than 50% is used for diapers or hygiene products and absorbs water rather than repels itself naturally (hydrophobic) (hydrophilic) ) Is processed as follows. Other interesting nonwoven uses include filters for air, gases and liquids, allowing fibers to be formed into sheets or webs, pleated and filtered with varying efficiencies in the 0.5-30 micron range. A cartridge or layer can be formed. Such applications can be found in the house as water purification filters or air-conditioning filters. High surface area and naturally hydrophobic polypropylene nonwovens are ideal oil spill absorbers with floating barriers that are easy to use near the oil spill above the river.

  A common use for polypropylene is as biaxially oriented polypropylene (BOPP). These BOPP sheets are used to make various materials including transparent bags. When polypropylene is biaxially oriented, it becomes clear and clear and serves as an excellent packaging material for artistic and retail products.

  The most common medical use of polypropylene is Ethicon Inc. In synthetic nanoabsorbable suture Prolene manufactured by

  Polypropylene is most commonly used for plastic molding that is poured into a mold while melting and forms complex shapes at relatively low cost and high volume, examples include bottle tops, bottles and joinery .

  In recent years it has been produced in sheet form, which is widely used for the production of stationery folders, packaging and storage boxes. Due to its wide color range, durability and stain resistance, it becomes ideal as a protective cover for paper and other materials. It is also used in Rubik's cube stickers because of these features.

  Expanded polypropylene (EPP) is a foamed polypropylene. EPP has very good impact properties due to its low stiffness; this allows the EPP to regain its shape after impact. EPP is widely used by enthusiasts in model airplanes and other radio control vehicles. This is mainly due to its ability to absorb shocks, making it an ideal material for RC airplanes for beginners and amateurs.

Silicon dioxide (SiO2)
The compound silicon dioxide, also known as silica, is an oxide of silicon having the chemical formula SiO2. Silicon oxides commonly referred to as “SiOx” include silicon dioxide. Silica is found most commonly naturally as sand or quartz, as well as in diatom cell walls. It is the main component of many types of materials such as glass and concrete. Silica is the most abundant mineral in the crust.

  SiO2 has several different crystalline forms in addition to amorphous. With the exception of schisovite and fibrous silica, all crystal forms contain tetrahedral SiO4 units connected together by shared vertices in different arrangements. The silicon-oxygen bond length varies between different crystal forms. In quartz, the angle of Si—O—Si is 144 °. The only stable form under normal conditions is a-quartz, which is the form normally encountered by silicon dioxide crystals.

  Silicon dioxide is formed when silicon is exposed to oxygen (or air). A very thin layer of so-called “native oxide” (about 1 nm or 10 Å) is formed on the surface when silicon is exposed to air under ambient conditions. Good quality of silicon dioxide on silicon using high temperatures and alternative environments, for example at temperatures between 600-1200 ° C., using so-called “dry” or “wet” oxidation, using O 2 or H 2 O, respectively. To grow a controlled layer. The thickness of the silicon layer replaced by the dioxide is 44% of the thickness of the silicon dioxide layer produced. Alternative methods used to precipitate the layer of SiO 2 include low temperature oxidation of silane (400-450 ° C.); decomposition of tetraethylorthosilicate (TEOS) at 680-730 ° C .; TEOS at about 400 ° C. Plasma chemical vapor deposition used; polymerization of tetraethylorthosilicate (TEOS) at less than 100 ° C. using amino acids as catalysts.

  Calcined silica, which is a very fine particle form of silicon dioxide (sometimes called fumed silica or silica fume), burns SiCl4 in an oxygen-rich hydrocarbon flame to produce a "smoke" of SiO2. It is prepared by. Amorphous silica, silica gel, is produced by acidifying a solution of sodium silicate to produce a gelatinous precipitate, followed by washing and dehydration to produce colorless porous silica.

Aluminum oxide (Al2O3)
Aluminum oxide is an amphoteric oxide of aluminum having the chemical formula Al2O3. It is also commonly referred to as alumina, corundum, sapphire, ruby or aloxite. Aluminum oxide is an electrical insulator but has a high thermal conductivity (40 Wm-1K-1) for ceramic materials. In its most commonly present crystalline form, called corundum or a-aluminum oxide, its hardness makes it suitable for use as an abrasive and as a part in a cutting tool. Aluminum oxide causes the resistance of metal aluminum to weathering. Metallic aluminum is very reactive with atmospheric oxygen and a thin protective layer of alumina (4 nm thick) forms on the exposed aluminum surface within about 100 picoseconds. This layer protects the metal from further oxidation. The thickness and properties of this oxide layer can be enhanced using a process called anodization. Some alloys, such as aluminum bronze, take advantage of this property by including a certain percentage of aluminum in the alloy to enhance erosion resistance. Although the alumina produced by anodization is typically amorphous, discharge assisted oxidation processes such as plasma electrolytic oxidation result in a significant proportion of crystalline alumina in the coating and enhance its hardness. The most common form of crystalline alumina, a-aluminum oxide, is known as corundum. Alumina is also present in other phases. Each has a unique crystal structure and properties. Aluminum hydroxide mineral is the main component of bauxite, the main ore of aluminum. Alumina, for example, tends to be multiphase, comprising several alumina phases rather than just corundum.

Polyvinyl alcohol (PVOH, PVA, or PVAL)
Polyvinyl alcohol (PVOH, PVA, or PVAL) is a water-soluble synthetic polymer. Polyvinyl alcohol has excellent film forming properties, emulsifying properties, and adhesive properties. It is also resistant to oils, greases and solvents. It is odorless and non-toxic. It has high tensile strength and flexibility, and high oxygen and aroma barrier properties. However, these properties depend on humidity, in other words, the higher the humidity, the more water is absorbed. Water acting as a plasticizer then decreases its tensile strength but increases its elongation and tear strength. PVA is completely degradable and rapidly soluble. PVA has melting points of 230 ° C. and 180-190 ° C. for full and partial hydrolysis grades, respectively. Since it can be thermally decomposed at high temperatures, it decomposes rapidly at temperatures above 200 ° C.

  PVA is an atactic material but exhibits crystallinity because the hydroxyl groups are small enough to fit into the lattice without destroying it. Unlike many vinyl polymers, PVA is not prepared by polymerization of the corresponding monomer. The monomer vinyl alcohol exists almost exclusively as acetaldehyde, which is a tautomeric form. Instead, PVA is prepared by partial or complete hydrolysis of polyvinyl acetate to remove acetate groups.

A nanopolymer polymer nanocomposite (PNC) is a polymer or copolymer dispersed in its nanoparticles. These may be of different shapes (e.g. platelets, fibers, spheroids), but at least one dimension is in the range of 1-50 nm. The transition from microparticles to nanoparticles results in changes in physical and chemical properties. The two main factors in this are the increased surface area to volume ratio and the size of the particles. Increasing the surface area to volume ratio, which increases as the particles become smaller, results in an increasing dominance of atomic behavior over the surface area of the particles beyond that inside the particles. This affects the properties of the particles when they are reacting with other particles. Because of the higher surface area of the nanoparticles, there is more interaction with other particles in the mixture, which increases strength, heat resistance, etc., and many factors vary for the mixture.

  An example of a nanopolymer is a silicon nanosphere that exhibits completely different characteristics. Its particle size is 40-100 nm, which is much harder than silicon (its hardness is intermediate between that of sapphire and diamond). Many technical applications of biological objects such as proteins, viruses or bacteria such as chromatography, optical information technology, sensors, catalysts and drug delivery require its immobilization. Carbon nanotubes, gold particles and synthetic polymers are used for this purpose. This immobilization was achieved by incorporating these objects as guests in the host matrix to a lesser extent, mainly by adsorption or chemical bonding. In guest-host systems, the ideal way to immobilize biological objects and incorporate them into hierarchical structures is structured at the nanoscale to interact with biological nanoobjects and their environment. Should be easy. Numerous natural or synthetic polymers are available, and because of advances in technology developed to process such systems into nanofibers, rods, tubes, etc., polymers are used for immobilization of biological objects. Become a good platform.

  Polymer fibers are generally produced on a technical scale by extrusion, for example, polymer melt or polymer solution is pumped through a round die and rotated / pumped by a capture device. The resulting fiber typically has a diameter of 10 μm scale or greater. Electrospinning is still a major polymer processing technology still available today to reduce the diameter to the range of a few hundred nanometers or even to a few nanometers. A strong electric field on the scale of 103 V / cm is applied to the polymer solution droplets emerging from the round die. The charge that accumulates on the surface of the droplet causes deformation of the droplet along the direction of the electric field, even if surface tension opposes droplet evolution. In a supercritical electric field, the electric field strength overwhelms the surface tension and the fluid jet diverges from the droplet tip. The jet is accelerated towards the counter electrode. During this transport phase, until the solvent evaporates, the jet is subjected to a powerful electrically induced circular bending motion that causes strong stretching and thinning of the jet, and finally the solid nanofibers are deposited on the counter electrode To do.

  Electrospinning, co-electrospinning, and nanofiber based template methods, in principle, yield infinitely long nano objects. This infinite length is an advantage for a wide range of applications including catalysis, tissue engineering, and implant surface modification. However, in some applications such as inhalation therapy or synthetic drug delivery, a clearly defined length is required. The template method described below has the advantage that it allows the preparation of nanotubes and nanorods with very high accuracy. The method is based on the use of a well-defined porous template, such as porous aluminum or silicon. The basic concept of this method is to take advantage of the wetting process. The polymer melt or solution is contacted with pores placed in a material featuring a high energy surface such as aluminum or silicon. Wetting begins and a thin film having a thickness on the order of tens of nanometers is used to coat the pore walls. This process typically occurs within 1 minute for high viscosity polymers such as polytetrafluoroethylene, for temperatures above the melting point or glass transition temperature of about 50K, which is as high as 10,000. A hole having a certain aspect ratio is also retained. To obtain the nanotubes, the polymer / template system is cooled to room temperature or the solvent is evaporated and the resulting pores are coated with a solid layer. The resulting tubes can be removed mechanically for tubes up to 10 μm in length, for example by just pulling them out of the holes or by selectively dissolving the mold. Nanotube diameter, diameter distribution, uniformity along the tube, and length can be controlled.

  The size-dependent and pressure-dependent glass transition temperatures of free-standing films or supporting films that have weak interactions with the substrate decrease with decreasing pressure and size. However, the glass transition temperature of the supporting film that has a strong interaction with the substrate increases the pressure and decreases the size.

  A nanocomposite is a polymer structure containing a filler, typically a silicate nanoclay, with at least one dimension in the nanometer range. The filler separates into small platelets that are dispersed in the layer matrix. The barrier matrix of the modified polymer is improved because the layer matrix creates a complex path for the gas and attempts to penetrate through the film. However, the challenge is to ensure that the filler dispersion is consistent. In addition to better barrier properties, the nanocomposite modified film also has improved transparency because it has improved dimensional stability and rigidity and increased crystallinity. Nanocomposite masterbatches are commercially available for nylon and polyolefins. The oxygen barrier of the nylon nanocomposite film may be as much as 50 percent higher than unmodified nylon. The polyethylene and polypropylene nanocomposite structures showed 25-50 percent gas barrier improvement and 10-15 percent water vapor barrier improvement in the laboratory setting. Achieving consistent barrier properties on a commercial scale remains difficult. Nanocomposite technology is a very emerging science. It shows considerable promise and it has a significant impact on barrier material options as more options become available for film applications.

Saran Saran, along with other monomers, are trade names for some polymers made from vinylidene chloride (particularly polyvinylidene chloride or PVDC). Saran film has very low permeability to water vapor, flavor and aroma molecules, and oxygen compared to other plastics. A barrier to oxygen prevents damage to the food and a barrier to flavor and aroma molecules helps the food retain its flavor and aroma. Saran also has gas barrier properties.

Polytrimethylene terephthalate (PTT)
Polytrimethylene terephthalate (PTT) is a semi-crystalline polymer that has the same advantages as many PETs. PTT exhibits good tensile strength, bending strength, and stiffness. It has excellent flow and surface finish. PTT may have more uniform shrinkage and better dimensional stability than competing semi-crystalline materials in some applications. PTT has excellent resistance to a wide range of chemicals such as aliphatic hydrocarbons, gasoline, carbon tetrachloride, perchlorethylene, oils, fats, alcohols, glycols, esters, ethers and dilute acids and bases at room temperature . Strong bases can attack PTT compounds. Impact modifiers and reinforcing fibers (long glass, short glass, or carbon) can be used to increase the impact properties, strength and stiffness of PTT.

Polytrimethylene naphthalate (PTN)
Poly (trimethylene phthalate or naphthalate) and copolymers are 1,3-propanediol (PDO) and terephthalic acid (PTT), isophthalic acid (PTI) or naphthalic acid (PTN) and / or comonomers (isophthalic acid, 1,4 -An aromatic polyester prepared by polycondensation with butanediol or the like. PTN films have good barrier properties.

Polyethylene naphthalate (PEN)
Polyethylene naphthalate (PEN) is a polyester with good barrier properties (even better than polyethylene terephthalate). Because it provides a very good oxygen barrier, it is particularly suitable for bottling beverages that are sensitive to oxidation, such as beer. It is prepared from ethylene glycol and one or more naphthalenedicarboxylic acids by condensation polymerization.

Polyurethane Polyurethane is any polymer that consists of a chain of organic units linked by urethane (carbamate) bonds. Polyurethane polymers are formed by sequential polymerization by reacting a monomer containing at least two isocyanate functional groups with another monomer containing at least two hydroxyl (alcohol) groups in the presence of a catalyst. Polyurethane formulations contain an extremely wide range of stiffness, hardness, and density. The properties of polyurethane are mainly determined by the choice of polyol, but diisocyanates have some influence and must be suitable for their use. The cure rate is affected by the reactivity of the functional groups and the number of functional isocyanate groups. Mechanical properties are affected by functionality and molecular shape. The choice of diisocyanate also affects the stability of the polyurethane upon exposure to light. Polyurethanes made with aromatic diisocyanates turn yellow with exposure to light, while those made with aliphatic diisocyanates are stable. Softer, elastic, and more flexible polyurethanes typically occur when creating urethane linkages using linear bifunctional polyethylene glycol segments, called polyether polyols. This strategy is used to make spandex elastic fibers and soft rubber parts, as well as cellular rubber. When polyfunctional polyols are used, more rigid products are obtained, but these again create a three-dimensional cross-linked structure that may be in the form of low density bubbles.

Polyether block amide (PEBAX (registered trademark))
Polyether block amides are thermoplastic elastomers or flexible polyamides that do not contain a plasticizer consisting of a regular linear chain of rigid polyamide segments and flexible polyether segments.

Parylene C
Parylene is the trade name for various chemical vapor deposited poly (p-xylylene) polymers used as humidity barriers and electrical insulators. Of them, Parylene C is the most popular due to its combination of barrier properties, cost, and other manufacturing advantages.

Silicones , also called silicone polymerized siloxanes or polysiloxanes, are mixed inorganic-organic polymers with the chemical formula [R2SiO] n, where R is an organic group such as methyl, ethyl, or phenyl. These materials consist of an inorganic silicon-oxygen skeleton (...- Si-O-Si-O-Si-O -...) that is tetracoordinated and has organic side groups bonded to silicon atoms. In some cases, organic side groups can be used to link two or more of these -Si-O- skeletons together. By varying the length of the -Si-O-chain, side groups, and crosslinking, silicones with various properties and compositions can be synthesized. They may vary in consistency from liquid to gel, rubber, hard plastic. Many common siloxanes are linear polydimethylsiloxane (PDMS), silicone oil. The second largest group of silicone materials are silicone resins, formed by branched and caged oligosiloxanes.

Fabrication of composite walls Various layers of composite walls, including gas barrier layers, do not need to be placed in any particular order, but have excellent acidity, temperature, mechanical wear resistance, and excellent biocompatibility profiles Are preferably used as the layer in contact with the gastric environment. For example, those having excellent resistance to acidity and temperature are preferably used as the layer in contact with the central lumen of the balloon.

  The various layers of the wall may comprise a single layer or up to 10 or more different monolayers; however, 0.001 so that the resulting balloon is compressed to fit into a swallowable capsule. Film thicknesses from inches (0.0254 cm) to 0.004 inches (0.010 cm) are desirable. The resulting composite wall preferably has good performance specifications for each category listed in Tables 1a-b.

  Co-extruded films are advantageously used because some adhesives can contain exudates that are undesirable from a biocompatibility standpoint. In addition, coextrusion allows for better mixing such that when combined in this manner, the material retains its original properties and is less likely to undergo delamination when exposed to gastric motility. To.

Combining films with similar properties in the composite wall, for example two film layers with excellent gas barrier properties, for use in gastric balloons containing nitrogen, oxygen, CO ₂ or mixtures thereof as inflation gases, Or, it is advantageous if the external environment in which the product is placed, for example if the stomach contains a gas mixture containing CO ₂ . The main advantage of such a composite film is that limitations on film thickness can be observed without sacrificing gas barrier properties. Such a configuration also contributes to reducing the effects of damage due to processing damage (eg, manufacturing and compression) and exposure to conditions in vivo (eg, gastric motility).

  In a particularly preferred embodiment, the composite wall includes a plurality of layers. The first layer is an outer protective layer configured for exposure to the intragastric environment. This layer is resistant to mechanical forces, exposure to water (steam), wear, and high acidity levels. Nylon, or more specifically nylon 12, is particularly preferred for layers exposed to the gastric environment and is particularly resistant to mechanical forces.

  In an alternative embodiment, the polyurethane is RF welded to Saran to obtain a 6-7 mil thick composite wall. In another aspect, a five-layer system is provided that includes a layer of saran sandwiched between two polyurethane layers. There is a tie layer between the Saran layer and each polyurethane layer. The layers can be welded together, coextruded, or bonded using an adhesive. The three layers are then coextruded on each side against nylon and a final sealing layer (such as polyethylene) is added to one of the nylon layers for the entire composite wall. Representative examples of material combinations that are commercially available or manufacturable are provided in Table 2. Layer orientation (innermost-contact with central balloon lumen, or outermost-contact with gastric environment) is also shown when more than two layers are described as supporting the suggested composite wall It is.

Many of the film resins listed in Table 2 provide some gas barrier properties. Thus, many can be used alone to form the balloon wall as a monolayer film; however, they can be used with other film resins to increase the useful life of the balloon based on the inflation gas and the external environment in which the balloon is placed. The desired gas retention and mechanical specifications can also be met. These film resins can also be coated using the gas barrier coatings listed in Tables 1a-b. Additional layers can be added to form the entire composite wall. Such additional layers may not impart substantial barrier film properties, but they may be against other layers of the composite wall that are sensitive to structural and / or mechanical properties, water vapor, humidity, pH, etc. Protection or other desirable properties can be provided. Film layers can be assembled using various adhesives, by coextrusion, by lamination, and / or using tie layers, etc., with special gas retention properties, for at least 25 days, or up to 90 days or more Composite walls can be created that meet the requirements of intragastric balloons suitable for a wide range of uses. Table 2 provides a list of layers and layer combinations suitable for use in composite walls for intragastric balloons. Lists composite material descriptions, resin abbreviations, configurations (single layer, double layer, triple layer, etc.) and commercially available combination trade names. The number of layers shown does not include any adhesive layer or tie layer used to fabricate the composite wall; a 6-layer composite wall is, for example, two or three adhesive layers that make up the entire composite wall and / or Or it may have a bonding layer, so the total number of layers may be 8 or 9 in the final form. As used herein, the term “layer” is a broad term, given its ordinary and customary meaning to one of ordinary skill in the art (and is not limited to a special or customized meaning) Although not, a single thickness of a uniform material (eg, a coating such as SiOx, or a layer such as PET, or a uniform polymer mixture), and a support layer having a coating thereon (where “ “Coating” refers to, for example, a material typically used with a substrate that provides structural support to the coating layer). For example, a PET-SiOx “layer” refers herein to a layer of Si—Ox provided on a supporting PET layer. In the following tables, as well as other tables related to composite walls, a forward slash (“/”) indicates a boundary between specific chemical layers. The boundary may be discontinuous or may be a tie layer, adhesive layer, or other layer that separates the described chemical layers.
Table 2

  In particularly preferred embodiments, the composite wall has a thickness of 0.005 inches or less (5.0 mils or less); however, in certain embodiments, thicker composite walls may be tolerated. Typically, the composite wall has a thickness of 0.004 inches (4.0 mils) or less.

Balloon Fabrication To ensure good mechanical strength of the balloon, it is preferable to thermoform and seal so that the ends of the pieces used to form the balloon overlap. This can be achieved by any suitable method. For example, two flat sheet materials can be placed in a frame having magnetized edges to hold the two sheets in place. Looseness can be added to the film strip to direct the material to retain its properties after the thermoforming process. The frame can be placed on a balloon mold which is a hemisphere. A heater (eg, a 4520 watt infrared heater) can be used to form the material and depressurize. The material that has loosened before the vacuum is applied will redirect the material so that it is more evenly distributed around the hemisphere. The material is preferably made thickest at the center and thinner at the sides, where it is welded to the second piece to create a sphere or ellipsoid having a substantially uniform wall thickness. Can do. For example, starting from a 0.0295 ″ film, the middle or subsequent tip of the film has a final film thickness of 0.0045 ″ and the ends are of subsequent overlay during the welding process. Therefore, it has a final thickness of 0.0265 ″.

  The bulb may be bonded to one (eg, polyethylene, PE) side of the hemisphere and protrude from the opposite (eg, nylon) side. One hemisphere is typically made of nylon as the outermost layer, and the second hemisphere typically has polyethylene (sealing web) as the outermost layer. The ends of the two hemispheres are preferably aligned so that they overlap at least 1 mm and no more than 5 mm. The alignment and overlay of the two hemispheres is done to offset the thinning at the edges during the thermoforming process and then inhibit the rupture of the seam in vivo. Place each half of the sphere on the fixture and cut off excess from the thermoforming process. On the multilayer film, a sealing layer, PE or similar layer is bonded to the sealing layer of the second film half. To do this, a hemispherical film with nylon exposed to the outside environment is 1/2 along the edge of the sphere so that it can be bonded to the hemisphere using polyethylene on the outermost layer. Fold 2

  The two film pieces are then sealed using a roller bonder or band heater. In a roller bonder, air provides compression, a heater provides sealing heat, and a motor that moves the bonder around the area controls the time required to ensure proper sealing. In band heaters, there are heating elements, expandable plugs that provide compression, and timers. The band is metal, preferably copper, and fasteners such as spools provide the required compression. The use of film layers of different melting points helps to ensure the integrity of the barrier layer of the final balloon configuration. An insulator can be used when welding two similar materials. In a preferred embodiment, one sphere is provided with an outwardly facing nylon layer and the second sphere has an outwardly facing PE layer.

The largest percentage of malfunctions of balloon intragastric balloons that are resistant to spontaneous contraction is due to spontaneous contraction. Spontaneous contractions are: (1) external puncture of the intragastric balloon due to gastric motility, (2) overexpansion due to increased balloon pressure resulting from uptake of gas and water vapor in the gastric environment, and (3) excess Can result from underexpansion of the balloon resulting in fatigue of the material and subsequent balloon puncture. By managing these two variables and adjusting these variables to withstand the dynamic gastric environment, the balloon system is adjusted to ensure that it remains inflated throughout its useful life Can do. This example of spontaneous contraction in the intragastric balloon can be minimized by the choice of the starting inflation gas along with the choice of composite wall material and construct. The choice of gas permeation characteristics for water vapor permeation and gas permeability of the composite wall to take advantage of the properties of the gastric space contents can control the rate of gas diffusion into and out of the balloon. This method allows a tunable method for preventing underexpansion and overexpansion.

  Another phenomenon seen with gastric balloons and obesity is generally gastric adaptation. In the process of gastric adaptation, the stomach grows to accommodate space-occupying devices or excess food consumed. In the process of gastric adaptation, the volume of the stomach containing the intragastric balloon grows with time and the patient becomes hungry. However, by controlling gas diffusion and water vapor permeation across the balloon wall over time, the size of the balloon can be adjusted to maintain weight loss, starting inflation gas and other in vivo gas permeability characteristics of water and film. Can be increased over time by selecting. In addition to spontaneous contraction, select the permeability characteristics of the composite wall in conjunction with the starting gas, and use the gas and water movement inside the balloon from the gastric environment to make the balloon durable in response to gastric adaptation. Can be designed to grow over a lifetime.

Experiments were conducted to select various starting inflation gases with a changing external gas environment that mimics the gastric and water environment in vivo. The gastric environment consists of water, acid (hydrochloric acid), a mixture of gases, and sputum (a partially digested food semi-fluid mass released by the stomach into the duodenum). Gastric gas usually results from swallowing air while eating. The composition of air is: nitrogen (N ₂ ) 78.084%; oxygen (O ₂ ) 20.9476%; argon (Ar) 0.934%; carbon dioxide (CO ₂ ) 0.0314%; neon (Ne) 0 Methane (CH ₄ ) 0.0002%; Helium (He) 0.000524%; Krypton (Kr) 0.000114%; Hydrogen (H ₂ ) 0.00005%; and Xenon (Xe) 0.0000087 %.

Five gases: N ₂ , O ₂ , CO ₂ , H ₂ and methane account for over 99% of the gas in the gastrointestinal system, with nitrogen predominating. The pCO ₂ of the stomach is closely parallel to the pCO ₂ value of the local (visceral) artery and outflow venous blood. Gastric acid neutralization can also produce gas. For example, when gastric acid reacts with bicarbonate in the digestive fluid (eg when present in certain antacids), the chemical process produces CO ₂ and is normally absorbed into the bloodstream. Mainly via the fermentation by colonic bacteria, digestion of food in the intestine, CO _2, H _2, and to produce methane. Microorganisms are considered to be the only source of all hydrogen and methane produced in the gut. These arise from the fermentation and digestion of nutrients (polysaccharides derived from fruits and vegetables are not digested in the small intestine). Small amounts of several other gases such as hydrogen sulfide, indole, and ammonia can also be generated.

In certain embodiments, it is preferred that the composition of the initial fill gas is substantially characteristic of the composition of the gas mixture in the in vivo gastric environment. Such initial charge gases may contain only N ₂ and CO ₂ , or may contain only N ₂ , CO ₂ , and O ₂ , or are present in the N ₂ and CO ₂ and in vivo environment. One or more other gases (eg, water vapor, H ₂ , CH ₄ , Ar, H ₂ S, or NH ₃ ) may be included. Argon or another inert gas (or multiple inert gases) can be partially or wholly replaced with N _2, which is considered an inert gas in the context of the preferred embodiment. In embodiments where the fill gas comprises only N ₂ or CO ₂ , the initial fill gas is about 75% v / v to about 96% v / v N ₂ , about 5% v / v to about 15% (vol.). O ₂ , and about 1% v / v to about 10% v / v CO ₂ , more preferably about 80% (vol.) To about 85% (vol.) N ₂ , about 5% (vol.). to about _{13% (vol.) O 2} , and about 4% (vol.) to about 8% (vol.) preferably comprises a CO ₂ for. In embodiments where the fill gas contains only N ₂ or CO ₂ , the initial fill gas contains about 4% (vol.) To about 8% (vol.) CO ₂ with the remainder being N ₂ or another inert gas. Preferably there is. In embodiments where the initial charge gas includes other gases in addition to CO ₂ and inert gas, the initial charge gas preferably includes from about 4% (vol.) To about 8% (vol.) CO ₂ .

Controlled self-inflation of the intragastric balloon in an in vivo environment using a semi-permeable or permeable composite wall in the balloon and a single preselected gas such as N ₂ or O ₂ initially in the balloon This can be achieved by filling. Balloons take advantage of gas concentration differences and water concentration differences between the internal balloon environment and the in vivo external environment (GI / stomach) to increase and / or decrease volume and / or pressure over time. In order to achieve a controlled drop in volume and / or pressure, the permeability to a single gas used to inflate the balloon is relative to other gases present in the in vivo gastrointestinal environment. High walls can be used. For example, when nitrogen gas is used as an inflation gas over time in an in vivo environment, the volume and / or pressure in the balloon decreases as nitrogen diffuses through the oxygen permeable wall into the in vivo environment. Similarly, when oxygen gas is used as an inflation gas over time in an in vivo environment, the volume and / or pressure in the balloon decreases as oxygen diffuses through the oxygen permeable wall into the in vivo environment. The difference between the partial pressure of the single gas in the balloon (higher) and the partial pressure of the in vivo environment (lower) induces the process until equilibrium or homeostasis is achieved. To achieve a controlled increase in volume and / or pressure, it is relatively less permeable to a single gas used to inflate the balloon than other gases present in the in vivo gastrointestinal environment Walls can be used. For example, when nitrogen gas is used as an inflation gas over time in an in vivo environment, the volume and / or pressure in the balloon is such that CO ₂ present in the gastric environment, and all other gases are CO ₂ permeable walls. Increases as it diffuses through and into the balloon. The difference between the partial pressure of the permeable gas in the balloon (lower) and the partial pressure of the in vivo environment (higher) induces the process until equilibrium is achieved.

In addition, balloon inflation is maintained and / or controlled using the concentration difference between the internal balloon environment and the external gastric environment to increase or decrease the balloon volume / pressure as necessary to increase the useful life of the product. It can be extended. One reason for reducing the pressure is to first inflate the balloon with larger but more diffusible / soluble gas molecules such as CO ₂ as well as more inert gases such as nitrogen. The balloon may be pre-stretched, the soluble gas diffuses out of the balloon, and other gases originally present in the balloon move to fill the balloon.

An inflation gas can be selected to start with most of the gas in the balloon, including large inert gases or gases with low diffusivity through selected composite walls. Examples of inert gases include, but are not limited to, nitrogen and SF ₆ , C ₂ F ₆ , C ₃ F ₈ , C ₄ F ₁₀ , C ₄ F ₈ , C ₄ F ₈ , C ₃ F _6, CF _4, and CClF ₂ -CF ₃ and the like. Combining the inert gas with a less inert gas that is more soluble in the gastric environment so that the inert gas contains a starting balloon inflation gas composition that is in excess of the more soluble / diffusible gas Can do. In certain embodiments, nitrogen as a more soluble / diffusible gas and SF ₆ , C ₂ F ₆ , C ₃ F ₈ , C ₄ F ₁₀ , C ₄ F ₈ , C ₄ F ₈ , C ₃ F Preferably, a combination with a less diffuse / soluble gas such as ₆ , CF ₄ , and CClF ₂ —CF ₃ is used. For example, certain embodiments of the fill gas may include 95% (vol.) Less soluble / diffusible inert gas (e.g., 5% (vol.) With a highly soluble / diffusible inert gas (e.g., 5% 95% SF ₆ with N ₂ of N); or 90% soluble / diffusible inert gas with 10% highly soluble / diffusible inert gas (eg, 90% with 10% N ₂ SF ₆ ); or 15% soluble / diffusible inert gas, 85% less soluble / diffusible inert gas (eg, 85% SF ₆ with 15% N ₂ ); or 20% 80% soluble / diffusible inert gas with 80% soluble / diffusible inert gas (eg 80% SF ₆ with 20% N ₂ ); or 25% highly soluble / diffusible 75% soluble / diffusible with inert gas Low inert gas (e.g., with 25% N ₂ 75% of the SF _6); with or 30% of the soluble / diffusible high inert gas, 70% of the soluble / diffusible low inert gas (e.g., 70% SF ₆ with 30% N ₂ ); or 35% highly soluble / diffusible inert gas and 65% less soluble / diffusible inert gas (eg, 65% with 35% N ₂ % SF ₆ ); or 40% soluble / diffusible inert gas and 60% less soluble / diffusible inert gas (eg, 60% SF ₆ with 40% N ₂ ); or 45% soluble / diffusible inert gas, 55% less soluble / diffusible inert gas (eg, 55% SF ₆ with 45% N ₂ ); or 50% soluble / diffusible 50% soluble with high inert gas / Diffusivity low inert gas (e.g., SF ₆ 50% with 50% of N ₂₎ may contain. In certain embodiments, an initial charge gas consisting of 20% inert gas with low solubility / diffusivity and the remainder with inert gas having high solubility / diffusivity is used; or 19-21% solubility / diffusivity Use an initial charge gas consisting of a low inert gas and the remainder soluble / diffusible inert gas; or 18-22% inert / low diffusible inert gas and the remainder soluble / diffusible Use an initial charge gas consisting of a high inert gas; or use an initial charge gas consisting of 17-23% inert / less diffusible inert gas and the remainder soluble / diffusible inert gas. Or use an initial charge gas consisting of 16-24% inert gas with low solubility / diffusivity and the remainder with inert gas with high solubility / diffusivity; or 15-25% low solubility / diffusivity Inactivity And the gas, the remainder is used the initial gas charge consisting of the soluble / diffusible high inert gas. For example, with 18-20% SF ₆ , the remainder with an initial fill gas containing nitrogen, or 19-21% SF ₆ , the remainder with an initial fill gas containing nitrogen; or 18-22% SF ₆ with a remainder Is an initial fill gas containing nitrogen; or, with 17-23% SF ₆ , the remainder is an initial fill gas containing nitrogen; or with 16-24% SF ₆ , the remainder is an initial fill gas containing nitrogen; or 15-25 An initial charge gas containing nitrogen with% SF ₆ can be used.

The patient's diet and medication can also affect / control the inflation state of the balloon, mainly by the effect of CO ₂ concentration produced in the gastric environment. In addition, gastric pH also affects CO ₂ concentration. This particular method is also based on whether composite wall materials, such as barrier / non-barrier and diffusing gas, are maintained longer in the balloon if they have barrier and non-barrier walls. Allows adjustment to a high degree of service life. This particular form of self-inflation can be achieved with a self-expanding gastric balloon (eg, initially inflated by a gas-producing reaction in the balloon initiated after swallowing), or an inflatable gastric balloon (eg, nasogastric or Delivered by any other delivery method, inflated with a catheter, with or without the aid of an endoscope. This method can be used with any swallowable balloon and any gastric balloon, such as, for example, a balloon placed in the stomach by endoscopic methods. This method is particularly preferred for use with intragastric devices; however, it can also be applied for use in, for example, pulmonary artery wedge catheters and urinary incontinence balloon devices. Advantages to this technique include the ability to compensate for gastric adaptation, which allows the balloon to fit into the stomach and maintains the patient's fullness by increasing volume over time. Thereby, it is also possible to start with a smaller amount of inflation gas component for a self-expanding balloon. By using a diffusion gradient between the gastric balloon system and the in vivo gastric environment, it can prevent spontaneous contractions.

In a particularly preferred embodiment, used with a suitable inert gas such as SF ₆ and / or N ₂ as expansion gas (with or without CO ₂ as additional expansion gas), a multilayer co-layer for the wall layer is used. An extruded mixture is used. A particularly preferred configuration is nylon 12 / ethyl methyl acrylate / polyvinylidene chloride / ethyl methyl acrylate / nylon 12 / linear low density polyethylene + low density polyethylene (also called coextruded nylon 12 encapsulated PVDC-nylon 12-LLDPE + LDPE multilayer). is there. Another particularly preferred configuration is coextruded multilayer nylon 12 / linear low density polyethylene + low density polyethylene. Varying the choice of resin for composite wall construction (as well as the choice of coextrusion method or use of adhesives), compliance (stretchability), puncture resistance, thickness, adhesion, hermetic bond strength, orientation, acid resistance, and The permeability to gas and water vapor to achieve a specific effect can be controlled.

A mechanism for reliably controlling the timing of deflation is provided for the self- deflating (also referred to as self-expanding) or inflating (also referred to as manual inflating) intragastric balloons of intragastric balloon systems. In a preferred embodiment, the balloon self-deflates, passes through the stomach, passes through the lower gastrointestinal tract and exits the body at the end of its predetermined useful life (involuntary), preferably between 30 and 90 days. Time can be adjusted to contract into the stomach. In preferred embodiments described below, the timing of contraction is achieved by the external gastric environment (eg, by temperature, humidity, solubility, and / or pH conditions) or by the environment within the lumen of the inflated balloon. Can do. It is preferable for consistency to control the start of the self-deflation process by manipulating the internal balloon environment.

  In other embodiments, one or more additional patches or other structures applied to the patch and / or balloon construct applied to allow an inverted seam as described above may be erodible, degradable, or Made from a soluble material (natural or synthetic) and incorporated into the balloon wall. The patch is of sufficient size to ensure an opening with sufficient surface area to cause rapid contraction and to prevent reinflation due to leakage of gastric fluid into the balloon. The balloon patch comprises a material that can be applied to the balloon such that a substantially flat surface is maintained, and preferably comprises a single layer or a multilayer material. Patches are erodible, disintegrating, degradable or preferably other materials that are tissue compatible and degrade into non-toxic products, or slowly hydrolyze and / or degrade over time. Materials such as poly (lactic acid-co-glycolic acid) (PLGA), poly (lactide-co-glycolide) (PLG), polyglycolic acid (PGA), polycaprolactone (PCL), polyesteramide (PEA), poly Hydroxyalkanoate (PHBV), polybutylene succinate adipate (PBSA), aromatic copolyester (PBAT), poly (lactide-co-caprolactone) (PLCL), polyvinyl alcohol (PVOH), polylactic acid (PLA), poly -L-lactic acid PLAA, pullulan, polyethylene glycol (P G), polyanhydrides, polyorthoesters, poly aryl ether ketone (PEEK), multiblock polyether esters, Porigurekapuron, polydioxanone, is constructed using polytrimethylene carbonate, and other similar materials). These erodible, disintegratable, or degradable materials can be used alone or in combination with other materials, or cast / coextruded into a mold with a non-erodible polymer such as PET, It can be laminated and / or dip coated and used in the construction of balloons. Degradation / erosion occurs by the gastric environment (eg, by temperature, humidity, solubility, and / or pH conditions), is initiated and / or controlled, or balloons based on what the patch is exposed to In the lumen (eg, depending on humidity and / or induced pH conditions). The environment that affects the polymer thickness and the timing of degradation and exposure can also facilitate the timing of degradation. Degradation / erosion is timed so that they occur once a given balloon service life is complete (eg, inflation occurs in the stomach before degradation / erosion results in the formation of an opening that allows contraction). maintained in vivo for 25-90 days). Instead of (or in conjunction with) a degradable material for the patch, the patch is adhered or welded to the balloon using a similar fluid retention barrier film or weak adhesive, or for a specified amount of time. Later, it may include the same film as the remaining wall of the balloon that peels away from the area where the patch is applied and is bonded so that the opening for inflation fluid discharge allows for deflation. Alternatively, the composite wall of the entire balloon can be made from an erodible material if deemed necessary for rapid deflation. Mechanisms using erodible materials or materials that become mechanically non-functional after a predetermined time are similar for all aspects relating to the contraction mechanism described below as well. The timing of degradation or erosion can be controlled using the external gastric environment (eg, by temperature, humidity, solubility, and / or pH conditions) and / or by conditions within the lumen of the balloon (eg, , Depending on the humidity and / or pH conditions of the residual liquid in the balloon).

  In other embodiments, a plug or a plurality of plugs (optionally with another degradable retention structure) can be incorporated into the balloon construct, all or part of the above (eg, PLGA, PLAA, It may consist of erodible, disintegratable or otherwise degradable synthetic or natural polymers similar to PEG). Plugs can be formed into various shapes (eg, cylindrical shapes) to achieve various surface: volume ratios to provide a preselected and predictable bulk degradation pattern for erodible polymers it can. The plug is chemically exposed after decomposition / erosion has begun, creating a passage for fluid release and subsequent balloon contraction, as the septum or plug material jumps out of the balloon or falls into the interior of the balloon. It may include a release mechanism that can be initiated. Mechanical adjuncts that can be used with the plug are housed within a degradable / erodible / degradable material or retaining structure or plug structure that holds the plug (eg, of non-degradable or degradable material) in place. Including a compression spring. More specifically, one preferred embodiment for achieving shrinkage may include a housing, a radial seal, a solid erosion core, and a protective film attached to the outer surface of the erosion core. The interior of the erodible core is exposed to the inner balloon liquid. The core creates a compressive force that holds the seal against the housing. As the core erodes, the compression between the housing and the radial seal decreases until there is a clearance between the housing and the seal. Once there is clearance, the gas can move freely from the inside of the balloon to the outside environment. The seal may fall from the housing and enter the balloon. The diameter, length, and type of material can be adjusted to create a contraction at a desired time. Exemplary materials for each part used to achieve this contraction mechanism may be as follows: Enclosure: biocompatible, capable of withstanding sufficient radial force to form an air seal Structural material. Possible materials include polyethylene, polypropylene, polyurethane, UHMWPE, titanium, stainless steel, cobalt chrome, PEEK, or nylon. Radial seal: A radial seal needs to be composed of a biocompatible elastic material that can provide a liquid and gas barrier to an acidic environment. Possible materials include silicon, polyurethane, and latex. Eroded Core: The eroded core needs to be a material that can break at a predictable rate in a given environmental condition. Possible materials include PLGA, PLA, or any other material listed above that provides other polyanhydride or erosion properties that can lose integrity over time.

  For the spring mechanism, once the material has decomposed, the spring is released and / or the plug / septum is pulled into or pushed out of the balloon, so once the spring mechanism is released and the plug is When the opening is created by extrusion or drawing, the fluid is released.

  Another preferred embodiment includes a septum, a moisture erosion material inside the injection port, and a moisture absorption expanding material. When the erodible material is exposed to moisture, it slowly erodes and eventually exposes the moisture absorbing extension material. When the moisture expanding material begins to absorb moisture, the expansion pulls the septum out of position on the head by pushing against the septum lip or ring attached to the septum. Pulling the septum out of position causes an immediate deflation of the balloon. To protect the expansion material from moisture to a desired point in time, the expansion material can be covered in a water barrier material such as parylene as well as a material that slowly decomposes water. Moisture contact can be controlled by a small injection port. The injection port may be a small hole or a wick material that draws moisture in a controlled manner. The desired shrinkage time is achieved by a combination of erodible material, barrier material, and injection port size.

In certain embodiments, the balloon may include one or more plugs in the wall of the balloon containing the compressed pellets or gas release pellets. The pellet may comprise any combination of components that release CO ₂ gas when activated (eg, sodium bicarbonate and citric acid, or potassium bicarbonate and citric acid). The pellets are preferably erodible, disintegrating, or degradable materials that are tissue compatible and break down into non-toxic products or slowly hydrolyze and / or dissolve like plugs and patches described above ( For example, poly (lactic acid-co-glycolic acid) (PLGA), polyvinyl alcohol (PVOH), polylactic acid (PLA), poly-L-lactic acid PLAA, pullulan, polyethylene glycol, polyanhydride, polyorthoester, polyarylether It may be in tablet or rod form protected by ketones (PEEK), multi-block polyether esters, polygrecaprone, polydioxanone, polytrimethylene carbonate, and other similar materials. Plug decomposition / erosion initiates the reaction of the two chemicals in the pellet, followed by the formation of a gas (eg, CO ₂ ). When enough gas is captured or built up, eventually enough pressure is generated to push out the softened polymer material and create larger channels for the CO ₂ gas in the balloon to escape. External pressure (eg, throttling) applied by the stomach to the balloon can contribute to the process of creating larger channels. The dimensions and properties of the plug containing the polymer (diameter, thickness, composition, molecular weight, etc.) guide the timing of degradation.

  In other embodiments, plugs or patches of different shapes or sizes similar to those of the plugs described above can be used in the balloon lumen in a multi-layer configuration including a semipermeable membrane to facilitate balloon deflation. Plugs or patches are degradable / erodible / soluble materials similar to those described above (eg, poly (lactic acid-co-glycolic acid) (PLGA), polyvinyl alcohol (PVOH), polylactic acid (PLA), PLAA, A semipermeable membrane (impervious to osmolite) made of solute or osmolyte (glucose, sucrose, other sugars, salts, or combinations thereof) made from pullulan, and other similar materials Contain the compartments encased by. Once the plug or patch begins to break down or erode, water molecules move down the semipermeable membrane down the water gradient from the higher water concentration region to the lower water concentration region by osmosis. Move into the hypertonic solution in the compartment. The compartment containing the osmolite expands and eventually ruptures, extruding the membrane and disassembled plugs or patches, thereby causing a rapid loss of gas through the newly created channel or area.

  In certain embodiments, a balloon is used that is comprised of a septum, a moisture eroding material inside the injection port, and a moisture absorbing and expanding material. When the erodible material is exposed to moisture, it slowly erodes and eventually exposes the moisture absorbing extension material. When the moisture expanding material begins to absorb moisture, the expansion pulls the septum out of position on the head by pushing against the septum lip or ring attached to the septum. Pulling the septum out of position causes an immediate deflation of the balloon. To protect the expansion material from moisture to a desired point in time, the expansion material can be covered in a water barrier material such as parylene as well as a material that slowly decomposes water. Moisture contact can be controlled by a small injection port. The injection port may be a small hole or a wick material that draws moisture in a controlled manner. The desired shrinkage time is achieved by a combination of erodible material, barrier material, and injection port size.

  Another mechanism for self-shrinking is to create a forced stripping scheme that can provide a larger surface area to ensure rapid shrinkage. For example, in a balloon having a three-layer wall, the outermost layer is substantially strong enough to hold an inflation fluid (eg, polyethylene terephthalate (PET)) and the central layer as a whole is an erodible material (eg, PVOH). Etc.), but the inner layer comprises a weaker material (eg, polyethylene (PE), etc.). The PET or outermost layer is “scored” or hatched with an erodible material to create a small channel that erodes over time. This creates a channel in which gastric juice penetrates into the balloon layer and begins to break down the fully erodible material. When the erodible layer degrades or dissolves, it also erodes, decomposes or dissolves because the material that makes up the innermost layer is not strong enough to naturally withstand the force / environment of the stomach. The balloon then collapses itself and eventually passes through the lower gastrointestinal tract. When the erodible layer is sandwiched between a strong layer and a weak layer, the timing of erosion is facilitated by creating a longer path length than the erodible plug or patch affected by the gastric environment. The distance between the scores or openings can also be selected to provide the desired rate of contraction.

  In another aspect of providing a sudden deflation of the balloon after the desired time has elapsed, the composite wall or part of the composite wall (patch) of the entire balloon is injected inside the balloon during the manufacturing process or during the inflation process. Several layers of material that are slowly permeated by the treated water. This water penetrates through the layers and eventually reaches the substantially expanding material, rupturing the thin outer protective layer, creating a large hole for the gas to escape and the balloon to deflate. The water expansion material is protected from the liquid by a coating or sheath such as parylene that allows a controllable amount of moisture exposure. Once the water reaches the expansion material, it exerts a force against the protective outer layer, causing its rupture. The outer layer may be created using weakened bond areas, partially grooved areas, or other methods to ensure the desired rupture location and facilitate the desired timing when autoshrink occurs. Good. There may be any number of layers between the moist environment and the moisture extension center. Each material layer may have a different erosion rate (eg, fast or slow), which is a predetermined time (eg, 30 days, 60 days, or longer) when shrinkage is desired to occur. After) can be selected. By changing the number, thickness, and speed of each circumferential layer, the time to shrinkage can be accurately controlled.

  Alternatively, a pressure seal button that is adhesively bonded onto the perforations in the balloon material can be provided for deflation. The adhesive that binds the button erodes over time when it comes in contact with moisture derived from gastric juice or injected into the balloon. Once the adhesive is no longer able to bond between the adhesive and the button and the airtight seal cannot be created, the balloon rapidly deflates. By controlling hole size and adhesive moisture exposure, the erosion time can be accurately predicted.

  Shrinkage can also be facilitated by creating a series of connection ports in a septum attached to the balloon composite wall or on another similar structure. Ports can be constructed using biocompatible, poorly permeable materials, such as gelatin, that are soluble in water or acid. The hole diameter, number of holes, channel width, and channel length can all be adjusted to control the dissolution parameters. Once the material in the ports and channels has dissolved, there is a clear path for the gas trapped in the balloon to escape and ultimately cause the balloon to contract. The water can be gastric fluid or can be controlled internally by including water inside the balloon during assembly or during the inflation process. There may be a plurality of port openings to ensure gas permeation. In addition, there are several variables that can be adjusted to control the dissolution time: the size of the port opening; the number of port openings; the length of the internal channel; the width of the internal channel; and the rate of material dissolution. The port / channel layout design can ensure that only a small amount of surface area is exposed to moisture at any particular time, thereby controlling the rate of erosion and final shrinkage.

  Mechanisms for facilitating passage include erosion mechanisms that can break the balloon to a size that has a higher probability of predictably passing through the lower digestive system. Preferably, the size of the deflated balloon is 5 cm long and less than 2 cm thick (similar to various foreign objects of similar size that have been shown to pass through the pyloric sphincter predictably and easily). This can be accomplished by providing the balloon with an “erodible seam”. One seam, or more seams, is provided that breaks the balloon opening into (half) two halves so that multiple smaller balloon pieces are created in the dissociation reaction. The number of seams used is based on the original surface area of the balloon and what is required to dissociate the balloon into small pieces that are sized to pass through the digestive tract more easily and predictably. You can choose based on. The rate of seam erosion can be controlled, for example, by using materials that are affected by the external gastric environment, pH, liquid, humidity, temperature, or combinations thereof. The seam may be a single layer made of only an erodible material or a multilayer. The timing of self-shrinkage can be further controlled by the design of the seam layer, for example, the reaction and / or disassembly of the seam material can depend on the balloon's internal environment instead of the external environment. By manipulating the reaction so that erosion or degradation is initiated by the internal environment (eg, the internal pH of the balloon, humidity, or other factors), gastric variability (pH) that can affect the timing of erosion Etc.). The internal balloon environment can be manipulated by adding excess water at the time of injection to create a humider internal environment, or the pH can be manipulated by varying the amount of components added.

Confirmation of deflation of the intragastric balloon system Whether the balloon is self-contracting or non-self-contracting, various mechanisms can be implemented to confirm deflation of the balloon. In a preferred embodiment, the balloon is deflated and releases a sensory stimulus configured to elicit a response by one of the patient's sensations. In some embodiments, the device may emit an odor that the patient smells. In some embodiments, the device may emit a taste that the patient enjoys. In some embodiments, the device may release a colorant that is visually visible after the patient has passed the colorant, eg, in a toilet. In some embodiments, the sensory stimulus may cause a physiological response indicative of contraction. For example, a deflated balloon may release a substance that facilitates passage through the intestine.

  In some embodiments, flavoring agents can be used to indicate contraction to the patient. These may in some embodiments be the same as or different from flavoring agents that may be used with, for example, ingestible event markers for power generation or pH based placement systems. Therefore, flavoring agents such as peppermint, winter green oil and cherry flavor can be used. In addition, it is desirable to add a colorant to make the dosage form more attractive in appearance or useful for product identification.

Electromagnetic and magnetic tracking and visualization sub-part tracking and visualization functions can be incorporated into the devices and systems described above. As used herein, “visualization” is the identification, tracking, positioning, magnetic field strength, magnetic field orientation, magnetic field temporal characteristics, magnetic field effects on magnetic sensors, and magnetic or magnetized items of interest. Auditory, visual, tactile, or other based on magnetic field data, such as other attributes of the magnetic field that may be used to facilitate and characterize, and magnetic data characterizing the magnetized item of interest Is widely used to refer to identifying items of interest in the body in several ways, such as by Because of the non-invasive nature of the device of the present invention, the physician may wish to determine or confirm the position and orientation of the device prior to expansion, during the course of treatment, or after contraction. Accordingly, an intragastric device is provided that includes a magnetic component configured to be able to determine and verify the position, orientation and status of the intragastric device at all stages of administration.

  This section considers magnetic components that may be implemented in the electromagnetic and / or magnetic aspects described herein. The terms “electromagnetic” and “magnetic” may be used interchangeably in this disclosure, but the electromagnetic embodiment includes an “active” sensor that generates a current in response to the magnetic field, and the magnetic embodiment uses the magnetic field. It is understood to include a “passive” sensor that produces. Specific aspects of the electromagnetic and magnetic systems are described, for example, in the sections "Electromagnetic real time confirmation of position" and "Magnetic real time confirmation of position", respectively.

The marker electromagnetic or magnetic marker component may include various materials or objects that generate and / or respond to a magnetic field. A magnetic field is a force that attracts other ferromagnetic materials, such as iron, and attracts or repels other magnets.

  Magnetism is a class of physical phenomena that includes the forces exerted by magnets on other magnets. It originates from the current and the fundamental magnetic moment of elementary particles. These produce magnetic fields that act on other currents and moments. All materials are affected to some extent by magnetic fields. The strongest effect is for permanent magnets with a persistent magnetic moment caused by ferromagnetism. Many materials do not have a permanent moment. Some are attracted to a magnetic field (paramagnetism); others are rejected by a magnetic field (diamagnetism); others have a much more complex relationship with applied magnetic fields (spin glass behavior and Antiferromagnetic). Substances that are negligibly affected by a magnetic field are known as non-magnetic substances. These include copper, aluminum, gas, and plastic. Pure oxygen exhibits magnetic properties when cooled to a liquid state.

  Magnetic behavior such as that exhibited by permanent magnets, ferromagnetic and ferrimagnetic materials, paramagnetic materials, and diamagnetic materials can be used in various aspects of magnetic placement systems used with intragastric devices.

  In some embodiments, the magnetic configuration system may use a ferromagnetic material or a ferrimagnetic material. Ferromagnetic and ferrimagnetic materials are what are usually considered magnetic; they are attracted to a magnet strong enough to feel an attractive force. These materials are the only ones that can retain magnetization and become magnets. Ferrimagnetic materials, including ferrite and the oldest magnetic materials, magnetite and rodeston, are similar but weaker than ferromagnets. The difference between a ferromagnetic material and a ferrimagnetic material is related to its microscopic structure.

  In some embodiments, the magnetic configuration system may use paramagnetic materials. Paramagnetic materials such as platinum, aluminum, and oxygen are weakly attracted to either pole of the magnet. This attraction is hundreds of thousands of times weaker than that of ferromagnetic materials, so it can only be detected by using sensitive devices or by using very strong magnets. Magnetic ferrofluids are made from a small amount of ferromagnetic particles suspended in a liquid, but may be considered paramagnetic because they cannot be magnetized.

  In some embodiments, the magnetic configuration system may use a diamagnetic material. The diamagnetic material is repelled by both poles of the magnet. Compared to paramagnetic and ferromagnetic materials, diamagnetic materials such as carbon, copper, water, and plastic are repelled even weaker by magnets. The permeability of the diamagnetic material is lower than that of reduced pressure. All materials that do not have one of the other types of magnetism are diamagnetic; this includes many materials. Although the force on a diamagnetic object derived from a normal magnet is too weak to feel, a very strong superconducting magnet can be used to levitate a diamagnetic object such as a small piece of lead. A superconductor repels a magnetic field from the inside and is strongly diamagnetic.

  There are various other types of magnetism, such as spin glass, superparamagnetism, superdiamagnetism, and metamagnetism, each of which may be used in various aspects of the magnetic configuration system.

  An electromagnet is made from a coil of wire that acts as a magnet when current passes through it but stops being a magnet when the current stops. Often the coil is wrapped around a core of a “soft” ferromagnetic material such as steel that greatly enhances the magnetic field generated by the coil.

  Various properties of magnets and magnetized objects may be used in aspects of magnetic placement systems for intragastric devices. These properties include, but are not limited to, magnetic field, magnetic moment, and magnetization.

  The magnetic flux density (also called magnetic field B or simply magnetic field, usually denoted B) is a vector field. The magnetic field vector B at a given point in space has two characteristics: 1) its orientation along the compass needle orientation, and 2) how strongly the compass needle is oriented along that orientation. It is specified by its magnitude (also called intensity), which is proportional. In SI units, the strength of the magnetic field B is given in Tesla.

The magnetic moment of a magnet (also called a magnetic dipole moment, usually denoted as μ) is a vector that characterizes the overall magnetic properties of the magnet. For bar magnets, the direction of the magnetic moment point points from the south pole of the magnet to its north pole, and the magnitude relates to how strong these poles are and how far apart. In SI units, the magnetic moment is specified in units of A · m ² (ampere × square meter).

  The magnet itself generates a magnetic field and responds to the magnetic field. The strength of the magnetic field generated by a magnet is at any given point that is proportional to the magnitude of its magnetic moment. Furthermore, when the magnet is placed in an external magnetic field generated by a different source, it applies a magnetic moment to a torque that tends to be oriented parallel to the magnetic field. This amount of torque is proportional to both the magnetic moment and the external magnetic field. The magnet may also be subjected to a force that induces it in one direction or another depending on the position and orientation of the magnet and source. If the magnetic field is uniform in space, the magnet will not receive a net force, but it will receive a torque.

  A round wire having an area A and carrying a current I is a magnet, and the magnitude of the magnetic moment is equal to IA.

The magnetization of a magnetized material is the local value of its magnetic moment per unit volume, usually denoted as M, and having the unit A / m. Since different areas in a magnet can be magnetized in different directions and intensities, it is a vector field rather than just a vector (like a magnetic moment). A good bar magnet may have a magnetic moment of magnitude 0.1 A · m ² and a volume of 1 cm ³ , or 1 × 10 ⁻⁶ m ³ , and thus the average magnetization magnitude is 100,000 A / m. . Iron may have a magnetization of about 1 million amperes per meter. Such a large value explains why iron is so effective in generating a magnetic field.

  Various magnets and their magnetic properties may be implemented in a magnetic intragastric device placement system along with magnetic markers and magnetic sensors or detectors. A magnetic marker includes any magnetic or magnetized material, material, or object to which a sensor or detector is responsive.

  Flexible magnetic materials can also be used in various embodiments. Such materials typically include a ferromagnetic compound (eg, iron oxide) mixed with a polymeric binder. Magnetic materials suitable for use in the various embodiments include magnetic tape, magnetic sheets, magnetic rolls, ink jet printed magnets, and the like. Magnetic tape typically includes a layer of magnetic material that includes an adhesive on one side. The magnetic sheet may include a layer of magnetic material that can be adhered to another layer or incorporated between other polymer layers. Magnetic rolls are typically prepared by, for example, extrusion, laminating, or other techniques known in polymer processing and thin film formation, in which one or more support layers or barrier layers are incorporated. Including a magnetic layer. Such flexible magnetic materials may be isotropic or anisotropic in magnetic response.

  Ink-jet printed magnets include liquids containing magnetic particles that can be deposited on a substrate using ink-jet or bubble jet technology. Alternatively, the magnetic particles can be printed on the substrate using laser jet technology.

  Although iron oxide can provide a low cost advantage, in certain embodiments, other magnetic materials such as strontium, barium, neodymium, such as NdFeB, samarium cobalt, platinum cobalt, and platinum iron are used. Is desirable.

  In certain aspects, the magnetic material is provided as one or more flexible layers in the device. The flexible magnetic layer can be incorporated into the composite wall as one of the layers comprising the wall, for example as a support layer. The magnetic layer may include the entire area of the composite wall or a partial area of the composite wall. For example, one or more narrow strips or one or more patterns of dots, rings, squares, circles, or similar structures are inserted between layers in the composite wall, or on the interior or exterior surface of the composite wall Can be attached or otherwise glued. The magnetic material may be in sheet or roll form, as described above, or composite using any suitable printing technique (inkjet, bubble jet, laser jet, screen printing, lithography, etc.). It can be printed on one or more layers of the wall.

  In certain embodiments, the magnetic component is any rigid component that is incorporated into the intragastric balloon, eg, as a retaining ring, or a heavy component configured to adapt the balloon to the intragastric space (eg, balloon material). Plugs, buttons, pellets, or other solid shapes attached to or incorporated into) or provided as freely moving or “loose” parts in the interior volume of the balloon.

  The magnetic field appears to be concentrated (more localized) when the volume occupied subcomponent is in its contracted state, and the magnetic field is more diffuse when the volume occupied subcomponent is contracted As can be seen, the magnetic marker may be applied to the volume occupancy subpart when the volume occupancy subpart is in a saddle or folded state. Alternatively, a magnetic marker may be applied or incorporated into the volume occupancy subcomponent to facilitate identification and placement of various subcomponents of the device, such as valves, heads, or weights. Magnetic markers may be printed or painted on the surface of the volume occupancy subcomponent or between layers of material forming the volume occupancy subcomponent. Alternatively, the volume occupancy subcomponent may be identified and / or positioned using the magnetic coating described below as a magnetic marker. The magnetic coating for visualizing the volume occupancy subcomponent may comprise iron or any suitable magnetized metallic material as described above. Alternatively, the magnetic marker may be applied to an elastomeric sleeve that covers all or part of the volume occupying subcomponent.

  In another aspect, the volume occupancy subcomponent includes a subcomponent that changes mechanically upon expansion of the volume occupancy subcomponent, and the mechanical change can be visualized using a magnetic field detection equipment. For example, the mechanical portion of a volume occupancy subcomponent that contains a magnetic marker may stretch upon increasing pressure in the volume occupancy subcomponent, resulting in a more diffuse magnetic field.

  Alternatively, magnetized markers may be formed using a metalized mesh or other pattern placed between layers of material from which the volume occupancy subcomponent is constructed. The pattern or patterns formed by the embedded magnetization markers can be placed when the volume occupancy subcomponent is in an expanded and deployed state.

It is envisioned that electromagnetically detected magnetic marker material may be incorporated into the volume occupancy subcomponent to facilitate various magnetic arrangements and visualization systems, including various methods and apparatus for sensing and detecting magnetic markers. .

  In some embodiments, the magnetic placement system includes a magnetic field proximity sensor. This sensor detects the strength and orientation of the magnetic field generated by the magnetic marker.

  In some embodiments, the magnetic detector is similar in configuration to a commercially available magnetic stud detector that uses a small fixed magnet to detect nails or screws placed in the stud during wall manufacture. Also good. A hand-held fixed magnet detector uses a small (fixed) magnet to detect a magnetic marker placed with the device. It is a “pull” of the magnetic marker on the magnet that alerts the user holding the device to the presence of the magnetic marker. The amount of “pull” is proportional to the distance of the fixed magnet from the magnetic marker. For example, compared to a fixed magnetic detector, a weaker tension indicates a deeper depth in the body, while a stronger tension indicates a shallower depth.

  In another aspect, the magnetic placement system uses a movable magnet to detect the magnetized portion of the device. The moving magnet detector is an enhancement that includes a neodymium magnet suspended to move freely in response to a magnetic marker. The strength of this rare earth magnet, along with the ease of movement of the magnet, allows the mobile magnetic finder to expand its detection range to include patients of various sizes (eg, adaptable to morbidly obese patients). it can). Thus, a magnetic marker remote from the detector can be placed with this type of device. Suspend the magnet so that it is always in its “home” position until it moves directly on the magnetic marker. Once the magnet goes near the marker, it is pulled towards the body with an acceleration proportional to the distance between the magnet and the metal. For a marker placed at a shallow position, the magnet moves toward the body at a speed that makes a different sound. For magnetic markers that are deeper in the body, the movement speed is reduced, so the sound of clicking is a more clicking sound. The body tissue is not expected to show an “insulating” effect with respect to the magnetic field. Instead, the strength of the magnetic field is expected to be a function of the distance of the detector relative to the placement device and the strength of the magnetic field generated by the placement device. The fixed magnetic detector can be pre-calibrated to accurately identify the position of the device. The body tissue is not expected to show an “insulating” effect with respect to the magnetic field. Thus, the device can be calibrated (eg, experimentally or by calculation) to output values for distance and direction.

  In some embodiments, the magnetic placement system uses an internal capacitor to detect changes in the dielectric constant of the human body as the sensor moves over the body. The change in dielectric constant indicates a dense object in the body.

  Some embodiments using an internal capacitor may be an edge sensor, a center sensor, or an instant metal finder. In some embodiments, the magnetic placement system further includes a path near the body to which the sensor passively moves when the sensor tracks a magnetic marker traveling through the body.

  In some embodiments, the sensor comprises a large magnetic sheet that is fixed as the sensor travels through the body and is placed near the body that passively detects the position of the magnetic marker.

  In various embodiments, a passive magnetic system can be used, or an active electromagnetic system can be used. In a passive system, magnetic components in the intragastric space are detected using a suitable detector. The magnetic component can passively generate a magnetic field, for example, by a magnetic field induced in the magnetic component as a permanent magnet or by an ex vivo device configured to induce a magnetic field in the magnetic component. In contrast, in an active system, an electromagnetic field is generated and the electromagnetic component is brought into the presence of the electromagnetic field, thereby causing a current through or voltage across the in vivo electromagnetic component for interaction with the electromagnetic field. Generated. The electromagnetic component is in electrical communication with a current or voltage source ex vivo, for example via a conductive wire or conductive trace.

In a preferred type of magnetometer , a magnetometer (also called a magnetic sensor or a magnetic field sensing device) is used to place and / or track the intragastric device. The magnetometer can be divided into a scalar device that measures only the strength of the magnetic field and a vector device that also measures the direction of the magnetic field.

  The magnetometer can detect magnetic (iron) metal at a large distance, for example, several tens of meters. In recent years, magnetometers have been miniaturized to the extent that they can be incorporated into integrated circuits at a very low cost.

  Scalar magnetometers measure the total strength of the magnetic field on which they are applied, not the direction of the magnetic field. A proton precession magnetometer, PPM, or simply mag, also known as a proton magnetometer, measures the resonance frequency of protons (hydrogen nuclei) in the magnetic field to be measured for nuclear magnetic resonance (NMR). Since the precession frequency depends only on the atomic constant and the strength of the surrounding magnetic field, the accuracy of this type of magnetometer can reach 1 ppm. The direct current in the solenoid creates a strong magnetic field around the fluid rich in hydrogen, causing some protons to align themselves with the magnetic field. The current is then interrupted and when protons realign themselves with the surrounding magnetic field, they precess at a frequency that is directly proportional to the magnetic field. This is a digital frequency that is picked up by (sometimes separate) inductors and amplified electronically, typically the output is scaled and displayed directly as magnetic field strength or output as digital data Generates a weak rotating magnetic field supplied to the counter.

  Overhauser effect magnetometers or overhauser magnetometers use the same basic effects as proton precession magnetometers to take measurements. By adding free radicals to the measurement fluid, the proton precession magnetometer can be significantly improved by utilizing the nuclear overhauser effect. Rather than aligning protons using a solenoid, a low-power radio frequency field is used to align (polarize) the free-radical electron spins and then conjugate with the protons via the Overhauser effect. This has two main advantages: RF field induction that captures little energy (allowing a lighter battery for portable units), and electron-proton coupling when measurements are taken. Faster sampling that can happen simultaneously. The Overhauser magnetometer produces readings with a standard deviation of 0.01 nT to 0.02 nT while sampling once per second.

The optically pumped cesium vapor magnetometer is a highly sensitive (300 fT / Hz ^0.5 ) and high accuracy device used in various applications. It is one of several alkali vapors (including rubidium and potassium) and helium used in this way.

  Vector magnetometers have the ability to measure the component of a magnetic field in a particular direction relative to the spatial orientation of the device. A vector magnetometer can be advantageously used to place the intragastric device. A vector is a numerical entity that has both magnitude and direction. The earth's magnetic field at a given point is a vector. Vector magnetometers measure both the magnitude and direction of the total magnetic field. Using these orthogonal magnetometers, the components of the magnetic field in all three dimensions can be measured to provide an accurate position of the medical device. Magnetometers are also “absolute” if the strength of the magnetic field can be calibrated from a known internal constant per se, or “relative” if they need to be calibrated with reference to a known magnetic field. being classified. Also, if the magnetometers measure magnetic fields where they change relatively rapidly in time (> 100 Hz), they are “AC” and they change only slowly (quasi-static) or are static When measuring a magnetic field, it can also be classified as “DC”.

  Vector magnetometers electronically measure one or more components of a magnetic field. Using three diameter magnetometers, both azimuth and dip (tilt angle) can be measured. By taking the square root of the sum of the squares of the components, the total magnetic field strength (also called the total magnetic strength, also called TMI) can be calculated by the Pythagorean theorem. Vector magnetometers depend on temperature drift and dimensional instability of the ferrite core. They also require leveling to obtain component information, unlike total magnetic (scalar) devices. For these reasons, they are no longer used for mineral exploration.

  In a rotating coil magnetometer, the magnetic field induces a sine wave in the rotating coil. As long as it is uniform, the amplitude of the signal is proportional to the strength of the magnetic field and proportional to the sine of the angle between the axis of rotation of the coil and the field line. This type of magnetometer is obsolete.

  In the Hall effect magnetometer, a voltage proportional to the applied magnetic field is generated and the polarity is detected. The magnetoresistive device is made from a thin strip of permalloy (NiFe magnetic film) whose electrical resistance varies with the charge in the magnetic field. They have well-defined axis sensitivity, can be produced in 3-D versions, and can be produced on a large scale as integrated circuits. They have a response time of less than 1 microsecond and can be sampled in a carrier moving up to 1,000 times / second. They can be used in a compass that reads within 1 °, where the basic sensor must reliably resolve 0.1 °. The fluxgate magnetometer consists of a small, magnetically sensitive core wrapped by two coils of wire. An alternating current is passed through one coil to drive the core through alternating cycles of magnetic saturation; ie, magnetized, demagnetized, reverse magnetized, etc. This constantly changing magnetic field induces a current in the second coil, and this output current is measured by a detector. In a magnetically neutral background, the input and output currents match. However, if the core is exposed to a background magnetic field, it will easily saturate if it matches that field, and not the other way. Therefore, the alternating magnetic field and the induced output current are not synchronized with the input current. The extent to which this is true depends on the strength of the background magnetic field. Often, the current in the output coil is integrated to obtain an output analog voltage that is proportional to the magnetic field.

  Various sensors are currently available and are used to measure magnetic fields. The fluxgate compass and gradiometer measure the direction and magnitude of the magnetic field. The fluxgate is affordable, sturdy and compact. This, in addition to its typically low power consumption, makes them ideal for various sensing applications.

  A typical fluxgate magnetometer consists of a “sensing” (secondary) coil around an internal “drive” (primary) coil wound around a permeable core material. Each sensor has a magnetic core element that can be viewed as two carefully matched halves. An alternating current is applied to the drive winding that drives the core to plus and minus saturation. The instantaneous drive current in each core half is driven with the opposite polarity for any external magnetic field. In the absence of an external magnetic field, the flux in one core half cancels that of the other, so the total flux seen by the sensing coil is zero. If an external magnetic field is applied here, it assists the flux in one core half and inhibits the flux in the other at a given moment. This causes a net flux imbalance between the halves, which no longer cancel each other. Here, current pulses are induced in the sense coil windings on all drive current phase reversals (or on the second and all even harmonics). This gives a signal that depends on both the external magnetic field and the polarity.

  There are additional factors that affect the size of the resulting signal. These factors include the number of turns in the sensing winding, the magnetic permeability of the core, the gating flux rate of the change with respect to sensor shape and time. Using synchronous detection, these harmonic signals are converted to a DC voltage proportional to the external magnetic field.

The SQUID, or superconducting quantum interference device, measures an extremely small magnetic field. They are vector magnetometer very sensitive, the noise level is small 3FTHz ^-1/2 in commercial devices, which is 0.4FTHz ^-1/2 in lab device. Many liquid helium cooled commercial SQUIDs achieve a flat noise spectrum from near DC (below 1 Hz) to tens of kilohertz, making such devices ideal for time domain biomagnetic signal measurements. Laboratory-proven SERF atomic magnetometers have so far achieved a competitive noise floor, albeit in a relatively small frequency range.

  SQUID magnetometers require cooling with liquid helium (4.2K) or liquid nitrogen (77K) to operate, and therefore the packaging requirements for using them are from both a thermo-mechanical and magnetic standpoint. Rather strict. SQUID magnetometers are most commonly used to measure magnetic fields generated by brain or heart activity (magnetogram and magnetocardiogram, respectively). Geophysical surveys sometimes use SQUIDs, but the facilities are much more complex than coil-based magnetometers.

Very high sensitivity can be achieved with sufficiently high atomic density. A spin exchange-no relaxation (SERF) atomic magnetometer containing potassium, cesium or rubidium vapors operates similarly to the cesium magnetometer described above, but can achieve a sensitivity of less than ¹ fTHz ^−1/2 . The SERF magnetometer operates only in small magnetic fields. The Earth's magnetic field is about 50 μT; the SERF magnetometer operates in a magnetic field of less than 0.5 μT.

The large volume detector achieved a sensitivity of 200a THz ^-1/2 . This technique is more sensitive per unit volume than the SQUID detector. This technique can also result in a very small magnetometer that may be replaced with a coil to detect changing magnetic fields in the future. This technique may result in a magnetic sensor having all of its input and output signals in the form of light on a fiber optic cable ^[10] . Thereby, a magnetic measurement can be performed in a place where a high voltage exists.

  The computing system may be implemented in a magnetic placement system. The computing system includes hardware and software that receives data from the magnetic sensor and calculates information regarding the placement, orientation, and / or status of the intragastric device according to a particular algorithm.

  In some aspects, the hardware may include a central processing unit, a memory, an analog to digital converter, an analog circuit, and a display.

  In some embodiments, the software proceeds through several steps including calculation of various desired outputs such as calibration, initialization, prediction, estimation, measurement of sensor data, placement, orientation, and configuration.

  In some embodiments, the computing system predicts or estimates the placement, position, orientation, state, or configuration of the magnetic marker, determines a corresponding estimated or predicted magnetic field, and the magnetic marker Is used to determine the actual placement, position, orientation, state, or configuration of the magnetic marker based on the difference between the predicted and actual magnetic field values.

  In embodiments that use estimation or prediction, the calculations may be performed using iterative calculations and / or neural networks, and the hardware may further include an estimation processor.

  The processor output regarding the placement, orientation and / or status of the intragastric device may be communicated to the user in several ways. In some embodiments, the output is shown visually on the display.

  In some embodiments, the processor output regarding the placement, orientation, and / or status of the intragastric device is audibly communicated to the user via a speaker.

  In some embodiments, the processor output regarding the placement, orientation, and / or status of the intragastric device is communicated to the user via a combination of methods. For example, the system may use a visual graphic display with an audible alert sent through a speaker.

  In some embodiments, the magnetic placement system is calibrated prior to use. Magnetic markers and sensors are placed at pre-planned positions and orientations to verify that the output signal is within the expected range.

  In some embodiments, the magnetic placement system is calibrated or otherwise verified using a human patient simulator or dummy to test the magnetic placement system as the magnetic marker moves through the simulator.

  In some embodiments, the magnetic placement system is checked for stray signals from nearby magnetic disturbances.

  Once ingested, the intragastric device may be placed using a magnetic intragastric placement system.

  Once ingested, the orientation of the device may be confirmed using a magnetic intragastric placement system.

  Further, various sizes and configurations of devices once ingested may be characterized using a magnetic gastric placement system. For example, balloon inflation, or inflation or configuration of multiple balloons may be characterized and evaluated.

  A magnetic placement system may also be used with a contraction system to characterize the contraction process.

  The timing and other attributes of various administration methods can be characterized using the disclosed magnetic gastric placement system. Whether the device is administered using endoscopic technology or orally, the progress of the device can be tracked using a magnetic placement system as it advances toward the stomach. For example, the swallowing effect of a device using hard gelatin or water or other consumables may be characterized by tracking the position and orientation when it is ingested.

Electromagnetic real-time confirmation of position In certain embodiments, commercially available electromagnetic tracking techniques are used. Suitable systems include, but are not limited to, Salt Lake City, Sherlock ^* II Tip Location System, manufactured by UT's Bard Access Systems, or NDI Medical, Inc. of Ontario, Canada. Aurora Electromagnetic Tracking System manufactured by

Aurora System
In some embodiments, the catheter is adapted for integration into the Aurora System sensor by placing the sensor inside the catheter. In other embodiments, the sensors may be placed on other parts of the system, such as balloons or intragastric devices, or other features described herein. The compatible NDI Aurora System Hardware component allows tracking of sensors placed inside a swallowable catheter using a real-time electromagnetic tracking system that delivers sub-millimeter, sub-accuracy. The software was modified to create a graphic user interface suitable for GE use and detection of capsules in the gastrointestinal tract.

  FIG. 1 describes aspects of an electromagnetic tracking system 1500 for deploying a sensor 1521. System 1500 includes a catheter 1503 having an electromagnetic field generator 1510, a system control unit 1535, a sensor interface unit 1530, and a digital sensor 1521. In the embodiment shown, the electromagnetic field generator 1510 generates an electromagnetic field. In other aspects described herein, the electromagnetic field generator 1510 may generate pressure waves for use in, for example, ultrasound-based systems (see FIGS. 27-40). As shown in FIG. 1, the electromagnetic field generator 1510 may include one or more mounting holes 1511. The attachment holes 1511 allow the generator 1510 to be attached to a wall, support, or other accessory. Electromagnetic field generator connector 1512 connects electromagnetic field generator cable 1514 to system control unit 1535. The electromagnetic field generator connector 1512 is a 19-pin round metal connector, but other connectors may be used.

  As shown, the electromagnetic field generator 1510 may be planar. The planar electromagnetic field generator 1510 emits a low intensity, varying electromagnetic field and establishes the location of the volume to track (see FIG. 6). Planar electromagnetic field generator 1510 contains several large coils (not shown) that generate a known electromagnetic field. The electromagnetic field generator 1510 produces a series of changing magnetic fields that produce a known volume of changing magnetic flux. This solution is called the characterized measurement volume. The shape of the characterized measurement volume depends on the type of electromagnetic field generator and the method by which it is characterized. The characterized measurement volume is the volume from which data was collected and used to characterize the electromagnetic field generator 1510. It is a subset of the detection area. The detection area is the total volume that the electromagnetic field generator can detect the sensor regardless of accuracy. The measurement volume for the generated magnetic field will now be discussed in more detail, for example with respect to FIG. The volume protruded outward from the front surface of the electromagnetic field generator 1510 and was shifted by 50 mm from the electromagnetic field generator 1510.

  The planar electromagnetic field generator 1510 may have an attachment point 1509 designed to attach the electromagnetic field generator 1510 to, for example, an attachment arm described in further detail herein with respect to FIG. The electromagnetic field generator 1510 may have one or more mounting holes 1511 that allow the electromagnetic field generator 1510 to be securely attached to a fixture. As shown, the two mounting holes 1511 are M8 tapped holes (screw pitch 1.25 mm, depth 13 mm) x4, two per side. However, fewer or more than two mounting holes 1511 may exist in various shapes and sizes.

  The electromagnetic field generator 1510 may also be a tabletop electromagnetic field generator (not shown). A tabletop electromagnetic field generator may be designed to be placed on the patient table between the patient and the table. The tabletop electromagnetic field generator includes a thin barrier that minimizes tracking strain caused by conductive or ferromagnetic material located under the tabletop electromagnetic field generator. A tabletop electromagnetic field generator contains several large coils that generate a known electromagnetic field. The volume may protrude outward from the front surface of the tabletop electromagnetic field generator and may be offset by 120 mm from the tabletop electromagnetic field generator. A desktop electromagnetic field generator may include any or all of the features and functions of the planar electromagnetic field generator described above.

  The electromagnetic field generator 1510 is connected to the system control unit 1535. Generator 1510 may be connected to system control unit 1535 by a cable 1514 that allows communication of signals therebetween. The system control unit 1535 may include, for example, a power cable 1505 and an auxiliary cable 1504, such as a USB cable or a serial RS-232 cable, for connection to a computer or other component. The system control unit 1535 may supply power to the electromagnetic field generator 1510.

  The system control unit 1535 is connected to the sensor interface unit 1530. The system control unit 1535 may be connected to the sensor interface unit 1530 by a cable 1534. There may be more than one system interface unit 1530 connected to the system control unit 1535 by a plurality of cables 1534. Cable 1534 allows electrical communication of signals between system control unit 1535 and one or more sensor interface units 1530.

  System control unit 1535 may control the operation of system 1500. In some aspects, system control unit 1535 provides an interface between components of system 1500. System control unit 1535 may also supply power to electromagnetic field generator 1510 and / or control the electromagnetic output of electromagnetic field generator 1510. The system control unit 1535 may also collect sensor data (by the sensor interface unit 1530) and calculate the position and orientation of the sensor. The system control unit 1535 then sends the position and orientation data to the host computer (see FIG. 2). Thus, the system control unit 1535 may also work with a computer. System control unit 1535 may also provide an indication of the visual state.

  The sensor interface unit 1530 is connected to the catheter 1503. Catheter 1503 includes a sensor 1521 at the distal end of catheter 1503. In some embodiments, sensor 1521 may be integrated with an intragastric device. The sensor 1521 is an electromagnetic sensor. In some embodiments, sensor 1521 may be an ultrasound or voltage sensor or marker. The use of a voltage sensor is discussed in further detail herein, for example with respect to FIG. 10C. A sensor 1521 that may be embedded in the tool is connected to the sensor interface unit 1530 via one or more system interface units 1530. When the electromagnetic sensor 1521 is placed inside the measurement volume, a voltage is induced in the sensor 1521 and caused by the changing magnetic field produced by the electromagnetic field generator 1510. The characteristics of the induced voltage depend on the combination of the position and orientation of the sensor 1521 in the measurement volume and the changing magnetic field strength and phase.

  FIG. 2 describes an embodiment of an electrical phase tracking system 1501 having an electromagnetic sensor 1506 for positioning the intragastric device 1520. System 1501 includes an intragastric device 1520 coupled to a catheter 1502 that includes one or more sensors 1506. System 1501 further includes a sensor interface unit 1530, a system control unit 1535, and an electromagnetic field generator 1510 that are in electrical communication with computer 1540.

  As shown, system 1501 includes an intragastric device 1520 that is non-toxic, does not cause sensitization, and is non-irritating. The intragastric device 1520 may be any of the balloons described herein or other intragastric devices.

  Intragastric device 1520 is connected to catheter 1502. Catheter 1502 includes an electromagnetic sensor 1506 at the distal end of catheter 1502 near intragastric device 1520. In some aspects, the sensor 1506 may be implanted with other features of the system 1501, such as an intermediate connector between the catheter 1503 and the intragastric device 1520. Catheter 1502 may be a small 2Fr diameter catheter. Catheter 1502 may include sensor 1506 as one or more small inductive sensors. In addition, an external reference sensor 1622 (see FIG. 3A) may be placed on the patient, such as on the skin. External reference sensor 1622 is intended to provide a reference anatomical framework between electromagnetic field generator 1510 and the patient. Catheter sensors 1506 provide position data as they travel across the GE junction, through the esophagus, and into the stomach. The data collected by reference sensor 1622 and catheter sensor 1506 is then displayed on the laptop computer. Electromagnetic sensors can be characterized for 5 or 6 degrees of freedom.

  The catheter 1502 is connected to the sensor interface unit 1530. In some aspects, the catheter 1502 is directly connected to the sensor interface unit 1530. In other aspects, the catheter 1502 is indirectly connected to the sensor interface unit 1530 via, for example, an intermediate jumper cable, described in more detail herein with respect to FIG. 3A. The sensor interface unit 1530 amplifies and digitizes the electrical signal from the sensor 1506. The sensor interface unit 1530 also provides increased distance between the system control unit 1535 and the sensor 1506 while minimizing the possibility of data noise.

  The system 1501 includes a system control unit 1535. System control unit 1535 is connected to system interface unit 1530 by a cable that allows electrical communication therebetween. The system control unit 1535 collects information from the system interface unit 1530, calculates the position and orientation of each sensor 1506, and works with the computer 1540.

  System control unit 1535 is connected to electromagnetic field generator 1510 by a cable that allows electrical communication therebetween. The electromagnetic field generator 1510 generates a magnetic field 1515. The magnetic field 1515 includes an intragastric device 1520 and a sensor 1506 disposed near the intragastric device 1520 in the catheter 1502. The interaction of magnetic field 1515 and sensor 1506 creates an electrical signal that is detected and transmitted to system interface unit 1530, transmits the signal to system control unit 1535, and transmits the signal to computer 1540.

  The computer 1540 is connected to the system control unit 1535 by a cable 1504. Cable 1504 allows electrical communication between computer 1540 and system control unit 1535. Computer 1540 includes a display 1542. Display 1542 shows identifier 1544. Identifier 1544 indicates the location of various sensors disposed with intragastric device 1520 and catheter 1502. As shown, there are a plurality of identifiers 1544 that correspond to the location of the sensor 1506 on the intragastric device 1520 as well as the location of other reference anatomical sensors discussed herein in more detail with respect to FIG. 3, for example.

  System 1501 can be powered on to detect changes in the presence, movement, and orientation of catheter sensor 1506. In some aspects, sensor 1506 is detected when placed within a 30 cm range from the center point of electromagnetic field generator 1510. In some embodiments, the detection range for sensor 1506 is greater than 45 cm at the center point of electromagnetic field generator 1510. In some aspects, when the system 1501 is placed within a 30 cm range from the center point of the electromagnetic field generator 1510, the two lower corners of the electromagnetic field generator 1510 are distant within a ± 2 cm boundary in the X direction. A position sensor 1506 can be disposed.

  FIG. 3A describes an embodiment of an electromagnetic tracking system 1601 for using a sensor to place an intragastric device 1620 in the body of a human patient. System 1601 includes an electromagnetic field generator 1610 mounted on a support 1605. The support 1605 may be a support structure formed from metal, plastic or other suitable material. The support 1605 may be adjustable to adjust the position of the electromagnetic field generator 1610 relative to the position of the patient. In some aspects, the support 1605 can move up and down to accommodate the changing height of the patient. In this manner, the electromagnetic field generator 1610 may be positioned such that a magnetic field is generated on the area of interest, for example, on the patient's upper body and abdomen.

  As shown, the patient may stand in front of an electromagnetic field generator 1610, which may be an electromagnetic field generator 1510. The patient may be an intragastric device 1520 and is ingesting an intragastric device 1620 that is now in the patient's body. The intragastric device 1620 is connected to a catheter 1602, which may be a catheter 1502. Catheter 1602 includes an electromagnetic sensor (not shown) disposed distally near the intragastric device 1620. Thus, the electromagnetic field generator 1610 generates a magnetic field that interacts with the electromagnetic sensor. The electromagnetic sensor is in electrical communication with a sensor interface unit 1630, which may be a sensor interface unit 1535. Electrical communication is provided by wires connected to sensors that extend through the catheter 1602 to the sensor interface unit 1630. The electrical signal generated by the electromagnetic sensor due to the presence of the magnetic field is transmitted to the sensor interface unit 1630.

  System 1601 also includes an external anatomical reference sensor 1622. External reference sensor 1622 may provide a reference anatomical framework between electromagnetic field generator 1610 and the patient. Although small induced currents are generated by sensor 1622, they are inside the tracking volume. As illustrated, three anatomical reference sensors 1622 are included, but only two are shown in FIG. 3A. In some embodiments, there may be more or fewer than three anatomical reference sensors 1622. The sensor 1622 is connected to the sensor interface unit 1630 by an electric cable 1623. Sensor 1622 is responsive to a magnetic field 1611 generated by electromagnetic field generator 1610. In the presence of a magnetic field, the sensor 1622 generates a current or other signal that is transmitted to the sensor interface unit 1630.

  System 1601 also includes a jumper cable 1626. Jumper cable 1626 contains an SROM chip that provides electrical continuity from catheter 1602 to sensor interface unit 1630. Jumper cable 1626 may provide a male-female converter of connectors to prevent misconnections between sensor interface unit 1630 and catheter 1602. Further details of jumper cable 1626 are described herein, for example with respect to FIG.

  The system control unit 1635 is connected to the computer 1640 by a cable 1604. Cable 1604 allows electrical communication between system control unit 1635 and computer 1640. The computer includes a display 1642. Display 1642 shows the location of sensor identifier 1644 as well as the location of three anatomical identifiers 1646. Sensor identifier 1644 indicates the location of the sensor and the distal end of catheter 1602. Anatomic identifier 1646 indicates the position of anatomical reference sensor 1622.

  The anatomical reference sensor 1622 is fixed on the patient and provides a reference framework for placing the electromagnetic sensor. By having a fixed known position, the anatomical reference sensor 1622 may be used to accurately position the electromagnetic sensor and thus the intragastric device 1620. The location of the reference sensor 1622 is shown on the display 1642 as an anatomical identifier 1646, while the electromagnetic sensor is shown on the display 1642 as a sensor identifier 1644. By knowing the position of the sensor 1622 on the patient's body and the relative position of the sensor identifier 1644 relative to the anatomical identifier 1646, the position of the electromagnetic sensor in the body and thus the intragastric device 1620 can be determined.

  Computer 1640, which may be a laptop computer, contains a system specific software program designed to provide the end user with a “real time” indication of the position of catheter 1602 as well as the position of reference sensor 1622. System 1601 may be calibrated before each use. The sensor makes a background measurement of the surrounding magnetic field during the calibration cycle and when the catheter 1602 is in range, the sensor detects the change in the magnetic field and communicates that data to a software program residing in the computer 1640. . The software analyzes the data and presents various sensor locations on the computer display 1642. In some embodiments, no or little magnetic energy is generated by the sensor or computer 1640.

  Intragastric device 1620 is administered by swallowing by a patient in a balloon capsule attached to a swallowable catheter 1602. Administration of the catheter can be performed while the catheter is visible as it moves from the esophagus into the stomach through the GE junction. Instructions for use (not shown) may be provided with the system 1601. The instructions may provide information on how to administer the catheter 1602, what the patient should expect during and after administration, and how to retrieve the catheter 1602 after the procedure is complete.

  The intragastric device 1620 connected to the catheter 1602 is designed to be swallowed and is tracked by various sensors as it moves through the GE junction toward the stomach. Device 1620 is designed to initiate separation of the outer capsule after it has been swallowed. In some aspects, the device 1620 begins external capsule separation approximately 2 minutes after being swallowed. Complete placement and removal of the catheter 1602 may take about 10 minutes for each swallowing procedure. In some embodiments, the patient may swallow three catheters, so the total time of the swallowing procedure for these subjects is about 30 minutes. After completion of each swallowing procedure, the catheter 1602 is removed by simply pulling it back through the mouth.

  System 1601 may be controlled using an application program interface (API) (not shown). The API is a command set that allows configuration and requests information from the system 1601. System 1601 may return information only when requested by computer 1640. In some aspects, the system 1601 may return information automatically, eg, at set intervals or continuously.

  If system 1601 is tracking device 1620, it returns information about the sensor to computer 1640. The system 1601 may return the position of the origin of each sensor given in mm in the coordinate system of the electromagnetic field generator 1610. System 1601 may return the orientation of each sensor, given in quaternion form. The quaternion value is rounded, so the returned value may not be normalized. System 1601 may return the error indication value between 0 and 9.9 (where 0 is the absence of error and 9.9 is the highest error indication). The system 1601 may return the state of each sensor, indicating whether the sensor is out of electromagnetic field volume, partially out of volume, or lost. The system 1601 may return the number of frames of conversion for each sensor. The frame counter begins as soon as the system 1601 is powered on and can be reset using an API command. The number of frames returned with a transition matches the frame from which the data used to calculate the transition was collected. System 1601 may return a state of system 1601 that may include a system error.

  The various sensors may be 5 degrees of freedom (5 DOF) or 6 degrees of freedom (6 DOF). A degree of freedom of 5 provides information about any two of the three translation values on the x, y, and z axes and the three rotation values, roll, pitch, and yaw. The six degrees of freedom provides information about three translation values on the x, y and z axes and three rotation values, roll, pitch and yaw. In embodiments where only one sensor is incorporated, rotation about the longitudinal axis of the sensor cannot be determined. Thus, for a single sensor embodiment, only 5 degrees of freedom (5 DOF) can be determined. For example, how much the needle physically rotates is not as important as where it points and where the tip is located. Thus, the needle may be a 5 DOF tool and only one sensor is incorporated into the design.

  In an embodiment that includes two sensors that are fixed and ideally orthogonal to each other, the system can determine 6 degrees of freedom (6 DOF). First, the system determines 5 DOF information for each center. The system then combines and compares this information, applies fixed position data, and determines 6 degrees of freedom (6 DOF).

  For example, an ultrasound engineer needs to know its position as the ultrasound probe moves over the object, and match that knowledge to the actual physical position on the object. Incorporating the two sensors into the ultrasound probe results in a 6 DOF measurement and ensures that all translation and rotation values of the probe are captured.

  The electromagnetic field generator 1610 may use a coordinate system having an origin located substantially on the surface of the electromagnetic field generator 1610. This global coordinate system may be defined during manufacturing. System 1601 may report a transition in the global coordinate system. However, in some embodiments using a reference tool (not shown), the software can calculate and report a transformation in the reference tool's local coordinate system.

  Each sensor has its own local coordinate system defined by an origin and three axes. The local coordinate system is part of the measurement process. In some embodiments, a single sensor may be present. The local coordinate system of a single sensor is directly based on that of the sensor. By default, the system assigns a z-axis along the length of the sensor and assigns an origin to the center of the sensor. The origin can be moved along the z-axis. Since the rotation about the z axis cannot be determined, the x and y axes are not fixed.

  In some embodiments, there may be a dual sensor with 5 DOF. The dual 5DOF sensor is essentially two single sensors connected to the same sensor body connector. Thus, the sensor actually has two local coordinate systems, each based on one of the sensors incorporated in its design. These local coordinate systems are determined in the same way as for a single sensor.

  In some aspects, the system 1601 comprises a metal object such as a tablet, tool, fastener. This can create problems when using electromagnetic sensors, and thus the system 1601 may therefore be resistant to certain metals. The problem caused by placing metal near the electromagnetic measurement system is related to eddy currents. Eddy currents are caused when a conductive material is exposed to a dynamic magnetic field. The changing magnetic field induces a circulating flow of electrons in the conductive material, resulting in a current. These circulating currents (sometimes known as eddy currents) create their own electromagnetic effects and create a magnetic field that opposes the original external magnetic field. The higher the electrical conductivity of the conductor, the more eddy currents are generated (more magnetic field is created).

  When a conductive metal crosses the electromagnetic field 1611, the corresponding magnetic field created by the resulting eddy currents destroys the magnetic field and affects the generated conversion data. One way to mitigate this effect is to adjust the position of both the sensor being measured and the object generating the eddy current. By moving the sensor so that the distance between the sensor and the electromagnetic field generator 1610 is less than that near the object that creates the eddy current, the effect of the eddy current on the sensor measurement may be reduced.

  Another situation to consider is the effect of eddy currents in the metal loop. Loops may occur in structures such as metal table frames or concrete reinforced bars. Cutting the loop reduces the effect of eddy currents. If loop cutting is not an option, system 1601 is arranged to minimize the effect of the loop. In some aspects, the system 1601 uses special techniques to take into account effects such as eddy currents. The following metal alloys work well with the system 1601 when applied in amounts similar to those used in medical tool construction: cobalt-chromium alloys, steel DIN 1.441, titanium (TiA16V4) and 300 series Stainless steel.

  Furthermore, ferromagnetic materials generally have little or no net magnetic properties. However, if it is placed in the magnetic field 1611, the region may be redirected parallel to the magnetic field and remain redirected even when the electromagnetic field 1611 stops. Even metals containing only a small amount of iron material may have these reactions.

  The magnetic field generated in the ferromagnetic object attracts the external magnetic field 1611 and bends the external magnetic field 1611 toward the object itself. Thus, the introduction of a ferromagnetic object into the electromagnetic field 1611 of the system 1601 causes distortion that can affect the generated conversion data.

  FIG. 3B is a rear view of the patient from the system 1601 shown in FIG. 3A. As shown in FIG. 3B, the patient has three external anatomical reference sensors 1622 attached to the back of the patient. Sensors 1622 are typically arranged in a triangular configuration. In some aspects, the sensors 1622 may be arranged in different configurations, such as right angle, annular, or others. Sensor 1622 is connected to other components of system 1601, such as sensor interface unit 1630, by cable 1623. In some aspects, sensor 1622 may be wirelessly connected to other components of system 1601. As further shown, the patient stands directly in front of the electromagnetic field generator 1610. In some embodiments, the patient need not stand directly in front of the generator 1610.

  FIG. 4 describes an embodiment of an electromagnetic tracking system 1650 that includes a support 1655 and uses a sensor (not shown) to place an intragastric device (not shown) within the body of a human patient 1651. System 1650 includes a patient 1651 standing in front of an electromagnetic field generator 1660, which may be an electromagnetic field generator 1510, 1610 as described herein. Generator 1660 is coupled with an adjustable arm 1670. The arm 1670 may be adjusted so that the electromagnetic field generator 1660 is located next to the patient 1651. Arm 1670 may also adjust it so that electromagnetic field generator 1660 generates a magnetic field near the stomach of patient 1651. The arm 1670 may adjust the electromagnetic field generator 1660 vertically as well as horizontally. The arm 1670 can also rotate the electromagnetic field generator 1660 to accommodate, for example, a lying patient.

  System 1650 includes a support 1655 that supports a computer 1690. The support 1655 can be adjusted in the vertical direction. In some aspects, the support 1655 may be adjustable in other directions, for example, it may be adjusted horizontally, rotated, etc. The support 1655 includes a surface on which the computer 1690 and other components of the system 1650 may be placed or attached. The support 1655 also includes four wheels 1666 on which the support 1655 can be rolled. In some embodiments, the support 1655 may include fewer or more than four wheels 1666.

  Support 1655 may be designed to avoid overturning. In some embodiments, the support 1655 may withstand a 10 ° tilt from a horizontal plane in any X or Y direction without tipping. In some embodiments, the support 1655 may withstand a load equal to 25% of the total weight in any X or Y direction without tipping.

  FIG. 5 describes a display embodiment that can be used with the system of FIGS. Display 1700 includes a screen 1710. The screen 1710 displays various identifier positions corresponding to various sensors. Screen 1710 may be a display on a computer. Screen 1710 may also be on a variety of other machines.

  As shown, display 1700 includes the locations of identifiers 1720 and 1725. Identifier 1720 corresponds to the position of the sensor associated with the catheter. For example, identifier 1720 may correspond to the location of electromagnetic sensor 1506 and catheter 1502. The identifier 1720 may also correspond to the location of the sensor associated with the intragastric device 1620 and the catheter 1602.

  Display 1700 may also include trace 1722. Trace 1722 may show the way the identifier 1720 traveled over time. Thus, the trace 1722 may indicate the way the sensor has moved within the patient's body. As shown, trace 1722 may have a vertical cross-section as shown, then a bend near the bottom of trace 1722. In some embodiments, the bends in trace 1722 indicate the path of the sensor moving through the patient's stomach. Thus, the path of trace 1722 may indicate the position of the sensor and thus the position of the intragastric device.

  The identifier 1725 may correspond to the location of an external anatomical reference sensor. For example, the identifier 1725 may correspond to the position of three anatomical reference sensors 1622. As shown, the identifier 1725 generally forms a triangle shape. This may correspond, for example, to a triangular configuration of sensors 1622 that are typically placed on the patient's back. By knowing the position of the identifier 1725 relative to the patient and the relative position of the identifier 1720 relative to the identifier 1725, the position of the sensor and thus the position of the intragastric device within the body may be determined. As shown in FIG. 5, the location of the identifier 1720 may indicate an intragastric device that has been successfully placed inside the stomach. The display 1700 shown is merely an example and other suitable displays may be implemented. In some aspects, the screen 1710 may include markings or other reference points to facilitate placement of various identifiers.

  FIG. 6 describes aspects of an electromagnetic field generator and corresponding magnetic field envelope that may be used with the system of FIGS. The envelope 1815 represents the volume that the sensor may interact with the generated magnetic field from the electromagnetic field generator 1810. The envelope 1815 is generally shown in a cylindrical shape. In some aspects, the envelope 1815 may have various shapes.

  FIG. 7 describes aspects of the control panel 1915 on the system control unit 1910 that may be implemented with the system of FIGS. Panel 1915 may be on the back of system control unit 1910.

  Panel 1915 includes an electromagnetic field generator port 1920, a plurality of sensor interface unit ports 1925 and a status indicator light 1926. The port 1920 may be used to synchronize the system control unit 1910 with other equipment. The sensor interface unit 1925 connects the sensor interface unit to the system control unit and enables communication with the connected sensor. For example, the sensor interface unit 1630 may be connected to the system control unit 1635 using the port 1925 to enable communication with the sensor 1506. A status indicator light 1926 may indicate whether the corresponding port 1925 is connected to a sensor or catheter.

  FIG. 8 describes aspects of a sensor interface unit 2030 that may be implemented with the systems of FIGS. The sensor interface unit 2030 is an interface between a sensor and a system control unit such as the system control unit 1535 or 1635. The main function of the sensor interface unit 2030 is to convert an analog signal generated by the sensor into a digital signal. The digital signal is sent to the system control unit for processing. Another function of the sensor interface unit 2030 is to increase the distance between the system control unit and the sensor, eliminate the need for long tool cables, and retain bulky system components far from the application space. Furthermore, the shorter the tool cable, the less noise that appears on the signal from the sensor. In some aspects, each sensor interface unit 2030 can support up to two 5 DOF sensors, or one 6 DOF sensor.

  The sensor interface unit 2030 includes a sensor port 2040 and a cable 2045. The sensor port 2040 connects the sensor interface unit 2030 to a sensor such as the sensor 1506. The sensor port 2040 may be a 10-pin round plastic connector. Cable 204 electrically connects sensor interface unit 2030 to a system control unit, such as system control unit 1535 or 1635.

  FIG. 9 describes an embodiment of a catheter 2100 that includes an integrated sensor 2115 that may be used with the systems of FIGS. Catheter 2100 includes a shaft 2110 that extends along the length of catheter 2100. Shaft 2110 extends the wire to form a hollow channel that may be attached to sensor 2115. Catheter 2100 may include a plug 2120 at the end opposite to sensor 2115. Plug 2120 may couple with a sensor interface unit such as sensor interface unit 1530 or 1630. In some aspects, the plug 2120 couples with a jumper cable that is attached to the system control unit.

  FIG. 10A describes another embodiment of the catheter 2101 and sensor 2114 that may be used with the system of FIGS. The catheter is a flexible hydrophilic coated containing a swallowable catheter (about 30 inches) coupled to an about 40 inch polyurethane extension tube to allow connection to the sensor interface unit. 2-Fr catheter. The distal end of the catheter contains two small inductive sensors, one at the distal end and the second at about 6 inches from the distal tip. As the sensor in catheter 2101 moves from the esophagus into the stomach through the GE junction, the sensor provides an electrical signal to the sensor interface unit. The characteristics of these electrical signals depend on the distance and angle between the sensor and the electromagnetic generator.

  In some embodiments, the distal ends of various catheters, such as catheter 2100 or 2101, are sealed using adhesive plugs. Attached to the distal end of the catheter is a 31 x 12.41 mm pharmaceutical grade porcine gelatin capsule with a hydrophilic coating containing food grade sugar. Catheter 2101 may include a 2Fr catheter shaft formed from Pebax® (polyether block amide) and polyvinylpyrrolidone to provide a swallowable catheter with a hydrophilic coating to provide lubricity. The catheter may include a sensor that includes a copper coil encased in epoxy that provides an electrical signal for tracking the catheter. The catheter is manufactured by Torpac, Inc., which contains food grade sugars that mimic the food bolus weight for swallowing. External capsules formed from USP grade hard pig gelatin capsules supplied by (New Jersey, USA) may also be included. The outer capsule may have a polyvinylpyrrolidone hydrophilic coating to provide lubricity. The catheter may include distal strain relief formed from a thermoplastic polyurethane elastomer that provides the strength to hold the gelatin capsule on the catheter shaft. The catheter may include an elongated tube formed from a thermoplastic polyurethane elastomer that extends the length of the catheter for attachment to the sensor interface unit. The catheter may include a marker band formed from 316 stainless steel to provide visibility to the tip of the catheter during visualization. The catheter may include an adhesive that is UV curable to connect the extruded parts of the catheter together and to seal the sensor from fluid contact. The catheter may include a 4-pin connector that provides communication between the catheter and the sensor interface unit. The connector may be formed from a PBT-steel-brass material. The catheter may include a heat shrink connector that provides strain relief for attaching the 4-pin connector to the elongated tube. The heat shrink connector may be formed from a fluoropolymer.

  As shown in FIG. 10A, the catheter 2101 may include a proximal luer hub 2111. Luer hub 211 may attach peripheral components or hold catheter 2101. Catheter 2101 may also include a catheter inner assembly 2112 that includes a catheter needle, a monofilament thread, and a needle holder. The catheter 2101 may also include a needle sleeve 2114 that surrounds and protects the needle assembly 2112. Catheter 2101 is shown with sensor 2116. In some embodiments, the sensor 2116 is a Northern Digital Inc. of Ontario, Canada. It is a 5 DOF sensor of 0.3x13 mm manufactured by However, other sensors may be implemented.

  Catheter 2101 may also include a Y port 2118. Y port 2118 may be a splitter that connects various features of catheter 2101 together. In some aspects, Y port 2118 connects luer hub 2111 and strain relief tube 2122 with catheter bump tube 2126. The strain relaxation tube 2122 may extend off-axis from the Y port 2118 and be connected to the connector 2124. The connector 2124 may include a connector spacer 2128 and a UV curable adhesive 2130. Adhesive 2130 may also be used at other locations on catheter 2101, such as the interface of sensor 2116 and catheter protruding tube 2126, and other locations shown.

  The catheter 2101 may have strong mechanical properties. In some embodiments, the catheter 2101 can be bent 180 ° on a 0.5 cm radius mandrel without twisting at the central portion of the Peebax catheter shaft. The intragastric device may be detached from the catheter 2101 when submerged in 37 ° C. water. Bonding of capsule to catheter 2101 with adhesive 2130 will not work if it exceeds 150 grams if preconditioned for 20 seconds in water at room temperature. Bonding of strain relief tube 2122 and catheter tube 2126 with adhesive 2130 will fail at more than one foot pound. The coupling between the catheter 2101 and the marker band will fail at more than 1 foot pound. The connection between the extension tube and the catheter tube 2126 will fail at more than 1 foot pound.

  FIG. 10B describes aspects of an electromagnetic sensor 2116 that may be implemented with the catheter of FIG. 10A. The sensor 2116 includes a sensor body 2117. The main body 2117 is elongated and generally cylindrical. However, the body 2117 may have various shapes. The body 2117 is formed from a metal or other material that is responsive to an electromagnetic field. The body 2117 is symmetric with respect to the longitudinal axis 2119. The body 2117 includes a geometric center 2121.

  Sensor 2116 has its own local coordinate system defined by geometric center 2121 and longitudinal axis 2119. The remaining two axes are orthogonal to the vertical axis 2119 and intersect the center 2121. In some embodiments, the z-axis extends along the length of the sensor and therefore coincides with the longitudinal axis 2119 as shown, whose origin is the center 2121 of the sensor. However, the origin can be moved along the z-axis. For the 5DOF sensor 2116, the rotation about the z axis cannot be determined, so the orthogonal X and Y axes are not fixed.

  For a 5DOF sensor 2116, information about any two of the three translation values on the x, y, and z axes and the three rotation values, roll, pitch, and yaw may be provided. However, the rotation around the longitudinal axis 2119 of the sensor cannot be determined. Thus, only 5 degrees of freedom (5 DOF) can be determined for a single sensor aspect.

  FIG. 10C describes aspects of a voltage sensor 2160 that may be implemented with the catheter of FIG. 10A. In some embodiments, the voltage sensor 2160 may include a micro-sized integrated circuit (IC) developed for event markers that can be consumed by Proteus Digital Health of Redwood, California. A micro-sized integrated circuit (IC) is embedded inside a swallowable balloon capsule. When a circuit is exposed to gastric juice, it provides electrolyte to the circuit and powers a battery built on the surface of the circuit. The IC is then turned on and communicates with a receiver attached to the body. The receiver then communicates with an external device, such as a smartphone or tablet computer, to provide information to the healthcare provider regarding when the capsule reaches the patient's gastric juice.

  In some aspects, the IC is coupled to an intragastric device, such as a device 1520 or 1620 of an electromagnetic tracking system. Once the device reaches the stomach, it provides power to the battery and is provided with an electrolyte to communicate with its receiver, indicating that the device is inside the stomach. The IC is then separated from the balloon capsule and naturally passes through the digestive tract.

  An alternative aspect involves creating an electrical potential near the intragastric device by implanting anode 2165 and cathode 2170 in sensor 2160, as shown in FIG. 10C. In some embodiments, anode 2165 and cathode 2170 are embedded in a catheter, such as catheter 2101. Anode 2165 and cathode 2170 create a potential between the electrodes when in the presence of an electrolyte (such as gastric juice). This generated voltage is passed through the catheter using a small magnetic wire, connected to a system that analyzes the voltage and reports confirmation of a threshold voltage level with sufficient confidence that the catheter has entered the stomach. Once the threshold voltage confirmation is received, after the balloon is inflated, the electrode-attached catheter is withdrawn from the body, thus eliminating the potential risk of ingesting the anode / cathode material.

  The advantage of voltage sensor 2160, having either an IC system or an anode / cathode configuration, is that voltage sensor 2160 only provides location confirmation when it is in the presence of gastric fluid, so the physician can It is possible to prevent the balloon from being permanently inflated.

  Another advantage of the catheter electrode system is that no extraneous material is left in the patient's body after the balloon is deployed (other than the balloon system itself).

  Another aspect involves the use of a specific coating on the intragastric device or catheter that controls the timing when the electrode is exposed to gastric fluid and thus can control the timing of voltage generation. These coatings may be hydrophilic to accelerate exposure time, soluble only at low pH values (less than 5.0), or enteric coated to delay exposure time.

  FIG. 11 describes aspects of an external reference sensor assembly 2200 that may be used as an anatomical reference sensor with the systems of FIGS. Assembly 2200 includes a sensor 2215 connected to cable 2210. At the opposite end of cable 2210 is a connector 220 for connecting assembly 2200 to a system control unit, such as system control unit 1535 or 1635. The sensor 2215 may be attached and secured to the patient's back. The sensor 2215 may be secured to the patient using mechanical means or other suitable means such as an adhesive or clip for attachment to clothing.

  FIG. 12 describes an embodiment of a jumper cable 2300 that may be used with the system of FIGS. The jumper cable 2300 may provide a connector male-female converter to prevent misconnection between the sensor interface unit and the catheter, for example, the sensor interface unit 1630 and the catheter 1602 of the system 1601 of FIG. 3A. Cable 2300 includes a connector 2310. The connector 2310 may be a 4-pin female connector, but other connector types may be used. Cable 2300 further includes a heat shrink tube 2340 along the length of cable 2300. At the end opposite to the connector 2310 is a second connector 2330 having an EPROM chip 2320. Second connector 2330 may be a 10-pin male connector, but other connector types may be used.

Magnetic real-time confirmation of position In certain embodiments, commercially available magnetic tracking techniques are used. Suitable systems include, but are not limited to, Kirkland, WA's Lucent Medical Systems, Inc. Magnetic sensor system developed by NDI, Inc. above. Note that embodiments using electromagnetic-based systems, such as embodiments including the Aurora system from US, use the active electromagnetic sensor described above. This is in contrast to embodiments that use passive magnetic sensors, such as those including the Lucent System, and those described in more detail below.

Lucent System
Lucent Medical Systems technology is described in US Pat. No. 5,879,297, US Pat. No. 6,129,668, US Pat. No. 6,216,028, and US Pat. No. 6,263,230. The contents of which are hereby incorporated by reference in their entirety. Lucent technology generally relates to a system and method for detecting the position of an intragastric device within a patient's body, and more specifically to a detection device that senses the magnetic field strength generated by a magnet coupled to the intragastric device.

  Using the Lucent system to place one or more portions of an intragastric device, eg, an intragastric balloon, or a catheter used to place, inflate, deflate, and / or remove an intragastric balloon Can do. The position of the intragastric device is determined by sensing a magnetic field generated by a permanent magnet coupled to the intragastric device. As used herein, the term “couples to” means permanently fixed to the intragastric device, releasably attached, or placed near it. In one aspect, the magnet is coupled to the catheter at a position above the intragastric balloon. In another embodiment, the magnet is coupled to the intragastric balloon itself. The magnet may be a small, cylindrical, rotatably mounted rare earth magnet. Suitable magnets include rare earth magnets such as samarium cobalt and neodymium iron boron, both of which produce high magnetic field strength per unit volume. Magnets that produce high magnetic field strength per size are preferred, but weaker magnets such as alnico, ceramic, or iron magnets may be used.

  Since the magnet is permanent, it does not require a power source. Thus, the magnet maintains its magnetic field indefinitely, allowing long-term placement and detection of intragastric devices without the disadvantages associated with internal or external power sources. In particular, avoiding the use of a power supply avoids undesirable electrical connections necessary for the use of the power supply. Therefore, there is no risk of an electric shock (or the possibility of patient electrocution) to the patient. Furthermore, the static magnetic field of the magnet passes through body tissue and bone without attenuation. This property allows the use of the device to detect an intragastric device at any location within the patient's body.

  One known technique for placing a medical tube within a patient's body is described in US Pat. No. 5,425,382, which is hereby incorporated by reference in its entirety. A tube with a permanent magnet at its tip is inserted into the patient, eg, a feeding tube is inserted into the patient's nose and the esophagus is placed down into the stomach. A sensing device is used to sense the static magnetic field strength of the magnet while entering the magnetic field around the earth at two different distances. By measuring the static magnetic field strength at two different distances, the detector determines the magnetic field gradient. As the detector moves around the patient's body, higher and smaller magnetic field gradients are shown. The tube is placed by moving the detector until the maximum size is indicated by the detector.

  The detection apparatus described in US Pat. No. 5,425,382, which is hereby incorporated by reference in its entirety, uses first and second magnetic sensors. The magnetic sensors may each include a fluxgate toroidal sensor for detecting a magnetic field gradient. An alternative magnetic field gradient detector system is described in US Pat. No. 5,622,169, which is hereby incorporated by reference in its entirety. The magnetic sensor includes three orthogonally arranged fluxgate toroidal sensor elements, respectively. The magnetic sensor includes magnetic sensor elements arranged orthogonally to measure magnetic field strength in three orthogonal directions. Similarly, the magnetic sensor includes magnetic sensor elements for measuring magnetic field strength in the x, y, and z directions, respectively. Sensors may be used to determine the magnetic field gradient in the x, y, and z directions. Using magnetic field gradient measurements in three directions, the position of the magnet may be easily determined using conventional vector mathematics. A numerical indication of the magnetic gradient indicates the direction of the magnetic field dipole of the magnet. The magnet, and therefore the intragastric device, is geometrically configured to zero detection of the surrounding uniform magnetic field (eg, the Earth's magnetic field) while still detecting the magnetic field strength gradient generated by the magnet Detection is performed using a known detection device containing at least two static magnetic field strength sensors. The magnet detection device detects the position of the magnet based on the difference in magnetic field strength between the two sensors. However, it is possible to construct magnetic field detection devices with different sensor configurations to provide further data regarding the position and orientation of the magnets. Various aspects relate to techniques for magnet detection using a multi-sensor array and a convergence algorithm that can accurately position magnets in three dimensions.

  One aspect of the passive magnetic detector system 100 is shown in FIG. Detector system 100 includes a housing 102, a control switch 104 such as a power switch and a reset switch, and a display 106. In the exemplary embodiment, display 106 is a two-dimensional liquid crystal display. The display 106 may have an opaque background or have a transparent area where a health care provider can see the skin under the surface of the detector system 100. The ability to view external patient landmarks greatly assists in catheter placement using the detector system 100. Alternatively, the display 106 may be an external display such as a video monitor.

  Also, the first, second, third, and fourth magnetic sensors 108, 110, 112, and 114 are mounted in the housing 102, respectively. In a preferred embodiment, the static magnetic sensors 108-112 are spaced to provide maximum separation within the housing 102. In an exemplary embodiment, the magnetic sensors 108-112 are disposed in a substantially planar manner within the housing 102 and are disposed near the corners of the housing.

The orientation of the magnetic sensors 108-114, illustrated in Figure 14, wherein the magnetic sensor 108-114, near the corner of the housing 102, respectively, are disposed at a position S ₁ to S _4. Although the system 100 described in FIGS. 13 and 14 illustrates a rectangular configuration for the magnetic sensors 108-114, the principles can be readily applied to any multi-sensor array. Thus, the system is not limited by the specific physical arrangement of the magnetic sensor.

  In the exemplary embodiment, each magnetic sensor 108-114 includes three independent magnetic sensing elements arranged orthogonally to provide three-dimensional measurements in the x, y, and z directions. The sensing elements of the magnetic sensors 108-114 are aligned with respect to a common origin so that each magnetic sensor senses a static magnetic field in the same x, y, and z directions. Thereby, it becomes possible to detect the magnetic field intensity in the three-dimensional space by the respective magnetic sensors 108 to 114. The arrangement of the magnetic sensors 108 to 114 enables magnet detection in a three-dimensional space within the patient. That is, in addition to placing magnets in the patient, the detector system 100 provides depth information.

  The configuration of the magnetic sensors 108-114 can be easily changed for special applications. For example, a plurality of magnetic sensors may be configured in a spherical arrangement around the patient's waist to detect the position of the magnet 120 in the stomach. Furthermore, the magnetic sensing elements need not be arranged orthogonally. For example, the magnetic sensing elements may be configured in a planar array or other convenient configuration suitable for a particular application (eg, a spherical arrangement). The detector system must have at least as many sensing elements to provide data that there are unknowns in the equation to be solved and that the position and orientation of the magnetic sensing elements are known. is there.

  It is desirable to detect the position and orientation of the magnet 120 in a three-dimensional space. This results in five unknown parameters that may conveniently be considered x, y, z, θ, and φ, where x, y, and z are 3 relative to the origin, such as the center of the housing 102. The coordinates of the magnet 120 in the dimensional space are represented, θ is the angular orientation of the magnet in the YZ plane, and φ is the angular orientation of the magnet in the XY plane. Furthermore, the earth's magnetic field contribution in the x, y, and z directions is unknown. Thus, the model used by detector system 100 has 8 unknown parameters that require 8 independent measurements. In the exemplary embodiment of detector system 100 described herein, a set of 12 magnetic sensing elements is used to provide oversampling. This results in higher reliability and accuracy while maintaining computational requirements at a reasonable level.

  The mathematical description provided below can be most easily understood with respect to a Cartesian coordinate system using magnetic sensing elements arranged orthogonal to the x, y, and z directions. However, it should be clearly understood that this embodiment is not limited to such an arrangement. Any alignment of the magnetic sensing elements may be used with the detector system 100 as long as the position and orientation of the magnetic sensors 108-114 are known. Thus, the system is not limited by the particular configuration of the magnetic sensing element.

  As illustrated in FIG. 14, the magnet 120 is disposed at the position α. As is known in the art, magnet 120 has a magnetic dipole represented by vector m. The vector m represents the strength and orientation of the magnetic dipole. Under ideal conditions, the magnetic sensors 108-114 can measure the static magnetic field generated by the magnet 120 and determine the position of the magnet at position α in a single measurement. However, due to the presence of the earth's magnetic field, stray magnetic fields that may be present near the magnet 120, internal noise from the magnet sensors 108-114, internal noise generated by electronics associated with magnetic sensors such as amplifiers, It is virtually impossible to perform measurements under “ideal” conditions. In order to provide accurate position information about the magnet 120 in the presence of various forms of noise, the detector system 100 provides a known equation for the magnetic field strength and an accurate reading of the position and orientation of the magnet 120. Use the actual sensor measurements as input to the estimation algorithm that converges to.

  The elements used to process data from the magnetic sensors 108-114 are illustrated in the functional block diagram of FIG. 15A where the magnetic sensors 108-114 are coupled to the analog circuit 140. The particular form of analog circuit 140 depends on the particular form of magnetic sensor 108-114. For example, if the magnetic sensors 108-114 are orthogonally arranged fluxgate toroidal sensors similar to those illustrated in FIG. 14, the analog circuit 140 is a U.S. patent that is incorporated herein by reference in its entirety. Amplifiers and integrators such as those discussed in US Pat. Nos. 5,425,382 and 5,622,669 may be included. In another exemplary embodiment, the magnetic sensors 108-114 include magnetoresistive elements that change resistance with the strength of the magnetic field. Each magnetic sensor 108-114 includes three orthogonally arranged magnetoresistive sensing elements that sense static magnetic fields in the x, y, and z directions, respectively.

  However, the magnetic sensors 108 to 114 may be any form of magnetic sensor. Several different types of magnetic sensors such as, but not limited to, Hall effect, fluxgate, winding lead induction, squid, magnetoresistance, nuclear precession sensor, as described elsewhere May be used in the implementation of the method of embodiments. Commercially available magnetic field gradient sensors in the form of integrated circuits can also be used with the detector system 100. Furthermore, the magnetic sensors 108-114 need not be the same type of sensor. For example, the magnetic sensors 108-112 may be one type of sensor, but the magnetic sensor 114 may be a different type.

  The analog path 140 is designed to work with certain forms of magnetic sensors 108-114.

  The output of analog circuit 140 is coupled to an analog to digital converter (ADC) 142. The ADC 142 converts the analog output signal from the analog circuit 140 into a digital form. The operation of ADC 142 is well known to those skilled in the art and will not be described in detail here. Detector system 100 also includes a central processing unit (CPU) 146 and memory 148. In an exemplary embodiment, CPU 146 is a microprocessor such as Pentium®. Memory 148 may include both read-only memory and random access memory. Various components such as ADC 142, CPU 146, memory 148, and display 106 are coupled together by bus system 150. As can be appreciated by one skilled in the art, bus system 150 illustrates a typical computer bus system and may carry power and control signals in addition to data.

  Also illustrated in the functional block diagram of FIG. 15A is an estimation processor 152. The estimation processor 152 performs an iterative comparison between the estimated position of the magnet 120 and the measured position of the magnet 120 based on data derived from the magnetic sensors 108-114. The iterative process continues until the estimated and measured positions converge, resulting in an accurate measurement of the position 120 of the magnet 120 (see FIG. 14). It should be noted that the estimation processor 152 is preferably implemented by computer instructions stored in the memory 148 and executed by the CPU 146. However, for clarity, the functional block diagram of FIG. 15A illustrates the estimation processor 152 as an independent block because it performs an independent function. Alternatively, the estimation processor 152 can be implemented by other conventional computer components, such as a digital signal processor (not shown).

  The detector system 100 speculates that the magnetic sensors 108-114 are sufficiently far from the position [alpha] of the magnet 120 that can treat the magnet as a point dipole source. Furthermore, it is speculated that the spatial variation of any extraneous magnetic field, such as the Earth's magnetic field, is small compared to the non-uniformity caused by the presence of a point dipole source. However, under some circumstances, perturbations of the Earth's magnetic field may be caused by extraneous sources such as nearby electrical equipment, metallic building elements, and the like. The detector system 100 can be easily calibrated to offset such perturbations.

  The equations used by the estimation processor 152 are easily derived from basic laws of physics relating to electricity and magnetism. A static magnetic field B generated by a magnetic dipole of strength m, placed at position α and measured at position s is given by

(Where || s-α || ⁵ are all known modulus values in matrix mathematics (eg, || s-α || ² is the square modulus))
Given by. Note that the values of α, m, s, and B are all vector values. The term “static magnetic field” is intended to describe the magnetic field generated by the magnet 120 as opposed to a time-varying electromagnetic field or an alternating magnetic field. The magnet 120 generates a fixed, constant (ie, static) magnetic field. The strength of the magnetic field detected by the detector system 100 depends on the distance between the magnet 120 and the magnetic sensors 108-114. One skilled in the art can appreciate that the detected magnetic field strength may change as the magnet 120 moves within the patient or as the detector system 100 moves relative to the magnet. However, relative movement between the detector system 100 and the magnet 120 is not essential. The detector system 100 can easily determine the position and orientation of the magnet 120 in three-dimensional space, even when the detector system and the magnet are not moving relative to each other.

The values from the magnetic sensors 108-114, using the equation (1), respectively, it is possible to determine the intensity of the magnetic field B at locations S ₁ to S _4. The change in magnetic field B over distance is defined as the gradient G (s) of B, which is a derivative of B relative to s. The gradient G (s) is derived from equation (1) and has the following form:

(Where T is matrix transposition and I is of the form:

3x3 identity matrix with
It can be represented by a 3 × 3 matrix represented by

  It should be noted that equation (1) can be solved directly for the value α taking into account the values B, m and s. However, such calculations are difficult to solve and may require significant computational power. The iterative estimation process described below estimates the position α and compares the predicted or estimated magnetic field resulting from the magnet 120 located at the estimated position with the actual measured magnetic field measured by the magnetic sensors 108-114. The position α and the orientation of the magnet 120 are determined. The iterative process changes the estimated position in a controlled manner until the predicted magnetic field exactly matches the measured magnetic field. In that regard, the estimated position and orientation are consistent with the actual position α and orientation of the magnet 120. Such an iterative process can be performed very quickly by the detector system 100 without the need for the extensive computer calculations required to solve for the position α directly using equation (1). . The difference between the predicted magnetic field and the actually measured magnetic field is an error or error function that may be used to quantitatively determine the position α of the magnet 120. The error function is used in an iterative process to refine the estimated position of the magnet 120. Equation (2) representing the gradient G (s) is used by the estimation processor 152 (see FIG. 3A) to determine the magnitude and direction of the error at the estimated position. Thus, equation (1) is used to generate the predicted value, and equation (2) uses the error result to determine how to change the estimated position of the magnet 120.

Magnetic field strength B, respectively, are measured at each location S ₁ to S ₄ by the magnetic sensor 108-114. FIGS. 13-15A illustrate only four magnetic sensors, each providing a measurement of B (s _i ) (where i = 1 to n) at point s _1. Thus, the measurement may be generalized to n sensors. The estimation processor 152 calculates the quantity Δ _ij (measurement) = B (s _i ) −B (s _j ). This calculation provides a measure of the gradient from magnetic sensor i to magnetic sensor j and cancels out the effects of the earth's magnetic field, which is constant at magnetic sensor i and magnetic sensor j (ie, gradient = 0). The estimation processor 152 also calculates a predicted value Δ _ij (prediction) from equation (1). The estimate for the value α is adjusted until the measured value Δ _ij (measured) and the predicted value Δ _ij (predicted) match as closely as possible. For example, the detector system 100 may first infer that the position α of the magnet 120 is centered under the housing 102. Based on this estimated position, the estimation processor 152 calculates a predicted value for the magnetic field strength at each of the magnetic sensors 108-114 that occurs when the magnet 120 is actually at the estimated position. In an exemplary embodiment, the sensing element of each magnetic sensor 108-114 provides a measure of the magnetic field B in three orthogonal directions, where the magnetic field strength values B _xi , B _yi , and B _zi (where i is 1 to 1). equal to n). Similarly, the gradient G (s) is also calculated for each of the three orthogonal directions.

The estimation processor 152 also uses the measured magnetic field strength values from the respective magnetic sensors 108-114 to compare A (predicted) and Δ _ij (measured). Based on the difference between Δ _ij (prediction) and Δ _ij (measurement), the estimation processor 152 generates a new estimated position for the magnet 120 (see FIG. 14), and Δ _ij (prediction) becomes Δ _ij (measurement). ) Until the exact match.

The degree of coincidence between delta _ij (predicted) and delta _ij (measured), was determined by the cost function including a sum of the square of the difference between delta _ij (predicted) and delta _ij (measured), nonlinear iterative optimization algorithm May be used to minimize the value of the cost function. The necessary slope of the cost function is calculated using the above equation (2). Many different well-known cost functions and / or optimization techniques, for example, a quasi-Newton method, using the estimation processor 152, delta _ij be achieved the desired degree of coincidence between (prediction) and delta _ij (measured) Good.

  The iterative measurement process performed by the estimation processor 152 can be performed in a short period of time. A typical measurement cycle is performed in fractions of seconds. As the tube and associated magnet 120 move within the patient, the position and orientation of the magnets change. However, because the measurement cycle is very short, the change in magnet position and orientation is very small during any given measurement cycle, and therefore when the magnet moves inside the patient or when the housing 102 is Facilitates real-time tracking of the magnet as it moves over the patient's surface.

  As discussed above, the estimation processor performs an iterative comparison of the estimated position of the magnet and the measured position of the magnet. The initial estimated position is derived by several possible techniques such as random selection, position under the sensor elements 108-114 having the strongest initial reading, or, for example, the detector system 100 is a housing 102. The position α of the magnet 120 centered below may be estimated initially. However, the neural network 154 shown in FIG. 15A can be used to provide a more accurate initial estimate of the position α of the magnet 120. Neural network 154 is preferably implemented by computer instructions stored in memory 148 and executed by CPU 146. However, for clarity, the functional block diagram of FIG. 15A illustrates the neural network 154 as an independent block because it performs an independent function. Alternatively, the neural network 154 can be implemented by other conventional computer components such as a digital signal processor (not shown). Neural networks can receive and process large amounts of data and generate solutions to problems with many variables thanks to the learning process. The operation of neural networks is generally known in the art and is therefore described here only for specific applications. That is, the operation of the neural network 154 for generating the initial position estimate is considered.

  The neural network 154 has a learning mode and an operation mode. In the learning mode, the neural network 154 is provided with actual measurement data from the magnetic sensors 108-114. Since each magnetic sensor 108-114 has three different sensing elements, a total of 12 parameters are provided as input values to the neural network 154. Based on the twelve parameters, neural network 154 estimates the position and orientation of magnet 120. The neural network 154 is then provided with data indicating the actual position and orientation of the magnet 120. This process is repeated many times so that the neural network 154 “learns” to accurately estimate the position and orientation of the magnet 120 based on the twelve parameters. In the case of the present invention, the above learning process (eg, providing 12 parameters, estimating the placement and providing the actual placement) was repeated 1,000 times. Neural network 154 learns the best estimated position for a set of 12 parameters. It should be noted that the user of detector system 100 need not operate neural network 154 in a learning mode. Rather, data from the learning mode process is provided with the detector system 100. In normal operation, the neural network 154 is used only in the operation mode.

  In the operating mode, twelve parameters from the magnetic sensors 108-114 are provided to the neural network 154 to generate an initial estimate of the position and orientation of the magnet 120. Based on experiments performed by the inventors, the neural network 154 can provide an initial estimate of the placement of the magnet 120 within about ± 2 cm. Such accurate initial estimation reduces the number of iterations required by the estimation processor 152 to accurately determine the position α of the magnet 120. It should be noted that the magnetic sensors 108-114 provide very low signal levels when the position [alpha] of the magnet 120 is sufficiently far from the detector system 100. Thus, the neural network 154 does not generate an initial estimate until the parameter (ie, 12 input signals from the magnetic sensors 108-114) is above the minimum threshold, and thus provides a reliable signal. Can do.

  In view of accurate initial estimation, the estimation processor 152 can perform the above iterative process to determine the position α of the magnet 120 within ± 1 mm.

  Detector system 100 also includes a display interface 156, shown in FIG. 15A, that can display an image of the magnet on an external display (not shown). Those skilled in the art will appreciate that many components of detector system 100, such as CPU 146 and memory 148, are conventional computer components. Similarly, the display interface 156 may be a conventional interface that can display an image of the detector system on a PC display or other monitor, such as a live image monitor 168 (see FIG. 15B).

  One advantage of an external display is that the housing 102 may remain in a fixed position with respect to the patient. In this embodiment, the four magnetic sensors 108-114 may be replaced with a number of sensors (eg, 16 sensors) uniformly distributed throughout the housing 102 to form an array of magnetic sensors (see FIG. 16). See). As the magnet 120 moves relative to the housing 102, its movement is detected by three or more magnetic sensors, and the position of the magnet is calculated and shown on the external display. In this aspect, the user does not need to reposition the housing, but simply look at an external display where the array of magnetic sensors can track the position of the magnet 120.

  Another advantage of an external video display is the ability to combine images generated by detector system 100 with image data generated by conventional techniques. For example, FIG. 15B illustrates the operation of detector system 100 in conjunction with fluoroscope system 160. The fluoroscope 160 is a conventional system that includes a fluoroscope head 162, a fluoroscope image processor 164, and an image storage system that includes a stored image monitor 166 and a live image monitor 168. Further, a conventional video cassette recorder 170 or other recording device (computer memory, DVD, etc.) can record images generated by the fluoroscope system 160 and images generated by the detector system 100. The operation of the fluoroscope system 160 is well known in the art.

  The detector system 100 is fixedly attached to the fluoroscope head 162 in a known spatial relationship. A single “snapshot” image of the patient can be acquired using the fluoroscope system 160 and displayed, for example, on the live image monitor 168. As the catheter containing the magnet 120 (see FIG. 14) is inserted into the patient, the detector system 100 detects the position α of the magnet 120 in the manner described above and, along with a snapshot image of the patient, a live image monitor. An image of the magnet can be projected on 168. In this manner, the user may advantageously use the snapshot fluoroscope image provided by the fluoroscope system 160 in combination with live image data provided by the detector system 100.

  It is preferable to have a proper alignment between the fluoroscope 160 and the detector system 100 for satisfactory operation. This alignment or “registration” may be accomplished by placing a radiopaque marker on the patient's chest and aligning the radiopaque marker with a corner of the detector system 100. When the fluoroscope system 160 produces a snapshot image, the corners of the detector system 100 are shown on the live image monitor 168 thanks to radiopaque markers. An advantage of image overlay using the detector system 100 is that the patient is exposed to X-rays from the fluoroscope system 160 for a moment. The snapshot image is then displayed with the image from detector system 100 superimposed on the snapshot image. Although this process has been described with respect to the fluoroscope system 160, those skilled in the art will recognize any image guided surgical process where the system uses x-ray, magnetic resonance imaging (MRI), positron emission tomography (PET), etc. Can be applied to

  The earth's magnetic field is also detected by magnetic sensors 108-114. However, assuming that the earth's magnetic field is constant across the housing 102, the contribution of the earth's magnetic field to reading from the magnetic sensors 108-114 is the same. By generating a differential signal between any two of the magnetic sensors 108-114, the effects of the earth's magnetic field may be effectively canceled out. However, as discussed above, there may be perturbations or inhomogeneities in the earth's magnetic field caused by metallic elements such as equipment, hospital bed rails, and metal building elements. Due to the unpredictable nature of such interfering elements, proper operation of the detector system 100 requires calibration. The detector system 100 can be readily calibrated to offset local perturbations in the Earth's magnetic field using the calibration processor 158 shown in FIG. 15A. It should be noted that calibration processor 158 is preferably implemented by computer instructions stored in memory 148 and executed by CPU 146. However, for clarity, the functional block diagram of FIG. 15A illustrates the calibration processor 158 as an independent block because it performs an independent function. Alternatively, the calibration processor 158 can be implemented by other conventional computer components, such as a digital signal processor (not shown).

  The initial calibration is performed before the magnet 120 is introduced to the patient. Thus, the initial calibration is performed outside the presence of the magnetic field generated by the magnet 120. Measurements are performed using the detector system 100. Under ideal conditions, in the absence of local perturbations in the Earth's magnetic field, the signals generated by the magnetic sensors 108-114 are the same. That is, each sensing element oriented in the x direction has the same reading, but each sensing element oriented in the y direction has the same reading, and each element oriented in the z direction has the same reading. Has a value. However, under normal operating conditions there is a local perturbation in the Earth's magnetic field. Under these circumstances, the signals generated by the respective sensor elements of the magnetic sensors 108-114 all have somewhat different values based on the detection of the earth's magnetic field. Any two readings of the magnetic sensors 108-114 may be combined differentially, theoretically canceling out the earth's magnetic field. However, there may be an offset value associated with the reading due to local perturbations in the Earth's magnetic field.

  The calibration processor 158 determines an offset value associated with each magnetic sensor and cancels the offset value during the measurement cycle. That is, the offset value for each magnetic sensor 108-114 is subtracted from the reading generated by the ADC 142 (see FIG. 15A). Thus, the differential reading between any two of the magnetic sensors 108-114 is zero before the magnet 120 is introduced. Thereafter, as the magnet 120 is introduced, the differential readings from the magnetic sensors 108-114 have non-zero values due to the static magnetic field generated by the magnet 120. If the detector system 100 is stationary, as shown in FIG. 15B, to offset the effects of the Earth's magnetic field, such as local perturbations caused by external objects such as metallic equipment, building elements, etc. For this, a single calibration process is sufficient.

  However, in certain aspects, it may be desirable to move the detector system 100 over the patient's surface. As the detector system 100 moves to a new position on the patient, the local perturbation in the earth's magnetic field may cause a decrease in the accuracy of the detector system 100 because the effects of local perturbations are no longer completely offset. However, the calibration processor 158 allows continuous automatic recalibration of the detector system 100 even in the presence of the magnet 120. This is illustrated in FIG. 15C where the detector system 100 is fixedly attached to the digitizing arm 180. The digitizing arm 180 is a conventional part that allows three-dimensional movement. The digitizing arm 180 may be conveniently attached to the patient's bedside. In a preferred embodiment, detector system 100 is attached to a digitizing arm and the three-dimensional movement of the digitizing arm is oriented to correspond to the x, y, and z axes, respectively, of detector system 100. As the user moves the detector system 100, the digitizing arm accurately tracks the position of the detector system and generates data indicative of the position. The detector system 100 uses this position data to calculate the change in the measured magnetic field caused by the magnet 120 as the detector system 100 moves. In this manner, local effects of the magnet 120 may be removed, and the resulting measurements indicate a local perturbation of the earth's magnetic field at the new location of the detector system 100.

  The automatic recalibration process is particularly useful in situations such as a peripherally inserted central catheter (PICC) that may typically be inserted into a patient's arm and passed through the venous system into the heart. Using conventional techniques, the surgeon typically places a mark on the patient's chest to mark the expected path of insertion of the catheter. Without using position sensing techniques, the surgeon must insert the catheter blindly and verify its position using, for example, fluoroscopy. However, the detector system 100 allows the surgeon to track the position of the PICC.

  In the above example, the detector system 100 may be placed on the patient's arm where the PICC is first inserted. After initial calibration (in the absence of magnet 120), detector system 100 is calibrated to offset the effects of the Earth's magnetic field, including any local perturbations. When magnet 120 is introduced, detector system 100 detects and displays magnet position α in the manner previously described. It is desirable to track the progress of the PICC by repositioning the detector system as the surgeon inserts the PICC (with the magnet 120 attached). Using the digitizing arm 180, the surgeon repositions the detector system 100 to a new location. For example, assume that the detector system 100 has moved 6 inches in the y direction, 3 inches in the x direction, and has not moved in the z direction. Based on the new position of the detector system 100 and using the techniques described above, the estimation processor 152 (see FIG. 15A) can calculate the magnetic field at the new position due to the magnet 120. Considering the contribution to the magnetic field at the new location arising from the magnet 120, the effect of the magnet 120 can be subtracted. In the absence of a magnetic field from magnet 120, the remaining or "residual" magnetic field is presumed to be the result of the earth's magnetic field. By processing the residual reading in the manner described above for initial calibration, the detector system 100 can be zeroed or recalibrated to include the Earth's local perturbation at the new location. Cancel the magnetic field. After this recalibration process, a measurement cycle may be initiated using the resulting measurement of the magnetic field due solely to the presence of the magnet 120.

  The user may manually recalibrate the detector system 100 at any time. However, an advantage of the above technique is that when using the detector system 100, the detector system 100 may be automatically recalibrated on a continuous basis. The digitizing arm 180 provides a continuous reading of the position of the detector system 100, thus allowing accurate tracking of the position of the detector system. As the detector system 100 moves, it is always recalibrated to recancel the Earth's magnetic field. In the above example, the detector system 100 can be moved freely when the PICC is inserted into the heart without worrying that external influences such as a hospital bed fence cause a decrease in measurement accuracy. Movement may be tracked. Although a recalibration system has been described above with respect to digitizing arm 180, it can be appreciated that other position sensing systems may be readily used.

  For example, commercially available tracking systems are manufactured by Ascension Technology and Polhemus. A system manufactured by Ascension Technology, known as “Bird Tracker”, measures 6 degrees of freedom and provides accurate measurements within 1/2 inch at 5 feet distance, and 1 at 5 feet distance. / Includes an array of sensors that provide rotation information within 2 degrees. A sensing element used in the Bird Tracker may be attached to the housing 102 and the position of the housing may be tracked using a commercially available system. Similarly, Polhemus' device, known as “3-D Tracker”, provides similar position measurements without the need for digitizing arm 180.

  For example, another application of position tracking using the digitizing arm 180 may allow the surgeon to provide digitized landmarks that are shown on the display. A common surgical technique for assisting in catheter insertion is to place landmarks on the patient's surface that approximate the path taken by the catheter. For example, using conventional techniques, the surgeon may place a series of x on the patient's chest with a marker pen as a landmark to assist in the insertion of an electrical pacemaker lead. Using the principles described herein, the digitizing arm 180 may be used to electronically record landmarks identified by the surgeon. This aspect is illustrated in FIG. 17A with a computer input touch pen 182 or other electronic input device attached to the digitizing arm 180. A computer input touch pen 182 may be attached to the detector system 100 or attached to the digitizing arm 180 at a location corresponding, for example, to the center of the detector system. Prior to insertion of the catheter with magnet 120, the surgeon may electronically generate the landmarks illustrated in FIG. 17A with a series of x using digitizing arm 180 and computer touch pen 182. The computer touch pen 182 electronically “marks” the patient, but there is no need to place an actual mark on the patient. In the above example, when inserting a cardiac pacemaker lead, the surgeon may place a series of electronic landmarks from the neck toward the heart along the path of inserting the pacemaker lead. At each landmark, the digitizing arm 180 records the position marked by the surgeon. In subsequent operations, when a catheter having magnet 120 is inserted into the patient, digitizing arm 180 notes the position of magnet 120 relative to the landmark previously marked by the surgeon. The landmark is shown on the external display 184 shown in FIG. 17B, along with the position of the magnet 120 indicated by the arrow. As the surgeon inserts the magnet 120, progress is shown on the external display 184 such that the magnet 120 passes along landmark 1 to landmark 2 to landmark 3 and the like. Using this technique, the surgeon can easily detect deviations from the expected path. For example, if the catheter and magnet 120 inadvertently deviate to different veins, the surgeon easily notes deviations from the marked path and quickly identifies the problem. The catheter and magnet 120 may be withdrawn and reinserted to track the marked path.

  The general operation of the detector system 100 is illustrated in the flowchart of FIG. 18A. At start 200, a magnet 120 (see FIG. 14) was inserted into the patient. In step 201, the system undergoes an initial calibration. In the exemplary embodiment, the initial calibration is performed before the magnet 120 is introduced. Thus, the system 100 cancels the effects of the earth's magnetic field, such as local perturbations, in the absence of contributions from the magnet 120. Alternatively, the magnet 120 may be placed in a known position with respect to the housing 102 so that the effect of the magnetic field caused by the magnet 120 is known and can be offset in the manner described above for the automatic recalibration process. That is, the contribution to the measured magnetic field caused by the magnet 120 at a known location can be subtracted from the measured reading with the resulting residual value caused only by the earth's magnetic field. After the initial calibration, in step 202, the detector system 100 measures sensor values from the magnetic sensors 108-114. In step 204A, the estimation processor 152 (see FIG. 15A) calculates an initial estimate of the position α and orientation of the magnet 120. The initial estimate includes sensor position data from step 208 and magnet calibration data from step 209. The sensor position data calculated in step 208 provides data regarding the position of each magnetic sensor 108-114 relative to the selected origin. For example, one magnetic sensor (eg, magnetic sensor 108) may be arbitrarily selected as a numerical origin for determining the relative positions of other magnetic sensors (eg, magnetic sensors 110-114). A common origin provides a reference framework for mathematical calculations. As previously discussed, the magnetic sensors 108-114 are aligned with respect to a common origin, and each magnetic sensor measures a magnetic field in the same x, y, and z directions. Any selected origin can be used satisfactorily with the detector system 100, as will be appreciated by those skilled in the art.

  The magnetic calibration data derived in step 209 is typically provided by the magnet manufacturer and includes data regarding the strength of the magnetic dipole m (see FIG. 14) and the size and shape of the magnet 120. . The measured sensor value, sensor position data, and magnet calibration data are provided as input values to the estimation processor 152 (see FIG. 15A) in step 204A.

  In the exemplary embodiment, an initial estimate of the position α is provided by the neural network 154 (see FIG. 15A) based on the measured sensor value derived in step 202. As previously discussed, the neural network 154 may require a minimum value from the magnetic sensors 108-114 to infer a reliable initial estimate. Neural network 154 provides an initial estimate of magnet position and orientation.

In step 210, the estimation processor 152 (see FIG. 15A) calculates a predicted sensor value. As mentioned above, this requires a measured value Δ _ij (prediction) for each combination of magnetic sensors 108-114 in each of the three orthogonal directions x, y, and z. In step 212, the estimation processor 152 compares the predicted sensor value (ie, Δ _ij (predicted)) with the measured sensor value (ie, Δ _ij (measured)). In decision 216, the estimation processor 152 determines whether the predicted and measured sensor values match within a desired tolerance range. If the predicted sensor value does not exactly match the measured sensor value, the result of decision 216 is NO. In that event, the estimation processor 152 calculates a new estimate of the magnet position α and orientation in step 218. After calculating the new estimated position α of the magnet 120, the estimation processor 152 returns to step 210 to calculate a new set of predicted sensor values using the new estimate of the magnet position and orientation. The estimation processor 152 continues this iterative process of adjusting the estimated position α and orientation of the magnet 120 and comparing the predicted sensor value with the measured sensor value until an exact match is achieved. If an exact match between the predicted sensor value and the measured sensor value is achieved, the result of decision 216 is YES. In that event, in step 220A, detector system 100 displays the position α and orientation of the magnet on display 106 (see FIGS. 15A, 15B, and 16). Further, the detector system 100 may display a confidence value indicating the confidence that the position α and orientation of the magnet 120 has been determined. Calculation of confidence values based on statistical data is well known in the art and need not be described in detail here. After displaying the position and orientation data in step 220A, the detector system 100 returns to step 202 and repeats the process for the new set of measured sensor values. If the cost function is too large, an exact match may not be achieved in decision 216. Such a condition may occur, for example, in the presence of an external magnetic field. In practice, the exact match has a cost function in the range of 1-2, but it has been determined that the minimum cost function for inaccurate minima is orders of magnitude greater. If an exact match cannot be achieved (i.e., the cost function is too large), the detector system 100 will either start a new measurement process with a new estimated position or an error that indicates an unacceptably high cost function. A message can be generated.

  The flowchart of FIG. 18B illustrates the steps performed by the calibration processor 158 when automatic recalibration is implemented in the detector system 100. In this implementation, after completion of step 220A, the system 100 may optionally move to step 224 illustrated in FIG. 18B, where the calibration processor 158 is a digital that indicates the current position of the detector system 100. Position data is obtained from the digitizing arm 180 (see FIG. 15C). Considering the new position of the detector system 100 and the known position α of the magnet 120, the calibration processor 158 calculates the magnetic field resulting from the magnet and subtracts the magnet effect from the current measurement in step 226. As a result of this process, the remaining residual values measured by magnetic sensors 108-114 (see FIG. 15A) are due to the effects of the Earth's magnetic field, such as local perturbations.

  In step 228, this residual value is used to zero the detector system 100 again to offset the effect of the Earth's magnetic field at the new location. After the recalibration process, the detector system 100 returns to step 202 shown in FIG. 18A to perform a further measurement cycle with the detector system 100 at the new location and recalibrate for operation at the new location.

  It should be noted that the automatic recalibration process illustrated in the flowchart of FIG. 18A automatically and continuously recalibrates the detector system 100. However, in an alternative aspect, the calibration processor 158 performs recalibration only when the detector system 100 is moved by a predetermined amount. This prevents unnecessary recalibration if the detector system 100 does not move.

  The iterative estimation process using the difference in magnetic intensity B provided by different pairs of magnetic sensors 108-114 has been described above. Alternatively, the detector system 100 can use the measured magnetic field gradient value G. In this aspect, equation (2) may be adapted to the measurement in the manner described above with respect to an iterative process for fitting the measurement of B. With reference to the flowchart of FIG. 18A, step 202 provides a slope value for the pair of magnetic sensors 108-114. For example, the magnetic gradient measurement value can be calculated using the magnetic field B measured by the magnetic sensor 114 with respect to the magnetic field measured by each of the remaining magnetic sensors 108 to 112, respectively. In step 204A, the estimation processor 152 determines an initial estimate of the magnet position and orientation, and in step 210 calculates a predicted sensor value using equation (2). In step 212, the measured sensor value is compared to the predicted sensor value using conventional techniques such as the cost function described above. The iterative process continues until the measured sensor value and the predicted sensor value match within a predetermined tolerance range.

  In yet another alternative technique, the detector system 100 directly solves equation (2) using the measured data. The direct solution approach uses the fact that G is a symmetric matrix with positive eigenvalues. The eigenvalues and eigenvectors of the matrix G may be calculated and used algebraically to solve directly for the positions α and m. This assumes that the magnitude is known, not the direction of m. In fact, the magnitude m is known because the magnet calibration data is provided by the manufacturer. It should be noted that this technique requires an additional magnetic sensor to determine the orientation of the magnetic dipole. Mathematically, the orientation of the magnetic dipole is indicated by a + or − symbol. The symbol of the mathematical function is determined using a further magnetic sensor that only needs to measure the magnetic field strength B. Further, a combination of these various techniques may be used by the detector system 100 to determine the position α of the magnet 120.

In yet another alternative, a Kalman filter may be used with equations (1) and (2) above to track the position of the magnetic dipole m with respect to the multiple detector array formed by the magnetic sensors 108-114. Good. As known to those skilled in the art, the Kalman filter is a statistical prediction filter that uses statistical signal processing and optimal estimation. Y. Bar-Shalom and R.A. E. Several textbooks, such as “Tracking And Data Association” by Fortmann, Academic Press, Boston, 1988, provide details on the theory and operation of Kalman filters. In addition to the individual techniques described above, any or all of these combinations of techniques can be used, such as the sum of cost functions for each sensor type. For example, the difference between Δ _ij (prediction) and Δ _ij (measurement) may need to match within a certain tolerance. If multiple mathematical techniques cannot identify a solution where all the difference values meet its tolerance, the display 106 can be used to signal the operator (see FIG. 15A). The estimation of the error of each sensor measurement is irrelevant and small, and the uncertainty in the estimation of the position α can be calculated, for example, using the Cramer-Rao limit. Thus, the degree of redundancy between measurement techniques can be advantageously implemented by the detector system 100. Such redundancy is highly desirable for biomedical applications.

  FIG. 13 illustrates the operation of detector system 100 for a particular configuration of magnetic sensors 108-114. However, the techniques described above may be generalized to virtually any fixed sensor configuration. Assuming that the intensity of the magnetic dipole m is known, a minimum of one gradient sensor or eight magnetic field sensors are required to measure G (s) and B (s), respectively. The magnetic sensor can be relatively arbitrarily configured and thus easily placed in position within the housing 102 (see FIG. 13) based on device design and / or other signal or noise considerations. May be.

The magnetic sensors 108-114 may be configured using a known earth magnetic field. In the absence of an inhomogeneous magnetic field (ie, far from any strong magnetic dipole), the X sensor elements of all sensors 108-114 can be read simultaneously. Similarly, all Y and Z sensor elements can be read simultaneously. In any configuration, the sum of the squares of the average readings of the magnetic field strength for each orthogonal direction (ie, B _x , B _y , and B _z ) should be constant. Using a constant value of the Earth's magnetic field, an appropriate calibration factor for each magnetic sensor can be determined using conventional algebraic and least squares fitting methods.

  An alternative calibration technique uses a known low strength magnet that is placed in one or more positions relative to the magnetic sensors 108-114. Measurements are performed at each of one or more locations to determine an appropriate calibration factor for each magnetic sensor. Other techniques such as the use of electromagnetic cages, Helmholtz cages, etc. may be used to calibrate the magnetic sensors 108-114.

  Display 106 (see FIG. 13) provides a graphical representation of the position of magnet 120 relative to housing 102. 19A-19D illustrate several different techniques used by detector system 100 to indicate the position α of magnet 120 (see FIG. 14). In the aspect illustrated in FIG. 19A, the display 106 uses a circle 250 and a pair of orthogonal lines 252a and 252b to indicate the position α of the magnet 120 relative to the housing 102. The orthogonal lines 252a and 252b provide the health care provider with visual indicators to help determine when the magnet 120 is centered under the detector system 100.

  In an alternative embodiment illustrated in FIG. 19B, fixed indicators 254, such as orthogonal lines 254a and 254b, form a line of sight on the center of display 106. A circle 250, or other indicator, is used to provide a visual indication of the position α of the magnet 120 relative to the housing 102. Circle 250 is centered on the line of sight at the center of display 106 when magnet 120 is centered directly under detector system 100.

  In yet another aspect shown in FIG. 19C, the display 106 provides different indicators, such as arrows 260, to provide a visual indication of the position α of the magnet 120. Further, the orientation of the magnet 120 may be instructed using the arrow 260.

  The depth of the magnet 120 below the patient's surface can be shown on the display 106 in various ways. For example, the portion 106a of the display 106 can provide a visual indication of the depth of the magnet 120 using a bar graph, such as that shown in FIG. 19D. However, the depth indicator portion 106a of the display 106 can also provide a numerical readout of the depth of the magnet 120 in absolute units, such as centimeters, or in relative units.

  The internal display 106 and the external display are two-dimensional display devices, but the magnet 120 can be displayed using shadow and graph functions to create the appearance of a three-dimensional object. Conventional display techniques used in video games and other computer applications can be easily applied to the system 100 so that the magnet 120 is a three-dimensional arrow to indicate the position and orientation of the magnetic dipole, or An arrow extending from it may then be used to make it look like a donut to simulate the shape of the magnet. The techniques used for such three-dimensional graph display are well known in the art and need not be described in more detail.

  In addition to displaying the magnet 120 as a three-dimensional graph image, the system 100 can display the magnet from any viewpoint. For example, FIG. 17B illustrates the position of the magnet as viewed from the top of the patient, and thus illustrates the position of the magnet in the XY plane. However, in some situations it is desirable to view the magnet from a different viewpoint, such as the YZ plane. This viewpoint allows the user to see the movement of the magnet 120 as it moves up and down within the patient (ie, movement on the Z axis). A user selectable display viewpoint is particularly useful in applications such as image guided surgery where the user must be able to visualize the motion of the intragastric device in any plane. For example, it is important to see directional motion in all three dimensions when inserting a cardiac catheter. There are known techniques that allow the display of the magnet 120 from any viewpoint. For example, MICROSOFT (R) WINDOWS (R) includes a feature that allows a user to select a display viewpoint using a mouse, keyboard, or other input device.

  Thus, the detector system 100 determines the position α of the magnet 120 in three-dimensional space and provides an easily readable visual indication of the magnet position, including the depth indication, as well as the orientation of the magnet dipole. The case 102 is exemplified as a rectangular case in which the magnetic sensors 108 to 114 are distributed at equal distances in the case 102, but the rectangular shape is selected because it is easy for a medical provider to grasp. . However, the housing 102 may have any shape or size. Further, the display 106 is illustrated as a liquid crystal display, but may be any convenient two-dimensional display, such as a dot matrix display. Thus, this aspect is not limited by the particular size or shape of the housing 102 or the particular type of display 102. Furthermore, the detector system 100 can operate satisfactorily with a variety of different magnetic sensors. Thus, the system is not limited by the particular number or type of magnetic sensors used in detector system 100.

  Various techniques for detecting the three-dimensional position and angular orientation of a single magnet have been described above. However, the principle of the aspect may be extended to detection of multiple magnets. The system 100 includes a first peripherally inserted central catheter (PICC) 300 that is inserted into one arm of a patient and has a magnet 302 coupled to a distal portion thereof, such as that illustrated in FIG. The position of the two intragastric devices can be detected. The second PICC 304 is inserted through the other arm of the patient and includes a magnet 306 coupled to its distal portion. One skilled in the art will recognize that FIG. 20 serves only to illustrate the use of multiple tubes with multiple magnets. Any combination of known intragastric devices can be placed using the techniques described herein. Thus, aspects are not limited by the particular type of medical tube (eg, catheter) or device.

As previously described, the position and orientation of a single magnet may be described in three-dimensional space with five parameters. Similarly, the position and orientation of the magnet 306 is also characterized by the same five parameters, but the corresponding parameters are likely to have different values. Thus, the position and orientation of magnets 302 and 306 may be characterized by a total of 10 unknown parameters. Furthermore, the earth's magnetic field contribution in the x, y, and z directions is unknown. Thus, the model used by detector system 100 for two magnets has 13 unknowns and requires 13 independent measurements. In the exemplary embodiment of the detector system illustrated in FIG. 21, the five magnetic sensors located at positions S _{1 to} S ₅ each having three orthogonally oriented sensing elements include 15 magnetic sensing elements. Provide set. This is sufficient to detect the position and orientation of magnets 302 and 306.

As illustrated in FIG. 21, the magnet 302 is disposed at the position α ₁ . As is known in the art, the magnet 302 has a magnetic dipole represented by the vector m ₁ . Similarly, magnet 306 has a magnetic dipole located at position α ₂ and represented by vector m ₂ . Vectors m ₁ and m ₂ represent the strength and orientation of the magnetic dipoles of magnets 302 and 306, respectively.

Magnetic sensors arranged at positions S _{1 to} S ₅ detect the total magnetic field generated by both magnets 302 and 306. Thus, the vector sensed by each magnetic sensor at positions S ₁ -S ₅ is a combination of magnetic dipole m ₁ and m ₂ vectors. However, the system 100 knows the strength of the magnetic dipoles m ₁ and m ₂ and the position and orientation of the respective sensors at the positions S _{1 to} S ₅ . Considering this information, as well as 15 separate measurements, the system can accurately detect the position and orientation of magnets 302 and 306. The measurement technique using the above equation can be applied to two magnets. Although the process described here can place two magnets, the principle can be further extended to more magnets. In the above example, 13 parameters characterize the Earth's magnetic field (3 parameters) and 2 magnets 302 and 306 (5 parameters each). A third magnet (not shown) can be characterized by the same five parameters discussed above. Thus, 18 independent sensors are needed to characterize the three magnets, 23 sensors are needed to characterize the four magnets, and so on.

  The initial estimated positions of magnets 302 and 306 may also be determined using neural network 154 (see FIG. 15A) or other techniques described herein. As described in more detail below, the system 100 may include an array of magnetic sensors (see FIG. 16). In this aspect, the estimation processor 152 can select a subset of sensors having measured magnetic field strength values that exceed a predetermined threshold. The initial position of the magnet may be based on a value derived from a magnetic sensor whose reading exceeds a predetermined threshold.

  Further, the system 100 may perform the above iterative process to determine the position and orientation of the magnets 302 and 306. An optimization process for minimizing the error (or cost) function for multiple magnets can be readily ascertained based on the above description. For brevity, the description will not be repeated here.

  If a single magnet is associated with the intragastric device, the position and angular orientation of the magnet and thus the intragastric device can be determined in the manner described above. The above technique is sufficient to detect the five degrees of freedom of the magnet and its associated intragastric device. However, one skilled in the art can understand that a dipole magnet is symmetric about its axis of magnetization. Thus, the intragastric device may rotate along the axis of magnetization and the magnets generate the same magnetic field. Therefore, the above system cannot determine the angular rotation of the intragastric device.

In another aspect, both magnets 302 and 306 are coupled to a single intragastric device. As illustrated in FIG. 22, magnets 302 and 306 are oriented so that their axes of magnetization are not aligned with each other. In the example illustrated in FIG. 22, the magnetization axis of the magnet 302 is orthogonal to the magnetization axis of the magnet 306. Given the knowledge of the strength of the magnetic dipoles m ₁ and m ₂ and the orientation of the axis of magnetization and the physical position of the magnet 302 relative to the magnet 306, the system 100 thereby detects the sixth degree of freedom of the intragastric device. can do. This is illustrated in FIG. 22 as the rotational displacement ω. The technique for determining the position and orientation of magnets 302 and 306 is the same as described above. However, in view of the fixed orientation of the axis of magnetization and further knowledge of the physical position of the magnet 302 relative to the magnet 306, the rotational displacement 10 of the intragastric device can be detected. For example, the intragastric device may be an endoscope guided by an image shown on a display 106 (see FIG. 15A) or an external display. The system 100 can advantageously calculate the six degrees of freedom (x, y, z, θ, φ, and ω) of the intragastric device coupled with the magnets 302 and 306.

  As previously described, a number of magnetic sensors may be arranged to form a sensor array as illustrated in FIG. The housing 102 may be sufficiently large (eg, 9 inches × 12 inches). In this manner, the housing 102 may remain fixed in a fixed position on the patient's measurement surface. Since magnet 120 (see FIG. 14) or magnets 302 and 306 (see FIG. 20) are located near housing 102, one or more sensors detect the presence of a magnetic field. As noted above, a sufficient number of magnetic sensors must detect the magnetic field and provide data in order to accurately characterize the position and orientation of the magnet. As noted above, a sufficient number of magnetic sensors must detect the magnetic field and provide data in order to accurately characterize the position and orientation of the magnet.

FIG. 16 illustrates an array of 16 magnetic sensors that are uniformly distributed in the housing at positions S ₁ -S ₁₆ . As previously described, each magnetic sensor may include individual magnetic sensing elements arranged in three orthogonal dimensions, which may be conveniently characterized as x, y, and z. The orientation of the sensor along the x, y, and z axes provides a convenient means for describing a magnetic sensor. However, the principle of the embodiment does not require a specific orientation of any sensor at positions S ₁ -S ₁₆ , and in fact the sensors need not be evenly distributed at positions S ₁ -S ₁₆ . However, proper operation of the system 100 requires that the position and orientation of each magnetic sensor and magnetic sensing element be known.

  As described above, a small detector array may be moved relative to the patient to track the insertion of the intragastric device in the coupled magnet. As the magnetic sensor moves, the effect of the Earth's magnetic field may change. Therefore, recalibration is necessary when the sensor is moved relative to the patient. The advantage of the large array illustrated in FIG. 16 is that the housing 102 does not need to be moved relative to the patient. Thus, it is only necessary to measure and cancel out the effects of the Earth's magnetic field over a single time.

As previously described, the initial position of the magnet may be determined using the sensor array of FIG. 16 using magnetic fields detected from four sensors having maximum values or values above a predetermined threshold. . For example, assuming that the initial position of the magnet is unknown, the magnetic sensors at positions S ₅ , S ₆ , S ₉ and S ₁₀ all have detection values above a predetermined threshold or are at other positions. It has a higher value than that detected by the sensor. As an initial estimate, the estimation processor 152 (see FIG. 15A) causes the magnet 120 (see FIG. 14) to be positioned equidistant from the magnetic sensors at positions S ₅ , S ₆ , S ₉ and S _10. Then you may guess. Alternatively, the positions within the boundaries defined by these positions S ₅ , S ₆ , S ₉ and S ₁₀ may be weighted based on the values detected by the respective sensors at these positions. For example, the sensor at position S S ₆ may have the highest value of the sensors at positions S ₅ , S ₆ , S ₉ and S ₁₀ . Therefore, estimation processor 152, the position S _5, S _6, may calculate an initial position about the magnet 120 closer to the position S S ₆ rather than equidistant from each of S ₉ and S _10. In addition, the estimation processor 152 may use other weight functions.

In yet another alternative aspect, the values detected by the sensors at positions S ₅ , S ₆ , S ₉ and S ₁₀ may be provided to neural network 154 and processed in the manner described above. Accordingly, the system 100 provides various techniques for determining the initial estimated position of the magnet 120. Through the above iterative process, the position and orientation of one or more magnets can be easily detected and tracked by the system 100.

[ Example ]
Incorporating Parts into the Device FIG. 23 depicts one embodiment of a balloon 1100 that incorporates a pellet 1110 in the enclosed volume of the intragastric balloon. The pellet 1110 may be an electromagnetic sensor, magnetic sensor, acoustic sensor, power generation sensor, pH sensor and / or other sensor or marker as described herein. The pellet 1110 may be unfixed or attached to the wall of the intragastric balloon. FIG. 24 depicts one embodiment of a balloon 1200 that incorporates a button 1210 attached to the opposite side of the intragastric balloon. Button 1210 may be electromagnetic, magnetic, acoustic, power generation, pH, and / or other buttons, sensors or markers described herein. FIG. 25A depicts a cross section of a valve system 1300 that includes a septum plug 1310, a head unit 1312, a ring stop 1314, a tube septum 1316, and a retaining ring 1318. The retaining ring can include electromagnetic, magnetic, acoustic, power generation, pH, and / or other sensors or markers. 25B is a top view of the valve system represented by a cross-section along line 1D-1D in FIG. 13A. FIG. 25C is a top view of the valve system of FIGS. 13A and 13B incorporated into the wall of the intragastric balloon 1320. FIG. FIG. 26 represents a gel cap 1400 containing the intragastric balloon of FIGS. 25A-C in an uninflated form. The gel cap containing the uninflated balloon is routed by the intragastric balloon valve system through the press-fit connection structure 1414 incorporating magnetized components, such as a needle (not shown). Engages with a dual catheter system including.

Acoustic Tracking and Visualization Subcomponent Various aspects can implement acoustic tracking and visualization functionality in the devices and systems described above. As used herein, “visualization” is used broadly and refers to ultrasonic and other acoustic wave data, such as wave intensity, wave orientation, wave temporal properties, wave effects on sensors, and tracking of desired items. By audio, visual, tactile or other output based on ultrasound, acoustic and other attributes that can be used to facilitate placement, identification and characterization, and ultrasound data characterizing the item of interest Refers to placing, characterizing, or otherwise identifying the item of interest within the body in several ways. As used herein, “acoustic” refers to the use of mechanical waves in gases, liquids or solids and includes the use of techniques such as vibration, sound, ultrasound and very low frequency sound. While the acoustic aspects are described primarily in the context of ultrasound, it is understood that the aspects can also be implemented with other acoustic techniques, such as those noted above and not explicitly indicated. . Accordingly, the ultrasound techniques described herein can be implemented in other acoustical manners. Because of the non-invasive nature of acoustic-based devices, the physician may wish to determine or confirm the position and orientation of the device before inflation or during the procedure. Accordingly, acoustic related devices and methods are disclosed for determining and confirming the position, orientation and / or status of intragastric devices at all stages of administration. Such acoustic-based devices and technologies include ultrasound-related means, examples of which include, but are not limited to, ultrasound examinations or ultrasonic imaging, “highly directional” Doppler systems , Doppler imaging systems, and systems related to intravascular ultrasound diagnostic techniques.

  Ultrasound is a vibrating sound pressure wave having a frequency that exceeds the upper limit of the human audible range. Thus, ultrasound is not distinguished from “normal” (audible) sound by differences in physical properties, but only by the fact that humans cannot hear it. This limit varies from person to person, but is approximately 20 kilohertz (20,000 hertz) in healthy young adults. Ultrasonic devices operate at frequencies from 20 kHz to several gigahertz.

  Diagnostic sonography (ultrasound) is an ultrasound-based diagnosis used to visualize body structures, including tendons, muscles, joints, blood vessels and internal organs, for possible medical conditions or lesions Imaging technology. The practice of examining pregnant women using ultrasound is called obstetric sonography and is widely used. In physics, “ultrasound” refers to sound waves with a frequency that is too high to be heard by humans. By sending ultrasonic pulses to the tissue using an ultrasonic transducer (probe), an ultrasonic image (sonic examination drawing) is created. Sound reflects and reverberates from tissue. This echo is recorded and presented as an image to the operator. The techniques employed to image tissues and organs using ultrasound can be applied for imaging one or more intragastric devices of the embodiment.

  Many different types of images can be formed using ultrasound. The best known type is a B-mode image, which displays a two-dimensional cross-sectional view of the tissue being imaged. Other types of images can display a three-dimensional region, allowing for accurate placement of intragastric devices within the gastric system. In certain embodiments, the application of ultrasound can also be used to rupture the device, facilitating removal of the contracted device from the body at the end of its useful life.

  Compared to other well-known methods of medical imaging, ultrasonic examination has several advantages. It provides images in real time (not after acquisition or processing delay), it can be carried and brought to the bedside of sick patients, it is substantially lower in cost and it is harmful ionizing radiation Is not used. Each of these features is particularly advantageous for placement or tracking of intragastric devices.

  Common diagnostic sonography scanners operate at frequencies in the range of 2-18 megahertz, while bioscopy uses frequencies up to 50-100 megahertz. The choice of frequency is a trade-off between the spatial resolution of the image and the imaging depth. Lower frequencies result in smaller resolution but image deeper in the body. Higher frequency sound waves have smaller wavelengths and can therefore be reflected or scattered from smaller structures. Higher frequency sound waves have a greater attenuation coefficient and are therefore readily absorbed by the tissue, limiting the depth of sound wave penetration into the body. Different frequencies can be employed depending on the state of the intragastric device at the time of imaging. For example, when imaging in the throat region where the device is expected to be close to the body surface, due to the smaller cross-section, the compressed, unexpanded intragastric device may have a higher imaging wavelength ( (E.g. 7-18 MHz), but if the distance to the skin surface is farther and lower axial and lateral resolution but greater penetration is observed, A lower imaging wavelength (e.g., 1-6 MHz) may be desirable for the larger bulged intragastric device.

  Ultrasound can use a hand-held probe (called a transducer) that is placed and moved directly on the patient. Sonography is effective in imaging the soft tissue of the body. Superficial structures such as muscles, tendons, testes, breasts, thyroid and parathyroid glands, and neonatal brain are imaged at higher frequencies (7-18 MHz), providing better axial and lateral resolution. The Deeper structures, such as the liver and kidneys, are imaged at lower frequencies of 1-6 MHz with lower axial and lateral resolution but greater penetration.

  In the case of ultrasound, sound waves are typically generated with piezoelectric transducers or capacitive micromachined transducers housed in a housing that can take several forms. A strong short electrical pulse from the ultrasonic machine creates the transducer ring at the desired frequency. The frequency may be anywhere between 2 MHz or less and 18 MHz or more. The sound is focused either by the shape of the transducer, the lens in front of the transducer, or a complex set of control pulses (beamforming) from an ultrasonic scanner machine. This focusing produces arc-like sound waves from the transducer surface. The waves move into the body and focus at the desired depth.

  To allow the sonography machine to change the direction and depth of focus, the transducers focus their beams with a physical lens or use phased array technology. Almost all piezoelectric transducers are made of ceramic. The material on the surface of the transducer allows sound to be transmitted efficiently into the body (eg, rubber-like coating, impedance matching form). In addition, an aqueous gel is typically placed between the patient's skin and the probe. Aspect techniques can be applied to the administration of gastric devices to patients with empty stomachs or patients having a stomach partially filled with liquid and / or solid stomach contents.

  Sound waves can be partly from layers between different tissues, or from the interface between the compressed form of the device and the surrounding tissue, or from the interface between the swollen form of the device and the surrounding tissue or gastric fluid or contents. Is reflected. Specifically, the sound is reflected anywhere where there is a density change, so that some of the reflection returns to the transducer. The return of the sound wave to the transducer results in the same process it took to send the sound wave, except in the reverse case. Return sound waves oscillate the transducers, which convert the vibrations into electrical pulses that travel to an ultrasonic scanner where they are processed and converted into digital images. The sonographic scanner determines from each received echo how long it took since the sound was transmitted until the echo was received or how powerful the echo was. For a phased array, the focal length that allows a clear image of the echo at that depth can also be determined. Ultrasonic image energy is delivered as pulses with a specific carrier frequency. Moving objects change this frequency by reflection, so having a simultaneous Doppler sonography that allows motion imaging is only an electronics issue. The received image is then digitally displayed.

  Ultrasound inspection (sonic inspection) uses a probe containing a plurality of acoustic transducers to send a pulse of sound into a material. As in the case of a compressed or inflated intragastric device, each time a sound wave encounters a material of a different density (sound impedance), a portion of the sound wave is reflected back to the probe and detected as an echo. The time it takes for the echo to travel to the probe is measured and used to calculate the depth of the tissue interface that causes the echo. The greater the difference between the acoustic impedances, the greater the echo. If the pulse strikes a gas or solid, the difference in density is very large and most of the acoustic energy is reflected, making it impossible to look deeper. This feature is advantageous for imaging of swollen intragastric devices.

  The frequency used for imaging is generally in the range of 1-18 MHz. Higher frequencies have correspondingly smaller wavelengths and can be used to create more detailed sonographs. However, since sound attenuation increases at higher frequencies, lower frequencies (3-5 MHz) are used to provide better penetration of deeper tissue.

  It is very difficult to see deep into the body with sonography. Some acoustic energy is lost each time an echo is generated, but most (approximately) of it is lost from sound absorption. The speed of sound is different when it travels through different materials and depends on the acoustic impedance of the material. However, the sonograph assumes that the speed of sound is constant at 1540 m / s. The result of this assumption is that in a real body with inhomogeneous tissue, the beam is slightly out of focus and image resolution is reduced. However, in various embodiments, the profile of the device in its different shape (compressed, inflated, inflated, deflated, deflated) is generally easily ascertained despite the lower image resolution. The

  The ultrasonic beam is swept to generate a two-dimensional (2D) image. The transducer can be mechanically swept by rotating or rocking. Alternatively, a one-dimensional phased array transducer can be used to electronically sweep the beam. Received data is processed and used to construct an image. In that case, the image is a 2D representation of a cross section of the body. 2D images are acceptable to determine the longitudinal passage of the device through the gastrointestinal tract. Once in place, it may be desirable to image the device in the stomach in three dimensions. A 3D image can be generated by acquiring a series of adjacent 2D images. As commonly used in cardiac imaging, a 2D phased array transducer that can sweep the beam in 3D may be employed. Doppler sonography is used to image the motion. Different detected velocities are represented in color for ease of interpretation. Alternatively, the color can be used to represent the amplitude of the received echo. Such an ultrasound examination can advantageously be employed to image the device as it descends the esophagus.

  Several modes of ultrasound used in medical imaging can be employed in various ways. The A mode (amplitude mode) is the simplest type of ultrasonic wave. A single transducer scans a line through the body with echoes plotted on the screen as a function of depth. A-mode ultrasound also allows precise and precise focusing of destructive wave energy, for example, for use in deflating a swollen intragastric device. In B-mode (luminance mode) ultrasound, a linear array of transducers simultaneously scans a plane through the body that can be viewed as a two-dimensional image on the screen. This mode is now more commonly known as the 2D mode. The C-mode image is formed on a prescribed plane in the B-mode image. A gate is used that selects data from a specific depth from the A-mode line. The transducer is then moved in a 2D plane to sample the entire area at this fixed depth. As the transducer traverses the area in a spiral, a 100 cm 2 area can be scanned in approximately 10 seconds. In M-mode (motion mode) ultrasound, pulses are emitted in rapid succession-each time either an A-mode or B-mode image is taken. Over time, this is similar to recording a video with ultrasound. This can be used to determine the velocity of the intragastric device, as the boundary of the intragastric device produces a reflection that moves relative to the probe. The Doppler mode uses the Doppler effect in measuring and visualizing moving objects such as intragastric devices. The speed information can be presented as a color-coded overlay on the B-mode image. Doppler information can be sampled continuously along a line through the body, and all velocities detected at each time point are presented (in the timeline). In pulsed wave (PW) Doppler, Doppler information is sampled from only a small sample volume (defined by 2D images) and presented in the timeline. Dual mode is used to refer to simultaneous presentation of 2D and (usually) PW Doppler information. Color Doppler can be called triple mode. In pulse reversal mode, two successive pulses with opposite signs are emitted and then drawn from each other. This means that any linear response component will disappear and the gas with non-linear compressibility will be noticeable. Pulse inversion can also be used in a similar manner, as in the harmonic mode where the deep penetration fundamental frequency is released into the body and overtones are detected. In this way, noise and artifacts due to reverberation and aberrations are greatly reduced. The penetration depth can be obtained with improved lateral resolution. An additional extension or additional technique of ultrasound is biplanar ultrasound, where the probe has two 2D surfaces that are perpendicular to each other, providing more efficient localization and detection. The omniplane probe is capable of rotating 180 ° to obtain a double image. In 3D ultrasound, many 2D surfaces are added together digitally to create a three-dimensional image of the object.

In contrast-enhanced ultrasound, the microbubble contrast agent enhances the ultrasound, resulting in increased contrast. Similarly, advantageously, the intragastric device can be completely or partially filled with a heavy gas, such as perfluorocarbon or nitrogen, to enhance contrast. Heavy gases suitable for use include, but are not limited to, nitrogen, argon, SF ₆ and halogenated carbons such as C ₂ F ₆ , C ₃ F ₈ , C ₄ F ₁₀ , C ₄ F ₈ , C ₃ F ₆ , CF ₄ and CClF ₂ —CF ₃ are included.

  Sonography is augmented with Doppler measurements that employ the Doppler effect to assess whether a structure such as an intragastric device is moving towards or away from the probe and the relative velocity of the structure. be able to. By calculating the frequency shift of a particular sample volume, such as the flow rate within an artery or the jet of blood flow over a heart valve, its velocity and direction can be determined and visualized. This is particularly beneficial in cardiovascular studies (vascular and cardiac sonography) and is essential in determining blood reflux in the liver vasculature in many areas, such as portal hypertension. Doppler information is displayed graphically using spectral Doppler, or as an image using color Doppler (directional Doppler) or power Doppler (omnidirectional Doppler). This Doppler shift is provided to be in the audible range and often heard using stereo speakers. This produces a synthetic but very characteristic pulsating sound. Most modern sonographs use a pulse Doppler for speed measurement. A pulse wave machine transmits and receives a series of pulses. The frequency shift of each pulse is ignored. However, the relative phase change of the pulse is used to obtain the frequency shift (since the frequency is the rate of phase change). The main advantage of pulse Doppler over continuous wave is that distance information is obtained (the time between transmitted and received pulses can be converted to distance with knowledge of the speed of sound) and gain correction is applied. It is. The disadvantage of pulse Doppler is that the measurement can suffer from aliasing. The term “Doppler ultrasound” or “Doppler sonography” is accepted to apply to both pulsed and continuous Doppler systems, despite the different mechanisms of measuring velocity. There is no standard for the display of color Doppler. The general rule is to use red to indicate the flow towards the transducer and blue for the flow away from the transducer, or a red shift that represents a longer wave of echoes (scattered) from the target. Is to display.

  Ultrasonography offers several advantages over imaging intragastric devices in vivo. Ultrasound inspection is particularly useful for imaging the solid surface very well and accurately representing the interface between the solid and the fluid-filled space, both in the compressed and expanded form of the solid, or contracted Even imaging of shaped devices is possible. This method allows the acquisition of live images showing the movement and position of the intragastric device. This method has no known long-term side effects and rarely causes discomfort to the patient. The device is widely available and relatively flexible. Small and easy to carry scanners are available so that examinations can be performed in a doctor's office or clinic. This technique is relatively inexpensive compared to other methods such as CAT imaging or magnetic resonance imaging. Spatial resolution is better with high frequency ultrasound transducers than in most other imaging modalities, allowing accurate tracking of intragastric devices.

  It is known that it may be difficult to image tissue structures deep in the body using ultrasound, especially in obese patients. The body shape has a great influence on the quality of the image. Image quality and diagnostic accuracy are limited in obese patients, and the upper subcutaneous fat attenuates the sound beam, requiring lower frequency transducers (lower resolution). However, the solid compressed form of the device provides satisfactory image contrast. Especially when containing nitrogen, SF6 or other halogenated carbons, the expanded form of the device shows excellent contrast unlike in vivo tissue structures, allowing easy imaging even in morbidly obese bodies.

  In some embodiments, the ultrasonic sensor includes a non-contact sensor. Ultrasonic levels or sensors or sensing systems do not require contact with the target. In the medical industry, this is an advantage over in-line sensors that may otherwise interfere with the target marker or item. In some embodiments, the sensor is a microphone.

  In some embodiments, a pulse wave system is used. The principle of pulsed ultrasonic technology is that the transmitted signal consists of short bursts of ultrasonic energy. After each burst, the sensor electronics looks for a return signal in a small time window corresponding to the time it takes for the energy to pass through the target medium. Only signals received during this window are eligible for additional signal processing. In some embodiments, a continuous wave system is used. In a pulsed, continuous or other wave system, the sensor may be a microphone that receives the return wave signal.

  In some embodiments, the marker can transmit an ultrasound signal. For example, ultrasound identification (USID) automatically tracks the position of the intragastric device in real time using simple and inexpensive nodes (badges / tags) attached or embedded in the ultrasound device, Which can then be used to identify and then transmit ultrasonic signals to convey their position to an ultrasonic sensor such as a microphone.

  A computer system can be implemented with an ultrasonic placement system. The computer system includes hardware and software that receives data from the ultrasound sensor and calculates information related to the position, orientation, and / or status of the intragastric device according to a specific algorithm. In some aspects, the hardware may include a central processing unit, memory, analog to digital converter, analog circuitry, display. In some embodiments, the software performs various desired output calculations, including calibration, initialization, prediction, estimation, measurement of magnetic sensor data, position, orientation, size, configuration, etc., according to the techniques discussed herein. It goes through several steps, including:

  The output of the processor regarding the position, orientation and / or status of the intragastric device can be communicated to the user in several ways. In some embodiments, the output is shown visually on the display.

  In some embodiments, the output of the processor related to the position, orientation and / or status of the intragastric device is communicated to the user through a speaker.

  In some embodiments, processor output related to the position, orientation and / or status of the intragastric device is communicated to the user through a combination of methods. For example, the system can employ a visual graphic display along with an audible alert sent through a speaker.

  In some embodiments, the ultrasound placement system is calibrated prior to use. In order to verify that the output signal is within the expected range, the ultrasonic markers and sensors are placed in a predetermined position and orientation. In some embodiments, the ultrasound placement system is calibrated or otherwise validated with a human patient simulator or dummy to examine the ultrasound placement system as the ultrasound marker moves through the simulator. The In some embodiments, the ultrasound placement system is inspected for a stray signal from nearby acoustic interference.

  In various embodiments, an ultrasonic sensor can be used with one or more markers to place or otherwise characterize an ingested intragastric device. In some embodiments, off-the-shelf intragastric devices, such as swallowable, inflatable balloons, can be used without modification with any ultrasound marker. Ultrasonic sensors that pulse sound waves with the device and sense their return signals with a microphone can be used outside the body. The device can be swallowed in a contracted state and then expanded or expanded upon entering the stomach. The ultrasonic sensor can be used to position or otherwise characterize the device by pulsing the device and receiving a return signal according to the techniques described above.

  Ingested devices can be placed using an ultrasonic intragastric placement system. In some embodiments, the device can be placed on the sensor by pulsing at various positions and analyzing the return signal. For example, by correlating the return wave signal with the position of the body before swallowing the device, a return signal corresponding to a body organ without the device can be determined in advance. This would create an ultrasound map of the organ or body without the device. Then, after swallowing the device and by operating the sensor on the body, the position of the device is thus determined if a different signal is returned for the corresponding position of the body. This can be performed according to the techniques described above.

  The orientation of the ingested device can be confirmed using an ultrasonic intragastric placement system. In some embodiments, by pulsing and sensing at various locations on the device and analyzing the return signal, the sensor can determine the orientation of the intragastric device. For example, the device can be pulsed in various orientations so that there is a predefined database of known correlations between the return wave signature and the orientation of the device prior to ingestion by the patient. This can be done for devices that are deflated, expanded or otherwise. Next, after ingestion, the device can be pulsed and the return signal compared to a predefined database to determine the orientation of the device according to the techniques described above.

  In addition, an ultrasonic intragastric placement system can be used in accordance with the techniques described above to characterize the various sizes and configurations of ingested devices. For example, balloon inflation or inflation or configuration of multiple balloons can be characterized and evaluated. In some aspects, the sensor can characterize one or more devices by pulsing and sensing at various locations on the device and analyzing the return signal. For example, a deflated device will return a different pulse signature than a dilated device. In this way, the device can be characterized as being inflated, deflated, or in some other state. The inflated device could be further characterized prior to ingestion by the patient so that a return signal signature is predetermined and serves as a guide for assessing the condition of the device. In some embodiments, the ultrasound placement system can be used with a contraction system to characterize the contraction process.

  The disclosed ultrasonic intragastric placement systems and techniques can be used to characterize the timing and other attributes of various methods of administration. Regardless of whether the device is administered using endoscopic techniques or orally, the progress of the device as it travels to the stomach can be tracked with an ultrasound placement system. For example, the effects of swallowing the device with hard gelatin or water or other consumables can be characterized by tracking the position and orientation while it is ingested. In some embodiments, an endoscope employed to deliver an intragastric device incorporates an ultrasound transmission device at a preselected distance from the deployed intragastric device. Ultrasound transmission allows for precise placement of the intragastric balloon as well as monitoring the inflation process due to changes in the transmitted ultrasound due to proximal inflation of the intragastric device.

  In some embodiments, the ultrasound placement system can characterize an intragastric device having a circular or elliptical cross section. Two Ultrasonic modules placed in the device allow the system to measure the size and composition of the device using time-of-flight ultrasound technology.

  Using the speed of sound, the distance can be calculated from the time between transmission and reception. The time between sending an ultrasonic pulse and receiving an echo is given by t = 2d / U or d = Ut / 2, (53), where U is the speed of sound in the target medium, d is the diameter of the device. If transmission occurs in two orthogonal directions, the two dimensions of the intragastric device can be determined, and thus the area of the device can be calculated. Assuming that the device is an ellipse, the equation for determining the area of the ellipse using the major axis (a) and minor axis (b) is as follows:

  If the inside of the expanded device is clear, a clear echo signal is obtained, and the time of flight of the ultrasonic pulse is obtained in the clear area to determine the area of the device. Two methods can be used to detect the presence of foreign or otherwise objects in the device. First, compare the orthogonality signal, which is the amplitude of the scattered ultrasonic pulse in the orthogonal direction, with the echo return of the original pulse. Second, the amount of false return in the original pulse echo can even determine the ratio of solid to liquid objects at the analyzed cross-section of the device.

  The intragastric device can include two orthogonal ultrasonic transmitter / receiver ("transceiver") modules. One transceiver is a front / rear (a / p) ultrasonic module and the other transceiver is a lateral ultrasonic module. The device further includes a microprocessor that measures the time of flight from each transceiver module. The microprocessor can distinguish between device echoes and empty device interiors. The microprocessor can also prepare the signal for transmission. The microprocessor communicates electrically with the computer. In some embodiments, the computer and the microprocessor are integrated into the same part. In at least one aspect, the computer may be a look-up table that can determine the major radius, minor radius, and scatter associated with the device.

  The intragastric device can also include a transmitter that can transmit signals from the device to a location outside the body. The transmitter can include an antenna for transmission, or an antenna in a band (not shown) can be in electrical communication with the transmitter. The device can also include a module that contains a battery or can inductively power the intragastric device electronics. The antenna for receiving the transmitted signal and the receiver in operative communication with the antenna may be external to the patient. A computer having software capable of decrypting and processing signals transmitted by the transmitter and received by the receiver may be included. Computer software can measure the time of flight of horizontal and vertical ultrasonic pulses to determine the length and width of the intragastric device, and determine the area by combining the length and width. It should be noted that the presence of any material in the device can be determined from the scattering of the horizontal receiver to the vertical receiver and the scattering of the vertical receiver to the horizontal receiver.

  Various ultrasonic markers and their acoustic properties can be implemented in an ultrasonic intragastric device placement system together with an ultrasonic sensor or detector. An ultrasonic marker includes any substance, material or object to which an ultrasonic sensor or detector responds. As noted, the ultrasound “marker” used herein includes the intragastric device itself, so that an off-the-shelf unmodified intragastric device is responsive to the ultrasound placement system disclosed herein. It may already contain materials that may or may not be used with it.

  In some embodiments, the marker is a node attached and / or implanted and / or otherwise connected to the intragastric device. Such a node may be, for example, a badge or tag that is responsive to the applied ultrasonic energy. The node can also emit or transmit an ultrasonic signal to communicate its position to the microphone sensor. Nodes can be incorporated into intragastric devices in a variety of arrangements.

Acoustic Location Referring now to FIGS. 27 and 28, a system for otherwise characterizing an intragastric device using ultrasound is illustrated in accordance with at least one aspect of the present invention. The system 10B of FIG. 27 is used to measure device characteristics, such as size, using external tuning circuitry and passive coils embedded in or on the device. System 10B includes a first coiled conductor 12 (or internal coil) placed in intragastric device 14 (shown in more detail in FIG. 28). The phrases “internal coil” and “interpolated coil” are also used herein to describe the first coiled conductor 12. The system further includes circuitry external to the device and patient, including adjustable frequency generator 16, spectrum analyzer 18, and second coiled conductor 20. The phrases “external coil” and “outer coil” are also used herein to describe the second coiled conductor 20. The frequency oscillator may be a variable frequency oscillator, for example. The phrase “frequency oscillator” is used to describe any type of electrical or electronic device that produces repetitive electrical or electronic signals. For example, the frequency oscillator may be an electronic device capable of generating a repeating sine wave. The phrase “spectrum analyzer” is used to describe any electrical or electronic device capable of measuring the frequency and amplitude of a signal.

  As described in detail below, the system further includes appropriate capacitance, inductance, and resistance to allow resonance both when the patient is absent and when the patient is present. For example, the system shown in FIG. 27 includes a variable capacitor 22 that can be adjusted to achieve resonance. Rather than providing a variable capacitor, in some embodiments, the capacitor may be of a fixed value and may include a variable inductor.

  System 10B may also include a device 24 for controlling heating within the internal coil 12 shown in FIG. As seen in FIG. 28, the device 24, eg, a resistor, is in electrical communication with the internal coil. In some embodiments, two electrical leads attached to a two-terminal resistor can be extended from the intragastric device, thereby allowing measurements to be taken. That is, the first terminal of the resistor can be in electrical communication with the first end of the first electrical lead, and the second terminal of the resistor is the first end of the second electrical lead. Can be electrically communicated with. The second ends of the first and second electrical leads can extend outside the exterior of the intragastric device 14.

  In at least one aspect, the electrical lead is accessible through an access port on the patient's body as seen in FIG. FIG. 29 represents an intragastric device 14 having an inner coil 12 having an inflatable portion 26, a solid substrate 28 and a placement tab 30. As can be seen, the electrical lead 32 extends from the injection port 34 to the internal coil 12 to allow measurement of current in the coil. In some embodiments, these leads can be conductively connected to the external circuit such that the external circuit includes its internal coil in the intragastric device 14 and the tuning circuit.

  It should be noted that in the above aspect, no battery or radio frequency (RF) module is required because the current in the intragastric device 14 is the result of induction.

  The system is represented in FIG. 27 with software capable of performing calculations based on the current in the first coiled conductor and the resonant frequency of the external circuit to determine the size of the intragastric device 14. A computer 35B can further be included. The derivation, calculation and theory of system operation are shown below.

To calculate the size, orientation or other characteristics of intragastric device 14, two aspects of the present invention utilize guidance. A first aspect using induction that should be considered is when the interpolated and external coils are placed concentrically and coaxially with respect to each other, as schematically shown in FIG. 30A. Such an aspect occurs when the external coil is placed around the patient's body such that the insertion coil in or on the intragastric device 14 is concentric with the external coil. The number of turns N of each solenoid is equal to the number of turns per unit length (n) * solenoid length (d). Accordingly, the number of turns of the external solenoid in FIG. 30A is given by the formula N ₁ = n ₁ * d ₁ . The external coil is assumed to be excited with the following current:
I = I ₀ sin ωt, (1)
Here, ω is the angular frequency of the current source, and I ₀ is the maximum current of the current source. Next, the magnetic field B of the relatively long coil is given by the following relation:
B = μ · N ₁ I ₀ · sin (ω · t) / d ₁ , (2)
Here, N ₁ is the number of turns in the coil, and d ₁ is the length of the coil. The magnetic flux from the larger external coil inherent in the intragastric device 14 is as follows:
Φ = A ₂ · B = A ₂ · μ · N ₁ · I ₀ · sin (ω · t) / d ₁ , (3)
Here, μ is the magnetic sensitivity of the material contained in the area A _{2 of the} interpolated coil, B is the magnetic field density, and N ₁ is the number of turns in the coil. The electromotive force (emf) generated in coil 2 by coil 1 is given by the following relation:
E = −dΦ / dt = −A ₂ · B = A ₂ μ · N ₁ · ω ₁ · I ₀ · (cosωt) / d ₁ (4)
The voltage induced across the intragastric device 14 is given by the following relationship:
E _T = N ₂ · E = −A ₂ · μ · N ₁ · N ₂ · ω ₁ · I ₀ · cos (ω · t) / d ₁ (5)
The self-inductance (L) of the coil is defined as follows:
L = N · Φ / i = N · A · μ · N / l = N ² · A · μ / d ₁ (6)
Next, the self-guided emf in the coil is as follows:
V = −LdI / dt = −ω · N ² · A · μ · I ₀ · cos (ω · t) / d ₁ (7)
The mutual inductance (M) of the two coils is defined as follows:
M ₂₁ = N ₂ · Φ ₂₁ i ₁ , (8)
Here, the current of the coil 1 generates a bundle in the coil 2.

_{N 2 · Φ 21 = N 2} · B 1 · π · R 2 2, (9)
further,
N ₂ · Φ ₂₁ = N ₂ · N ₁ · π · μ ₀ · R ₂ ² · _i1 / 2 · R ₁ , (10)
Thus, the mutual inductance of the device and the external coil can be given by:
_{M 21 = N 2 · N 1} · π · μ 0 · R 21 2/2 · R 1 (11)
It should be noted that the magnetic field generated by the larger coil is essentially constant throughout the smaller coil, but this is not the case for the larger one induced by the smaller coil. However, the mutual inductance of the larger coil on the smaller one is equal to that of the smaller coil on the larger one.

In the continuation of the derivation, the voltage of the circuit is the sum of the voltages resulting from resistance (VR), capacitance (VC) and inductance (VL), so that V = V _R + V _C + V _L , (12)
Or as a function of time in integral differential form,
ν (t) = I ₁ · R + L ₁ · dI ₁ / dt + 1 / C · ∫I ₁ dt, (13)
Or completely represented by the following differential equation (14):

  Variable frequency oscillator

(14) can be described as follows if the following excitation is applied to the external coil and associated resistors and capacitors:

  A tuned (or resonant) circuit that includes an outer loop has a natural frequency given by:

  The quality factor of the resonant circuit, ie Q, is given by:

  The bandwidth (ω2-ω1) of the frequency plot (ie, the width at half-maximal response as measured with a spectrum analyzer) is given by:

  If the induction emf in the LAGB coil is known,

  Considering an external tuning circuit that does not include LAGB:

It is a general formula for a series RLC circuit. Therefore,

  The proportional half power frequency is given by the following relation:

  Here, an inductive circuit (which is a single conductive loop without other resistance) is included in the external circuit that includes the intragastric device 14 or marker. If the external coil is circuit 1 and the intragastric device 14 or marker is circuit 2:

However, because the device has an applied voltage and because the resistance of the device is small,

  Since we only observe the current parameters of the external coil circuit, the current in LAGB can be eliminated, leaving:

Then, substituting into equation (27) gives the following equation:

  Taking the derivative of equation (30):

this is,

Is equal to

be equivalent to.

  As shown below, the resonant frequency of the external coil varies in the presence of LAGB, as does the frequency bandwidth.

  Comparing the square of the resonant frequency of the external coil when separated and concentric with LAGB gives the following ratio:

Here, ω _{no_lap_band} is a natural frequency without lap band or intragastric device 14 coil in the circuit, and ω _{lap_band} is a natural frequency having lap band or intragastric device 14 coil in the circuit. Equation (36) assumes that the orientation of the external coil relative to LAGB is such that the resonant frequency is smaller in the presence of LAGB. The bandwidth ratio is given by:

The values of L ₁ , L ₂ and M depend on the coil geometry. As described above, the first mode is aimed at a configuration in which the insertion coil and the external coil are placed concentrically and coaxially as in the case of FIG. 4A. In such embodiments,

Where R ₁ and R ₂ are the radii of the two coils, d ₁ and d ₂ are the lengths of the two coils, and A ₁ and A ₂ are the respective areas enclosed by the coils. .

  Based on equations (38)-(40) for M, L1, L2,

  Substituting into equation (36) results in:

  Solving the area A2 of the interpolating coil results in the following:

  A second aspect using induction that should be considered is when the interpolated coil 12 and the external coil 20 are placed in a coaxial non-concentric arrangement relative to each other, as shown schematically in FIG. 30B. . There is an impedance Z shown at 21 between the coils. Such an aspect occurs when the external coil is placed below or above the patient's body rather than around.

  As specified earlier, the values of L1, L2 and M depend on the coil geometry. In the second aspect, ie the geometry of the two coaxial non-concentric coils, L1, L2 and M are as follows:

  Based on equations (44)-(46) for M, L1, L2,

  Substituting into equation (36) results in:

  Solving the area A2 of the interpolating coil results in the following:

  The area of the concentric coaxial aspect of Equation (43) and the non-concentric coaxial aspect of Equation (49) can be summarized by the following equation:

Here, k depends on the coil geometry. Thus, the area is proportional to one absolute value minus the ratio of the squares of the maximum resonance frequencies measured with the spectrum analyzer.

  Thus, both the change in resonance frequency peak and the change in bandwidth can be used to determine the product of the area and magnetic sensitivity of the intragastric device 14 or marker. In both aspects of the guidance method, the external coil can be adjusted in height and orientation relative to the device coil to provide maximum resonance frequency variation from separation to ensure proper relative position. The use of a highly magnetically sensitive fluid in the device or marker ensures that only the area of the device or marker is measured, rather than including stomach tissue.

  As previously specified, the system can include a computer for calculating the area of the intragastric device 14 or marker. Based on the above, as shown in equations (43) and (49) above, those skilled in the art will readily understand how to write software to calculate the area of the interpolated coil.

  In order to adjust the external coil to generate the maximum resonant frequency, some aspects of the invention include a coil holder that secures the external coil. Referring now to FIG. 31A, one embodiment of a coil holder for a concentric coaxial guide embodiment is shown. The coil holder is used to orient the external coil with the internal coil. Since the above calculation is based on the orientation between the two coils, the use of a coil holder can simplify the setup of the system by securing the external coil. As seen in FIG. 31A, the coil holder 36 may simply be an arm that movably engages a vertical mount 37. It is important that the coil holder 36 can be raised and lowered. It is also important that the coil holder 36 can be tilted, for example about a point 38 on the coil holder. In this way, the outer coil 20 can be placed concentrically and coaxially around the inner coil 12 in the patient. There are many other possible aspects of the coil holder.

  Referring now to FIG. 31B, another aspect of the coil holder is shown. Specifically, FIG. 31B represents a coil holder for a non-concentric, coaxial guiding aspect. As seen in FIG. 31B, the coil holder 36 may simply be a small table-like device placed under the seat of the chair 39. It is important that the coil holder 36 can be tilted as before, thereby aligning with the internal coil in the patient aligning the external coil 20. In such an embodiment, the patient sits on the chair 39 and orients the coil holder 36 under the chair until the resonant frequency is achieved. There are many other possible aspects of the coil holder. In some embodiments, the coil can be placed on top of the patient rather than below (not shown).

  Referring now to FIG. 32, a method 40 for characterizing an intragastric device or a marker thereon is shown in accordance with at least one aspect of the present invention. The method 40 includes providing 42 a system for characterizing the intragastric device or a marker thereon. Such system aspects are described above. The method further includes a step 44 of tuning a circuit external to the device or marker to the first resonance frequency in the absence of the patient. This allows the practitioner to tune and measure the circuit without the influence of the coil in the marker. The first resonant frequency to be measured is recorded at step 46 of the method. The method further includes the step 48 of placing the external coil near the patient. As described above, the external coil can be placed near the patient in two ways: concentric and coaxial, and non-concentric and coaxial. The coil is placed around or under the patient at an approximate level of the device or marker. The method further includes a step 50 of providing a marker for the patient to swallow.

  The measured characteristics of the device, such as the area, are based on the surge that occurs at the resonance frequency after the patient swallows the marker. The marker may be a non-toxic paramagnetic material, such as water mixed with a solution of magnetic resonance imaging (MRI) contrast agent. In some embodiments, the marker may simply be water. In many cases, the method is sensitive enough to detect device or marker size or other features without ingesting MRI contrast agents or even at very low concentrations. The method further includes the step 52 of tuning a circuit external to the device or marker to the second resonant frequency in the presence of the patient. In some aspects of the method, the external coil can be moved to obtain a maximum change in the resonant frequency of the external circuit. For example, the outer coil can be moved up and down, left and right, and tilted to align with the inner coil. Finally, the method includes calculating 54 the size, orientation or other characteristics of the marker or device based on the difference between the first resonance frequency and the second resonance frequency. From the change in resonance frequency of the external tuning circuit, the area of the device or marker is calculated to know the magnetic sensitivity of the MRI contrast agent.

  Reference is now made to FIGS. 33A-36, a setup and method for device verification using a gastric magnetically sensitive phantom. FIG. 33A represents a top view of a basic phantom setup for device verification. The setup includes a peristaltic pump 60 having a longitudinal axis 63 (shown in FIG. 33B), lumen 64, tissue 66 and three examination laparoscopic adjustable gastric markers 68, eg, a gastric band. It should be noted that more markers 68 can be used depending on the accuracy desired.

  The peristaltic pump is filled with magnetic contrast agent and the pump is set at a speed consistent with human swallowing speed. As shown in FIG. 33B, which is a side view of the embodiment shown in FIG. 33A, gastroscopic markers adjustable with the examination laparoscope are placed in three positions around the pump 60, P1, P2 and P3. The first, second and third markers are offset from each other along the longitudinal axis 63 of the pump.

  Referring now to FIG. 34, the adjustable external coil 70 is moved to be placed around the marker 68. The resonant frequency of each of the markers 68 placed around the pump is measured. The resonant frequency is measured while the magnetic material enters the receiver 72 through the phantom and back through the pump. The value of the resonance frequency is detected by the pickup coil 74 and transmitted to the external electronics 76 for further calculation. The maximum deviation of the resonance frequency is determined from a spectrum analyzer.

  The above techniques do not give an image of the intragastric device or the surrounding anatomy in the body. However, the collected data can be displayed graphically as shown in FIG. As seen in FIG. 35, the change in frequency can be graphically correlated with geometric features such as marker areas A1, A2 and A3 placed at positions P1, P2 and P3, respectively. Thus, the practitioner may be confident that the external coil is operating properly by comparing the known good values of A1, A2 and A3 against the values measured during the verification procedure. it can.

  Note that the previously described external frequency oscillator can be modified to scan the entire gastric lumen using appropriate high frequency excitation, thereby mimicking a trace flow sensing magnetic resonance imaging device. Should. Such a device would provide images using suitable frequency domain software.

  FIG. 36 shows a method of determining the size of the gastric lumen using the gastric magnetic sensitivity phantom. The method includes a step 82 of filling the peristaltic pump with water or an aqueous solution containing a magnetic resonance imaging contrast agent. The method further includes the step 84 of placing the previously described first, second and third markers or devices with the internal coil around the peristaltic pump. The first, second and third markers are offset from each other along the longitudinal axis of the pump. The method further includes a step 86 of setting the pump to approximately the same speed as the human swallowing speed. The method further includes the step 88 of delivering contrast agent through the pump. This method places the external coil 70 of FIG. 34 around the first, second and third markers in turn and each of the first, second and third markers from the spectrum analyzer while delivering contrast agent through the pump. A step 90 of determining a maximum deviation of the resonance frequencies of The method further includes calculating 92 the area of each of the first, second and third markers based on their resonant frequencies.

  It should be noted that the method steps described in FIG. 36 need not be performed in the order shown, and thus the method should not be limited to a particular order. Rather, those skilled in the art will recognize that this method works equally well if, for example, the pump is set to a constant speed before filling with an aqueous solution.

  With reference now to FIGS. 37-40, a system for characterizing an intragastric device, eg, for measuring the size of the device, is illustrated in accordance with at least one aspect of the present invention. FIG. 37 is similar to FIG. However, the embodiment depicted in FIG. 37 has two ultrasonics placed in the device that cause the system to measure the size and composition of the marker and / or device using time-of-flight ultrasound technology instead of an internal coil. Has a module.

  The time between sending an Ultrasonic pulse and receiving an echo is given by:

Where U is the speed of sound in the medium, typically water, and d is the diameter of the target device or marker.

  If the speed of sound is known, the dimensions can be calculated from the time between transmission and reception. If transmission occurs in two orthogonal directions, the two dimensions of the marker can be determined, and thus the area of the marker can be calculated. Assuming that the lumen is an ellipse, the equation for determining the area of the ellipse using the major axis (a) and minor axis (b) is as follows:

  By instructing the patient to drink water and thus flushing the stomach area, the marker can be distinguished from stomach tissue. If the marker is clear, a clear echo signal is obtained and the time of flight of the ultrasonic pulse is obtained in the clear area to determine the marker area.

  Two methods are used to detect the presence of persistent solid objects. First, compare the orthogonality signal, which is the amplitude of the scattered ultrasonic pulse in the orthogonal direction, with the echo return of the original pulse. Second, the amount of false return in the original pulse echo can even determine the solid to liquid object ratio at the cross section of the region surrounded by the marker.

  Referring now to FIG. 37, intragastric device 14 includes two orthogonal ultrasonic transmitter / receiver (“transceiver”) modules 100A, 102A. Transceiver 100A is a front / rear (a / p) ultrasonic module and transceiver 102A is a lateral ultrasonic module.

  Device 14 further includes a microprocessor 104A that measures the time of flight from each transceiver module. The microprocessor can distinguish between tissue echoes and empty markers. The microprocessor can also prepare the signal for transmission. The microprocessor is in electrical communication with computer 105. In some embodiments, the computer and the microprocessor are integrated into the same part. In at least one aspect, the computer may be a look-up table that can determine the major radius, minor radius, and scatter associated with the lumen.

  The intragastric device 14 also includes a transmitter 106A that can transmit signals from the marker to a location outside the body. Transmitter 106A can include an antenna for transmission, or an antenna in a band (not shown) can be in electrical communication with the transmitter. The device 14 also includes a module 108A that can inductively power gastric band electronics that incorporates a battery or can be adjusted by a laparoscope.

  An antenna 110A for receiving the transmitted signal and a receiver 112 in operative communication with the antenna are external to the patient. As before, a computer 35B having software capable of decoding and processing signals transmitted by transmitter 106A and received by receiver 112 may be included. The computer software can measure the time of flight of horizontal and vertical ultrasonic pulses to determine the length and width of the device 14 and / or marker, and can determine the area by combining the length and width. is there. It should be noted that the object in the region of interest can be determined from the scattering of the horizontal receiver to the vertical receiver and the scattering of the vertical receiver to the horizontal receiver.

  The ultrasonic system can be calibrated in a manner similar to that described above with respect to FIGS. The above technique does not give an image of the device 14 or marker or internal anatomy. However, as shown in FIG. 38, the collected data can be displayed graphically. As can be seen in FIG. 38, the lateral and horizontal time of flight can be graphically correlated with the areas A1, A2 and A3 of the markers or devices 14 placed at positions P1, P2 and P3, respectively.

  In some embodiments, the device 14 or marker has an inner side and an outer side, where the inner side is closer to the gastric lumen than the outer side, and the two ultrasonic modules are placed on the outer side of the device, as in FIG. It is burned.

  FIG. 39 represents a pulse timing diagram representing the time of flight using the Ultrasonic module. Here, it is assumed that the device 14 or marker is a gastric band around the lumen. As seen in FIG. 39, the time of flight can be determined based on the time through the gastric band bladder, the time through the stomach tissue and the time through the gastric lumen.

  FIG. 40 is a graphical representation of the collected data for both the Ultrasonic aspect 120A and the guidance aspect 130A. Ultrasonic embodiment 120A can detect any solid mass 122 in the lumen. In the guiding feature 130A, the area 132 from the guiding feature and the area 134 from the adjustable gastric band tab circumference minus the area from the guiding region are represented.

  In some embodiments, the ultrasound marker is a liquid, a solid or a combination thereof. Various materials can be contained in the sac in or on the intragastric device. The properties of the liquid can be adjusted so that the acoustic signature is easily identified.

  The above technique can be used with an ultrasound marker so that when the volume occupancy subcomponent is in its contracted state, the marker has a characteristic ultrasound visualization or sign and the volume occupancy subcomponent expands. Can be applied to the volume occupancy subpart when the volume occupancy subpart is folded or folded so that the marker has another characteristic ultrasound visualization or sign. Alternatively, the ultrasonic marker can be applied to or incorporated into the volume occupancy sub-parts to facilitate identification and placement of various sub-parts of the device, such as valves, heads or weights. The ultrasonic marker can be printed or painted between the surface of the volume occupancy subcomponent or the layer of material forming the volume occupancy subcomponent. Alternatively, an acoustically responsive coating can be used as an ultrasonic marker to assist in the identification and / or placement of volumetric subcomponents. Alternatively, the ultrasonic marker can be applied to an elastomer sleeve that covers all or part of the volume-occupying sub-part.

  In another aspect, the volume occupancy subcomponent incorporates a subcomponent that changes mechanically as a result of expansion of the volume occupancy subcomponent, and the mechanical change can be determined using an ultrasound visualization device. For example, a mechanical portion of a volume occupancy subcomponent that includes an ultrasound visualization marker can stretch as a result of an increase in pressure of the volume occupancy subcomponent.

  Alternatively, the ultrasonic marker can be formed using a mesh, for example a metal mesh, located between the layers of material from which the volume occupancy subcomponent is constructed. When the volume occupancy sub-part is inflated and in a deployed state, one or more patterns formed by the embedded ultrasonic marker appear.

  In some aspects, the ultrasonic sensor includes a non-contact sensor. Ultrasonic levels or sensors or sensing systems do not require contact with the target. In the medical industry, this is an advantage over in-line sensors that may otherwise interfere with the target marker or item. In some aspects, the sensor is a microphone.

  In some aspects, a pulsed wave system is used. The principle of pulsed ultrasonic technology is that the transmitted signal consists of short bursts of ultrasonic energy. After each burst, the sensor electronics looks for a return signal in a small time window corresponding to the time it takes for the energy to pass through the target medium. Only signals received during this window are eligible for additional signal processing. In some aspects, a continuous wave system is used. In a pulsed, continuous or other wave system, the sensor may be a microphone that receives the return wave signal.

  In some aspects, the marker can transmit an ultrasound signal. For example, ultrasound identification (USID) automatically tracks the position of the intragastric device in real time using simple and inexpensive nodes (badges / tags) attached or embedded in the ultrasound device, Which can then be used to identify and then transmit ultrasonic signals to convey their position to an ultrasonic sensor such as a microphone.

  A computer system can be implemented with an ultrasonic placement system. The computer system includes hardware and software that receives data from the ultrasound sensor and calculates information related to the position, orientation, and / or status of the intragastric device according to a specific algorithm. In some aspects, the hardware can include a central processing unit, a memory, an analog to digital converter, an analog circuit, and a display. In some aspects, the software performs various desired output calculations including calibration, initialization, prediction, estimation, measurement of magnetic sensor data, position, orientation, size, configuration, etc., according to the techniques discussed herein. It goes through several steps, including:

  The output of the processor regarding the position, orientation and / or status of the intragastric device can be communicated to the user in several ways. In some aspects, the output is shown visually on the display.

  In some aspects, the output of the processor related to the position, orientation and / or condition of the intragastric device is communicated to the user through a speaker.

  In some aspects, processor output related to the position, orientation, and / or status of the intragastric device is communicated to the user through a combination of methods. For example, the system can employ a visual graphic display along with an audible alert sent through a speaker.

  In some aspects, the ultrasound placement system is calibrated prior to use. In order to verify that the output signal is within the expected range, the ultrasonic markers and sensors are placed in a predetermined position and orientation. In some aspects, the ultrasound placement system is calibrated or otherwise verified using a human patient simulator or dummy to inspect the ultrasound placement system as the ultrasound marker moves through the simulator. The In some aspects, the ultrasound placement system is inspected for stray signals from nearby acoustic interference.

  In various aspects, an ultrasonic sensor can be used with one or more markers to place or otherwise characterize an ingested intragastric device. In some aspects, off-the-shelf intragastric devices, such as swallowable, inflatable balloons, can be used without modification with any ultrasound marker. Ultrasonic sensors that pulse sound waves with the device and sense their return signals with a microphone can be used outside the body. The device can be swallowed in a contracted state and then expands upon entering the stomach. The ultrasonic sensor can be used to position or otherwise characterize the device by pulsing the device and receiving a return signal according to the techniques described above.

  Ingested devices can be placed using an ultrasonic intragastric placement system. In some aspects, the device can be placed on the sensor by pulsing at various locations and analyzing the return signal. For example, by correlating the return wave signal with the position of the body before swallowing the device, a return signal corresponding to a body organ without the device can be determined in advance. This would create an ultrasound map of the organ or body without the device. Then, after swallowing the device and by operating the sensor on the body, the position of the device is thus determined if a different signal is returned for the corresponding position of the body. This can be performed according to the techniques described above.

  The orientation of the ingested device can be confirmed using an ultrasonic intragastric placement system. In some aspects, the sensor can determine the orientation of the intragastric device by pulsing and sensing at various locations on the device and analyzing the return signal. For example, the device can be pulsed in various orientations so that there is a predefined database of known correlations between the return wave signature and the orientation of the device prior to ingestion by the patient. This can be done for devices that are deflated, expanded or otherwise. Next, after ingestion, the device can be pulsed and the return signal compared to a predefined database to determine the orientation of the device according to the techniques described above.

  In addition, an ultrasonic intragastric placement system can be used in accordance with the techniques described above to characterize the various sizes and configurations of ingested devices. For example, balloon inflation or inflation or configuration of multiple balloons can be characterized and evaluated. In some aspects, the sensor can characterize one or more devices by pulsing and sensing at various locations on the device and analyzing the return signal. For example, a deflated device will return a different pulse signature than a dilated device. In this manner, the device can be characterized as being inflated, deflated, or in some other state. The inflated device could be further characterized prior to ingestion by the patient so that a return signal signature is predetermined and serves as a guide for assessing the condition of the device. In some aspects, the ultrasound placement system can be used with a contraction system to characterize the contraction process.

  The disclosed ultrasonic intragastric placement systems and techniques can be used to characterize the timing and other attributes of various methods of administration. Regardless of whether the device is administered using endoscopic techniques or orally, the progress of the device as it travels to the stomach can be tracked with an ultrasound placement system. For example, the effects of swallowing the device with hard gelatin or water or other consumables can be characterized by tracking the position and orientation while it is ingested.

  In some aspects, the ultrasound placement system can characterize an intragastric device having a circular or elliptical cross section. Two Ultrasonic modules placed in the device allow the system to measure the size and composition of the device using time-of-flight ultrasound technology.

Using the speed of sound, the distance can be calculated from the time between transmission and reception. The time between sending an ultrasonic pulse and receiving an echo is given by t = 2d / U or d = Ut / 2, (53), where U is the speed of sound in the target medium, d is the diameter of the device. If transmission occurs in two orthogonal directions, the two dimensions of the intragastric device can be determined, and thus the area of the device can be calculated. Assuming that the device is an ellipse, the equation for determining the area of the ellipse using the major axis (a) and minor axis (b) is as follows:
A = π · a · b = (π · U ² · t ₁ · t ₂ ) / 16
If the inside of the expanded device is clear, a clear echo signal is obtained, and the time of flight of the ultrasonic pulse is obtained in the clear area to determine the area of the device. Two methods can be used to detect the presence of foreign or otherwise objects in the device. First, compare the orthogonality signal, which is the amplitude of the scattered ultrasonic pulse in the orthogonal direction, with the echo return of the original pulse. Second, the amount of false return in the original pulse echo can even determine the ratio of solid to liquid objects at the analyzed cross-section of the device.

  The intragastric device can include two orthogonal ultrasonic transmitter / receiver ("transceiver") modules. One transceiver is a front / rear (a / p) ultrasonic module and the other transceiver is a lateral ultrasonic module. The device further includes a microprocessor that measures the time of flight from each transceiver module. The microprocessor can distinguish between device echoes and empty device interiors. The microprocessor can also prepare the signal for transmission. The microprocessor communicates electrically with the computer. In some embodiments, the computer and the microprocessor are integrated into the same part. In at least one aspect, the computer may be a look-up table that can determine the major radius, minor radius, and scatter associated with the device.

  The intragastric device can also include a transmitter that can transmit signals from the device to a location outside the body. The transmitter can include an antenna for transmission, or an antenna in a band (not shown) can be in electrical communication with the transmitter. The device can also include a module that contains a battery or can inductively power the intragastric device electronics. The antenna for receiving the transmitted signal and the receiver in operative communication with the antenna may be external to the patient. A computer having software capable of decrypting and processing signals transmitted by the transmitter and received by the receiver may be included. Computer software can measure the time of flight of horizontal and vertical ultrasonic pulses to determine the length and width of the intragastric device, and determine the area by combining the length and width. It should be noted that the presence of any material in the device can be determined from the scattering of the horizontal receiver to the vertical receiver and the scattering of the vertical receiver to the horizontal receiver.

  In some embodiments, the ultrasonic system can be calibrated. The collected data can be displayed in a graphical manner, with lateral and horizontal flight times being graphically correlated with various regions of the intragastric device.

  In some embodiments, the intragastric device has an inside and an outside, where the inside is closer to the interior of the intragastric device than the outside, and the two ultrasonic modules are placed outside the intragastric device. The time of flight can be determined based on the time to pass through the intragastric device.

Power Generation Tracking and Visualization Subcomponent Tracking and visualization functions can be incorporated into the devices and systems described above. As used herein, “visualization” is intended in the body in several ways, including by providing a sensor or marker for generating a voltage in response to the gastric environment encountered by the voltage sensor or marker. Widely used to refer to identifying items. Due to the non-invasive nature of the device, the physician may wish to determine or confirm the position and orientation of the device before inflation, during treatment or after deflation. Accordingly, an intragastric device is provided that incorporates a power generation sensing component configured to allow determination and confirmation of the position, orientation and / or status of the intragastric device at all stages of administration.

  In some aspects, the power generation tracking and visualization subcomponent can be implemented in other aspects described herein. For example, as described above, FIG. 10C represents an embodiment of a power generation sensor that can be implemented with the catheter of FIG. 10A. This is just one example, and other aspects can implement a power generation sensor. Specific power generation sensor aspects that can be implemented in or on the sensor of FIG. 10C or other systems described herein are described below.

  In some aspects, an ingestible event marker (ie, IEM) and / or a personal signal receiver is implemented in the intragastric device. An aspect of the IEM includes an identifier that may or may not be present on a physiologically acceptable carrier. The identifier is activated as a result of contact with a target internal physiological site of the body (eg, a specific target environment including a target chemical environment, a target physical environment, etc.), eg, a gastrointestinal internal target site including the stomach It is characterized by. The personal signal receiver is configured to receive signals from, for example, an IEM as related to a physiological location within or on the body. In use, the IEM broadcasts or otherwise conveys a signal that can be received by the personal signal receiver and used as an indication of the position of the sensor. For example, the generated signal can be an indicator of a power generation sensor placed in the stomach. If desired, the signal receiver performs one or more subsequent operations, such as relaying the signal to a third external device, recording the signal, processing the recorded signal with additional data points, etc. To do.

  Embodiments include an ingestible event marker composition having an identifier that is stably associated therewith. The identifier of the IEM composition is one that generates (ie, emits) a detectable signal after contact between the identifier and the target physiological site. The identifier of the composition may vary according to the particular embodiment and the intended application of the composition, as long as they are activated (ie, turned on) as a result of contact with the target physiological location, eg, the stomach. it can. Thus, the identifier may be an identifier that emits a signal when it contacts a target body (ie, physiological) site. The identifier may be any component or device capable of providing a detectable signal after activation, for example as a result of contact with the target site. In certain embodiments, for example as summarized above, the identifier emits a signal when the composition contacts the physiological target site.

  Depending on the embodiment, the target physiological site or location may vary, where representative target physiological sites of interest include, but are not limited to: the gastrointestinal tract, eg, mouth, esophagus, Location in the stomach, small intestine, large intestine, etc. In certain embodiments, the identifier is configured to be activated as a result of contact with the fluid at the target site, regardless of the specific composition of the target site. In some embodiments, the identifier is configured to be activated only after contact with a target site or region of interest, eg, the stomach, eg, to confirm the location of the intragastric device.

  The signal obtained from the identifier can be a general signal, such as a signal that simply identifies that the composition has contacted the target site, or a unique signal, such as identification from a group or groups of different markers in a batch It may be a signal that specifically identifies in some way that the ingestible event marker has contacted the target physiological site. In yet another aspect, the identifier emits a signal that specifically identifies that particular identifier. Thus, in certain aspects, the identifier emits a unique signal that distinguishes one class of identifier from another type of identifier. In certain aspects, the identifier emits a unique signal that distinguishes it from other identifiers. In certain aspects, the identifier emits a signal that is unique, i.e. identifiable, from a signal emitted by any other identifier generated so far, where such signal is universal Specific signals (eg, different from any other fingerprint of any other individual, and thus similar to a human fingerprint that specifically identifies an individual at a universal level). In one aspect, the signal can convey information about a given event directly, or can be used to retrieve information about an event from a database, ie, a database that associates an identification code with a composition. Code can be provided.

  The identifier can generate a variety of different types of signals including, but not limited to: power generation, RF signals, magnetic signals, conductive (near field) signals, acoustic signals, etc. The identifier transmission time can vary, and in certain embodiments, the transmission time includes from about 1 microsecond to about 48 hours or more, such as from about 0.1 microsecond to about 24, including from about 1 minute to about 10 minutes. It may be in the range of time or longer, such as from about 0.1 microseconds to about 4 hours or longer, such as from about 1 second to about 4 hours. According to a given aspect, the identifier can transmit the signal once, or it can transmit the signal more than once, and the signal can be viewed as a redundant signal.

In certain embodiments, the identifier is sized to be orally ingestible by itself or in combination with a physiologically acceptable carrier part of the composition, such as a swallowable catheter or balloon. . Thus, in certain embodiments, the identifier element has a width in the range of about 0.05 to about 2 mm or more, such as about 0.05 mm to about 1 mm, such as about 0.1 mm to about 0.2 mm; .05 to about 2 mm or more, for example about 0.05 mm to about 1 mm, for example a length in the range of about 0.1 mm to about 0.2 mm, and about 0.05 to about 2 mm or more, for example about 0.1 mm to about It is sized to have a height in the range of about 0.05 mm to about 0.3 mm, including 1 mm, for example about 0.1 mm to about 0.2 mm. In certain embodiments, the identifier is less 1 mm ³ containing 0.2 mm ³ or less, for example, at 0.1 mm ³ or less. The identifier element can take a variety of different configurations, such as, but not limited to: a tip configuration, a cylinder configuration, a spherical configuration, a disc configuration, etc., and is specific based on the intended application, method of manufacture, etc. A configuration can be selected.

  In certain aspects, the identifier may be programmable after manufacture. For example, the signal generated by the identifier can be determined after the identifier is generated, where the identifier can be field programmable, mass programmable, fuse programmable, and even reprogrammable. Also good. Such an aspect is of interest if an uncoded identifier is first generated and then encoded to generate an identification signal for the composition following incorporation into the composition. Any convenient programming technique can be employed. In certain aspects, the programming technology employed is RFID technology. RFID smart tag technologies for purposes that can be employed with subject identifiers include, but are not limited to, US Pat. Nos. 7,035,877; 7,035,818; 7,032,822. 7,031,946, as well as published application 20050131281, the disclosure of which is fully incorporated herein by reference. With RFID or other smart tag technology, the manufacturer / sales company can associate a unique ID code with a given identifier even after the identifier is incorporated into the composition. In certain embodiments, each individual or entity involved in handling the composition prior to use, for example, as described in US Pat. No. 7,031,946, the disclosure of which is hereby incorporated by reference in its entirety. In addition, information can be introduced into the identifier, for example in the form of programming relating to the signal emitted by the identifier.

  Certain aspects of the identifier include a memory element, and the memory element may differ with respect to its capacity. In certain embodiments, the memory element has a capacity in the range of about 1 bit to 1 gigabyte or more, such as 1 bit to 1 megabyte, including about 1 bit to about 128 bits. The particular capacity employed may vary according to the application, for example depending on whether the signal is a general signal or a code signal, where the signal may contain some additional information, eg the name of the active agent associated with the identifier Such annotations may or may not be added.

  Some aspects of the identifier component include: (a) an activation component; and (b) a signal generation component, the signal generation component is activated by the activation component, eg, as described above, to generate an identification signal To do.

  An activation component is a component that activates the signal-generating element of the identifier following contact of the composition with a target target physiological site, such as the stomach, to provide a signal, for example, by transmission or by interrogation. Identifier activation can be accomplished in a number of different ways, and such approaches include, but are not limited to, battery completion, battery connection, and the like.

  An embodiment of an activation element based on a battery completion format employs a battery that, when completed, includes a cathode, an anode, and an electrolyte, the electrolyte being composed at least in part of a fluid present at a target physiological site (e.g., If the stomach is the target physiological site, gastric juice present in the stomach). For example, when gastric juice-activated IEM is ingested, it can travel through the esophagus with, for example, a swallowable catheter and / or an intragastric device and travel into the stomach. The cathode and anode provided on the IEM do not constitute a complete battery. However, when the cathode and anode are exposed to gastric juice, the gastric juice serves as the battery electrolyte component, completing the battery. Thus, a power source is provided that activates the identifier as the IEM contacts the target site. Thereafter, a data signal is transmitted.

  In certain embodiments, the battery employed is one that includes two different electrochemical materials that make up the two electrodes (eg, anode and cathode) of the battery. When the electrode material is exposed and in contact with bodily fluids such as gastric acid or other types of fluids, a potential difference (ie, voltage) is generated between the electrodes as a result of the respective redox reactions that occur on the two electrode materials. Two different materials in the electrolyte are at different potentials. As an example, copper and zinc have different potentials when placed in a cell. Similarly, gold and magnesium have different potentials.

  Materials for the anode include, but are not limited to, metals such as magnesium, zinc, sodium, lithium, iron and alloys thereof. Materials for the cathode include, but are not limited to, salts such as copper salts including iodides, chlorides, bromides, sulfates, formates (other anions are possible); or Fe3 + salts such as Orthophosphate, pyrophosphate (other anions are also possible); or platinum, gold or other catalyst surface oxygen or hydrogen. Intercalation compounds can also be used. For the anode, the material includes graphite with Li, K, Ca, Na, Mg, and for the cathode, the material includes vanadium oxide and manganese oxide.

  Certain high energy anode materials such as Li, Na and other alkali metals are unstable in their pure form in the presence of water or oxygen. However, if stable, they can be used in an aqueous environment. One example of this stabilization is the so-called “protected lithium anode” developed by Polyplus Corporation (Berkeley, Calif.), Where it is protected from rapid oxidation and in an aqueous environment or ambient air. In order to allow its use, a polymer film is deposited on the surface of the lithium metal. (Polyplus has a pending IP for this). (.Dagger..dagger.) Dissolved oxygen can also act as a cathode. In this case, dissolved oxygen in the body fluid will be reduced to OH- with a suitable catalyst surface, such as Pt or gold. Other catalysts are possible. The dissolved hydrogen in the hydrogen reduction reaction is also interesting.

  In certain embodiments, one or both of the metals may be doped with a non-metal, for example to enhance the voltage output of the battery. In certain embodiments, non-metals that can be used as doping agents include, but are not limited to, sulfur, iodine, and the like.

  In certain embodiments, the electrode material is copper iodide (CuI) or cuprous chloride as the cathode and magnesium (Mg) metal or magnesium alloy as the anode. An aspect of the present invention uses an electrode material that is not harmful to the human body. In some of these embodiments, the battery power source can be viewed as a power source that exploits electrochemical reactions in ionic solutions such as gastric fluid, blood or other body fluids and some tissues.

  FIG. 41 provides a diagram of an identifier 30M according to an aspect of the present invention. The first and second electrode materials 32M and 33M are in an ionic solution 39M (for example, gastric juice). This configuration generates a low voltage (V−) and a high voltage (V +) as applied to the electronic circuit 40M. The two outputs of the electronic circuit 40M are electrodes 41M and 42M, which are signal transmission electrodes. In an alternative embodiment, the signal generating element 30M includes a single pole. In an alternative aspect, a coil for communication can be provided. In certain aspects, a larger structure is provided, such as a membrane, than the chip that defines the path of current travel.

  With reference to FIG. 41, electrodes 32M and 33M may be made of any two materials suitable for the environment in which identifier 30M operates. An active material is any pair of materials having different electrochemical potentials. For example, in some embodiments where the ionic solution 39M includes gastric acid, the electrodes 32M and 33M may be made of a noble metal (eg, gold, silver, platinum, palladium, etc.) so that they do not corrode prematurely. Alternatively, the electrodes may be made of aluminum or any other conductive material that has a durable time in an applicable ionic solution that is long enough to allow the identifier 30M to perform its intended function. Suitable materials are not limited to metals, and in certain embodiments, the pair of materials is selected from a pair consisting of a metal and a non-metal, such as a metal (such as Mg) and a salt (such as CuI). With respect to the active electrode material, any combination of materials with moderately different electrochemical potentials (voltages) and low interface resistances—metals, salts or intercalation compounds—is suitable.

  In certain aspects, the IEM is characterized in that it includes a series battery structure, wherein these series battery structures substantially eliminate, but do not eliminate, short circuits between electrode elements of different battery structures in series. It can be configured to reduce. Since the battery of the present invention is a series battery, the battery includes two or more single battery structures or units, where the number of battery structures that can be present in a given series battery of the present invention is There may be two or more, three or more, four or more, five or more, etc. as desired for a given application. Each single battery structure includes at least one anode and at least one cathode, where the anode and cathode are on the surface of a solid support, and the support for each of the anode and cathode is the same or different. Good.

  The side of the series battery includes a configuration that substantially reduces, if not eliminates, a short circuit between two or more of a given series battery. This elimination of a short circuit is provided despite a small area occupied by two or more batteries in series, for example even when the battery unit is present on the surface of a solid support. Embodiments of the subject series battery include configurations where the resistance between the electrodes of two different battery structures in the series battery is significantly greater than the resistance between the electrodes in a given battery structure. In certain embodiments, the ratio of ionic resistance between the electrodes of two different battery structures compared to the electrodes (ie, anode and cathode) in a single battery structure is about 1.5 times, including about 10 times or more. For example, it is about 5 times or more.

  Depending on the particular series battery configuration, a variety of different approaches can be used to reduce, if not eliminate, shorts between batteries. Certain approaches that can be employed are reviewed in more detail below, but the approaches below may or may not be used in combination depending on the particular battery configuration of interest.

In certain embodiments, two or more battery structures are provided in series, where each battery structure includes a chamber having an anode and a cathode placed in a chamber, eg, on the same inner wall or different inner walls. The chambers can vary and in certain embodiments range from about 10 ⁻¹² to about 10 ⁻⁵ L, including from about 10 ⁻¹⁰ to about 10 ⁻⁸ L, such as from about 10 ⁻¹¹ to about 10 ⁻⁷ L. Have a capacity that is within. In certain aspects, for example, the chamber can contain an amount of dry conductive media, as described in PCT Application No. PCT / US07 / 82563, the disclosure of which is hereby incorporated by reference in its entirety.

  In certain embodiments, a given chamber includes at least one fluid inlet and at least one fluid outlet port so that when the composition in which the battery is present reaches the target site of interest, a liquid, such as gastric juice, is contained in the chamber. Gas can enter the chamber after liquid intrusion. Although the dimensions of the fluid entry and exit ports may vary, in certain embodiments, the ports have a diameter in the range of about 0.01 μm to about 2 mm, such as about 5 μm to about 500 μm.

  In order to allow efficient ingress of fluid into the chamber and escape of gas therefrom, the port of a given chamber is located relative to the ports of other chambers and also two or more different in series batteries It is also arranged so that there is virtually no short circuit between the chambers. Thus, the location of the port is selected taking into account both the battery structure itself and its physical relationship with other battery structures in the series battery. Any configuration of fluid ports can be selected as long as the configuration provides the desired resistance ratio, eg, as described above.

  FIG. 58 provides an overhead view of a series battery according to one aspect. In FIG. 58, the series battery 150 is composed of two different battery structures 151A and 151B present on the surface 152X of the solid support 153. Battery structure 151A includes cathode 154A and anode 155A, and structure 151B includes cathode 154B and anode 155B. As shown, the cathode and anode of each battery structure is in a chamber defined by boundaries 156A and 156B. Ports 157A and 158A that allow fluid to enter and exit the chamber are present in the wall 156A of structure 151A. Ports 157A and 158A of structure 151A are positioned relative to ports 157B and 158B of structure 151B so that the possibility of a short circuit between the electrodes of structures 151A and 151B is substantially but not completely eliminated. In the configuration shown in FIG. 28, ports 157A and 158A are located on the opposite wall of boundary 156A, and ports 157B and 158B are located on the opposite wall of boundary 156B. Further, ports 157A and 158A are on the opposite wall of the boundary elements 156A with respect to the placement of ports 157B and 158B in the boundary elements 156B.

  FIG. 59 provides an overhead view of a series battery according to one aspect. In FIG. 59, the series battery 160A is composed of two different battery structures 161A and 161B present on the surface 162 of the solid support 163. The battery structure 161A includes a cathode 164A and an anode 165A, and the structure 161B includes a cathode 164B and an anode 165B. The structure shown in FIG. 59 is different from that shown in FIG. 58 because the battery structures are stacked on top of each other. As shown, the cathode and anode of each battery structure is in a chamber defined by boundaries 166A and 166B. Ports 167A and 168A that allow fluid to enter and exit the chamber are present in the wall 166A of structure 161A. Ports 167A and 168A of structure 161A are positioned relative to ports 167B and 168B of structure 161B so that the possibility of a short circuit between the electrodes of structures 161A and 161B is substantially but not completely eliminated.

  In addition to or instead of arranging the fluid ports to provide the desired resistance ratio, the fluid ports can be modified to provide the desired resistance between the battery structures. For example, the port can include a selective semipermeable membrane. Any convenient semipermeable membrane can be employed. Semipermeable membranes are ePTFE, Dacron. RTM. , Polyurethane, silicone rubber, poly (lactide-co-glycolide) (PLGA), poly (caprolactone) (PCL), poly (ethylene glycol) (PEG), collagen, polypropylene, cellulose acetate, poly (vinylidene fluoride) (PVDF) ), Nafion or other biocompatible materials. The pore size of the membrane may vary depending on the particular configuration, and in certain embodiments, the membrane has a pore size (less than about 1000d, including no more than about 250d, such as no more than about 500d, eg no more than about 100d, eg no more than about 50d. MW cutoff). In certain embodiments, the membrane is a water only permeable membrane so that water and few other fluid components, if any, at the target site pass through the membrane to the dry conductive media precursor of the identifier. .

  In certain embodiments, the solid supports 153, 163 are circuit support elements. The support element of the circuit can take any convenient configuration, and in one particular embodiment is an integrated circuit (IC) chip. The surface on which the electrode element is disposed may be a top surface, bottom surface or other surface, such as a side surface, as desired, and in certain embodiments, the surface on which the electrode element is at least partially present is the top surface of the IC chip. is there.

In certain embodiments, the series battery has a small form factor. Battery includes a 0.1 mm ³ or less, including a 0.02 mm ³ or less, about 20 mm ³ or less, such as about 10 mm ³ or less, or may be for example 1.0 mm ³ or less. In certain embodiments, the battery element has a width in the range of about 0.01 mm to about 100 mm, such as about 0.1 mm to about 20 mm, including about 0.5 mm to about 2 mm; About 0.01 mm to about 100 mm, for example about 0.1 mm to about 20 mm, including about 0.1 mm to about 0.5 mm, about 0.01 mm to about 10 mm, for example about 0.05 mm Sized to have a height in the range of ~ 2 mm.

  Series battery embodiments include those further described in US Provisional Application No. 60 / 889,871, the disclosure of which is hereby fully incorporated by reference. The signal generating component of the identifier element is a structure that emits a detectable signal that can be received, for example, by a receiver upon activation by the activation component, for example, as described in more detail below. Certain aspects of the signal generation component may be any convenient component capable of generating a detectable signal and / or modulating the converted broadcast power as a result of activation by the activation component, or It may be an element. Target detectable signals include, but are not limited to, conductive signals, acoustic signals, and the like. The signal emitted from the signal generator may be a general or specific signal, and is not limited to a typical type of signal of interest, but is limited to a frequency shift code signal; an amplitude modulation signal; A frequency modulation signal is included.

  In certain aspects, the signal generating element includes circuitry that generates or generates a signal. The type of circuit selected may depend at least in part on the drive power supplied by the identifier power supply. For example, when the driving power is 1.2 volts or more, a standard CMOS circuit can be adopted. In other embodiments where the drive power is in the range of about 0.7 to about 1.2V, a subthreshold circuit design can be employed. For drive power below about 0.7V, a zero threshold transistor design can be employed. In some embodiments, as discussed in further detail herein, the power source may be a voltage generated by contact between the power generation sensor and the stomach environment.

  In certain aspects, the signal generation component includes a voltage controlled oscillator (VCO) that can generate a digital clock signal in response to activation by the activation component. The VCO can be controlled by a digital circuit that is assigned an address and can control the VCO with a control voltage. This digital control circuit can be embedded in a chip including an activation component and an oscillator. An identification signal is transmitted using amplitude modulation or phase shift keying to encode the address.

  The signal generating component can include different transmitter components that are useful for transmitting the generated signal to a remote receiver that may be internal or external to the patient. When present, the transmitter components can take a number of different configurations depending on, for example, the type of signal being generated and transmitted. In certain aspects, the transmitter component is comprised of one or more electrodes. In certain aspects, the transmitter component is comprised of one or more wires, for example in the form of antenna (s). In certain aspects, the transmitter component is comprised of one or more coils. As such, the signal transmitter can include a variety of different transmitters, such as electrodes, antenna (eg, in the form of wires) coils, and the like. In certain embodiments, the signal is transmitted on one or two electrodes or on one or two wires (a two-electrode transmitter is a dipole; a one-electrode transmitter forms a monopole) . In certain aspects, the transmitter only requires one diode voltage drop of power. In some aspects, the transmitter unit uses an electric dipole or electric monopole antenna to transmit the signal. In certain aspects, the identifier employs conductive near-field mode communication, where the body itself is employed as the conductive medium. In such an aspect, the signal is not a magnetic signal or a radio frequency (RF) signal.

  FIG. 42 shows details of one implementation of an electronic circuit that can be employed with an identifier according to some aspects. On the left side are two battery electrodes, a first metal 32M and a second metal 33M. These metals form a battery that, when in contact with the electrolyte, provides power to the oscillator 61M, which in this case is shown schematically. The metal 32M provides a low voltage (ground) to the oscillator 61M. The metal 33M provides a high voltage (high V) to the oscillator 61M. As oscillator 61M becomes operational, it generates clock signal 62M and reverse clock signal 63M, which are diametrically opposed to each other. These two clock signals enter the counter 64M, which simply counts the number of clock cycles and stores the count number in several registers. In the example shown here, an 8-bit counter is employed. Therefore, the output of the counter 64M starts from a value of “00000000”, changes to “00000001” in the first clock cycle, and continues to “11111111”. The 8-bit output of the counter 64M is connected to the input of an address multiplexer (mux) 65M. In one aspect, the mux 65M contains an address interpreter that can be wired in the circuit to generate a control voltage for controlling the oscillator 61M. The Mux 65M uses the output of the counter 64M to recover the address with a serial bit string, which is further sent to the signal transmission drive circuit. The Mux65M can also be used to control the signal transmission duty cycle. In one aspect, the mux 65M turns on signal transmission on the occasion of only 1/16 with the clock count generated by the counter 64M. Such a low duty cycle saves power and also allows other devices to transmit without clogging their signals. The address of a given chip may be 8 bits, 16 bits or 32 bits.

  According to one aspect, mux 65M generates a control voltage that is used to continuously code addresses and change the output frequency of oscillator 61M. By way of example, when the control voltage is low, that is, when the serial address bit is 0, a 1 megahertz signal is generated by the oscillator. When the control voltage is high, that is, when the address bit is 1, a signal of 2 MHz is generated by the oscillator. Alternatively, this may be 10 megahertz and 20 megahertz, or a phase shift keying approach where the device is limited to phase modulation. The purpose of the mux65M is to control the AC frequency of the oscillator frequency or the oscillation amplification signal.

  The output of the mux 65M is connected to an electrode drive 66M, which drives the electrodes to impose a differential potential on the solution, passes an oscillating current through the coil to generate a magnetic signal, or charges to or from the solution. A single electrode can be driven to add or withdraw.

  In this manner, the device broadcasts a sequence of 0s and 1s that make up the address stored in mux 65M. The address will be broadcast repeatedly, and the broadcast will continue until the metal 32M or metal 33M is consumed and dissolved in the solution and the battery is no longer operating.

  Other configurations for signal generating components are of course possible. Other configurations of interest include, but are not limited to, PCT application number PCT / US2006 / 016370 and provisional application number 60/11 filed July 11, 2006, the disclosures of each of which are incorporated herein by reference. 807,060 are included.

  In certain embodiments, the activation component includes a power storage element. For example, a duty cycle configuration may be employed, where slow energy generation from the battery is stored with a power storage element, such as a capacitor, which in turn provides the power burst utilized by the signal generating component. In certain embodiments, the activation component includes a timed element that modulates, eg, delays, the delivery of power to the signal generating element, eg, different compositions administered at substantially the same time, eg, different IEMs. Are generated at different times and are therefore identifiable.

  In certain aspects, the ingestible event marker identifier component or functional block resides on an integrated circuit, which includes several different functional blocks, or modules. For example, within a given identifier, two or more, including at least some, eg, all, functional blocks, eg, power supplies, transmitters, etc., may be present on a single integrated circuit in the receiver. A single integrated circuit means a single circuit structure that includes all of the different functional blocks. Thus, an integrated circuit is a monolithic integrated circuit (IC, microcircuit, microchip, which is a miniaturized electronic circuit (which can include semiconductor elements as well as passive elements) manufactured on the surface of a thin substrate of semiconductor material. Also known as silicon chip, computer chip or chip). One particular aspect of the integrated circuit of the present invention may be a hybrid integrated circuit, which is a miniaturized electronic circuit constructed with individual semiconductor elements and passive elements coupled to a substrate or circuit board.

  Aspects of the invention automatically activate itself after the marker contacts the patient's body fluid, send a predetermined signal based on locally generated power, and deactivate itself after a certain time A low power, small ingestible marker is provided that includes an integrated circuit (IC). In these embodiments, as described above, the IEM uses a patient's bodily fluid, such as gastric acid, to form a power cell. In addition, the IEM uses a special circuit that changes the impedance of the closed circuit that forms the power generation cell, thereby forming an external signal by modulating the amplitude and waveform of the current flowing through the patient's tissue and fluid. . As described in more detail below, such a circuit configuration causes the circuit to operate at a low voltage while generating a sufficiently strong signal for detection by a receiver in contact with the patient's body. Make it possible to do.

  An IEM IC can be packaged with an integrated power cell that can be fabricated on the same substrate as the IC circuit. This wafer level integration significantly reduces the chip and simplifies the manufacturing process. As a result, the cost of each IEM can be significantly reduced. In one aspect, the anode and cathode electrode material is fabricated on each side of the substrate so that the IC logic is between the two electrodes. In one aspect, the logic circuit is in a position selected to minimize the area that overlaps the anode or cathode electrode vertically.

  FIG. 43 illustrates an exemplary device configuration of an IEM IC according to one aspect. In one embodiment, the IC chip substrate 204A is connected to the anode (S1) of the power generation cell, which may be a magnesium (Mg) layer 206A coated on the back of the substrate 204A. On the opposite side of the substrate 204A is a layer of cathode (S2) material 202A, which in this example is copper chloride (CuCl). Electrodes 202A and 206A and the body fluid that serves as the electrolyte form a power generation battery. The IEM IC circuit fabricated on the substrate 204A is an “external” circuit that forms a return circuit for the power generation battery. In essence, the IEM IC changes the impedance of this “external” circuit, thereby changing the total amount of current flowing through the body fluid. A receiving circuit in contact with bodily fluids, for example on a personal health receiver described in more detail below, can detect this current change and receive the encoded message.

  It should be noted that the two electrodes S1 and S2 of the power generation battery also serve as transmission electrodes for the IC. This configuration significantly reduces the complexity of the IC chip. In addition, since the fluid-metal interface often exhibits high impedance, using a separate pair of electrodes different from the battery electrode introduces additional high impedance into the circuit, thereby reducing transmission efficiency and reducing power consumption. There is a possibility to increase. Therefore, using the power battery electrode for transmission also improves the power efficiency of the IC circuit.

  When powered on, the IEM IC functions as an ingestible transmitter that transmits a unique identification code. This IC can be packaged, for example, in a pharmaceutically acceptable vehicle as described above. When the IEM is swallowed and in the stomach, the integrated power generation battery or battery uses gastric acid as the battery electrolyte to power up the main chip and then initiate a broadcast or otherwise electrical communication. In addition, several pills can be ingested and transmitted simultaneously. During operation, a unique identification code is broadcast, for example using BPSK modulation. This broadcast can be received and demodulated by a receiver, eg, a sensor interface unit. The receiver can decode and store the identification code with a time stamp.

  In one aspect, the IEM IC includes an impedance detection circuit. The circuit is configured to detect an impedance between the anode and the cathode electrode. When the electrodes are not immersed in an electrolyte solution, such as stomach acid, the impedance between the electrodes is high and the IC is not activated. The IC is activated when the electrode contacts the electrolyte and the impedance detection circuit detects a drop in impedance.

  Some aspects allow the power generation sensor to operate at a low voltage. In general, an IC can operate with a power supply of 0.8-2V. In one aspect, the IC is configured to operate with a power supply of approximately 1.0-1.6V. Furthermore, the power generation battery exhibits an internal impedance of 200 to 10 K ohms. In one aspect, the power cell exhibits an internal impedance of approximately 500-5 K ohms. The IC also provides a super stable carrier clock frequency, thereby facilitating error resistant communication.

  In one aspect, the IC includes three parts of the circuit. The first part is an impedance detection circuit that uses a battery as a power supply. The second part is a main circuit that broadcasts messages. The impedance detection circuit can hold the main circuit with substantially zero power consumption before the battery detects an impedance of less than 10K ohms. When the impedance drops to approximately 10K ohms, the main circuit is activated and the impedance detection circuit can isolate itself from the battery. The third part is a watchdog circuit designed to protect patient safety when a dangerous situation occurs.

  FIG. 44 provides an exemplary schematic diagram illustrating the design of an IEM IC according to one aspect of the present invention. Generally, an IEM chip has a battery portion 302A and an IC circuit 304A. The battery portion 302A includes a power cell electrode, which when combined with the electrolyte solution forms a power cell. The two battery electrodes are respectively connected to the high voltage rail (VCC) and ground of the IC circuit. IC circuit 304A includes transmission switch transistor 306A, recharge transistor 308A, recharge protection diode 310A, recharge capacitor 316A, local oscillator 314A, and control logic 312A. The local oscillator 314A generates one or more carrier frequencies that are used by the control logic 312A to issue a transmit command (labeled “broadcast”) to turn the transmit switch transistor 306A on and off. For example, oscillator 316A can generate a 20 kHz signal based on which control logic 312A can generate a binary phase shift keying (BPSK) code message. Control logic 312A then turns transistor 306A on and off to transmit these messages.

  When transistor 312A is turned on, a low impedance external return circuit is provided between the two battery cell electrodes. As a result, the current flowing through the patient's body also increases. When transistor 312A is turned off, the external return circuit between the two power cell electrodes exhibits a high impedance. Correspondingly, the current flowing through the patient's body is much lower. Note that the current draw of the rest of the circuit, eg, oscillator 314A and control logic 312A, is sufficiently low so that there is a significant difference in body current between broadcast time and silence time.

  When the transistor 306A is turned on, the two power cell electrodes are effectively shorted. As a result, the voltage provided by the electrode is much lower than when transistor 306A is turned off. To ensure that control logic 312A continues to operate properly, recharge capacitor 316A provides the necessary voltage (VCC) to control logic 312A. Note that recharge capacitor 316A is recharged when the IC chip is in silence, ie, transistor 306A remains off. When the transistor 306A causing the voltage drop between the battery electrodes is on, the diode 310A prevents the charge stored in the capacitor 316A from flowing back to the battery electrode. In one aspect, diode 310A is a Schottky diode that ensures rapid switch time.

  During the transmission time, oscillator 314A and / or control logic 312A may drain the charge stored in capacitor 316A and reduce VCC below a certain threshold. For example, the voltage supplied by recharge capacitor 316A may drop below the voltage supplied by the power generation battery. The difference between these two voltages may not be large enough to turn on Schottky diode 310A. In this case, the control logic 312A can issue a recharge signal to turn on the recharge switching transistor 308A, which connects the battery voltage to the capacitor 316A to recharge the capacitor 316A.

  In one aspect, the communication between the IEM IC and the receiver is simplex. That is, the IEM IC only sends a signal without receiving any signal. Communication is performed through direct coupling between the IC electrode and the receiver circuit through the patient's body tissue and fluid. Transmission is performed at two frequencies, for example one at 10 kHz and the other at 20 kHz. Other frequencies and frequency values are possible. In general, different data packet formats can be used in the system of the present invention. In one aspect, the transmitted data packet is 40 bits long, of which 16 bits are used as a synchronization / preamble pattern. The remaining 24 bits carry a payload encoding the IEM identifier. In one aspect, the payload can also include a forward error correction (FEC) code so that transmission is more robust. In one aspect, the data bits occupy 16 cycles of the carrier clock. The bits are BPSK coded. Other code schemes are possible. In a further aspect, the 16-bit sync / preamble pattern includes 12 bits for synchronization and 4 bits as the preamble.

  FIG. 45 illustrates an exemplary transmission sequence for a “0010” bit pattern in accordance with an aspect of the present invention. Each bit is represented by 16 clock cycles. Depending on the battery configuration, it may be desirable to limit the duty cycle of the drive transistor 306A in order to maintain sufficient power to the oscillator. In one aspect, the “on” state of the drive transistor 306A is maintained substantially below 25 μs. Thus, during a 20 kHz transmission with a clock cycle of 50 μs, the driver is on for 25 μs and off for 25 μs. During 10 kHz transmission, the drive is on for 25 μs and off for 75 μs. A logical “0” transmission starts from the rising edge of the data clock cycle and lasts for 16 clock cycles. Correspondingly, a logical “1” transmission starts from the falling edge of the data clock cycle and also lasts for 16 cycles. Note that other duty cycle configurations and code schemes are possible.

  FIG. 46 presents exemplary waveforms for a 20 kHz transmission of sequence “10101” in accordance with an aspect of the present invention. Note that for purposes of illustration, each logical bit occupies 3 clock cycles instead of 16 cycles. FIG. 47 presents exemplary waveforms for a 10 kHz transmission of sequence “10101” in accordance with an aspect of the present invention. Note that each logical bit is also shortened to 3 clock cycles.

  In certain aspects, IEM operations can be divided into four periods: storage, retention period, broadcast period, and power down. During the storage period, the IC is turned off and typically consumes less than 5 mA. During the holding period, the IC is turned on. However, broadcast is disabled because the oscillator clock signal is stable. In one aspect, the packet is transmitted 256 times during the broadcast period. During each transmission, the transmission driver transistor operates to transmit a packet and is then turned off for a while. When the transmitter driver transistor is off, the rest of the IEM IC remains on. In one aspect, the average duty cycle during the entire broadcast period is maintained at approximately 3.9%. Other values for the average duty cycle are possible. During the power down period, the IEM IC is politely powered down. Broadcast is completely turned off.

  FIG. 48 provides an exemplary state diagram illustrating the operation of an IC according to one aspect. During operation, the system first enters the storage period 702, at which time the impedance detection circuit operates to detect the impedance between the two battery electrodes. Meanwhile, the IC is power gate off. After the impedance detection circuit detects a low impedance, for example, an impedance of approximately 10 kilohms, the circuit releases the IEM IC from the power gate off state. Correspondingly, the system enters a retention period 704. During the hold period 704, the chip broadcast function is disabled for approximately 10 seconds for the clock signal to stabilize. Next, the system enters a broadcast period 706. During this period, data packets are broadcast twice per cycle, once at 10 kHz, once at 20 kHz, and the cycle pattern is 32 ms on (10 kHz) -768 ms off-64 ms on (20 kHz) -1536 ms off. . Each cycle is approximately 2.4 seconds and the system finishes 256 cycles in approximately 10 minutes. Note that at each frequency, the transmit duty cycle of the chip is maintained at approximately 3.9%. For the remaining 96.1% time, the recharge capacitor is recharged. The system then enters a power down state 708, at which time the oscillator is stopped and the chip is power gated down. Note that if for some reason the chip continues to broadcast before the end of the 10 minute broadcast period, the system resets the chip's power supply and the broadcast process begins again. Such a situation may occur, for example, when the stomach conductivity falls sharply until the oscillator and its generated clock are so low that they cannot function properly.

In some aspects, the operating parameters for the IC may be the following: the operating temperature may be 20-45 degrees Celsius; the storage temperature may be 0-60 degrees Celsius The storage humidity may be 20% to 90% relative humidity; the human body conductivity / pH value may be 0.01 / 4 to 1000/11 S · m ⁻¹ / pH.

  In some aspects, the IEM circuit may have the following DC parameters: power supply for the main chip ("Vcc") and output driver other than the impedance detection circuit is 1.0-1.8. Volts, typically about 1.6 volts; DC current for the chip during recharging (“I (s2)”) was 8-12 uA, typically about 1.6 uA. The battery voltage ("V (s2)") may be 1.0-1.8 volts, typically 1.6 volts; the ON resistance of the output driver ("Zon") ( The “Vbattery” function) may be 7-55 ohms, typically 11 ohms; the output driver's OFF resistance (“Zoff”) is about 75K-500k ohms, typically 100K ohms. Yes; completely The battery voltage ("Vbattery") when being applied may be about 1.0-1.8 volts, typically about 1.6 volts; the conductivity of the solution for the chip to function properly ("Rbattery") may be about 500-5K ohms, generally about 1K-3K ohms.

  In some aspects, the IEM circuit may have the following AC parameters (for actual chip design, the target values are +/− 5% to the temperature, power supply voltage, and transistor threshold voltage ranges Note that it may have +/− 10%): The oscillator frequency (“f_osc”) may be 256-384 kHz, typically about 320 kHz; low broadcast frequency (“f1_broadcast”) May be about 8-12 kHz, typically about 10 kHz; the high broadcast frequency (“f2_broadcast”) may be about 16-24 kHz, typically about 20 kHz; The hold time (“T_brdcsten”) before enabling broadcast is about 8-12 seconds, typically about It may be zero seconds; time for the broadcast ( "T_brdcstoff") is about 8 to 12 minutes, may be generally about 10 minutes.

The physical size of the IEM chip may be between 0.1 mm ² to 10 mm ^2. Because of the special IC configuration, embodiments of the present invention can provide an IEM chip that is small enough to be included in most types of pills. For example, an IEM IC chip can have a size of less than 2 × 2 mm ² . In one aspect, the IC chip may be 1 × 1 mm ² or less. In one aspect, the tip is 1 mm x 1 mm. The bottom side of the chip substrate serves as the S1 electrode, and S2 is a pad fabricated on the upper side of the substrate. The pad size may be between 2500 μm ^{2 and} 0.25 mm ² . In one aspect, the pad is approximately 85 μm × 85 μm.

  While the previous description discloses a chip configuration that uses the same electrode for battery and signal transmission, in certain embodiments, separate electrodes are employed for power generation and signal transmission.

  FIG. 49 illustrates one exemplary IEM chip configuration in which two separate electrodes are used for battery and signal transmission, respectively, in the power generation sensor. The ground electrode 802 is manufactured on the bottom side of the substrate 800. Above the substrate 800 is a battery electrode 804 and a transmission electrode 806. A circuit region 808 is also fabricated on the substrate 800. During operation, the battery formed by electrodes 802 and 804 provides power to the circuitry in region 808. The circuit drives the transmit electrodes 806 and 802 to generate a current change in the patient's body. The current flowing from the transmission electrode 806 to the ground electrode 802 can flow under the circuit region 808 and can cause a potential change in the circuit element. Such a potential change may cause unwanted latch-up on the transistors in circuit area 808.

  One approach to avoiding such latch-up is to separate the transmit electrode area from the circuit area so that there is minimal side current flow that will change the potential under the circuit. For example, the substrate contact can be placed in an area where the current flow can be changed from the circuit area.

  FIG. 50 illustrates an exemplary chip configuration that minimizes circuit latch-up in accordance with an aspect of the present invention. As shown in FIG. 50, it is possible to place substrate contact areas at the four corners of the substrate. As a result, the electrode current flowing in the direction of the substrate is changed to four corners away from the circuit area at the center. Similarly, special layout designs can be used for merged electrode chip configurations.

  FIG. 51 illustrates an exemplary layout that minimizes latch-up with an IEM chip. As shown in FIG. 51, the Mg electrode 1002 is on the bottom of the substrate 1000. Above the substrate 1000 is a CuCl electrode 1006. The electrodes 1002 and 1006 serve as both battery electrodes and transmission electrodes. Below the CuCl electrode 1006 are a number of transmit driver circuit areas 1004 that are located at the periphery of the layout. The control logic circuit area 1008 is arranged at the center of the chip. In this way, the current flowing from the transmission drive in the direction of the Mg electrode 1002 is changed away from the control logic area 1008, thereby avoiding any latch-up at the transistor.

  FIG. 52 is an exploded view of an embodiment of an IEM that can be used with a power generation sensor. In FIG. 52, the IEM 1200 includes a silicon dioxide substrate 1201 having a thickness of, for example, 300 μm. On the bottom surface is a magnesium electrode layer 1202 having a thickness of, for example, 8 μm. A titanium layer 1203 having a thickness of 1000 angstroms, for example, is disposed between the Mg electrode layer 1202 and the bottom surface of the substrate 1201. An electrode layer (CuCl) 1204 having a thickness of, for example, 6 μm is disposed on the upper surface of the substrate 1201. Between the upper electrode layer 1204 and the substrate 1201, a titanium layer 1205 having a thickness of 1000 Å, for example, and a gold layer 1206 having a thickness of 5 μm, for example, are disposed.

  The above signal generation and transmission protocols are described at substantially the same time, eg, activation and transmission that occurs following contact with the target site and / or environment, but in certain embodiments, the activity of the IEM Conversion and signaling may be separate events, i.e. may occur at different times separated by some time. For example, the IEM can include a conductive medium that allows activation prior to ingestion. In certain embodiments, the IEM is encapsulated in a fluid, electrolyte sponge or other conductive medium so that it can be activated externally prior to digestion. In these aspects, the receiver is configured to detect the transmitted signal only when the signal is transmitted from the target site of interest. For example, the system can be configured such that transmission occurs only after contact with body tissue to ensure proper event marking. For example, activation can occur with IEM processing. A pressure sensitive membrane that breaks upon treatment or contact may be employed, where the break causes the electrolyte material to allow connection of the battery element. Alternatively, degradation of the gel capsule in the stomach can release the stored electrolyte and activate the IEM. Encapsulating the IEM in a sponge (composed of a conductive material that holds water close to the IEM) causes activation in the presence of a small amount of liquid. This configuration counteracts the poor transmission capability in the absence of conductive fluid.

  Note that other layout designs are possible. In addition, silicon-over-insulator (SOI) fabrication techniques can be used to insulate the logic control circuit area from the conductive substrate so that the transmission current cannot interfere with the control circuit.

  In certain embodiments, the identifier composition is destroyed upon administration to the subject. Thus, in certain embodiments, the composition undergoes physical disruption, eg, dissolution, degradation, erosion, etc., following delivery to the body, eg, by ingestion, injection, etc. The compositions of these embodiments are distinguished from devices that are ingested and configured to survive gastrointestinal tract transport while remaining intact but substantially intact.

  In certain embodiments, the identifier does not include an imaging system, such as a camera or other visualization or imaging element, or a component thereof, such as a CCD element, illumination element, or the like. In certain embodiments, the identifier does not include a sensing element for sensing physiological parameters, for example, in addition to an activator that detects contact with a target physiological site. In certain aspects, the identifier does not include a propulsion element. In certain embodiments, the identifier does not include a sampling element, such as a fluid recovery element. In certain embodiments, the identifier does not include an activatable active agent delivery element, eg, an element that retains the active agent with the composition until a signal is received that causes the delivery element to release the active agent.

  The identifier can be produced using any convenient processing technique. In certain embodiments, a planar processing protocol is employed to fabricate a power supply having surface electrodes, where the surface electrodes include at least partially at least an anode and a cathode on the same surface of the circuit support element. In certain embodiments, a planar processing protocol is employed in a wafer bonding protocol for generating a battery source. Planar processing techniques, such as micro-electromechanical system (MEMS) fabrication techniques including surface micromachining and bulk micromachining techniques can be employed. Deposition techniques that can be employed in certain aspects of fabricating the structure include, but are not limited to, the following: electrodeposition (eg, electroplating), cathodic arc deposition, plasma spraying. , Sputtering, e-beam evaporation, physical vapor deposition, chemical vapor deposition, plasma accelerated chemical vapor deposition, etc. Material removal techniques include but are not limited to: reactive ion etching, anisotropic chemical etching, isotropic chemical etching, such as chemical mechanical polishing, laser removal, Planarization technology such as electron discharge machining (EDM). Lithography protocols are also of interest. In certain embodiments, the structure is constructed and / or removed from the originally planar substrate surface (s) using a variety of different material removal and deposition protocols applied sequentially to the substrate. Interested in using the planar treatment protocol. An exemplary fabrication method of interest is described in more detail in PCT application number PCT / US2006 / 016370, the disclosure of which is hereby incorporated by reference in its entirety.

  In certain production protocols, a sacrificial layer is used. For example, in certain three-dimensional aspects where gaps or spaces are desired, such as those described in more detail below, a sacrificial layer can be employed during fabrication, in which case such a layer is a battery. All or part is removed before use. Sacrificial layer materials of interest include, but are not limited to, photoresists that may be hard baked to make them stable. Once the deposition of the upper electrode is complete, the photoresist sacrificial layer can be removed using any convenient protocol, for example with acetone. Other materials that can be used as the sacrificial layer include, but are not limited to, silicon nitride, silicon dioxide, henzocyclobutene or tungsten. Other methods of removing the sacrificial layer include, but are not limited to, vapor phase removal, dry etch removal, and hydrogen peroxide.

  In some embodiments, a planar process, such as a MEMS fabrication protocol, is employed to fabricate a battery that includes an anode and a cathode that are at least partially present on the same surface of the circuit support element. “At least partially present on the same surface of the circuit support element” means that at least a portion of the cathode and at least a portion of the anode are present on the same surface of the circuit support element, Both electrodes may be present entirely on the surface of the circuit support element, one electrode may be completely present on the surface and the other electrode may be only partially present on the surface, for example in that case The other electrode includes a portion that is present on a different surface than the surface on which the first electrode is disposed, and both electrodes are partially present on the same surface and then partially present on different surfaces . The implantable on-chip battery can be deposited on the chip in various ways. The support element of the circuit can take any convenient configuration, and in one particular embodiment is an integrated circuit (IC) chip. The surface on which the electrode element is disposed may be a top surface, bottom surface or other surface, such as a side surface, as desired, and in certain embodiments, the surface on which the electrode element is at least partially present is the top surface of the IC chip. is there.

  Using MEMS fabrication techniques, some aspects of the battery can be manufactured in very small sizes, eg, as reviewed above. The battery electrodes can be deposited in various thicknesses, for example, ranging from about 0.001 to about 1000 μm, for example, from about 0.5 to about 10 μm. If a gap exists between the electrodes, the gap can have a width in the range of about 0.001 to about 1000 μm, such as about 1 to about 10 μm.

  In one embodiment, two cathodes are deposited on the surface of the chip with an anode separating the two cathodes. A dielectric layer is deposited between the electrode and the circuit chip, and circuit contacts are transmitted through the chip surface. This configuration allows multiple batteries to be placed in series, which allows a larger voltage to be applied to the circuit chip by activating the battery by contact with the target site. FIG. 60 shows the planar battery layout. A dielectric material 9 is deposited on the circuit chip 5 containing the circuit contacts 7. The anode 3 separates the first cathode 1 from the second cathode 2. Embodiments employing this configuration include embodiments where the batteries are in series (eg, as described above), which provides a higher voltage that the circuit can use by contact with the target physiological site. In certain embodiments, this configuration also provides a low battery impedance because the electrodes are placed fairly tightly. This embodiment is characterized in that both the cathode and anode elements are completely present on the same surface of the tip.

  In some embodiments, at least one of the anode and cathode elements is partially present on the same surface as the other electrodes, but is also partially present on another surface of the tip, such as the side, bottom, etc. For example, the anode can be on a small portion on one side of the surface of the circuit chip and wrap around that side to cover the bottom of the circuit chip. The cathode is present on the rest of the top surface of the circuit chip, providing a small gap between the cathode and anode. In one embodiment, a large cathode plate covers most of the top surface of the circuit chip and an anode covers the bottom surface of the circuit chip and wraps the side up to the top surface. Both electrodes, eg plates, can be connected to the circuit chip through circuit contacts through a dielectric layer on the top surface of the chip.

  FIG. 61 shows the dielectric material 9 covering the circuit chip 5. The cathode 1 is deposited on most of the top surface of the dielectric material 9. The anode 3 is deposited on the rest of the top surface and on the side and bottom surfaces of the circuit chip 5 to keep the separation between the upper cathode 1 and the anode 3. In certain embodiments, the separation is in the range of about 0.001 to about 1000 μm, such as about 0.1 to about 100 μm, such as about 2.0 μm. In certain embodiments, the circuit chip 5 may be inverted during fabrication to deposit the anode 3 on the bottom surface of the chip 5. Circuit contacts 7 for the anode 3 and the cathode 1 are provided on the upper surface of the circuit chip 5 and travel down through the dielectric 9. This configuration utilizes one of the top and bottom and sides of the circuit chip 5 and thus provides a very large electrode area.

  In another aspect, the cathode is disposed on the top surface of the circuit chip and is present as a layer deposited, for example, on a dielectric on the top surface of the circuit chip. During fabrication, a sacrificial layer is then deposited on the cathode layer. Another layer is then deposited on the sacrificial layer. The sacrificial layer can then be removed, leaving a gap that provides a region for the target site fluid, eg, electrolyte gastric fluid, to contact the anode and cathode. Using this embodiment, additional electrode layers can be stacked on top of each other after depositing another sacrificial layer on the anode. In that case, for example, if a vertical series configuration is desired, an implantable on-chip battery can be placed in series.

  FIG. 62 shows the dielectric layer 9 disposed on the circuit chip 5. The cathode 1 is deposited on the dielectric layer 9 through the circuit contacts 7. A sacrificial layer (not shown) is deposited on the cathode 1 to provide a basis for the deposition of the anode 3. Once the sacrificial layer is deposited, its surface can be etched to provide a rougher surface. Thus, when the anode 3 is deposited on the sacrificial layer, the bottom of the anode 3 coincides with a rough surface. The sacrificial layer could be deposited using a cathodic arc that is coarse and porous. In order to provide multiple voltages to the chip circuit 5, multiple anodes 3 can be deposited in multiple sizes. Once the anode 3 is deposited, the sacrificial layer can be removed to create a gap, in which case, in certain embodiments, the gap includes from about 0.001 to about 1000 μm, including from about 1 to about 10 μm, such as It is in the range of about 0.1 to about 100 μm. In certain embodiments, the gap between anode 3 and cathode 1 is selected to provide the desired impedance and different currents to the battery. The region of the anode 3 can also be manufactured to provide different voltages to the circuit chip 5 as desired. Thus, the anode 3 can be manufactured to provide multiple voltages and multiple impedances and currents for the same chip with minimal use of chip space.

  In some embodiments, the cathode layer is deposited on the dielectric on the chip surface, and multiple anodes are deposited on different areas of the cathode. During fabrication, a sacrificial layer is deposited to separate the anode from the cathode, and removal results in a gap between the common cathode and two or more anodes disposed over the cathode. As shown in FIG. 63, the anode 3 may be fixed to the external region of the circuit chip 5. It is at point 4 that the circuit contact for node 3 can be placed. FIG. 63 differs from FIG. 62 in that only two anodes 3 are deposited on the cathode 1. The two anodes 3 are also of different sizes and thus provide different surface areas. The anode 3 can be manufactured to meet the application requirements. If multiple voltages are desired, the anode 3 may be made of different materials. If multiple currents are desired, the anode 3 may be manufactured in multiple sizes. If multiple impedances are desired, the anode 3 may be deposited with different sized gaps between the anode 3 and the cathode 1.

  In some embodiments, the two anode plates are present on the surface of the circuit chip and the cathode circuit contact is deposited in the center of the surface. The cathode is then attached to a circuit contact over the anode, thereby forming a gap between the cathode and the anode. FIG. 64 shows another aspect of the implantable on-chip capacitor that utilizes the space above the circuit chip 5. The insulating layer 171 is formed on the surface of the circuit chip 5. The circuit contact for the cathode 1 is formed in the center of the chip and the anode 3 is formed on either side, leaving a gap between the circuit contact and the anode 3. During fabrication, a sacrificial layer is then deposited on the anode 3 to form the basis for the cathode 1. When the cathode 1 is deposited, the sacrificial layer is removed to provide a space for liquid to enter.

  In some embodiments, the cathode is on the surface of the circuit chip and the anode is positioned to be sufficient to provide an open chamber above and at least partially around the cathode. An opening is provided that allows the electrolyte solution to flow into a chamber that creates a current path between the anode and the cathode. Multiple openings may be provided as desired, for example to ensure that no air is trapped in the chamber. In FIG. 65, the anode 3 surrounds the cathode 1 and forms a chamber 173 into which the electrolyte solution enters. The insulating layer 11 separates the cathode 1 from the circuit chip 5. As a result of contact with the target site, the electrolyte solution enters the chamber 173 through the opening 175. In order to ensure that no air is trapped in, the opening 175 may be placed at the opposite corner of the chamber 173. In certain cases, the configuration of FIG. 65 may be desirable. For the case where there is no abundant amount of electrolyte in the stomach, an implantable on-chip battery may be fabricated to contain the fluid it contacts around the electrodes, as shown, for example, in FIG. Doing so will ensure a continuous reaction of the battery, but if it is open, fluid can enter and exit the reaction area and can cause the battery to shut down.

  For example, if a given battery unit includes a chamber, as shown in FIG. 65, a surface coating that modulates the inflow and outflow of fluid into the chamber may be employed if desired. In certain embodiments, some surfaces of the chamber, such as the inner surface of the chamber, may be modified to provide the desired flow characteristics. For example, the surface energy of one or more surfaces of the chamber and fluid port can be modified to provide increased flow to the chamber. For example, the surface energy of one or more surfaces of the chamber can be increased so that the surface becomes more hydrophilic. A variety of different surface energy modification protocols can be employed, in which case the particular protocol chosen can depend on the particular composition of the barrier and the desired surface energy characteristics. For example, if the surface energy of a given surface is to be increased, the surface is subjected to plasma treatment and surface energy modification, e.g., each disclosure is hereby fully incorporated herein for all purposes. You may make it contact with the surface modification polymer solution described in 5,948,227 and 6,042,710 etc. In certain embodiments, for example, the disclosure is hydrophilic to attract and retain electrolyte solution in the chamber, as described in PCT Application No. PCT / US07 / 82563, which is hereby incorporated by reference in its entirety. Substances may be employed.

  In certain embodiments, one or more surfaces of the battery, such as the inner surface of the chamber, are modified to modulate bubble formation and location on the surface. For example, battery activation may result in bubble generation, eg, hydrogen gas bubble generation. Surface modifications can be employed such that, for example, bubbles generated on the active cathode during activation are pulled away from the cathode to another location, such as a location away from the cathode, a location outside the chamber, and the like.

  The above embodiment is an example of a battery produced with a planar processing protocol where at least one anode and at least one cathode are present on the same surface of the circuit support element. The above description is in no way limiting, as other embodiments having the common features described above can be produced.

  In some embodiments, a planar processing protocol is employed in a wafer bonding protocol for generating a battery source. In some such embodiments, a dielectric can be deposited on the circuit chip. A cathode layer can then be deposited over the dielectric. The anode can be deposited on a separate support wafer. The anode can then be bonded to the bottom of the circuit chip, at which point the support wafer can be etched to bring the anode surface into contact with the electrolyte solution. Thus, another fabrication technique that can be used in the fabrication of implantable on-chip batteries is wafer bonding.

  The implantable on-chip battery can be manufactured using two wafers as in the embodiment of FIG. 66, for example. The circuit chip 5 provides the basis for the cathode 1 deposited on the dielectric 9. This constitutes the first wafer assembly 179. The second wafer assembly 178 is composed of a support wafer 177 and the anode 3. The anode 3 is deposited on the surface of the support wafer 177. The anode 3 is then bonded to the circuit chip 5 and the bulk support wafer 177 is etched to expose the area of the anode 3. The amount of support wafer 177 removed by etching depends on the area required for the anode 3. This fabrication method may be beneficial for implantable on-chip batteries, as more circuitry is required and can be placed on the support wafer 177.

  These aspects and others described above can be modified to switch the cathode to the anode, and vice versa, and provide additional disclosed configurations of the present invention. Additional aspects of the purpose produced by the planar process include those described in US Provisional Application No. 60 / 889,868, the disclosure of which is hereby incorporated by reference in its entirety.

  In addition to the identifier component described above, the ingestible event marker is a physiologically acceptable carrier component that aids in the intake of the identifier and / or protects the identifier until it reaches the target site of interest, For example, it can be present in (ie, combined with) the composition or vehicle. “Physiologically acceptable carrier component” means an ingestible composition that may be a solid or a fluid (eg, a liquid). Such a marker can be removed by any of the methods described herein, for example by incorporation into an intermediate device connecting the catheter with the intragastric device or other intragastric device, such as a catheter with a balloon. It can be incorporated into an internal placement system. The marker can be configured to be released from any structure of the intragastric placement system, for example after location is confirmed. Such markers can be implemented on physiologically acceptable carrier components that assist in the passage, disposal, etc. of the markers.

  Common carriers and excipients such as corn starch or gelatin, lactose, glucose, sucrose, microcrystalline cellulose, kaolin, mannitol, dicalcium phosphate, sodium chloride and alginate are of interest. Disintegrants commonly used in the formulations of the present invention include croscarmellose, microcrystalline cellulose, corn starch, sodium starch glycolate and alginic acid.

  Liquid compositions are suspensions or solutions of a compound or pharmaceutically acceptable salt in a suitable liquid carrier (s), such as ethanol, glycerin, sorbitol, non-aqueous solvents such as polyethylene glycol, oil or water. In combination with suspending, preserving, surfactant, wetting, flavoring or coloring agents. Alternatively, liquid formulations can be prepared from reconstitutable powders. For example, a powder containing the active compound, suspension, sucrose and sweetener can be reconstituted with water to form a suspension, and a syrup is prepared from the powder containing the active ingredient, sucrose and sweetener be able to.

  A composition in the form of a tablet or pill can be prepared using any suitable pharmaceutical carrier (s) conventionally used to prepare solid compositions. Examples of such carriers include magnesium stearate, starch, lactose, sucrose, microcrystalline cellulose and binders such as polyvinylpyrrolidone. Tablets may also be provided with a colorant included as part of the color film coating or carrier (s). In addition, the active compound can be formulated in controlled release dosage forms as tablets containing a hydrophilic or hydrophobic matrix.

  “Controlled release”, “sustained release” and similar terms are used when the active agent is released from the delivery vehicle at a identifiable and controllable rate over a period of time, rather than being dispersed immediately after application or injection. Used to describe the mode of active drug delivery that occurs. Controlled or sustained release may be extended to hours, days or months and can vary as a function of a number of factors. For the pharmaceutical compositions of the present invention, the release rate depends on the type of excipient selected and the concentration of excipient in the composition. Another determinant of the release rate is the rate of hydrolysis of the bonds between and within the units of the polyorthoester. The hydrolysis rate can then be controlled by the composition of the polyorthoester and the number of hydrolyzable bonds in the polyorthoester. Other factors that determine the rate of release of the active agent from the pharmaceutical composition include particle size, acidity of the medium (inside or outside of the matrix) and the physical and chemical properties of the active agent in the matrix. It is.

  A composition in the form of a capsule can be prepared using routine encapsulation procedures, for example by incorporation of the active compound and excipients into a hard gelatin capsule. Alternatively, a semi-solid matrix of the active compound and high molecular weight polyethylene glycol can be prepared and filled into hard gelatin capsules, or a solution of the active compound in polyethylene glycol, or an edible oil such as liquid paraffin or coconut oil Can be prepared and filled into soft gelatin capsules.

  Tablet binders that may be included are gum arabic, methylcellulose, sodium carboxymethylcellulose, polyvinylpyrrolidone (povidone), hydroxypropylmethylcellulose, sucrose, starch and ethylcellulose. Lubricants that can be used include magnesium stearate or other metal stearates, stearic acid, silicone oil, talc, waxes, oils and colloidal silica.

  Flavoring agents such as peppermint, winter green oil, cherry flavor and the like can also be used. In addition, it may be desirable to add a colorant to make the dosage form more attractive in appearance or to help identify the product. These may be similar to the flavoring agents used in some embodiments to signal the user that the intragastric balloon has been deflated, as described herein.

  Other components suitable for use in the formulations of the present invention include Remington's Pharmaceutical Sciences, Mace Publishing Company, Philadelphia, Pa. , 17th edition (1985).

  The positioning system is configured to receive a signal from an identifier of the IEM, i.e., to receive a signal emitted by the IEM upon contact with the IEM and the target physiological site after ingestion of the IEM. Machine can be included. The signal receiver may vary considerably depending on the nature of the signal generated by the signal generating element, for example as reviewed below. Thus, the signal receiver, as shown above, can produce a variety of different types of signals, such as, but not limited to: RF signals, magnetic signals, conductive (near field) signals, acoustic signals, etc. It can be configured to receive.

  In certain aspects, the receiver is configured to conductively receive signals from another component, eg, an identifier of an IEM, so that the two components utilize the patient's body as a communication medium. Thus, the signal transmitted between the IEM identifier and the receiver travels through the body and requires the body as a conducting medium. The signal originating from the identifier can be transmitted and received through the skin of the subject's body and other body tissues in the form of an electrical alternating current (ac) voltage signal conducted through the body tissue. . As a result, sensor data is exchanged directly through the subject's skin and other body tissues, so such aspects are used to transmit sensor data from the autonomous sensor unit to the central transceiver unit and other components of the system. No additional cable or wiring connection or even wireless link connection is required. This communication protocol allows the receiver to be positioned to fit any desired location on the subject's body, so that the receiver automatically adjusts to the electrical conductors necessary to achieve signal transmission. Connected, ie, signal transmission has the advantage that it is performed through electrical conductors provided by the subject's skin and other body tissues. If the receiver includes a sensing element (see below), it can have multiple receiver / sensor elements distributed throughout the body and communicating with each other via this body conductive media protocol. Such body-based data transmission further has the advantage that the transmission power required for it is very small. This avoids the occurrence of interference with the electrical operation of other devices, and also helps prevent unexpected interception or eavesdropping and monitoring of sensitive medical data. The resulting very low power consumption is further advantageous to achieve long-term monitoring goals, particularly in applications where power supply is limited.

  The signal receiver is configured to receive a signal from the identification element of the IEM. In this way, the signal receiver is configured so that it can recognize the signal originating from the identifier of the IEM. In certain aspects, the signal detection component is activated upon detection of a signal originating from the identifier. In certain aspects, the signal receiver is capable of simultaneously detecting multiple, eg, 2 or more, 5 or more, 10 or more, etc. compositions enabled by pharmaceutical informatics (ie, Configured as such).

  A signal receiver can include a variety of different types of signal receiving elements, where the nature of the receiving element necessarily depends on the nature of the signal generated by the signal generating element. In certain aspects, the signal receiver includes one or more electrodes (eg, multiple, eg, two or more, three or more, four or more pairs) for detecting a signal emitted by the signal generating element. Two or more electrodes, including three or more electrodes). In certain aspects, the receiver device is provided with two electrodes that are distributed at a distance, eg, a distance that allows the electrodes to detect a differential voltage. This distance can vary and in certain embodiments is in the range of about 0.1 to about 5 cm, such as about 0.5 to about 2.5 cm, such as about 1 cm. In certain embodiments, the first electrode is in contact with a conductive body element, such as blood, and the second electrode is a body element that is electrically insulating with respect to the conductive body element, such as adipose tissue (fat). In contact with. In an alternative embodiment, a receiver utilizing a single pole is employed. In certain aspects, the signal detection component can include one or more coils for detecting a signal emitted by the signal generating element. In certain aspects, the signal detection component includes an acoustic detection element for detecting a signal emitted by the signal generating element. In certain aspects, multiple pairs of electrodes (eg, as reviewed above) are provided, eg, to increase the detection probability of the signal.

  Target signal receivers include external and implantable signal receivers. In the external aspect, the signal receiver is ex vivo, which means that the receiver is outside the body during use. If the receiver is implanted, the signal receiver is in vivo. The signal receiver is configured to be stably associated with the body, for example in vivo or ex vivo, at least while it receives a signal transmitted from the IEM.

  In the broadest sense, the receivers of the present invention may be mobile or fixed with respect to the patient in which they are configured to operate. Mobile aspects of the signal receiver include those that are sized to stably associate with the biological object in a manner that does not substantially affect the operation of the biological object. As such, the signal receiver has dimensions that do not allow the subject to experience any difference in ability to move when employed in a subject, eg, a human subject. In these aspects, the receiver is sized such that its size does not impair the ability of the object to physically move.

In certain aspects, the signal receiver can be configured to have a very small size. If the signal receiver has a small size, there in certain embodiments, the signal receiver is about 5 cm ³ or less, including about 1 cm ³ or less, occupies example about 3 cm ³ less void volume. In certain aspects, the desired function of the signal receiver is achieved with one rechargeable battery.

  In addition to receiving a signal from an ingestible event marker identifier, the signal receiver may further include the ability to sense one or more different physiological parameters. By the ability to sense physiological parameters is meant the ability to sense physiological parameters or biomarkers, such as, but not limited to, the chemical composition of a fluid.

  In certain aspects, the signal receiver includes a set of two or more electrodes that provide a dual function of signal reception and sensing. For example, in addition to receiving a signal, the electrode can also serve an additional sensing function.

  In certain aspects, a signal receiver that can be viewed as an autonomous sensor unit is included. In some of these aspects, the sensor unit includes a sensor and a pair of transmit / receive electrodes that are adjusted to be placed on the subject's skin or body surface. The receiver may further include a central transceiver unit and a portable data recording unit that are adjusted to be placed on the subject's body. The autonomous sensor unit is capable of indicating the position of the marker, i.e. medical and / or physical data, e.g. pulse rate, blood oxygen content, blood sugar content, other blood composition data, blood pressure data, electrocardiogram data And one or more of electroencephalogram data, respiratory rate data, sweating data, body temperature data, activity, movement, electrode impedance, etc. are adjusted to be acquired from the subject's body. In addition, the component includes the ability to receive signals from an identifier of an internal device, such as an IEM. Since the transmit / receive electrodes of each autonomous sensor unit are coordinated to transmit acquired sensor data to the subject's body, these sensor data are transmitted through the subject's skin and / or other body tissue to a central transmit / receive unit, eg Sent to the sensor interface unit described above with respect to the electromagnetic placement system. Other signals, such as monitoring signals and polling signals, can be transmitted from the central transceiver unit to the sensor unit through the body tissue of interest, in which case these signals are picked up by the transmit / receive electrodes of the respective sensor unit.

  Additional elements that can be present in the signal receiver include, but are not limited to: a signal demodulator for decoding a signal emanating from an ingestible event marker; for example a signal A signal transmitter for sending signals from the receiver to an external location; for example, a data storage element for storing data relating to received signals, physiological parameter data, medical record data, etc .; A clock element for associating with; a preamplifier; for example, a microprocessor for coordinating one or more of the different functions of the signal receiver.

  An aspect of an implantable version of a signal receiver is that it is inductively powered by a biologically compatible enclosure, two or more sensing electrodes, a primary or rechargeable battery, or a broadcast to a coil. You may have a power supply. The signal receiver may also have circuitry including a demodulator that decodes the transmitted signal, some storage that records the event, a clock, and a method of transmitting out of the body. The clock and transmission function may be omitted in certain aspects. The transmitter may be an RF link or a conductive link that conveys information from a local data storage device to an external data storage device.

  When present, the demodulator component may be any convenient demodulator configured to demodulate a signal originating from an identifier of a pharmaceutical composition enabled by pharmaceutical informatics. In certain aspects, the demodulator is an in vivo transmit decoder that enables accurate signal decoding of low level signals using a small chip that consumes very low power, even in the presence of significant noise. It is. In one aspect, the in vivo transmit decoder is designed to decode signals modulated using two-phase phase modulation (BPSK). The signal can then be demodulated using a Costas loop. By applying a symbol recovery technique to the Costas loop output, the binary code is recovered. In some aspects, the in vivo transmit decoder may include an automatic gain control (AGC) block. The AGC block can determine the most powerful frequency component and signal power of the input signal. The strongest frequency of the signal can be used to tune the filter and voltage controlled oscillator in other parts of the algorithm. This can help the receiver to actively adapt to input signal frequency variations and input signal frequency drift. By measuring the signal power, the AGC block can then calculate and apply the gain required to normalize the signal power to a predetermined value. This gain can be further adjusted by reading the signal power in the Costas loop. In one aspect, the in vivo transmit decoder can actively adjust the sampling rate of the input signal to accommodate conditions such as the amount of noise present. For example, if the signal to noise ratio (SNR) is sufficient, the sampling rate can be maintained at a low value. If the SNR decreases below the set threshold during the decryption process, the sampling rate can be increased. In this manner, the sampling rate can be kept as low as possible without compromising the accuracy of the recovered signal. By actively adjusting the sampling rate as low as possible, the algorithm saves power. A further aspect of such an in vivo transmit decoder is provided in US Provisional Application No. 60 / 866,581 entitled “In-Vivo Transmission Decoder”, the disclosure of which is fully incorporated herein by reference.

  In certain aspects, the receiver components or functional blocks reside on an integrated circuit, and the integrated circuit includes a number of different functional blocks or modules. Within a given receiver, two or more, including at least some, eg, all, of the functional blocks can reside on a single integrated circuit within the receiver. A single integrated circuit means a single circuit structure that includes all of the different functional blocks. Thus, an integrated circuit is a monolithic integrated circuit (IC, microcircuit, microchip, which is a miniaturized electronic circuit (which can include semiconductor elements as well as passive elements) manufactured on the surface of a thin substrate of semiconductor material. Also known as silicon chip, computer chip or chip). One particular aspect of the integrated circuit of the present invention may be a hybrid integrated circuit, which is a miniaturized electronic circuit constructed with individual semiconductor elements and passive elements coupled to a substrate or circuit board.

  FIG. 53 provides a schematic diagram of a functional block diagram in accordance with aspects of the present invention. In FIG. 53, the receiver 10C includes first and second electrodes 11C and 12C, respectively, which are separated by a distance X and serve as an antenna for receiving a signal generated by an identifier. This distance X can vary, and in certain embodiments is in the range of about 0.5 to about 5 cm, such as about 0.5 to about 1.5 cm, such as about 1 cm. Amplifier 13C detects the differential signal across the electrodes. The detected signal enters the demodulator 14C next. A memory 15C for storing demodulated data is also shown. Clock 16C that writes events to its memory that records the date and time. The transmission circuit (Tx) (16) transmits data from the memory to the external receiver (not shown). There is also a power supply 17C that supplies power to all microelectronics. In the depicted embodiment, there is also a microprocessor 18C that coordinates functions between all of these blocks. Finally, a coil 19C wound around the periphery provides RF transmission. As summarized above, all of the different functional blocks shown in the embodiment of FIG. 53 may be on the same integrated circuit.

Another embodiment is represented in FIG. In FIG. 54, the main part of the receiver 20C includes all of the functions listed above and the electrode 21C. An electrode 22C at the end of wire 23C is also shown. This configuration minimizes the overall size of the receiver 20C while providing sufficient distance between e ₀ and e ₁ to act as an effective receiver.

  In some aspects, the signal receiver may be external. If the signal receivers are external, they may be configured in any convenient manner. If desired, the external configuration can include any of the elements described above with respect to the implantable embodiment. Thus, the external receiver can include the circuitry depicted in FIG. 53 and described above. Thus, if desired, the above elements, such as signal receivers, transmitters, memories, processors, demodulators, etc. may be present in the external receiver of the present invention. For example, functional diagrams of circuits that can be present in the external receiver of the present invention are shown in FIGS. 55A and 55B.

  FIG. 55A provides a functional block diagram of a receiver 70C according to one aspect, where the receiver includes an external interface block 71C, which includes a wireless communication element (eg, antenna), serial port, conductive interface, etc. Can be included. There is also a signal receiver circuit block 72C. There is also a receiver electrode functional block 73C. FIG. 55B provides a diagram of a circuit 74C found in a receiver according to an aspect of the present invention. The circuit 74C includes an external interface 75C, a memory 76C, a digital signal processor (DSP) 77C, and a real time clock (RTC) 78C. Also shown is an analog-to-digital converter (ADC) 79C, a preamplifier 80C, an optional reference (in-phase cancellation circuit) 81C and an electrode 82C.

  In certain external aspects, the receiver may be configured to contact or associate with the patient only temporarily, i.e., transiently, e.g., while an ingestible event marker is actually ingested. it can. For example, the receiver may be configured as an external device having two finger electrodes or handgrips. Upon receipt of the IEM, the patient or health care provider touches the electrode or fully grasps the handgrip to create a receiver and conduction circuit. After transmission of the signal from the IEM, for example when the IEM contacts the stomach, the signal transmitted by the IEM identifier is picked up by the receiver. At this point, the receiver can provide an indication to the patient or healthcare provider that the signal from the IEM has been received, for example in the form of an audible or visual signal. As indicated above, in certain external aspects, the receiver may contact the patient only temporarily, i.e., transiently, for example, during intragastric devices, ingestible markers, etc. To be configured or related.

  In some embodiments, the marker may be taken by the subject using any convenient means capable of producing the desired result, where the route of administration is, for example, as reviewed above, Depending at least in part on the particular format of the composition, including ingesting an ingestible event marker, for example, by swallowing the IEM composition with an intragastric device and / or a swallowable catheter. Depending on the particular application, the method can include ingesting the event marker alone or with another composition of matter, such as an intragastric device. For example, as reviewed above, when an ingestible event marker reaches the target physiological site, the IEM identifier emits a detectable signal. The signal receiver can handle the received data (eg, in the form of a signal emitted from an ingestible event marker) in various ways. In some aspects, the signal receiver may simply re-send the data to an external device (eg, using a wire that extends through the catheter, using conventional RF communications, or otherwise), eg, immediately or after some time. Transmit, in which case the data is stored in a storage element of the receiver. Thus, in certain aspects, the signal receiver receives for subsequent retransmission to an external device or for use in subsequent processing of data (eg, detecting changes in some parameters over time). Store the data. For example, an implanted collector includes conventional RF circuitry (eg, operating in a 405 MHz medical device band) that can be communicated by a practitioner using, for example, a data retrieval device, eg, a wand known in the art. be able to. In other aspects, the signal receiver transmits some action, such as operating an effector under its control, activating a visual or audible alarm, transmitting a control signal to an effector located elsewhere in the body The received data is processed to determine whether to take action such as The signal receiver can perform any combination of these and / or other operations with the received data.

  FIG. 56 is a side view of an embodiment of an intragastric system 5600 having a balloon capsule 5610 attached to a delivery / inflation catheter 5620, with the balloon having a power generation sensor 5630 therein. Capsule 5610 and catheter 5620 may be any of the aspects described herein. Sensor 5630 may be any of the aspects of ingestible event markers described herein. A sensor 5630 is shown positioned at the end of the capsule 5610 opposite the connection with the catheter 5620. However, this is just one example and the sensor 630 may be in any suitable location inside or outside the capsule 5610.

  FIG. 57 is a side view of an embodiment of an intragastric balloon system 5700 that includes a balloon 5710 and a catheter 5720 with an anode 5750 and a cathode 5740 having a specific pH coating 5760. The pH coating 5760 can be selected to control the exposure of the anode and cathode to the gastric environment, eg, gastric fluid. Catheter 5720 can have a wire 5720 for transmitting an electrical signal, eg, a voltage, received by the system. The wire 5720 can be electrically connected to the sensor interface unit, for example, as described herein.

  FIG. 67 illustrates the use in a patient of an embodiment of a power generation deployment system 6700 with event markers. System 6700 includes a balloon capsule 6710 that is exposed to gastric juice in the patient's stomach. Capsule 6710 may be taken by any of the methods described herein. Capsule 6710 is connected to balloon catheter 6720. In some embodiments, the catheter 6720 is connected to an ingestible event marker. In some embodiments, the capsule 6710 is connected to a marker. In some aspects, the balloon system 5600 of FIG. 56 can be implemented with the system 6700 shown in FIG. As further shown in FIG. 67, the system 6700 can further include a signal receiver 6730 that can be external to the patient. In some embodiments, the receiver 6730 is placed near the patient's stomach. System 6700 can also include a mobile device 6740 that communicates with a receiver 6730, such as a smartphone or tablet.

  FIG. 68 illustrates use of a power generation deployment system 6800 embodiment having an anode and a cathode in a patient. System 6800 can include a balloon capsule 6810 that is exposed to gastric fluid in the patient's stomach. Capsule 6810 may be taken by any of the methods described herein. Capsule 6810 is electrically connected by a wire in balloon catheter 6820. In some embodiments, the catheter 6820 includes an anode and a cathode at its distal end near the balloon 6810. As described herein, when the anode and cathode are in contact with gastric juice, the anode and cathode can provide a voltage signal to confirm placement in the stomach. System 6800 can also include a voltage lead 6830 in electrical communication with the cathode and anode. A voltage lead can connect the anode and cathode to a signal receiver 6840 that measures the voltage. The receiver 6840 can report to a user of the system 6800 when the voltage level reaches a predetermined threshold, eg, a voltage level indicative of the stomach environment of the stomach.

Tracking and visualization subcomponent based on pH Tracking and visualization functionality can be incorporated into the devices and systems described above. As used herein, “visualization” is used broadly to identify an item of interest in the body in several ways, including measuring the pH level encountered by an intragastric device or part thereof. Point to. Due to the non-invasive nature of the device, the physician may wish to determine or confirm the position and orientation of the device before inflation, during treatment or after deflation. Accordingly, an intragastric device is provided that incorporates a pH sensing component configured to allow determination and confirmation of the position, orientation and / or status of the intragastric device at all stages of administration.

  Various pH measurement systems can be used to indicate pH levels along the gastrointestinal tract encountered by intragastric devices. FIG. 69A represents an optional embodiment of a patient internal gastric device 10A (shown in FIG. 69B) with an external controller 86, as well as a separate display device 87, showing what is in use by the patient. As shown, the external controller 86 can be integrated with the device. FIG. 69A also illustrates how the controller 86 can be connected to a separate display device 87 for a larger or more elaborate display.

  FIG. 69B illustrates aspects of intragastric device 10A and wireless external display 88. FIG. As shown, the external display 88 could be used with the intragastric device 10A or its accessory when wireless communication was utilized. While monitoring the data, the physician was able to change the orientation, position, etc. of the intragastric device to ensure that it was within a range, such as the ideal position and orientation. Device 10A could have the ability to collect and analyze data with an algorithm that determines whether the device is in the ideal position, orientation, etc.

  In some embodiments, the intragastric device and / or accessory thereof is a procedure for monitoring one or more parameters, such as pH, in the intragastric device or within the gastrointestinal tract including the esophagus, stomach and / or intestine. One or more sensors for use in FIG. 69C depicts a side view of an embodiment of the pH sensor 28B of the intragastric device 20B positioned over the intragastric device 16B, eg, a balloon, within the stomach cross section. In some embodiments, sensor 28B will be tuned for accurate monitoring of pH with fine resolution, low hysteresis and will be tuned for tissue contact. The sensor can have a very small surface contact area or a wider surface contact area.

  System 20B can include equipment separate from intragastric device 16B and can be constructed with a shaft for placement under the esophagus and possibly an arm for manipulation. The system can further include accessories that can be attached to or contact the intragastric device 16B and removed after placement of the device.

  In some embodiments, sensor 28B is used as a guide during placement of intragastric device 16B to monitor placement, performance, adjustments or other data as needed. Sensor 28B is used when placing an intragastric device or performing an obese surgical procedure that induces weight loss by various weight loss mechanisms. The sensor can be used to ensure that the intragastric device is in place. The weight loss mechanism can include a space occupancy device such as that shown in FIG. 69C, such as an inflatable intragastric balloon, or other similar device described herein, for example suitable for weight loss. Sensors can be used to ensure achievement of fill volume. Intragastric device 16B with sensor 28B can also collect placement or adjustment data to customize placement and / or to adapt to the patient for improved long-term performance.

  Regardless of whether a wired or wireless sensor 28B is used, the external display may have the ability to collect and record data regarding ambient pH levels surrounding the intragastric device 16B. In some aspects, the external display may be above the controller 86, external display 87, and / or wireless external display 88 shown in FIGS. 69A-B. The external display may also have the ability to perform an analysis of the collected data for further diagnostic capabilities. An external display can have the ability to collect data and display it in various representations. It can display raw data, averages, or analyze the data and diagnose the general condition as appropriate or inappropriate. For example, an inappropriate state can be displayed with red light and an appropriate state can be displayed with green light. Similarly, the external display can be shown as a bright bar graph, where more appropriate states are indicated by more bars and less appropriate states are indicated by fewer bars. When a wired sensor is used, an external display 87 (FIG. 69A) may be connected to and integrated with the system 20B in order to read parameter data. If a wireless sensor is used, a wireless external display 88 (FIG. 69B) may be wirelessly connected to system 20B.

  In some embodiments, intragastric device 16B or a portion thereof may contain an array of sensors 28B disposed on or incorporated into a thin flexible sheet or element. The element may take various shapes including strips, disks, frusto cones, spheres, or any other part of them. If an array of sensors 28B is used, the display can show a 2D or 3D color plot or illustration of the pH mapping of the entire sensor array. Various visual displays may be used to represent the condition of device 16B.

  In some embodiments, multiple sensor arrays may be disposed on a single arm 24 or multiple arms 24. To cover the area of interest, a single arm 24 may take a loop, a bent wire, a spiral, a cylinder, a cone, or a plurality of these, or other shapes and forms. One or more arms 24 may be articulated to allow manipulation for ideal placement of device 16B during introduction into the body. In some embodiments, sensor 28B can be incorporated into a device with a narrow cross-section to adapt to the working channel of the gastrocamera. Alternatively, it may require larger sizing for additional functions such as articulating arms, but small enough to fit into the esophagus next to the gastrocamera for proper manipulation outside the body It may be long enough. If there are dilation or articulation features, the device 16B or accessory may have sufficient ability to collapse into a long narrow profile to facilitate placement under the esophagus. Device 16B can also be contoured to be smooth and reduce the potential for tissue stimulation.

  Sensor 28B may be in indirect contact with the patient, eg, outside the sizing balloon or outside the tube, in which case the gastrointestinal tract contacts the balloon or tube. Sensor 28B or device 16B may be reusable or disposable. After the placement, adjustment or treatment of device 16B is complete, the equipment used to place sensor 28B or device 16B, such as a catheter, may be removed.

  The equipment or accessories used to place device 16B may be made of many different materials or combinations of materials. For devices, the material will be acid resistant for temporary contact with the stomach for single or repeated use. For device accessories that are intended to remain on device 16B, the accessories may require more acid resistant properties. The elements of device 16B are Nitinol, shape memory / plastic, shape memory gel, stainless steel, superalloy, titanium, silicone, elastomer, Teflon (registered trademark), polyurethane, polynorvolene, styrene butadiene copolymer, crosslinked polyethylene, crosslinked polycyclooctene. , Polyethers, polyacrylates, polyamides, polysiloxanes, polyetheramides, polyetheresters and urethane butadiene copolymers, other polymers, or combinations above, or other suitable materials, or elsewhere here It may be made of a material.

  In some aspects, the system 20B may have a wireless or wired sensor 28B. If a wired sensor 28B is used in the device 20, a data transmission wire may be included in the shaft 22B and the data is directly from the sensor 28B to the display for monitoring, eg, FIG. 69A. The controller 86 may be sent to a small display or larger display device 87, or to a microprocessor for analysis, and then to a display. The microprocessor or external display may be integrated directly into system 20B, or system 20B may be connected to another larger external display 87 (shown in FIG. 69A).

  When wireless sensor 28B is used in system 20B, an external display, such as wireless external display 88 shown in FIG. 69B, can be used to send and receive signals remotely through telemetry from sensor 28B. The external display 88 may display data for monitoring or may contain a microprocessor for analysis and then display the data.

  In one aspect, wireless or wired sensor 28B is used in system 20B to communicate with a separate external display device, whether it is a small display of controller 86, a larger wired display 87, or a wireless display 88. be able to. It may be desirable to control sensor 28B from an external display device. The external display device can send a command to sensor 28B to query it to begin data collection. The external display device can also send separate or simultaneous commands to send data. Sensor 28B can receive commands from an external display device and then transmit or respond to collect and / or transmit data. When sufficient data is received, a command can be sent from an external display device to sensor 28B to tell sensor 28B to stop collecting and / or transmitting data.

  In addition, the sensor 28B and memory module of system 20B can be communicatively connected to the transmitter, receiver, or both to allow communication of data or other information with external receivers and transmitters. The transmitter can send a signal received from the sensor or signal data stored in the memory module.

  In some aspects, sensor 28B can assist in placement of intragastric device 16B. Device 16B can be placed under the esophagus and then filled with saline, air or other fluid through the filling tube, or filled to the appropriate volume as described herein. In this system 20B, sensor 28B may be placed between balloon 16 and the surrounding anatomy to measure the pH level. System 20B may be used to later adjust device 16B by filling or removing fluid with device 16B to customize the suitability of each patient over time. In some cases, it may be necessary to increase the fill volume of device 16B to increase weight loss. For example, if the balloon is overfilled during installation, it may be necessary to remove fluid from device 16B to reduce intolerance. Since device 16B is free to move and rotate in the stomach, it can also monitor orientation.

  The sensor 28B determines performance, placement, patient status, or whether adjustments need to be made for the adjustable intragastric device 16B, or whether the device 16B needs to be replaced or resized. It may be used to collect important patient data for understanding. The sensed pH can detect whether the device is not in an ideal state and can display this information on the external display 86.

  The appropriate algorithm (s) can determine and / or control the ideal parameter condition (s), or such condition (s) may be based on the parameter range. For example, data may be collected from sensor 28B for a fixed time. The external controller 86 or the microprocessor of the display 87, 88 may then calculate an average over time, minimum value, maximum value, standard deviation or time variation of standard deviation, or other suitable analysis. Based on the analysis, the microprocessor can determine whether the intragastric device 16B is in an ideal position or adjustment.

  FIG. 70A is a schematic side view of a human having a pH monitor 18B that can be incorporated into an intragastric device in the esophagus. FIG. 70A shows how physiological parameter data such as pH can be transmitted to a high frequency receiver or a radio receiver 32B placed outside the human 40P by a monitor 18B placed in the esophagus 30E. Illustrated. As shown in FIG. 70A, multiple monitors 18B can be combined with an intragastric device (not shown in FIG. 70A) so that data can be obtained from multiple locations. Further, monitor 18B may be any pH sensor discussed herein, for example sensor 28B with respect to FIGS. 69A-69C.

  In certain aspects, this data transmission is accomplished in real time through wireless telemetry. The wireless receiver 32B receives the physiological parameter data within 12 seconds from the measurement by the monitor 18B. After receipt of this data, the wireless receiver 32B device can record, manipulate, interpret and / or display the data using techniques well known to those skilled in the art. In certain embodiments, the patient may wear the receiver 32 and recorder, for example, on a belt, bracelet, arm or leg band or necklace during pH analysis.

  In certain aspects, monitor 18B can record and compress physiological parameter data, such as pH levels, as it is collected, rather than transmitting data in real time. An external transceiver can be used to download a pulse of enriched data after the evaluation period or during an intermittent period therein. As will be appreciated by those skilled in the art, data transmission may be initiated at predetermined intervals or by an activation signal sent to monitor 18B from an external transceiver or other activation device. In this way, a tabletop transceiver can be utilized at a patient's home or in a doctor's office or other clinical site.

  In other embodiments, monitor 18B can use memory chips and microprocessors to record, compress and store physiological parameter data as it is collected. Human 40P can drain monitor 18B into his or her stool and monitor 18B can be recovered. The data stored on the monitor 18B can then be downloaded to an external data retrieval device, which may be a computer or other analytical instrument placed outside the patient's body. This download can be accomplished by IR or RF transmission in response to the activation signal using magnetic field or radio frequency techniques well known to those skilled in the art.

  FIG. 70B is a schematic diagram of one embodiment of an electrical circuit for the pH monitor 18B. FIG. 70B illustrates a simplified circuit for a monitor 18B of physiological parameters, eg, pH level. This monitor 18B can also be referred to as a “probe” or “pill” and can be combined with the intragastric device described herein. In the particular embodiment illustrated in FIG. 70B, pH is a physiological parameter that is sensed, which is detected with a transducer 110C that also includes a pH sensor and preferably a reference sensor. In the present invention, the monitoring transducer may be any transducer that senses a physiological parameter and provides a signal, and one of the electrical properties of the signal, such as current or voltage, is measured Proportional to parameter.

  Although a pH sensor is described herein, those skilled in the art will appreciate that a variety of other physiological parameters, such as either pressure or temperature sensors, can be detected and monitored. Sometimes temperature and / or pressure are sensed and adjusted with pH to adjust or calibrate pH readings to make them more accurate or to provide additional data useful for patient condition analysis. Converted. Furthermore, the present invention can be used to detect and analyze the concentration of ions or other solutes present in body fluids. For example, ions such as sodium, potassium, calcium, magnesium, chlorine, bicarbonate or phosphoric acid can be measured. Other solutes whose concentration in body fluids is important and can be measured by the present invention include glucose, bilirubin (total, conjugated or unconjugated), creatinine, blood urea nitrogen, urine nitrogen, renin, among others And angiotensin. Any combination of two or more of the previous parameters can be sensed with transducer 110C. A reference sensor may or may not be required for any physiological parameter sensed and converted by the transducer.

  FIG. 70B also illustrates a high frequency transmitter circuit 112C and a power source 114C. The high-frequency transmitter circuit 112C can include an antenna (or antenna coil), and the antenna may be at least partially outside the monitor 18B. Alternatively, if present, the antenna may be completely self contained within the monitor 18B. As an alternative to RF transmission, a signal indicative of the parameter being monitored can be propagated through the patient's tissue from an electrical contact on the probe to a conductive skin electrode or other conductor in contact with the patient.

  When placed in the monitor 18B, the power source 114C may be a battery or capacitor or any other device capable of storing charge at least temporarily. In battery powered embodiments, battery life can be extended by disconnecting the battery from other circuit components, thereby limiting the parasitic current drain. This can be accomplished in various ways, for example by including a magnetic activation switch in the monitor 18B. This switch can be used to connect or disconnect the battery as required. By packaging the monitor 18B with an adjacent permanent magnet, the switch can be opened, thereby disconnecting the battery and thus extending the lifetime of the device. Removing the monitor 18B from the packaging (and the adjacent permanent magnet) closes the switch and connects the battery to power the monitor 18B.

  In some embodiments, the power source to monitor 18B may be external to monitor 18B. For example, the monitor 18B can derive power from an external electromagnetic radio frequency (RF) source, such as occurs with passive RF telemetry techniques well known to those skilled in the art, eg, RF coupling. The monitor 18B may be energized by a time-varying RF wave transmitted by an external transceiver 32, also known as an "interrogator", which can also act as a reader for data from the monitor 18B. As the RF field passes through an antenna coil located in the monitor 18B, an AC voltage is induced across the coil. This voltage is rectified to supply power to the monitor 18B. The physiological parameter data stored on the monitor 18B is transmitted back to the interrogator 32 (FIG. 70A) in a process often referred to as “backscatter”. By detecting the backscatter signal, the data stored in the monitor 18B can be completely transmitted.

  Other possible power sources for monitor 18B include light, body heat, and potential differences in voltage that can be generated with body fluids and detected with electrodes made of various materials. The use of such a power source for biotelemetry purposes is described in R.A. Stuart Mackay: Bio-Medical Telemetry, Sensing and Transmitting Biological Information from Animals and Man, 2d ed. , IEEE Press, New York, 1993, and that section entitled “Electronics: Power Sources” is hereby fully incorporated herein by reference.

  FIG. 70C is a schematic diagram of an embodiment of a pH monitor circuit where the circuit also includes a microprocessor 116. In some embodiments, the microprocessor 116 includes temporary storage or storage of data, reception of input signals from transducers, and conversion between analog and digital signals, among other functions that will be apparent to those skilled in the art. More than one function can be performed. There is also a transducer 110C, a high frequency transmitter 112C and a power source 114C. In other aspects of the monitor, many other circuit components that can help generate, amplify, modify or clarify the electrical signal may be used. Such components include, among other things, buffers, amplifiers, signal cancellation controllers, signal increase controllers, low pass filters, output voltage clamps and AD converters. Many of the possible circuit characteristics of portable pH monitoring devices, all of which can be used in the present invention, are described in detail in US Pat. No. 4,748,562 by Miller et al., The disclosure of which is hereby incorporated by reference. Fully integrated.

  In certain embodiments, the monitor 18B further includes a digital recorder or memory chip (not shown) that records the converted physiological parameter data. This recorder or memory chip allows temporary storage of this data accumulated over time.

  71A-71H show various views of various aspects of intragastric systems and devices that use chemical property indicating media to detect pH levels. In some embodiments, the intragastric device can include a detection indicator and a housing. The detection indicator can be configured to change from a first visual indicator to a second visual indicator upon contact with the fluid based on fluid characteristics, such as acidity. The housing can include an internal chamber configured to receive the fluid and provide contact between the fluid and the detection indicator. The housing may be further configured to removably engage a lumen inserted into the patient for receiving fluid from the patient through the lumen. In some aspects, the first opening of the removable housing is engaged to the proximal end of the lumen inserted into the patient. Movement of the fluid sample from the distal end of the lumen through the lumen and through the first opening to the removable housing such that the fluid sample contacts a detection indicator connected to the removable housing. Can cause. To determine the characteristics of the fluid sample, a visual comparison of the detection indicator with a reference indicator connected to the removable housing can then be performed. The first opening of the removable housing may be removed from the proximal end of the lumen.

  In some embodiments, the intragastric tube or guide element is a chemical property indicating medium to facilitate verification that the intragastric tube and / or the intragastric device thereon has been properly inserted into the patient's stomach. Can be incorporated. The fluid present in the patient's stomach has an acidic pH of less than 5.0. By exposing the indicator media to the fluid surrounding the distal end of the intragastric tube, the indicator media verifies that the pH of those fluids is less than 5.0, and therefore the appropriate location, It makes it possible to confirm the correct insertion of the intragastric tube in orientation, condition etc. If the indicating medium is incorporated into the intragastric tube, the fluid surrounding the distal end of the tube can be aspirated through the tube and contacted with the medium, which can then be observed by the user. If the indicating medium is incorporated into the guide element, the fluid surrounding the distal end of the tube will contact the medium without any additional obvious action by the user, but the guide element is then used to allow the condition of the medium to be observed. Must be pulled from. An indicator can generally be used to obtain a measurement of gastric pH.

  FIG. 71A shows a side view of an exemplary embodiment of an intragastric tube 810 in which a chemical property indicating medium is incorporated near its proximal end portion 114D. 71B is a cross-sectional view of exemplary embodiment tube 810 taken along section line 44-44 of FIG. 71A.

  As shown in FIGS. 71A-71B, the intragastric tube 810 can include a generally tubular proximal end portion 114D having an inner wall 814 that defines at least one lumen 146D. Where multiple lumens are provided in tube 810, lumen 146D may be tailored for use in aspirating fluid near the distal end of the tube. The intragastric tube 810 can include a portion 812 for receiving a chemical property indicating medium 820. Portion 812 may be enlarged compared to the diameter of other portions of the intragastric tube. A channel 822 is preferably provided in which the chemical property indicating medium 820 is captured. In order to allow fluid communication between the lumen 146D and the channel 822, several openings 816 are preferably provided between the lumen line of the lumen 146D and the channel 822. Opening 816, channel 822, and media 820 are preferably adjusted so that when fluid is present in lumen 146D, it immerses channel 822 and exposes media 820.

  In some embodiments, the media 820 provides a visual indication of a chemical property, such as pH, that can be manifested, for example, in hue change, reflectance, and the like. Portion 812 may be transparent or translucent to allow media 820 to be viewed from the outside. The shape of portion 812 can act as a magnifying lens to allow easy viewing of small media. Any suitable chemical property indication, including but not limited to litmus, pH indicator strips, paper, cloth or any other substrate impregnated with, or including, a pH indicator, etc. to implement media 820 Media can be used. The location and size of portion 812 is preferably selected so that the condition of the indicator strip is visually apparent when fluid is first aspirated through lumen 146D, so that the gastric tube in the patient's stomach There is no need for the user to take any additional steps to confirm correct insertion.

  FIG. 71C shows a side view of an additional exemplary embodiment of an intragastric tube 830 in which a chemical property indicating medium is incorporated near its proximal end portion 114D. FIG. 71D shows a side view of an additional exemplary embodiment of an intragastric tube 840 in which a chemical property indicating medium is incorporated near its proximal end portion 114D. 71E is a cross-sectional view of embodiment 830 taken along section line 47-47 thereof. FIG. 71F is a cross-sectional view of aspect 840 taken along section line 48-48 thereof.

  As shown in FIGS. 71C-71F, in some embodiments, each of the intragastric tubes 830 and 840 includes a generally tubular proximal end portion 114D having an inner wall 814 that defines at least one lumen 146D. . Where multiple lumens are provided in tube 830 or 840, lumen 146D may be tailored for use in aspirating fluid near the distal end of the tube. The intragastric tube 830 can include a chemical property indicating medium applied to the inner wall 814 in the form of a plurality of indicating elements 832 spaced circumferentially along the inner wall 814. The intragastric tube 840 can include a chemical property indicating medium applied to the inner wall 814 in the form of an indicating element 842 that covers the circumference of the inner wall 814. These particular configurations of indicating elements 832 and 842 are examples. Other configurations may be used.

  In some embodiments, indicator elements 832 and 842 are formed using any suitable chemical property indicator medium or material including, but not limited to, coatings, litmus, pH indicator strips, paper, cloth, and the like. be able to. For example, the medium may be formed as a coating or gelatin containing phenolphthalein. The term medium is also intended to refer to any indicator material, whether or not the indicator chemical or component is carried in or on a substrate, matrix or similar carrier. Other indicating media may be used. Where the media is integrated with a substrate such as a paper strip, such a substrate can be applied to the inner wall 814 using any suitable bonding or securing technique including infrared or ultrasonic bonding. The location and size of the indicating elements 832 and 842 are preferably selected such that the state of the indicating element is visually apparent when fluid is first aspirated through the lumen 146D, so that the stomach in the patient's stomach There is no need for the user to take any additional steps to confirm correct insertion of the inner tube. For some applications, the aspirated fluid that contacts the indicating medium may be reintroduced to the patient or otherwise contact the patient.

  In some embodiments, is the indicator medium attached to the inner wall 814 to prevent particles or fragments of the indicator medium itself from being inadvertently introduced into the patient through the intragastric tube or otherwise coming into contact with the patient? Or stick. In some embodiments, the indicator medium is preferably selected for biocompatibility so as to avoid any potential toxic effects.

  FIG. 71G shows a side view of an additional exemplary embodiment of an intragastric tube 850 in which a chemical property indicating medium is incorporated near its proximal end portion 114D. As shown in FIG. 71G, a plurality of different indicating elements, eg, 852, 854 and 856, are provided, each having a medium for visually and clearly indicating different chemical properties or different values of chemical properties. The indicating elements 852, 854 and 856 can change appearance, for example, to indicate that a different pH threshold has been sensed, or are specific in fluid aspirated from near the distal end of the gastric tube The appearance can be changed to indicate the presence or absence of a chemical, protein or other detectable component. This will not only provide a measure of gastric pH, but will also verify the proper placement, orientation, condition, etc. of the gastric tube and / or device. The activated appearance of each of the indicating elements 852, 854, 856 may be visually characteristic. For example, they can appear identifiably different colors, thereby minimizing ambiguity as to which indicator has been activated. The indicating element is shown in the form of a dot, but any suitable shape may be used, and the element can be provided in any practical size and number. Any suitable indicating medium may be used to implement the indicating elements 852, 854, and 856, such as those described in connection with aspects 830 and 840 of FIGS. 71C-71D.

  FIG. 71H shows a side view of an additional exemplary embodiment of an intragastric tube 860 in which a chemical property indicating medium is incorporated near its proximal end portion 114D. As shown in FIG. 71H, a plurality of different indicating elements, eg 862, 864 and 866, are provided, each having a medium for visually and clearly indicating different chemical properties or different values of chemical properties. , Each having a different shape, size or other characteristic so that there is no ambiguity as to which indicator is activated. The indicating elements 862, 864, and 866 can change appearance, for example, to indicate that a different pH threshold has been sensed, or are specific in fluid aspirated from near the distal end of the intragastric tube The appearance can be changed to indicate the presence or absence of a chemical, protein or other detectable component. The shape, size or other characteristics of the indicating element can be selected to correspond to the indicated property. In some embodiments, the indicator elements 862, 864 and 866 may be designed to change appearance when the fluid pH exceeds a specific pH threshold of 4.0, 5.0 and 3.0, respectively. Elements may be formed as recognizable characters, symbols or glyphs corresponding to these thresholds. Other characteristic shapes and shapes that define the correspondence between the visual peculiarities of the indicating elements and the perceived characteristics, and other schemes may be used. The activated appearance of each of the indicating elements 862, 864, 866 is in addition to their shape, eg, as a distinctly different color, to further minimize ambiguity as to which indicator is activated. It may be visually distinctive in the way it appears. Any suitable indicating medium may be used to implement the indicating elements 862, 864, and 866, such as those described in connection with aspects 830 and 840 of FIGS. 71C and 71D, respectively.

  FIG. 72 shows a further embodiment of an intragastric device 19B having a space filler 22A and a sensor 22C, eg, a pH sensor, along with delivery means for device and sensor implantation and retrieval. In some embodiments, sensor 22C includes a pH sensor element for sensing the pH of the patient's stomach, where the pH sensor element is a transmission for wirelessly transmitting the sensed pH to a receiver outside the patient's body. A machine can further be included. To assess the position, orientation, condition, performance, etc. of intragastric device 19B, the sensed pH or changes in sensed pH can be analyzed. FIG. 72 shows an embodiment of an intragastric device 19B having space fillers 22A that are fixed to the sensor 22C and arranged vertically. In some embodiments, the space filler 22A is fixed to and parallel to the sensor 22C. In some embodiments, the space filler 22A and the sensor 22C of the intragastric device 19B are configured to be aligned vertically within the gastric pouch.

  In some embodiments, there may be more than one space filler 22A. In some embodiments, sensor 22C may be a second space filler. In some embodiments, two or more space fillers are aligned with each other. In some embodiments, the two or more space fillers are parallel to each other. In some embodiments, the second space filler is wholly or partially enclosed within the first space filler 22A.

  In some embodiments, at least a portion of one or both of the two space fillers is made of a biodegradable material, and one or both are properties of the contents around, in or near the space filler (s) Has a sensor 22C for measuring, where the characteristics include pH. In some embodiments, more than two space fillers 22A and / or sensors 22C are incorporated into or otherwise integrated into the intragastric device 19B.

  In some embodiments, the catheter sheath 25 or delivery device for the intragastric device 19B enters the patient's stomach 40Z through the esophagus 24 and cardia notch. When it is delivered to the stomach, the space filler (s) 22A and / or sensor 22C is inflated. As shown in FIG. 72, in some embodiments, the intragastric device 19B includes a plurality of connecting members 36Z between the first space filler 22A and the second space filler or sensor 22C, where the first The space filler 22A is connected to the injection tubing 23 through a sealed inlet.

  In some embodiments, capsule technology may be incorporated into the intragastric device to sense pH levels. FIG. 73A is a schematic illustration of an embodiment of a capsule device that can be incorporated into an intragastric device to sense pH levels. FIG. 73B is a schematic diagram of a system that can be incorporated into an intragastric device for measuring pH, having two capsules connected to each other.

  In FIG. 73A, aspects of the capsule device and its components are illustrated. As shown, the capsule device includes a pH electrode 8B disposed on the capsule device to allow direct contact with the environment surrounding the capsule device. The pH electrode 8B is further in electrical contact with the reference electrode 9B. Furthermore, the capsule device comprises means that can be connected to a transmitter 5B for transmitting pH measurement data to the recording and / or analysis unit.

  In some embodiments, the capsule device includes a securing means 10B that preferably includes a drainable well and a pin. The device can be secured to the intragastric device through a securing means, which may be mechanical, chemical or other means for attaching and securing the capsule to the device.

  In some embodiments, the capsule device can have a pH sensor that is used with an imaging system. The pH level can indicate a possible position, orientation, location, etc., and the imaging system can be used to confirm or provide verification of the position, etc. In some aspects, the capsule device can include an optical window 1B and an imaging system for obtaining images from within the esophagus. The imaging system can include an illumination source 2B, such as a white LED, an imaging camera 3B that detects the image, and an optical system 4B that focuses the image on the imaging camera 3B. The irradiation source 2B can illuminate the inside of the esophagus through the optical window 1B. The capsule device further includes a transmitter 5B and an antenna 6B for transmitting the video signal of the image camera 3B, and a power source 7B, such as a battery, for supplying power to the electrical elements of the capsule device.

  Reference is now made to FIG. 73B, which schematically illustrates a plurality of connected capsules 11B and 12B according to aspects of the present invention. The plurality of capsules can be connected by, for example, a thread, a tube, a cable, a wire, or a flexible thin shaft 13B. In some aspects, multiple connecting wires or shafts can be used to connect two or more capsules. The connecting line 13B can physically and / or electrically connect two or more capsules and can be any suitable length from a few millimeters to centimeters or more. A flexible connection between two capsules can make the capsule more mobile and maneuverable in the esophagus than a single rigid or partially flexible capsule device of the same size or mass. In some aspects, the first capsule 11B can include components necessary for pH measurement, and components for securing the capsule device to, in or on the intragastric device. Thus, the second capsule 12B can also include components necessary for pH measurement and / or components for securing the capsule device to, within or on the intragastric device. In some embodiments, two or more capsules are used, each of which can be used for pH sensing and / or fixation. In some embodiments, the first capsule 11B can include components necessary for pH measurement and components for securing the capsule device to the stomach wall surface, where the second capsule 12B can include the components necessary to image the stomach and / or intragastric device.

  FIG. 74 shows an embodiment of a capsule system 2C with one or more pH sensors 61D for incorporation into an intragastric device, having two hard capsule-like units 11E, 11F and a soft flexible tube 12D connecting the capsule units. Is illustrated. The capsule-type system 2C includes a first capsule 11E and a second capsule 11F as two capsule-like hard units having different diameters, and a soft flexible having a diameter smaller than the diameter of the two capsules 11E and 11F. It includes a tube 12D and has a structure in which two capsules 11E and 11F are connected by a tube.

  The capsule-type system 2C can have a structure in which one or more sensors 61D, such as a pH sensor, are provided in the first capsule 11E, for example. Sensor 61D (s) is secured to an external member of the capsule, eg, transparent cover 15D, such that the sensing zone of sensor 61D is exposed to the outside and the interior of the capsule is maintained in a watertight state.

  Data such as body fluid chemical parameters (eg, pH values) are obtained from the sensing zone. The resulting data is temporarily stored in a memory (not shown) located in the capsule, and then transmitted to the receiver, eg, an external unit located outside the body, by a transmit / receive circuit and antenna. The

  In some embodiments, the pH sensor 61D can be used with an imaging system. For example, in the first capsule 11E, the cylindrical peripheral portion of the hard capsule frame may be watertight with the dome-shaped hard transparent cover 15D through the seal member. The imaging device and the irradiation device can be housed in the first capsule. In some embodiments, the objective lens 16D constituting the imaging device may be installed on the light-shielding lens frame 17D and disposed on the opposite side of the transparent cover 15D at the center of the internal space covered with the dome-shaped transparent cover 15D. . An imaging element, such as a CMOS imaging device, can be placed at the image forming position of the objective lens. In some embodiments, the white LEDs 19D are arranged as illumination devices at a plurality of locations around the lens frame 17D, and the light emitted by the white LEDs 19D passes through the transparent cover 15D and illuminates the outer space. There may be an elastic resin cover 28D outside the second capsule 11F. In some aspects, the imaging device may be used to verify the position, orientation, condition, etc. of the intragastric device after the pH sensor 61D indicates a particular pH level.

  The pH sensor can be incorporated into the gastric placement system in several ways. For example, as shown in FIG. 23, the balloon 1100 can incorporate pellets 1110 that are pH sensor pellets. The pellet may be unfixed or attached to the wall of the intragastric balloon 1100. As another example, as shown in FIG. 24, one embodiment of the balloon 1200 can incorporate a button 1210 as a pH sensor button attached to the opposite side of the intragastric balloon 1200. As another example, as shown in the cross section of FIG. 25A, the valve system 1300 can include a retaining ring 1318 that includes a pH sensor. FIG. 25B is a top view of a valve system 1300 that can include a pH sensor, represented in cross section along line 1D-1D in FIG. 25A. FIG. 25C is a top view of the valve system of FIGS. 25A and 25B incorporated into the wall of an intragastric balloon 1320 that may include a pH sensor. As another example, FIG. 26 depicts a gel cap 1400 containing the intragastric balloon of FIGS. 25A-C in an uninflated form that can include a pH sensor. The gel cap containing the uninflated balloon can be routed through a press-fit connection structure 1414 that can incorporate a pH sensor, eg, a needle (not shown), by the valve system of the intragastric balloon. Engages with a dual catheter system including.

  The previous example and / or any other aspect of the device can be used in various ways. FIG. 75 is a flowchart of an embodiment of a method 1100 for using pH detection to deploy and / or characterize an intragastric device. The method 1100 can include a block 1110 in which an intragastric device system having a pH sensor is provided. The intragastric device system having a pH sensor may be any of the examples or embodiments described herein, for example with respect to FIGS. The method 1100 can further include a block 1120 where an intragastric device is inserted into the patient. The intragastric device can be inserted into the patient by any of the methods described herein, for example, by swallowing a balloon, inserting a catheter with the balloon, and the like.

  The method 1100 may further include a block 1130 that senses ambient pH levels. The ambient pH level may be the pH level of the ambient fluid in the digestive tract that the device encounters. For example, the pH level of the esophagus and / or stomach can be sensed as the device moves through each section of the tube. The method can further include a block 1140 in which data regarding the pH level is transmitted to the computer. A computer shall include any device that receives a signal containing data, such as a receiver. In some aspects, the data is transmitted wirelessly to the receiver. In some embodiments, data is transmitted by wire from a wired sensor to a connected computer or receiver. Any of the examples and / or aspects discussed herein may be used at block 1140 to transmit pH data.

  The method 1100 may further include a block 1150 that analyzes the pH data. The pH data can be analyzed numerically and / or otherwise in any of the ways discussed herein, for example, by visual reading on a display. In some embodiments, the pH data is analyzed with a computer. In some embodiments, pH data is analyzed by a physician or technician.

  Finally, the method 1100 can further include a block 1160 where the position, orientation, status, etc. of the intragastric device is determined based on the pH data. In some embodiments, the analysis of the pH data indicates a possible position, orientation, state, etc. of the device. For example, a lower pH level can indicate that the device is in the stomach and a higher pH level can indicate that the device is in the esophagus. Such information may be useful, for example, when determining whether a balloon should be inflated.

Commercial Systems In some aspects, commercial systems can be incorporated into the present disclosure to provide pH sensing. One such commercial system is the BRAVO® pH monitoring system by Given Imaging. The BRAVO® pH monitoring system is a catheter-free mobile pH test that utilizes small pH capsules that transmit pH data for up to 96 hours. While this system is useful for measuring and monitoring the pH of gastric reflux to assist clinicians in diagnosing reflux esophagitis (GERD), this system is useful for the location, orientation of intragastric devices in the body. It can also be incorporated into aspects of the present disclosure to verify status and the like.

In some embodiments, a system is implemented that uses two major components for pH sensing. The first major component is a small pH capsule of approximately the same size as the gel cap that is integrated into or otherwise integrated into the intragastric device and transmits data to the receiver. The second major component is a pager sized receiver that receives pH data from the capsule. Data from the receiver can be uploaded to pH analysis software using infrared technology. The capsule can be incorporated into the intragastric system in several ways. In addition, multiple capsules can be incorporated into the intragastric device at various locations. In some embodiments, the capsule is placed on the opposite side of the intragastric device, eg, top / bottom, front / back and left / right. Individual readings from each sensor can provide an indication of device orientation in addition to position, status, etc. Another commercial system that can be incorporated into some embodiments is Sierra Scientific, Los Angeles, California. VersaFlex ™ system from Instruments. The system has a probe, such as a pH sensor, inserted into the gastric lumen and connected to a pH recording device, such as a Digitrapper from Sierra Scientific Instruments, Los Angeles, California. The probe is small and flexible to ensure maximum comfort for the patient. Probes are available in single or dual channel configurations. The tubing may be a 1.5 mm (4 Fr) diameter tubing with a smooth surface that eliminates the large “lumps” commonly found in sensor chips. For easier intubation that softens at body temperature for greater patient comfort, they can further have optimal stiffness. The dual channel configuration features two sensors spaced 5 cm apart. Since the pH probe must be soaked and calibrated before any procedure, a calibration kit is provided that contains a pH buffer and a disposable tube and provides a convenient solution to streamline pre-procedural work. . The calibration kit can include, for example, pH 7 and pH 4 buffers and deionized water for rinsing.

  FIG. 76 is a perspective view of an embodiment of a suitcase kit 3800 for the intragastric placement system of the present disclosure. Kit 3800 can include any of the tracking systems discussed herein, eg, system 1501 or 1601. Kit 3800 provides a self-contained portable assembly for carrying various systems. Kit 3800 includes a case 3810. Case 3810 may resemble a standard suitcase with a handle for easy transport. Case 3810 includes an upper portion 3815 and a bottom portion 3820. The top 3815 is rotatably attached to the bottom 3820 so that the top 3815 rotates and opens and closes. The top 3815 includes a display 3825 that can be electrically connected to other features of the system.

  The bottom 3820 can define a cavity 3830 therein. The cavity 3820 can include space for storing various components of various systems. For example, components of system 1501 or 1601 can be stored in cavity 3820. By closing the top 3815, the contents of the cavity 3830 can be protected from theft or elements. The bottom 3820 can further include a set of vertical supports 3835 and horizontal supports 3840. Supports 3835 and 3840 can be coupled to rotate relative to each other and allow reception in the bottom 3820. As shown, supports 3835, 3840 are stretched so that case 3810 is raised. Supports 3835, 3840 can be rotatably connected at joint 3842, which can be a pin or bushing that allows rotation.

  FIG. 77 is a perspective view of an embodiment of a backpack kit 3900 for the gastric placement system of the present disclosure. Kit 3900 can include any of the tracking systems discussed herein, eg, system 1501 or 1601. As shown, kit 390 includes a case 3910. Case 3910 can store various components of various systems and can allow easy transfer of those components to and from different kits 3900. Case 3910 is shown held on support member 3908 by strap 3915. The strap 3915 can allow the case 3910 to be secured to the member 3908. The strap 3915 may be required to carry the case 3910 like a general backpack.

  Support member 3908 is coupled to support surface 3920. Surface 3920 provides a high platform for placing items while performing a procedure in the system. Surface 3920 supports display 3925. Display 3925 can be used to show identifiers that indicate the location of various sensors. Surface 3920 also includes a foldable tip portion 3930. The tip portion 3930 is shown in a down position. It can also rotate up to provide more area on the surface 3920. Surface 3920 and tip portion 3920 are supported on frame 3935. The frame 3935 can include a compartment for storing items such as patient records or system components such as disposable catheters. In some aspects, the frame 3935 includes a drawer for storing items. The frame 3935 is supported by a mount 3940 having a wheel 3944 that allows the kit 3900 to move easily by rolling on the wheel 3842.

Film Permeability Various different composite films for gas permeability measured by CO ₂ diffusion at 37 ° C. and suitability for use as materials for walls or other components of various embodiments of gastric devices Was tested. As shown in Table 3 data, evaluate the permeability of the various composite wall structure by their resistance to CO ₂ diffusion rate, determined, where the higher the permeability test results smaller, more of the gas diffusion The film provides a high barrier. As noted, the permeability of the film and the degree of barrier that the film provides for gas diffusion was derived using 37 ° C. CO ₂ , one of the most permeable gases. This is when evaluated at 25 ° C., generally CO ₂ is rather 3-5 times faster diffusion than the oxygen across the membrane, substitute nitrogen for oxygen transmission rate than 0.2-0.4 times faster other gas diffusion rate It can be used as a product. As Table 3 shows, film permeability is also affected by film orientation (layers are first exposed to CO ₂ gas) and relative humidity. The walls were tested under conditions of low relative humidity (0%, representative of conditions inside the balloon after filling) and high relative humidity (100%, representative of in vivo conditions). In certain embodiments, composite walls having a permeability of <10 cc / m ² / day are generally preferred. However, higher permeabilities> 10 cc / m ² / day may be desirable under in vivo conditions, depending on the desired effects of expansion and re-expansion with in vivo gases such as CO ₂ . For example, each of the table films can be adapted for use in various selected embodiments, so that the resulting balloon wall has a CO ₂ permeability that exceeds> 10 cc / m ² / day, eg,> 50 cc / m ² / day,> 100 cc / m ² / day,> 200 cc / m ² / day,> 300 cc / m ² / day,> 400 cc / m ² / day,> 500 cc / m ² / day,> 750 cc / m ² / day,> 1000 cc / m ² / day,> 1500 cc / m ² / day,> 2000 cc / m ² / day,> 2500 cc / m ² / day,> 3000 cc / m ² / day,> 3500 cc / m ² / Day, or even> 4000 cc / m ² / day permeability. In selected embodiments, between about 1,2,3,4,5,6,7,8,9, or 10 cc / m ² / day to about 15,20,25,30,35,40,45,50,60 70, 80, 90, 100, 110, 120, 130, 140 or 150 cc / m ² / day are generally preferred. Various films are listed in Table 3 and elsewhere. When a film includes more than one layer, “/” is used to indicate a layer of one material adjacent to another layer, optionally with an intervening layer or material. For example, “A / B / C” refers to the layer of A adjacent to the layer of B, with or without intervening layers or materials (eg, tie layers, adhesives, surface preparations, surface treatments, etc.) A film comprising a layer of B adjacent to a layer of C on the side of the opposite layer B on the side adjacent to A. For the first entry in Table 3, “PE / EVOH / PE” means the first layer of polyethylene adjacent to the layer of ethylene vinyl alcohol, and the opposite ethylene vinyl on the side adjacent to the first layer of polyethylene. Refers to a film comprising a layer of ethylene vinyl alcohol adjacent to a second layer of polyethylene on the alcohol side.
Table 3

Animal studies Two different composite walls were tested: material with high barrier material properties (nylon 12 / PvDC / nylon 12 / LLDPE + LDPE) and material with low barrier properties (multilayer nylon 12 / LLDPE + LDPE). A series of experiments was performed using a mixture of 75% N ₂ and 25% CO ₂ as the initial balloon filler. As shown in the data in Table 4, each of the balloons maintained pressure throughout the test period, but the volume increased substantially. Considering that the composite walls tested were not metal canisters (volume and pressure fluctuated due to material stretching), there was a significant change in the number of total gas molecules in the balloon from the initial gas filling. Since the internal balloon environment was initiated with CO ₂ and nitrogen, additional CO ₂ was most likely invaded due to the environment to which the balloon was exposed (N ₂ and CO ₂ headspace), but in the air Other existing gases as well as water vapor are most likely diffused in the balloon wall.
Table 4.

The capacity increase was higher for the barrier material composite wall than for the non-barrier wall. Analysis of the gas in the balloon after explantation (Tables 5a and 5b) showed an increase in oxygen, hydrogen and argon in addition to the nitrogen and carbon dioxide already present in the balloon upon initial inflation. Balloons with both superior barrier composite walls (Table 5a) and inferior barrier composite walls (Table 5b) both increased in overall volume after 30 days in vivo while maintaining the pressure. Balloon explant results with composite walls containing excellent barrier material (# 2, Table 5a) showed a slightly higher increase in carbon dioxide than walls without barrier material (# 3, Table 5b). Not only is it less likely that nitrogen has diffused into or out of the balloon due to its inertness, but there is no (or insignificant) nitrogen gas diffusion gradient, so the external stomach environment has an internal concentration of nitrogen. Is most likely to match.
Table 5a.

Table 5b.

  The data shows that non-barrier composite wall materials may be preferred over barrier walls when it is desirable to minimize the increase in capacity over the useful life of the device. This observation goes against conventional insights that seek to maintain the initial filling of gas in the balloon by maximizing the barrier properties of the intragastric balloon wall.

Balloons constructed with simulated gastric environment non-barrier film composite walls (multilayer nylon 12 / LLDPE + LDPE) were tested in simulated gastric environment (1.2 pH HCl with NaCl and pepsin at 40 ° C. with variable N ₂ / CO ₂ headspace. A tank containing the solution; samples were taken in the tank with 50% peak CO ₂ and 0% trough CO ₂ ). The balloon was initially filled with pure N ₂ or a mixture of N ₂ (75%) and CO ₂ (25%), and pressure, volume and gas increase were monitored over time. Balloons filled with pure nitrogen showed a significantly higher increase in CO ₂ compared to balloons filled with N ₂ / CO ₂ mixture. If increased capacity (appearing with increased CO ₂ gas) is desired, pure nitrogen is desirable as the initial fill gas along with the non-barrier film. Experimental data is provided in Table 6.
Table 6.

Balloons constructed with various composite walls, barrier material nylon 12 / PvDC / nylon 12 / LLDPE + LDPE) and non-barrier material (multilayer nylon 12 / LLDPE + LDPE) were tested in a simulated gastric environment (variable N ₂ / CO ₂ headspace (Tank containing 1.2 pH HCl solution containing NaCl and pepsin at 40 ° C. according to (75% / 25% to 100% / 0%)). The balloon was initially filled with a mixture of N ₂ (75%) and CO ₂ (25%). Balloons made of CO ₂ barrier material maintained pressure and volume over the test period, while balloons made of CO ₂ non-barrier material showed a substantial pressure increase over the same period, with the volume increase being smaller. It was. The results are shown in Table 7.
Table 7.

Composite walls with high CO ₂ barrier properties (experiments 1, 2 and 3) (nylon 12 / PvDC / nylon 12 / LLDPE + LDPE) and walls with high CO ₂ permeability consisting of multilayer nylon 12 / LLDPE + LDPE (experiments 4, 5 and The balloon constructed in 6) was exposed to a simulated gastric environment. The simulated gastric environment included a tank containing a 1.2 pH HCl solution containing NaCl and pepsin at 40 ° C. The head space in the tank was circulated from a gas mixture containing 75% N ₂ /25% CO ₂ head space to one containing 100% N ₂ /0% CO ₂ . The balloon was initially filled with various mixtures of N ₂ and CO ₂ and the volume was monitored. Data regarding the capacity change is provided in Table 8. Balloons constructed with walls with higher CO ₂ permeability have substantially increased capacity compared to those with high CO ₂ barrier properties. For balloons constructed with walls with higher CO ₂ permeability, those having a higher N ₂ to CO ₂ ratio as the initial fill gas have a lower N ₂ to CO ₂ ratio The capacity increase was smaller. Data demonstrate the ability adopt this process to assist the penetration of CO ₂ into the balloon fabricated by a wall having a higher CO ₂ permeability occurs rapidly in the stomach environment, and the initial expansion of the implant To do.
Table 8.

Balloons constructed with non-barrier film composite walls were tested in vivo for 30 days in 10 patients in a human gastric environmental clinical trial. The balloon wall included multilayer nylon 12 / LLDPE + LDPE. One balloon was administered per patient. The balloon was filled with gas mixture to approximately 245 cc and the average starting pressure of the balloon was 1.01 psi above atmospheric pressure. The initial fill gas was 95% nitrogen and 5% CO _2. At the end of 30 days, the balloon remained full and tight, but the final pressure and volume could not be visually / endoscopically recognized. Of the 10 balloons collected, 10 balloons yielded internal gas samples and 8 provided meaningful data. Table 9 provides data collected from the balloon. The final gas sample reflects the gastric environment and the average is as follows: 82.4% N ₂ , 10.6% O ₂ , 5.9% CO ₂ and 0.84% Ar. Thus, the internal balloon environment reflects that of the average gastric environment gas concentration. Experimental data is provided in Table 9.
Table 9.

  In certain embodiments where it is desirable to maintain the starting pressure and volume of the device, this can be accomplished by closely matching the internal balloon environment (ie, fill gas) at the time of implantation with the gastric environment. In such embodiments, the balloon can be inflated with an initial gas fill gas comprising approximately 80-85% nitrogen, 8-12% oxygen, and 4-8% carbon dioxide. The concentrations of argon and other in vivo gases can be considered insignificant for the total volume / pressure and can be omitted for convenience or included as desired. In order to facilitate balloon inflation in vivo, the starting concentration of oxygen and / or carbon dioxide can be reduced.

Experiments were performed to determine the pressure in various balloons over time for different initial fill gases. With respect to Figure 43, the initial filling gas include: (volume%): 100% SF _6; in combination with 75% N _2; to 100% N _2; 50% in combination with 50% N ₂ SF ₆ 25% SF _6; and 78-80% N ₂ in combination with 18-20% SF _6. One type of balloon tested included a composite polymer wall comprising a 3.5 mil polyethylene layer and a nylon layer. Another type of balloon tested included an ethylene vinyl alcohol layer on the composite polymer wall. As the data presented in FIG. 43 shows, balloons containing 100% N ₂ as the fill gas show a slight increase in pressure over the first approximately 2-4 weeks of the test, followed by a decrease in pressure over time. Indicated. Balloons containing an ethylene vinyl alcohol layer were able to maintain the pressure at a level equal to or exceeding the initial fill pressure for approximately 4 months, whereas balloons containing polyethylene / nylon walls maintained such pressure for approximately 1 month. Could be maintained for a while. Balloons containing 100% SF ₆ showed a substantial increase in pressure over the first approximately 2-3 months, when the pressure tended to remain flat during the test period. By adding N ₂ to SF ₆ , the pressure at which leveling occurred was reduced. Approximately 18-20% of the SF ₆ and remaining N ₂ mixture showed a mild increase in pressure over a period of approximately 1 month followed by a maintenance of a substantially horizontal pressure over a period of approximately 4 months.

  The invention has been described above with reference to specific embodiments. However, other embodiments are equally possible within the scope of the present invention. Different method steps than those described above may be provided within the scope of the present invention. Different features and processes of the invention may be combined in combinations other than those described. The scope of the present invention is only limited by the appended claims.

  All references cited herein are hereby fully incorporated by reference. To the extent that publications and patents or patent applications incorporated by reference contradict the disclosure contained herein, this specification shall supersede and / or supersede such conflicting materials.

  To the extent the publications and patents or patent applications incorporated herein by reference contradict the disclosure contained herein, the specification will supersede and / or supersede such conflicting materials.

  Unless otherwise noted, all terms (including technical and scientific terms) are given their ordinary and ordinary meaning to those of ordinary skill in the art and are specifically or customized unless expressly so specified herein. Should not be limited to the meaning.

  Unless expressly stated otherwise, terms and expressions used in this application and variants thereof should be construed as open-ended for limitation. As an example above, the term “including” should be construed to mean “including but not limited to”. As used herein, the term “comprising” is synonymous with “including”, “containing” or “characterizing” and is inclusive or open-ended, with additional non-enumerated elements It does not exclude process steps. The term “example” is used to provide an illustrative example of an item under discussion and is not an exhaustive or limiting list thereof. Adjectives such as “known”, “normal”, “standard” and similar terms are interpreted to limit the items described to items available at a given time or at a given time. Should instead be construed as encompassing known, normal or standard techniques that are available or known at any time, now or in the future, and include the terms “preferably”, “preferred”, The use of the words "desired" or "desirable" and similar meanings is understood to mean that a particular feature is critical, essential or even important to the structure or function of the invention It should be understood that, instead, it is merely intended to highlight alternative or additional features that may or may not be available in certain aspects of the invention. Similarly, unless expressly specified otherwise, a group of items concatenated with the conjunction “and” should not be construed as requiring that each of those items be in the group; / Or ". Similarly, unless expressly specified otherwise, a group of items concatenated with the conjunction “or” should not be construed as requiring mutual exclusivity within the group, as “and / or” Should be interpreted. Further, as used in this application, the articles “a” and “an” should be construed to refer to one or more (ie, at least one) of the grammatical objects of the article. By way of example, “an element” means one element or more than one element.

  The presence of broadening words and phrases in some cases, such as “one or more”, “at least”, “but not limited to” or other similar phrases, is the absence of such broadening phrases Should not be construed to imply that a narrower case is intended or required.

  It should be understood that all numbers representing component amounts, reaction conditions, etc. as used herein are modified in all cases by the term “about”. Thus, unless specified otherwise, the numerical parameters shown herein are approximations that may vary depending on the desired characteristics that one desires to obtain. While at a minimum, the application of the principle of equality is not intended to limit the scope of any claims of any application claiming priority to this application, Interpretation should take into account the rounding approach. Where a range of values is provided, it is understood that the upper and lower limits of the range and each intermediate value between the upper and lower limits are encompassed within the scope of the embodiments.

  Furthermore, while the foregoing has been described in some detail by way of illustration and example for purposes of clarity and understanding, it will be apparent to those skilled in the art that certain changes and modifications may be practiced. Accordingly, the description and examples should not be construed to limit the scope of the invention to the specific embodiments and examples described herein, but all modifications and alternatives with the true scope and spirit of the invention. Should also be interpreted as covering.
Below, the claims at the beginning of the application are appended as embodiments.
[1] An electromagnetic system for placing an intragastric device in the body,
An electromagnetic field generator configured to generate an electromagnetic field;
A swallowable electromagnetic sensor configured to couple with the system and further configured to generate a current when exposed to an electromagnetic field in an in vivo gastric environment; and
A valve system configured to introduce an initial fill fluid into the intragastric device when the intragastric volume occupying device is in the in vivo intragastric environment, releasably coupled to the intragastric device The system comprising the valve system, comprising a swallowable catheter configured.
[2] The system of [1], wherein the electromagnetic sensor is configured to couple with the swallowable catheter.
[3] The system of [2], wherein the electromagnetic sensor is configured to couple with a distal end of the swallowable catheter.
[4] The system of [1], wherein the electromagnetic sensor is configured to couple with the intragastric device.
[5] The system according to any one of [1] to [4], further comprising at least one external reference sensor configured to generate an electric current when placed outside the body and exposed to a magnetic field. .
[6] The system according to any one of [1] to [5], further including three external reference sensors that are placed outside the body and configured to generate a current when exposed to a magnetic field.
[7] The system of any one of [5]-[6], further comprising a sensor interface unit configured to electrically communicate with the electromagnetic sensor and the at least one external reference sensor.
[8] The system of [7], further comprising a system control unit configured to be in electrical communication with the sensor interface unit and the electromagnetic field generator.
[9] The system of [8], further comprising a computer in electrical communication with the system control unit and configured to display an identifier indicating the location of the electromagnetic sensor in the body.
[10] At least one external reference sensor placed outside the body and configured to generate an electric current when exposed to a magnetic field, wherein the computer indicates a position of the at least one external reference sensor The system of [8], further configured to display two second identifiers.
[11] The system according to any one of [9] to [10], wherein the computer is further configured to display a trace indicating a path propagated by the electromagnetic sensor in the body.
[12] The system according to any one of [1] to [11], further including the intragastric device, wherein the intragastric device is a balloon.
[13] The gastric device further comprises the initial filling fluid, wherein the intragastric device is 10 cc / m under conditions of the in vivo gastric environment. ² / CO more than a day ₂ A polymer wall configured to be permeable to CO, so that the CO from the in vivo gastric environment through the polymer wall to the lumen of the gastric device ₂ The system of [12], wherein the rate and amount of diffusion is controlled at least in part by the concentration of inert gas in the initial fill fluid.
[14] CO in which the polymer wall includes an ethylene vinyl alcohol layer ₂ The system of [13], comprising a barrier material.
[15] The two-layer CO in which the polymer wall includes a nylon layer and a polyethylene layer ₂ The system of [13], comprising a barrier material.
[16] The three-layer CO in which the polymer wall includes a nylon layer, a polyvinylidene chloride layer, and a polyethylene layer ₂ The system of [13], comprising a barrier material.
[17] The three-layer CO in which the polymer wall includes a nylon layer, an ethylene vinyl alcohol layer, and a polyethylene layer ₂ The system of [13], comprising a barrier material.
[18] The initial filling fluid is gas N ₂ The system according to any one of [13] to [17], consisting essentially of:
[19] The initial filling fluid is gas N ₂ And gaseous CO ₂ The system according to any one of [13] to [17], consisting essentially of:
[20] The initial filling fluid is gas N ₂ And gaseous CO ₂ Consisting essentially of the gas N ₂ Gas CO in the initial fill fluid ₂ The system according to any one of [13] to [17], wherein the concentration is excessive with respect to.
[21] One or more SFs in which the initial filling fluid is in liquid, vapor, or gaseous form ₆ The system according to any one of [13] to [17], including:
[22] The initial filling fluid is gas N ₂ And gas SF ₆ The system according to any one of [13] to [17], including:
[23] The polymer wall is 50 cc / m under conditions of an in vivo gastric environment. ² / CO more than a day ₂ The system according to any one of [13] to [22], wherein the system is configured to be permeable to each other.
[24] A method for electromagnetically placing an intragastric device in a patient's body, comprising:
Generating an electromagnetic field using an electromagnetic field generator installed outside the patient's body;
The intragastric device comprising an uninflated intragastric balloon releasably coupled to a catheter and coupled to an electromagnetic sensor configured to generate an electric current in the presence of an electromagnetic field generated by the magnetic field generator Is introduced into the patient's body by swallowing;
Sensing the current induced in the electromagnetic sensor by an electromagnetic field; and
Determining the position of the non-inflated intragastric balloon within the patient based on sensing current induced in the electromagnetic sensor.
[25] The method according to [24], wherein the position of the uninflated intragastric balloon inside the patient is the patient's stomach.
[26] 10 cc / m under conditions of in vivo stomach environment ² / CO more than a day ₂ Introducing the initial filling fluid through the catheter into a lumen of the non-inflated intragastric balloon, comprising a polymer wall configured to have a permeability of;
Further exposing the inflated intragastric balloon to the in vivo intragastric environment for a useful life of at least 30 days, and from the in vivo intragastric environment through the polymer wall to the lumen of the balloon. CO ₂ The method of any one of [24]-[25], wherein the rate and amount of diffusion of is controlled at least in part by the concentration of inert gas in the initial fill fluid.
[27] The three-layer CO in which the polymer wall includes a nylon layer, a polyvinylidene chloride layer, and a polyethylene layer ₂ The method of [26], comprising a barrier material.
[28] The three-layer CO in which the polymer wall includes a nylon layer, an ethylene vinyl alcohol layer, and a polyethylene layer ₂ The method of [26], comprising a barrier material.
[29] Two layers of CO in which the polymer wall includes a nylon layer and a polyethylene layer ₂ The method of [26], comprising a barrier material.
[30] CO in which the polymer wall includes an ethylene vinyl alcohol layer ₂ The method of [26], comprising a barrier material.
[31] The initial filling fluid is gas N ₂ The method according to any one of [26] to [30], consisting essentially of:
[32] The initial filling fluid is gas N ₂ And gaseous CO ₂ The method according to any one of [26] to [31], consisting essentially of:
[33] The initial filling fluid is gas N ₂ And gaseous CO ₂ Consisting essentially of the gas N ₂ Gas CO in the initial fill fluid ₂ The method according to any one of [26] to [31], wherein the concentration is excessive with respect to.
[34] One or more SFs in which the initial filling fluid is in liquid, vapor, or gaseous form ₆ The method according to any one of [26] to [31], comprising:
[35] The initial filling fluid is gas N ₂ And gas SF ₆ The method according to any one of [26] to [31], comprising:
[36] The polymer wall is 50 cc / m under conditions of an in vivo gastric environment. ² / CO more than a day ₂ The method according to any one of [26] to [31], wherein the method is configured to be permeable to the liquid.
[37] Confirming the position of the non-expanded intragastric balloon inside the patient based on sensing of the current induced in the electromagnetic sensor displays an identifier indicating the position of the electromagnetic sensor on a computer The method according to any one of [24] to [36], comprising the step of:
[38] placing at least one external reference sensor configured to generate an electric current when exposed to an electromagnetic field outside the patient's body; and
38. The method of any one of [24]-[37], further comprising sensing current induced in the at least one external reference sensor by an electromagnetic field.
[39] Locating the position of the non-inflated intragastric balloon within the patient based on sensing current induced in the electromagnetic sensor indicates at least one position of the at least one external reference sensor. The method of [38], comprising displaying two second identifiers on a computer.
[40] The method according to any one of [24] to [38], wherein the electromagnetic sensor is coupled to the catheter.
[41] The method according to any one of [24] to [38], wherein the electromagnetic sensor is coupled to the intragastric device.
[42] A magnetic system for placing an intragastric device in the body,
A magnetic field sensor configured to sense a magnetic field;
A swallowable magnetic marker configured to couple with the system and further configured to generate a local magnetic field in an in vivo intragastric environment; and
A valve system configured to introduce an initial fill fluid into an intragastric volume occupying device when the intragastric device is in the in vivo intragastric environment, releasably coupled to the intragastric device The system comprising the valve system, comprising a swallowable catheter configured.
[43] The system of [42], wherein the magnetic marker is configured to couple with the swallowable catheter.
[44] The system of [43], wherein the magnetic marker is configured to couple with a distal end of the swallowable catheter.
[45] The system of [42], wherein the magnetic marker is configured to couple with the intragastric device.
[46] The system of any one of [42]-[45], further comprising at least one external reference sensor placed outside the body and configured to sense a local magnetic field.
[47] The system of any one of [42]-[45], further comprising a sensor interface unit configured to be in electrical communication with the magnetic marker.
[48] The system of [47], further comprising a system control unit configured to be in electrical communication with the sensor interface unit and the magnetic field sensor.
[49] The system of [48], further comprising a computer in electrical communication with the system control unit and configured to display an identifier indicating the position of the magnetic marker in the body.
[50] The system of [49], wherein the computer is further configured to display an indication of a path propagated by the magnetic marker in the body.
[51] The system according to any one of [42] to [50], further including the intragastric device, wherein the intragastric device is a balloon.
[52] Further comprising the initial filling fluid, wherein the intragastric device is 10 cc / m under conditions of the in vivo intragastric environment. ² / CO more than a day ₂ A polymer wall configured to be permeable to CO, so that the CO from the in vivo gastric environment through the polymer wall to the lumen of the gastric device ₂ The system of [51], wherein the rate and amount of diffusion of is controlled at least in part by the concentration of inert gas in the initial fill fluid.
[53] CO in which the polymer wall includes an ethylene vinyl alcohol layer ₂ The system of [52], comprising a barrier material.
[54] The two polymer layers wherein the polymer wall comprises a nylon layer and a polyethylene layer ₂ The system of [52], comprising a barrier material.
[55] The three-layer CO in which the polymer wall includes a nylon layer, a polyvinylidene chloride layer, and a polyethylene layer. ₂ The system of [52], comprising a barrier material.
[56] The three-layer CO in which the polymer wall includes a nylon layer, an ethylene vinyl alcohol layer, and a polyethylene layer ₂ The system of [52], comprising a barrier material.
[57] The initial filling fluid is gas N ₂ The system according to any one of [52] to [56], consisting essentially of:
[58] The initial filling fluid is gas N ₂ And gaseous CO ₂ The system according to any one of [52] to [56], consisting essentially of:
[59] The initial filling fluid is gas N ₂ And gaseous CO ₂ Consisting essentially of the gas N ₂ Gas CO in the initial filling fluid ₂ The system according to any one of [52] to [56], wherein the concentration is excessive.
[60] one or more SFs in which the initial filling fluid is in liquid, vapor, or gaseous form ₆ The system according to any one of [52] to [56], including:
[61] The initial filling fluid is gas N ₂ And gas SF ₆ The system according to any one of [52] to [56], including:
[62] The polymer wall is 50 cc / m under conditions of an in vivo gastric environment. ² / CO more than a day ₂ [52] The system according to any one of [52] to [61], which is configured to be permeable to each other.
[63] A method for magnetically placing an intragastric device in a patient's body, comprising:
The intragastric device, including an uninflated intragastric balloon, releasably coupled to a catheter and coupled to a magnetic marker configured to be sensed by a magnetic field sensor, is swallowed into the patient's body. Introducing;
Sensing a magnetic field using the magnetic field sensor; and
Determining the location of the uninflated intragastric balloon within the patient based on sensing the magnetic field.
[64] The method of [63], wherein the position of the uninflated intragastric balloon inside the patient is the patient's stomach.
[65] 10 cc / m under conditions of in vivo stomach environment ² / CO more than a day ₂ Introducing the initial filling fluid through the catheter into a lumen of the non-inflated intragastric balloon, comprising a polymer wall configured to have a permeability of;
Further exposing the inflated intragastric balloon to the in vivo intragastric environment for a useful life of at least 30 days, and from the in vivo intragastric environment through the polymer wall to the lumen of the balloon. CO ₂ The method of any one of [63]-[64], wherein the rate and amount of diffusion of is controlled at least in part by the concentration of inert gas in the initial fill fluid.
[66] Three layers of CO wherein the polymer wall comprises a nylon layer, a polyvinylidene chloride layer, and a polyethylene layer. ₂ The method of [65], comprising a barrier material.
[67] The three-layer CO in which the polymer wall includes a nylon layer, an ethylene vinyl alcohol layer, and a polyethylene layer ₂ The method of [65], comprising a barrier material.
[68] Two layers of CO wherein the polymer wall comprises a nylon layer and a polyethylene layer ₂ The method of [65], comprising a barrier material.
[69] CO wherein the polymer wall includes an ethylene vinyl alcohol layer ₂ The method of [65], comprising a barrier material.
[70] The initial filling fluid is gas N ₂ The method according to any one of [65] to [69], consisting essentially of:
[71] The initial filling fluid is gas N ₂ And gaseous CO ₂ The method according to any one of [65] to [69], consisting essentially of:
[72] The initial filling fluid is gas N ₂ And gaseous CO ₂ Consisting essentially of the gas N ₂ Gas CO in the initial fill fluid ₂ [65] The method according to any one of [65] to [69], wherein the concentration is excessive.
[73] one or more SFs in which the initial fill fluid is in liquid, vapor, or gaseous form ₆ The method according to any one of [65] to [69], comprising:
[74] The initial filling fluid is gas N ₂ And gas SF ₆ The method according to any one of [65] to [69], comprising:
[75] The polymer wall is 50 cc / m under conditions of an in vivo gastric environment. ² / CO more than a day ₂ [65] The method according to any one of [65] to [69], wherein the method is configured to be permeable to the liquid.
[76] Confirming the position of the uninflated intragastric balloon inside the patient based on sensing of a magnetic field generated by the magnetic marker causes an identifier indicating the position of the magnetic marker to be displayed on a computer The method according to any one of [63] to [75], comprising:
[77] The method according to any one of [63] to [75], wherein the magnetic marker is coupled to the catheter.
[78] The method according to any one of [63] to [75], wherein the electromagnetic sensor is coupled to the intragastric device.
[79] A power generation system for placing an intragastric device in the body,
A swallowable power generation sensor configured to couple with the system and further configured to generate a voltage in an in vivo intragastric environment; and
A valve system configured to introduce an initial fill fluid into an intragastric volume occupying device when the intragastric device is in the in vivo intragastric environment, releasably coupled to the intragastric device The system comprising the valve system, comprising a swallowable catheter configured.
[80] The system of [79], wherein the power generation sensor is configured to couple with the swallowable catheter.
[81] The system of [80], wherein the power generation sensor is configured to couple with a distal end of the swallowable catheter.
[82] The system of [79], wherein the power generation sensor is configured to couple with the intragastric device.
[83] The method of any one of [79]-[82], further comprising at least one receiver placed outside the body and configured to receive a signal associated with a voltage generated by the power generation sensor. System.
[84] The system of any one of [79]-[83], further comprising a sensor interface unit configured to be in electrical communication with the power generation sensor.
[85] The system of [84], further comprising a system control unit configured to be in electrical communication with the sensor interface unit and the power generation sensor.
[86] The system of [85], further comprising a computer in electrical communication with the system control unit and configured to display an identifier indicating the position of the power generation sensor in the body.
[87] The system according to any one of [79] to [86], further including the intragastric device, wherein the intragastric device is a balloon.
[88] Further comprising the initial filling fluid, wherein the intragastric device is 10 cc / m under conditions of the in vivo intragastric environment. ² / CO more than a day ₂ A polymer wall configured to be permeable to CO, so that the CO from the in vivo gastric environment through the polymer wall to the lumen of the gastric device ₂ The system of [87], wherein the rate and amount of diffusion is controlled, at least in part, by the concentration of inert gas in the initial fill fluid.
[89] CO wherein the polymer wall comprises an ethylene vinyl alcohol layer ₂ The system of [88], comprising a barrier material.
[90] The two-layer CO in which the polymer wall includes a nylon layer and a polyethylene layer ₂ The system of [88], comprising a barrier material.
[91] The three-layer CO in which the polymer wall includes a nylon layer, an ethylene vinyl alcohol layer, and a polyethylene layer ₂ The system of [88], comprising a barrier material.
[92] The three-layer CO in which the polymer wall includes a nylon layer, a polyvinylidene chloride layer, and a polyethylene layer ₂ The system of [88], comprising a barrier material.
[93] The initial filling fluid is gas N ₂ The system according to any one of [88] to [92], consisting essentially of:
[94] The initial filling fluid is gas N ₂ And gaseous CO ₂ The system according to any one of [88] to [92], consisting essentially of:
[95] The initial filling fluid is gas N ₂ And gaseous CO ₂ Consisting essentially of the gas N ₂ Gas CO in the initial fill fluid ₂ [88] The system according to any one of [88] to [92], wherein the concentration is excessive.
[96] One or more SFs in which the initial fill fluid is in liquid, vapor, or gaseous form ₆ The system according to any one of [88] to [92], including:
[97] The initial filling fluid is gas N ₂ And gas SF ₆ The system according to any one of [88] to [92], including:
[98] The polymer wall is 50 cc / m under conditions of an in vivo gastric environment. ² / CO more than a day ₂ [88] The system according to any one of [88] to [97], which is configured to be permeable to each other.
[99] A method for power generating placement of an intragastric device in a patient's body comprising:
Swallowing said intragastric device comprising an uninflated intragastric balloon, releasably coupled to a catheter and coupled to a power generation sensor configured to generate a voltage in the presence of the gastric environment, Introducing into the patient's body;
Generating a voltage using the power generation sensor responsive to contact with the gastric environment; and
Determining the location of the uninflated intragastric balloon within the patient based on sensing the generated voltage.
[100] The method of [99], wherein the position of the uninflated intragastric balloon inside the patient is the patient's stomach.
[101] 10 cc / m under conditions of in vivo stomach environment ² / CO more than a day ₂ Introducing the initial filling fluid through the catheter into a lumen of the non-inflated intragastric balloon, comprising a polymer wall configured to have a permeability of;
Further exposing the inflated intragastric balloon to the in vivo intragastric environment for a useful life of at least 30 days, and from the in vivo intragastric environment through the polymer wall to the lumen of the balloon. CO ₂ The method of any one of [99] to [100], wherein the rate and amount of diffusion of is controlled at least in part by the concentration of inert gas in the initial fill fluid.
[102] Three layers of CO wherein the polymer wall comprises a nylon layer, a polyvinylidene chloride layer, and a polyethylene layer ₂ The method of [101], comprising a barrier material.
[103] The three-layer CO in which the polymer wall includes a nylon layer, an ethylene vinyl alcohol layer, and a polyethylene layer ₂ The method of [101], comprising a barrier material.
[104] Two layers of CO wherein the polymer wall comprises a nylon layer and a polyethylene layer ₂ The method of [101], comprising a barrier material.
[105] CO in which the polymer wall includes an ethylene vinyl alcohol layer ₂ The method of [101], comprising a barrier material.
[106] The initial filling fluid is gas N ₂ The method according to any one of [101] to [105], consisting essentially of:
[107] The initial filling fluid is gas N ₂ And gaseous CO ₂ The method according to any one of [101] to [105], consisting essentially of:
[108] The initial filling fluid is gas N ₂ And gaseous CO ₂ Consisting essentially of the gas N ₂ Is the gaseous CO in the initial liquid ₂ [101] The method according to any one of [101] to [105], wherein the concentration is excessive.
[109] One or more SFs in which the initial fill fluid is in liquid, vapor, or gaseous form ₆ The method according to any one of [101] to [105], comprising:
[110] The initial filling fluid is gas N ₂ And gas SF ₆ The method according to any one of [101] to [105], comprising:
[111] The polymer wall is 50 cc / m under conditions of an in vivo gastric environment. ² / CO more than a day ₂ [101] The method according to any one of [101] to [110], which is configured to be permeable to.
[112] The method according to any one of [99] to [111], wherein the power generation sensor is coupled to the catheter.
[113] The method according to any one of [99] to [111], wherein the power generation sensor is coupled to the intragastric device.
[114] A pH-based system for placing an intragastric device in the body comprising:
A swallowable pH sensor configured to be coupled to the system and further configured to sense a pH level of fluid in an in vivo gastric environment; and
A valve system configured to introduce an initial fill fluid into an intragastric volume occupying device when the intragastric device is in the in vivo intragastric environment, releasably coupled to the intragastric device The system comprising the valve system, comprising a swallowable catheter configured.
[115] The system of [114], wherein the pH sensor is configured to couple with the swallowable catheter.
[116] The system of [115], wherein the pH sensor is configured to couple with a distal end of the swallowable catheter.
[117] The system of [114], wherein the pH sensor is configured to couple with the intragastric device.
[118] The method of any one of [114]-[117], further comprising at least one receiver placed outside the body and configured to receive a signal associated with a pH level sensed by the pH sensor. The described system.
[119] The system of any one of [114]-[118], further comprising a sensor interface unit configured to be in electrical communication with the pH sensor.
[120] The system of [119], further comprising a system control unit configured to be in electrical communication with the sensor interface unit and the pH sensor.
[121] The system of [120], further comprising a computer in electrical communication with the system control unit and configured to display an identifier indicating the location of the pH sensor in the body.
[122] The system according to any one of [114] to [121], further including the intragastric device, wherein the intragastric device is a balloon.
[123] Further comprising the initial filling fluid, wherein the vgastric device is 10 cc / m under conditions of the in vivo gastric environment. ² / CO more than a day ₂ A polymer wall configured to be permeable to CO, so that the CO from the in vivo gastric environment through the polymer wall to the lumen of the gastric device ₂ The system of [122], wherein the rate and amount of diffusion of is controlled at least in part by the concentration of inert gas in the initial fill fluid.
[124] CO wherein the polymer wall comprises an ethylene vinyl alcohol layer ₂ The system of [123], comprising a barrier material.
[125] Two layers of CO in which the polymer wall comprises a nylon layer and a polyethylene layer ₂ The system of [123], comprising a barrier material.
[126] The three-layer CO in which the polymer wall includes a nylon layer, a polyvinylidene chloride layer, and a polyethylene layer ₂ The system of [123], comprising a barrier material.
[127] The three-layer CO in which the polymer wall includes a nylon layer, an ethylene vinyl alcohol layer, and a polyethylene layer ₂ The system of [123], comprising a barrier material.
[128] The initial filling fluid is gas N ₂ The system according to any one of [123] to [127], consisting essentially of:
[129] The initial filling fluid is gas N ₂ And gaseous CO ₂ The system according to any one of [123] to [127], consisting essentially of:
[130] The initial filling fluid is gas N ₂ And gaseous CO ₂ Consisting essentially of the gas N ₂ Gas CO in the initial filling fluid ₂ [123] The system according to any one of [123] to [127], wherein the concentration is excessive.
[131] One or more SFs in which the initial fill fluid is in liquid, vapor, or gaseous form ₆ The system according to any one of [123] to [127], including:
[132] The initial filling fluid is gas N ₂ And gas SF ₆ The system according to any one of [123] to [127], including:
[133] The polymer wall is 50 cc / m under conditions of an in vivo gastric environment. ² / CO more than a day ₂ The system according to any one of [123] to [132], which is configured to be permeable to the liquid.
[134] A method for placing an intragastric device in a patient's body based on sensing the pH level of fluid in the body,
The intragastric device comprising an uninflated intragastric balloon releasably coupled to a catheter and coupled to a pH sensor configured to sense the pH level of the fluid in the intragastric environment within the body. Introducing into the patient's body by swallowing;
Sensing the pH level of the fluid in response to contact of the pH sensor with the gastric environment; and
Determining the location of the uninflated intragastric balloon within the patient based on sensing the pH level.
[135] The method of [134], wherein the position of the uninflated intragastric balloon within the patient is the patient's stomach.
[136] 10 cc / m under conditions of n vivo intragastric environment ² / CO more than a day ₂ Introducing an initial filling fluid through the catheter into the lumen of the uninflated intragastric balloon, comprising a polymer wall configured to have a permeability of;
Further exposing the inflated intragastric balloon to the in vivo intragastric environment for a useful life of at least 30 days, and from the in vivo intragastric environment through the polymer wall to the lumen of the balloon. CO ₂ The method of any one of [134]-[135], wherein the rate and amount of diffusion of is controlled at least in part by the concentration of inert gas in the initial fill fluid.
[137] Three layers of CO wherein the polymer wall includes a nylon layer, a polyvinylidene chloride layer, and a polyethylene layer. ₂ The method of [136], comprising a barrier material.
[138] The three-layer CO in which the polymer wall includes a nylon layer, an ethylene vinyl alcohol layer, and a polyethylene layer ₂ The method of [136], comprising a barrier material.
[139] Two layers of CO wherein the polymer wall comprises a nylon layer and a polyethylene layer ₂ The method of [136], comprising a barrier material.
[140] CO wherein the polymer wall includes an ethylene vinyl alcohol layer ₂ The method of [136], comprising a barrier material.
[141] The initial filling fluid is gas N ₂ The method according to any one of [136] to [140], consisting essentially of:
[142] The initial filling fluid is gas N ₂ And gaseous CO ₂ The method according to any one of [136] to [140], consisting essentially of:
[143] The initial filling fluid is gas N ₂ And gaseous CO ₂ Consisting essentially of the gas N ₂ Gas CO in the initial fill fluid ₂ [136] The method according to any one of [136] to [140], wherein the concentration is excessive.
[144] One or more SFs in which the initial fill fluid is in liquid, vapor, or gas form ₆ The method according to any one of [136] to [140], comprising:
[145] Initial filling fluid is gas N ₂ And gas SF ₆ The method according to any one of [136] to [140], comprising:
[146] The polymer wall is 50 cc / m under conditions of an in vivo gastric environment. ² / CO more than a day ₂ [136] The method according to any one of [136] to [140], which is configured to be permeable to the liquid.
[147] The method according to any one of [136] to [146], wherein the pH sensor is coupled to the catheter.
[148] The method according to any one of [136] to [146], wherein the pH sensor is coupled to the intragastric device.
[149] An acoustic system for placing an intragastric device in the body comprising:
An acoustic signal generator configured to generate an acoustic signal;
Configured to couple with the system and in response to the generated acoustic signal
a swallowable acoustic marker further configured to generate an acoustic response in the in vivo gastric environment; and
A valve system configured to introduce an initial fill fluid into an intragastric volume occupying device when the intragastric device is in the in vivo intragastric environment, releasably coupled to the intragastric device The system comprising the valve system, comprising a swallowable catheter configured.
[150] The system of [149], wherein the acoustic marker is configured to couple with the swallowable catheter.
[151] The system of [150], wherein the acoustic marker is configured to couple with a distal end of the swallowable catheter.
[152] The system of [149], wherein the acoustic marker is configured to couple with the intragastric device.
[153] The system of any one of [149]-[152], further comprising at least one external acoustic sensor placed outside the body and configured to sense the acoustic response of the acoustic marker.
[154] The system of [153], further comprising a sensor interface unit configured to be in electrical communication with the acoustic marker and the acoustic sensor.
[155] The system of [154], further comprising a system control unit configured to be in electrical communication with the sensor interface unit.
[156] The system of [155], further comprising a computer in electrical communication with the system control unit and the acoustic sensor and configured to display an identifier indicative of a position of the acoustic marker in the body.
[157] The system of [156], wherein the computer is further configured to display an indication of a path propagated by the magnetic marker in the body.
[158] The system according to any one of [149] to [157], further including the intragastric device, wherein the intragastric device is a balloon.
[159] Further comprising the initial filling fluid, wherein the intragastric device is 10 cc / m under conditions of the in vivo intragastric environment. ² / CO more than a day ₂ A polymer wall configured to be permeable to CO, so that the CO from the in vivo gastric environment through the polymer wall to the lumen of the gastric device ₂ 158. The system of [158], wherein the rate and amount of diffusion is controlled at least in part by the concentration of inert gas in the initial fill fluid.
[160] CO where the polymer wall comprises an ethylene vinyl alcohol layer ₂ The system of [159], comprising a barrier material.
[161] The two-layer CO in which the polymer wall includes a nylon layer and a polyethylene layer ₂ The system of [159], comprising a barrier material.
[162] The three-layer CO in which the polymer wall includes a nylon layer, a polyvinylidene chloride layer, and a polyethylene layer ₂ The system of [159], comprising a barrier material.
[163] The three-layer CO in which the polymer wall includes a nylon layer, an ethylene vinyl alcohol layer, and a polyethylene layer ₂ The system of [159], comprising a barrier material.
[164] The initial filling fluid is gas N ₂ The system according to any one of [159] to [163], consisting essentially of:
[165] The initial filling fluid is gas N ₂ And gaseous CO ₂ The system according to any one of [159] to [163], consisting essentially of:
[166] The initial filling fluid is gas N ₂ And gaseous CO ₂ Consisting essentially of the gas N ₂ Gas CO in the initial filling fluid ₂ [159] The system according to any one of [159] to [163], wherein the concentration is excessive.
[167] one or more SFs in which the initial fill fluid is in liquid, vapor, or gaseous form ₆ The system according to any one of [159] to [160], including:
[168] The initial filling fluid is gas N ₂ And gas SF ₆ The system according to any one of [159] to [163].
[169] The polymer wall is 50 cc / m under conditions of an in vivo gastric environment. ² / CO more than a day ₂ [159] The system according to any one of [159] to [168], which is configured to be permeable to the liquid crystal.
[170] The system according to any one of [149] to [169], wherein the acoustic signal is an ultrasonic signal.
[171] A method for acoustically placing an intragastric device in a patient's body, comprising:
An intragastric device comprising an uninflated intragastric balloon, wherein the intragastric device is releasably coupled to a catheter and coupled to an acoustic marker configured to generate an acoustic response in response to the acoustic signal. Introducing into the patient's body by swallowing;
Generating an acoustic signal; and
Locating the uninflated intragastric balloon within the patient based on an acoustic response generated in response to the acoustic signal.
[172] The method of [171], wherein the position of the uninflated intragastric balloon inside the patient is the patient's stomach.
[173] 10 cc / m under conditions of in vivo stomach environment ² / CO more than a day ₂ Introducing the initial filling fluid through the catheter into a lumen of the non-inflated intragastric balloon, comprising a polymer wall configured to have a permeability of;
Further exposing the inflated intragastric balloon to the in vivo intragastric environment for a useful life of at least 30 days, and from the in vivo intragastric environment through the polymer wall to the lumen of the balloon. CO ₂ The method of any one of [171]-[172], wherein the rate and amount of diffusion is controlled at least in part by the concentration of inert gas in the initial fill fluid.
[174] The three-layer CO in which the polymer wall includes a nylon layer, a polyvinylidene chloride layer, and a polyethylene layer ₂ The method of [73], comprising a barrier material.
[175] The three-layer CO in which the polymer wall includes a nylon layer, an ethylene vinyl alcohol layer, and a polyethylene layer ₂ The method of [173], comprising a barrier material.
[176] Two layers of CO wherein the polymer wall comprises a nylon layer and a polyethylene layer ₂ The method of [173], comprising a barrier material.
[177] CO wherein the polymer wall comprises an ethylene vinyl alcohol layer ₂ The method of [173], comprising a barrier material.
[178] The initial filling fluid is gas N ₂ The method according to any one of [173] to [177], consisting essentially of:
[179] The initial filling fluid is gas N ₂ And gaseous CO ₂ The method according to any one of [173] to [177], consisting essentially of:
[180] The initial filling fluid is gas N ₂ And gaseous CO ₂ Consisting essentially of the gas N ₂ Gas CO in the initial filling fluid ₂ The method according to any one of [173] to [177], wherein the concentration is excessive with respect to.
[181] One or more SFs in which the initial fill fluid is in liquid, vapor, or gaseous form ₆ The method according to any one of [173] to [177], comprising:
[182] The initial filling fluid is gas N ₂ And gas SF ₆ The method according to any one of [173] to [177], comprising:
[183] The polymer wall is 50 cc / m under conditions of an in vivo gastric environment. ² / CO more than a day ₂ The method according to any one of [173] to [177], wherein the method is configured to be permeable to the liquid.
[184] Locating the position of the uninflated intragastric balloon within the patient based on sensing the acoustic response includes displaying an identifier indicating the position of the acoustic marker on a computer. 173] to [178].
[185] The method according to any one of [173] to [174], wherein the acoustic marker is coupled to the catheter.
[186] The method according to any one of [173] to [184], wherein the acoustic marker is coupled to the intragastric device.
[187] The method according to any one of [173] to [186], wherein the acoustic sensor is an ultrasonic sensor and the acoustic marker is an ultrasonic marker.
[188] A system substantially as described in the specification and / or drawings.
[189] A method substantially as described in the specification and / or drawings.

Claims (10)

An electromagnetic system for placing an inflatable intragastric device in the body,
An electromagnetic field generator configured to generate an electromagnetic field;
And swallowable catheter comprising a swallowable electromagnetic sensor at the distal end, wherein said swallowable electromagnetic sensor generates a current when exposed to an electromagnetic field in the gastric environment in vivo (in vivo) Is configured as
A inflatable intragastric devices in swallowable capsule, when the inflatable intragastric device is in the gastric environment of the in vivo (in vivo), introducing the initial filling fluid into said inflatable intragastric device The inflatable intragastric device with a valve system configured such that the valve system is releasably coupled to the swallowable catheter and the swallowable electromagnetic sensor is the swallowable Adapted to be characterized with 5 or 6 degrees of freedom when a catheter is coupled to the valve system of the inflatable intragastric device;
At least one external reference sensor configured to generate an electric current when placed outside the body and exposed to a magnetic field;
A sensor interface unit configured to be in electrical communication with the electromagnetic sensor and the at least one external reference sensor;
A system control unit configured to be in electrical communication with the sensor interface unit and the electromagnetic field generator;
Including electromagnetic system. Placed outside the body, further comprising a three external reference sensors configured to generate a current when exposed to a magnetic field, the electromagnetic system of claim 1. Said system control unit and electrical communication, further comprising a computer configured to display an identifier indicating a position of the electromagnetic sensor in the body, the electromagnetic system of claim 1. And further comprising at least one external reference sensor configured to generate an electrical current when placed outside the body and exposed to a magnetic field, wherein the computer indicates a position of the at least one external reference sensor. The electromagnetic system of claim 3 , further configured to display the identifier. The electromagnetic system according to claim 3 or 4 , wherein the computer is further configured to display a trace that indicates a path propagated by the electromagnetic sensor in the body. A polymer wall further comprising the initial filling fluid, wherein the inflatable intragastric device is configured to be permeable to CO ₂ greater than 10 cc / m ² / day under conditions of the in vivo gastric environment. So that the rate and amount of diffusion of CO ₂ from the in vivo gastric environment through the polymer wall into the lumen of the inflatable gastric device is at least partially determined by the initial filling fluid 6. The electromagnetic system according to claim 5 , which is controlled by the concentration of inert gas therein. The electromagnetic system of claim 6 , wherein the initial fill fluid comprises gas N ₂ and gas SF ₆ . Electromagnetic system described in the polymer wall is configured to have a permeability to CO ₂ of 10~50cc / m ² / day under the conditions of the gastric environment in vivo, according to claim 6 or 7. The electromagnetic system according to any one of claims 1 to 8, wherein the swallowable catheter is a flexible small catheter and has a diameter of 4 French (1.35 mm) or less. 10. An electromagnetic system according to any one of the preceding claims, wherein the swallowable catheter binds or wraps itself for delivery with the swallowable capsule.