U.S. patent application number 14/880121 was filed with the patent office on 2016-03-03 for systems and methods for locating and/or characterizing intragastric devices.
The applicant listed for this patent is Obalon Therapeutics, Inc.. Invention is credited to Mark C. Brister, Neil R. Drake, Sheldon Nelson, Daniel J. Proctor.
Application Number | 20160058322 14/880121 |
Document ID | / |
Family ID | 53274096 |
Filed Date | 2016-03-03 |
United States Patent
Application |
20160058322 |
Kind Code |
A1 |
Brister; Mark C. ; et
al. |
March 3, 2016 |
SYSTEMS AND METHODS FOR LOCATING AND/OR CHARACTERIZING INTRAGASTRIC
DEVICES
Abstract
Devices and methods for treating obesity are provided. More
particularly, intragastric devices and methods of fabricating,
deploying, inflating, locating, tracking, monitoring, deflating,
and retrieving the same are provided.
Inventors: |
Brister; Mark C.; (Carlsbad,
CA) ; Drake; Neil R.; (Carlsbad, CA) ; Nelson;
Sheldon; (Carlsbad, CA) ; Proctor; Daniel J.;
(Carlsbad, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Obalon Therapeutics, Inc. |
Carlsbad |
CA |
US |
|
|
Family ID: |
53274096 |
Appl. No.: |
14/880121 |
Filed: |
October 9, 2015 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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14407923 |
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PCT/US2014/068458 |
Dec 3, 2014 |
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14880121 |
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61911958 |
Dec 4, 2013 |
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62062081 |
Oct 9, 2014 |
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Current U.S.
Class: |
600/409 |
Current CPC
Class: |
A61F 5/0003 20130101;
A61B 1/041 20130101; A61B 5/073 20130101; A61F 5/0089 20130101;
A61B 5/062 20130101; A61B 2034/2051 20160201; A61B 8/461 20130101;
A61B 2090/3966 20160201; A61F 5/003 20130101; A61B 5/4238 20130101;
A61B 5/0024 20130101; A61B 5/6861 20130101; A61B 1/00009 20130101;
A61F 5/0013 20130101; A61F 5/0076 20130101; A61F 5/0043 20130101;
A61B 5/6853 20130101; A61B 2562/168 20130101; A61B 2562/162
20130101; A61F 5/004 20130101; A61F 5/0046 20130101; A61M 2025/1054
20130101; A61B 5/14539 20130101; A61F 5/0036 20130101; A61B 8/0833
20130101; A61B 5/6852 20130101; A61B 5/14507 20130101; A61B
2034/2072 20160201; A61B 1/00 20130101; A61B 50/13 20160201; A61B
2034/2063 20160201; A61B 2090/3929 20160201; A61B 5/0028 20130101;
A61B 8/56 20130101; A61B 5/065 20130101; A61B 5/742 20130101 |
International
Class: |
A61B 5/06 20060101
A61B005/06; A61F 5/00 20060101 A61F005/00; A61B 5/00 20060101
A61B005/00 |
Claims
1. A magnetic system for locating an intragastric device inside the
body, the system comprising: a magnetic field sensor configured to
sense a magnetic field; a swallowable magnetic marker configured to
couple with the system and further configured to produce a local
magnetic field in an in vivo gastric environment; and a valve
system configured for introducing an initial fill fluid into a
volume occupying intragastric device when the intragastric device
is in the in vivo gastric environment, the valve system comprising
a swallowable catheter configured to releasably couple with the
intragastric device.
2. The system of claim 1, wherein the magnetic marker is configured
to couple with a distal end of the swallowable catheter.
3. The system of claim 1, wherein the magnetic marker is configured
to couple with the intragastric device.
4. The system of claim 1, further comprising at least one external
reference sensor configured to be placed outside the body and to
sense a local magnetic field.
5. The system of claim 1, further comprising a sensor interface
unit configured to electrically communicate with the magnetic
marker.
6. The system of claim 5, further comprising a system control unit
configured to electrically communicate with the sensor interface
unit and with the magnetic field sensor.
7. The system of claim 6, further comprising a computer configured
to electrically communicate with the system control unit and to
display an identifier indicating the location of the magnetic
marker inside the body.
8. The system of any of claim 7, wherein the computer is further
configured to display a trace indicating a path travelled by the
magnetic marker inside the body.
9. The system of claim 1, further comprising the intragastric
device, wherein the intragastric device is a balloon.
10. The system of claim 9, further comprising the initial fill
fluid, wherein the intragastric device comprises a polymeric wall
configured to have, under conditions of the in vivo gastric
environment, a permeability to CO.sub.2 of more than 10
cc/m.sup.2/day, such that a rate and an amount of diffusion of
CO.sub.2 from the in vivo gastric environment into a lumen of the
intragastric device through the polymeric wall is controlled, at
least in part, by a concentration of an inert gas in the initial
fill fluid.
11. The system of claim 10, wherein the initial fill fluid
comprises SF.sub.6 in one or more of liquid form, vapor form, or
gaseous form.
12. The system of claim 10, wherein the initial fill fluid
comprises gaseous N.sub.2 and gaseous SF.sub.6.
13. A method for magnetically locating an intragastric device
inside the body of a patient, the method comprising: introducing
into the body of the patient, via swallowing, the intragastric
device comprising an uninflated gastric balloon, the intragastric
device releasably coupled with a catheter and coupled with a
magnetic marker, the magnetic marker configured to be sensed by the
magnetic field sensor; sensing the magnetic field with the magnetic
field sensor; and confirming a location of the uninflated gastric
balloon inside the patient based on sensing the magnetic field.
14. The method of claim 13, wherein the location of the uninflated
gastric balloon inside the patient is the patient's stomach.
15. The method of claim 13, further comprising: introducing an
initial fill fluid into a lumen of the uninflated gastric balloon
through the catheter, the intragastric balloon comprising a
polymeric wall configured to have, under conditions of an in vivo
gastric environment, a permeability to CO.sub.2 of more than 10
cc/m.sup.2/day; and exposing the inflated intragastric balloon to
the in vivo intragastric environment for a useful life of at least
30 days, wherein a rate and an amount of diffusion of CO.sub.2 from
the in vivo gastric environment into the lumen of the balloon
through the polymeric wall is controlled, at least in part, by a
concentration of an inert gas in the initial fill fluid.
16. The method of claim 15, wherein the initial fill fluid
comprises SF.sub.6 in one or more of liquid form, vapor form, or
gaseous form.
17. The method of claim 15, wherein the initial fill fluid
comprises gaseous N.sub.2 and gaseous SF.sub.6.
18. The method of claim 13, wherein confirming a location of the
uninflated gastric balloon inside the patient based on sensing the
magnetic field generated by the magnetic marker comprises
displaying on a computer an identifier indicating the location of
the magnetic marker.
19. The method of claim 13, wherein the magnetic marker is coupled
with the catheter.
20. The method of claim 13, wherein the electromagnetic sensor is
coupled with the intragastric device.
Description
INCORPORATION BY REFERENCE TO RELATED APPLICATIONS
[0001] Any and all priority claims identified in the Application
Data Sheet, or any correction thereto, are hereby incorporated by
reference under 37 CFR 1.57. This application is a continuation of
U.S. application Ser. No. 14/407,923, filed Dec. 12, 2014, which is
the national stage of PCT International Application No.
PCT/US14/68458, filed Dec. 3, 2014, which claims priority to U.S.
Provisional Application No. 61/911,958, filed Dec. 4, 2013, and to
U.S. Provisional Application No. 62/062,081, filed Oct. 9, 2014.
Each of the aforementioned applications is incorporated by
reference herein in its entirety, and each is hereby expressly made
a part of this specification.
FIELD
[0002] Devices and methods for treating obesity are provided. More
particularly, intragastric devices and methods of fabricating,
deploying, inflating, locating, tracking, monitoring, deflating,
and retrieving the same are provided.
BACKGROUND
[0003] Obesity is a major health problem in developed countries.
Obesity puts you at greater risk of developing high blood pressure,
diabetes and many other serious health problems. In the United
States, the complications of being overweight or obese are
estimated to affect nearly one in three American adults, with an
annual medical cost of over $80 billion and, including indirect
costs such as lost wages, a total annual economic cost of over $120
billion. Except for rare pathological conditions, weight gain is
directly correlated to overeating.
[0004] Noninvasive methods for reducing weight include increasing
metabolic activity to burn calories and/or reducing caloric intake,
either by modifying behavior or with pharmacological intervention
to reduce the desire to eat. Other methods include surgery to
reduce the stomach's volume, banding to limit the size of the
stoma, and intragastric devices that reduce the desire to eat by
occupying space in the stomach.
[0005] Intragastric volume-occupying devices provide the patient a
feeling of satiety after having eaten only small amounts of food.
Thus, the caloric intake is diminished while the person is
satisfied with a feeling of fullness. Currently available
volume-occupying devices have many shortcomings. For example,
complex gastric procedures are required to insert some devices.
[0006] U.S. Pat. No. 4,133,315, the contents of which are
incorporated herein by reference in their entirety, discloses an
apparatus for reducing obesity comprising an inflatable,
elastomeric bag and tube combination. The bag can be inserted into
the patient's stomach by swallowing. The end of the attached tube
distal to the bag remains in the patient's mouth. A second tube is
snaked through the nasal cavity and into the patient's mouth. The
tube ends located in the patient's mouth are connected to form a
continuous tube for fluid communication through the patient's nose
to the bag. Alternatively, the bag can be implanted by a gastric
procedure. The bag is inflated through the tube to a desired degree
before the patient eats so that the desire for food is reduced.
After the patient has eaten, the bag is deflated. The tube extends
out of the patient's nose or abdominal cavity throughout the course
of treatment.
[0007] U.S. Pat. Nos. 5,259,399, 5,234,454 and 6,454,785, the
contents of which are incorporated herein by reference in their
entirety, disclose intragastric volume-occupying devices for weight
control that must be implanted surgically.
[0008] U.S. Pat. Nos. 4,416,267, 4,485,805, 4,607,618, 4,694,827,
4,723,547, 4,739,758, and 4,899,747 and European Patent No.
246,999, the contents of which are incorporated herein by reference
in their entirety, relate to intragastric, volume-occupying 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
contents of which are incorporated herein by reference in their
entirety relate to balloons whose surface is contoured in a certain
way to achieve a desired end. In U.S. Pat. Nos. 4,416,267 and
4,694,827, the contents of which are incorporated herein by
reference in their entirety, the balloon is torus-shaped with a
flared central opening to facilitate passage of solids and liquids
through the stomach cavity. The balloon of U.S. Pat. No. 4,694,827,
the contents of which are incorporated herein by reference in their
entirety, has a plurality of smooth-surfaced convex protrusions.
The protrusions reduce the amount of surface area which contacts
the stomach wall, thereby reducing the deleterious effects
resulting from excessive contact with the gastric mucosa. The
protrusions also define channels between the balloon and stomach
wall through which solids and liquids may pass. The balloon of U.S.
Pat. No. 4,739,758, the contents of which are incorporated herein
by reference in their entirety, has blisters on its periphery that
prevent it from seating tightly against the cardia or pylorus.
[0009] The balloons of U.S. Pat. Nos. 4,899,747 and 4,694,827, the
contents of which are incorporated herein by reference in their
entirety, are inserted by pushing the deflated balloon and
releasably attached tubing down a gastric tube. U.S. Pat. No.
4,723,547, the contents of which are incorporated herein by
reference in their entirety discloses a specially adapted insertion
catheter for positioning its balloon. In U.S. Pat. No. 4,739,758,
the contents of which are incorporated herein by reference in their
entirety, the filler tube effects insertion of the balloon. In U.S.
Pat. No. 4,485,805, the contents of which are incorporated herein
by reference in their entirety, the balloon is inserted into a
finger cot that is attached by string to the end of a conventional
gastric tube that is inserted down the patient's throat. The
balloon of European Patent No. 246,999 is inserted using a
gastroscope with integral forceps.
[0010] In U.S. Pat. Nos. 4,416,267, 4,485,805, 4,694,827,
4,739,758, and 4,899,747 and European Patent No. 246,999, the
contents of which are incorporated herein by reference in their
entirety, the balloon is inflated with a fluid from a tube
extending down from the patient's mouth. In these patents, the
balloon also is provided with a self-sealing hole (U.S. Pat. No.
4,694,827, the contents of which are incorporated herein by
reference in their entirety), injection site (U.S. Pat. Nos.
4,416,267 and 4,899,747, the contents of which are incorporated
herein by reference in their entirety), self-sealing fill valve
(U.S. Pat. No. 4,485,805, the contents of which are incorporated
herein by reference in their entirety), self-closing valve
(European Patent No. 246,999, the contents of which are
incorporated herein by reference in their entirety) or duck-billed
valve (U.S. Pat. No. 4,739,758, the contents of which are
incorporated herein by reference in their entirety). U.S. Pat. No.
4,723,547, the contents of which are incorporated herein by
reference in their entirety, uses an elongated thick plug and the
balloon is filled by inserting a needle attached to an air source
through the plug.
[0011] U.S. Pat. No. 4,607,618, the contents of which are
incorporated herein by reference in their entirety, describes a
collapsible appliance formed of semi-rigid skeleton members joined
to form a collapsible hollow structure. The appliance is not
inflatable. It is endoscopically inserted into the stomach using an
especially adapted bougie having an ejector rod to release the
collapsed appliance. Once released, the appliance returns to its
greater relaxed size and shape.
[0012] U.S. Pat. No. 5,129,915, the contents of which are
incorporated herein by reference in their entirety, relates to an
intragastric balloon that is intended to be swallowed and that
inflates automatically under the effect of temperature. Three ways
that an intragastric balloon might be inflated by a change in
temperature are discussed. A composition comprising a solid acid
and non-toxic carbonate or bicarbonate is separated from water by a
coating of chocolate, cocoa paste or cocoa butter that melts at
body temperature. Alternatively, citric acid and an alkaline
bicarbonate coated with non-toxic vegetable or animal fat melting
at body temperature and which placed in the presence of water, can
produce the same result. Lastly, the solid acid and non-toxic
carbonate or bicarbonate are isolated from water by an isolation
pouch of low-strength synthetic material which it will suffice to
break immediately before swallowing the bladder. Breaking the
isolation pouches causes the acid, carbonate or bicarbonate and
water to mix and the balloon to begin to expand immediately. A
drawback of thermal triggering of inflation is that it does not
afford the degree of control and reproducibility of the timing of
inflation that is desirable and necessary in a safe self-inflating
intragastric balloon.
[0013] After swallowing, food and oral medicaments typically reach
a patient's stomach in under a minute. Food is retained in the
stomach on average from one to three hours. However, the residence
time is highly variable and dependent upon such factors as the
fasting or fed state of the patient. Accordingly, proper timing of
inflation of an intragastric balloon is a factor in successful
deployment of the intragastric devices of various embodiments.
Timing is selected to avoid premature inflation in the esophagus
that could lead to an esophageal obstruction or belated inflation
that could lead to intestinal obstruction.
[0014] Methods for verifying that the intragastric device is in the
stomach are useful in that they do not rely on mere timing after
administration of the intragastric device. Verification of location
can be done with radiography. After a patient swallows an
encapsulated balloon, radiography can be done to ensure the balloon
is in the stomach after swallowing, with the encapsulated balloon
visualized by a radio-opaque marker. Radiographic techniques
include x-ray or fluoroscopy techniques that provide real-time
images of the balloon using radiation. However, radiation may be
harmful to the body if prolonged or administered in high doses.
While fluoroscopy typically uses low doses of radiation, repeated
use may create a risk of harm to a patient. Further, there is the
risk of accidental administration of too high of a dose to a
patient.
[0015] Electromagnetic-based systems and methods provide advantages
over, e.g., radiography. Electromagnetism refers generally to the
magnetic fields corresponding to electric currents. A current may
be induced in a conducting material by the presence of a magnetic
field. A magnetic field may also be induced by the presence of a
current running through a conductive material. Electromagnetism has
been used in many different contexts, and it presents advantages
when used in the intragastric device locating and characterizing
context.
[0016] Voltage-based systems and methods also provide advantages
over e.g., radiography. Voltages are created when the electric
potential of one point is different from that of another point.
Voltage has been used in many different contexts, and it presents
advantages when used in the intragastric device locating and
characterizing context.
[0017] U.S. Pat. No. 8,858,432, the contents of which are
incorporated herein by reference in their entirety, discloses
ingestible markers incorporating a signal generating circuit. The
ingestible event marker systems include 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 target internal physiological site of
a body, such as digestive tract internal target site. The personal
signal receiver is configured to be associated with a physiological
location, e.g., inside of or on the body, and to receive a signal
the IEM. During use, the IEM broadcasts a signal which is received
by the personal signal receiver.
[0018] U.S. Pat. No. 8,836,513, the contents of which are
incorporated herein by reference in their entirety, describes a
system having an ingestible product indicating that it has been
consumed. The system includes a conductive element, an electronic
component, and a partial power source in the form of dissimilar
materials. Upon contact with a conducting fluid, a voltage
potential is created and the power source is completed, which
activates the system. The electronic component controls the
conductance between the dissimilar materials to produce a unique
current signature. The system can be associated with food and
communicate data about ingestion of food material to a
receiver.
[0019] U.S. Pat. No. 8,847,766, the contents of which are
incorporated herein by reference in their entirety, describes a
system for physical delivery of a pharmaceutical agent. The system
includes an identifier that transmits a conductive signal and
consumable electrodes formed of dissimilar materials. The
electrodes are configured to both generate a voltage to energize
the identifier and transmit the conductive signal to the body when
the first and second electrodes contact the bodily fluid.
[0020] Ultrasound-based systems and methods also provide advantages
over, e.g., radiology. Ultrasound is an oscillating sound pressure
wave with a frequency greater than the upper limit of the human
hearing range. Ultrasound is thus not separated from `normal`
(audible) sound based on differences in physical properties, only
the fact that humans cannot hear it. Although this limit varies
from person to person, it is approximately 20 kilohertz (20,000
hertz) in healthy, young adults. Ultrasound devices operate with
frequencies from 20 kHz up to several gigahertz.
[0021] Ultrasonic devices may be used to detect objects and measure
distances. Ultrasonic imaging (sonography) is used in both
veterinary medicine and human medicine. In the nondestructive
testing of products and structures, ultrasound is used to detect
invisible flaws. Industrially, ultrasound is used for cleaning and
for mixing, and to accelerate chemical processes. Animals such as
bats and porpoises use ultrasound for locating prey and
obstacles.
[0022] Ultrasonics is the application of ultrasound. Ultrasound can
be used for medical imaging, detection, measurement and cleaning.
At higher power levels, ultrasonics is useful for changing the
chemical properties of substances.
[0023] Medical sonography (ultrasonography) is an ultrasound-based
diagnostic medical imaging technique used to visualize muscles,
tendons, and many internal organs, to capture their size, structure
and any pathological lesions with real time tomographic images.
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. The technology is relatively inexpensive and
portable, especially when compared with other techniques, such as
magnetic resonance imaging (MRI) and computed tomography (CT).
Ultrasound is also used to visualize fetuses during routine and
emergency prenatal care. Such diagnostic applications used during
pregnancy are referred to as obstetric sonography. As currently
applied in the medical field, properly performed ultrasound poses
no known risks to the patient. Sonography does not use ionizing
radiation, and the power levels used for imaging are too low to
cause adverse heating or pressure effects in tissue.
[0024] Ultrasound is also increasingly being used in trauma and
first aid cases, with emergency ultrasound becoming a staple of
most EMT response teams. Furthermore, ultrasound is used in remote
diagnosis cases where teleconsultation is required, such as
scientific experiments in space or mobile sports team diagnosis.
Ultrasounds are also useful in the detection of pelvic
abnormalities and can involve techniques known as abdominal
(transabdominal) ultrasound, vaginal (transvaginal or endovaginal)
ultrasound in women, and also rectal (transrectal) ultrasound in
men.
[0025] Ultrasound has been used in many different contexts, and it
presents advantages when used in the intragastric device locating
and characterizing context.
[0026] Medical imaging is employed to diagnose a large number of
diseases. The oldest method, dye X-ray technology, delivers
high-resolution images within 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 using
radiation. With said ultrasound imaging, ultrasound signals are
sent via an ultrasound transducer into the object to be examined
and a corresponding control device receives the reflected
ultrasound signals and processes the receive signals for imaging
purposes.
[0027] U.S. Pat. No. 8,535,230, the contents of which are
incorporated herein by reference in their entirety, describes an
ultrasound device including an ultrasound transducer on a robotic
arm to track an object as it moves. However, such a system is
incompatible with tracking a device inside the body.
[0028] U.S. Pat. No. 8,105,247, the contents of which are
incorporated herein by reference in their entirety, describes use
of ultrasonic transceivers to measure the size of a gastric banding
device. However, that system is intended for a stationary gastric
banding device and is not directly applicable to locating and
characterizing a translating, rotating and transforming
intragastric device.
SUMMARY
[0029] There remains a need for a device and method of locating and
characterizing in vivo an intragastric balloon device that avoids
exposure to radiation and
[0030] A free-floating or tethered intragastric volume-occupying
device or devices that maintain volume and/or internal pressure
within a predetermined range over time, or which undergoes a
predetermined adjustment in volume and/or internal pressure over
time, is disclosed. By maintaining a predetermined volume and/or
internal pressure, stresses on the device leading to a breach in
structural integrity can be minimized, which prevents premature
and/or uncontrolled deflation or other device failure. 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 devices can be self-inflating (also referred
to as automatic inflating) or inflatable (also referred to as
manually inflating via a tether).
[0031] Volume-occupying devices and methods for manufacturing,
deploying, inflating, tracking, locating, deflating and retrieving
of such devices are provided. The devices and methods of the
preferred embodiments may be employed for treating over weight and
obese individuals. Methods employing the device of the preferred
embodiments need not utilize invasive procedures, but rather the
device may simply be swallowed by a patient, with or without a
catheter attached. Once in the stomach of the patient, the device
is inflated with a preselected fluid, e.g., a gas, liquid, vapor or
mixtures thereof, to a preselected volume. Therefore, the use of
one fluid, such as a "gas", e.g., an initial fill gas, to describe
the various embodiments herein, does not preclude the use of other
fluids as well. Further, a "fluid," such as an initial fill fluid,
also includes a material or materials in the solid, liquid, vapor,
or gas phase that are incorporated within, mixed within, carried
within or otherwise entrained in a fluid such as a gas or liquid. A
fluid can comprise one substance, or mixtures of different
substances, and may be or include saline, physiologically
acceptable fluids or substances, etc. as further described herein.
The wall of the device is preselected for its particular fluid,
e.g. gas, diffusion properties. Once in the in vivo environment,
the gas(es) within the device diffuse out through the wall of the
device, and gases diffuse into the device from the in vivo
environment. By preselecting the device wall and gas(es) initially
employed to inflate the device, taking into account diffusion
properties of gases into the device from the in vivo environment,
the volume and/or internal pressure of the device can be maintained
within a preselected range, or can follow a preselected profile of
volume and/or pressure changes. After a predetermined time period,
the device can be removed using endoscopic tools or will decrease
in volume or deflate so as to pass through the remainder of the
patient's digestive tract.
[0032] Inflation may be achieved by use of a removable catheter
that initially remains in fluid contact with the device after it
has been swallowed by the patient. Alternatively, inflation may be
achieved by a self-inflation process, e.g., generation of gas in
the device once it reaches the stomach by reaction of
gas-generating components contained within the device upon
swallowing, or by introduction of one or more components in the gas
generating process into the device by use of a removable
catheter.
[0033] The volume-occupying subcomponent of devices may be formed
by injection, blow or rotational molding of a flexible,
gas-impermeable, biocompatible material, such as, for example,
polyurethane, nylon or polyethylene terephthalate. Materials that
may be used to control the gas permeability/impermeability of the
volume-occupying subcomponent include, but are not limited to,
silicon oxide (SiOx), gold or any noble metal, saran, conformal
coatings and the like, when it is desired to reduce permeability.
To enhance gas-impermeable characteristics of the wall of the
device, if desirable, the volume-occupying subcomponent may be
further coated with one or more gas-barrier compounds, or be formed
of a Mylar polyester film coating or kelvalite, silver or aluminum
as a metalized surface to provide a gas impermeable barrier.
[0034] In further embodiments, the device employs a delivery state
in which the device is packaged such that the device may be
swallowed while producing minimal discomfort to the patient. In a
delivery state, the device may be packaged into a capsule.
Alternatively, the device may be coated with a material operable to
confine the device and facilitate swallowing. Various techniques
may also be employed to ease swallowing of the device including,
for example, wetting, temperature treating, lubricating, and
treating with pharmaceuticals such as anesthetics.
[0035] The devices incorporate a tracking or visualization
component or components that enable physicians to determine the
location and/or orientation and/or state of the device within the
patient's body using electromagnetic, magnetic, voltaic, pH, and/or
acoustic (e.g., ultrasonic) methods. The tracking or visualization
component can be the balloon or a component thereof or therein, or
an additional component added to or affixed to the balloon or a
component thereof or therein, or an additional component having a
property indicative of placement of the balloon.
[0036] In some embodiments, tracking subcomponents may incorporate
materials that emit electromagnetic energy. The device may be
tracked and located using a complementary electromagnetic energy
sensor that is responsive to the electromagnetic properties of the
device. Such techniques may also be used to obtain certain device
specific information and specifications while the device remains
inside the patient's body, including but not limited to device
location, orientation, size or state as it travels inside the body.
The electromagnetic-responsive sensor outside the body can detect
and process information related to the electromagnetic energy
relayed by the internal device, which energy may be reflected off,
created by, or otherwise propagated from the intragastric device or
materials or objects in or on the intragastric device. This
information can then be interpreted to identify the device's
location, orientation, size and other attributes while still inside
the body. An electromagnetic system provides a simple, non-invasive
and less harmful method of tracking, locating and characterizing
intragastric devices.
[0037] In some embodiments, tracking subcomponents may incorporate
materials that are responsive to ultrasonic or other acoustic
energy. The device may be tracked and located using a complementary
ultrasonic energy sensor that is responsive to the acoustic
properties of the device. Such techniques may also be used to
obtain certain device specific information and specifications while
the device remains inside the patient's body, including but not
limited to device location, orientation, size or state as it
travels inside the body. The acoustically-responsive sensor outside
the body can detect and process information related to the acoustic
energy relayed by the internal device, which energy may be
reflected off, created by, or otherwise propagated from the
intragastric device or materials or objects in or on the
intragastric device. This information can then be interpreted to
identify the device's location, orientation, size and other
attributes while still inside the body. An ultrasound system
provides a simple, non-invasive and less harmful method of
tracking, locating and characterizing intragastric devices.
[0038] In some embodiments, an electromagnetic system or portions
thereof may be combined with an acoustic system or portions
thereof. The combination of the systems or portions thereof may be
implemented for further enhancing the locating and/or
characterizing of the intragastric device in vivo.
[0039] Such techniques may also be used to obtain certain device
specific information and specifications while the device remains
inside the patient's body, including but not limited to device
location, orientation, size or state as it travels inside the body.
The magnetically-responsive sensor, e.g., a sensor outside of the
body, can detect and relay information related to the magnetic
field of the internal device. This information can then be
interpreted to identify the device's location, orientation, size
and other attributes while still inside the body. A magnetic field
detecting system provides a simple, non-invasive and less harmful
method of tracking, locating and characterizing intragastric
devices.
[0040] In a first aspect, an electromagnetic system is provided for
locating an intragastric device inside the body, the system
comprising: an electromagnetic field generator configured to
generate an electromagnetic field; a swallowable electromagnetic
sensor configured to couple with the system and further configured
to produce an electric current when exposed to the electromagnetic
field in an in vivo gastric environment; and a valve system
configured for introducing an initial fill fluid into a volume
occupying intragastric device when the intragastric device is in
the in vivo gastric environment, the valve system comprising a
swallowable catheter configured to releasably couple with the
intragastric device.
[0041] In an embodiment of the first aspect, the electromagnetic
sensor is configured to couple with the swallowable catheter.
[0042] In an embodiment of the first aspect, the electromagnetic
sensor is configured to couple with a distal end of the swallowable
catheter.
[0043] In an embodiment of the first aspect, the electromagnetic
sensor is configured to couple with the intragastric device.
[0044] In an embodiment of the first aspect, the system further
comprises at least one external reference sensor configured to be
placed outside the body and to produce an electric current when
exposed to the magnetic field.
[0045] In an embodiment of the first aspect, the system further
comprises three external reference sensors configured to be placed
outside the body and to produce an electric current when exposed to
the magnetic field.
[0046] In an embodiment of the first aspect, the system further
comprises a sensor interface unit configured to electrically
communicate with the electromagnetic sensor and the at least one
external reference sensor.
[0047] In an embodiment of the first aspect, the system further
comprises a system control unit configured to electrically
communicate with the sensor interface unit and with the
electromagnetic field generator.
[0048] In an embodiment of the first aspect, the system further
comprises a computer configured to electrically communicate with
the system control unit and to display an identifier indicating the
location of the electromagnetic sensor inside the body.
[0049] In an embodiment of the first aspect, the system further
comprises at least one external reference sensor configured to be
placed outside the body and to produce an electric current when
exposed to the magnetic field, wherein the computer is further
configured to display at least one second identifier indicating the
location of the at least one external reference sensor.
[0050] In an embodiment of the first aspect, the computer is
further configured to display a trace indicating a path travelled
by the electromagnetic sensor inside the body.
[0051] In an embodiment of the first aspect, the system further
comprises the intragastric device, wherein the intragastric device
is a balloon.
[0052] In an embodiment of the first aspect, the system further
comprises the initial fill fluid, wherein the intragastric device
comprises a polymeric wall configured to have, under conditions of
the in vivo gastric environment, a permeability to CO.sub.2 of more
than 10 cc/m.sup.2/day, such that a rate and an amount of diffusion
of CO.sub.2 from the in vivo gastric environment into a lumen of
the intragastric device through the polymeric wall is controlled,
at least in part, by a concentration of an inert gas in the initial
fill fluid.
[0053] In an embodiment of the first aspect, the polymeric wall
comprises a CO.sub.2 barrier material comprising an ethylene vinyl
alcohol layer.
[0054] In an embodiment of the first aspect, the polymeric wall
comprises a two layer CO.sub.2 barrier material comprising a nylon
layer and a polyethylene layer.
[0055] In an embodiment of the first aspect, the polymeric wall
comprises a three layer CO.sub.2 barrier material comprising a
nylon layer, a polyvinylidene chloride layer, and a polyethylene
layer.
[0056] In an embodiment of the first aspect, the polymeric wall
comprises a three layer CO.sub.2 barrier material comprising a
nylon layer, an ethylene vinyl alcohol layer, and a polyethylene
layer.
[0057] In an embodiment of the first aspect, the initial fill fluid
consists essentially of gaseous N.sub.2.
[0058] In an embodiment of the first aspect, the initial fill fluid
consists essentially of gaseous N.sub.2 and gaseous CO.sub.2.
[0059] In an embodiment of the first aspect, the initial fill fluid
consists essentially of gaseous N.sub.2 and gaseous CO.sub.2, and
wherein the gaseous N.sub.2 is excess in concentration to the
gaseous CO.sub.2 in the initial fill fluid.
[0060] In an embodiment of the first aspect, the initial fill fluid
comprises SF.sub.6 in one or more of liquid form, vapor form, or
gaseous form.
[0061] In an embodiment of the first aspect, the initial fill fluid
comprises gaseous N.sub.2 and gaseous SF.sub.6.
[0062] In an embodiment of the first aspect, the polymeric wall is
configured to have, under conditions of an in vivo gastric
environment, a permeability to CO.sub.2 of more than 50
cc/m.sup.2/day.
[0063] In a second aspect, a method is provided for
electromagnetically locating an intragastric device inside the body
of a patient, the method comprising: generating an electromagnetic
field with an electromagnetic field generator situated outside of
the body of the patient; introducing into the body of the patient,
via swallowing, the intragastric device comprising an uninflated
gastric balloon, the intragastric device releasably coupled with a
catheter and coupled with an electromagnetic sensor, the
electromagnetic sensor configured to produce an electrical current
in the presence of the electromagnetic field generated by the
magnetic field generator; sensing a current induced in the
electromagnetic sensor by the electromagnetic field; and confirming
a location of the uninflated gastric balloon inside the patient
based on sensing the current induced in the electromagnetic
sensor.
[0064] In an embodiment of the second aspect, the location of the
uninflated gastric balloon inside the patient is the patient's
stomach.
[0065] In an embodiment of the second aspect, the method further
comprises: introducing an initial fill fluid into a lumen of the
uninflated gastric balloon through the catheter, the intragastric
balloon comprising a polymeric wall configured to have, under
conditions of an in vivo gastric environment, a permeability to
CO.sub.2 of more than 10 cc/m.sup.2/day; and exposing the inflated
intragastric balloon to the in vivo intragastric environment for a
useful life of at least 30 days, wherein a rate and an amount of
diffusion of CO.sub.2 from the in vivo gastric environment into the
lumen of the balloon through the polymeric wall is controlled, at
least in part, by a concentration of an inert gas in the initial
fill fluid.
[0066] In an embodiment of the second aspect, the polymeric wall
comprises a three layer CO.sub.2 barrier material comprising a
nylon layer, a polyvinylidene chloride layer and a polyethylene
layer.
[0067] In an embodiment of the second aspect, the polymeric wall
comprises a three layer CO.sub.2 barrier material comprising a
nylon layer, an ethylene vinyl alcohol layer, and a polyethylene
layer.
[0068] In an embodiment of the second aspect, the polymeric wall
comprises a two layer CO.sub.2 barrier material comprising a nylon
layer and a polyethylene layer.
[0069] In an embodiment of the second aspect, the polymeric wall
comprises a CO.sub.2 barrier material comprising an ethylene vinyl
alcohol layer.
[0070] In an embodiment of the second aspect, the initial fill
fluid consists essentially of gaseous N.sub.2.
[0071] In an embodiment of the second aspect, the first gas
consists essentially of gaseous N.sub.2 and gaseous CO.sub.2.
[0072] In an embodiment of the second aspect, the first gas
consists essentially of gaseous N.sub.2 and gaseous CO.sub.2, and
wherein the gaseous N.sub.2 is excess in concentration to the
gaseous CO.sub.2 in the first gas.
[0073] In an embodiment of the second aspect, the first gas
comprises SF.sub.6 in one or more of liquid form, vapor form, or
gaseous form.
[0074] In an embodiment of the second aspect, the first gas
comprises gaseous N.sub.2 and gaseous SF.sub.6.
[0075] In an embodiment of the second aspect, the polymeric wall is
configured to have, under conditions of an in vivo gastric
environment, a permeability to CO.sub.2 of more than 50
cc/m.sup.2/day.
[0076] In an embodiment of the second aspect, confirming a location
of the uninflated gastric balloon inside the patient based on
sensing the current induced in the electromagnetic sensor comprises
displaying on a computer an identifier indicating the location of
the electromagnetic sensor.
[0077] In an embodiment of the second aspect, the method further
comprises placing at least one external reference sensor outside
the body of the patient, the at least one external reference sensor
configured to produce an electric current when exposed to the
electromagnetic field, and sensing a current induced in the at
least one external reference sensor by the electromagnetic
field.
[0078] In an embodiment of the second aspect, confirming a location
of the uninflated gastric balloon inside the patient based on
sensing the current induced in the electromagnetic sensor comprises
displaying on a computer at least one second identifier indicating
the location of the at least one external reference sensor.
[0079] In an embodiment of the second aspect, the electromagnetic
sensor is coupled with the catheter.
[0080] In an embodiment of the second aspect, the electromagnetic
sensor is coupled with the intragastric device.
[0081] In a third aspect, a magnetic system is provided for
locating an intragastric device inside the body, the system
comprising: a magnetic field sensor configured to sense a magnetic
field; a swallowable magnetic marker configured to couple with the
system and further configured to produce a local magnetic field in
an in vivo gastric environment; and a valve system configured for
introducing an initial fill fluid into a volume occupying
intragastric device when the intragastric device is in the in vivo
gastric environment, the valve system comprising a swallowable
catheter configured to releasably couple with the intragastric
device.
[0082] In an embodiment of the third aspect, the magnetic marker is
configured to couple with the swallowable catheter.
[0083] In an embodiment of the third aspect, the magnetic marker is
configured to couple with a distal end of the swallowable
catheter.
[0084] In an embodiment of the third aspect, the magnetic marker is
configured to couple with the intragastric device.
[0085] In an embodiment of the third aspect, the system further
comprises at least one external reference sensor configured to be
placed outside the body and to sense a local magnetic field.
[0086] In an embodiment of the third aspect, the system further
comprises a sensor interface unit configured to electrically
communicate with the magnetic marker.
[0087] In an embodiment of the third aspect, the system further
comprises a system control unit configured to electrically
communicate with the sensor interface unit and with the magnetic
field sensor.
[0088] In an embodiment of the third aspect, the system further
comprises a computer configured to electrically communicate with
the system control unit and to display an identifier indicating the
location of the magnetic marker inside the body.
[0089] In an embodiment of the third aspect, the computer is
further configured to display a trace indicating a path travelled
by the magnetic marker inside the body.
[0090] In an embodiment of the third aspect, the system further
comprises the intragastric device, wherein the intragastric device
is a balloon.
[0091] In an embodiment of the third aspect, the system further
comprises the initial fill fluid, wherein the intragastric device
comprises a polymeric wall configured to have, under conditions of
the in vivo gastric environment, a permeability to CO.sub.2 of more
than 10 cc/m.sup.2/day, such that a rate and an amount of diffusion
of CO.sub.2 from the in vivo gastric environment into a lumen of
the intragastric device through the polymeric wall is controlled,
at least in part, by a concentration of an inert gas in the initial
fill fluid.
[0092] In an embodiment of the third aspect, the polymeric wall
comprises a CO.sub.2 barrier material comprising an ethylene vinyl
alcohol layer.
[0093] In an embodiment of the third aspect, the polymeric wall
comprises a two layer CO.sub.2 barrier material comprising a nylon
layer and a polyethylene layer.
[0094] In an embodiment of the third aspect, the polymeric wall
comprises a three layer CO.sub.2 barrier material comprising a
nylon layer, a polyvinylidene chloride layer, and a polyethylene
layer.
[0095] In an embodiment of the third aspect, the polymeric wall
comprises a three layer CO.sub.2 barrier material comprising a
nylon layer, an ethylene vinyl alcohol layer, and a polyethylene
layer
[0096] In an embodiment of the third aspect, the initial fill fluid
consists essentially of gaseous N.sub.2.
[0097] In an embodiment of the third aspect, the initial fill fluid
consists essentially of gaseous N.sub.2 and gaseous CO.sub.2.
[0098] In an embodiment of the third aspect, the initial fill fluid
consists essentially of gaseous N.sub.2 and gaseous CO.sub.2, and
wherein the gaseous N.sub.2 is excess in concentration to the
gaseous CO.sub.2 in the initial fill fluid.
[0099] In an embodiment of the third aspect, the initial fill fluid
comprises SF.sub.6 in one or more of liquid form, vapor form, or
gaseous form.
[0100] In an embodiment of the third aspect, the initial fill fluid
comprises gaseous N.sub.2 and gaseous SF.sub.6.
[0101] In an embodiment of the third aspect, the polymeric wall is
configured to have, under conditions of an in vivo gastric
environment, a permeability to CO.sub.2 of more than 50
cc/m.sup.2/day.
[0102] In a fourth aspect, a method is provided for magnetically
locating an intragastric device inside the body of a patient, the
method comprising: introducing into the body of the patient, via
swallowing, the intragastric device comprising an uninflated
gastric balloon, the intragastric device releasably coupled with a
catheter and coupled with a magnetic marker, the magnetic marker
configured to be sensed by the magnetic field sensor; sensing the
magnetic field with the magnetic field sensor; and confirming a
location of the uninflated gastric balloon inside the patient based
on sensing the magnetic field.
[0103] In an embodiment of the fourth aspect, the location of the
uninflated gastric balloon inside the patient is the patient's
stomach.
[0104] In an embodiment of the fourth aspect, the method further
comprises: introducing an initial fill fluid into a lumen of the
uninflated gastric balloon through the catheter, the intragastric
balloon comprising a polymeric wall configured to have, under
conditions of an in vivo gastric environment, a permeability to
CO.sub.2 of more than 10 cc/m.sup.2/day; and exposing the inflated
intragastric balloon to the in vivo intragastric environment for a
useful life of at least 30 days, wherein a rate and an amount of
diffusion of CO.sub.2 from the in vivo gastric environment into the
lumen of the balloon through the polymeric wall is controlled, at
least in part, by a concentration of an inert gas in an initial
fill fluid.
[0105] In an embodiment of the fourth aspect, the polymeric wall
comprises a three layer CO.sub.2 barrier material comprising a
nylon layer, a polyvinylidene chloride layer, and a polyethylene
layer.
[0106] In an embodiment of the fourth aspect, the polymeric wall
comprises a three layer CO.sub.2 barrier material comprising a
nylon layer, an ethylene vinyl alcohol layer, and a polyethylene
layer.
[0107] In an embodiment of the fourth aspect, the polymeric wall
comprises a two layer CO.sub.2 barrier material comprising a nylon
layer and a polyethylene layer.
[0108] In an embodiment of the fourth aspect, the polymeric wall
comprises a CO.sub.2 barrier material comprising an ethylene vinyl
alcohol layer.
[0109] In an embodiment of the fourth aspect, the initial fill
fluid consists essentially of gaseous N.sub.2.
[0110] In an embodiment of the fourth aspect, the first gas
consists essentially of gaseous N.sub.2 and gaseous CO.sub.2.
[0111] In an embodiment of the fourth aspect, the initial fill
fluid consists essentially of gaseous N.sub.2 and gaseous CO.sub.2,
and wherein the gaseous N.sub.2 is excess in concentration to the
gaseous CO.sub.2 in the first gas.
[0112] In an embodiment of the fourth aspect, the initial fill
fluid comprises SF.sub.6 in one or more of liquid form, vapor form,
or gaseous form.
[0113] In an embodiment of the fourth aspect, the initial fill
fluid comprises gaseous N.sub.2 and gaseous SF.sub.6.
[0114] In an embodiment of the fourth aspect, the polymeric wall is
configured to have, under conditions of an in vivo gastric
environment, a permeability to CO.sub.2 of more than 50
cc/m.sup.2/day.
[0115] In an embodiment of the fourth aspect, confirming a location
of the uninflated gastric balloon inside the patient based on
sensing the magnetic field generated by the magnetic marker
comprises displaying on a computer an identifier indicating the
location of the magnetic marker.
[0116] In an embodiment of the fourth aspect, the magnetic marker
is coupled with the catheter.
[0117] In an embodiment of the fourth aspect, the electromagnetic
sensor is coupled with the intragastric device.
[0118] In a fifth aspect, a voltaic system is provided for locating
an intragastric device inside the body, the system comprising: a
swallowable voltaic sensor configured to couple with the system and
further configured to produce a voltage in an in vivo gastric
environment; and a valve system configured for introducing an
initial fill fluid into a volume occupying intragastric device when
the intragastric device is in the in vivo gastric environment, the
valve system comprising a swallowable catheter configured to
releasably couple with the intragastric device.
[0119] In an embodiment of the fifth aspect, the voltaic sensor is
configured to couple with the swallowable catheter.
[0120] In an embodiment of the fifth aspect, the voltaic sensor is
configured to couple with a distal end of the swallowable
catheter.
[0121] In an embodiment of the fifth aspect, the voltaic sensor is
configured to couple with the intragastric device.
[0122] In an embodiment of the fifth aspect, the system further
comprises at least one receiver configured to be placed outside the
body and to receive a signal related to the voltage produced by the
voltaic sensor.
[0123] In an embodiment of the fifth aspect, the system further
comprises a sensor interface unit configured to electrically
communicate with the voltaic sensor.
[0124] In an embodiment of the fifth aspect, the system further
comprises a system control unit configured to electrically
communicate with the sensor interface unit and with the voltaic
sensor.
[0125] In an embodiment of the fifth aspect, the system further
comprises a computer configured to electrically communicate with
the system control unit and to display an identifier indicating the
location of the voltaic sensor inside the body.
[0126] In an embodiment of the fifth aspect, the system further
comprises the intragastric device, wherein the intragastric device
is a balloon.
[0127] In an embodiment of the fifth aspect, the system further
comprises the initial fill fluid, wherein the intragastric device
comprises a polymeric wall configured to have, under conditions of
the in vivo gastric environment, a permeability to CO.sub.2 of more
than 10 cc/m.sup.2/day, such that a rate and an amount of diffusion
of CO.sub.2 from the in vivo gastric environment into a lumen of
the intragastric device through the polymeric wall is controlled,
at least in part, by a concentration of an inert gas in the initial
fill fluid.
[0128] In an embodiment of the fifth aspect, the polymeric wall
comprises a CO.sub.2 barrier material comprising an ethylene vinyl
alcohol layer.
[0129] In an embodiment of the fifth aspect, the polymeric wall
comprises a two layer CO.sub.2 barrier material comprising a nylon
layer and a polyethylene layer.
[0130] In an embodiment of the fifth aspect, the polymeric wall
comprises a three layer CO.sub.2 barrier material comprising a
nylon layer, an ethylene vinyl alcohol layer, and a polyethylene
layer.
[0131] In an embodiment of the fifth aspect, the polymeric wall
comprises a three layer CO.sub.2 barrier material comprising a
nylon layer, a polyvinylidene chloride layer, and a polyethylene
layer.
[0132] In an embodiment of the fifth aspect, the initial fill fluid
consists essentially of gaseous N.sub.2.
[0133] In an embodiment of the fifth aspect, the initial fill fluid
consists essentially of gaseous N.sub.2 and gaseous CO.sub.2.
[0134] In an embodiment of the fifth aspect, the initial fill fluid
consists essentially of gaseous N.sub.2 and gaseous CO.sub.2, and
wherein the gaseous N.sub.2 is excess in concentration to the
gaseous CO.sub.2 in the initial fill fluid.
[0135] In an embodiment of the fifth aspect, the initial fill fluid
comprises SF.sub.6 in one or more of liquid form, vapor form, or
gaseous form.
[0136] In an embodiment of the fifth aspect, the initial fill fluid
comprises gaseous N.sub.2 and gaseous SF.sub.6.
[0137] In an embodiment of the fifth aspect, the polymeric wall is
configured to have, under conditions of an in vivo gastric
environment, a permeability to CO.sub.2 of more than 50
cc/m.sup.2/day.
[0138] In a sixth aspect, a method is provided for voltaically
locating an intragastric device inside the body of a patient, the
method comprising: introducing into the body of the patient, via
swallowing, the intragastric device comprising an uninflated
gastric balloon, the intragastric device releasably coupled with a
catheter and coupled with a voltaic sensor, the voltaic sensor
configured to produce a voltage in the presence of a gastric
environment; producing a voltage with the voltaic sensor in
response to contact with the gastric environment; and confirming a
location of the uninflated gastric balloon inside the patient based
on sensing the produced voltage.
[0139] In an embodiment of the sixth aspect, the location of the
uninflated gastric balloon inside the patient is the patient's
stomach.
[0140] In an embodiment of the sixth aspect, the method further
comprises: introducing an initial fill fluid into a lumen of the
uninflated gastric balloon through the catheter, the intragastric
balloon comprising a polymeric wall configured to have, under
conditions of an in vivo gastric environment, a permeability to
CO.sub.2 of more than 10 cc/m.sup.2/day; and exposing the inflated
intragastric balloon to the in vivo intragastric environment for a
useful life of at least 30 days, wherein a rate and an amount of
diffusion of CO.sub.2 from the in vivo gastric environment into the
lumen of the balloon through the polymeric wall is controlled, at
least in part, by a concentration of an inert gas in the initial
fill fluid.
[0141] In an embodiment of the sixth aspect, the polymeric wall
comprises a three layer CO.sub.2 barrier material comprising a
nylon layer, a polyvinylidene chloride layer and a polyethylene
layer.
[0142] In an embodiment of the sixth aspect, the polymeric wall
comprises a three layer CO.sub.2 barrier material comprising a
nylon layer, an ethylene vinyl alcohol layer, and a polyethylene
layer.
[0143] In an embodiment of the sixth aspect, the polymeric wall
comprises a two layer CO.sub.2 barrier material comprising a nylon
layer and a polyethylene layer.
[0144] In an embodiment of the sixth aspect, the polymeric wall
comprises a CO.sub.2 barrier material comprising an ethylene vinyl
alcohol layer.
[0145] In an embodiment of the sixth aspect, the initial fill fluid
consists essentially of gaseous N.sub.2 and gaseous CO.sub.2.
[0146] In an embodiment of the sixth aspect, the initial fill fluid
consists essentially of gaseous N.sub.2.
[0147] In an embodiment of the sixth aspect, the first gas consists
essentially of gaseous N.sub.2 and gaseous CO.sub.2, and wherein
the gaseous N.sub.2 is excess in concentration to the gaseous
CO.sub.2 in the initial fill fluid.
[0148] In an embodiment of the sixth aspect, the initial fill fluid
comprises SF.sub.6 in one or more of liquid form, vapor form, or
gaseous form.
[0149] In an embodiment of the sixth aspect, the initial fill fluid
comprises gaseous N.sub.2 and gaseous SF.sub.6.
[0150] In an embodiment of the sixth aspect, the polymeric wall is
configured to have, under conditions of an in vivo gastric
environment, a permeability to CO.sub.2 of more than 50
cc/m.sup.2/day.
[0151] In an embodiment of the sixth aspect, the voltaic sensor is
coupled with the catheter.
[0152] In an embodiment of the sixth aspect, the voltaic sensor is
coupled with the intragastric device.
[0153] In a seventh aspect, a pH based system is provided for
locating an intragastric device inside the body, the system
comprising: a swallowable pH sensor configured to couple with the
system and further configured to sense the pH level of fluid in an
in vivo gastric environment; and a valve system configured for
introducing an initial fill fluid into a volume occupying
intragastric device when the intragastric device is in the in vivo
gastric environment, the valve system comprising a swallowable
catheter configured to releasably couple with the intragastric
device.
[0154] In an embodiment of the seventh aspect, the pH sensor is
configured to couple with the swallowable catheter.
[0155] In an embodiment of the seventh aspect, the pH sensor is
configured to couple with a distal end of the swallowable
catheter.
[0156] In an embodiment of the seventh aspect, the pH sensor is
configured to couple with the intragastric device.
[0157] In an embodiment of the seventh aspect, the system further
comprises at least one receiver configured to be placed outside the
body and to receive a signal related to the pH level sensed by the
pH sensor.
[0158] In an embodiment of the seventh aspect, the system further
comprises a sensor interface unit configured to electrically
communicate with the pH sensor.
[0159] In an embodiment of the seventh aspect, the system further
comprises a system control unit configured to electrically
communicate with the sensor interface unit and with the pH
sensor.
[0160] In an embodiment of the seventh aspect, the system further
comprises a computer configured to electrically communicate with
the system control unit and to display an identifier indicating the
location of the pH sensor inside the body.
[0161] In an embodiment of the seventh aspect, the system further
comprises the intragastric device, wherein the intragastric device
is a balloon.
[0162] In an embodiment of the seventh aspect, the system further
comprises the initial fill fluid, wherein the intragastric device
comprises a polymeric wall configured to have, under conditions of
the in vivo gastric environment, a permeability to CO.sub.2 of more
than 10 cc/m.sup.2/day, such that a rate and an amount of diffusion
of CO.sub.2 from the in vivo gastric environment into a lumen of
the intragastric device through the polymeric wall is controlled,
at least in part, by a concentration of an inert gas in the initial
fill fluid.
[0163] In an embodiment of the seventh aspect, the polymeric wall
comprises a CO.sub.2 barrier material comprising an ethylene vinyl
alcohol layer.
[0164] In an embodiment of the seventh aspect, the polymeric wall
comprises a two layer CO.sub.2 barrier material comprising a nylon
layer and a polyethylene layer.
[0165] In an embodiment of the seventh aspect, the polymeric wall
comprises a three layer CO.sub.2 barrier material comprising a
nylon layer, a polyvinylidene chloride layer, and a polyethylene
layer.
[0166] In an embodiment of the seventh aspect, the polymeric wall
comprises a three layer CO.sub.2 barrier material comprising a
nylon layer, an ethylene vinyl alcohol layer, and a polyethylene
layer.
[0167] In an embodiment of the seventh aspect, the initial fill
fluid consists essentially of gaseous N.sub.2.
[0168] In an embodiment of the seventh aspect, the initial fill
fluid consists essentially of gaseous N.sub.2 and gaseous
CO.sub.2.
[0169] In an embodiment of the seventh aspect, the initial fill
fluid consists essentially of gaseous N.sub.2 and gaseous CO.sub.2,
and wherein the gaseous N.sub.2 is excess in concentration to the
gaseous CO.sub.2 in the initial fill fluid.
[0170] In an embodiment of the seventh aspect, the initial fill
fluid comprises SF.sub.6 in one or more of liquid form, vapor form,
or gaseous form.
[0171] In an embodiment of the seventh aspect, the initial fill
fluid comprises gaseous N.sub.2 and gaseous SF.sub.6.
[0172] In an embodiment of the seventh aspect, the polymeric wall
is configured to have, under conditions of an in vivo gastric
environment, a permeability to CO.sub.2 of more than 50
cc/m.sup.2/day.
[0173] In an eighth aspect, a method is provided for locating an
intragastric device inside the body of a patient based on sensing a
pH level of fluid inside the body, the method comprising:
introducing into the body of the patient, via swallowing, the
intragastric device comprising an uninflated gastric balloon, the
intragastric device releasably coupled with a catheter and coupled
with a pH sensor, the pH sensor configured to sense the pH level of
the fluid in a gastric environment inside the body; sensing the pH
level of the fluid in response to contact of the pH sensor with the
gastric environment; and confirming a location of the uninflated
gastric balloon inside the patient based on sensing the pH
level.
[0174] In an embodiment of the eighth aspect, the location of the
uninflated gastric balloon inside the patient is the patient's
stomach.
[0175] In an embodiment of the eighth aspect, the method further
comprises: introducing an initial fill fluid into a lumen of the
uninflated gastric balloon through the catheter, the intragastric
balloon comprising a polymeric wall configured to have, under
conditions of an in vivo gastric environment, a permeability to
CO.sub.2 of more than 10 cc/m.sup.2/day; and exposing the inflated
intragastric balloon to the in vivo intragastric environment for a
useful life of at least 30 days, wherein a rate and an amount of
diffusion of CO.sub.2 from the in vivo gastric environment into the
lumen of the balloon through the polymeric wall is controlled, at
least in part, by a concentration of an inert gas in an initial
fill fluid.
[0176] In an embodiment of the eighth aspect, the polymeric wall
comprises a three layer CO.sub.2 barrier material comprising a
nylon layer, a polyvinylidene chloride layer and a polyethylene
layer.
[0177] In an embodiment of the eighth aspect, the polymeric wall
comprises a three layer CO.sub.2 barrier material comprising a
nylon layer, an ethylene vinyl alcohol layer, and a polyethylene
layer.
[0178] In an embodiment of the eighth aspect, the polymeric wall
comprises a two layer CO.sub.2 barrier material comprising a nylon
layer and a polyethylene layer.
[0179] In an embodiment of the eighth aspect, the polymeric wall
comprises a CO.sub.2 barrier material comprising an ethylene vinyl
alcohol layer.
[0180] In an embodiment of the eighth aspect, the initial fill
fluid consists essentially of gaseous N.sub.2.
[0181] In an embodiment of the eighth aspect, the initial fill
fluid consists essentially of gaseous N.sub.2 and gaseous
CO.sub.2.
[0182] In an embodiment of the eighth aspect, the initial fill
fluid consists essentially of gaseous N.sub.2 and gaseous CO.sub.2,
and wherein the gaseous N.sub.2 is excess in concentration to the
gaseous CO.sub.2 in the first gas.
[0183] In an embodiment of the eighth aspect, the initial fill
fluid comprises SF.sub.6 in one or more of liquid form, vapor form,
or gaseous form.
[0184] In an embodiment of the eighth aspect, the initial fill
fluid comprises gaseous N.sub.2 and gaseous SF.sub.6.
[0185] In an embodiment of the eighth aspect, the polymeric wall is
configured to have, under conditions of an in vivo gastric
environment, a permeability to CO.sub.2 of more than 50
cc/m.sup.2/day.
[0186] In an embodiment of the eighth aspect, the pH sensor is
coupled with the catheter.
[0187] In an embodiment of the eighth aspect, the pH sensor is
coupled with the intragastric device.
[0188] In a ninth aspect, an acoustic system is provided for
locating an intragastric device inside the body, the system
comprising: an acoustic signal generator configured to generate an
acoustic signal; a swallowable acoustic marker configured to couple
with the system and further configured to produce an acoustic
response in an in vivo gastric environment in response to the
generated acoustic signal; and a valve system configured for
introducing an initial fill fluid into a volume occupying
intragastric device when the intragastric device is in the in vivo
gastric environment, the valve system comprising a swallowable
catheter configured to releasably couple with the intragastric
device.
[0189] In an embodiment of the ninth aspect, the acoustic marker is
configured to couple with the swallowable catheter.
[0190] In an embodiment of the ninth aspect, the acoustic marker is
configured to couple with a distal end of the swallowable
catheter.
[0191] In an embodiment of the ninth aspect, the acoustic marker is
configured to couple with the intragastric device.
[0192] In an embodiment of the ninth aspect, the system further
comprises at least one external acoustic sensor configured to be
placed outside the body and to sense the acoustic response of the
acoustic marker.
[0193] In an embodiment of the ninth aspect, the system further
comprises a sensor interface unit configured to electrically
communicate with the acoustic marker and with the acoustic
sensor.
[0194] In an embodiment of the ninth aspect, the system further
comprises a system control unit configured to electrically
communicate with the sensor interface unit
[0195] In an embodiment of the ninth aspect, the system further
comprises a computer configured to electrically communicate with
the system control unit and the acoustic sensor and to display an
identifier indicating the location of the acoustic marker inside
the body.
[0196] In an embodiment of the ninth aspect, the computer is
further configured to display a trace indicating a path travelled
by the magnetic marker inside the body.
[0197] In an embodiment of the ninth aspect, the system further
comprises the intragastric device, wherein the intragastric device
is a balloon.
[0198] In an embodiment of the ninth aspect, the system further
comprises the initial fill fluid, wherein the intragastric device
comprises a polymeric wall configured to have, under conditions of
the in vivo gastric environment, a permeability to CO.sub.2 of more
than 10 cc/m.sup.2/day, such that a rate and an amount of diffusion
of CO.sub.2 from the in vivo gastric environment into a lumen of
the intragastric device through the polymeric wall is controlled,
at least in part, by a concentration of an inert gas in the initial
fill fluid.
[0199] In an embodiment of the ninth aspect, the polymeric wall
comprises a CO.sub.2 barrier material comprising an ethylene vinyl
alcohol layer.
[0200] In an embodiment of the ninth aspect, the polymeric wall
comprises a two layer CO.sub.2 barrier material comprising a nylon
layer and a polyethylene layer.
[0201] In an embodiment of the ninth aspect, the polymeric wall
comprises a three layer CO.sub.2 barrier material comprising a
nylon layer, a polyvinylidene chloride layer, and a polyethylene
layer.
[0202] In an embodiment of the ninth aspect, the polymeric wall
comprises a three layer CO.sub.2 barrier material comprising a
nylon layer, an ethylene vinyl alcohol layer, and a polyethylene
layer.
[0203] In an embodiment of the ninth aspect, the initial fill fluid
consists essentially of N.sub.2.
[0204] In an embodiment of the ninth aspect, the initial fill fluid
consists essentially of gaseous N.sub.2 and gaseous CO.sub.2.
[0205] In an embodiment of the ninth aspect, the initial fill fluid
consists essentially of gaseous N.sub.2 and gaseous CO.sub.2, and
wherein the gaseous N.sub.2 is excess in concentration to the
gaseous CO.sub.2 in the initial fill fluid.
[0206] In an embodiment of the ninth aspect, the initial fill fluid
comprises SF.sub.6 in one or more of liquid form, vapor form, or
gaseous form.
[0207] In an embodiment of the ninth aspect, the initial fill fluid
comprises N.sub.2 and SF.sub.6.
[0208] In an embodiment of the ninth aspect, the polymeric wall is
configured to have, under conditions of an in vivo gastric
environment, a permeability to CO.sub.2 of more than 50
cc/m.sup.2/day.
[0209] In an embodiment of the ninth aspect, the acoustic signal is
an ultrasound signal.
[0210] In a tenth aspect, a method is provided for acoustically
locating an intragastric device inside the body of a patient, the
method comprising: introducing into the body of the patient, via
swallowing, the intragastric device comprising an uninflated
gastric balloon, the intragastric device releasably coupled with a
catheter and coupled with an acoustic marker, the acoustic marker
configured to produce an acoustic response in response to an
acoustic signal; generating an acoustic signal; and confirming a
location of the uninflated gastric balloon inside the patient based
on the acoustic response produced in response to the acoustic
signal.
[0211] In an embodiment of the tenth aspect, the location of the
uninflated gastric balloon inside the patient is the patient's
stomach.
[0212] In an embodiment of the tenth aspect, the method further
comprises: introducing an initial fill fluid into a lumen of the
uninflated gastric balloon through the catheter, the intragastric
balloon comprising a polymeric wall configured to have, under
conditions of an in vivo gastric environment, a permeability to
CO.sub.2 of more than 10 cc/m.sup.2/day; and exposing the inflated
intragastric balloon to the in vivo intragastric environment for a
useful life of at least 30 days, wherein a rate and an amount of
diffusion of CO.sub.2 from the in vivo gastric environment into the
lumen of the balloon through the polymeric wall is controlled, at
least in part, by a concentration of an inert gas in an initial
fill fluid.
[0213] In an embodiment of the tenth aspect, the polymeric wall
comprises a three layer CO.sub.2 barrier material comprising a
nylon layer, a polyvinylidene chloride layer and a polyethylene
layer.
[0214] In an embodiment of the tenth aspect, the polymeric wall
comprises a three layer CO.sub.2 barrier material comprising a
nylon layer, an ethylene vinyl alcohol layer, and a polyethylene
layer.
[0215] In an embodiment of the tenth aspect, the polymeric wall
comprises a two layer CO.sub.2 barrier material comprising a nylon
layer and a polyethylene layer.
[0216] In an embodiment of the tenth aspect, the polymeric wall
comprises a CO.sub.2 barrier material comprising an ethylene vinyl
alcohol layer.
[0217] In an embodiment of the tenth aspect, the initial fill fluid
consists essentially of gaseous N.sub.2.
[0218] In an embodiment of the tenth aspect, the first gas consists
essentially of N.sub.2 and CO.sub.2.
[0219] In an embodiment of the tenth aspect, the initial fill fluid
consists essentially of gaseous N.sub.2 and gaseous CO.sub.2, and
wherein the gaseous N.sub.2 is excess in concentration to the
gaseous CO.sub.2 in the first gas.
[0220] In an embodiment of the tenth aspect, the initial fill fluid
comprises SF.sub.6 in one or more of liquid form, vapor form, or
gaseous form.
[0221] In an embodiment of the tenth aspect, the initial fill fluid
comprises gaseous N.sub.2 and gaseous SF.sub.6.
[0222] In an embodiment of the tenth aspect, the polymeric wall is
configured to have, under conditions of an in vivo gastric
environment, a permeability to CO.sub.2 of more than 50
cc/m.sup.2/day.
[0223] In an embodiment of the tenth aspect, confirming a location
of the uninflated gastric balloon inside the patient based on
sensing the acoustic response comprises displaying on a computer an
identifier indicating the location of the acoustic marker.
[0224] In an embodiment of the tenth aspect, the acoustic marker is
coupled with the catheter.
[0225] In an embodiment of the tenth aspect, the acoustic marker is
coupled with the intragastric device.
[0226] In an embodiment of the tenth aspect, the acoustic sensor is
an ultrasound sensor and the acoustic marker is an ultrasound
marker.
[0227] In an eleventh aspect, a system is provided substantially as
described in the specification and/or drawings.
[0228] In a twelfth aspect, a method is provided substantially as
described in the specification and/or drawings.
[0229] Any of the aforementioned embodiments can be combined with
other embodiments or with other aspects and associated embodiments.
For example, any of the methods of the second aspect can be
employed in association with the system of the first aspect, any of
the methods of the fourth aspect can be employed in association
with the system of the third aspect, any of the methods of the
sixth aspect can be employed in association with the system of the
fifth aspect, any of the methods of the eighth aspect can be
employed in association with the system of the seventh aspect, or
any of the methods of the tenth aspect can be employed in
association with the system of the ninth aspect, etc. Similarly,
any embodiment of any of the aspects can be employed in combination
with one or more other embodiments of any of the aspects. Further,
any or all of the embodiments may use a gas or liquid phase
material as the "fluid." Thus, recitation of "gas" in any
embodiment is not meant to limit it to just a gaseous material, but
may also include liquid phase materials as well, as is described in
further detail herein.
BRIEF DESCRIPTION OF THE DRAWINGS
[0230] FIG. 1 depicts an embodiment of an electromagnetic tracking
system for locating a sensor.
[0231] FIG. 2 depicts an embodiment of an electromagnetic tracking
system that uses a sensor for locating an intragastric device.
[0232] FIG. 3A depicts an embodiment of an electromagnetic tracking
system for using a sensor to locate an intragastric device inside
the body of a human patient.
[0233] FIG. 3B is a rear view of the patient of FIG. 3A showing an
embodiment of external reference sensors for an anatomical frame of
reference.
[0234] FIG. 4 depicts an embodiment of an electromagnetic tracking
system on a support that uses a sensor to locate an intragastric
device inside the body of a human patient.
[0235] FIG. 5 depicts an embodiment of a display that can be used
with the systems of FIGS. 2-4.
[0236] FIG. 6 depicts an embodiment a field generator and
corresponding magnetic field envelope that may be used with the
systems of FIGS. 2-4.
[0237] FIG. 7 depicts an embodiment of a control panel on a system
control unit that may be implemented with the systems of FIGS.
2-4.
[0238] FIG. 8 depicts an embodiment of a sensor control unit that
may be implemented with the systems of FIGS. 2-4.
[0239] FIG. 9 depicts an embodiment of a catheter with integrated
sensor that may be used with the systems of FIGS. 2-4.
[0240] FIG. 10A depicts another embodiment of a catheter and sensor
that may be used with the systems of FIGS. 2-4.
[0241] FIG. 10B depicts an embodiment of an electromagnetic sensor
that may be implemented with the catheter of FIG. 10A.
[0242] FIG. 10C depicts an embodiment of a voltage sensor that may
be implemented with the catheter of FIG. 10A.
[0243] FIG. 11 depicts an embodiment of an external reference
sensor that may be used as anatomical reference markers with the
systems of FIGS. 2-4.
[0244] FIG. 12 depicts an embodiment of a jumper cable that may be
used with the systems of FIGS. 2-4.
[0245] FIG. 13 is a top plan view of an embodiment of a detector
illustrating one possible arrangement of magnetic sensors.
[0246] FIG. 14 illustrates the generation of magnetic field
strength vectors using the magnetic sensor configuration of FIG. 3
to determine the location of a magnet.
[0247] FIG. 15A is a functional block diagram of an exemplary
embodiment of a system configured to determine the location of a
magnet.
[0248] FIG. 15B is a functional block diagram illustrating the
operation of the system of FIG. 15A to display the location of a
magnet in conjunction with a conventional imaging system.
[0249] FIG. 15C illustrates an embodiment of the system of FIG. 15A
to monitor the location of the detector system.
[0250] FIG. 16 illustrates a large number of magnetic sensors
disposed within a predefined area to form a sensor array.
[0251] FIG. 17A illustrates the use of the system of FIG. 15C to
select landmark locations on a patient.
[0252] FIG. 17B illustrates the display of the selected locations
and the location of a magnet.
[0253] FIG. 18A is a flowchart used by the system of FIG. 15A to
determine the location of a magnet.
[0254] FIG. 18B is a flowchart illustrating the automatic
calibration function of the system of FIG. 15A.
[0255] FIG. 19A illustrates one embodiment of the visual display
used by the detector of FIG. 13.
[0256] FIG. 19B is an alternative embodiment of the indicator used
with the detector of FIG. 13.
[0257] FIG. 19C is yet another alternative embodiment of the
display used with the detector of FIG. 13.
[0258] FIG. 19D is yet another alternative embodiment of the
display of the detector of FIG. 13 with a depth indicator
indicating the distance of the magnet from the detector.
[0259] FIG. 20 illustrates the location of multiple magnets fixed
to the ends of medical tubes positioned within the body of a human
patient.
[0260] FIG. 21 illustrates the generation of magnet field strength
vectors using an arbitrary magnetic sensor configuration to
determine the location of multiple magnets.
[0261] FIG. 22 illustrates the orientation of two magnets on a
single tube to detect the rotational angle of the tube.
[0262] FIG. 23 depicts a balloon of one embodiment incorporating an
electromagnetic, magnetic or magnetizable pellet in an enclosed
volume of the intragastric balloon. The pellet can be loose or
attached to a wall of the intragastric balloon.
[0263] FIG. 24 depicts a balloon of one embodiment incorporating
electromagnetic, magnetic or magnetizable buttons attached to
opposite sides of the intragastric balloon.
[0264] FIG. 25A depicts a cross section of a valve system including
a septum plug, head unit, ring stop, tube septum, and an
electromagnetic or magnetized retaining ring.
[0265] FIG. 25B is a top view of the valve system, depicted in
cross-section along line 1D-1D in FIG. 25A.
[0266] FIG. 25C is a top view of the valve system of FIGS. 25A and
25B incorporated into the wall of an intragastric balloon.
[0267] FIG. 26 depicts a gel cap 1400 containing an intragastric
balloon of FIGS. 25A-C in uninflated form. The gel cap containing
the uninflated balloon is engaged via the valve system of the
intragastric balloon to a dual catheter system comprising a 2FR
tube and a 4FR tube via a press-fit connecting structure
incorporating an electromagnetic, magnetic, or magnetized
component.
[0268] FIGS. 27-28 depict an embodiment of a system for locating or
otherwise characterizing an intragastric device using
ultrasound.
[0269] FIG. 29 depicts an embodiment of an intragastric device for
use in the system of FIGS. 27-28, where the device has an internal
coil, having an inflatable section a solid substrate, and placement
tabs.
[0270] FIG. 30A depicts an embodiment of an ultrasound sensing
mechanism using induction showing an inner coil and an outer coil
placed concentrically and coaxially relative to one another.
[0271] FIG. 30B depicts another embodiment of an ultrasound sensing
mechanism using induction showing an inner coil and an outer coil
placed in a coaxial non-concentric arrangement relative to one
another.
[0272] FIG. 31A depicts an embodiment of a coil holder that may use
the concentric, coaxial induction sensing mechanism of FIG.
30A.
[0273] FIG. 31B depicts an embodiment of a coil holder that may use
the non-concentric, coaxial induction sensing mechanism of FIG.
30B.
[0274] FIG. 32 depicts an embodiment of an ultrasound method for
characterizing an intragastric device or marker thereon.
[0275] FIG. 33A is a top view of an embodiment of a system for
equipment verification using a gastric magnetic susceptibility
phantom.
[0276] FIG. 33B is a side view of the system of FIG. 33A.
[0277] FIG. 34 is a side view of another embodiment of a system for
equipment verification using a gastric magnetic susceptibility
phantom showing movement of an adjustable outer coil.
[0278] FIG. 35 is graph showing display of frequency data measured
with the systems of FIGS. 33-34.
[0279] FIG. 36 is a flowchart showing an embodiment of a method for
determining the size of a gastric lumen using the systems of FIGS.
33-34.
[0280] FIG. 37 depicts an embodiment of a system for characterizing
an intragastric device, the system having two ultrasonic modules
placed in the device that allow the system to measure the size and
composition of the marker and/or device using time of flight
ultrasound technology.
[0281] FIG. 38 is graph showing display of data measured with the
system of FIG. 37.
[0282] FIG. 39 depicts an embodiment of a pulse timing diagram
depicting the time of flight using ultrasonic modules.
[0283] FIG. 40 shows embodiments of graphical representations of
data collected with ultrasonic systems and induction systems of the
present disclosure.
[0284] FIG. 41 depicts a diagrammatic representation of an
embodiment of an identifier that may be used in a voltaic based
intragastric locating system.
[0285] FIG. 42 provides detail of certain implementations of an
electronic circuit of various embodiments of a voltaic sensor that
may be used with a voltaic based intragastric locating system.
[0286] FIG. 43 illustrates an embodiment of a voltaic device
configuration of an ingestible event marker (IEM) integrated
circuit (IC) in accordance with one embodiment.
[0287] FIG. 44 is a schematic diagram illustrating an embodiment of
a design for an IEM IC.
[0288] FIG. 45 illustrates an embodiment of a transmission sequence
for a bit pattern of "0010" in accordance with one embodiment of
the voltaic sensor.
[0289] FIG. 46 illustrates an embodiment of a waveform for a 20 kHz
transmission of a sequence "10101" in accordance with one
embodiment of a voltaic sensor.
[0290] FIG. 47 illustrates an embodiment of a waveform of a 10 kHz
transmission of a sequence "10101" in accordance with one
embodiment of a voltaic sensor.
[0291] FIG. 48 is a state diagram illustrating the operation of an
embodiment of an IEM IC in accordance with one embodiment of a
voltaic sensor.
[0292] FIG. 49 illustrates an embodiment of an IEM chip
configuration where two separate electrodes are used for battery
and signal transmission, respectively, in a voltaic sensor.
[0293] FIG. 50 illustrates an exemplary chip configuration that
minimizes circuit latch-ups in accordance with one embodiment of a
voltaic sensor.
[0294] FIG. 51 illustrates an embodiment of a layout for an IEM
chip that minimizes latch-ups in an IEM.
[0295] FIG. 52 is an exploded view of an embodiment of an IEM that
may be used with a voltaic sensor.
[0296] FIG. 53 is a diagram showing an embodiment of a signal
receiver that may be incorporated with a voltaic sensor.
[0297] FIG. 54 is a diagram of an embodiment of a signal receiver
that may be incorporated with a voltaic sensor.
[0298] FIGS. 55A and 55B provide additional information about
various aspects of embodiments of external receivers according to
embodiments of the voltaic sensor.
[0299] FIG. 56 is a side view of an embodiment of an intragastric
balloon capsule attached to a delivery/inflation catheter where the
balloon has a voltaic sensor therein.
[0300] FIG. 57 is a side view of an embodiment of an intragastric
balloon system having an anode and a cathode with pH coating.
[0301] FIG. 58 depicts an embodiment of a series battery that may
be incorporated with the voltaic sensor locating system.
[0302] FIG. 59 depicts another embodiment of a series battery that
may be incorporated with the voltaic sensor locating system.
[0303] FIG. 60 shows an embodiment of a planar or interdigitated
battery for an on-chip battery with two cathodes and one anode that
may be incorporated with the voltaic sensor locating system.
[0304] FIG. 61 shows an embodiment of a large plate configuration
for an on-chip battery that may be incorporated with the voltaic
sensor locating system.
[0305] FIG. 62 shows an embodiment of a 3-d configuration of an
on-chip battery with three anodes bridged over the cathode that may
be incorporated with the voltaic sensor locating system.
[0306] FIG. 63 is a perspective view of a 3-d configuration of an
on-chip battery that may be incorporated with the voltaic sensor
locating system.
[0307] FIG. 64 depicts another embodiment of an on-chip battery
that may be incorporated with the voltaic sensor locating
system.
[0308] FIG. 65 depicts another embodiment of an on-chip battery
that may be incorporated with the voltaic sensor locating
system.
[0309] FIG. 66 depicts another embodiment of an on-chip battery
that uses wafer bonding that may be incorporated with the voltaic
sensor locating system.
[0310] FIG. 67 illustrates use with a patient of an embodiment of a
voltaic locating system having an event marker.
[0311] FIG. 68 illustrates use with a patient of an embodiment of a
voltaic locating system having an anode and cathode.
[0312] FIG. 69A depicts an embodiment of the present disclosure
with an integrated controller and display, as well as a separate
controller unit option, demonstrated during use with a patient.
[0313] FIG. 69B depicts an embodiment of the present disclosure
with a wireless external controller used near the patient.
[0314] FIG. 69C depicts a side view of an embodiment of pH sensors
of the present disclosure located on an intragastric device within
a cross-section of a stomach.
[0315] FIG. 70A is a schematic side view of a person with a pH
monitor which may be incorporated with an intragastric device
within the esophagus.
[0316] FIG. 70B is a schematic view of one embodiment of an
electrical circuit for the pH monitor of FIG. 70A.
[0317] FIG. 70C is a schematic view of an embodiment of a pH
monitor circuit, wherein the circuit also includes a
microprocessor.
[0318] FIG. 71A is a side view of a proximal end section of an
embodiment of an intragastric tube showing a chemical-property
indicating element thereof for pH level detection.
[0319] FIG. 71B is a cross section view of the alternate embodiment
of the intragastric tube of FIG. 71A, taken along the section lines
44-44 of FIG. 71A;
[0320] FIG. 71C is a side view of the proximal end section of a
further embodiment of an intragastric tube showing a
chemical-property indicating medium thereof for pH level detection
in a first example configuration.
[0321] FIG. 71D is a side view of the proximal end section of a
further embodiment of an intragastric tube showing a
chemical-property indicating medium thereof for pH level detection
in a second example configuration.
[0322] FIG. 71E is a cross section view of the alternate embodiment
of the intragastric tube of FIG. 71C, taken along the section lines
47-47 of FIG. 71C;
[0323] FIG. 71F is a cross section view of the alternate embodiment
of the intragastric tube of FIG. 71D, taken along the section lines
48-48 of FIG. 71D;
[0324] FIG. 71G is a side view of a further embodiment of an
intragastric tube, showing a chemical-property indicating medium
thereof for pH level detection in a third example
configuration.
[0325] FIG. 71H is a side view of a further alternate embodiment of
an intragastric tube, showing a chemical-property indicating medium
thereof for pH level detection in a fourth example
configuration.
[0326] FIG. 72 shows an embodiment of an intragastric device having
a pH sensor connected in tandem with a space filler.
[0327] FIG. 73A is a schematic illustration of a capsule device
that may be incorporated with an intragastric device to detect pH
level.
[0328] FIG. 73B is a schematic illustration of a system that may be
incorporated with an intragastric device for measuring pH having
two capsules connected to each other.
[0329] FIG. 74 illustrates an embodiment of a capsule system with
one or more pH sensors, for incorporation with an intragastric
device, having two hard capsule-like units and a soft flexible tube
connecting the capsule units.
[0330] FIG. 75 is a flowchart of an embodiment of a method for
using a pH sensor with an intragastric device to determine the
location, orientation, and/or state of the intragastric device. The
method may be used with other systems, including electromagnetic,
magnetic, voltaic, and ultrasound systems.
[0331] FIG. 76 is a perspective view of a suitcase embodiment of
the intragastric locating systems of the present disclosure.
[0332] FIG. 77 is a perspective view of a backpack embodiment of
the intragastric locating systems of the present disclosure.
[0333] FIG. 78 provides experimental data for pressure in various
intragastric balloons over time for various concentrations of
SF.sub.6 and/or N.sub.2 as a fill gas. Line A refers to a first
balloon having a wall comprising a layer of polyethylene and a
layer of nylon (PE/Nylon) and filled with 100% SF.sub.6. Line B
refers to a second balloon having a wall comprising a layer of
polyethylene and a layer of nylon (PE/Nylon) and filled with 100%
SF.sub.6. Line C refers to a balloon having a wall comprising a
layer of polyethylene and a layer of nylon (PE/Nylon) and filled
with 75% SF.sub.6/25% N.sub.2. Line D refers to a balloon having a
wall comprising a layer of polyethylene and a layer of nylon
(PE/Nylon) and filled with 50% SF.sub.6/50% N.sub.2. Line E refers
to a balloon having a wall comprising a layer of polyethylene and a
layer of nylon (PE/Nylon) and filled with 25% SF.sub.6/75% N.sub.2.
Line F refers to a balloon having a wall comprising a layer of
polyethylene and a layer of nylon (PE/Nylon) and filled with 18-20%
SF.sub.6/78-80% N.sub.2. Line G refers to a balloon having a wall
comprising a layer of ethylene vinyl alcohol (EVOH) and filled with
100% N.sub.2. Line H refers to a balloon having a wall comprising a
layer of 3.5 mil polyethylene and a layer of nylon (PE/Nylon) and
filled with 100% N.sub.2.
DETAILED DESCRIPTION
[0334] The following description and examples illustrate a
preferred embodiment of the present invention in detail. Those of
skill in the art will recognize that there are numerous variations
and modifications of this invention that are encompassed by its
scope. Accordingly, the description of a preferred embodiment
should not be deemed to limit the scope of the present
invention.
[0335] The term "degradable" as used herein is a broad term, and is
to be given its ordinary and customary meaning to a person of
ordinary skill in the art (and is not to be limited to a special or
customized meaning), and refers without limitation to a process by
which structural integrity of the balloon is compromised (e.g., by
chemical, mechanical, or other means (e.g., light, radiation, heat,
etc.) such that deflation occurs. The degradation process can
include erosion, dissolution, separation, digestion,
disintegration, delamination, commination, and other such
processes. Degradation after a predetermined time, or within a
predetermined window of time, after ingestion is particularly
preferred.
[0336] The term "CO.sub.2 barrier material" as used herein is a
broad term, and is to be given its ordinary and customary meaning
to a person of ordinary skill in the art (and is not to be limited
to a special or customized meaning), and refers without limitation
to a material having a permeability to CO.sub.2 of 10
cc/m.sup.2/day or less under simulated in vivo conditions (100%
humidity and body temperature of 37.degree. C.). As used herein,
the term "in vivo conditions" as used herein 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.sub.2 may vary depending upon the conditions under which it is
measured.
[0337] The term "swallowable" as used herein is a broad term, and
is to be given its ordinary and customary meaning to a person of
ordinary skill in the art (and is not to be limited to a special or
customized meaning), and refers without limitation to ingestion of
a balloon by a patient such that the outer capsule and its
constituents are delivered to the stomach via normal peristalsis
movement. While the systems of preferred embodiments are
swallowable, they are also configured by ingestion by methods other
than swallowing. The swallowability of the system is derived, at
least in part, by the outer container size for the self-inflating
system and the catheter and outer container size for the manual
inflation system. For the self-inflating system, the outer capsule
is sufficient to contain the inner container and its constituents,
an amount of activation agent injected prior to administration, the
balloon size, and the balloon material thickness. The system is
preferably of a size less than the average normal esophagus
diameter.
[0338] Described herein is a system for an orally ingestible device
with magnetic, electromagnetic and/or ultrasonic locating,
tracking, and/or otherwise sensing of the device or state of the
device. In preferred embodiments, the device is able to traverse
the alimentary canal. The device may be useful, for example, as an
intragastric volume-occupying device. The device overcomes one or
more of the above-described problems and shortcomings found in
current intragastric volume-occupying devices. While in certain
embodiments specific devices are described, it is understood that
the materials and methods can also be applied to other devices.
[0339] In order to more clearly describe the subject matter of the
preferred embodiments, different embodiments of the same
subcomponent will be described under a single relevantly-titled
subheading. This organization is not intended to limit the manner
in which embodiments of different subcomponents may be combined in
accordance with the present invention. The various subcomponents
for use in the presently disclosed magnetic, electromagnetic and
ultrasonic systems may be discussed under their respective
subheaded sections or in any other section, including any section
or sections discussing various tracking and visualization
subcomponents.
Swallowable Intragastric Balloon System
[0340] A swallowable, self-inflating or inflatable intragastric
balloon system according to selected preferred embodiments includes
the following components: self-sealing valve system for addition of
fluid to the lumen of the balloon or to the inner container ("valve
system"), a balloon in a deflated and compacted state ("balloon")
and an outer capsule, container, or coating ("outer container")
that contains the balloon. For self-inflating balloons, an inner
capsule or other container ("inner container") that contains one or
more CO.sub.2 generating components is present inside the lumen of
the balloon. The system may also include various components for
facilitating delivery ("delivery components") of the balloon to the
mouth and/or through the esophagus.
[0341] For inflatable balloons, an inflation fluid source, a
catheter, and tubing ("inflation assembly") are provided for
inflating the balloon after ingestion or placement in the stomach.
In the self-inflating balloon configuration, the valve is
preferably attached to the inner surface of the balloon by an
adhesive or other means (e.g., welding), and provided with an
inoculation spacer to prevent puncture of the wall of the balloon
and inner container by a needle or other means for injecting an
liquid activation agent into the lumen of the balloon via the
self-sealing valve. A valve providing releasable attachment of the
tubing to the balloon is provided in the inflatable balloon
configuration. Preferably, the self-sealing valve system attached
to the balloon (e.g., on its inside surface) in the inflatable
configuration is "universal" or compatible with a swallowable
catheter or a physician-assisted catheter. The valve system serves
to allow for balloon inflation using a miniature catheter that
includes a needle assembly and also provides a mechanism for
detachment of the catheter after inflation has been completed.
[0342] The outer container preferably incorporates the balloon in a
compacted state (e.g., folded and rolled), preferably with
sufficient space to allow for activation liquid to be injected into
the balloon in the self-inflating balloon configuration, wherein
the liquid activation agent initiates separation, erosion,
degradation, and/or dissolution of the inner container and
generation of CO.sub.2 upon contact with the inflation agent
contained within the inner container, which subsequently causes
outer container separation, erosion, degradation, and/or
dissolution due to CO.sub.2 gas pressure. In the inflatable balloon
configuration, the outer container need only incorporate the
balloon in a compacted state.
[0343] Selected components of a swallowable intragastric balloon
system of a preferred embodiment can include a silicone head with
radioopacity ring, trimmed 30 D silicone septum, Nylon 6
inoculation spacer, compacted balloon, inner container (if
self-inflating), and outer container as constituents of the system
in unassembled form. A fully assembled outer container can include
a vent hole aligned with a septum for puncture to inject liquid
activation agent (if self-inflating) or a port for connection of
tubing (if inflatable). As discussed further below, the components
of particularly preferred systems possess the attributes described
herein; however, in certain embodiments systems can be employed
which utilize components having other attributes and/or values.
[0344] Devices according to the preferred embodiments are intended
for ingestion by a patient and deployment without the need to
resort to invasive methods. It is therefore desirable that the
device of the preferred embodiments be operable to conform to a
compact delivery state which can be swallowed by a patient with
minimal discomfort. Once in the stomach, it is desirable for the
device to assume a substantially larger deployed state. In order to
achieve the transition from a delivery state to a deployed state
the device is subjected to inflation.
Inner Container
[0345] In order to initiate inflation in the self-inflating
configuration, the inflation subcomponent may require outside
inputs such as an activation agent. The activation agent is
preferably injected using a syringe having a needle with a gauge
diameter of from 25 to 32. The needle length is preferably from
about 0.25 inches (0.6 cm) to 1 inches (2.54 cm) in length so as to
create a flow rate that allows for delivery of the full volume of
inflation agent within 30 seconds, but in a manner/stream/flow that
does not physically damage the inner container, thereby causing
premature CO.sub.2 generation and inflation. The activation agent
is preferably pure water, or a solution containing up to 50%
concentration of anhydrous citric acid at 20.degree. C., or the
equivalent thereof at varying solution temperatures based on
solubility of anhydrous citric acid. Preferably, the system is
configured to have an occupyable void space in the central lumen of
the balloon when in compacted form in the outer container of from
about 0.3 ml to about 4.5 ml, such that a corresponding volume of
activation agent can be injected into the void space.
[0346] In one embodiment, prior to folding, the free-floating inner
container with inflation agent for CO.sub.2 generation is
preferably vertically aligned with the self-sealing valve system
such that the septum/inoculation spacer is placed directly above
the tip of the capsule. The balloon contains an inner container. A
self-sealing valve system is adhesively adhered to the interior of
the wall of the balloon, and the inverted configuration of the
balloon is provided by inversion through a hole sealed with a
patch. The top approximate 1/4 of the balloon wall is folded over
the inner capsule, and the pleats where the capsule is are creased
similar to the pleats formed in the second step of making a paper
airplane, then folded over to the left or to the right. The bottom
approximate 3/4 of the sphere is then accordioned using no more
than 2 creases and folded over the capsule. The left half is then
folded over the right half of the capsule or vice versa so that the
wings touch. Then the material is rolled over until it creates a
tight roll. The device is then placed inside the outer
container.
[0347] In a self-inflating configuration, the balloon is folded so
as to form a pocket around the inner capsule, to insure that the
liquid injected through the self-sealing valve system is contained
in an area less than 10% of the entire balloon surface area. It is
not necessary to provide a pocket in the inflatable configuration,
as no inner capsule is provided. The balloon is folded such that
the number of total folds is minimized so as to minimize possible
damage to the outer material or compromise of barrier properties.
The number of total folds is preferably less than 10 folds. The
balloon material is rolled when at all possible such that the
number of creases required to fit the balloon in an outer container
is minimized. This is done in effort to also to prevent lumen
material damage. The self-sealing valve is also preferably
constructed off-center of the balloon so as to minimize the number
of folds that layer on top of each other.
[0348] In the self-inflating configuration, the material forming
the wall of the balloon is processed and folded to maximize
reaction efficiency by localizing the initiation agent injected
into the balloon so that it is maintained proximal to the reactants
within the inner container. The balloon is folded such that once
the reaction initiates and the outer container separates, the
balloon unfolds in a manner that creates the largest possible
surface area, which prohibits the balloon from readily passing
through the pyloric sphincter. The ratio of reactants in the
inflation agent and activation agent are selected such that the pH
of any remnant liquid inside the lumen of the balloon is acidic,
with a pH of less than 6, such that any balloon leakage or breach
that allows stomach acid to enter does not cause additional
CO.sub.2 generation and resulting unintentional re-inflation.
[0349] In a self-inflating configuration, an inflation agent is
compressed, formed or otherwise held in a shape which provides good
surface area availability for the reactants for CO.sub.2
generation, while minimizing the space and/or volume sufficient to
hold the inner container. Preferably, the inner container has a
length (longest dimension) of from about 0.748 inches (1.9 cm) to
1.06 inches (2.7 cm) and a diameter or width of from about 0.239
inches (0.6 cm) to about 0.376 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-fit gelatin capsule but a gelatin tape may be used in lieu of
a push-fit capsule. The container is preferably relied upon for
containing the inflation agent; however, additional sealing or
other encapsulation can be employed to control timing of inflation.
Gelatin is particularly preferred for use as the inner container;
however other materials can also be suitable for use, e.g.,
cellulose. In order to minimize the internal volume of the system,
it is generally preferred to include only a single inner container;
however, in certain embodiments two or more internal containers can
advantageously be employed. Timing of self-inflation is selected
based on a normal esophageal transit time and a normal time of
gastric emptying of large food particles, such that the balloon
does not inflate to a size that can block the esophageal passageway
or prematurely pass through the pyloric sphincter. Timing is also
controlled by compacting the balloon such that the activation agent
is substantially localized in the balloon next to the inner
capsule, creating an efficient CO.sub.2 self-inflation method.
Balloon inflation is initiated by the liquid activation agent
causing degradation of the inner container, such that the inflation
agent in the inner container contacts the liquid activation agent,
thereby initiating the gas generation reaction.
[0350] The inner container for the self-inflating balloon is
contained within the lumen of the balloon and contains the CO.sub.2
generator for balloon self-inflation. The CO.sub.2 generator
comprises an inflation agent mixture housed within the container.
Preferably, from about 10% to about 80% of the total inflation
agent used comprises powdered citric acid, with the remainder
comprising powdered sodium bicarbonate. Sufficient inflation agent
is provided such that upon completion of the CO.sub.2 generating
reaction, the balloon achieves inflation at the nominal inflation
pressure described above. Preferably, a total of from about 0.28 to
4 grams inflation agent mixture is employed, depending upon the
balloon size to be inflated; preferably up to 1.15 grams of sodium
bicarbonate is used with the remainder being powdered citric acid
to generate 300 cm.sup.3 of CO.sub.2 at nominal pressure.
Outer Container
[0351] The balloon is preferably provided in a deflated and folded
state in a capsule or other retaining, containing or coating
structure ("outer container"). The outer container is preferably in
the form of a standard push-fit gelatin capsule, with the push-fit
relied upon for containing the deflated/folded balloon; however, a
gelatin wrap can advantageously be employed in certain embodiments.
Gelatin is particularly preferred for use as the outer container;
however other materials can also be suitable for use, e.g.,
cellulose, collagen, and the like. Preferably, the outer container
has a length (longest dimension) of from about 0.95 inches (2.4 cm)
to 2.5 inches (6.3 cm) and a diameter or width of from about 0.35
inches (0.9 cm) to about 0.9 inches (2.4 cm). The volume of the
inner container is preferably from about 1.2 ml to about 8.25 ml.
In the self-inflating configuration, the outer container is
preferably configured with one or more holes, slits, passageways or
other egresses, preferably on each end, which act as vents such
that any gas created due to inflation agent exposure to
condensation or other ambient moisture present during processing
does not cause premature separation or degradation of the inner
container prior to 30 seconds after inoculation of the liquid
activation agent, which may have an undesirable effect on reaction
efficiency. Such egresses can also expedite dissolution of the
outer container to prepare the balloon for inflation in the
inflatable configuration. The process of the outer capsule
degrading (e.g., separates, dissolves, or otherwise opens) is
expedited by pressure build up caused by inflation (self-inflation
or inflation via catheter) of the balloon. The outer capsule can be
dipped in water for a brief time to soften the materials but not
release the balloon prior to swallowing to minimize the time lapse
between swallowing and balloon inflation. In the inflatable
configuration, the outer container is provided with a hole to house
the inflation tube needle assembly, wherein the diameter of the
catheter needle housing is mechanically compatible with the
diameter of the outer container hole such that the needle can be
inserted into the self-sealing valve while maintaining therein the
housed balloon to facilitate pushing or swallowing of the balloon
assembly. In a preferred embodiment, the outer container is a
capsule. The distal half of the capsule may be flared to prevent
abrasion of the balloon materials by the leading edge of the
capsule as the compacted balloon is inserted into the capsule. The
capsule can also comprise two parts held together with a gel band
and encompassing the folded balloon that allows for quicker
separation of the capsule so that inflation can take place more
expeditiously. The outer capsule degrades (e.g., separates,
dissolves, or otherwise opens) due to contact with ingested fluid
ingestion (e.g., water intake) and preferably degrades within 5
minutes or less, more preferably within 2 minutes or less, so as
not to cause discomfort to the patient while the balloon/catheter
tube is in place.
[0352] In a preferred embodiment, the device is fitted into a
standard sized gelatin capsule. The capsule may be formed of a
material that has a known rate of degradation such that the device
will not be released from the capsule or otherwise deployed prior
to entry into the stomach. For example, the capsule materials may
include one or more polysaccharide and/or one or more polyhydric
alcohols.
[0353] Alternatively, the device, in its delivery state, may be
coated in a substance that confines the device in its delivery
state while also facilitating swallowing. The coating may be
applied by a dipping, sputtering, vapor deposition, or spraying
process which may be conducted at an ambient or positive
pressure.
[0354] In certain preferred embodiments, the encapsulated or coated
device is lubricated or otherwise treated so as to facilitate
swallowing. For example, the encapsulated or coated device may be
wetted, heated, or cooled, prior to swallowing by the patient.
Alternatively, the encapsulated or coated device may be dipped in a
viscous substance that will serve to lubricate the device's passage
through the esophagus. Examples of possible coatings can be any
substances with lubricious and/or hydrophilic properties and
include glycerine, polyvinylpyrrolidone (PVP), petroleum jelly,
aloe vera, silicon-based materials (e.g. Dow 360) and
tetrafluoroethylene (TFE). The coating may also be applied by a
sputtering, vapor deposition or spraying process.
[0355] In additional embodiments the coating or capsule is
impregnated or treated with one or more local anesthetics or
analgesics to ease swallowing. Such anesthetics may include
anesthetics in the amino amide group, such as articaine, lidocaine
and trimecaine, and anesthetics in the amino ester group, such as
benzocaine, procaine and tetracaine. Such analgesics may include
chloraseptic.
[0356] In certain embodiments, the capsule may be weighted at a
certain end in order for it to be oriented appropriately when it is
administered, as it travels down the esophagus, and/or when it is
in the stomach. The weighting components may include polymer
materials or inflation reactants.
[0357] The swallowable, self-inflating intragastric balloon is
provided with mechanisms to reliably control timing of
self-inflation such that premature inflation while in the esophagus
during swallowing is avoided and sufficient inflation once in the
stomach so as to prevent passage through the pyloric sphincter is
ensured. Normal esophageal transit time for large food particles
has been documented as 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 is preferably configured to
separate, dissolve, degrade, erode, and/or otherwise allow the
deflated/folded balloon to begin unfolding not less than 60 seconds
but not more than 15 minutes after inoculation with liquid
activation agent. The inner container is preferably configured
chemically, mechanically or a combination thereof to retard the
initial CO.sub.2 generating chemical reaction such that sufficient
CO.sub.2 to begin inflating the balloon is not available earlier
than 30 seconds after inoculation with the liquid activation agent,
but to permit generation of sufficient CO.sub.2 such that at least
10% of the occupyable volume of the balloon is filled within 30
minutes, at least 60% of the occupyable volume of the balloon is
filled within 12 hours, and at least 90% of the occupyable volume
of the balloon is filled within 24 hours. This timing allows for
injection of the activation agent into the outer container by the
medical professional, passing the device to the patient, and
swallowing by normal peristaltic means by the patient. This timing
also prohibits potential passing of an uninflated balloon into the
duodenum by the balloon being inflated to a sufficient size such
that gastric emptying of the balloon cannot be easy, as objects
more than 7 mm in diameter do not readily pass.
Delivery Components
[0358] It certain embodiments, it may advantageous for an
administrator of the device to use a delivery tool for delivering
the device to the mouth or facilitating its passage through the
esophagus in the optimal orientation. A delivery tool may enable
the device administrator to inject the device with one or more
inflation agents or inflation gases as part of administering the
device to the patient. In a preferred embodiment, such injection
may be accomplished in the same mechanical action(s) of the
administrator that are employed to release the device from the
delivery tool into the mouth or esophagus. For example, the
delivery tool may include a plunger, a reservoir containing a
fluid, and an injection needle. The administrator pushes the
plunger which, either in sequence or approximately simultaneously,
forces the injection needle into the device and thereby injects the
liquid contained in reservoir into the device. Subsequent
application of force to the plunger pushes the device out of the
delivery tool and into the desired location within the patient.
Furthermore, the delivery tool may also include a subcomponent that
administers an anesthetic or lubricant into the patient's mouth or
esophagus to ease the swallowability of the device.
Balloon
[0359] The volume-occupying subcomponent ("balloon") of the
preferred embodiments is generally formed of a flexible material
forming a wall which defines an exterior surface and an interior
cavity. Various of the above-described subcomponents may be either
incorporated into the wall or interior cavity of the
volume-occupying subcomponent. The volume-occupying subcomponent
can vary in size and shape according to the patient's internal
dimensions and the desired outcome. The volume-occupying
subcomponent may be engineered to be semi-compliant, allowing the
volume-occupying subcomponent to stretch or expand with increases
in pressure and/or temperature. Alternatively, in some embodiments,
a compliant wall offering little resistance to increases in volume
may be desirable.
[0360] Spherical volume-occupying subcomponents are preferred in
certain embodiments. Alternatively, the volume-occupying
subcomponent may be constructed to be donut-shaped, with a hole in
the middle of it, and may be weighted and shaped in such a way that
it orients in the stomach to cover all or part of the pyloric
sphincter, similar to a check valve. The hole in the middle of the
volume-occupying subcomponent can then serve as the primary passage
for the contents of the stomach to enter the small intestine,
limiting the passage of food out of the stomach and inducing
satiety by reducing gastric emptying. Volume-occupying
subcomponents may be manufactured with different-sized donut-holes
according to the degree that gastric emptying is desired to be
reduced. Delivery, inflation and deflation of the volume-occupying
subcomponent may be accomplished by any of the methods described
above.
[0361] It is advantageous for the volume-occupying subcomponent
wall to be both high in strength and thin, so as to minimize the
compacted volume of the device as it travels the esophagus of the
patient. In certain embodiments, the volume-occupying subcomponent
wall materials are manufactured with a biaxial orientation that
imparts a high modulus value to the volume-occupying
subcomponent.
[0362] In one embodiment, the volume-occupying subcomponent is
constructed of a polymeric substance such as polyurethane,
polyethylene terephthalate, polyethylene naphthalate, polyvinyl
chloride (PVC), Nylon 6, Nylon 12, or polyether block amide (PEBA).
The volume-occupying subcomponent may be coated with one or more
layers of substances that modify (increase, reduce, or change over
time) gas-barrier characteristics, such as a thermoplastic
substance.
[0363] Preferably, the gas-barrier materials have a low
permeability to carbon dioxide or other fluids that may be used to
inflate the volume-occupying subcomponent. The barrier layers
should have good adherence to the base material. Preferred barrier
coating materials include biocompatible poly(hydroxyamino ethers),
polyethylene naphthalate, polyvinylidene chloride (PVDC), saran,
ethylene vinyl alcohol copolymers, polyvinyl acetate, silicon oxide
(SiOx), acrylonitrile copolymers or copolymers of terephthalic acid
and isophthalic acid with ethylene glycol and at least one diol.
Alternative gas-barrier materials may include
polyamine-polyepoxides. These materials are commonly acquired as a
solvent or aqueous based thermosetting composition and are
generally spray-coated onto a preform and then heat-cured to form
the finished barrier coating. Alternative gas-barrier materials
which may be applied as coatings to the volume-occupying
subcomponent include metals such as silver or aluminum. Other
materials that may be used to improve the gas impermeability of the
volume-occupying subcomponent include, but are not limited to, gold
or any noble metal, PET coated with saran, conformal coatings and
the like, as listed, for example, in Tables 1a-b.
[0364] In certain preferred embodiments, the volume-occupying
subcomponent is injection, blow or rotational molded. Either
immediately following such molding, or after a period of curing,
the gas-barrier coating may be applied if not already applied
within the composite wall.
[0365] In another embodiment, the intragastric volume-occupying
subcomponent is formed using a Mylar polyester film coating silver,
aluminum or kelvalite as a metalized surface, to improve the gas
impermeability of the volume-occupying subcomponent.
[0366] In the event that the volume-occupying subcomponent's wall
is composed of multiple layers of materials, it may be necessary to
use certain substances or methods to connect, attach or hold
together such multiple layers. Such substances can include a
solvent or an ether-based adhesive. Such multiple layers may also
be heat-bonded together. Once such layers are attached together to
form (for example) a sheet of material to be made into a
volume-occupying subcomponent, it may also be necessary to apply
additional treatment steps to such material to allow it to seal
together (for example, by application of a certain degree of heat
and pressure) in order to be made into a volume-occupying
subcomponent. Accordingly, it may be advantageous to include as an
additional layer in the volume-occupying subcomponent certain
materials that seal. For example, a volume-occupying subcomponent
comprised of a combination of PET and SiOx layers, which impart
favorable mechanical and gas impermeability characteristics to the
volume-occupying subcomponent, may be sealed by including a layer
of sealable polyethylene in such volume-occupying subcomponent.
[0367] According to another embodiment of the preferred
embodiments, the functionality of the volume-occupying subcomponent
and the deflation component is combined either in part or in whole.
For example, the volume-occupying subcomponent may be formed of a
substance that is degraded within the stomach over a desired period
of time. Once the degradation process has formed a breach in the
wall of the volume-occupying subcomponent, the volume-occupying
subcomponent deflates, continues to degrade and passes through the
remainder of the digestive tract.
[0368] Preferably, an automated process is employed that takes a
fully constructed volume-occupying subcomponent, evacuates all of
the air within the interior cavity and folds or compresses the
volume-occupying subcomponent into the desired delivery state. For
example, the evacuation of air from the volume-occupying
subcomponent may be actuated by vacuum or mechanical pressure (e.g.
rolling the volume-occupying subcomponent). In certain embodiments,
it is desirable to minimize the number of creases produced in the
volume-occupying subcomponent when in the delivery state.
[0369] Deflation and/or inflation of the volume-occupying
subcomponent may be achieved through one or more injection sites
within the wall of the volume-occupying subcomponent. For example,
two self-sealing injection sites can be incorporated at opposite
sides of the volume-occupying subcomponent. The volume-occupying
subcomponent may be positioned within a fixture that employs two
small-gauge needles to evacuate the air from the volume-occupying
subcomponent.
[0370] In one embodiment, the self-sealing injection sites may
further be used to insert chemical elements of the inflation
subcomponent into the interior of the volume-occupying
subcomponent. After injection of the chemical elements into the
volume-occupying subcomponent, the same needles may be used to
perform evacuation of the volume-occupying subcomponent.
[0371] It may be desirable that the volume-occupying subcomponent
is packed into the delivery state under, for example, a negative
vacuum pressure or under a positive external pressure.
[0372] The volume-occupying subcomponent wall materials may also be
engineered to, once they are initially punctured or torn, tear
relatively easily from the point of such puncture or tear. Such
properties can, for example, be advantageous if deflation of the
volume-occupying subcomponent were initiated by a tearing or
puncturing of the volume-occupying subcomponent wall, since such
initial tear or puncture may then increase in scope, hastening
and/or maximizing the deflation process.
[0373] The volume-occupying subcomponent may also be coated by a
lubricious substance that facilitates its passage out of the body
following its deflation. Examples of possible coatings can be any
substances with lubricious and/or hydrophilic properties and
include glycerine, polyvinylpyrrolidone (PVP), petroleum jelly,
aloe vera, silicon-based materials (e.g. Dow 360) and
tetrafluoroethylene (TFE). The coating may be applied by a dipping,
sputtering, vapor deposition or spraying process which may be
conducted at an ambient or positive pressure.
[0374] The balloon composite wall materials can be of similar
construction and composition as those described in U.S. Patent
Publication No. 2010-0100116-A1, the contents of which is hereby
incorporated by reference in its entirety. The materials are able
to contain a fluid, preferably in compressed or non-compressed gas
form, such as, e.g., N.sub.2, Ar, O.sub.2, CO.sub.2, or mixture(s)
thereof, or atmospheric air (composed of a mixture of N.sub.2,
O.sub.2, Ar, CO.sub.2, Ne, CH.sub.4, He, Kr, H.sub.2, and Xe) that
simulate gastric space concentrations. In certain embodiments, the
balloon is able to hold the fluid (gas) and maintain an acceptable
volume for up to 6 months, preferably for at least 1 to 3 months
after inflation. Particularly preferred fill gases include
non-polar, large molecule gases that can be compressed for
delivery.
[0375] Prior to placement in the outer container, the balloon is
deflated and folded. In the inverted configuration in a deflated
state, the balloon is flat, with the inverted seam extending around
the perimeter of the balloon. The self-sealing valve system is
affixed to the inner wall of the lumen close to the center of the
deflated balloon, with the inner container positioned adjacent to
the self-sealing valve system. The walls of the balloon are then
folded. As part of the balloon design, the self-sealing valve
system is manufactured in a manner such that it is placed "off
center" to minimize the number of folds upon themselves (e.g.,
doubling or tripling up) required to fit the balloon in the outer
container. For example, the self-sealing valve system can
advantageously be placed 1/2 r.+-.1/4 r from the center of the
balloon, wherein r is the radius of the balloon along a line
extending from the center of the balloon through the septum.
[0376] In a preferred embodiment, a self-inflating balloon is fully
sealed 360 degrees around. In the self-inflating configuration,
with injection of an inflation agent by needle syringe, there are
preferably no external openings or orifices to the central lumen.
In the inflatable configuration, a valve structure (either
protruding, recessed, or flush with the surface of the balloon) is
provided for providing an inflation fluid to the central lumen. The
balloon can have a "noninverted," "inverted," or "overlapped"
configuration. In a "noninverted" configuration, the seams or welds
and seam allowance, if any, are on the outside of the inflated
balloon. In an "overlapped" configuration, layers are overlapped,
optionally with one or more folds, and secured to each other via
welds, a seam, adhesive, or the like, resulting in a smooth
external surface. In an "inverted" configuration, the balloon has a
smooth external surface with seams, welds, adhesive bead, or the
like inside the inflated balloon. In order to create a balloon with
an inverted configuration, e.g., a balloon with no external seam
allowance (no wall material between the edge of the balloon and the
weld, seam, or other feature joining the sides together), two
balloon halves are joined together in some fashion (e.g., adhered
using adhesive or heat or the like based on the balloon material
used). One of the balloon halves encompasses an opening to allow
for the balloon to be pulled through itself after adherence of the
two halves and to have the seams of the balloon on the inside. The
opening created is preferably circular but can be any similar
shape, and the diameter of the opening preferably does not exceed
3.8 cm; however, in certain embodiments a larger diameter may be
acceptable. A patch of material is adhered (adhesively, heat
welded, or the like, based on the material used) to cover the
original balloon-half opening. The inversion hole thus created that
is subsequently patched is small enough that the forces exerted
during inflation do not compromise the material used to maintain
fluid in the balloon.
[0377] The preferred shape for the inflated balloon in final
assembly is ellipsoid, preferably spheroid or oblate spheroid, with
nominal radii of from 1 inch (2.5 cm) to 3 inches (7.6 cm), a
nominal height of from 0.25 inches (0.6 cm) to 3 inches (7.6 cm), a
volume of from 90 cm.sup.3 to 350 cm.sup.3 (at 37.degree. C. and at
internal nominal pressure and/or full inflation), an internal
nominal pressure (at 37.degree. C.) of 0 psi (0 Pa) to 15 psi
(103421 Pa), and a weight of less than 15 g. The self-inflating
balloon is configured for self-inflation with CO.sub.2 and is
configured to retain more than 75% of the original nominal volume
for at least 25 days, preferably for at least 90 days when residing
in the stomach. The inflatable balloon is configured for inflation
with an appropriate mixture of gases so as to deliver a preselected
volume profile over a preselected time period (including one or
more of volume increase periods, volume decrease periods, or steady
state volume periods).
[0378] In certain embodiments wherein a stable volume over the
useful life of the device is preferred, the balloon is configured
to maintain a volume of at least 90% to 110% of its original
nominal volume. In other embodiments, it can be desirable for the
balloon to increase and/or decrease in volume over its useful life
(e.g., in a linear fashion, in a stepwise fashion, or in another
non-linear fashion). In other embodiments, the balloon maintains a
volume of 75% to 125% of its original nominal volume, or 75% to
150%
[0379] The intragastric device can be a single free-floating or
tethered device. In some embodiments, it can be desirable to
provide multiple devices (2, 3, 4, 5, 6, or more), either
free-floating or tethered to each other, e.g., in a similar
configuration to a cluster of grapes. The individual devices can be
simultaneously inflated with one inflation system connected to all
of the devices, or each device can be provided with a separate
inflation system.
Valve System
[0380] In preferred embodiments, a self-sealing valve system which
contains a self-sealing septum housed within a metallic concentric
cylinder is provided. In the inflatable configuration, the
self-sealing valve system is preferably adhered to the underside of
the balloon material such that only a portion of the valve
protrudes slightly outside of the balloon surface to ensure a
smooth surface. The valve system for the inflatable configuration
can utilize the same self-sealing septum designed for the
self-inflating configuration. The septum preferably consists of a
material possessing a durometer of 20 Shore A to 60 Shore D. The
septum is inserted or otherwise fabricated into the smaller
cylinder of the concentric metallic retaining structure that is
preferably cylindrical in shape. The smaller cylinder within the
larger cylinder controls alignment of the catheter needle
sleeve/needle assembly with the septum, provides a hard barrier so
that the catheter needle does not pierce the balloon material
(needle stop mechanism), and provides compression such that the
valve/septum re-seals after inflation and subsequent needle
withdrawal.
[0381] The concentric valve system can also provide radio opacity
during implantation and is preferably titanium, gold, stainless
steel, MP35N (nonmagnetic, nickel-cobalt-chromium-molybdenum alloy)
or the like. Non-metallic polymeric materials can also be used,
e.g., an acrylic, epoxy, polycarbonate, nylon, polyethylene, PEEK,
ABS, or PVC or any thermoplastic elastomer or thermoplastic
polyurethane that is fabricated to be visible under x-ray (e.g.,
embedded with barium).
[0382] The septum is preferably cone shaped, so that the
compressive forces are maximized for self-sealing after inflation.
The self-sealing septum allows air to be evacuated from the balloon
for processing/compacting and insertion into the outer container,
and allows for piercing by an inflation agent syringe needle
(self-inflating configuration) or inflation catheter needle
(inflatable configuration), and then subsequent withdrawal of the
inflation agent syringe needle or detachment of the inflation
catheter and withdrawal of the catheter needle significantly
limiting gas leakage outside of the balloon during the inflation
process and needle withdrawal/catheter detachment. The septum is
inserted into the valve using a mechanical fit mechanism to provide
compression. An additional ring can be placed at the distal end of
the inner cylinder to provide additional compression to ensure the
septum material is dense enough to re-seal itself. The ring is
preferably metallic in nature, but can also be a non-metallic
polymeric material such as an acrylic, epoxy, or thermoplastic
elastomer or thermoplastic polyurethane. The ring material is
preferably the same material as the cylinder, titanium, but can
also be gold, stainless steel, MP35N or the like.
[0383] In the inflatable configuration, a larger, outer cylinder of
the concentric valve housing contains a slightly harder durometer
material than the inner cylinder (50 Shore A or greater), but is
also preferably silicone. The purpose of using a harder durometer
material is to ensure sealing when connected to the needle sleeve
for inflation. The silicone located in the outer ring of the
concentric valve is adhered to the balloon from the inside surface.
The entire outer cylinder is filled and a small circular lip of
this same material is provided that is slightly larger than the
diameter of the inner cylinder and extends to the outside surface
of the balloon. The lip is compatible with the bell shaped needle
sleeve and provides sealing to enhance connection of the valve to
the catheter to withstand the inflation pressures applied and also
increases the tensile force of the catheter. This silicone lip
preferably does not protrude past the balloon surface more than 2
mm to ensure that the balloon surface remains relatively smooth and
does not cause abrasion or ulcerations of the mucosa. It is
designed to provide compressive forces against the needle sleeve of
the catheter for inflation and detachment whereby when connected to
the needle sleeve of the inflation catheters, the connection force
during the inflation process can withstand up to 35 PSI. The seal
is then broken during detachment using hydrostatic pressure that is
more than 40 PSI less than 200 PSI to break the connection force.
Two additional retaining rings, preferably made of the same
material as concentric valve, are included in the valve system to
further enhance the seal between the metal and the valve silicone
and provide additional mechanical support to ensure proper
mechanical fit and are intended to disrupt slippage of the silicone
material from the hard (metallic) valve system (causing an increase
in tensile force).
[0384] The valve structure for the inflatable configuration uses a
mechanical fit mechanism to provide the functions of the
self-sealable valve for inflation by the catheter and subsequent
catheter detachment; however, primer and/or adhesive may be used to
provide additional support in maintaining the assembly. The
configuration can be modified by modifying the surfaces of the
metal components, making them more sticky or 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 detachment. Additional
assemblies can include overmolding the metallic portions or the
concentric system in silicone such that additional support rings to
ensure the mechanical fit and the tensile strength and forces
required to sustain the assembly during catheter inflation and
detachment can be omitted.
[0385] The total valve diameter in the inflatable configuration is
designed to fit a miniature catheter system that does not exceed 8
French (2.7 mm, 0.105 inches) in diameter. The total diameter does
not exceed 1 inch (2.54 cm) and is preferably less than 0.5 inches
(1.27 cm), to facilitate swallowing. Additional valves can be
added, if desired; however, it is generally preferred to employ a
single valve so as to maintain the volume of the deflated/folded
balloon (and thus the outer container dimensions) as small as
possible. The valve system is preferably attached to the inner
surface of the balloon such that a shear force greater than 9 lbs
(40 N) is required to dislodge the valve system.
[0386] In a self-inflating configuration, the valve system can be
attached to the balloon (e.g., on its inside surface) without the
use of an opening, orifice, or other conduit in the wall of the
balloon. The valve system can utilize a septum with a durometer of
20 Shore A to 60 Shore D. The valve can be inserted or otherwise
fabricated into a retaining structure that has a higher durometer,
e.g., 40 Shore D to 70 Shore D or more. The retaining structure can
be fabricated from a silicone, rubber, soft plastic or any suitable
non-metallic polymeric material such as an acrylic, an epoxy, a
thermoplastic elastomer, or thermoplastic polyurethane. Preferably,
a structure, such as a ring, that can be metallic or non-metallic
but radioopaque (e.g., barium) and visible under X-ray, or magnetic
or magnetizable and detectable by sensing of a magnetic field, can
be embedded in the retaining structure. Using a mechanical fit
mechanism of two structures of different durometers, one softer
(septum) with a large diameter, can be inserted into a snug, more
rigid durometer structure creates compressive forces in the once
open orifice to enable CO.sub.2 retention and reduce susceptibility
for CO.sub.2 gas leaks. The metallic ring for radio-opacity also
helps to create compressive forces on the septum. The self-sealing
septum allows air to be evacuated from the balloon for
processing/compacting and inserting in the outer container, and
also allows for the inflation agent to be injected into the outer
container for inflation initiation. Additional septums can be
provided, if desired; however, it is generally preferred to employ
a single septum so as to maintain the volume of the deflated/folded
balloon (and thus the outer capsule) as small as possible. The
valve system is preferably attached to the inner surface of the
balloon such that a shear force greater than 9 lbs (40 N) is
required to dislodge the valve system. A silicone head and opacity
ring of a self-sealing valve system can be employed, as can a
wedge-shaped septum.
[0387] In the self-inflating configuration, an inoculation spacer
is preferably incorporated to guide a needle into the self-sealing
valve for injection of liquid activation agent into the lumen of
the balloon and to prevent the needle from penetrating the wall of
the deflated/folded balloon elsewhere such that pressure within the
lumen of the balloon cannot be maintained. The inoculation spacer
also facilitates preventing liquid activation agent from
penetrating the inner container or the folded balloon material,
thereby focusing the activation agent in an appropriate manner to
properly mix the reactants for CO.sub.2 generation according to the
criteria described above. 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 the self-sealing
valve system with an adhesive or other fixing means; however, in
certain embodiments the inoculation spacer can be "free-floating"
and maintained in position by the folding or rolling of the walls
of the balloon. The inoculation spacer can comprise any suitable
material that can be passed after separation, erosion, degradation,
digestion, and/or dissolution of the outer container; however,
preferable materials include non-metallic materials with a minimum
Shore D durometer of 40 or more, any metallic material, or a
combination thereof. A cupped needle stop (inoculation spacer) can
be employed in preferred embodiments.
Inflation Assembly
[0388] In certain preferred embodiments, the volume-occupying
subcomponent is filled with a fluid using tubing which is
subsequently detached and pulled away from the volume-occupying
subcomponent. One end of the volume-occupying subcomponent has a
port connected to tubing of sufficient length that when unwound can
span the entire length of the esophagus, from mouth to stomach.
This tubing is connected to the volume-occupying subcomponent with
a self-sealable valve or septum that can tear away from the
volume-occupying subcomponent and self-seal once the
volume-occupying subcomponent is inflated. A physician or other
health care professional secures one end of the tubing as the
patient swallows the device. Once the device is residing within the
stomach, the physician uses the tube to transmit a fluid, such as
air, nitrogen, SF.sub.6, other gas(es), vapors, saline solution,
pure water, a liquid or vapor under external ambient conditions
(e.g., room temperature) that forms a vapor or gas, respectively,
at in vivo temperatures (e.g., SF.sub.6), or the like, into the
volume-occupying subcomponent and thereby inflate it. The fluid may
be or include a variety of other fluid or non-fluid materials as
well, including physiologically acceptable fluids, such as aqueous
fluids, e.g., water, water with one or more additives (e.g.,
electrolytes, nutrients, flavorants, colorants, sodium chloride,
glucose, etc.), saline solution, or the like. After the
volume-occupying subcomponent is fully inflated, the tubing is
released and can be pulled out from inside the patient.
[0389] The tube may be released in a number of manners. For
example, the tubing may be detached by applying a gentle force, or
tug, on the tubing. Alternatively, the tubing may be detached by
actuating a remote release, such as a magnetic or electronic
release. Additionally, the tubing may be released from the
volume-occupying subcomponent by an automatic ejection mechanism.
Such an ejection mechanism may be actuated by the internal pressure
of the inflated volume-occupying subcomponent. For example, the
ejection mechanism may be sensitive to a specific pressure beyond
which it will open so as to release any excess pressure and
simultaneously release the tube. This embodiment provides a
desirable feature through combining release of the tubing with a
safety valve that serves to avert accidental over inflation of the
volume-occupying subcomponent in the patient's stomach.
[0390] This automatic release embodiment also provides the benefit
that the device inflation step may be more closely monitored and
controlled. Current technology allows for a self-inflating
intragastric volume-occupying subcomponent which generally begins
to inflate in a four minute timeframe after injection with an
activation agent such as citric acid. In this approach, the
volume-occupying subcomponent may, in some instances, begin to
inflate prior to residing within the stomach (e.g., in the
esophagus), or, in patients with gastric dumping syndrome or rapid
gastric emptying, the volume-occupying subcomponent may end up in
the small intestine prior to the time that inflation occurs.
Accordingly, in certain embodiments it can be desirable to inflate
the volume-occupying subcomponent on command, once it is
ascertained that the volume-occupying subcomponent is residing in
the correct location.
[0391] In certain embodiments, it may also be advantageous for the
volume-occupying subcomponent to inflate gradually or in several
steps over time, or for the volume-occupying subcomponent to
maintain a volume and/or internal pressure within a preselected
range. For example, if gas escapes the volume-occupying
subcomponent prior to the desired deflation time, it can be
beneficial for the device to re-inflate in order to preserve it in
its expanded state.
[0392] An intragastric balloon system that is manually inflated by
a miniature catheter can be employed in certain embodiments. The
system preferably remains "swallowable." The balloon for delivery
is in a compacted state and is attached to a flexible, miniature
catheter, preferably no larger than 4 French (1.35 mm) in diameter.
The catheter is designed such that a portion of the catheter can be
bundled or wrapped upon itself for delivery with the encapsulated
balloon, allowing the patient to swallow both catheter and balloon
for delivery to the stomach. The balloon can contain a
self-sealable valve system for attachment of the catheter and
inflation of the balloon once it reaches the stomach cavity. The
proximal end of the catheter can be left just outside of the
patient's mouth, permitting connection to an inflation fluid
container that can house the preferred inflation fluid (gas or
liquid). After inflation the catheter can be detached from the
balloon valve and pulled back through the mouth. This method allows
for the intragastric balloon to maintain its swallowability but
allow for inflation by a fluid source or a mixture of fluid sources
via the catheter. Alternatively, a more rigid, pushable system can
be employed wherein the balloon valve is compatible with either the
swallowable, flexible catheter or the pushable, rigid catheter
assembly.
[0393] The inflation catheters (swallowable or
administrator-assisted pushable) described herein are configured to
deliver the balloon device orally and without any additional tools.
The administration procedure does not require conscious sedation or
other similar sedation procedures or require endoscopy tools for
delivery. However, other versions of the device can be used in
conjunction with endoscopy tools for visualization or can be
adapted such that the balloon device can be delivered
nasogastrically as well.
[0394] In operation, the proximal end of the inflation catheter is
connected to a valve or connector that allows for connection to the
inflation source or the disconnect source, this is preferably a
Y-arm connector or inflation valve. The connector materials may
consist of polycarbonate or the like and can connect to a single or
multi-lumen catheter tube. The distal end of the inflation catheter
is connected to the universal balloon valve of the balloon that has
been compacted and housed within a gelatin capsule or compacted
using gelatin bands. The catheter tube is preferably from 1 French
(0.33 mm) to 6 French (2 mm) in diameter. The catheter is
preferably long enough to extend out past the mouth (connected to
the inflation connector or valve) and transverse the esophagus down
to at least the middle of the stomach--approximately 50-60 cm.
Measurement ticks can be added to the tubing or catheter to aid in
identifying where the end of the tube is located. Timing for
inflation can be initiated by having the tube contain a pH sensor
that determines a location difference between the esophagus (pH
5-7) and the stomach (pH 1-4) based on the different pH between the
two anatomical sources, or can be derived or verified from the
expected pressure in a contained (i.e., esophagus) versus a
less-constrained space (i.e., stomach). The tube can also contain
nitinol that has a tunable transmission to the body temperature,
taking into account the timing for swallowing. The tube can also be
connected to a series of encapsulated or compacted balloons on a
single catheter. Each can be inflated and released separately. The
number of balloons released can be tune-able to the patient's needs
and desired weight loss. In certain embodiments, the intragastric
balloon or catheter is located or tracked in the body by sensing a
magnetic field of a magnetizable component of both or either
devices, as discussed in detail below.
[0395] In certain embodiments, a catheter with the balloon at the
distal end (inflated with air) is employed to temporarily and
firmly hold the balloon in place. A small deflated balloon catheter
can be positioned through the head of the gastric balloon (e.g., a
"balloon within the balloon"), and then inflated with air during
delivery to firmly hold the capsule and balloon in place and
prevent spontaneous detachment of balloon from the catheter. This
balloon catheter can incorporate a dual channel that can also allow
the bigger gastric balloon to be inflated (by gas or liquid). Once
the gastric balloon has been satisfactorily inflated, the small air
balloon catheter can be deflated and pulled out of the valve
(allowing the valve to self seal), and out of the body, leaving the
inflated gastric balloon in the stomach.
[0396] In other embodiments, the catheter may be coated to enhance
swallowability or is impregnated or treated with one or more local
anesthetics or analgesics to ease swallowing. Such anesthetics may
include anesthetics in the amino amide group, such as articaine,
lidocaine and trimecaine, and anesthetics in the amino ester group,
such as benzocaine, procaine and tetracaine. Such analgesics may
include chloraseptic.
Dual Lumen Catheter
[0397] In a preferred embodiment, a swallowable dual lumen catheter
is provided. The dual lumen catheter has two lumens with a diameter
of the complete assembly no larger than 5 French (1.67 mm),
preferably no larger than 4 French (1.35 mm). The inner lumen
preferably does not exceed 3 French (1 mm) and functions as the
inflation tube, and the outer lumen preferably does not exceed 5
French (1.67 mm) and functions as the disconnection tube; the inner
and outer lumen do not exceed 2 French (0.66 mm) and 4 French (1.35
mm), in diameter, respectively. The catheter assembly is connected
to a needle assembly, described in more detail below, at the distal
end and to a dual port inflation connector at the proximal end. The
tubing that the catheter assembly employs is flexible for
swallowability, is kink resistant, can withstand body temperature,
is resistant to acid, and is biocompatible as the tube transverses
the alimentary canal into the stomach cavity. The tube materials
are preferably soft and flexible and have moderate tensile strength
and a significant amount of hoop strength to handle applied
pressures. The lumens are preferably round and co-axial and
free-floating so as to provide flexibility. The dual lumen assembly
also preferably requires no adhesive or glue. Alternative lumen
configurations can include two D-lumens or a combination of a
D-lumen and round lumen, and can be used in stiffer configurations
of the final catheter assembly. Preferred materials for the tubing
include a thermo-resistant polyethylene tubing such as PEBAX.RTM.
or a thermo-resistant polyurethane tubing such as PELLETHANE.TM.,
PEEK or Nylon. The tubing can also be manufactured out of
bioresorbable materials such as polylactic acid (PLA),
poly-L-aspartic acid (PLAA), polylactic/glycolic acid (PLG),
polycaprolactone (PCL), DL-lactide-co-.epsilon.-caprolactone
(DL-PLCL) or the like, wherein the tube can be released after
inflation and detachment and swallowed as normal.
[0398] At the distal end of the catheter assembly, the inner lumen
or inflation tube is attached to the needle assembly that is used
to puncture the balloon's self-sealing valve, preferably located at
one of the apexes of the balloon housed inside of a gelatin capsule
as outer container. The outer lumen is connected to the needle
sleeve and provides connection force between the catheter assembly
and balloon providing the tensile strength to withstand balloon
inflation pressures, e.g., pressures of up to 10 psi or higher,
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, with a maximum size of 25 gauge (0.455 mm), preferably
no smaller than 30 gauge (0.255 mm) for inflation timing purposes.
The needle sleeve is preferably a soft material such as nylon or
the like, or can also be polycarbonate, polyethylene, PEEK, ABS or
PVC. The needle sleeve covers the length of the needle in its
entirety, such that the body is protected from the needle and the
needle can only pierce the balloon septum. Preferably the needle
sleeve is flush or extends out slightly more than the needle
length. The needle is inserted into the balloon septum prior to
swallowing and maintains a retention force of approximately 0.33 lb
(0.15 kg) when coupled to the silicone area of the balloon valve.
The needle sleeve is preferably slightly bell shaped or contains a
circular relief or lip so that when inserted into the silicone area
of the valve a lock and key mechanism is created to increase the
tensile strength of the assembly and enhance the sealing for
inflation.
[0399] At the proximal end, the catheter assembly is connected to a
Y-adapter assembly preferably made of polycarbonate. The y-adapter
is "keyed" so that the inflation gas and connection fluid are
connected to the catheter assembly appropriately and travel down
the correct lumen.
[0400] Prior to inflation, priming of the disconnection lumen may
be employed using a liquid. For example, the outer lumen is first
flushed with 2 cc of water, saline, DI water or the like prior to
balloon inflation. Thereafter, the inflation source container is
attached to the connector leading to the inner lumen. The inflation
source container works on the premise of the ideal gas law and a
pressure decay model. For a given compressed gas formulation, the
device is designed to equalize such that a higher starting pressure
is used to inflate the balloon than is the resulting end pressure
of the balloon. The starting pressure and volume are dependent upon
the gas formulation selected, as well as the length of the catheter
and the starting temperature (typically ambient temperature) and
ending temperature (typically body temperature).
[0401] After inflation, the balloon is detached 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, enough hydraulic pressure is exerted
such that the needle is ejected from the balloon valve.
Single Lumen Catheter
[0402] To further reduce the diameter of the inflation catheter,
thereby increasing swallowability comfort, a single lumen catheter
can be employed that does not exceed 2 French (0.66 mm) in
diameter.
[0403] The needle/needle sleeve assembly is similar in design to
that of the dual lumen catheter described herein. However, with the
single lumen system, the distal end of the catheter lumen connects
to the needle sleeve only and there is no second catheter inside.
Instead, a single thread attached to a needle hub runs co-axially
the length of the catheter to aid in tensile strength for
detachment and overall flexibility.
[0404] The needle sleeve is slightly bell shaped or contains a
circular relief or lip so that when inserted into the silicone area
of the valve a lock and key mechanism is created to increase the
tensile strength of the assembly, enhance the sealing for
inflation, and since this is a single lumen assembly, the lip
increases the force required to remove the needle from the valve so
this does not occur haphazardly during the inflation process.
[0405] The proximal end of the catheter is connected to a 3-way
valve and uses a method of exclusion for inflation and detachment
of the balloon. The distal end of the catheter contains the needle
sleeve, which is made of nylon or other similar source. The needle
is metallic and preferably stainless steel.
[0406] The tubing that the catheter assembly employs is flexible
for swallowability, is kink resistant, can withstand body
temperature, is resistant to acid, and is biocompatible as the tube
transverses the alimentary canal into the stomach cavity. The tube
materials are preferably soft and flexible, preferably co-axial,
and resistant to necking or buckling or kinking. For a single lumen
system, the catheter tubing is preferably made of PEBAX.RTM., but
can also comprise bioresorbable materials such as PLA, PLAA, PLG,
PCL, DL-PLCL or the like, wherein the tube can be released after
inflation and detachment and swallowed as normal. The wire inside
the catheter tubing attached to the needle is preferably a nylon
monofilament, but Kevlar or nitinol wire or other suitable
materials can also be used.
[0407] To inflate the balloon, the distal end of the catheter is
attached to the balloon capsule where the needle protrudes through
the self-sealable valve. The container is swallowed and a portion
of the inflation catheter remains outside of the mouth. The
inflation source container is connected to the proximal 3-way
valve, where the port for inflation gas is chosen by excluding the
other ports. The inflation fluid (preferably compressed nitrogen
gas or a mixture of gases) travels down the single catheter lumen,
whereby the inflation gas selects the path of least resistance, or
more specifically through the needle cavity and into the balloon.
The balloon is preferably inflated in less than 3 minutes.
[0408] To detach and withdraw the needle from the balloon valve, 2
cc or other suitable volume of water or other liquid is injected
into the catheter at a high pressure. Since water has a high
surface tension and viscosity, it occludes the needle pathway and
the pressure is transferred to the outside needle sleeve, thereby
breaking the fit between the needle sleeve and the balloon
valve.
[0409] If it is desired to place a substance inside the balloon,
such as water or acid or any alternative liquid, it can be done by
using a lower pressure to inject the liquid.
Miniature Stiff-Bodied Inflation Catheter
[0410] In certain embodiments, a stiff-bodied inflation catheter
can be employed, which can be placed orally or trans-nasally. This
system can be from 1 French (0.33 mm) to 10 French (3.3 mm),
preferably 8 French (2.7 mm) in diameter. A larger diameter is
typically preferred to enhance pushability, with wall thickness
also contributing to pushability and kink resistance. The length of
the tube can be approximately 50-60 cm. As discussed above,
measurement ticks can be added to the tubing to identify where the
end of the tube is located, or a pH or pressure sensor on the
catheter can be employed to detect location of the balloon.
[0411] This system for inflation/detachment is similar to the dual
lumen system described above, but with a larger needle sleeve to
accommodate the larger diameter tube. Materials that can be used in
the lumen include, e.g., expanded polytetrafluoroethylene (EPTFE)
for the outer lumen and polyetheretherketone (PEEK) for the inner
lumen. To also enhance pushability, a strain relief device can be
added to the distal and proximal ends. It is particularly preferred
to have strain relief at the distal end, e.g., 1 to 8 inches,
preferably 6 inches, to ensure the catheter bypasses the larynx and
follows into the esophagus. The proximal end can have strain relief
as well, e.g., to ensure fit of the Y-arm. The preferred material
for the strain relief is a polyolefin. The method for
inflation/detachment is the same method as for 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, the patient can swallow water or other suitable liquid
so as to distend esophageal tissue for smooth passage down of the
device. Patients can also be administered an anesthetic at the back
of the throat to numb the area and lessen the gag reflex.
[0412] The tube can also be connected to a series of encapsulated
or compacted balloons on a single catheter such that a total volume
of up to 1000 cc or more can be administered, as necessary. Each
can be inflated and released separately. The number of balloons
released can be tunable to the patient's needs and desired weight
loss.
[0413] In addition, a catheter can be used for administering a
gastric balloon that is similar to balloon catheters used in
angioplasty termed "over-the-wire" or rapid exchange catheters. In
this case where the patients attempts to swallow the catheter but
fails so the stiff catheter--or physician assisted catheter can
slide over the flexible catheter and the balloon can be pushed down
in the same manner as the physician-assisted catheter. Different
materials can be used to provide the varying degrees of flexibility
or one material that is fabricated with different diameters across
the length to vary the degree of stiffness can be used.
[0414] The swallowable self-inflating balloon construction method
and the swallowable inflation tube construction method both remove
the requirement for endoscopy to place the balloon and make the
balloon administration process less invasive. This also allows for
the total volume to be placed in a patient to be "titratable," or
adjustable. When a balloon is placed for 30 days, a patient may
report that over time they lose their feeling of fullness without
eating. To compensate, another balloon can be placed easily without
sedation and endoscopy. When a non-deflatable balloon is to be
removed endoscopically, it is desirable to color-code the balloon
composite walls with different colors so that the physician has a
visual marker for removing the balloon at the end of its useful
life while keeping the balloon that has remaining useful life in
the patient's stomach.
[0415] In addition, the balloon wall can be marked approximately
180.degree. from the self-sealing valve such that when the balloon
is punctured endoscopically it folds more efficiently on itself so
as to facilitate removal of the thin-walled structure without
causing esophageal perforations and/or other damage by the balloon
due to its shape, stiffness, and/or thickness of the wall
material.
Inflation Fluid Container
[0416] The inflation fluid container is employed to control the
amount or volume of fluid placed inside of the balloon. This can be
in the form of a canister of, e.g., PVC, stainless steel, or other
suitable material. The container can also be in syringe form. The
materials employed are able contain a fluid, preferably in gas
form, e.g., compressed or non-compressed N.sub.2, Ar, O.sub.2,
CO.sub.2, or mixture(s) thereof, or compressed or non-compressed
atmospheric air (a mixture of N.sub.2, O.sub.2, Ar, CO.sub.2, Ne,
CH.sub.4, He, Kr, H.sub.2, and Xe). The balloon composite wall
materials and respective diffusion gradients and gas permeability
characteristics are used to select a fluid for inflation of the
intragastric balloon, so as to provide a desired volume profile
over time for the inflated balloon. The inflation fluid container
materials are selected to ensure no or minimal diffusion or leakage
of the fluid before it is connected to the y-arm connector or valve
of the inflation catheter. The inflation fluid container preferably
incorporates a pressure gauge and a connector. It can also contain
a smart chip that notifies the healthcare professional of whether
inflation is successful or if the balloon should be detached due to
an error in the system.
[0417] To maintain "swallowability" of the balloon and to ensure
comfort of the patient during the procedure, it is preferred to
minimize the amount of time the catheter is placed in the
mouth/esophagus. Timing of inflation is can be selected so as to
minimize time in place. The outer container-catheter assembly, once
swallowed, takes approximately 4-8 seconds to reach the stomach.
Once in the stomach, the Inflation source container can be attached
to the valve or port of catheter system. Inflation timing can be
controlled by selecting the length of catheter, diameter of the
catheter tube, the starting temperature, and the starting pressure.
Using the Ideal Gas Law for nitrogen and Boyle's Law
(P.sub.1V.sub.1=P.sub.2V.sub.2) the amount of starting
volume/pressure can be derived, where temperature is controlled
inside the inflation source container to match that of the body. It
is desired to have an inflation time after swallow of less than 5
minutes, and preferably 2-3 minutes, before balloon detachment and
catheter withdrawal. The inputs use to derive inflation of the
balloon (preferably in less than 3 minutes) include inflation
container volume, type of inflation fluid (preferably a compressed
gas or compressed gas mixture), starting pressure, catheter length
and diameter, and desired end volume and pressure of the balloon.
Thus, due to differences in diameter, a 2 French catheter system
requires a higher starting pressure to achieve the same target
balloon volume and pressure in the same time frame, assuming use of
the same compressed gas formulation. In general, it is understood
that starting with a higher pressure with the same flow rate/volume
can decrease the inflation time.
[0418] The inflation source container provides feedback to the end
user based on a pressure decay system. Where there is an expected
starting pressure and expected ending pressure to indicate whether
the balloon is inflated properly, there is no need for endoscopic
visualization. Each scenario of expected pressure outputs can have
its own tolerances around it to reduce possibilities of false
positives, and the inflation fluid container can provide feedback
based on these tolerances as to the status of balloon inflation and
detachment. This is derived based on the Ideal Gas Law, where there
is an expected end pressure based on the fixed volume of the
balloon. If the pressure remains high and doesn't decay as
expected, this can indicate a failure in the system (e.g., the
balloon container did not dissolve, the balloon is expanding in the
esophagus because there is, e.g., a kink in the tube or other
failure in the catheter system). For example, for a successful
decay using nitrogen only as the inflation fluid, the starting
pressure is 22 PSI to inflate a balloon to 250 cc and 1.7 psi
(0.120 kg/cm.sup.2) for a nylon-based material. To indicate
successful balloon inflation, a math chip can be added to the
inflation source container that provides at least one of a visual,
audible, or tactile notification, or otherwise transmits a
notification to a healthcare professional or administrator of
whether inflation is successful or if there is an error in the
system based on the pressure curve and a set of predetermined
pressure tolerances and expected timing of inflation.
[0419] Another method for detection of any degree of constraint
that the balloon may be experiencing (e.g., capsule dissolved but
balloon is in the esophagus or duodenum, or balloon is in the
stomach and the capsule has not dissolved by reading the gauge
output is to employ an inflation canister that has at least two
reservoirs (one large and one small) and at least two gauges, with
one or more valves that allow for selection of gas release into the
second reservoir or into the balloon itself. With two reservoirs,
the larger reservoir can contain the total amount of fluid required
to fill the balloon. A small amount of fluid can be released from
the larger reservoir into the smaller reservoir first to determine
the location of the balloon and its readiness for full inflation.
If the 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
indicates that the balloon is still contained in the capsule and it
is not ready to be inflated. When the gauge reads back a medium
pressure level (e.g., 1-4 psi), this indicates that the balloon is
in a constrained space, such as the esophagus or duodenum, and
should not be inflated. When the balloon catheter's feedback as
read on the gauge is approximately 1 psi, this indicates that the
balloon is in the stomach and ready to be inflated. If the feedback
is at 0 psi, this indicates is a leak in the balloon valve catheter
system and that the device should be retrieved. Once the balloon is
detected in the stomach space, then the larger reservoir is opened
and the balloon is inflated to its desired pressure.
[0420] Alternatively, the balloon can be filled based on a starting
pressure by using a spring mechanism, a balloon-within-balloon
mechanism, or other pressure source. These mechanisms can
potentially result in more predictable/consistent pressure decay
curves, and again can have accompanying, predetermined tolerances
for feedback back to the end user.
Composite Wall
[0421] The materials selected for the composite wall of the balloon
may be optimized to maintain the original inflation gas without
significant diffusion, or may also allow for diffusion of the gases
located in the gastric environment, e.g., CO.sub.2, O.sub.2, argon,
or N.sub.2 to diffuse through the wall of the balloon to inflate,
partially or wholly, once the balloon is placed in the stomach. A
fluid (a liquid or gas) can also be added inside of the balloon
using the inflation catheter(s) described herein to change
diffusion direction of the balloon composite wall and when it
reaches stasis based on the internal and external environment.
[0422] A gastric balloon inflated by nitrogen, CO.sub.2 gas, a
single fluid (gas) or a mixture of gasses employs a composite wall
that provides barrier properties (fluid retention), properties
imparting resistance to pH and moisture conditions in the gastric
environment or the environment within the central lumen of the
balloon, and structural properties to resist gastric motility
forces, abrasion of the balloon wall in vivo, and damage during
manufacturing and folding of the balloon. Certain materials
employed in the balloon materials are able to withstand a hostile
gastric environment designed to break down foreign objects (e.g.,
food particles). Some of the variables that the gastric environment
encompasses are as follows: gastric liquid pH of from 1.5-5;
temperature of approx. 37.degree. C.; a relative humidity of
90-100%; ingress of gastric space gas content; and constant gastric
motility external pressures of from 0-4 psi at variable frequencies
and cycle times based on the fed state of the stomach. The external
pressure imparted by gastric motility can also cause abrasions on
the surface of the balloon. The inside of the balloon lumen may
contain moisture from a solution injected in the balloon for timing
of auto-deflation or any moisture that has transferred across the
membrane due to the external humid environment. In addition to
these environmental stresses the wall materials meet
biocompatibility requirements and are constructed such that the
total thickness of the wall (barrier material) is thin enough to be
compacted and placed inside of a swallowable-sized container
("outer container") without significant damage or lodging. The
outer container is small enough to transcend the esophagus (which
has a diameter of approximately 2.5 cm). The wall or barrier
material is also heat formable and sealable for balloon construct
and maintains a bond strength that can contain internal gas
pressures of up to 10 psi generated by the initial inflation
pressure as well as pressure due to the ingress of gas molecules
from the stomach cavity until the system's gas environment reaches
stasis. The film properties that are evaluated to determine
suitability for use in the composite wall of the balloon include pH
resistance, water vapor transmission rate, gas barrier properties,
mechanical strength/abrasion properties, temperature resistance,
formability, flex-crack (Gelbo) resistance, surface energy
(wettability) compliance, and heat bond potential.
[0423] The various layers in the composite wall can impart one or
more desirable properties to the balloon (e.g., CO.sub.2 retention,
resistance to moisture, resistance to acidic environment,
wettability for processing, and structural strength). A list of
polymer resins and coatings that can be combined into a multi-layer
preformed system ("composite wall") is provided in Tables 1a-b.
These films can be adhesively bonded together, co-extruded, or
adhered via tie layers or a combination thereof to obtain the
desired combination of properties for the composite wall, as
discussed below. The materials identified as film coatings in
Tables 1a-b are provided as coatings applied to a base polymer
film, e.g., PET, Nylon, or other structural layer.
TABLE-US-00001 TABLE 1a Film Resins Characteristics Good
Structural/ Behavior/ Good Fluid Good Mechanical Retention
Manufacturability/ Strength/ Barrier Surface Compliance Properties
Energy Properties FILM RESINS Polyethylene X X Terephthalate (PET)
Polytrimethylene Terephthalate (PTT) Liquid Crystal X X Polymer
(LCP) Polytrimethylene X X naphthalate (PTN) Polyethylene X X
naphthalate (PEN) Polyimide (PI) X X Linear Low Density X
Polyethylene (LLDPE) Ethylene Vinyl X Alcohol (EVOH) Polyamide:
Nylon X X (PA) and Nylon-6 (PAG)/Nylon 12 High Density X
Polyethylene (HDPE) Polypropylene (PP) X Polyurethane X PVDC
(Saran) X X Polyether Block X Amide (Pebax) Polyvinyl Alcohol X
(PVOH) Silicone X X
TABLE-US-00002 TABLE 1b Film Coatings Characteristics Good
Structural/ Behavior/ Good Fluid Good Mechanical Retention
Manufacturability/ Strength/ Barrier Surface Compliance Properties
Energy Properties FILM COATINGS Silicon Dioxide X (SiO2) Aluminum
Oxide X (Al.sub.2O.sub.3) Nanopolymers X (Nano/Clay) External
Organic X Coatings (e.g., epoxy amine) Inorganic Coatings X (e.g.,
Amorphous Carbon) Oxygen Scavengers X Parylene C X
Fluid Retention Layers
[0424] In preferred embodiments, a blended polymer resin using
multiple layers is employed to maintain the inflated balloon's
shape and volume by retaining the inflation fluid for the duration
of the intended use. Certain barrier films, widely used in the food
packaging and plastic bottling industries, can advantageously be
employed for this purpose in the composite wall of the balloon.
Preferably, the barrier materials have a low permeability to carbon
dioxide (or other gases, liquids, or fluids that are alternatively
or additionally used to inflate the volume-occupying subcomponent).
These barrier layers preferably have good adherence to the base
material. Preferred barrier coating materials and films include
polyethylene terephthalate (PET), linear low density polyethylene
(LLDPE), ethylene vinyl alcohol (EVOH), polyamides such as Nylon
(PA) and Nylon-6 (PA-6), polyimide (PI), liquid crystal polymer
(LCP), high density polyethylene (HDPE), polypropylene (PP),
biocompatible poly(hydroxyamino ethers), polyethylene naphthalate,
polyvinylidene chloride (PVDC), saran, ethylene vinyl alcohol
copolymers, polyvinyl acetate, silicon oxide (SiOx), silicon
dioxide (SiO.sub.2), aluminum oxide (Al.sub.2O.sub.3), polyvinyl
alcohol (PVOH), nanopolymers (e.g., nanoclay), polyimide thermoset
film, EVALCA EVAL EF-XL, Hostaphan GN, Hostaphan RHBY, RHB MI,
Techbarrier HX (SiOx-coated PET), Triad Silver (silver metalized
PET), Oxyshield 2454, Bicor 84 AOH, acrylonitrile copolymers, and
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 a solvent-based or aqueous-based thermosetting
composition and are typically spray-coated onto a preform and then
heat-cured to form the finished barrier coating. Alternative gas
barrier materials that can be applied as coatings to the
volume-occupying subcomponent include metals such as silver or
aluminum. Other materials that may be used to improve the gas
impermeability of the volume occupying subcomponent include, but
are not limited to, gold or any noble metal, PET coated with saran,
and conformal coatings.
[0425] One method that is used in the packaging industry to delay
diffusion of the inflation fluid is to thicken the material.
Thickening the material is generally not preferred, as the total
composite wall thickness preferably does not exceed 0.004 inches
(0.010 cm) in order for the balloon to be foldable into the desired
delivery container size for swallowing by a patient.
[0426] A multilayer polymer film that is able to withstand the
gastric environment over the course of the usable life of the
balloon includes linear low density polyethylene (LLDPE) adhesively
bonded to a Nylon 12 film. Alternatively, an additional film layer
with barrier properties, such as PVDC can be added to the composite
wall.
[0427] The layers providing gas barrier properties are preferably
situated as inner layers in the composite wall as they are less
mechanically robust than resins that are considered "structural"
such as Nylon and the like.
Structural Layers
[0428] Layers such as polyurethane, Nylon, or polyethylene
terephthalate (PET) can be added to the composite wall for
structural purposes, and are preferably placed as outermost
(proximal to the gastric environment or proximal to the central
lumen of the balloon) layers, provided that the pH resistance of
such layers can withstand the acidic environment of the stomach or
the central lumen of the balloon. Other layers may in addition or
alternatively be included, including but not limited to those
described in the following "Layer Chemistry" subsections.
Layer Chemistry
[0429] Polyethylene Terephthalate (PET)
[0430] Polyethylene terephthalate is a thermoplastic polymer resin
of the polyester family. Polyethylene terephthalate may exist as an
amorphous (transparent) or as a semi-crystalline material. The
semi-crystalline material can appear transparent
(spherulites<500 nm) or opaque and white (spherulites up to a
size of some .mu.m) depending on its crystal structure and
spherulite size. Its monomer (bis-.beta.-hydroxyterephthalate) can
be synthesized by the esterification reaction between terephthalic
acid and ethylene glycol with water as a byproduct, or by
transesterification reaction between ethylene glycol and dimethyl
terephthalate with methanol as a byproduct. Polymerization is
through a polycondensation reaction of the monomers (done
immediately after esterification/transesterification) with ethylene
glycol as the byproduct (the ethylene glycol is directly recycled
in production). Some of the trade names of PET products are Dacron,
Diolen, Tergal, Terylene, and Trevira fibers, Cleartuf, Eastman PET
and Polyclear bottle resins, Hostaphan, Melinex, and Mylar films,
and Amite, Ertalyte, Impet, Rynite and Valox injection molding
resins.
[0431] PET consists of polymerized units of the monomer ethylene
terephthalate, with repeating C10H8O4 units. PET can be semi-rigid
to rigid, depending on its thickness, and is very lightweight. It
makes a good gas and fair moisture barrier, as well as a good
barrier to alcohol and solvents. It is strong and impact-resistant.
It is naturally colorless with high transparency.
[0432] When produced as a thin film (biaxially oriented PET film,
often known by one of its trade names, "Mylar"), PET can be
aluminized by evaporating a thin film of metal onto it to reduce
its permeability, and to make it reflective and opaque (MPET).
These properties are useful in many applications, including
flexible food packaging. When filled with glass particles or
fibers, it becomes significantly stiffer and more durable. This
glass-filled plastic, in a semi-crystalline formulation, is sold
under the trade name Rynite, Arnite, Hostadur, and Crastin.
[0433] One of the most important characteristics of PET is
intrinsic viscosity. The intrinsic viscosity of the material,
measured in deciliters per gram (dl/g) is dependent upon the length
of its polymer chains. The longer the chains, the stiffer the
material, and therefore the higher the intrinsic viscosity. The
average chain length of a particular batch of resin can be
controlled during polymerization. An intrinsic viscosity of about:
0.65 dl/g-0.84 dl/g is preferred for use in a composite wall.
[0434] In addition to pure (homopolymer) PET, PET modified by
copolymerization is also available. In some cases, the modified
properties of copolymer are more desirable for a particular
application. For example, cyclohexane dimethanol (CHDM) can be
added to the polymer backbone in place of ethylene glycol. Since
this building block is much larger (6 additional carbon atoms) than
the ethylene glycol unit it replaces, it does not fit in with the
neighboring chains the way an ethylene glycol unit can. This
interferes with crystallization and lowers the polymer's melting
temperature. Such PET is generally known as PETG (Eastman Chemical
and SK Chemicals are the only two manufacturers). PETG is a clear
amorphous thermoplastic that can be injection molded or sheet
extruded. It can be colored during processing. Another common
modifier is isophthalic acid, replacing some of the 1,4-(para-)
linked terephthalate units. The 1,2-(ortho-) or 1,3-(meta-) linkage
produces an angle in the chain, which also disturbs crystallinity.
Such copolymers are advantageous for certain molding applications,
such as thermoforming. On the other hand, crystallization is
important in other applications where mechanical and dimensional
stability are important. For PET bottles, the use of small amounts
of CHDM or other comonomers can be useful: if only small amounts of
comonomers are used, crystallization is slowed but not prevented
entirely. As a result, bottles are obtainable via stretch blow
molding ("SBM"), which are both clear and crystalline enough to be
an adequate barrier to aromas and gases such as carbon dioxide in
carbonated beverages.
[0435] Crystallization occurs when polymer chains fold up on
themselves in a repeating, symmetrical pattern. Long polymer chains
tend to become entangled on themselves, which prevents full
crystallization in all but the most carefully controlled
circumstances. 60% crystallization is the upper limit for
commercial products, with the exception of polyester fibers.
[0436] PET in its natural state is a crystalline resin. Clear
products can be produced by rapidly cooling molten polymer to form
an amorphous solid. Like glass, amorphous PET forms when its
molecules are not given enough time to arrange themselves in an
orderly fashion as the melt is cooled. At room temperature the
molecules are frozen in place, but if enough heat energy is put
back into them, they begin to move again, allowing crystals to
nucleate and grow. This procedure is known as solid-state
crystallization.
[0437] Like most materials, PET tends to produce many small
crystallites when crystallized from an amorphous solid, rather than
forming one large single crystal. Light tends to scatter as it
crosses the boundaries between crystallites and the amorphous
regions between them. This scattering means that crystalline PET is
opaque and white in most cases. Fiber drawing is among the few
industrial processes that produces a nearly single-crystal
product.
[0438] Comonomers such as CHDM or isophthalic acid lower the
melting temperature and reduces the degree of crystallinity of PET
(especially important when the material is used for bottle
manufacturing). Thus the resin can be plastically formed at lower
temperatures and/or with lower force. This helps to prevent
degradation, reducing the acetaldehyde content of the finished
product to an acceptable (that is, unnoticeable) level. Other ways
to improve the stability of the polymer is by using stabilizers,
mainly antioxidants such as phosphites. Recently, molecular level
stabilization of the material using nanostructured chemicals has
also been considered.
[0439] Unreinforced PET has the following properties: Bulk Density
0.800-0.931 g/cc; Density 1.10-1.20 g/cc @Temperature
285-285.degree. C.; 1.25-1.91 g/cc; 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 .mu.m; Water Vapor Transmission
0.490-6.00 g/m.sup.2/day; Oxygen Transmission 5.10-23.0
cc-mm/m.sup.2-24 hr-atm; Viscosity Measurement 0.550-0.980;
Viscosity Test 74.0-86.0 cm.sup.3/g; Thickness 250-254 microns;
Linear Mold Shrinkage 0.00100-0.0200 cm/cm; Linear Mold Shrinkage,
Transverse 0.00200-0.0110 cm/cm; Hardness, Rockwell M 80.0-95.0;
Hardness, Rockwell R 105-120 105-120; Ball Indentation Hardness
160-170 MPa; Tensile Strength, Ultimate 22.0-207 MPa; Film Tensile
Strength at Yield, MD 55.0-59.0 MPa; Film Tensile Strength at
Yield, TD 53.0-57.0 MPa; Film Elongation at Break, MD 40.0-600%;
Film Elongation at Break, TD 200-600%; Film Elongation at Yield, MD
4.00-6.00%; Film Elongation at Yield, TD 4.00-6.00%; Tensile
Strength, Yield 47.0-90.0 MPa; Elongation at Break 1.50-600%;
Elongation at Yield 3.50-30.0%; Modulus of Elasticity 1.83-14.0
GPa; Flexural Modulus 1.90-15.2 GPa; Flexural Yield Strength
55.0-240 MPa; Compressive Yield Strength 20.0-123 MPa; Izod Impact,
Unnotched 2.67 J/cm-NB; Izod Impact, Unnotched Low Temp (ISO)
160-181 kJ/m.sup.2; Izod Impact, Notched, Low Temp (ISO) 3.10-4.20
kJ/m.sup.2; Charpy Impact Unnotched 3.00 J/cm.sup.2-NB; Charpy
Impact, Notched, Low Temp 0.270-0.500 J/cm.sup.2; Charpy Impact,
Notched 0.200-1.40 J/cm.sup.2; Impact Test 0.800-8.20 J
@Temperature -40.0.degree. C.; Coefficient of Friction 0.190-0.250;
Tear Strength, Total 15.0-120 N; Elmendorf Tear Strength, MD
3.14-4.00 g/micron; Elmendorf Tear Strength, TD 3.24-5.20 g/micron;
Dart Drop 1.08-2.00 g/micron; Taber Abrasion, mg/1000 Cycles; Film
Tensile Strength at Break, MD 13.8-60.0 MPa; Film Tensile Strength
at Break, TD 39.0-48.0 MPa; Izod Impact, Notched @-40.degree. C.
0.270-0.630 J/cm; Izod Impact, Notched 0.139-100 J/cm; Izod Impact,
Notched (ISO) 2.00-10.0 kJ/m.sup.2; Electrical Resistivity
5.00e+6-1.00e+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 175-600 V; Heat of Fusion 56.0-65.0 J/g;
CTE, linear 25.0-92.0 .mu.m/m-.degree. C.; CTE, linear, Transverse
to Flow 48.0-80.0 .mu.m/m-.degree. C.; Specific Heat Capacity
1.10-1.20 J/g-.degree. C.; 1.30-2.30 J/g-.degree. C. @Temperature
60.0-280.degree. C.; Thermal Conductivity 0.190-0.290 W/m-K;
Melting Point 200-255.degree. C.; Maximum Service Temperature, Air
100-225.degree. C.; Deflection Temperature at 0.46 MPa (66 psi)
66.0-245.degree. C.; Deflection Temperature at 1.8 MPa (264 psi)
60.0-240.degree. C.; Vicat Softening Point 74.0-85.0.degree. C.;
Minimum Service Temperature, Air -20.0.degree. C.; Glass
Temperature 70.0-78.0.degree. C.; UL RTI, Electrical
75.0-175.degree. C.; Haze 0.300-10.0%; Gloss 108-166%;
Transmission, Visible 67.0-99.0%; Gardner Color Number -3.00-85.0;
Processing Temperature 120-295.degree. C.; Mold Temperature
10.0-163.degree. C.; Drying Temperature 70.0-160.degree. C.; Dry
Time 3.00-8.00 hour; Moisture Content 0.0100-0.400%; Injection
Pressure 68.9-120 MPa; Back Pressure 8.00-18.0 MPa.
[0440] Polyethylene terephthalate films are available from
Mitsubishi Polyester Film of Wiesbaden, Germany under the trade
name Hostaphan.RTM.. Hostaphan.RTM. GN is a glass clear biaxially
oriented film, made of polyethylene terephthalate (PET) and is
characterized by its high transparency and surface gloss and its
low haze accompanied by its excellent mechanical strength and
dimensional stability. Hostaphan.RTM. GN is one or two side
chemically treated for improved slip and processability as well as
for improvement of the adhesion of coatings, printing inks or
metallic layers. Hostaphan.RTM. RHBY is a biaxially oriented film
made of polyethylene terephthalate (PET) with a structure optimized
to offer previously unattainable barrier properties against oxygen,
water vapor and other gases as well as aroma substances after
vacuum coating with aluminum, Al2O3 or SiOx.
[0441] Linear Low-Density Polyethylene (LLDPE)
[0442] Linear low-density polyethylene (LLDPE) is a substantially
linear polymer (polyethylene), with significant numbers of short
branches, commonly made by copolymerization of ethylene with
longer-chain olefins. Linear low-density polyethylene differs
structurally from conventional low-density polyethylene because of
the absence of long chain branching. The linearity of LLDPE results
from the different manufacturing processes of LLDPE and LDPE. In
general, LLDPE is produced at lower temperatures and pressures by
copolymerization of ethylene and such higher alpha olefins as
butene, hexene, or octene. The copolymerization process produces an
LLDPE polymer that has a narrower molecular weight distribution
than conventional LDPE and in combination with the linear
structure, significantly different rheological properties.
[0443] The production of LLDPE is initiated by transition metal
catalysts, particularly Ziegler or Philips type of catalyst. The
actual polymerization process can be done in either solution phase
or gas phase reactors. Usually, octene is the copolymer in solution
phase while butene and hexene are copolymerized with ethylene in a
gas phase reactor. The LLDPE resin produced in a gas phase reactor
is in granular form and may 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 elongates
under stress. It can be used to make thinner films, with better
environmental stress cracking resistance. It has good resistance to
chemicals and to ultraviolet radiation. It has good electrical
properties. However it is not as easy to process as LDPE, has lower
gloss, and narrower range for heat sealing.
[0444] LDPE and LLDPE have unique theoretical or melt flow
properties. LLDPE is less shear sensitive because of its narrower
molecular weight distribution and shorter chain branching. During a
shear process, such as extrusion, LLDPE remains more viscous,
therefore harder to process than an LDPE of equivalent melt index.
The lower shear sensitivity of LLDPE allows for a faster stress
relaxation of the polymer chains during extrusion and therefore the
physical properties are susceptible to changes in blow-up ratios.
In melt extension, LLDPE has lower viscosity at all strain rates.
This means it will not strain harden the way LDPE does when
elongated. As the deformation rate of the polyethylene increases,
LDPE demonstrates a dramatic rise in viscosity because of chain
entanglement. This phenomena is not observed with LLDPE because of
the lack of long-chain branching in LLDPE allows the chains to
"slide by" one another upon elongation without becoming entangled.
This characteristic is important for film applications because
LLDPE films can be downgauged easily while maintaining high
strength and toughness.
[0445] Properties of film grade LLDPE include: Density 0.902-0.960
g/cc; Moisture Vapor Transmission 0.240-0.470 cc-mm/m.sup.2-24
hr-atm; Water Vapor Transmission 6.00-8.00 g/m.sup.2/day; Oxygen
Transmission 0.720-236 cc-mm/m.sup.2-24 hr-atm; Oxygen Transmission
Rate 3500-5000 cc/m.sup.2/day; Viscosity 37000-79000 cP
@Temperature 190-190.degree. C.; 37000-79000 cP @Shear Rate
300-5000 l/s; 37000-79000 cP @Shear Rate 300-5000 l/s; Thickness
12.7-76.2 microns; Melt Flow 0.200-40.0 g/10 min; Base Resin Melt
Index 0.700-3.50 g/10 min; Antiblock Level 3500-9000 ppm; Slip
Level 0.000-1700 ppm; Tensile Strength, Ultimate 9.80-26.2 MPa;
Film Tensile Strength at Yield, MD 7.38-74.0 MPa; Film Tensile
Strength at Yield, TD 6.90-77.0 MPa; Film Elongation at Break, MD
80.0-1460%; Film Elongation at Break, TD 460-1710%; Film Elongation
at Yield, MD 435-640%; Film Elongation at Yield, TD 670-890%;
Tensile Strength, Yield 9.70-22.1 MPa; Elongation at Break
8.00-1000%; Modulus of Elasticity 0.0110-0.413 GPa; Secant Modulus,
MD 0.0103-0.717 GPa; Secant Modulus, TD 0.0106-0.869 GPa; Impact
48.0-65.0; Impact Test 0.452-5.00 J; Coefficient of Friction
0.100-2.00; Coefficient of Friction, Static 0.170-1.00; Elmendorf
Tear Strength MD 25.0-1080 g 2; 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; Dart Drop 1.57-42.5 g/micron;
Dart Drop Test 30.0-1350 g; Seal Strength 1800-2400 g/25 mm; Film
Tensile Strength at Break, MD 9.65-82.7 MPa; Film Tensile Strength
at Break, TD 7.24-55.1 MPa; Heat Seal Strength Initiation
Temperature 72.0-100.degree. C.; Melting Point 120-128.degree. C.;
Crystallization Temperature 104-115.degree. C.; Vicat Softening
Point 93.0-123.degree. C.; Haze 0.700-80.0%; Gloss 3.00-140%;
Processing Temperature 90.0-310.degree. C.; Die Opening
0.0810-0.254 cm; Blow-up Ratio (BUR) 1.50-4.00.
[0446] Ethylene Vinyl Alcohol (EVOH)
[0447] Ethylene Vinyl Alcohol is a formal copolymer of ethylene and
vinyl alcohol. Because the latter monomer mainly exists as its
tautomer acetaldehyde, the copolymer is prepared by polymerization
of ethylene and vinyl acetate followed by hydrolysis. The plastic
resin is commonly used in food applications, and in plastic
gasoline tanks for automobiles. Its primary purpose is to provide
barrier properties, primarily 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 plastics. EVOH copolymer is
defined by the mole % ethylene content: lower ethylene content
grades have higher barrier properties; higher ethylene content
grades have lower temperatures for extrusion.
[0448] Ethylene Vinyl Alcohol (EVOH) is one of the most common
clear high barrier films used today. It is applied as a discrete
layer in a coextrusion. EVOH provides excellent oxygen barrier
properties (0.006-0.12 cc-mil/100 in2-day). The barrier that a
particular EVOH film provides is dependent upon a number of
factors: mole percent--as the ethylene mole percent increases, the
barrier decreases; degree of crystallinity--as the degree of
crystallinity increases, the barrier properties improve;
thickness--as with all films, as the thickness increases, the
barrier increases; temperature--as the temperature increases, the
barrier decreases; humidity--at high humidity levels, the barrier
provided by EVOH drops rapidly (it is the humidity level at the
EVOH interface rather than ambient humidity that is critical). In
addition to providing an excellent oxygen barrier, EVOH is also an
excellent odor and aroma barrier. It has the added advantage of
being thermoformable making it popular for 3D applications.
[0449] EVALCA EVAL.RTM. EF-XL Ethylene Vinyl Alcohol Copolymer Film
has the following properties: Moisture Vapor Transmission 0.600
cc-mm/m.sup.2-24 hr-atm 40.degree. C., 90% RH; Oxygen Transmission
0.00400 cc-mm/m.sup.2-24 hr-atm 20.degree. C.; 65% RH (permeability
increases significantly at higher moisture content); thickness 15.2
microns; Film Elongation at Break, MD 100% 10%/min.; ASTM D638 Film
Elongation at Break, TD 100% 10%/min.; ASTM D638 Secant Modulus, MD
3.50 GPa; Youngs Modulus, ASTM D638, 10%/min.; Secant Modulus, TD
3.50 GPa; Youngs Modulus, ASTM D638, 10%/min.; Elmendorf Tear
Strength MD 260 g; ASTM D638 Elmendorf 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 Strength at
Break, 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-.degree. C.; Thermal Conductivity 0.340 W/m-K;
Melting Point 181.degree. C. DSC; Haze 0.500% 65% RH; Gloss 95.0%
65% RH. EVAL.RTM. ethylene vinyl alcohol films are available from
Kuraray America, Inc. of Houston, Tex.
[0450] Nylon
[0451] Nylon is a generic designation for a family of synthetic
polymers known generically as polyamides. Nylon is a thermoplastic
silky material. There are two common methods of making nylon for
fiber applications. In one approach, molecules with an acid (COOH)
group on each end are reacted with molecules containing amine (NH2)
groups on each end. The resulting nylon is named on the basis of
the number of carbon atoms separating the two acid groups and the
two amines. These are formed into monomers of intermediate
molecular weight, which are then reacted to form long polymer
chains.
[0452] Solid nylon is used for mechanical parts such as machine
screws, gears and other low- to medium-stress components previously
cast in metal. Engineering-grade nylon is processed by extrusion,
casting, and injection molding. Solid nylon is used in hair combs.
Type 6/6 Nylon 101 is the most common commercial grade of nylon,
and Nylon 6 is the most common commercial grade of molded nylon.
Nylon is available in glass-filled variants which increase
structural and impact strength and rigidity, and molybdenum
sulfide-filled variants which increase lubricity.
[0453] Aramids are another type of polyamide with quite different
chain structures which include aromatic groups in the main chain.
Such polymers make excellent ballistic fibers.
[0454] Nylons are condensation copolymers formed by reacting equal
parts of a diamine and a dicarboxylic acid, so that peptide bonds
form at both ends of each monomer in a process analogous to
polypeptide biopolymers. The numerical suffix specifies the numbers
of carbons donated by the monomers; the diamine first and the diced
second. The most common variant is nylon 6-6 which refers to the
fact that the diamine (hexamethylene diamine) and the diacid
(adipic acid) each donate 6 carbons to the polymer chain. As with
other regular copolymers like polyesters and polyurethanes, the
"repeating unit" consists of one of each monomer, so that they
alternate in the chain. Since each monomer in this copolymer has
the same reactive group on both ends, the direction of the amide
bond reverses between each monomer, unlike natural polyamide
proteins which have overall directionality. In the laboratory,
nylon 6-6 can also be made using adipoyl chloride instead of
adipic. It is difficult to get the proportions exactly correct, and
deviations can lead to chain termination at molecular weights less
than a desirable 10,000 daltons. To overcome this problem, a
crystalline, solid "nylon salt" can be formed at room temperature,
using an exact 1:1 ratio of the acid and the base to neutralize
each other. Heated to 285.degree. C., the salt reacts to form nylon
polymer. Above 20,000 daltons, it is impossible to spin the chains
into yarn, so to combat this some acetic acid is added to react
with a free amine end group during polymer elongation to limit the
molecular weight. In practice, and especially for nylon 6,6, the
monomers are often combined in a water solution. The water used to
make the solution is evaporated under controlled conditions, and
the increasing concentration of "salt" is polymerized to the final
molecular weight.
[0455] Homopolymer nylon 6, or polycaprolactam, is not a
condensation polymer, but formed by a ring-opening polymerization
(alternatively made by polymerizing aminocaproic acid). The peptide
bond within the caprolactam is broken with the exposed active
groups on each side being incorporated into two new bonds as the
monomer becomes part of the polymer backbone. In this case, all
amide bonds lie in the same direction, but the properties of nylon
6 are sometimes indistinguishable from those of nylon 6,6--except
for melt temperature (N6 is lower) and some fiber properties in
products like carpets and textiles. There is also nylon 9.
[0456] Nylon 5,10, made from pentamethylene diamine and sebacic
acid has superior properties, but is more expensive to make. In
keeping with this naming convention, "nylon 6,12" (N-6,12) or
"PA-6,12" is a copolymer of a 6C diamine and a 12C diacid.
Similarly for N-5,10 N-6,11; N-10,12, etc. Other nylons include
copolymerized dicarboxylic acid/diamine products that are not based
upon the monomers listed above. For example, some aromatic nylons
are polymerized with the addition of diacids like 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 others. Because of the way polyamides are
formed, nylon can seem to be limited to unbranched, straight
chains. But "star" branched nylon can be produced by the
condensation of dicarboxylic acids with polyamines having three or
more amino groups.
[0457] Above their melting temperatures, Tm, thermoplastics like
nylon are amorphous solids or viscous fluids in which the chains
approximate random coils. Below Tm, amorphous regions alternate
with regions which are lamellar crystals. The amorphous regions
contribute elasticity and the crystalline regions contribute
strength and rigidity. The planar amide (--CO--NH--) groups are
very polar, so nylon forms multiple hydrogen bonds among adjacent
strands. Because the nylon backbone is so regular and symmetrical,
especially if all the amide bonds are in the trans configuration,
nylons often have high crystallinity and make excellent fibers. The
amount of crystallinity depends on the details of formation, as
well as on the kind of nylon. Apparently it can never be quenched
from a melt as a completely amorphous solid.
[0458] Nylon 6,6 can have multiple parallel strands aligned with
their neighboring peptide bonds at coordinated separations of
exactly 6 and 4 carbons for considerable lengths, so the carbonyl
oxygens and amide hydrogens can line up to form interchain hydrogen
bonds repeatedly, without interruption. Nylon 5,10 can have
coordinated runs of 5 and 8 carbons. Thus parallel (but not
antiparallel) strands can participate in extended, unbroken,
multi-chain .beta.-pleated sheets, a strong and tough
supermolecular structure similar to that found in natural silk
fibroin and the .beta.-keratins in feathers (proteins have only an
amino acid a-carbon separating sequential --CO--NH-- groups). Nylon
6 will form uninterrupted H-bonded sheets with mixed
directionalities, but the .beta.-sheet wrinkling is somewhat
different. The three-dimensional disposition of each alkane
hydrocarbon chain depends on rotations about the 109.47.degree.
tetrahedral bonds of singly-bonded carbon atoms.
[0459] Block nylon tends to be less crystalline, except near the
surfaces due to shearing stresses during formation. Nylon is clear
and colorless, or milky, but is easily dyed. Multistranded nylon
cord and rope is slippery and tends to unravel. The ends can be
melted and fused with a heat source such as a flame or electrode to
prevent this.
[0460] When dry, polyamide is a good electrical insulator. However,
polyamide is hygroscopic. The absorption of water will change some
of the material's properties such as its electrical resistance.
Nylon is less absorbent than wool or cotton.
[0461] Nylon can be used as the matrix material in composite
materials, with reinforcing fibers like glass or carbon fiber, and
has a higher density than pure nylon. Such thermoplastic composites
(25% glass fiber) are frequently used in car components next to the
engine, such as intake manifolds, where the good heat resistance of
such materials makes them feasible competitors to metals.
[0462] All nylons are susceptible to hydrolysis, especially by
strong acids, a reaction essentially the reverse of the synthetic
reaction shown above. The molecular weight of nylon products so
attacked drops fast, and cracks form quickly at the affected zones.
Lower members of the nylons (such as nylon 6) are affected more
than higher members such as nylon 12. This means that nylon parts
cannot be used in contact with sulfuric acid for example, such as
the electrolyte used in lead-acid batteries. When being molded,
nylon must be dried to prevent hydrolysis in the molding machine
barrel since water at high temperatures can also degrade the
polymer.
[0463] Polyimide (PI)
[0464] Polyimide is a polymer of imide monomers. Thermosetting
polyimides are commercially available as uncured resins, stock
shapes, thin sheets, laminates and machines parts. Thermoplastic
polyimides are very often called pseudothermoplastic. There are two
general types of polyimides. One type, so-called linear polyimides,
is made by combining imides into long chains. Aromatic heterocyclic
polyimides are the other usual kind. Examples of polyimide films
include Apical, Kapton, UPILEX, VTEC PI, Norton TH and Kaptrex.
Polyimide parts and shapes include VTEC PI, Meldin, Vespel and
typical monomers include pyromellitic dianhydride and
4,4'-oxydianiline.
[0465] Thermosetting polyimides are known for thermal stability,
good chemical resistance, excellent mechanical properties, and
characteristic orange/yellow color. Polyimides compounded with
graphite or glass fiber reinforcements have flexural strengths of
up to 50,000 psi and flexural moduli of 3,000,000 psi. Thermoset
polyimides exhibit very low creep and high tensile strength. These
properties are maintained during continuous use to temperatures of
232.degree. C. and for short excursions, as high as 482.degree. C.
Molded polyimide parts and laminates have very good heat
resistance. Normal operating temperatures for such parts and
laminates range from cryogenic to those exceeding 260.degree. C.
Polyimides are also inherently resistant to flame combustion and do
not usually need to be mixed with flame retardants. Most carry a UL
rating of VTM-0. Polyimide laminates have a flexural strength
half-life at 249.degree. C. of 400 hours.
[0466] Typical polyimide parts are not affected by commonly used
solvents and oils including hydrocarbons, esters, ethers, alcohols
and freons. They also resist weak acids but are not recommended for
use in environments that contain alkalis or inorganic acids. Some
polyimides, such as CP1 and CORIN XLS, are solvent-soluble and
exhibit high optical clarity. The solubility properties lend them
towards spray and low temperature cure applications.
[0467] The polyimide materials are lightweight, flexible, resistant
to heat and chemicals. Therefore, they are used in the electronics
industry for flexible cables, as an insulating film on magnet wire
and for medical tubing. For example, in a laptop computer, the
cable that connects the main logic board to the display (which must
flex every time the laptop is opened or closed) is often a
polyimide base with copper conductors. The semiconductor industry
uses polyimide as a high-temperature adhesive; it is also used as a
mechanical stress buffer. Some polyimide can be used like a
photoresist; both "positive" and "negative" types of
photoresist-like polyimide exist in the market.
[0468] Thermoset film polyimide has the following properties:
Density 1.40-1.67 g/cc; Water Absorption 1.40-3.00%; Moisture
Absorption at Equilibrium 0.400-1.80%; Water Absorption at
Saturation 1.20-2.50%; Moisture Vapor Transmission 2.40-17.5
cc-mm/m.sup.2-24 hr-atm; Oxygen Transmission 9.90 cc-mm/m.sup.2-24
hr-atm; Thickness 22.0-187 microns; Film Tensile Strength at Yield,
MD 49.0-255 MPa; Film Tensile Strength at Yield, TD 100-160 MPa;
Film Elongation at Break, MD 10.0-85.0%; Film Elongation at Yield,
MD 40.0-50.0%; Film Elongation at Yield, TD 45.0-55.0%; Tensile
Strength, Yield 73.3-160 MPa; Elongation at Yield 10.0-45.0%;
Poisson Ratio 0.340; Secant Modulus 2.28-5.20 GPa; Secant Modulus,
MD 1.76-9.12 GPa; Impact Test 0.686-1.56 J; Coefficient of Friction
0.400-0.480; Coefficient of Friction, Static 0.630; Tear Strength
Test 7.20-430; 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 Resistivity 1.00e+10-2.30e+17 ohm-cm; 1.00e+15-1.00e+16
ohm-cm @Temperature 200.degree. C.; Surface Resistance
10000-1.00e+17 ohm; 1.00e+15-1.00e+15 ohm @Temperature 200.degree.
C.; Dielectric Constant 2.70-4.00; Dielectric Strength 48.0-272
kV/mm @Temperature 200.degree. C.; Dissipation Factor
0.00130-0.0100; CTE, linear 12.0-20.0 .mu.m/m-.degree. C.;
32.0-40.0 .mu.m/m-.degree. C. @Temperature 100-300.degree. C.;
Specific Heat Capacity 1.09-1.13 J/g-.degree. C.; Thermal
Conductivity 0.120-0.289 W/m-K; Maximum Service Temperature, Air
180-400.degree. C.; Minimum Service Temperature, Air -269.degree.
C.; Glass Temperature 360-500.degree. C.; Oxygen Index 37.0-66.0%;
Shrinkage 0.0100-0.200%; Refractive Index 1.70.
[0469] Liquid Crystal Polymer (LCP)
[0470] Liquid-crystal polymers (LCPs) are a class of aromatic
polyester polymers. They are extremely unreactive and inert, and
highly resistant to fire. Liquid crystallinity in polymers may
occur either by dissolving a polymer in a solvent (lyotropic
liquid-crystal polymers) or by heating a polymer above its glass or
melting transition point (thermotropic liquid-crystal polymers).
Liquid-crystal polymers are present in melted/liquid or solid form.
In liquid form liquid-crystal polymers have primarily applications
in liquid-crystal displays (LCDs). In solid form the main example
of lyotropic LCPs is the commercial aramid known as Kevlar. The
chemical structure of this aramid consists of linearly substituted
aromatic rings linked by amide groups. In a similar way, several
series of thermotropic LCPs have been commercially produced by
several companies (e.g., Vectra). A high number of LCPs, produced
in the 1980s, displayed order in the melt phase analogous to that
exhibited by nonpolymeric liquid crystals. Processing of LCPs from
liquid-crystal phases (or mesophases) gives rise to fibers and
injected materials having high mechanical properties as a
consequence of the self-reinforcing properties derived from the
macromolecular orientation in the mesophase. Today, LCPs can be
melt-processed on conventional equipment at high speeds with
excellent replication of mold details.
[0471] A unique class of partially crystalline aromatic polyesters
based on p-hydroxybenzoic acid and related monomers, liquid-crystal
polymers is capable of forming regions of highly ordered structure
while in the liquid phase. However, the degree of order is somewhat
less than that of a regular solid crystal. Typically LCPs have a
high mechanical strength at high temperatures, extreme chemical
resistance, inherent flame retardancy, and good weatherability.
Liquid-crystal polymers come in a variety of forms from sinterable
high temperature to injection moldable compounds. LCP can be
welded, though the lines created by welding are a weak point in the
resulting product. LCP has a high Z-axis coefficient of thermal
expansion.
[0472] LCPs are exceptionally inert. They resist stress cracking in
the presence of most chemicals at elevated temperatures, including
aromatic or halogenated hydrocarbons, strong acids, bases, ketones,
and other aggressive industrial substances. Hydrolytic stability in
boiling water is excellent. Environments that deteriorate the
polymers are high-temperature steam, concentrated sulfuric acid,
and boiling caustic materials. Because of their various properties,
LCPs are useful for electrical and mechanical parts, food
containers, and any other applications requiring chemical inertness
and high strength.
[0473] High-Density Polyethylene (HDPE)
[0474] High-density polyethylene (HDPE) or polyethylene
high-density (PEHD) is a polyethylene thermoplastic made from
petroleum. HDPE has little branching, giving it stronger
intermolecular forces and tensile strength than lower-density
polyethylene. It is also harder and more opaque and can withstand
somewhat higher temperatures (120.degree. C. for short periods,
110.degree. C. continuously). High-density polyethylene, unlike
polypropylene, cannot withstand normally-required autoclaving
conditions. The lack of branching is ensured by an appropriate
choice of catalyst (e.g., Ziegler-Natta catalysts) and reaction
conditions. HDPE contains the chemical elements carbon and
hydrogen. Hollow goods manufactured through blow molding are the
most common application area for HDPE.
[0475] Polypropylene (PP)
[0476] Polypropylene or polypropene (PP) is a thermoplastic
polymer, made by the chemical industry and used in a wide variety
of applications, including packaging, textiles (e.g. ropes, thermal
underwear and carpets), stationery, plastic parts and reusable
containers of various types, laboratory equipment, loudspeakers,
automotive components, and polymer banknotes. An addition polymer
made from the monomer propylene, it is rugged and unusually
resistant to many chemical solvents, bases and acids.
[0477] Most commercial polypropylene is isotactic and has an
intermediate level of crystallinity between that of low density
polyethylene (LDPE) and high density polyethylene (HDPE); its
Young's modulus is also intermediate. PP is normally tough and
flexible, especially when copolymerized with ethylene. This allows
polypropylene to be used as an engineering plastic, competing with
materials such as ABS. Polypropylene is reasonably economical, and
can be made translucent when uncolored but is not as readily made
transparent as polystyrene, acrylic or certain other plastics. It
is often opaque and/or colored using pigments. Polypropylene has
good resistance to fatigue.
[0478] Polypropylene has a melting point of .about.160.degree. C.
(320.degree. F.), as determined by Differential scanning
calorimetry (DSC). The MFR (Melt Flow Rate) or MFI (Melt Flow
Index) is a measure of PP's molecular weight. This helps to
determine how easily the molten raw material will flow during
processing. Higher MFR PPs fill the plastic mold more easily during
the injection or blow molding production process. As the melt flow
increases, however, some physical properties, like impact strength,
will decrease.
[0479] There are three general types of PP: homopolymer, random
copolymer and block copolymer. The comonomer used is typically
ethylene. Ethylene-propylene rubber or EPDM added to PP homopolymer
increases its low temperature impact strength. Randomly polymerized
ethylene monomer added to PP homopolymer decreases the polymer
crystallinity and makes the polymer more transparent.
[0480] Polypropylene is liable to chain degradation from exposure
to UV radiation such as that present in sunlight. For external
applications, UV-absorbing additives must be used. Carbon black
also provides some protection from UV attack. The polymer can also
be oxidized at high temperatures, a common problem during molding
operations. Anti-oxidants are normally added to prevent polymer
degradation.
[0481] The relative orientation of each methyl group relative to
the methyl groups on neighboring monomers has a strong effect on
the finished polymer's ability to form crystals, because each
methyl group takes up space and constrains backbone bending.
[0482] Like most other vinyl polymers, useful polypropylene cannot
be made by radical polymerization due to the higher reactivity of
the allylic hydrogen (leading to dimerization) during
polymerization. Moreover, the material that can result from such a
process can have methyl groups arranged randomly, so called atactic
PP. The lack of long-range order prevents any crystallinity in such
a material, giving an amorphous material with very little strength
and only specialized qualities suitable for niche end uses.
[0483] A Ziegler-Natta catalyst is able to limit incoming monomers
to a specific orientation, only adding them to the polymer chain if
they face the right direction. Most commercially available
polypropylene is made with such Ziegler-Natta catalysts, which
produce mostly isotactic polypropylene. With the methyl group
consistently on one side, such molecules tend to coil into a
helical shape; these helices then line up next to one another to
form the crystals that give commercial polypropylene many of its
desirable properties.
[0484] More precisely engineered Kaminsky catalysts have been made,
which offer a much greater level of control. Based on metallocene
molecules, these catalysts use organic groups to control the
monomers being added, so that a proper choice of catalyst can
produce isotactic, syndiotactic, or atactic polypropylene, or even
a combination of these. Aside from this qualitative control, they
allow better quantitative control, with a much greater ratio of the
desired tacticity than previous Ziegler-Natta techniques. They also
produce narrower molecular weight distributions than traditional
Ziegler-Natta catalysts, which can further improve properties.
[0485] To produce a rubbery polypropylene, a catalyst can be made
which yields isotactic polypropylene, but with the organic groups
that influence tacticity held in place by a relatively weak bond.
After the catalyst has produced a short length of polymer which is
capable of crystallization, light of the proper frequency is used
to break this weak bond, and remove the selectivity of the catalyst
so that the remaining length of the chain is atactic. The result is
a mostly amorphous material with small crystals embedded in it.
Since each chain has one end in a crystal but most of its length in
the soft, amorphous bulk, the crystalline regions serve the same
purpose as vulcanization.
[0486] Melt processing of polypropylene can be achieved via
extrusion and molding. Common extrusion methods include production
of melt blown and spun bond fibers to form long rolls for future
conversion into a wide range of useful products such as face masks,
filters, nappies and wipes. The most common shaping technique is
injection molding, which is used for parts such as cups, cutlery,
vials, caps, containers, housewares and automotive parts such as
batteries. The related techniques of blow molding and
injection-stretch blow molding are also used, which involve both
extrusion and molding.
[0487] The large number of end use applications for PP is often
possible because of the ability to tailor grades with specific
molecular properties and additives during its manufacture. For
example, antistatic additives can be added to help PP surfaces
resist dust and dirt. Many physical finishing techniques can also
be used on PP, such as machining. Surface treatments can be applied
to PP parts in order to promote adhesion of printing ink and
paints.
[0488] Since polypropylene is resistant to fatigue, most plastic
living hinges, such as those on flip-top bottles, are made from
this material. However, it is important to ensure that chain
molecules are oriented across the hinge to maximize strength. Very
thin sheets of polypropylene are used as a dielectric within
certain high performance pulse and low loss RF capacitors.
[0489] High-purity piping systems are built using polypropylene.
Stronger, more rigid piping systems, intended for use in potable
plumbing, hydronic heating and cooling, and reclaimed water
applications, are also manufactured using polypropylene. This
material is often chosen for its resistance to corrosion and
chemical leaching, its resilience against most forms of physical
damage, including impact and freezing, and its ability to be joined
by heat fusion rather than gluing.
[0490] Many plastic items for medical or laboratory use can be made
from polypropylene because it can withstand the heat in an
autoclave. Its heat resistance also enables it to be used as the
manufacturing material of consumer-grade kettles. Food containers
made from it will not melt in the dishwasher, and do not melt
during industrial hot filling processes. For this reason, most
plastic tubs for dairy products are polypropylene sealed with
aluminum foil (both heat-resistant materials). After the product
has cooled, the tubs are often given lids made of a less
heat-resistant material, such as LDPE or polystyrene. Such
containers provide a good hands-on example of the difference in
modulus, since the rubbery (softer, more flexible) feeling of LDPE
with respect to PP of the same thickness is readily apparent.
Rugged, translucent, reusable plastic containers made in a wide
variety of shapes and sizes for consumers from various companies
such as Rubbermaid and Sterilite are commonly made of
polypropylene, although the lids are often made of somewhat more
flexible LDPE so they can snap on to the container to close it.
Polypropylene can also be made into disposable bottles to contain
liquid, powdered or similar consumer products, although HDPE and
polyethylene terephthalate are commonly also used to make bottles.
Plastic pails, car batteries, wastebaskets, cooler containers,
dishes and pitchers are often made of polypropylene or HDPE, both
of which commonly have rather similar appearance, feel, and
properties at ambient temperature.
[0491] Polypropylene is a major polymer used in nonwovens, with
over 50% used for diapers or sanitary products where it is treated
to absorb water (hydrophilic) rather than naturally repelling water
(hydrophobic). Other interesting non-woven uses include filters for
air, gas and liquids where the fibers can be formed into sheets or
webs that can be pleated to form cartridges or layers that filter
in various efficiencies in the 0.5 to 30 micron range. Such
applications can be seen in the house as water filters or air
conditioning type filters. The high surface area and naturally
hydrophobic polypropylene nonwovens are ideal absorbers of oil
spills with the familiar floating barriers near oil spills on
rivers.
[0492] A common application for polypropylene is as Biaxially
Oriented polypropylene (BOPP). These BOPP sheets are used to make a
wide variety of materials including clear bags. When polypropylene
is biaxially oriented, it becomes crystal clear and serves as an
excellent packaging material for artistic and retail products.
[0493] Polypropylene's most common medical use is in the synthetic,
nonabsorbable suture Prolene, manufactured by Ethicon Inc.
[0494] Polypropylene is most commonly used for plastic moldings
where it is injected into a mold while molten, forming complex
shapes at relatively low cost and high volume, examples include
bottle tops, bottles and fittings.
[0495] Recently it has been produced in sheet form and this has
been widely used for the production of stationary folders,
packaging and storage boxes. The wide color range, durability and
resistance to dirt make it ideal as a protective cover for papers
and other materials. It is used in Rubik's cube stickers because of
these characteristics.
[0496] Expanded Polypropylene (EPP) is a foam form of
polypropylene. EPP has very good impact characteristics due to its
low stiffness; this allows EPP to resume its shape after impacts.
EPP is extensively used in model aircraft and other radio
controlled vehicles by hobbyists. This is mainly due to its ability
to absorb impacts, making this an ideal material for RC aircraft
for beginners and amateurs.
[0497] Silicon Dioxide (SiO2)
[0498] The chemical compound silicon dioxide, also known as silica,
is an oxide of silicon with a chemical formula of SiO2. Oxides of
silicon, commonly referred to as "SiOx," include silicon dioxide.
Silica is most commonly found in nature as sand or quartz, as well
as in the cell walls of diatoms. It is a principal component of
most types of glass and substances such as concrete. Silica is the
most abundant mineral in the Earth's crust.
[0499] SiO2 has a number of distinct crystalline forms in addition
to amorphous forms. With the exception of stishovite and fibrous
silica, all of the crystalline forms involve tetrahedral SiO4 units
linked together by shared vertices in different arrangements.
Silicon-oxygen bond lengths vary between the different crystal
forms. In a-quartz the Si--O--Si angle is 144.degree.. The only
stable form under normal conditions is a-quartz and this is the
form in which crystalline silicon dioxide is usually
encountered.
[0500] Silicon dioxide is formed when silicon is exposed to oxygen
(or air). A very thin layer (approximately 1 nm or 10 .ANG.) of
so-called `native oxide` is formed on the surface when silicon is
exposed to air under ambient conditions. Higher temperatures and
alternative environments are used to grow well-controlled layers of
silicon dioxide on silicon, for example at temperatures between 600
and 1200.degree. C., using the so-called "dry" or "wet" oxidation
with O2 or H2O, respectively. The thickness of the layer of silicon
replaced by the dioxide is 44% of the thickness of the silicon
dioxide layer produced. Alternative methods used to deposit a layer
of SiO2 include: Low temperature oxidation (400-450.degree. C.) of
silane; Decomposition of tetraethyl orthosilicate (TEOS) at
680-730.degree. C.; Plasma enhanced chemical vapor deposition using
TEOS at about 400.degree. C.; Polymerization of tetraethyl
orthosilicate (TEOS) at below 100.degree. C. using amino acid as
catalyst.
[0501] Pyrogenic silica (sometimes called fumed silica or silica
fume), which is a very fine particulate form of silicon dioxide, is
prepared by burning SiCl4 in an oxygen rich hydrocarbon flame to
produce a "smoke" of SiO2. Amorphous silica, silica gel, is
produced by the acidification of solutions of sodium silicate to
produce a gelatinous precipitate that is then washed and then
dehydrated to produce colorless microporous silica.
[0502] Aluminum Oxide (Al2O3)
[0503] Aluminum oxide is an amphoteric oxide of aluminum with 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 relatively high thermal conductivity
(40 Wm-1K-1) for a ceramic material. In its most commonly occurring
crystalline form, called corundum or a-aluminum oxide, its hardness
makes it suitable for use as an abrasive and as a component in
cutting tools. Aluminum oxide is responsible for resistance of
metallic aluminum to weathering. Metallic aluminum is very reactive
with atmospheric oxygen, and a thin passivation layer of alumina (4
nm thickness) forms in about 100 picoseconds on any exposed
aluminum surface. This layer protects the metal from further
oxidation. The thickness and properties of this oxide layer can be
enhanced using a process called anodizing. A number of alloys, such
as aluminum bronzes, exploit this property by including a
proportion of aluminum in the alloy to enhance corrosion
resistance. The alumina generated by anodizing is typically
amorphous, but discharge assisted oxidation processes such as
plasma electrolytic oxidation result in a significant proportion of
crystalline alumina in the coating, enhancing its hardness. The
most common form of crystalline alumina, a-aluminum oxide, is known
as corundum. Alumina also exists in other phases. Each has a unique
crystal structure and properties. Aluminum hydroxide minerals are
the main component of bauxite, the principal ore of aluminum.
Alumina tends to be multi-phase; e.g., constituting several of the
alumina phases rather than solely corundum.
[0504] Polyvinyl Alcohol (PVOH, PVA, or PVAL)
[0505] Polyvinyl alcohol (PVOH, PVA, or PVAL) is a water-soluble
synthetic polymer. Polyvinyl alcohol has excellent film forming,
emulsifying, and adhesive properties. It is also resistant to oil,
grease and solvent. It is odorless and nontoxic. It has high
tensile strength and flexibility, as well as high oxygen and aroma
barrier properties. However these properties are dependent on
humidity, in other words, with higher humidity more water is
absorbed. The water, which acts as a plasticizer, will then reduce
its tensile strength, but increase its elongation and tear
strength. PVA is fully degradable and is a quick dissolver. PVA has
a melting point of 230.degree. C. and 180-190.degree. C. for the
fully hydrolyzed and partially hydrolyzed grades, respectively. It
decomposes rapidly above 200.degree. C. as it can undergo pyrolysis
at high temperatures.
[0506] PVA is an atactic material but exhibits crystallinity as the
hydroxyl groups are small enough to fit into the lattice without
disrupting it. Unlike most vinyl polymers, PVA is not prepared by
polymerization of the corresponding monomer. The monomer, vinyl
alcohol, almost exclusively exists as the tautomeric form,
acetaldehyde. PVA instead is prepared by partial or complete
hydrolysis of polyvinyl acetate to remove acetate groups.
[0507] Nanopolymers
[0508] Polymer nanocomposite (PNC) is a polymer or copolymer having
dispersed in its nanoparticles. These may be of different shape
(e.g., platelets, fibers, spheroids), but at least one dimension is
in the range of 1 to 50 nm. The transition from micro- to
nano-particles leads to changes in physical as well as chemical
properties. Two of the major factors in this are the increase in
the ratio of the surface area to volume, and the size of the
particle. The increase in surface area-to-volume ratio, which
increases as the particles get smaller, leads to an increasing
dominance of the behavior of atoms on the surface area of particle
over that of those interior of the particle. This affects the
properties of the particles when they are reacting with other
particles. Because of the higher surface area of the nano-particles
the interaction with the other particles within the mixture is more
and this increases the strength, heat resistance etc. and many
factors do change for the mixture.
[0509] An example of a nanopolymer is silicon nanospheres which
show quite different characteristics. The particle size is 40-100
nm and it is much harder than silicon (a hardness between that of
sapphire and diamond). Many technical applications of biological
objects like proteins, viruses or bacteria such as chromatography,
optical information technology, sensors, catalysis and drug
delivery require their immobilization. Carbon nanotubes, gold
particles and synthetic polymers are used for this purpose. This
immobilization has been achieved predominantly by adsorption or by
chemical binding and to a lesser extent by incorporating these
objects as guests in host matrices. In the guest host systems, an
ideal method for the immobilization of biological objects and their
integration into hierarchical architectures should be structured on
a nanoscale to facilitate the interactions of biological
nano-objects with their environment. Due to the large number of
natural or synthetic polymers available and the advanced techniques
developed to process such systems to nanofibers, rods, tubes etc.
make polymers a good platform for the immobilization of biological
objects.
[0510] Polymer fibers are, in general, produced on a technical
scale by extrusion, e.g., a polymer melt or a polymer solution is
pumped through cylindrical dies and spun/drawn by a take-up device.
The resulting fibers have diameters typically on the 10-.mu.m scale
or above. To come down in diameter into the range of several
hundreds of nanometers or even down to a few nanometers,
electrospinning is today still the leading polymer processing
technique available. A strong electric field of the order of 103
V/cm is applied to the polymer solution droplets emerging from a
cylindrical die. The electric charges, which are accumulated on the
surface of the droplet, cause droplet deformation along the field
direction, even though the surface tension counteracts droplet
evolution. In supercritical electric fields, the field strength
overbears the surface tension and a fluid jet emanates from the
droplet tip. The jet is accelerated towards the counter electrode.
During this transport phase, the jet is subjected to strong
electrically driven circular bending motions that cause a strong
elongation and thinning of the jet, a solvent evaporation until,
finally, the solid nanofiber is deposited on the counter
electrode.
[0511] Electro spinning, co-electrospinning, and the template
methods based on nanofibers yield nano-objects which are, in
principle, infinitively long. For a broad range of applications
including catalysis, tissue engineering, and surface modification
of implants this infinite length is an advantage. But in some
applications like inhalation therapy or systemic drug delivery, a
well-defined length is required. The template method to be
described in the following has the advantage such that it allows
the preparation of nanotubes and nanorods with very high precision.
The method is based on the use of well-defined porous templates,
such as porous aluminum or silicon. The basic concept of this
method is to exploit wetting processes. A polymer melt or solution
is brought into contact with the pores located in materials
characterized by high energy surfaces such as aluminum or silicon.
Wetting sets in and covers the walls of the pores with a thin film
with a thickness of the order of a few tens of nanometers. This
process happens typically within a minute for temperatures about 50
K above the melting temperature or glass transition temperature,
even for highly viscous polymers, such as, for instance,
polytetrafluoroethylene, and this holds even for pores with an
aspect ratio as large as 10,000. To obtain nanotubes, the
polymer/template system is cooled down to room temperature or the
solvent is evaporated, yielding pores covered with solid layers.
The resulting tubes can be removed by mechanical forces for tubes
up to 10 .mu.m in length, e.g., by just drawing them out from the
pores or by selectively dissolving the template. The diameter of
the nanotubes, the distribution of the diameter, the homogeneity
along the tubes, and the lengths can be controlled.
[0512] The size-dependent and pressure-dependent glass transition
temperatures of free-standing films or supported films having weak
interactions with substrates decreases with decreasing of pressure
and size. However, the glass transition temperature of supported
films having strong interaction with substrates increases of
pressure and the decrease of size.
[0513] Nanocomposites are polymer structures that contain fillers,
typically silicate nanoclays, with at least one dimension in the
nanometer range. The fillers separate into tiny platelets that
disperse into a matrix of layers. Because the matrix of layers
creates a tortuous path for gasses trying to permeate through the
film, the barrier properties of the modified polymer are improved.
However, the challenge is to ensure that that the filler dispersion
is consistent. In addition to better barrier properties,
nanocomposites modified films also have improved dimensional
stability and stiffness and, because crystallinity is increased,
enhanced clarity. Nanocomposite masterbatches are commercially
available for nylon and polyolefins. The oxygen barrier of nylon
nanocomposite films can be as much as 50 percent higher than a
nonmodified nylon. Polyethylene and polypropylene nanocomposite
structures have shown improvement in gas barrier of 25 to 50
percent and in water vapor of 10 to 15 percent in laboratory
settings. Achieving consistent barrier properties on a commercial
scale remains challenging. Nanocomposite technology is very much an
emerging science. It shows a great deal of promise and as more
options become available for film applications it will have a
significant impact on barrier material options.
[0514] Saran
[0515] Saran is the trade name for a number of polymers made from
vinylidene chloride (especially polyvinylidene chloride or PVDC),
along with other monomers. Saran film has a very low permeability
to water vapor, flavor and aroma molecules, and oxygen compared to
other plastics. The barrier to oxygen prevents food spoilage, and
the barrier to flavor and aroma molecules helps food retain its
flavor and aroma. Saran also possesses gas barrier properties.
[0516] Polytrimethylene Terephthalate (PTT)
[0517] Polytrimethylene Terephthalate (PTT) is a semi crystalline
polymer that has many of the same advantages as PET. PTT exhibits
good tensile strength, flexural strength, and stiffness. It has
excellent flow and surface finish. PTT can have more uniform
shrinkage and better dimensional stability in some applications
than competing semicrystalline materials. PTT has excellent
resistance to a broad range of chemicals at room temperature,
including aliphatic hydrocarbons, gasoline, carbon tetrachloride,
perchloroethylene, oils, fats, alcohols, glycols, esters, ethers
and dilute acids and bases. Strong bases may attack PTT compounds.
Impact modifiers and reinforcing fibers (long glass, short glass,
or carbon) can be used to increase the impact properties, as well
as the strength and stiffness of PTT.
[0518] Polytrimethylene Naphthalate (PTN)
[0519] Poly(trimethylene phthalates or naphthalate) and copolymers
are aromatic polyesters made by polycondensation of 1,3-propanediol
(PDO) and terephthalic acid (PTT), isophthalic acid (PTI) or
naphthalic acid (PTN) and/or with comonomers (isophthalic acid,
1,4-butanediol, etc.). Films of PTN possess good barrier
properties.
[0520] Polyethylene Naphthalate (PEN)
[0521] 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
well-suited for bottling beverages that are susceptible to
oxidation, such as beer. It is prepared from ethylene glycol and
one or more naphthalene dicarboxylic acids by condensation
polymerization.
[0522] Polyurethane
[0523] A polyurethane is any polymer consisting of a chain of
organic units joined by urethane (carbamate) links. Polyurethane
polymers are formed through step-growth 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 cover an
extremely wide range of stiffness, hardness, and densities. Though
the properties of the polyurethane are determined mainly by the
choice of polyol, the diisocyanate exerts some influence, and must
be suited to the application. The cure rate is influenced by the
functional group reactivity and the number of functional isocyanate
groups. The mechanical properties are influenced by the
functionality and the molecular shape. The choice of diisocyanate
also affects the stability of the polyurethane upon exposure to
light. Polyurethanes made with aromatic diisocyanates yellow with
exposure to light, whereas those made with aliphatic diisocyanates
are stable. Softer, elastic, and more flexible polyurethanes result
when linear difunctional polyethylene glycol segments, commonly
called polyether polyols, are used to create the urethane links.
This strategy is used to make spandex elastomeric fibers and soft
rubber parts, as well as foam rubber. More rigid products result if
polyfunctional polyols are used, as these create a
three-dimensional cross-linked structure which, again, can be in
the form of a low-density foam.
[0524] Polyether Block Amide (PEBAX.RTM.)
[0525] Polyether block amide is a thermoplastic elastomer or a
flexible polyamide without plasticizer consisting of a regular
linear chain of rigid polyamide segments and flexible polyether
segments.
[0526] Parylene C
[0527] Parylene is the trade name for a variety of chemical vapor
deposited poly(p-xylylene) polymers used as moisture barriers and
electrical insulators. Among them, Parylene C is the most popular
due to its combination of barrier properties, cost, and other
manufacturing advantages.
[0528] Silicone
[0529] Silicones, also referred to as 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 backbone ( . . . --Si--O--Si--O--Si--O-- . . . )
with organic side groups attached to the silicon atoms, which are
four-coordinate. In some cases organic side groups can be used to
link two or more of these --Si--O-- backbones together. By varying
the --Si--O-- chain lengths, side groups, and crosslinking,
silicones can be synthesized with a wide variety of properties and
compositions. They can vary in consistency from liquid to gel to
rubber to hard plastic. The most common siloxane is linear
polydimethylsiloxane (PDMS), a silicone oil. The second largest
group of silicone materials is based on silicone resins, which are
formed by branched and cage-like oligosiloxanes.
Fabrication of the Composite Wall
[0530] The various layers of the composite wall, including the gas
barrier layers, need not be situated in any particular order, but
those of superior resistance to acidity, temperature, mechanical
abrasion, and superior biocompatibility profile are preferably
employed as layers contacting the gastric environment. Those with
superior resistance to, e.g., acidity and temperature, are
preferably employed as layers contacting the central lumen of the
balloon.
[0531] The various layers of the wall can include a single layer or
up to 10 or more different monolayers; however, a film thickness of
from 0.001 inches (0.0254 cm) to 0.004 inches (0.010 cm) thick is
desirable such that the resulting balloon compacted to fit into a
swallowable capsule. The resulting composite wall preferably has
good performance specifications with respect to each category
listed in Tables 1a-b.
[0532] Films that are co-extruded are advantageously employed, as
some adhesives may contain leachables that are undesirable from a
biocompatibility perspective. In addition, coextrusion allows for
better blending such that the materials maintain their original
properties when combined in this fashion and are less likely to be
subject to delamination when exposed to gastric motility
forces.
[0533] Combining films with similar properties, e.g., two film
layers with excellent gas barrier properties, in a composite wall
is advantageous for use in a gastric balloon containing nitrogen,
oxygen, CO.sub.2 or a mixture thereof as the inflation gas or where
the external environment the product is to be placed in, contains a
mixture of gases including CO.sub.2, e.g., the stomach. A primary
advantage of such composite films is that restrictions on film
thickness can be observed without sacrifice of gas barrier
properties. Such a configuration also contributes to reducing the
effects of processing damage (e.g., manufacturing and compacting)
and damage due to exposure to in vivo conditions (e.g., gastric
motility forces).
[0534] In a particularly preferred embodiment, the composite wall
includes a plurality of layers. The first layer is an outer
protective layer that is configured for exposure to the gastric
environment. This layer is resistant to mechanical forces, exposure
to water (vapor), abrasion, and high acidity levels. Nylon or more
specifically, Nylon 12 is particularly preferred for the layer
exposed to the gastric environment, and is especially resistant to
mechanical forces.
[0535] In an alternative embodiment, polyurethane is RF welded to
saran to yield a 6-7 mil thick composite wall. In another
embodiment, a five layer system is provided comprising a layer of
saran sandwiched between two polyurethane layers. Between the saran
layer and each of the polyurethane layers is a tie layer. The
layers can be welded together, co-extruded or adhered using an
adhesive. This tri-layer is then co-extruded to Nylon on each side,
and then a final sealing layer (polyethylene or the like) is added
to one of the nylon layers for the total composite wall. A
representative example of material combinations that are
commercially available or manufacturable is provided in Table 2.
The orientation of the layers (innermost--in contact with the
central balloon lumen, or outermost--in contact with the gastric
environment) is also indicated if more than two layers are
described to support a suggested composite wall.
[0536] Most of the film resins listed in Table 2 provide some
degree of gas barrier properties. Therefore, many can be used
solely to form the balloon wall as a monolayer film; however they
can also be used in conjunction with other film resins to meet the
desired gas retention and mechanical specifications for the useful
life of the balloon based on the inflation gas and external
environment the balloon is to be placed in. These film resins can
also be coated with gas barrier coatings listed in Tables 1a-b.
Additional film layers can be added to form the total composite
wall. While such additional layers may not impart substantial
barrier properties, they can provide structural and/or mechanical
properties, protection for the other layers of the composite wall
that are susceptible to water vapor, humidity, pH, or the like, or
other desirable properties. The film layers can be assembled using
various adhesives, via co-extrusion, via lamination, and/or using
tie layers and such to create a composite wall that meets the
requirements of an intragastric balloon suitable for use for at
least 25 days, or up to 90 days or more, with the specified gas
retention properties. Table 2 provides a list of layers and layer
combinations suitable for use in composite walls for an
intragastric balloon. The composite description, resin
abbreviation, configuration (single layer, bilayer, trilayer, or
the like) and trade name of commercially available combinations are
listed. The number of layers indicated does not include any
adhesive layers or tie layers used to fabricate the composite wall,
such that a 6-layer composite wall may, for example, have two or
three adhesive layers and/or tie layers that make up the total
composite wall, and therefore the total number of layers can be
eight or nine in final form. The term "layer" as used herein is a
broad term, and is to be given its ordinary and customary meaning
to a person of ordinary skill in the art (and is not to be limited
to a special or customized meaning), and refers without limitation
to a single thickness of a homogenous substance (e.g., a coating
such as SiOx, or a layer such as PET, or a uniform polymeric
blend), as well as to a supporting layer having a coating thereon
(wherein a "coating" is, e.g., a material typically employed in
conjunction with substrate that provides structural support to the
coating layer). For example, a PET-SiOx "layer" is referred to
herein, wherein a layer of Si-Ox is provided on a supporting PET
layer. In the following table, as well as other tables referring to
composite walls, a forward slash ("/") is used to indicate a
boundary between layers of the specified chemistries. The boundary
can be a discontinuity, or can be a tie layer, adhesive layer, or
other layer separating the layers of recited chemistry.
TABLE-US-00003 TABLE 2 Example Film Composite Walls* Abbreviation
Trade name polyethylene terephthalate PET Mylar metalized oriented
polyethylene metalized OPET Custom terephthalate polyvinyl alcohol
coated oriented PVOH coated OPP Bicor polypropylene metalized
biaxially oriented nylon 6 metalized OPA6 Custom Biaxally oriented
Nylon/ethylene OPA/EVOH/OPA Honeywell vinyl alcohol/biaxially
oriented Oxyshield Plus Nylon Nylon/ethylene vinyl alcohol/Low
Nylon/EVOH/LDPE Custom Density Polyethylene polyvinylidene chloride
coated PVDC/OPET Mylar oriented polyethylene terephthalate
polyvinylidene chloride coated PVCD/OPP Custom oriented
polypropylene polyvinylidene chloride coated PVCD/OPA6 Honeywell
biaxially oriented Nylon 6 Oxyshield high density
polyethylene/ethylene HDPE/EVOH Custom vinyl alcohol
polypropylene/ethylene vinyl PP/EVOH Custom alcohol laminate
polyethylene PET/EVOH Custom terephthalate/ethylene vinyl alcohol
metalized oriented polypropylene metalized OPP Custom sealable PVDC
coated oriented PVDC coated PP Custom polypropylene polyvinylidene
fluoride PVDF Custom Polyvinyl chloride PVC Custom polyvinyl
fluoride PVF Tedlar polychlorofluoroethylene PCTFE ACLAR UltRx,
SupRx, Rx amine-based epoxy coated Nylon epoxy coated PA6 Bairocade
polyvinyl chloride-polyvinylidene PVC-PVDC Custom chloride
copolymer medium density polyethylene MDPE Custom
Nylon/Polypropylene Nylon/PP laminate Custom Nylon-High Density
Polyethylene Nylon-HDPE laminate Custom Nylon 12/Ethyl Methyl
Co-extruded Nylon 12- Custom Co- Acrylate/Polyvinylidene Chloride/
encapsulated PVDC-Nylon 12- extruded blend Ethyl Methyl
Acrylate/Nylon LLDPE + LDPE 12/Linear Low Density Polyethylene +
Low Density Polyethylene Multi-layer Nylon 12/Linear Low
Co-extruded multi-layer Nylon 12- Custom Co- Density Polyethylene +
Low LLDPE + LDPE Extruded Blend Density Polyethylene acetylene
plasma coating on PET/A Custom polyester difluoroethylene coating
on PET/DA Custom polyethylene terephthalate oriented polypropylene
OPP Custom cast propylene CPP Custom high density polyethylene HDPE
Custom cyclic olefin copolymer COC Custom oriented polystyrene OPS
Custom Fluorinated Ethylene Propylene FEP Custom difluoroethylene
coating on low LDPE/D Custom density polyethylene difluoroethylene
coating on PP/D Custom polypropylene acetylene plasma coating on
PP/A Custom polypropylene acetylene plasma coating on low LDPE/A
Custom density polyethylene polybutylene terephthalate TPC-ET
Hytrel polyether glycol copolymer polyether block amide TPE PEBA
Pebax oxide coated biaxially oriented oxide coated PA Honeywell
Nylon Oxyshield Ultra Nanoclay/nylon MXD6/Nanoclay Imperm/Aegis
OXCE Polyethylene PET/SiOx BestPET/ Terephthalate/Silicone Dioxide
TechBarrier Polyethylene PET + 02 Scavengers MonoxBar
Terephthalate/Oxygen scavengers Modified Polyethylene Modified PET
DiamondClear Terephthalate Polyethylene Terephthalate/Nylon 6
PET/MXD6 HP867 Amorphous polyvinyl alcohol Amorphous PVOH Nichigo
G- Polymer Nylon 6/Ethyl vinyl Nylon 6/EVOH/LLDPE Custom
alcohol/Linear Low Density Polyethylene Ethyl vinyl alcohol/Poly-
EVOH/PP/EVOH Custom Propylene/Ethyl vinyl alcohol Ethyl vinyl
alcohol/Nylon EVOH/Nylon Custom Polyethylene/Ethyl vinyl PE/EVOH/PE
Custom alcohol/Polyethylene Polyethylene/Ethyl vinyl alcohol/
PE/EVOH/PET Custom Polyethylene Terephthalate Silicon
dioxide-coated PET-SiOx/LLDPE/EVOH/LLDPE Custom Polyethylene
Terephthalate/Linear Low Density Polyethylene/Ethyl vinyl
alcohol/Linear Low Density Polyethylene Aluminum Oxide-coated
PET-Al.sub.2O.sub.3/LLDPE Custom Polyethylene
Terephthalate/Polyethylene Polyethylene/Ethyl vinyl PE/EVOH/LLDPE
Custom alcohol/Linear Low Density Polyethylene Polyethylene
Terephthalate/ PET/PE/OEVOH/PE Custom Polyethylene/Polyethylene/Bi-
axially oriented Ethyl vinyl alcohol Polyethylene Terephthalate/
PET/PE/EVOH/EVOH/EVOH/PE Custom Polyethylene/Ethyl vinyl alcohol/
Ethyl vinyl alcohol/Ethyl vinyl alcohol/Polyethylene Polyethylene
Terephthalate/ PET/PE/Nylon 6/EVOH/Nylon Custom Polyethylene/Nylon
6/Ethyl vinyl 6/PE alcohol/Nylon 6/Polyethylene Silicon
dioxide-coated PET-SiOx/PE/EVOH/PE Custom Polyethylene
Terephthalate/ Polyethylene/Ethyl vinyl alcohol/ Polyethylene
Polyethylene/Ethyl vinyl PE/EVOH/PVDC Custom
alcohol/polyvinylchloride Polyethylene Terephthalate/
PET/LLDPE/EVOH/LLDPE Custom Linear Low Density Polyethylene/Ethyl
vinyl alcohol/ Linear Low Density Polyethylene Kurrarister C-coated
Polyethylene PET-Kurrarister-C/PE/EVOH/PE Custom
Terephthalate/Polyethylene/Ethyl vinyl alcohol/Polyethylene
Polyethylene Terephthalate/ PET/PE/Nylon 6/EVOH/Nylon Custom
Polyethylene/Nylon 6/Ethyl vinyl 6/PE alcohol/Nylon 6/Polyethylene
Nylon 6/Ethyl vinyl alcohol/ Nylon 6/EVOH/PVDC/Nylon Custom
Polyvinylchloride/Low Density 6/LDPE Polyethylene Polyimide PI
Custom Polyimide/Linear Low Density PI/LLDPE Custom Polyethylene
Polyimide/Polyvinylchloride PI/PVdC Custom
Polyimide/Polyvinylchloride/ PI/PVdC/LLDPE Custom Linear Low
Density Polyethylene
[0537] In particularly preferred embodiments, the composite wall
has a thickness of 0.005 inches or less (5.0 mil or less); however,
in certain embodiments a thicker composite wall may be acceptable.
Generally it is preferred that the composite wall have a thickness
of no more than 0.004 inches (4.0 mil).
Fabrication of the Balloon
[0538] To ensure good mechanical strength of the balloon, the
balloon is preferably thermoformed and sealed such that the edges
of the pieces used to form the balloon are overlapping. This can be
accomplished by any suitable method. For example, two flat sheets
of material can be placed in a frame with magnetized edges to hold
the two sheets in place. Slack can be added to the piece of film to
orient the material such that it maintains its properties after the
thermoforming process. The frame can be placed over a mold that
represents a hemisphere the balloon. A heater (e.g., a 4520 watt
infrared heater) can be used to form the material, and a vacuum can
be pulled. The material, with slack put in it prior to vacuum being
applied, re-orients the material such that it is more evenly
distributed around the hemisphere shape. The material is preferably
thickest in the middle and is made thinner on the sides where it
will be welded to a second piece to create a sphere or ellipsoid
having a substantially uniform wall thickness. For example,
starting with a 0.0295'' film, the middle of the film or subsequent
apex has an ending film thickness of 0.0045'' and the edges have an
ending thickness of 0.0265'' for subsequent overlapping during the
welding process.
[0539] The valve can be adhered to the (e.g., polyethylene, PE)
side of one of the hemispheres and protrude out of the opposite
(e.g., nylon) side. One hemisphere typically consists of Nylon as
the outermost layer and the second hemisphere typically has
polyethylene (sealing web) as the outermost layer. The edges of the
two hemispheres are preferably aligned such that they overlap by at
least 1 mm and no more than 5 mm. Alignment and overlay of the two
hemispheres is done to compensate for the thinning at the edges
during the thermoforming process, which in turn inhibits seam
bursts in vivo. Each half of the spheroid is placed on a fixture
and the excess from the thermoforming process is trimmed. On a
multi-layer film, the sealing layer, a PE or similar layer is
bonded to the sealing layer of the second film half. To do this the
film of the hemisphere that has the nylon exposed to the external
environment is folded up along the edges of the sphere on one half
such that it can be bonded to the hemisphere with the polyethylene
on the outermost layer.
[0540] The two film pieces are then sealed using a roller bonder or
a band heater. In the roller bonder, the air provides the
compression, the heater provides the sealing heat, and a motor that
moves the bonder around the area controls the time that is required
to ensure proper sealing. In the band heater, there is a heating
element, an expandable plug that provides the compression, and a
timer. The band is a metal, preferably copper and a spool-like
fixture provides the compression needed. Using film layers of
different melt temperatures helps ensure integrity of the barrier
layers of the final balloon configuration. If two similar materials
are welded, then an insulator can be employed. In a preferred
embodiment, one sphere is provided with the Nylon layer facing out
and the second sphere has a PE layer facing out.
Balloons with Resistance to Spontaneous Deflation
[0541] The largest percentage of intragastric balloon malfunctions
is due to spontaneous deflations. Spontaneous deflations can occur
due to (1) external puncture of the intragastric balloon due to
gastric motility forces, (2) over inflation of the balloon due to
increased internal pressure of the balloon from uptake of the
gastric environment of the gasses and water vapor and (3) under
inflation of the balloon that leads to fatiguing of the excess
material and subsequent puncture of the balloon. By managing these
two variables and tuning these variables to withstand the dynamic
gastric environment, the balloon system can be tailored to ensure
it remains inflated throughout its useful life. Instances of
spontaneous deflation in this intragastric balloon can be minimized
by selection of the starting inflation gas in conjunction with
selection of the composite wall materials and construction.
Selection of the permeability characteristics with respect to water
vapor transmission and gas permeability of the composite wall so as
to take advantage of the properties of the gastric space contents
can enable the rate of diffusion of gases into and out of the
balloon to be controlled. This method allows for a tunable method
for prevention of under inflation and over inflation.
[0542] Another phenomenon seen with gastric balloons and obesity in
general is stomach accommodation. In the process of stomach
accommodation, the stomach grows to accommodate the space occupying
device or excess food that is ingested. In the process of stomach
accommodation, the volume of a stomach containing an intragastric
balloon grows over time, such that the patient becomes hungrier.
However, by controlling gas diffusion and water vapor transmission
across the balloon wall over time, the balloon size can also be
increased over time by selecting the starting inflation gas(es) and
water and other in vivo gas permeability characteristics of the
film so as to maintain weight loss. In addition to spontaneous
deflations, selecting the permeability characteristics of the
composite wall in conjunction with the starting gases and utilizing
the transfer of gases and water inside of the balloon from the
gastric environment, the balloon can be designed to grow over its
useful life in response to stomach accommodation.
[0543] Experiments were performed wherein various starting
inflation gases were selected in conjunction with varying external
gas environments that mimic the stomach gas and water environment
in vivo. The stomach environment consists of water, acid
(hydrochloric acid), a mixture of gases, and chyme (the semifluid
mass of partly digested food expelled by the stomach into the
duodenum). Stomach gas usually arises from swallowing air during
eating. The composition of air is nitrogen (N.sub.2) 78.084%;
oxygen (O.sub.2) 20.9476%; argon (Ar) 0.934%; carbon dioxide
(CO.sub.2) 0.0314%; neon (Ne) 0.001818%; methane (CH.sub.4)
0.0002%; helium (He) 0.000524%; krypton (Kr) 0.000114%; hydrogen
(H.sub.2) 0.00005%; and xenon (Xe) 0.0000087%.
[0544] Five gases constitute greater than 99% of the gases in
gastrointestinal system: N.sub.2, O.sub.2, CO.sub.2, H.sub.2 and
methane, with nitrogen predominating. Gastric pCO.sub.2 closely
parallels local (splanchnic) arterial and draining venous blood
pCO.sub.2 values. Neutralization of stomach acid can also generate
gas. For example, when the stomach acid reacts with bicarbonates
(e.g., as are present in certain antacids) in the digestive juices,
the chemical process creates CO.sub.2, which is normally absorbed
into the blood stream. Digestion of food in the intestines, mainly
through fermentation by colonic bacteria, generates CO.sub.2,
H.sub.2, and methane. Microbes appear to be the sole source of all
of the hydrogen and methane produced in the intestine. These arise
from fermentation and digestion of nutrients (polysaccharides from
fruits and vegetables are not digested in the small intestines).
Small quantities of a few other gases, including hydrogen sulfide,
indoles, and ammonia can also be generated.
[0545] In certain embodiments, it is preferred that the composition
of the initial fill gas is substantially characteristic of the
composition of the mixture of gases in the in vivo gastric
environment. Such an initial fill gas can include only N.sub.2 and
CO.sub.2, or can include only N.sub.2, CO.sub.2, and O.sub.2, or
can include N.sub.2 and CO.sub.2 as well as one or more other gases
present in the in vivo environment (e.g., water vapor, H.sub.2,
CH.sub.4, Ar, H.sub.2S, or NH.sub.3). Argon or another inert gas
(or inert gases) can be substituted in part or in whole for
N.sub.2, which is considered an inert gas in the context of the
preferred embodiments. In those embodiments wherein the fill gas
includes only N.sub.2 or CO.sub.2, it is preferred that the initial
fill gas comprises from about 75% v/v to about 96% v/v N.sub.2,
from about 5% v/v to about 15% (vol.) O.sub.2, and from about 1%
v/v to about 10% v/v CO.sub.2, more preferably from about 80%
(vol.) to about 85% (vol.) N.sub.2, from about 5% (vol.) to about
13% (vol.) O.sub.2, and from about 4% (vol.) to about 8% (vol.)
CO.sub.2. In those embodiments wherein the fill gas includes only
N.sub.2 or CO.sub.2, it is preferred that the initial fill gas
comprises from about 4% (vol.) to about 8% (vol.) CO.sub.2, with
the remainder N.sub.2 or another inert gas. In embodiments wherein
the initial fill gas comprises other gases in addition to CO.sub.2
and the inert gas(es), it is preferred that the initial fill gas
comprises from about 4% (vol.) to about 8% (vol.) CO.sub.2.
[0546] Controlled self-inflation of the intragastric balloon in the
in vivo environment can be achieved by using a semi-permeable or
permeable composite wall in the balloon and initially filling the
balloon with a preselected single gas, such as N.sub.2 or O.sub.2.
The balloon utilizes differences in concentrations of gases and
water concentration differences between the internal balloon
environment and the external environment in vivo (GI/stomach) to
increase and/or decrease the volume and/or pressure over time. To
achieve a controlled decrease in volume and/or pressure, a wall can
be employed that has a relatively higher permeability to the single
gas used to inflate the balloon than to other gases present in the
in vivo gastrointestinal environment. For example, if nitrogen gas
is employed as the inflation gas, over time in the in vivo
environment, the volume and/or pressure in the balloon will
decrease as nitrogen diffuses out into the in vivo environment
through the oxygen permeable wall. Similarly, if oxygen gas is
employed as the inflation gas, over time in the in vivo
environment, the volume and/or pressure in the balloon will
decrease as oxygen diffuses out into the in vivo environment
through the oxygen permeable wall. The differential in partial
pressure of the single gas in the balloon (higher) versus the in
vivo environment (lower) will drive the process until equilibrium
or homeostasis is reached. To achieve a controlled increase in
volume and/or pressure, a wall can be employed that has a
relatively lower permeability to the single gas used to inflate the
balloon than to other gases present in the in vivo gastrointestinal
environment. For example, if nitrogen gas is employed as the
inflation gas, over time in the in vivo environment, the volume
and/or pressure in the balloon will increase as CO.sub.2, and all
of the other gases present in the gastric environment, diffuse into
the balloon through the CO.sub.2 permeable wall. The differential
in partial pressure of the permeable gas in the balloon (lower)
versus the in vivo environment (higher) will drive the process
until equilibrium is reached.
[0547] In addition, maintaining and/or controlling inflation of the
balloon can also be done using the differences in concentrations
between the internal balloon environment and external gastric
environment in which the balloon volume/pressure can be increased
or decreased as needed to extend the useful life of the product.
One reason to decrease the pressure can be to first inflate the
balloon with a large, but highly diffusible/soluble gas molecule
such as CO.sub.2 in addition to a more inert gas like nitrogen to
pre-stretch the balloon, with the soluble gas diffusing out of the
balloon and other gases not originally present in the balloon
migrating in to fill the balloon.
[0548] Inflation gases can be selected to start with the majority
of the gas in the balloon comprising a large, inert gas or a gas
that has low diffusivity through the selected composite wall.
Examples of inert gases include but are not limited to nitrogen, as
well as SF.sub.6, C.sub.2F.sub.6, C.sub.3F.sub.8, C.sub.4F.sub.10,
C.sub.4F.sub.8, C.sub.4F.sub.8, C.sub.3F.sub.6, CF.sub.4, and
CClF.sub.2--CF.sub.3. An inert gas in conjunction with a less inert
gas(es) that are more soluble in the gastric environment, can be
combined to comprise the starting balloon inflation gas composition
where the inert gas would be in excess to the more
soluble/diffusible gas. In certain embodiments, it is preferred to
combine nitrogen as a more soluble/diffusible gas with a gas of
lower diffusivity/solubility such as SF.sub.6, C.sub.2F.sub.6,
C.sub.3F.sub.8, C.sub.4F.sub.10, C.sub.4F.sub.8, C.sub.4F.sub.8,
C.sub.3F.sub.6, CF.sub.4, and CClF.sub.2--CF.sub.3. For example, a
fill gas of certain embodiments can comprise 5% (vol.) of the more
soluble/diffusible inert gas in combination with 95% (vol.) of the
less soluble/diffusible inert gas (e.g., 5% N.sub.2 in combination
with 95% SF.sub.6); or 10% of the more soluble/diffusible inert gas
in combination with 90% of the less soluble/diffusible inert gas
(e.g., 10% N.sub.2 in combination with 90% SF.sub.6); or 15% of the
more soluble/diffusible inert gas in combination with 85% of the
less soluble/diffusible inert gas (e.g., 15% N.sub.2 in combination
with 85% SF.sub.6); or 20% of the more soluble/diffusible inert gas
in combination with 80% of the less soluble/diffusible inert gas
(e.g., 20% N.sub.2 in combination with 80% SF.sub.6); or 25% of the
more soluble/diffusible inert gas in combination with 75% of the
less soluble/diffusible inert gas (e.g., 25% N.sub.2 in combination
with 75% SF.sub.6); or 30% of the more soluble/diffusible inert gas
in combination with 70% of the less soluble/diffusible inert gas
(e.g., 30% N.sub.2 in combination with 70% SF.sub.6); or 35% of the
more soluble/diffusible inert gas in combination with 65% of the
less soluble/diffusible inert gas (e.g., 35% N.sub.2 in combination
with 65% SF.sub.6); or 40% of the more soluble/diffusible inert gas
in combination with 60% of the less soluble/diffusible inert gas
(e.g., 40% N.sub.2 in combination with 60% SF.sub.6); or 45% of the
more soluble/diffusible inert gas in combination with 55% of the
less soluble/diffusible inert gas (e.g., 45% N.sub.2 in combination
with 55% SF.sub.6); or 50% of the more soluble/diffusible inert gas
in combination with 50% of the less soluble/diffusible inert gas
(e.g., 50% N.sub.2 in combination with 50% SF.sub.6). In certain
embodiments, an initial fill gas consisting of 20% of the less
soluble/diffusible inert gas with the remainder a more
soluble/diffusible inert gas is employed; or an initial fill gas
consisting of 19-21% of the less soluble/diffusible inert gas with
the remainder a more soluble/diffusible inert gas is employed; or
an initial fill gas consisting of 18-22% of the less
soluble/diffusible inert gas with the remainder a more
soluble/diffusible inert gas is employed; or an initial fill gas
consisting of 17-23% of the less soluble/diffusible inert gas with
the remainder a more soluble/diffusible inert gas is employed; or
an initial fill gas consisting of 16-24% of the less
soluble/diffusible inert gas with the remainder a more
soluble/diffusible inert gas is employed; or an initial fill gas
consisting of 15-25% of the less soluble/diffusible inert gas with
the remainder a more soluble/diffusible inert gas is employed. For
example, an initial fill gas comprising 18-20% SF.sub.6 with the
remainder as nitrogen can be employed, or 19-21% SF.sub.6 with the
remainder as nitrogen; or 18-22% SF.sub.6 with the remainder as
nitrogen; or 17-23% SF.sub.6 with the remainder as nitrogen; or
16-24% SF.sub.6 with the remainder as nitrogen; or 15-25% SF.sub.6
with the remainder as nitrogen.
[0549] Patient diet and medications can also affect/control balloon
inflation status--primarily by CO.sub.2 concentration effects
produced in the gastric environment. In addition, gastric pH also
affects CO.sub.2 concentration. This particular method can also
allow for a greater degree of tuning of the device's useful life
based on the composite wall material, e.g., barrier/non-barrier and
whether the gas that diffuses in is maintained longer in the
balloon if it has a barrier wall versus a non-barrier wall. This
particular form of self-inflation can be employed using a
self-inflating gastric balloon (e.g., initially inflated by a gas
generating reaction in the balloon initiated after swallowing), or
an inflatable gastric balloon (e.g., inflated using a catheter,
with or without endoscopic assistance, delivered nasogastrically or
any other delivery method). The method can be used with any gastric
balloon, including swallowable balloons and balloons placed in the
stomach by, e.g., endoscopic methods. The method is particularly
preferred for use in connection with intragastric devices; however,
it can also be applied to use in, e.g., pulmonary wedge catheters
and urinary incontinence balloon devices. The advantages to this
technology include the ability to compensate for stomach
accommodation, allowing the balloon to adapt to a stomach that may
increase in volume over time, thereby maintaining patient satiety.
It also permits starting with a smaller amount of inflation gas
constituents for a self-inflating balloon. It can prevent
spontaneous deflations by utilizing diffusion gradients between
gastric balloon systems and the in vivo gastric environment.
[0550] In a particularly preferred embodiment, used in connection
with a suitable inert gas such as SF.sub.6 and/or N.sub.2 (with or
without CO.sub.2 as an additional inflation gas) as the inflation
agent, a multi-layer co-extruded blend for the wall layers is
employed. 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
referred to as co-extruded Nylon 12-encapsulated PVDC-Nylon
12-LLDPE+LDPE multilayer). Another particularly preferred
configuration is a co-extruded multi-layer Nylon 12/Linear Low
Density Polyethylene+Low Density Polyethylene. Selection of the
resins for the composite wall construction (as well as selection of
using a coextrusion method or adhesives) can be varied to control
compliance (stretchiness), puncture resistance, thickness,
adhesion, sealing bond strength, orientation, acid resistance, and
permeability characteristics to gasses and water vapor to achieve a
particular effect.
Automatic Deflation of Intragastric Balloon Systems
[0551] The self-inflating (also referred to as automatic inflating)
or inflatable (also referred to as manually inflating) intragastric
balloon is provided with mechanisms to reliably control timing of
deflation. In preferred embodiments, the balloon auto-deflates and
passes through the stomach, through the lower gastrointestinal
tract, and out of the body at the end of its pre-determined useful
life (non-spontaneous), preferably between 30 and 90 days but can
be timed to deflate within 6 months. In the preferred embodiments
described below, the timing of deflation can be accomplished via
the external gastric environment (by conditions of temperature,
humidity, solubility, and/or pH, for example) or via the
environment within the lumen of the inflated balloon. It is
preferable for consistency to control the initiation of the
self-deflation process by manipulating the internal balloon
environment.
[0552] In other embodiments, the patch applied to allow for
inverted seams as described above and/or one or more additional
patches or other structures added to the balloon construction are
made out of an erodible, degradable, or dissolvable material
(natural or synthetic) and are incorporated into the wall of the
balloon. The patch(s) are of sufficient size to ensure opening of a
sufficient surface area to cause rapid deflation, and to prevent
re-inflation by seepage of stomach fluid into the balloon. The
balloon patch(s) comprise materials that can be applied to the
balloon such that a substantially smooth surface is maintained, and
preferably comprise a single layer or multi-layered material. The
patch(s) are constructed using an erodible, disintegrable,
degradable or other such material that is preferably
tissue-compatible and degrades into non-toxic products or is a
material that slowly hydrolyzes and/or dissolves over time (e.g.,
poly(lactic-co-glycolic acid) (PLGA), poly(lactide-co-glycolide)
(PLG), polyglycolic acid (PGA), polycaprolactone (PCL),
polyesteramide (PEA), polyhydroxyalkanoate (PHBV), polybutylene
succinate adipate (PBSA), aromatic copolyesters (PBAT),
poly(lactide-co-caprolactone) (PLCL), polyvinyl alcohol (PVOH),
polylactic acid (PLA), poly-L-lactic acid PLAA, pullulan,
polyethylene glycol (PEG), polyanhydrides, polyorthoesters,
polyaryletherketones (PEEK), multi-block polyetheresters,
poliglecaprone, polydioxanone, polytrimethylene carbonate, and
other similar materials). These erodible, disintegrable, or
degradable materials can be used alone, or in combination with
other materials, or can be cast into/co-extruded, laminated, and/or
dip coated in conjunction with non-erodible polymers (e.g., PET or
the like) and employed in the construction of the balloon.
Degradation/erosion occurs, is initiated by, and/or is controlled
by the gastric environment (e.g., by conditions of temperature,
humidity, solubility, and/or pH, for example), or is controlled
within the lumen of the balloon (e.g., by conditions of humidity
and/or derived pH, for example) based on what the patch is exposed
to. Thickness of the polymer as well as environment which affects
degradation and time of exposure can also facilitate degradation
timing. Degradation/erosion are timed such that they occur once the
pre-determined balloon useful life is completed (e.g., inflation is
maintained for from 25 to 90 days in vivo in the stomach before
degradation/erosion results in formation of an opening permitting
deflation). As an alternative to (or in connection with) using an
degradable material for the patch, the patch can comprise a similar
fluid retention barrier film or the same film as the remaining wall
of the balloon which is adhered to the balloon using a weak
adhesive, or welded or adhered such that after a specified amount
of time the patch delaminates from the applied area and allows for
an opening for inflation fluid release for deflation. Or if deemed
necessary for rapid deflation the entire balloon composite wall can
be made of the erodible material. The mechanism of using an
erodible material or a material that mechanically fails after a
pre-specified time is be similar for all embodiments for deflation
mechanisms described below as well. The timing of degradation or
erosion can be controlled using the external gastric environment
(e.g., by conditions of temperature, humidity, solubility, and/or
pH, for example) and/or can be controlled by conditions within the
lumen of the balloon (e.g., by conditions of humidity and/or pH of
residual liquid in the balloon).
[0553] In other embodiments, a plug or plugs (optionally in
conjunction another degradable retaining structure) can be
incorporated into the balloon construction and can consist, all or
in part, of an erodible, disintegrable, or otherwise degradable
synthetic or natural polymer similar to those described above
(e.g., PLGA, PLAA, PEG, or the like). The plug can be formed into
various shapes (e.g., cylinder shape) to achieve various
surface-to-volume ratios so as to provide a preselected and
predictable bulk degradation pattern for the erodible polymer. The
plug can incorporate a releasing mechanism that can be chemically
initiated after degradation/erosion begins, such that the septum or
plug material pops out of the balloon or falls inside of the
balloon, thereby creating a passageway for fluid release and
subsequent deflation of the balloon. Mechanical additions that can
be used in conjunction with a plug include a
degradable/erodible/disintegrable material that holds a plug (e.g.,
of a non-degradable or degradable material) in place or a
compressed spring housed within the retaining structure or plug
structure. More specifically one preferred embodiment to achieve
deflation can comprise a housing, a radial seal, a solid eroding
core, and a protective film attached to the external surface of the
eroding core. The inside of the eroding core is exposed to the
internal 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 is reduced
until there is clearance between the housing and the seal. Once
there is clearance, gas can move freely from the inside of the
balloon to the outside environment. The seal can fall out of the
housing and into the balloon. The diameter, length, and material
types can be adjusted in order to create the deflation at a desired
time point. Example materials for each component used to achieve
this deflation mechanism can be as follows: Housing: Biocompatible
structural material, capable of withstanding enough radial force to
form an air tight seal. Possible materials include: polyethylene,
polypropylene, polyurethane, UHMWPE, titanium, stainless steel,
cobalt chrome, PEEK, or nylon; Radial Seal: The radial seal needs
to be composed of a biocompatible elastic material, capable of
providing liquid and gas barrier to acidic environments. Possible
materials include: silicon, polyurethane, and latex; Eroding Core:
The eroding core needs to be a material capable of breaking down at
a predictable rate at given environmental conditions. Possible
materials include: PLGA, PLA, or other polyanhydrides that are
capable of losing integrity over time or any materials listed above
that provide erodible characteristics.
[0554] For the spring mechanism, once the material degrades, the
spring is released and/or the plug/septum is pulled into the
balloon or pushed out of the balloon, thus releasing fluid once an
orifice has been created by release of the spring mechanism and
pushing out or pulling in of the plug.
[0555] Another preferred embodiment is comprised of a septum,
moisture eroding material inside an inlet port, and moisture
absorbing expansion material. The eroding materials slowly erode
away when exposed to moisture, eventually exposing the moisture
absorbing expansion material. When the moisture expanding material
begins to absorb moisture, the expansion pulls the septum out of
position in the head by pushing against a septum lip or a ring
attached to the septum. Pulling the septum out of position causes
an immediate deflation of the balloon. In order to protect the
expanding material from moisture until a desired timepoint, the
expanding material can be sheathed in water blocking materials,
such as parylene, as well as slowly water degrading materials. The
moisture contact can be controlled by small inlet ports. The inlet
ports can be small holes, or a wick material that draws moisture in
a controlled manner. The desired deflation time is achieved through
a combination of eroding materials, blocking materials, and inlet
port sizing.
[0556] In certain embodiments, the balloon can incorporate one or
more plugs in the wall of the balloon that contain a compressed
pellet or gas releasing pellet. The pellet can be comprised of any
combination of constituents that, when activated, emit CO.sub.2 gas
(e.g., sodium bicarbonate and citric acid, or potassium bicarbonate
and citric acid, or the like). The pellet can be in tablet or rod
form protected by an erodible, disintegrable, or degradable
material that is preferably tissue-compatible and degrades into
non-toxic products or that slowly hydrolyzes and/or dissolves
similarly to the plugs and patches described above (e.g.,
poly(lactic-co-glycolic acid) (PLGA), polyvinyl alcohol (PVOH),
polylactic acid (PLA), poly-L-lactic acid PLAA, Pullulan,
Polyethylene Glycol, polyanhydrides, polyorthoesters,
polyaryletherketones (PEEK), multi-block polyetheresters,
poliglecaprone, polydioxanone, polytrimethylene carbonate, and
other like materials). Degradation/erosion of the plug initiates
the reaction of the two chemicals in the pellet and subsequently
leads to formation of gas (e.g., CO.sub.2). As sufficient gas is
trapped or built up, sufficient pressure is eventually generated to
push out the softened polymer material and create a larger channel
for the CO.sub.2 gas in the balloon to escape. External pressure
applied by the stomach to the balloon (e.g., squeezing) can
contribute to the process of creating a larger channel. Dimensions
and properties of the plug (diameter, thickness, composition,
molecular weight, etc.) comprised of the polymer drives the timing
of degradation.
[0557] In other embodiments, plugs or patches of different shapes
or sizes similar to those of the plugs described above can be
employed within the balloon lumen in a multi-layer configuration
including a semi-permeable membrane to facilitate balloon
deflation. The plug or patch is made of similar
degradable/erodible/dissolvable material as described above (e.g.,
poly(lactic-co-glycolic acid) (PLGA), polyvinyl alcohol (PVOH),
polylactic acid (PLA), PLAA, pullulan, and other like materials)
and contains a compartment enclosed by a semi-permeable membrane
(impermeable to an osmolyte) that contains a concentrated solution
of a solute or osmolyte (such as glucose, sucrose, other sugars,
salts, or combination thereof). Once the plug or patch begins to
degrade or erode, the water molecules move by osmosis down the
water gradient from the region of greater water concentration to
the region of lower water concentration across the semi-permeable
membrane into the hypertonic solution in the compartment. The
compartment containing the osmolyte swells and eventually bursts,
pushing the membranes and the degraded plug or patch out, thereby
allowing rapid gas loss through the newly created channels or
areas.
[0558] In certain embodiments, a balloon composed of a septum,
moisture eroding material inside an inlet port, and moisture
absorbing expansion material is employed. The eroding materials
slowly erode away when exposed to moisture, eventually exposing the
moisture absorbing expansion material. When the moisture expanding
material begins to absorb moisture, the expansion pulls the septum
out of position in the head by pushing against a septum lip or a
ring attached to the septum. Pulling the septum out of position
causes an immediate deflation of the balloon. In order to protect
the expanding material from moisture until a desired time point has
been reached, the expanding material can be sheathed in water
blocking materials, such as parylene, as well as slowly water
degrading materials. The moisture contact can be controlled by
small inlet ports. The inlet ports can be small holes, or a wick
material that draws moisture in a controlled manner. The desired
deflation time is achieved through a combination of eroding
materials, blocking materials, and inlet port sizing.
[0559] Another mechanism for self-deflation is to create a forced
de-lamination scheme, which can provide a larger surface area to
ensure rapid deflation. In, e.g., a balloon having a tri-layer
wall, the outermost layer is substantially strong enough to hold
the inflation fluid (e.g., polyethylene terephthalate (PET) or the
like), the middle layer is comprised entirely of an erodible
material (e.g., PVOH or the like) while the inner layer is
comprised of a weaker material (e.g., polyethylene (PE) or the
like). The PET or outermost layer is "scored" or hatched with
erodible material to create small channels that erode over time.
This creates channels such that the gastric fluid seeps into the
balloon layers and starts degrading the fully erodible material.
When the erodible layer degrades or dissolves, the material that
composes the innermost layer also erodes, degrades or dissolves
since it is not strong enough to withstand the gastric
forces/environment on its own. The balloon then collapses on itself
and eventually passes through the lower gastrointestinal tract.
Having an erodible layer sandwiched between a strong and weak layer
facilitates timing of erosion by creating a longer path length than
an erodible plug or patch affected by the gastric environment. The
distance between scores or openings can also be selected so as to
provide a desired deflation rate.
[0560] In another embodiment providing abrupt deflation of the
balloon after a desired period of time has elapsed, the composite
wall of the entire balloon or a section of the composite wall
(patch) includes several material layers that are slowly penetrated
by water that has been injected inside the balloon during the
manufacturing process or during the inflation process. This water
penetrates through the layers, eventually reaching a material that
substantially expands, rupturing a thin external protective later,
and creating a large hole for gas to escape and the balloon to
deflate. The water expanding material is protected from liquid via
a coating or sheath, such as parylene, which allows a controllable
amount of moisture exposure. Once water reaches the expansion
material, it exerts a force on the protective outer layer, causing
it to rupture. The outer layer may be created with a weakened
bonding area, a partially scored area, or other methods of ensuring
a desired rupture location and to facilitate desired timing for
auto-deflation to take place. There can be any number of layers
between the moist environment and the moisture expanding center.
Each material layer can have different erosion rates (e.g., fast or
slow) and can be selected by the predetermined time deflation is
desired to occur (e.g., after 30 days, 60 days, or more). By
varying the number, thickness, and rate of each of the
circumferential layers, the time to deflation can be accurately
controlled.
[0561] Alternatively a pressure sealing button that is adhesively
bonded over a perforation in the balloon material can be provided
for deflation. The adhesive bonding the button erodes over time
when it comes into contact with moisture derived from the gastric
fluid or that has been injected inside the balloon. Once the
adhesive can no longer bond and create an airtight seal between the
adhesive and the button, the balloon will rapidly deflate. By
controlling the hole size and moisture exposure of the adhesive,
the erosion time can be accurately predicted.
[0562] Deflation can also be facilitated by creating a series of
connecting ports within the septum or on another similar structure
attached to the balloon composite wall. The ports can be
constructed using a water- or acid-dissolving, biologically
compatible, low permeability substance, such as gelatin. The
diameter of the hole, number of holes, channel width, and channel
length can all be adjusted to control the dissolving parameters.
Once the material in the ports and channel is dissolved, there is a
clear path for gas trapped in the balloon to escape, eventually
resulting in a deflated balloon. The water can be gastric fluid or
controlled internally by including water inside the balloon at
assembly or during the inflation process. There can be a plurality
of port openings to guarantee gas transmits. Additionally, there
are several variables that can be adjusted to control dissolution
time: size of the port openings; 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 ultimately deflation.
[0563] A mechanism to facilitate passing involves an erosion
mechanism that allows for the balloon to be broken down into a size
that has a higher probability of predictably passing through the
lower gastrointestinal system. Preferably, the size of the balloon
as deflated is less than 5 cm long and 2 cm thick (similar to
various foreign objects of similar size that have been shown to
pass predictably and easily through the pyloric sphincter). This
can be accomplished by providing the balloon with "erodible seams."
One seam that breaks the balloon open into (at a minimum) two
halves, or more seams are provided so that a plurality of smaller
balloon pieces is produced in the dissociation reaction. The number
of seams used can be selected based on the original surface area of
the balloon and what is required to dissociate the balloon into
pieces that are of a size that can predictably pass through the
gastrointestinal tract more easily. The rate of seam erosion can be
controlled by using a material affected by, e.g., the external
gastric environment pH, liquid, humidity, temperature, or a
combination thereof. Seams can be single layer consisting of only
erodible material, or multi-layer. The timing of self-deflation can
be further controlled by the design of the seam layers, e.g.,
making the reaction and/or degradation of the seam material
dependent on the internal environment of the balloon instead of the
external environment. By manipulating the reaction such that
erosion or degradation is initiated by the internal environment
(e.g., the balloon's internal pH, humidity, or other factors), any
impact of person-to-person gastric variability (pH, etc.) that can
affect erosion timing is minimized. The internal balloon
environment can be manipulated by adding excess water at injection
to create a more humid internal environment, or the amount of
constituents added can be varied to manipulate the pH, etc.
Confirmation of Deflation of Intragastric Balloon Systems
[0564] Whether the balloon is self-deflating or non self-deflating,
various mechanisms may be implemented to confirm deflation of the
balloon. In preferred embodiments, the balloon deflates and emits a
sensory stimulant that is configured to trigger a response by one
of the patient's senses. In some embodiments, the device may emit
an odor that is smelled by the patient. In some embodiments, the
device may emit a taste that is tasted by the patient. In some
embodiments, the device may emit a coloring agent that the patient
can visually see after passing the agent, for example in a toilet.
In some embodiments, the sensory stimulant may cause a
physiological response indicative of deflation. For example, the
deflated balloon may emit a substance that encourages passage
through the bowels.
[0565] In some embodiments, flavorants may be used to indicate
deflation to the patient. Theses may be the same or different as
the flavoring agents that may be used in some embodiments, for
example with the ingestible event markers for a voltaic or pH based
locating system. Thus, flavorants such as peppermint, oil of
wintergreen, cherry flavoring or the like can also be used.
Additionally, it may be desirable to add a coloring agent to make
the dosage form more attractive in appearance or to help identify
the product.
Electromagnetic and Magnetic Tracking and Visualization
Subcomponents
[0566] Tracking and visualization functionality can be incorporated
into devices and systems described above. As used herein,
"visualization" is used broadly to refer to identifying an item of
interest in the body in a number of ways, including by magnetic
field data such as field strength, field orientation, temporal
characteristics of the field, the effects of the field on a
magnetic sensor, and other attributes of a magnetic field that may
be used to facilitate tracking, locating, identifying, and
characterizing a magnetic or magnetized item of interest, as well
as audio, visual, tactile, or other output based on the magnetic
data that characterizes the magnetized item of interest. Due to the
non-invasive nature of the present device, physicians may desire to
determine, or confirm, the location and orientation of the device
prior to inflation, during the course of treatment, or after
deflation. Accordingly, intragastric devices are provided that
incorporate magnetic components configured for enabling determining
and confirming the location, orientation and state of an
intragastric device at all phases of administration.
[0567] This section discusses magnetic components that may be
implemented in the electromagnetic and/or the magnetic embodiments
described herein. Although the terms "electromagnetic" and
"magnetic" may be used interchangeably in this disclosure, it is
understood that the electromagnetic embodiments include an "active"
sensor that generates a current in response to a magnetic field,
and that magnetic embodiments include a "passive" sensor that
generates a magnetic field. Particular embodiments of
electromagnetic and magnetic systems are described herein, for
example in the "Electromagnetic Real-Time Confirmation of
Placement" and the "Magnetic Real-Time Confirmation of Placement"
sections, respectively.
Markers
[0568] An electromagnetic or magnetic marker component may comprise
a variety of materials or objects that produce and/or are
responsive to a magnetic field. A magnetic field is a force that
attracts other ferromagnetic materials, such as iron, and attracts
or repels other magnets.
[0569] Magnetism is a class of physical phenomena that includes
forces exerted by magnets on other magnets. It has its origin in
electric currents and the fundamental magnetic moments of
elementary particles. These give rise to a magnetic field that acts
on other currents and moments. All materials are influenced to some
extent by a magnetic field. The strongest effect is on permanent
magnets, which have persistent magnetic moments caused by
ferromagnetism. Most materials do not have permanent moments. Some
are attracted to a magnetic field (paramagnetism); others are
repulsed by a magnetic field (diamagnetism); others have a much
more complex relationship with an applied magnetic field (spin
glass behavior and antiferromagnetism). Substances that are
negligibly affected by magnetic fields are known as non-magnetic
substances. They include copper, aluminum, gases, and plastic. Pure
oxygen exhibits magnetic properties when cooled to a liquid
state
[0570] Magnetic behavior including that exhibited by permanent
magnets, ferromagnetic and ferrimagnetic materials, paramagnetic
substances, and diamagnetic substances, can be employed in various
embodiments of a magnetic locating system to be used with
intragastric devices.
[0571] In some embodiments, the magnetic locating system may use
ferromagnetic or ferrimagnetic materials. Ferromagnetic and
ferrimagnetic materials are the ones normally thought of as
magnetic; they are attracted to a magnet strongly enough that the
attraction can be felt. These materials are the only ones that can
retain magnetization and become magnets. Ferrimagnetic materials,
which include ferrites and the oldest magnetic materials magnetite
and lodestone, are similar to but weaker than ferromagnetics. The
difference between ferro- and ferrimagnetic materials is related to
their microscopic structure.
[0572] In some embodiments, the magnetic locating system may use
paramagnetic substances. Paramagnetic substances, such as platinum,
aluminum, and oxygen, are weakly attracted to either pole of a
magnet. This attraction is hundreds of thousands of times weaker
than that of ferromagnetic materials, so it can only be detected by
using sensitive instruments or using extremely strong magnets.
Magnetic ferrofluids, although they are made of tiny ferromagnetic
particles suspended in liquid, are sometimes considered
paramagnetic since they cannot be magnetized.
[0573] In some embodiments, the magnetic locating system may use
diamagnetic substances. Diamagnetic materials are those repelled by
both poles of a magnet. Compared to paramagnetic and ferromagnetic
substances, diamagnetic substances, such as carbon, copper, water,
and plastic, are even more weakly repelled by a magnet. The
permeability of diamagnetic materials is less than the permeability
of a vacuum. All substances not possessing one of the other types
of magnetism are diamagnetic; this includes most substances.
Although force on a diamagnetic object from an ordinary magnet is
far too weak to be felt, using extremely strong superconducting
magnets, diamagnetic objects such as pieces of lead can be
levitated. Superconductors repel magnetic fields from their
interior and are strongly diamagnetic.
[0574] There are various other types of magnetism, such as spin
glass, superparamagnetism, superdiamagnetism, and metamagnetism,
each of which may be employed in various embodiments of the
magnetic locating system.
[0575] An electromagnet is made from a coil of wire that acts as a
magnet when an electric current passes through it but stops being a
magnet when the current stops. Often, the coil is wrapped around a
core of "soft" ferromagnetic material such as steel, which greatly
enhances the magnetic field produced by the coil.
[0576] Various properties of magnets and magnetized objects may be
used in embodiments of the magnetic locating system for
intragastric devices. These properties include, but are not limited
to, the magnetic field, magnetic moment, and magnetization.
[0577] The magnetic flux density (also called magnetic B field or
just magnetic field, usually denoted B) is a vector field. The
magnetic B field vector at a given point in space is specified by
two properties: 1) Its direction, which is along the orientation of
a compass needle, and 2) Its magnitude (also called strength),
which is proportional to how strongly the compass needle orients
along that direction. In SI units, the strength of the magnetic B
field is given in teslas.
[0578] A magnet's magnetic moment (also called magnetic dipole
moment and usually denoted .mu.) is a vector that characterizes the
magnet's overall magnetic properties. For a bar magnet, the
direction of the magnetic moment points from the magnet's south
pole to its north pole, and the magnitude relates to how strong and
how far apart these poles are. In SI units, the magnetic moment is
specified in terms of Am.sup.2 (amperes times meters squared).
[0579] A magnet both produces its own magnetic field and responds
to magnetic fields. The strength of the magnetic field it produces
is at any given point proportional to the magnitude of its magnetic
moment. In addition, when the magnet is put into an external
magnetic field, produced by a different source, it is subject to a
torque tending to orient the magnetic moment parallel to the field.
The amount of this torque is proportional both to the magnetic
moment and the external field. A magnet may also be subject to a
force driving it in one direction or another, according to the
positions and orientations of the magnet and source. If the field
is uniform in space, the magnet is subject to no net force,
although it is subject to a torque.
[0580] A wire in the shape of a circle with area A and carrying
current I is a magnet, with a magnetic moment of magnitude equal to
IA.
[0581] The magnetization of a magnetized material is the local
value of its magnetic moment per unit volume, usually denoted M,
with units A/m. It is a vector field, rather than just a vector
(like the magnetic moment), because different areas in a magnet can
be magnetized with different directions and strengths. A good bar
magnet may have a magnetic moment of magnitude 0.1 Am.sup.2 and a
volume of 1 cm.sup.3, or 1.times.10.sup.-6 m.sup.3, and therefore
an average magnetization magnitude is 100,000 A/m. Iron can have a
magnetization of around a million amperes per meter. Such a large
value explains why iron magnets are so effective at producing
magnetic fields.
[0582] The various magnets and their magnetic properties may be
implemented in the magnetic intragastric device locating system
with magnetic markers and magnetic sensors or detectors. The
magnetic markers comprise any magnetic or magnetized substance,
material, or object, to which the sensors or detectors are
responsive.
[0583] Flexible magnetic materials can also be employed in various
embodiments. Such materials typically comprise a ferromagnetic
compound (e.g., ferric oxide) mixed with a polymeric binder.
Magnetic materials suitable for use in the various embodiments
include magnetic tape, magnetic sheeting, magnetic rolls,
inkjet-printed magnets, and the like. Magnetic tape typically
comprises a layer of magnetic material with an adhesive on one
side. Magnetic sheeting can include a layer of magnetic material
that can be adhered to another layer, or incorporated between other
polymeric layers. Magnetic rolls typically comprise a magnetic
layer with one or more supporting or barrier layers incorporated
therein, e.g., prepared by extrusion, lamination, or other
techniques as are known in polymer processing and thin film
formation. Such flexible magnetic materials can be isotropic or
anisotropic in magnetic response.
[0584] Inkjet-printed magnets include a liquid comprising magnetic
particles that can be deposited on a substrate using inkjet or
bubblejet technology. Alternatively, magnetic particles can be
printed on a substrate using laser jet technology.
[0585] While ferric oxide can offer advantages of low cost, in
certain embodiments it may be desirable to employ other magnetic
materials, e.g., strontium, barium, neodymium, e.g., NdFeB,
samarium cobalt, platinum cobalt, and platinum iron.
[0586] In certain embodiments, the magnetic material is provided as
one or more flexible layers in the device. A flexible magnetic
layer can be incorporated into the composite wall as one of the
layers comprising the wall, e.g., as a supporting layer. The
magnetic layer can comprise an 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 can be inserted between layers in
the composite wall, or affixed or otherwise adhered to an interior
or exterior surface of the composite wall. The magnetic material
can be in sheet or roll form, as described above, or can be printed
onto one or more of the layers of the composite wall using any
suitable printing technology (inkjet, bubblejet, laser jet, screen
printing, lithography, etc.)
[0587] In certain embodiments, the magnetic component can be
provided as any of the rigid components incorporated into the
intragastric balloon, e.g., as a retaining ring, or as a weight
component configured to orient the balloon in the intragastric
space (e.g., a plug, button, pellet, or other solid shape affixed
to or incorporated into the materials of the balloon), or as a
free-moving or "loose" component in the interior volume of the
balloon.
[0588] A magnetic marker may be applied to the volume-occupying
subcomponent when the volume-occupying subcomponent is in a creased
or folded state such that when the volume-occupying subcomponent is
in its deflated state the magnetic field appears concentrated (more
localized), and when the volume-occupying subcomponent is inflated
the magnetic field appears more diffuse. Alternatively, the
magnetic marker may be applied or incorporated into the
volume-occupying subcomponent so as to facilitate identification
and location of the various subcomponents of the device, such as a
valve, head, or weight. The magnetic marker may be printed or
painted onto a surface of the volume-occupying subcomponent or
between layers of the material forming the volume-occupying
subcomponent. Alternatively, a magnetic coating as described below
may be used as a magnetic marker to identify and/or locate the
volume-occupying subcomponent. Magnetic coatings for visualizing
the volume-occupying subcomponent may include 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.
[0589] In another embodiment, the volume-occupying subcomponent
incorporates a subcomponent that changes mechanically upon
inflation of the volume-occupying subcomponent, which mechanical
change can be visualized using magnetic field detection equipment.
For example, a mechanical portion of the volume-occupying
subcomponent containing a magnetic marker may elongate upon an
increase in pressure in the volume-occupying subcomponent,
resulting in a more diffuse magnetic field.
[0590] Alternatively, a magnetized marker may be formed using a
metallized mesh or other pattern located between layers of the
material from which the volume-occupying subcomponent is
constructed. The pattern or patterns formed by the imbedded
magnetized marker will be locatable when the volume-occupying
subcomponent is in an inflated, deployed state.
Electromagnetic Detection
[0591] It is envisioned that magnetic marker materials may be
incorporated into the volume-occupying subcomponent to facilitate
various magnetic locating and visualization systems comprising a
variety of methods and apparatuses for sensing and detecting a
magnetic marker.
[0592] In some embodiments, a magnetic locating system comprises a
magnetic field proximity sensor. The sensor detects the strength
and orientation of the magnetic field generated by the magnetic
marker.
[0593] In some embodiments, the magnetic detector can be of similar
configuration to commercially available magnetic stud detectors
that use a small stationary magnet to detect the nails or screws
placed into studs during the manufacturing of the wall. Handheld
stationary magnetic detectors use a small (stationary) magnet to
detect the magnetic marker placed with devices. It is the "pull" of
the magnetic marker on the magnet that alerts the user holding the
device to the presence of a magnetic marker. The amount of "pull"
is proportional to the distance of the stationary magnet from the
magnetic marker. For example, a weaker pull indicates a deeper
depth in the body while a stronger pull indicates a shallower
depth, relative to the stationary magnetic detector.
[0594] In another embodiment, the magnetic locating system uses a
moving magnet to detect the magnetized portion of the device.
Moving magnet detectors are an enhancement involving a neodymium
magnet that is suspended such that it is free to move in response
to magnetic markers. The strength of this rare earth magnet, along
with the ease of movement of the magnet, allows the moving magnetic
finder to extend its range of detection to include various sizes of
patients (e.g., capable of accommodating morbidly obese patients).
Accordingly, magnetic markers far from a detector can be located
with this type of device. The magnet is suspended in such a way
that it always sits in its "home" position until it is moved
directly over a magnetic marker. Once the magnet is in the vicinity
of the marker, it is pulled towards the body at a rate of
acceleration that is proportional to the distance between the
magnet and the metal. For markers located in shallow positions, the
magnet moves towards the body with such velocity that it makes a
distinct thud sound. For magnetic markers deeper in the body, the
thud becomes more of a click since the speed of movement is
reduced. The tissues of the body are not expected to exhibit an
"insulating" effect as to the magnetic field. Instead, the strength
of the field is expected to be a function of the distance of the
detector to the locating device, and the strength of the magnetic
field generated by the locating device. The stationary magnetic
detector can be precalibrated to accurately identify the position
of the device. The tissues of the body are not expected to exhibit
an "insulating" effect as to the magnetic field. Accordingly, the
device can be calibrated (e.g., experimentally, or by calculation)
to output a value for distance and direction.
[0595] In some embodiments, the magnetic locating system uses an
internal capacitor to detect changes in the dielectric constant of
a person's body as the sensor is moved over the body. A change in
the dielectric constant indicates a dense object in the body.
[0596] Some embodiments using an internal capacitor may be edge
sensors, center sensors, or instant metal finders. In some
embodiments, a magnetic locating system further comprises a track
near the body on which the sensor passively travels as it follows a
magnetic marker that is progressing through the body.
[0597] In some embodiments, the sensor comprises a large magnetic
sheet placed near the body that remains stationary and passively
detects the location of the magnetic marker as it progresses
through the body.
[0598] In various embodiments a passive magnetic system can be
employed or an active electromagnetic system can be employed. In
the passive system, a magnetic component in the intragastric space
is detected using a suitable detector. The magnetic component can
passively generate a magnetic field, e.g., as a permanent magnet or
by a magnetic field induced in the magnetic component 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 an electromagnetic component is brought
within the presence of the field, and a current through or voltage
across the in vivo electromagnetic component is thereby generated
due to interaction with the electromagnetic field. The
electromagnetic component is in electrical communication with an ex
vivo current or voltage source, e.g, via a conductive wire or a
conductive trace.
[0599] Types of Magnetometers
[0600] In preferred embodiments, a magnetometer (also referred to
as a magnetic sensor or magnetic field sensing device) is employed
to locate and/or track the intragastric device. Magnetometers can
be divided into scalar devices which only measure the intensity of
the field and vector devices which also measure the direction of
the field.
[0601] Magnetometers can detect magnetic (ferrous) metals at large
distances, e.g., at tens of meters. In recent years magnetometers
have been miniaturized to the extent that they can be incorporated
in integrated circuits at very low cost.
[0602] Scalar magnetometers measure the total strength of the
magnetic field to which they are subjected, but not its direction.
Proton precession magnetometers, also known as proton
magnetometers, PPMs or simply mags, measure the resonance frequency
of protons (hydrogen nuclei) in the magnetic field to be measured,
due to nuclear magnetic resonance (NMR). Because the precession
frequency depends only on atomic constants and the strength of the
ambient magnetic field, the accuracy of this type of magnetometer
can reach 1 ppm. A direct current flowing in a solenoid creates a
strong magnetic field around a hydrogen-rich fluid, causing some of
the protons to align themselves with that field. The current is
then interrupted, and as protons realign themselves with ambient
magnetic field, they precess at a frequency that is directly
proportional to the magnetic field. This produces a weak rotating
magnetic field that is picked up by a (sometimes separate)
inductor, amplified electronically, and fed to a digital frequency
counter whose output is typically scaled and displayed directly as
field strength or output as digital data.
[0603] The Overhauser effect magnetometer or Overhauser
magnetometer uses the same fundamental effect as the proton
precession magnetometer to take measurements. By adding free
radicals to the measurement fluid, the nuclear Overhauser effect
can be exploited to significantly improve upon the proton
precession magnetometer. Rather than aligning the protons using a
solenoid, a low power radio-frequency field is used to align
(polarize) the electron spin of the free radicals, which then
couples to the protons via the Overhauser effect. This has two main
advantages: driving the RF field takes a fraction of the energy
(allowing lighter-weight batteries for portable units), and faster
sampling as the electron-proton coupling can happen even as
measurements are being taken. An Overhauser magnetometer produces
readings with a 0.01 nT to 0.02 nT standard deviation while
sampling once per second.
[0604] The optically pumped cesium vapor magnetometer is a highly
sensitive (300 fT/Hz.sup.0.5) and accurate device used in a wide
range of applications. It is one of a number of alkali vapors
(including rubidium and potassium) that are used in this way, as
well as helium.
[0605] Vector magnetometers have the capability to measure the
component of the magnetic field in a particular direction, relative
to the spatial orientation of the device. Vector magnetometers can
advantageously be employed to locate the intragastric device. A
vector is a mathematical entity with both magnitude and direction.
The Earth's magnetic field at a given point is a vector. A vector
magnetometer measures both the magnitude and direction of the total
magnetic field. Three orthogonal magnetometers can be employed
measure the components of the magnetic field in all three
dimensions, providing precise location of the medical device.
Magnetometers are also classified as "absolute" if the strength of
the field can be calibrated from their own known internal constants
or "relative" if they need to be calibrated by reference to a known
field. Magnetometers can also be classified as "AC" if they measure
fields that vary relatively rapidly in time (>100 Hz), and "DC"
if they measure fields that vary only slowly (quasi-static) or are
static.
[0606] Vector magnetometers measure one or more components of the
magnetic field electronically. Using three orthogonal
magnetometers, both azimuth and dip (inclination) can be measured.
By taking the square root of the sum of the squares of the
components the total magnetic field strength (also called total
magnetic intensity, TMI) can be calculated by Pythagoras's theorem.
Vector magnetometers are subject to temperature drift and the
dimensional instability of the ferrite cores. They also require
leveling to obtain component information, unlike total field
(scalar) instruments. For these reasons they are no longer used for
mineral exploration.
[0607] In a rotating coil magnetometer, the magnetic field induces
a sine wave in a rotating coil. The amplitude of the signal is
proportional to the strength of the field, provided it is uniform,
and to the sine of the angle between the rotation axis of the coil
and the field lines. This type of magnetometer is obsolete.
[0608] In a Hall effect magnetometer, a voltage proportional to the
applied magnetic field is generated and polarity is detected.
Magnetoresistive devices are made of thin strips of permalloy (NiFe
magnetic film) whose electrical resistance varies with a change in
magnetic field. They have a well-defined axis of sensitivity, can
be produced in 3-D versions and can be mass-produced as an
integrated circuit. They have a response time of less than 1
microsecond and can be sampled in moving vehicles up to 1,000
times/second. They can be used in compasses that read within
1.degree., for which the underlying sensor must reliably resolve
0.1.degree.. A fluxgate magnetometer consists of a small,
magnetically susceptible core wrapped by two coils of wire. An
alternating electrical current is passed through one coil, driving
the core through an alternating cycle of magnetic saturation; i.e.,
magnetized, unmagnetized, inversely magnetized, and so forth. This
constantly changing field induces an electrical current in the
second coil, and this output current is measured by a detector. In
a magnetically neutral background, the input and output currents
will match. However, when the core is exposed to a background
field, it will be more easily saturated in alignment with that
field and less easily saturated in opposition to it. Hence the
alternating magnetic field, and the induced output current, will be
out of step with the input current. The extent to which this is the
case will depend on the strength of the background magnetic field.
Often, the current in the output coil is integrated, yielding an
output analog voltage, proportional to the magnetic field.
[0609] A wide variety of sensors is currently available and used to
measure magnetic fields. Fluxgate compasses and gradiometers
measure the direction and magnitude of magnetic fields. Fluxgates
are affordable, rugged and compact. This, plus their typically low
power consumption makes them ideal for a variety of sensing
applications.
[0610] The typical fluxgate magnetometer consists of a "sense"
(secondary) coil surrounding an inner "drive" (primary) coil that
is wound around permeable core material. Each sensor has magnetic
core elements that can be viewed as two carefully matched halves.
An alternating current is applied to the drive winding, which
drives the core into plus and minus saturation. The instantaneous
drive current in each core half is driven in opposite polarity with
respect to any external magnetic field. In the absence of any
external magnetic field, the flux in one core half cancels that in
the other, and so the total flux seen by the sense coil is zero. If
an external magnetic field is now applied, it will, at a given
instance in time, aid the flux in one core half and oppose flux in
the other. This causes a net flux imbalance between the halves, so
that they no longer cancel one another. Current pulses are now
induced in the sense coil winding on every drive current phase
reversal (or at the 2nd, and all even harmonics). This results in a
signal that is dependent on both the external field magnitude and
polarity.
[0611] There are additional factors that affect the size of the
resultant signal. These factors include the number of turns in the
sense winding, magnetic permeability of the core, sensor geometry
and the gated flux rate of change with respect to time. Phase
synchronous detection is used to convert these harmonic signals to
a DC voltage proportional to the external magnetic field.
[0612] SQUIDs, or superconducting quantum interference devices,
measure extremely small magnetic fields. They are very sensitive
vector magnetometers, with noise levels as low as 3 fT Hz.sup.-1/2
in commercial instruments and 0.4 fT Hz.sup.-1/2 in experimental
devices. Many liquid-helium-cooled commercial SQUIDs achieve a flat
noise spectrum from near DC (less than 1 Hz) to tens of kilohertz,
making such devices ideal for time-domain biomagnetic signal
measurements. SERF atomic magnetometers demonstrated in
laboratories so far reach competitive noise floor but in relatively
small frequency ranges.
[0613] SQUID magnetometers require cooling with liquid helium (4.2
K) or liquid nitrogen (77 K) to operate, hence the packaging
requirements to use them are rather stringent both from a
thermal-mechanical as well as magnetic standpoint. SQUID
magnetometers are most commonly used to measure the magnetic fields
produced by brain or heart activity (magnetoencephalography and
magnetocardiography, respectively). Geophysical surveys use SQUIDS
from time to time, but the logistics are much more complicated than
coil-based magnetometers.
[0614] At sufficiently high atomic density, extremely high
sensitivity can be achieved. Spin-exchange-relaxation-free (SERF)
atomic magnetometers containing potassium, cesium or rubidium vapor
operate similarly to the cesium magnetometers described above, yet
can reach sensitivities lower than 1 fT Hz.sup.-1/2. The SERF
magnetometers only operate in small magnetic fields. The Earth's
field is about 50 .mu.T; SERF magnetometers operate in fields less
than 0.5 .mu.T.
[0615] Large volume detectors have achieved a sensitivity of 200 aT
Hz.sup.-1/2. This technology has greater sensitivity per unit
volume than SQUID detectors. The technology can also produce very
small magnetometers that may in the future replace coils for
detecting changing magnetic fields. This technology may produce a
magnetic sensor that has all of its input and output signals in the
form of light on fiber-optic cables..sup.[10] This would allow the
magnetic measurement to be made in places where high electrical
voltages exist.
[0616] A computing system may be implemented in the magnetic
locating system. The computing system comprises hardware and
software that receives data from the magnetic sensor and calculates
information related to the location, orientation, and/or state of
an intragastric device according to certain algorithms.
[0617] In some embodiments, the hardware may comprise a central
processing unit, memory, an analog to digital converter, analog
circuitry, a display.
[0618] In some embodiments, the software proceeds through a number
of steps including calibration, initialization, prediction,
estimation, measuring magnetic sensor data, calculating various
desired outputs including location, orientation, size, and
configuration.
[0619] In some embodiments, the computing system predicts or
estimates a location, position, orientation, state, or
configuration of a magnetic marker, determines a corresponding
estimated or predicted magnetic field, takes an actual measurement
of the magnetic field generated by the magnetic marker, and
determines the actual location, position, orientation, state, or
configuration of a magnetic marker based on a difference between
the values of the predicted field and actual field.
[0620] In embodiments using estimation or prediction, the
computation may be done using iterative calculations and/or neural
networks, and the hardware may further include an estimation
processor.
[0621] The processor's output relating to the location, orientation
and/or state of an intragastric device may be communicated to a
user in a number of manners. In some embodiments, the output is
shown visually on a display.
[0622] In some embodiments, the processor's output related to an
intragastric device's location, orientation, and/or state is
audibly communicated to a user through a speaker.
[0623] In some embodiments, the processor's output related to an
intragastric device's location, orientation, and/or state is
communicated to a user through a combination of methods. For
instance, the system may employ a visual graphical display with
audible alerts sent through speakers.
[0624] In some embodiments, the magnetic locating system is
calibrated before use. The magnetic marker and the sensor are
positioned in pre-planned locations and orientations to verify the
output signal is within an expected range
[0625] In some embodiments, the magnetic locating systems are
calibrated or otherwise verified using a human patient simulator,
or dummy, to test the magnetic locating system as a magnetic marker
travels through the simulators
[0626] In some embodiments, the magnetic locating system is checked
for stray signals from nearby magnetic interferences.
[0627] The intragastric devices once ingested may be located using
the magnetic intragastric locating system.
[0628] The orientation of the devices once ingested may be
ascertained using the magnetic intragastric locating system.
[0629] Further, the various sizes and configurations of the devices
once ingested may be characterized using the magnetic intragastric
locating system. For instance, inflation of a balloon, or the
inflation or configuration of multiple balloons, may be
characterized and assessed.
[0630] The magnetic locating system may also be used in conjunction
with a deflating system to characterize the deflation process.
[0631] The timing and other attributes of the various methods of
administration can be characterized using the disclosed magnetic
intragastric locating system. Whether the device is administered
using endoscopic techniques or orally, the progress of the device
as it makes its way to the stomach can be tracked with the magnetic
locating system. For instance, the effects of swallowing the device
with hard gelatin or water or other consumables may be
characterized by tracking the location and orientation as it is
ingested.
Electromagnetic Real-Time Confirmation of Placement
[0632] In certain embodiments, an electromagnetic tracking
technology as is commercially available is employed. Suitable
systems include, but are not limited to, the Sherlock* II Tip
Location System as manufactured by Bard Access Systems of Salt Lake
City, Utah, or the Aurora Electromagnetic Tracking System
manufactured by NDI Medical, Inc. of Ontario, Canada.
[0633] The Aurora System
[0634] In some embodiments, a catheter is adapted to integrate the
Aurora System sensors by situating the sensors inside the catheter.
In other embodiments, the sensors may be situated in other
components of the system, such as the balloon or intragastric
device, or other features as described herein. The compatible NDI
Aurora System Hardware components allow for tracking of the sensors
placed inside the swallowable catheter using real time
electromagnetic tracking system that delivers sub-millimetric,
sub-degree accuracy. The software was modified to make the graphic
user interface appropriate for GE use and detection of the capsule
in the alimentary canal.
[0635] FIG. 1 depicts an embodiment of an electromagnetic tracking
system 1500 for locating a sensor 1521. The system 1500 includes a
field generator 1510, a system control unit 1535, the sensor
interface unit 1530, and a catheter 1503 having a distal sensor
1521. In the embodiment shown, the field generator 1510 generates
an electromagnetic field. In other embodiments described herein,
the field generator 1510 may generate a pressure wave for use, for
example, in an ultrasound-based system (see FIGS. 27-40). As shown
in FIG. 1, the field generator 1510 may include one or more
mounting holes 1511. The mounting holes 1511 allow the generator
1510 to be mounted to a wall, support, or other attachments. A
field generator connector 1512 connects a field generator cable
1514 to the system control unit 1535. The field generator connector
1512 is a nineteen pin circular metal connector, however other
connectors maybe used.
[0636] As shown, the field generator 1510 may be planar. A planar
field generator 1510 emits a low-intensity, varying electromagnetic
field and establishes the position of a tracking volume (see FIG.
6). The planar field generator 1510 contains a number of large
coils (not shown) that generate known electromagnetic fields. The
field generator 1510 produces a series of varying magnetic fields,
creating a known volume of varying magnetic flux. This volume is
referred to as the characterized measurement volume. The shape of
the characterized measurement volume is dependent on the field
generator type and how it was characterized. The characterized
measurement volume is the volume where data was collected and used
to characterize the field generator 1510. It is a subset of the
detection region. The detection region is the total volume in which
the field generator can detect a sensor, regardless of accuracy.
The measurement volumes for the generated magnetic fields are
discussed in further detail herein, for example with respect to
FIG. 6. The volume is projected outwards from the field generator's
1510 front face, offset by 50 mm from the field generator 1510.
[0637] The planar field generator 1510 may have a mounting point
1509 designed to attach the field generator 1510 to a mounting arm,
described in further detail herein, for example with respect to
FIG. 4. The field generator 1510 may have one or more mounting
holes 1511 that allow the field generator 1510 to be attached
firmly to a fixture. As shown, the two mounting holes 1511 are M8
tapped holes (thread pitch 1.25 mm, depth 13 mm).times.4, 2 per
side. However, there may be fewer or more than two mounting holes
1511 and in a variety of shapes and sizes.
[0638] The field generator 1510 may also be a tabletop field
generator (not shown). The tabletop field generator may be designed
to be placed on a patient table in between the patient and the
table. The tabletop field generator incorporates a thin barrier
that minimizes any tracking distortions caused by conductive or
ferromagnetic materials located below the tabletop field generator.
The tabletop field generator contains a number of large coils that
generate known electromagnetic fields. The volume may be projected
outwards from the tabletop field generator's front face, offset by
120 mm from the tabletop field generator. The tabletop field
generator may include any or all features and functionalities as
the planar field generator described above.
[0639] The field generator 1510 is connected to the system control
unit 1535. The generator 1510 may be connected to the system
control unit 1535 by the cable 1514 allowing for communication of
signals therebetween. The system control unit 1535 may include a
power cable 1505 and an auxiliary cable 1504, for example a USB
cable or Serial RS-232 cable, for example to connect to a computer
or other component. The system control unit 1535 may provide power
to the field generator 1510.
[0640] 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 via multiple cables 1534. The cables 1534 allow
for electronic communication of signals between the system control
unit 1535 and the one or more sensor interface units 1530.
[0641] The system control unit 1535 may control the operation of
the system 1500. In some embodiments, the system control unit 1535
provides an interface between components of the system 1500. The
system control unit 1535 may also supply power to the field
generator 1510 and/or control the field generator's 1510
electromagnetic output. The system control unit 1535 may also
collect sensor data (via the sensor interface unit 1530) and
calculates sensor positions and orientations. The system control
unit 1535 then sends the position and orientation data to a host
computer (see FIG. 2). Therefore, the system control unit 1535 may
also interface with the computer. The system control unit 1535 may
also provide visual status indications.
[0642] The sensor interface unit 1530 is connected to the catheter
1503. The catheter 1503 includes a sensor 1521 at the distal end of
the catheter 1503. In some embodiments, the sensor 1521 may be
integrated with an intragastric device. The sensor 1521 is an
electromagnetic sensor. In some embodiments, the sensor 1521 may be
an ultrasound or voltage sensor or marker. Use of a voltage sensor
is discussed in further detail herein, for example with respect to
FIG. 10C. The sensor 1521, which may be embedded in tools, are
connected to the sensor interface unit 1530 via the one or more
system interface units 1530. If the electromagnetic sensor 1521 is
placed inside the measurement volume, a voltage will be induced in
the sensors 1521, caused by the varying magnetic fields produced by
the field generator 1510. The characteristics of the induced
voltage depend on a combination of the sensor 1521 position and
orientation in the measurement volume, and the strength and phase
of the varying magnetic fields.
[0643] FIG. 2 depicts an embodiment of an electromagnetic tracking
system 1501 with an electromagnetic sensor 1506 for locating an
intragastric device 1520. The system 1501 includes the intragastric
device 1520 coupled with a catheter 1502 that includes one or more
sensors 1506. The system 1501 further includes the sensor interface
unit 1530, the system control unit 1535 and the field generator
1510 in electrical communication with a computer 1540.
[0644] As shown, the 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 or other intragastric devices as described herein.
[0645] The intragastric device 1520 is connected to a catheter
1502. The catheter 1502 includes the electromagnetic sensor 1506 at
the distal end of the catheter 1502 near the intragastric device
1520. In some embodiments, the sensor 1506 may be embedded with
other features of the system 1501, such as an intermediate
connector between the catheter 1503 and the intragastric device
1520. The catheter 1502 may be a small 2 Fr diameter catheter. The
catheter 1502 may include the sensor 1506 as one or more small
inductive sensors. In addition, external reference sensors 1622
(see FIG. 3A) may be placed on the patient, such as on the skin.
The external reference sensors 1622 are intended to provide an
anatomical frame of reference between the field generator 1510 and
the patient. The catheter sensors 1506 will provide location data
as they travel through the esophagus across the GE junction and
into the stomach. Data collected by the reference sensors 1622 and
the catheter sensors 1506 are then displayed on a laptop computer.
The electromagnetic sensor can be characterized for five or six
degrees of freedom.
[0646] The catheter 1502 is connected to a sensor interface unit
1530. In some embodiments, the catheter 1502 is connected directly
to the sensor interface unit 1530. In other embodiments, the
catheter 1502 is connected indirectly to the sensor interface unit
1530 via an intermediate jumper cable, as described in further
detail herein, for example with respect to FIG. 3A. The sensor
interface units 1530 amplify and digitize the electrical signals
from the sensors 1506. The sensor interface units 1530 also provide
an increased distance between the system control unit 1535 and
sensors 1506, while minimizing the potential for data noise.
[0647] The system 1501 includes the system control unit 1535. The
system control unit 1535 is connected to the system interface unit
1530 by a cable allowing for electrical communication therebetween.
The system control unit 1535 collects information from the system
interface unit 1530 and calculates the position and orientation of
each sensor 1506 and interfaces with the computer 1540.
[0648] The system control unit 1535 is connected to the field
generator 1510 by a cable allowing electrical communication there
between. The field generator 1510 generates a magnetic field 1515.
The magnetic field 1515 encompasses the intragastric device 1520
and the sensor 1506 located near the intragastric device 1520 in
the catheter 1502. The interaction of the magnetic field 1515 with
the sensor 1506 creates an electrical signal that is detected and
transmitted to the system interface unit 1530, which transmits a
signal to the system control unit 1535, which transmits a signal to
the computer 1540.
[0649] The computer 1540 is connected to the system control unit
1535 by a cable 1504. The cable 1504 allows for electronic
communication between the computer 1540 and the system control unit
1535. The computer 1540 includes a display 1542. The display 1542
shows identifiers 1544. The identifiers 1544 indicate the locations
of the various sensors located with the intragastric device 1520
and the catheter 1502. As shown, there are multiple identifiers
1544 corresponding to the location of the sensor 1506 on the
intragastric device 1520 as well as the location of other reference
anatomical sensors, discussed in further herein, for example with
respect to FIG. 3
[0650] The system 1501 can power on and detect the presence,
motion, and changes in orientation of the catheter sensors 1506. In
some embodiments, the sensors 1506 are detected when placed at a
range of 30 cm from the center point of the field generator 1510.
In some embodiments, the range of detection for the sensors 1506 is
greater than 45 cm at the center point of the field generator 1510.
In some embodiments, the system 1501 can locate with the distal
sensor 1506 the two lower corners of the field generator 1510
within a .+-.2 cm boundary in the X-direction when placed at a
range of 30 cm from the center point of the field generator
1510.
[0651] FIG. 3A depicts an embodiment of an electromagnetic tracking
system 1601 for using a sensor to locate an intragastric device
1620 inside the body of a human patient. The system 1601 includes a
field generator 1610 mounted on a support 1605. The support 1605
may be a supporting structure formed from metal, plastic or other
suitable materials. The support 1605 may be adjustable in order to
adjust the location of the field generator 1610 relative to the
location of a patient. In some embodiments, the support 1605 can
move up and down to accommodate varying heights of patients. In
this manner, the field generator 1610 may be positioned so that a
magnetic field is generated on a region of interest, for example
the patient's upper body and abdomen.
[0652] As shown, the patient may stand in front of the field
generator 1610, which may be the field generator 1510. The patient
has ingested the intragastric device 1620, which may be the
intragastric device 1520, and is now inside the patient's body. The
intragastric device 1620 is connected to a catheter 1602, which may
be the catheter 1502. The catheter 1602 includes the
electromagnetic sensor (not shown) at its distal and located near
the intragastric device 1620. Therefore, the field generator 1610
will generate 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 the
sensor interface unit 1535. Electrical communication is provided by
wiring connected to the sensor that extends through the catheter
1602 to the sensor interface unit 1630. Electrical signals
generated by the electromagnetic sensor due to the presence of the
magnetic field are transmitted to the sensor interface unit
1630.
[0653] The system 1601 also includes external anatomical reference
sensors 1622. The external reference sensors 1622 may provide an
anatomical frame of reference between the field generator 1610 and
the patient. Small inductive currents are generated by the sensors
1622 while 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, may be more or fewer
than three anatomical reference sensors 1622. The sensors 1622 are
connected to the sensor interface unit 1630 by electronic cables
1623. The sensors 1622 are responsive to the magnetic field 1611
generated by the field generator 1610. In the presence of the
magnetic field, the sensors 1622 generate a current or other signal
that is transmitted to the sensor interface unit 1630.
[0654] The system 1601 also includes a jumper cable 1626. The
jumper cable 1626 contains an SROM chip which provides electrical
continuity from the catheter 1602 to the sensor interface unit
1630. The jumper cable 1626 may provide a connector gender changer
to prevent misconnection between the sensor interface unit 1630 and
the catheter 1602. Further detail of the jumper cable 1626 is
described herein, for example with respect to FIG. 12.
[0655] The system control unit 1635 is connected to the computer
1640 by a cable 1604. The cable 1604 allows for electronic
communication between the system control unit 1635 and the computer
1640. The computer includes a display 1642. The display 1642 shows
the location of a sensor identifier 1644 as well as the locations
of three anatomical identifiers 1646. The sensor identifier 1644
indicates the location of the sensor and the distal end of the
catheter 1602. The anatomical identifiers 1646 indicate the
locations of the anatomical reference sensors 1622.
[0656] The anatomical reference sensors 1622 are fixed on the
patient and provide a frame of reference by which to locate the
electromagnetic sensor. By having a fixed and known location, the
anatomical reference sensors 1622 may be used to accurately locate
the electromagnetic sensor, and thus the intragastric device 1620.
The locations of the reference sensors 1622 shows up on the display
1642 as anatomical identifiers 1646 while the electromagnetic
sensor shows up on the display 1642 as the sensor identifier 1644.
By knowing the location of the sensors 1622 on the patient's body,
and the relative location of the sensor identifier 1644 relative to
the anatomical identifier 1646, the location of the electromagnetic
sensor, and thus of the intragastric device 1620, inside the body
can be determined.
[0657] The computer 1640, which may be a laptop computer, contains
a system specific software program designed to provide the end user
with a "real time" display of the catheter's 1602 location, as well
as the location of the reference sensors 1622. The system 1601 may
be calibrated prior to each use. The sensor takes a background
measurement of the ambient magnetic field during a calibration
cycle and when the catheter 1602 is brought within range, the
sensor detects the change in the magnetic field and communicates
the data to the software program residing in the computer 1640. The
software analyses the data and presents the location of the various
sensors on the computer display 1642. In some embodiments, no or
little magnetic energy is generated by the sensor or the computer
1640.
[0658] The intragastric device 1620 is administered via a patient
swallow of the balloon capsule that is adhered to the swallowable
catheter 1602. The administration of the catheter can be done while
visualizing the catheter as it traverses the esophagus past the GE
junction into the stomach. 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 completion of the procedure.
[0659] The intragastric device 1620 connected to the catheter 1602
is designed to be swallowed and tracked by the various sensors as
it traverses to the stomach past the GE junction. The device 1620
is designed to start outer capsule separation after being
swallowed. In some embodiments, the device 1620 starts outer
capsule separation after being swallowed in approximately 2
minutes. Full placement and removal of the catheter 1602 may take
approximately 10 minutes for each swallow procedure. In some
embodiments, patients may swallow three catheters, and therefore
the total time of the swallow procedure for these subjects is
approximately 30 minutes. After completion of each swallow
procedure, the catheter 1602 is removed by simply pulling it back
through the mouth.
[0660] The system 1601 may be controlled using an application
program interface (API) (not shown). The API is a set of commands
that allow configuration and requesting information from the system
1601. The system 1601 may return information only when requested by
the computer 1640. In some embodiments, the system 1601 may return
information automatically, for instance at set intervals or
continuously.
[0661] When the system 1601 is tracking the device 1620, it returns
information about the sensors to the computer 1640. The system 1601
may return the position of each sensor's origin, given in mm, in
the coordinate system of the field generator 1610. The system 1601
may return the orientation of each sensor, given in quaternion
format. The quaternion values are rounded off, so the returned
values may not be normalized. The system 1601 may return an error
indicator value, between 0 and 9.9 (where 0 is the absence of error
and 9.9 is the highest indication of error). The system 1601 may
return the status of each sensor, indicating whether the sensor is
out of the electromagnetic field volume, partially out of the
volume, or missing. The system 1601 may return the frame number for
each sensor transformation. The frame counter starts as soon as the
system 1601 is powered on, and can be reset using API commands. The
frame number returned with a transformation corresponds to the
frame in which the data used to calculate that transformation was
collected. The system 1601 may return the system 1601 status, which
may include system errors.
[0662] The various sensors may be five degrees of freedom (5DOF) or
six degrees of freedom (6DOF). Five degrees of freedom provides
information on the three translation values on the x, y and z-axes
and any two of the three rotation values--roll, pitch and yaw. Six
degrees of freedom provides information on the three translation
values on the x, y and z-axes and the three rotation values roll,
pitch and yaw. In embodiments with only one sensor incorporated,
the rotation around the sensor's longitudinal axis cannot be
determined. As such, only five degrees of freedom (5DOF) can be
determined for single sensor embodiments. For example, how much a
needle physically rolls is not as important as where it is pointing
and where the tip is located. As such, a needle can be a 5DOF tool,
with only one sensor incorporated into its design.
[0663] In embodiments that incorporate two sensors fixed relative
to each other and ideally orthogonal, the system can determine six
degrees of freedom (6DOF). First, the system determines 5DOF
information for each sensor. Next, the system combines and compares
this information, applies the fixed location data, and determines
six degrees of freedom (6DOF).
[0664] For example, an ultrasound technician needs to know the
location of the ultrasound probe as it moves over a subject, in
order to match its findings to actual physical locations on that
subject. Incorporating two sensors into the ultrasound probe
produces 6DOF measurements and ensures that all translation and
rotation values of the probe are captured.
[0665] The field generator 1610 may use a coordinate system with
the origin located approximately on the surface of the field
generator 1610. This global coordinate system may be defined during
manufacture. The system 1601 may report the transformations in the
global coordinate system. However, in some embodiments that use a
reference tool (not shown), software can calculate and report
transformations in the local coordinate system of the reference
tool.
[0666] Each sensor has its own local coordinate system that is
defined by an origin and three axes. Local coordinate systems are
part of the measurement process. In some embodiments, there may be
a single sensor. The single sensor's local coordinate system is
based directly on that of the sensor. By default, the system
assigns the z-axis along the sensor's length, with an origin at the
sensor's center. It is possible to move the origin along the
z-axis. The x and y axes are not fixed, due to the inability to
determine rotation about the z-axis.
[0667] In some embodiments, there may be dual sensors having 5DOF.
A dual 5DOF sensor is essentially two single sensors joined to the
same sensor body connector. As such, the sensor actually has two
local coordinate systems, each based on one of the sensors
incorporated into its design. These local coordinate systems are
determined in the same way as that of a single sensor.
[0668] In some embodiments, the system 1601 has metal objects, such
as tables, tools, braces, and the like. This may create problems
when using an electromagnetic sensor, and thus the system 1601 may
therefore be resistant to certain metals. The problems caused by
placing metal near an electromagnetic measurement system relate to
eddy currents. An eddy current is caused when a conductive material
is exposed to a dynamic magnetic field. The changing magnetic field
induces a circulating flow of electrons within the conductive
material, resulting in an electric current. These circulating
currents (sometimes known as eddy currents) produce an
electromagnetic effect of their own, creating magnetic fields that
oppose the original, external magnetic field. The greater the
electrical conductivity of the conductor, the greater the eddy
current developed (and the greater the opposing magnetic field
produced).
[0669] If a conductive metal intersects the electromagnetic field
1611, the opposing magnetic field created by resulting eddy
currents disrupts that field and affects the transformation data
produced. One method of reducing this effect is to adjust the
placement of both the sensor being measured and the object
producing the eddy currents. Moving the sensor so that the distance
between the sensor and the field generator 1610 is smaller than its
proximity to the object creating eddy currents may decrease the
effects of the eddy currents on sensor measurements.
[0670] Another situation to consider is the effect of eddy currents
in metallic loops. Loops may occur in structures like metallic
table frames, or concrete reinforcement bars. Cutting the loops
will reduce the effect of eddy currents. If cutting the loops is
not an option, then locate the system 1601 to minimize the effects
of the loops. In some embodiments, the system 1601 uses special
technology to take into account such effects as eddy currents. The
following metal alloys work well with the system 1601 when applied
in amounts similar to that used in medical tool construction:
cobalt-chrome alloy, steel DIN 1.441, titanium (TiAl6V4) and 300
series stainless steel.
[0671] Further, ferromagnetic material generally has little or no
net magnetic property. However, if it is placed in the magnetic
field 1611, its domains will re-orient in parallel with that field,
and may even remain re-oriented when the field 1611 is turned off.
Even metals with only small amounts of ferrous material in them may
have these reactions.
[0672] The magnetic field produced in a ferromagnetic object
attracts the external magnetic field 1611, resulting in the
external magnetic field 1611 bending towards the object itself. As
such, introducing a ferromagnetic object into the system's 1601
electromagnetic field 1611 will cause a distortion that can affect
the transformation data produced.
[0673] FIG. 3B is a rear view of the patient from system 1601 shown
in FIG. 3A. As shown in FIG. 3B, the patient has three external
anatomical reference sensors 1622 attached to the backside of the
patient. The sensors 1622 are arranged in a generally triangular
configuration. In some embodiments, the sensors 1622 may be
arranged in different configurations, such as rectangular,
circular, or others. The sensors 1622 are connected by the cable
1623 to other components of the system 1601, such as the sensor
interface unit 1630. In some embodiments, the sensors 1622 may be
wirelessly connected to other components of the system 1601. As
further shown, the patient is standing directly in front of the
field generator 1610. In some embodiments, the patient need not be
standing directly in front of the generator 1610.
[0674] FIG. 4 depicts an embodiment of an electromagnetic tracking
system 1650 that includes a support 1655 and that uses a sensor
(not shown) to locate an intragastric device (not shown) inside the
body of a human patient 1651. The system 1650 includes the patient
1651 standing in front of a field generator 1660, which may be the
field generators 1510, 1610 described herein. The generator 1660 is
coupled with an arm 1670 that is adjustable. The arm 1670 may be
adjusted such that the field generator 1660 is located next to the
patient 1651. The arm 1670 may also adjust the field generator 1660
such that it produces a magnetic field in the vicinity of the
patient's 1651 stomach. The arm 1670 may adjust the field generator
1660 vertically as well as horizontally. The arm 1670 can also
rotate the field generator 1660, for example to accommodate
patients who are lying down.
[0675] The system 1650 includes the support 1655 which supports a
computer 1690. The support 1655 is adjustable in the vertical
direction. In some embodiments, the support 1655 may be adjustable
in other directions, for example it may adjust in the horizontal
direction, rotate, etc. The support 1655 includes a surface upon
which the computer 1690 and other components of the system 1650 may
be placed or mounted. The support 1655 also includes four wheels
1666 that allow the support 1655 to be rolled around. In some
embodiments, the support 1655 may include fewer or more than four
wheels 1666.
[0676] The support 1655 may be designed to avoid tipping over. In
some embodiments, the support 1655 may withstand 10.degree. incline
from a horizontal plane in any X or Y direction without tipping
over. In some embodiments, the support 1655 may withstand a load
equal to 25% of total weight in any X or Y direction without
tipping over.
[0677] FIG. 5 depicts an embodiment of a display that can be used
with the systems of FIGS. 2-4. The display 1700 includes a screen
1710. The screen 1710 displays the locations of the various
identifiers corresponding to the various sensors. The screen 1710
may be a display on a computer. The screen 1710 may also be on a
variety of other machines.
[0678] As shown, the display 1700 includes the locations of the
identifiers 1720 and 1725. The identifier 1720 corresponds to the
location of the sensor coupled with the catheter. For example, the
identifier 1720 may correspond to the location of the
electromagnetic sensor 1506 and the catheter 1502. The identifier
1720 may also correspond to the location of the sensor coupled with
the intragastric device 1620 and the catheter 1602.
[0679] The display 1700 may also include a trace 1722. The trace
1722 may indicate the path that the identifier 1720 has traveled
over time. Therefore, the trace 1722 may indicate the path that the
sensor has travelled inside the patient's body. As shown, the trace
1722 may have a vertical section followed by a bend near the bottom
of the trace 1722 as illustrated. In some embodiments, the bend in
the trace 1722 is indicative of the path of a sensor traveling
through into the stomach of a patient. Therefore, the path of the
trace 1722 may be indicative of the location of the sensor and
therefore of the intragastric device.
[0680] The identifiers 1725 may correspond to the locations of
external anatomical reference sensors. For example, the identifiers
1725 may correspond to the locations of the three anatomical
reference sensors 1622. As shown, the identifiers 1725 form a
generally triangular shape. This may correspond, for example, to a
generally triangular configuration of the sensors 1622 located on
the back of the patient. By knowing the location of the identifiers
1725 relative to the patient, and the relative location of the
identifier 1720 relative to the identifiers of 1725, the location
of the sensor and therefore the intragastric device inside the body
may be determined. As shown in FIG. 5, the location of the
identifier 1720 may be indicative of an intragastric device being
success successfully placed inside the stomach. The display 1700
shown is merely one example and other suitable displays may be
implemented. In some embodiments, the screen 1710 may include
markings or other reference points to facilitate locating the
various identifiers.
[0681] FIG. 6 depicts an embodiment a field generator and
corresponding magnetic field envelope that may be used with the
systems of FIGS. 2-4. The envelope 1815 represents the volume in
which the sensors may interact with the generated magnetic field
from the field generator 1810. The envelope 1815 is shown in a
generally cylindrical shape. In some embodiments, the envelope 1815
may have a variety of shapes.
[0682] FIG. 7 depicts an embodiment of a control panel 1915 on a
system control unit 1910 that may be implemented with the systems
of FIGS. 2-4. The panel 1915 may be on the back side of the system
control unit 1910.
[0683] The panel 1915 includes a field generator port 1920 and
multiple sensor interface unit ports 1925 and status lights 1926.
The port 1920 may be used to synchronize the system control unit
1910 to other equipment. The sensor interface unit ports 1925
connect the sensor interface units to the system control unit,
allowing for communication with the connected sensors. For example,
the ports 1925 may be used to connect the sensor interface unit
1630 to the system control unit 1635 to enable communication with
the sensors 1506. The status lights 1926 may indicate whether the
corresponding port 1925 is connected with a sensor or catheter.
[0684] FIG. 8 depicts an embodiment of a sensor interface unit 2030
that may be implemented with the systems of FIGS. 2-4. The sensor
interface unit 2030 is the interface between the sensors and the
system control unit, such as the system control unit 1535 or 1635.
The main function of the sensor interface unit 2030 is to convert
the analog signals, produced by the sensors, to digital signals.
The digital signals are 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
sensors, removing the requirement for a long tool cable and keeping
bulky system components away from the application space. In
addition, the shorter the tool cable, the less noise will appear on
the signal from the sensors. In some embodiments, each sensor
interface unit 2030 can support up to two 5DOF sensors, or one 6DOF
sensor.
[0685] The sensor interface unit 2030 includes a sensor port 2040
and cable 2045. The sensor port 2040 connects the sensor interface
unit 2030 to sensors, such as the sensor 1506. The sensor port 2040
may be a 10-pin circular plastic connector. The cable 204
electrically connects the sensor interface unit 2030 to the system
control unit, such as the system control unit 1535 or 1635.
[0686] FIG. 9 depicts an embodiment of a catheter 2100 with an
integrated sensor 2115 that may be used with the systems of FIGS.
2-4. The catheter 2100 includes a shaft 2110 that extends along the
length of the catheter 2100. The shaft 2110 forms a hollow channel
through which electrical wires may be extended to attach to the
sensor 2115. The catheter 2100 may include a plug 2120 on the
opposite end as the sensor 2115. The plug 2120 may couple with the
sensor interface unit, such as the sensor interface unit 1530 or
1630. In some embodiments, the plug 2120 couples with a jumper
cable that is attached to the system control unit.
[0687] FIG. 10A depicts another embodiment of a catheter 2101 and
sensor 2114 that may be used with the systems of FIGS. 2-4. The
catheter is a flexible, hydrophilic coated, 2-Fr catheter which
contains a swallowable catheter (approximately 30 inches) which is
bonded to approximately 40 inches of pellethane extension tubing to
allow connection to the sensor interface unit. The distal end of
the catheter contains two small inductive sensors, one at the
distal end and the second approximately 6 inches from the distal
tip. As the sensors within the catheter 2101 move through the
esophageal tract into the stomach through the GE junction the
sensors provide electrical signals to the sensor interface unit.
The characteristics of these electrical signals are dependent on
the distance and angle between a sensor and the field
generator.
[0688] In some embodiments, the distal end of the various
catheters, such as the catheter 2100 or 2101, is sealed with an
adhesive plug. Attached to the distal end of the catheter is a
31.times.12.41 mm pharmaceutical grade porcine gelatin capsule with
a hydrophilic coating containing food-grade sugar. The catheter
2101 may include a 2 Fr catheter shaft formed from Pebax.RTM.
(Polyether Block Amids) and Polyvinylpyrrolidone to provide a
swallowable catheter with a hydrophilic coating to provide
lubricity. The catheter may include sensors that include a copper
coil encased in epoxy to provide electrical signals for tracking
the catheter. The catheter may include an outer capsule formed from
a USP-grade hard porcine gelatin capsule supplied by Torpac, Inc.
(New Jersey, USA) containing food grade sugar to mimic food bolus
weight for swallowing. The outer capsule may have a
polyvinylpyrrolidone hydrophilic coating to provide lubricity. The
catheter may include a distal strain relief formed from a
thermoplastic polyurethane elastomer to provide strength to hold
the gelatin capsule on the catheter shaft. The catheter may include
an extension tube formed from a thermoplastic polyurethane
elastomer to extend the length of the catheter for attachment to
the sensor interface unit. The catheter may include a markerband
formed from 316 stainless steel to provides visibility to the tip
of the catheter during visualization. The catheter may include
adhesive that is UV curable for joining extruded components of the
catheter together and to seal the sensors from fluid contact. The
catheter may include a 4-Pin connector to provide 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 to provide a strain relief for
attaching the 4-Pin connector to the extension tube. The heat
shrink-connector may be formed from a fluoropolymer.
[0689] As shown in FIG. 10A, the catheter 2101 may include a
proximal luer hub 2111. The luer hub 211 may allow for attaching
peripheral components or for grasping the catheter 2101. The
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. The catheter
2101 is shown with a sensor 2116. In some embodiments, the sensor
2116 is a 0.3.times.13 mm 5DOF sensor manufactured by Northern
Digital Inc. in Ontario, Canada. However, other sensors may be
implemented.
[0690] The catheter 2101 may also include a Y-port 2118. The Y-port
2118 may be a splitter that connects various features of the
catheter 2101 together. In some embodiments, the Y-port 2118
connects the luer hub 2111 and a strain relief tubing 2122 with a
catheter bump tubing 2126. The strain relief tubing 2122 may extend
off-axis from the Y-port 2118 and connect with a connector 2124.
The connector 2124 may include a connector spacer 2128 and UV cure
adhesive 2130. The adhesive 2130 may also be used in other
locations of the catheter 2101, for example at the interface of the
sensor 2116 and the catheter bump tubing 2126, and elsewhere as
shown.
[0691] The catheter 2101 may have robust mechanical properties. In
some embodiments, the catheter 2101 can bend 180.degree. over a 0.5
cm radius mandrel without kinking at the center portion of a Peebax
catheter shaft. The intragastric device may separate from the
catheter 2101 when submerged in 37.degree. C. water. The adhesive
2130 bond between a capsule and the catheter 2101 fails at more
than 150 grams when preconditioned for twenty seconds in room
temperature water. The adhesive 2130 bond between the strain relief
tube 2122 and the catheter tubing 2126 fails at more than one
foot-pound. The bond between the catheter 2101 and the marker band
fails at more than one foot pound. The bond between the extension
tube and the catheter tubing 2126 fails at more than one foot
pound.
[0692] FIG. 10B depicts an embodiment of the electromagnetic sensor
2116 that may be implemented with the catheter of FIG. 10A. The
sensor 2116 includes a sensor body 2117. The body 2117 is elongated
and generally cylindrical. However, the body 2117 may have a
variety of shapes. The body 2117 is formed from a metal or other
material that is responsive to an electromagnetic field. The body
2117 is symmetric about a longitudinal axis 2119. The body 2117
includes a geometric center 2121.
[0693] The sensor 2116 has its own local coordinate system that is
defined by the geometric center 2121 and the longitudinal axis
2119. The remaining two axes are orthogonal to the longitudinal
axis 2119 and intersect the center 2121. In some embodiments, the
z-axis extends along the sensor's length and thus corresponds with
the longitudinal axis 2119 as illustrated, with an origin at the
sensor's center 2121. However, it is possible to move the origin
along the z-axis. With a 5DOF sensor 2116, the orthogonal X and Y
axes are not fixed, due to the inability to determine rotation
about the z-axis.
[0694] With a 5DOF sensor 2116, information may be provided on the
three translation values on the x, y and z-axes and any two of the
three rotation values--roll, pitch and yaw. However, the rotation
around the sensor's longitudinal axis 2119 cannot be determined. As
such, only five degrees of freedom (5DOF) can be determined for
single sensor embodiments.
[0695] FIG. 10C depicts an embodiment of a voltage sensor 2160 that
may be implemented with the catheter of FIG. 10A. In some
embodiments, the voltage sensor 2160 may incorporate a micro sized
integrated circuit (IC) as developed for an ingestible event marker
by Proteus Digital Health, of Redwood, Calif. A micro size
integrated circuit (IC) is embedded inside the swallowable balloon
capsule. When the circuit is exposed to stomach fluid it provides
an electrolyte to the circuit that powers a battery constructed on
the surface of the circuit. The IC then powers up and communicates
with a body mounted receiver. The receiver then communicates with
an external device like a smart phone or tablet computer to provide
information to the health care provider about when the capsule has
reached the gastric fluid of the patient.
[0696] In some embodiments, the IC is coupled with the intragastric
device, such as the device 1520 or 1620, of the electromagnetic
tracking system. Once the device has reached the stomach it is
provided the electrolyte to power the battery and communicate with
its receiver indicating that the device is inside the stomach. The
IC would then separate from the balloon capsule and pass naturally
through the digestive tract.
[0697] An alternate embodiment includes creating a voltage
potential near the intragastric device by embedding an anode 2165
and a cathode 2170 into the sensor 2160 as shown in FIG. 10C. In
some embodiments, the anode 2165 and cathode 2170 is embedded in a
catheter, such as the catheter 2101. The anode 2165 and cathode
2170 create a voltage potential between electrodes when in the
presence of an electrolyte (such as stomach fluid). This generated
voltage is passed through the catheter using miniature magnet wire
and connected to a system that analyzes the voltage and reports
confirmation of a threshold voltage level that would be sufficient
to be confident that the catheter has entered the stomach. Once
confirmation of threshold voltage is received, the catheter with
attached electrodes would be withdrawn from the body after
inflating the balloon, thus removing any potential risk of
ingesting the anode/cathode materials.
[0698] The advantage of the voltage sensor 2160, with either the IC
system or the anode/cathode configuration, is that the voltage
sensor 2160 would only provide confirmation of position when it is
in the presence of gastric fluid--thus preventing the doctor from
prematurely inflating the balloon outside the stomach.
[0699] Another advantage of the catheter electrode system is that
no foreign materials would be left inside the patient's body after
balloon deployment (other than the balloon system itself).
[0700] Another embodiment includes the use of specific coatings on
the intragastric device or catheter that could control the timing
of when the electrodes are exposed to the stomach fluid, thus
controlling the timing of voltage generation. These coatings could
be hydrophilic to speed up exposure time, only soluble at low pH
values (less than 5.0), or enteric coated to delay the exposure
time.
[0701] FIG. 11 depicts an embodiment of an external reference
sensor assembly 2200 that may be used as anatomical reference
sensors with the systems of FIGS. 2-4. The assembly 2200 includes a
sensor 2215 connected to a cable 2210. On the opposite end of the
cable 2210 is a connector 220 for connecting the assembly 2200 to
the system control unit, such as the system control unit 1535 or
1635. The sensor 2215 may attach to the back side of a patient and
be fixed. The sensor 2215 may be fixed to the patient with
mechanical or other suitable means, for instance adhesive or clips
for attachment to clothing.
[0702] FIG. 12 depicts an embodiment of a jumper cable 2300 that
may be used with the systems of FIGS. 2-4. The jumper cable 2300
may provide a connector gender changer to prevent misconnection
between the sensor interface unit and the catheter, for instance
between the sensor interface unit 1630 and the catheter 1602 in the
system 1601 of FIG. 3A The cable 2300 includes a connector 2310.
The connector 2310 may be a four-pin female connector, but other
connector types may also be used. The cable 2300 further includes
heat shrink tubing 2340 along the length of the cable 2300. On the
opposite end as the connector 2310 is a second connector 2330 with
an EPROM chip 2320. The second connector 2330 may be a ten-pin male
connector, but other connector types may also be used.
Magnetic Real-Time Confirmation of Placement
[0703] In certain embodiments, a magnetic tracking technology as is
commercially available is employed. Suitable systems include, but
are not limited to, the magnetic sensor system as developed by
Lucent Medical Systems, Inc. of Kirkland, Wash. It is noted that
embodiments using an electromagnetic-based system, such as
embodiments incorporating the Aurora system from NDI, Inc.,
described above, employ active electromagnetic sensors, as
described above. This is in contrast to embodiments that employ
passive magnetic sensors, such as embodiments that incorporate the
Lucent System, and which embodiments are described in further
detail below.
[0704] The Lucent System
[0705] The Lucent Medical Systems technology is described in U.S.
Pat. No. 5,879,297, U.S. Pat. No. 6,129,668, U.S. Pat. No.
6,216,028, and U.S. Pat. No. 6,263,230, the contents of which are
hereby incorporated by reference in their entirety. The Lucent
technology is generally directed to a system and method for
detecting the location of an intragastric device within the body of
a patient and, more specifically, to a detection apparatus which
senses magnetic field strength generated by a magnet associated
with the intragastric device.
[0706] The Lucent system can be employed to locate the intragastric
device, e.g., the intragastric balloon, or one or more portions of
a catheter employed to place, inflate, deflate, and/or remove the
intragastric balloon. The location of the intragastric device is
determined by sensing the magnetic field produced by a permanent
magnet associated with the intragastric device. As used herein, the
term "associated with" means permanently fixed, removably attached,
or in close proximity with, the intragastric device. In one
embodiment, the magnet is associated with a catheter at a location
above the intragastric balloon. In another embodiment, the magnet
is associated with the intragastric balloon itself. The magnet can
be a small, cylindrical, rotatably attached, rare-Earth magnet.
Suitable magnets include rare Earth magnets such as samarium cobalt
and neodymium iron boron, both of which generate high field
strengths per unit volume. While magnets which generate a high
field strength for their size are preferred, weaker magnets such as
Alnico, ceramic, or ferric magnets may also be utilized.
[0707] Since the magnet is permanent, it requires no power source.
Accordingly, the magnet maintains its magnetic field indefinitely,
which allows long-term positioning and detection of the
intragastric device without the disadvantages associated with an
internal or external power source. In particular, by avoiding the
use of a power source, the undesirable electrical connections
necessary for the use of a power source are avoided. Thus, there is
no risk of electric shock to (or possible electrocution of) the
patient. Furthermore, the magnet's static magnetic field passes
unattenuated through body tissue and bone. This property allows the
use of the device to detect the intragastric device at any location
within the patient's body.
[0708] One known technique for locating a medical tube in the body
of a patient is described in U.S. Pat. No. 5,425,382, which is
incorporated herein by reference in its entirety. A tube with a
permanent magnet located in its tip is inserted into the patient,
e.g., a feeding tube that is inserted into the patient's nose, down
the esophagus, and into the stomach. A detection apparatus is used
to sense the magnet's static magnetic field strength at two
different distances and while immersed in the Earth's ambient
magnetic field. By measuring the static magnetic field strength at
two different distances, the detection apparatus determines the
magnetic field gradient. As the detection apparatus is moved about
the patient's body, greater and lesser magnetic field gradients are
indicated. The tube is located by moving the detection apparatus
until the greatest magnitude is indicated by the detection
apparatus.
[0709] The detection apparatus described in U.S. Pat. No.
5,425,382, incorporated herein by reference in its entirety,
utilizes first and second magnetic sensors. The magnetic sensors
may each comprise flux-gate toroidal sensors to detect the magnetic
field gradient. An alternative magnetic field gradient detector
system is described in U.S. Pat. No. 5,622,169, which is
incorporated herein by reference in its entirety. The magnetic
sensors each comprise three orthogonally arranged flux-gate
toroidal sensor elements. The magnetic sensor comprises magnetic
sensor elements that are orthogonally arranged to measure magnetic
field strength in three orthogonal directions. Similarly, the
magnetic sensor comprises magnetic sensor elements to measure
magnetic field strength in the x, y, and z directions,
respectively. Using the sensors, the magnetic field gradient may be
determined in the x, y, and z directions. With measurements of
magnetic field gradient in three directions, the location of the
magnet may be readily determined using conventional vector
mathematics. The mathematical sign of the magnetic gradient is
indicative of the direction of the magnetic field dipole of the
magnet. The magnet, and hence the intragastric device, is detected
using a known detection apparatus that contains at least two static
magnetic field strength sensors configured geometrically to null
detection of ambient, homogeneous magnetic fields (e.g., the
Earth's field), while still detecting the magnetic field strength
gradient produced by the magnet. The magnet detection apparatus
detects the location of the magnet based on the difference in
magnetic field strength at the two sensors. However, it is possible
to construct a magnetic field detection apparatus with different
sensor configurations to provide additional data related to the
position and orientation of the magnet. The various embodiments are
directed to a technique for detection of a magnet using a
multisensor array and a convergence algorithm that can accurately
locate the position of the magnet in three dimensions.
[0710] One embodiment of a passive magnetic detector system 100 is
shown in FIG. 13. The detector system 100 includes a housing 102,
control switches 104 such as a power switch and a reset switch, and
a display 106. In an exemplary embodiment, the display 106 is a
two-dimensional liquid crystal display. The display 106 may have an
opaque background, or have a transparent area which allows the
caregiver to view the skin below the surface of the detector system
100. The ability to view external patient landmarks significantly
aids in the placement of catheters using the detector system 100.
Alternatively, the display 106 may be an external display such as a
video monitor.
[0711] Also mounted within the housing 102 are first, second,
third, and fourth magnetic sensors 108, 110, 112, and 114,
respectively. In a preferred embodiment, the static magnetic
sensors 108-112 are spaced to provide maximal separation within the
housing 102. In an exemplary embodiment, the magnetic sensors
108-112 are arranged in a substantially planar fashion within the
housing 102 and located proximate the corners of the housing.
[0712] The orientation of the magnetic sensors 108-114 is
illustrated in FIG. 14 where the magnetic sensors 108-114 are
positioned at locations S.sub.1 to S.sub.4, respectively, near the
corners of the housing 102. Although the system 100 described in
FIGS. 13 and 14 illustrates a rectangular configuration for the
magnetic sensors 108-114, the principles of are readily applicable
to any multisensor array. Accordingly, the system is not limited by
the specific physical arrangement of the magnetic sensors.
[0713] In an exemplary embodiment, each of the magnetic sensors
108-114 comprise three independent magnetic sensing elements
orthogonally arranged to provide three-dimensional measurement in
the x, y, and z directions. The sensing elements of the magnetic
sensors 108-114 are aligned with respect to a common origin such
that each magnetic sensor senses the static magnetic field in the
same x, y, and z directions. This permits the detection of magnetic
field strength in a three-dimensional space by each of the magnetic
sensors 108-114. The arrangement of the magnetic sensors 108-114
permits the detection of a magnet in a three-dimensional space
within the patient. That is, in addition to locating the magnet
within the patient, the detector system 100 provides depth
information.
[0714] The configuration of the magnetic sensors 108-114 can be
readily changed for specialized application. For example, a
plurality of magnetic sensors may be configured in a spherical
arrangement around a patient's waist to detect the location of the
magnet 120 in the stomach. Furthermore, the magnetic sensing
elements need not be orthogonally arranged. For example, the
magnetic sensing elements may be configured in a planar array or
other convenient configuration suited to the particular application
(e.g., the spherical arrangement). The detector system must have at
least as many sensing elements to provide data as there are
unknowns in the equations to be solved and that the location and
orientation of the magnetic sensing elements be known.
[0715] It is desirable to detect the position and orientation of
the magnet 120 in three dimensional space. This results in five
unknown parameters, that may conveniently be considered as x, y, z,
.theta., and .phi. where x, y, and z represent coordinates of the
magnet 120 in three dimensional space relative to an origin such as
the center of the housing 102, .theta. is the angular orientation
of the magnet in the YZ plane and .phi. is the angular orientation
of the magnet in the XY plane. In addition, the contribution of the
Earth's magnetic field in the x, y, and z directions is unknown.
Thus, the model used by the detector system 100 has eight unknown
parameters that require eight independent measurements. In an
exemplary embodiment of the detector system 100 described herein, a
set of twelve magnetic sensing elements is used to provide over
sampling. This results in greater reliability and accuracy while
maintaining the computational requirements at a reasonable
level.
[0716] The mathematical description provided below may be most
easily understood with respect to a Cartesian coordinate system
using magnetic sensing elements orthogonally arranged in the x, y,
and z directions. However, it should be clearly understood that the
embodiments not limited to such an arrangement. Any alignment of
the magnetic sensing elements may be used with the detector system
100 so long as the location and orientation of the magnetic sensors
108-114 are known. Therefore, the system is not limited by the
specific configuration of magnetic sensing elements.
[0717] As illustrated in FIG. 14, a magnet 120 is positioned at a
location .alpha.. As is known in the art, the magnet 120 has a
magnetic dipole that is represented by the 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 location of the magnet at location .alpha. with a single
measurement. However, the presence of the Earth's magnetic field,
stray magnetic fields that may be present near the vicinity of the
magnet 120, internal noise from the magnet sensors 108-114,
internal noise generated by electronics associated with the
magnetic sensors, such as amplifiers and the like, make it
virtually impossible to perform a measurement under "ideal"
conditions. To provide accurate positional information for the
magnet 120 in the presence of various forms of noise, the detector
system 100 uses known formulas for magnetic field strength, plus
actual sensor measurements as inputs to an estimation algorithm
that converges to provide an accurate reading of the location and
orientation of the magnet 120.
[0718] The elements used to process data from the magnetic sensor
108-114 are illustrated in a functional block diagram of FIG. 15A
where the magnetic sensors 108-114 are coupled to analog circuitry
140. The specific form of the analog circuitry 140 depends on the
specific form of the magnetic sensors 108-114. For example, if the
magnetic sensors 108-114 are orthogonally positioned flux-gate
toroidal sensors, similar to those illustrated in FIG. 14, the
analog circuitry 140 may include amplifiers and integrators such as
discussed in U.S. Pat. Nos. 5,425,382 and 5,622,669, the contents
of which are hereby incorporated by reference in their entirety. In
another exemplary embodiment, the magnetic sensors 108-114 comprise
magneto-resistive elements whose resistance varies with the
strength of a magnetic field. Each magnetic sensor 108-114
comprises three orthogonally arranged magneto-resistive sensing
elements to sense the static magnetic field in the x, y, and z
directions, respectively.
[0719] However, the magnetic sensors 108-114 may be any form of
magnetic sensor. Several different types of magnetic sensors may be
used in the practice of the methods of embodiments, including, but
not limited to, Hall-effect, flux-gate, wound-core inductive,
squid, magneto-resistive, nuclear precession sensors, and the like,
as described elsewhere herein. Commercial magnetic field gradient
sensors in the form of an integrated circuit can also be used with
the detector system 100. Furthermore, the magnetic sensors 108-114
need not be identical types of sensors. For example, the magnetic
sensors 108-112 may be one type of sensor while the magnetic sensor
114 may be a different type.
[0720] The analog circuitry 140 is designed to operate with the
specific form of the magnetic sensors 108-114.
[0721] The output of the analog circuitry 140 is coupled to an
analog-to-digital converter (ADC) 142. The ADC 142 converts the
analog output signals from the analog circuitry 140 to a digital
form. The operation of the ADC 142 is well known to those of
ordinary skill in the art and will not be described in detail
herein. The detector system 100 also includes a central processing
unit (CPU) 146 and a memory 148. In an exemplary embodiment, the
CPU 146 is a microprocessor, such as a Pentium.TM. or the like. The
memory 148 may include both read-only memory and random access
memory. The various components, such as the ADC 142, CPU 146,
memory 148, and display 106 are coupled together by a bus system
150. As can be appreciated by those of ordinary skill in the art,
the bus system 150 illustrates a typical computer bus system and
may carry power and control signals in addition to data.
[0722] Also illustrated in the functional block diagram of FIG. 15A
is an estimation processor 152. The estimation processor 152
performs an iterative comparison between an estimated position of
the magnet 120 and a measured position of the magnet 120 based on
data derived from the magnetic sensors 108-114. The iterative
process continues until the estimated position and the measured
position converge, resulting in an accurate measurement of the
location .alpha. (see FIG. 14) of the magnet 120. 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 the sake of clarity, the functional block
diagram of FIG. 15A illustrates the estimation processor 152 as an
independent block since 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).
[0723] The detector system 100 assumes that the magnetic sensors
108-114 are sufficiently far from the location .alpha. of the
magnet 120 that the magnet may be treated as a point dipole source.
In addition, it is assumed that the spatial variation of any
extraneous magnetic fields, such as the Earth's magnetic field, is
small compared to the inhomogeneity produced by the presence of the
point dipole source. However, under some circumstances,
perturbations in the Earth's magnetic field may be caused by
extraneous sources such as nearby electrical equipment, metallic
building structural elements, and the like. The detector system 100
can be readily calibrated to compensate for such perturbations.
[0724] The equations used by the estimation processor 152 are
readily derived from the fundamental laws of physics related to
electricity and magnetism. A static magnetic field B produced by
the magnetic dipole of a strength m, and situated at a location
.alpha., and measured at a location s is given by the
following:
B ( s ) = 3 ( ( s - a ) m ) ( s - a ) - s - a 2 m s - a 5 ( 1 )
##EQU00001##
where .parallel.s-.alpha..parallel..sup.5 all is a modulus value
well known in matrix mathematics (e.g.,
.parallel.s-.alpha..parallel..sup.2 is a square modulus). It should
be noted that the values .alpha., 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 (i.e., 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. Those skilled in the art can
appreciate that the detected magnetic field strength may vary as
the magnet 120 is moved within the patient or as the detector
system 100 is moved with respect to the magnet. However, relative
movement between the detector system 100 and the magnet 120 is not
essential. The detector system 100 can readily determine the
location and orientation of the magnet 120 in three-dimensional
space even when the detector system and the magnet are not moving
with respect to each other.
[0725] The values from the magnetic sensors 108-114 can be used in
equation (1) to determine the strength of the magnetic field B at
locations S.sub.1-S.sub.4, respectively. Changes in the magnetic
field B over distance is defined as a gradient G(s) of B, which is
a derivative of B with respect to s. The gradient G(s) can be
represented by a 3.times.3 matrix derived from equation (1) and
expressed in the following form:
G ( s ) = - ( 15 ( ( s - a ) m ) ) ( s - a ) ( s - a ) T + 3 s - a
2 ( ( s - a ) m T + m ( s - a ) T + ( ( s - a ) m ) I ) s - a 7 ( 2
) ##EQU00002##
where T is a matrix transpose and I is a 3.times.3 identity matrix
having the following form:
I = [ 1 0 0 0 1 0 0 0 1 ] ##EQU00003##
[0726] It should be noted that equation (1) could be solved
directly for the value a given the values B, m, and s. However,
such a calculation can be difficult to solve and may require
significant computing power. The iterative estimation process
described below determines the location .alpha. and orientation of
the magnet 120 by estimating the location .alpha. and comparing a
predicted or estimated magnetic field that would result from the
magnet 120 being located at the estimated location with the actual
measured magnetic field as measured by the magnetic sensors
108-114. The iterative process varies the estimated location in a
controlled manner until the predicted magnetic field closely
matches the measured magnetic field. At that point, the estimated
location and orientation matches the actual location .alpha. and
orientation of the magnet 120. Such an iterative process can be
performed very quickly by the detector system 100 without the need
for extensive computational calculations required to solve for the
location .alpha. directly using equation (1). The difference
between the predicted magnetic field and the actual measured
magnetic field is an error, or error function, that may be used to
quantitatively determine the location .alpha. of the magnet 120.
The error function is used in the iterative process to refine the
estimated location of the magnet 120. Equation (2), indicating the
gradient G(s) is used by the estimation processor 152 (see FIG. 3A)
to determine the magnitude and a direction of error in the
estimated location. Thus, equation (1) is used to generate
predicted values and equation (2) uses the error results to
determine how to alter the estimated position of the magnet
120.
[0727] The magnetic field strength B is measured at each of the
locations S.sub.1-S.sub.4 by the magnetic sensors 108-114,
respectively. While only four magnetic sensors are illustrated in
FIG. 13 to FIG. 15A, the measurement may be generalized to n
sensors such that each of the magnetic sensors provides a
measurement of B(s.sub.i) at points s.sub.1, where i=1 to n. The
estimation processor 152 calculates quantities .DELTA..sub.ij
(measured)=B(s.sub.i)-B(s.sub.j). This calculation provides a
measure of the gradient from magnetic sensor i to magnetic sensor j
and also cancels out the effects of the Earth's magnetic field,
which is constant (i.e., gradient=0) at the magnetic sensor i and
the magnetic sensor j. The estimation processor 152 also calculates
predicted values .DELTA..sub.ij (predicted) from equation (1). The
estimate for the value a is adjusted until the measured values
.DELTA..sub.ij (measured) and predicted values .DELTA..sub.ij
(predicted) match as closely as possible. For example, the detector
system 100 may initially assume that the location .alpha. of the
magnet 120 is centered under the housing 102. Based on this
estimated location, the estimation processor 152 calculates the
predicted values for magnetic field strength at each of the
magnetic sensors 108-114 that would result if the magnet 120 were
actually at the estimated location. In an exemplary embodiment, the
sensing elements of each of the magnetic sensors 108-114 provide a
measure of the magnetic field B in three orthogonal directions
resulting in magnetic field strength values B.sub.xi, B.sub.yi, and
B.sub.zi where i equals 1 to n. Similarly, the gradient G(s) is
also calculated for each of the three orthogonal directions.
[0728] The estimation processor 152 also uses measured magnetic
field strength values from each of the magnetic sensors 108-114 and
compares A (predicted) with .DELTA..sub.ij (measured). Based on the
difference between .DELTA..sub.ij (predicted) and .DELTA..sub.ij
(measured), the estimation processor 152 generates a new estimated
location for the magnet 120 (see FIG. 14) and iterates the
prediction process until .DELTA..sub.ij (predicted) closely matches
.DELTA..sub.ij (measured).
[0729] The degree of match between .DELTA..sub.ij (predicted) and
.DELTA..sub.ij (measured) may be measured by a cost function
comprising the sum of the squares of the difference between
.DELTA..sub.ij (predicted) and .DELTA..sub.ij (measured) and then
using non-linear iterative optimization algorithms to minimize the
value of the cost function. The required gradients of the cost
function are calculated using equation (2) above. Many different,
well-known cost functions and/or optimization techniques, such as
quasi-Newton, may be used by the estimation processor 152 to
achieve the desired degree of match between .DELTA..sub.ij
(predicted) and .DELTA..sub.ij (measured).
[0730] The iterative measuring process performed by the estimation
processor 152 can be done in a short period of time. A typical
measurement cycle is performed in fractions of a second. As the
tube and associated magnet 120 are moved within the patient, the
position and orientation of the magnet will change. However,
because the measurement cycle is very short, the change in position
and orientation of the magnet will be very small during any given
measurement cycle, thus facilitating real-time tracking of the
magnet as the magnet is moved inside the patient or as the housing
102 is moved on the surface of the patient.
[0731] As discussed above, the estimation processor performs an
iterative comparison between an estimated position of the magnet
and a measured position of the magnet. The initial estimated
location may be derived by a number of possible techniques, such as
random selection, a location under the sensor element 108-114
having the strongest initial reading, or, by way of example, the
detector system 100 may initially estimate the location .alpha. of
the magnet 120 is centered under the housing 102. However, it is
possible to provide a more accurate initial estimation of the
location .alpha. of the magnet 120 using a neural network 154,
shown in FIG. 15A. It should be noted that the neural network 154
is preferably implemented by computer instructions stored in the
memory 148 and executed by the CPU 146. However, for the sake of
clarity, the functional block diagram of FIG. 15A illustrates the
neural network 154 as an independent block since 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, by virtue of
a learning process, are capable of receiving and processing large
amounts of data in order to generate solutions to problems with
many variables. The operation of a neural network is generally
known in the art, and thus will be described herein only with
respect to the specific application. That is, the operation of the
neural network 154 to generate an initial position estimate will be
discussed.
[0732] The neural network 154 has a learn mode and an operational
mode. In the learn mode, the neural network 154 is provided with
actual measurement data from the magnetic sensors 108-114. Since
each of the magnetic sensors 108-114 have three different sensing
elements, a total of 12 parameters are provided as inputs to the
neural network 154. Based on the 12 parameters, the neural network
154 estimates the location and orientation of the magnet 120. The
neural network 154 is then provided with data indicating the actual
location and orientation of the magnet 120. This process is
repeated a large number of times such that the neural network 154
"learns" to accurately estimate the location and orientation of the
magnet 120 based on the 12 parameters. In the present case, the
learning process described above (e.g., providing 12 parameters,
estimating the location, and providing the actual location) was
repeated 1,000 times. The neural network 154 learns the best
estimated position for a set of 12 parameters. It should be noted
that the user of the detector system 100 need not operate the
neural network 154 in the learn mode. Rather, data from the learn
mode process is provided along with the detector system 100. In
normal operation, the neural network 154 is utilized only in the
operational mode.
[0733] In the operational mode, the 12 parameters from the magnetic
sensors 108-114 are given to the neural network 154, which
generates an initial estimate of the location and orientation of
the magnet 120. Based on experiments performed by the inventors,
the neural network 154 can provide an initial estimate of the
location of the magnet 120 within approximately .+-.2 cm. Such an
accurate initial estimate reduces the number of iterations required
by the estimation processor 152 to accurately determine the
location .alpha. of the magnet 120. It should be noted that if the
location .alpha. of the magnet 120 is sufficiently far from the
detector system 100, the magnetic sensors 108-114 will provide very
low signal levels. Accordingly, the neural network 154 will not
generate an initial estimate until the parameters (i.e., the 12
input signals from the magnetic sensors 108-114) are above a
minimum threshold and can therefore provide a reliable signal.
[0734] Given an accurate initial estimate, the estimation processor
152 can perform the iteration process described above and determine
the location .alpha. of the magnet 120 within .+-.1 mm.
[0735] The detector system 100 also includes a display interface
156, shown in FIG. 15A, to permit the magnet image to be displayed
on an external display (not shown). As those skilled in the art
will appreciate, many of the components of the detector system 100,
such as the CPU 146 and the memory 148 are conventional computer
components. Similarly, the display interface 156 may be a
conventional interface that allows the detector system image to be
shown on a PC display or other monitor, such as a live image
monitor 168 (see FIG. 15B).
[0736] 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 large number of sensors (e.g., sixteen sensors) uniformly
distributed throughout the housing 102 to form an array of magnetic
sensors (see FIG. 16). As the magnet 120 is moved relative to the
housing 102, the movement is detected by three or more of the
magnetic sensors and the position of the magnet calculated and
shown on the external display. In this embodiment, the user need
not reposition the housing, but simply views the external display
where the array of magnetic sensors can track the position of the
magnet 120.
[0737] Another advantage of an external video display is the
ability to combine the image generated by the detector system 100
with image data generated by conventional techniques. For example,
FIG. 15B illustrates the operation of the detector system 100 in
conjunction with a fluoroscope system 160. The fluoroscope system
160 is a conventional system that includes a fluoroscopic head 162,
a fluoroscopic image processor 164, and an image storage system
that includes a stored image monitor 166 and the live image monitor
168. In addition, a conventional video cassette recorder 170 or
other recording device (computer memory, DVD, etc.) can record the
images generated by the fluoroscope system 160 and images generated
by the detector system 100. The operation of the fluoroscope system
160 is known in the art.
[0738] The detector system 100 is fixedly attached to the
fluoroscopic head 162 in a known spatial relationship. A single
"snapshot" image of the patient can be obtained using the
fluoroscopic system 160 and displayed, by way of example, on the
live image monitor 168. As a catheter containing the magnet 120
(see FIG. 14) is inserted in the patient, the detector system 100
detects the location .alpha. of the magnet 120 in the manner
described above and can project the image of the magnet on the live
image monitor 168 along with the snapshot image of the patient. In
this manner, the user may advantageously utilize the snapshot
fluoroscope image provided by the fluoroscope system 160 combined
with the live image data provided by the detector system 100.
[0739] For satisfactory operation, it is preferred to have proper
alignment between the fluoroscope system 160 and the detector
system 100. This alignment or "registration" may be accomplished by
placing a radio-opaque marker on the chest of the patient where the
radio-opaque marker is aligned with the corners of the detector
system 100. When the fluoroscope system 160 generates the snapshot
image, the corners of the detector system 100 are indicated on the
live image monitor 168 by virtue of the radio-opaque markers. The
advantage of the image overlay using the detector system 100 is
that the patient is only momentarily exposed to radiation from the
fluoroscope system 160. Thereafter, the snapshot image is displayed
with data from the detector system 100 overlaid on top of the
snapshot image. Although this process has been described with
respect to the fluoroscope system 160, those skilled in the art can
appreciate that the system is applicable to any image-guided
surgical process using X-ray, magnetic resonance imaging (MRI),
positron emission tomography (PET), and the like.
[0740] The Earth's magnetic field is also detected by the magnetic
sensors 108-114. However, assuming the Earth's magnetic field to be
constant across the housing 102, the contribution of the Earth's
magnetic field to the readings from the magnetic sensors 108-114
will be 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. However, as discussed
above, there may be perturbations or inhomogeneity in the Earth's
magnetic field caused by metallic elements, such as equipment,
hospital bed rails, metal building structural elements, and the
like. Because of the unpredictable nature of such interfering
elements, proper operation of the detector system 100 requires
calibration. The detector system 100 may be readily calibrated to
compensate for localized perturbations in the Earth's magnetic
field using a calibration processor 158, shown in FIG. 15A. It
should be noted that the calibration processor 158 is preferably
implemented by computer instructions stored in the memory 148 and
executed by the CPU 146. However, for the sake of clarity, the
functional block diagram of FIG. 15A illustrates the calibration
processor 158 as an independent block since 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).
[0741] An initial calibration is performed before the magnet 120 is
introduced into the patient. Thus, initial calibration occurs
outside the presence of the magnetic field generated by the magnet
120. A measurement is performed using the detector system 100.
Under ideal conditions, with no localized perturbations in the
Earth's magnetic field, the signals generated by the magnetic
sensors 108-114 will be the same. That is, each of the sensing
elements oriented in the x direction will have identical readings,
while each of the sensing elements oriented in the y direction will
have identical readings and each of the elements oriented in the z
direction will have identical readings. However, under normal
operating conditions, localized perturbations in the Earth's
magnetic field will exist. Under these circumstances, the signals
generated by each sensor element of the magnetic sensors 108-114
all have some different value based on the detection of the Earth's
magnetic field. The readings of any two of the magnetic sensors
108-114 may be differentially combined which, theoretically, will
cancel out the Earth's magnetic field. However, due to localized
perturbations in the Earth's magnetic field, there may be an offset
value associated with the reading.
[0742] The calibration processor 158 determines the offset values
associated with each of the magnetic sensors and compensates for
the offset values during the measurement cycle. That is, the offset
value for each of the magnetic sensors 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 will be zero before the magnet 120 is introduced.
Thereafter, as the magnet 120 is introduced, the differential
readings from the magnetic sensors 108-114 will have nonzero values
due to the static magnetic field generated by the magnet 120. If
the detector system 100 is stationary, as illustrated in FIG. 15B,
a single calibration process is sufficient to cancel out the
effects of the Earth's magnetic field, including localized
perturbations caused by external objects, such as metallic
equipment, building structural elements, and the like.
[0743] However, in certain embodiments, it is desirable to move the
detector system 100 over the surface of the patient. As the
detector system 100 is moved to a new position on the patient, the
localized perturbations in the Earth's magnetic field may cause a
degradation in the accuracy of the detector system 100 since the
effects of the localized perturbations may no longer be completely
canceled. However, the calibration processor 158 allows a
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 a digitizing
arm 180. The digitizing arm 180 is a conventional component that
allows three-dimensional movement. The digitizing arm 180 may be
conveniently attached to the patient bedside. In a preferred
embodiment, the detector system 100 is attached to the digitizing
arm and oriented such that the three dimensions of movement of the
digitizing arm correspond to the x axis, y axis, and z axis,
respectively, of the 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 utilizes this position data
to calculate the change in the measured magnetic field caused by
the magnet 120 as the detector system 100 is moved. In this manner,
the localized effects of the magnet 120 may be removed, with the
resultant measurement being indicative of the localized
perturbations of the Earth's magnetic field at the new position of
the detector system 100.
[0744] The automatic recalibration process is particularly useful
in a situation, such as a peripherally inserted central catheter
(PICC), which may typically be inserted in the patient's arm and
threaded through the venous system into the heart. Using
conventional technology, the surgeon would typically place marks on
the chest of the patient to mark the expected route over which the
catheter will be inserted. Without the use of location sensing
technology, the surgeon must blindly insert the catheter and verify
its location using, by way of example, fluoroscopy. However, the
detector system 100 permits the surgeon to track the placement of
the PICC.
[0745] In the example above, the detector system 100 may be located
over the arm of the patient where the PICC will be initially
inserted. Following the initial calibration (in the absence of the
magnet 120) the detector system 100 is calibrated and will
compensate for the effects of the Earth's magnetic field including
any localized perturbations. When the magnet 120 is introduced, the
detector system 100 detects and displays the location .alpha. of
the magnet in the manner previously described. As the surgeon
inserts the PICC (with the attached magnet 120), it may be
desirable to relocate the detector system to thereby track the
progress of the PICC. Using the digitizing arm 180, the surgeon
relocates the detector system 100 to a new location. For example,
assume that the detector system 100 is moved six inches in the y
direction, three inches in the x direction, and has not moved in
the z direction. Based on the new location of the detector system
100, and using the technology described above, the estimation
processor 152 (see FIG. 15A) can calculate the magnetic field at
the new location due to the magnet 120. Given the contribution to
magnetic field at the new location that results from the magnet
120, it is possible to subtract out the effects of the magnet 120.
In the absence of the magnetic field from the magnet 120, any
remaining or "residual" magnetic field is assumed to be the result
of the Earth's magnetic field. The residual reading is processed in
the manner described above for an initial calibration to thereby
rezero or recalibrate the detector system 100 to compensate for the
Earth's magnetic field, including localized perturbations, at the
new location. Following this recalibration process, a measurement
cycle may be initiated with the resultant measurement of the
magnetic field being due solely to the presence of the magnet
120.
[0746] The user may manually recalibrate the detector system 100 at
any point in time. However, the advantage of the technique
described above is that the detector system 100 may be
automatically recalibrated on a continuous basis as the detector
system 100 is used. The digitizing arm 180 provides a continuous
reading of the position of the detector system 100 and thus makes
it possible to accurately track the location of the detector
system. As the detector system 100 moves, it is constantly
recalibrated to recompensate for the Earth's magnetic field. In the
example above, the detector system 100 may be moved at will to
follow the movement of the PICC as it is inserted into the heart
without concern that external influences, such as a hospital bed
rail, will cause a degradation in the accuracy of the measurement.
Although the recalibration system has been described above with
respect to the digitizing arm 180, it can be appreciated that other
position sensing systems may also be readily utilized.
[0747] For example, commercial tracking systems are manufactured by
Ascension Technology and Polhemus. The system manufactured by
Ascension Technology, known as the "Bird Tracker" comprises an
array of sensors that measure six degrees of freedom and provide
accurate measurements within one-half inch at a distance of five
feet and provide rotational information within one-half degree at a
distance of five feet. The sensing elements used in the Bird
Tracker may be attached to the housing 102 and the position of the
housing tracked using the commercial system. Similarly, the
Polhemus device, known as the "3-D Tracker," provides similar
location measurements without the need of the digitizing arm
180.
[0748] Another application of position tracking, using, by way of
example, the digitizing arm 180 permits the surgeon to provide
digitized landmarks that will be shown on the display. A common
surgical technique to assist in insertion of a catheter is to place
landmarks on the surface of the patient that approximate the route
that will be taken by the catheter. For example, with conventional
technology the surgeon may place a series of x's on the patient's
chest with a marker pen as landmarks to assist in insertion of
electrical pacemaker leads. With the principles described herein,
the digitizing arm 180 may be used to electronically record
landmarks specified by the surgeon. This aspect is illustrated in
FIG. 17A, when a computer input stylus 182 or other electronic
input device is mounted to the digitizing arm 180. The computer
stylus 182 may be attached to the detector system 100 or attached
to the digitizing arm 180 in a position corresponding to, by way of
example the center of the detector system. Prior to insertion of
the catheter with the magnet 120, the surgeon may utilize the
digitizing arm 180 and the computer stylus 182 to electronically
generate landmarks, illustrated in FIG. 17A by a series of x's. It
should be noted that the computer stylus 182 electronically "marks"
the patient, but need not place any actual marks on the patient. In
the example above, where heart pacemaking leads will be inserted,
the surgeon may place a series of electronic landmarks from the
neck to the heart along the route in which the pacemaker leads will
be inserted. At each landmark, the digitizing arm 180 records the
position marked by the surgeon. In subsequent operation, when the
catheter with the magnet 120 is inserted into the patient, the
digitizing arm 180 notes the location of the magnet 120 with
respect to the landmarks previously marked by the surgeon. The
landmarks are shown on an external display 184, shown in FIG. 17B,
along with the position of the magnet 120, which is indicated by an
arrow. As the surgeon inserts the magnet 120, the progress is shown
on the external display 184 such that the magnet 120 passes along
from landmark 1 to landmark 2 to landmark 3, and so forth. With
this technique, the surgeon can readily detect divergence from the
expected route. For example, if the catheter and magnet 120 are
inadvertently diverted into a different vein, the surgeon will
readily note the divergence from the marked pathway and quickly
identify the problem. The catheter and magnet 120 may be withdrawn
and reinserted to follow the landmarked pathway.
[0749] The general operation of the detector system 100 is
illustrated in the flowchart of FIG. 18A. At a start 200 the magnet
120 (see FIG. 14) has been inserted into the patient. In step 201,
the system undergoes an initial calibration. In an exemplary
embodiment, the initial calibration is performed before the magnet
120 is introduced. Thus, the system 100 compensates for the effects
of the Earth's magnetic field, including localized perturbations,
in the absence of any contribution from the magnet 120.
Alternatively, the magnet 120 may be positioned in a known location
with respect to the housing 102 such that the effects of the
magnetic field caused by the magnet 120 are known and can be
canceled in the manner described above with respect to the
automatic recalibration process. That is, the contribution to the
measured magnetic field caused by the magnet 120 in the known
location can be subtracted from the measured readings with the
resultant residual value being caused only by the Earth's magnetic
field. Following 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 location .alpha. 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
relating the position of each of the magnetic sensors 108-114
relative to a selected origin. For example, one magnetic sensor
(e.g., magnetic sensor 108) may be arbitrarily selected as the
mathematical origin for purposes of determining the relative
positions of the other magnetic sensors (e.g., magnetic sensors
110-114). The common origin provides a frame of reference for
purposes of the mathematical calculations. As previously discussed,
the magnetic sensors 108-114 are aligned with respect to the common
origin so that each magnetic sensor measures the magnetic field in
the same x, y, and z directions. As those of ordinary skill in the
art can appreciate, any selected origin can be used satisfactorily
with the detector system 100.
[0750] The magnetic calibration data derived in step 209 is
typically provided by the magnet manufacturer and includes data
related to the strength of the magnetic dipole m (see FIG. 14), as
well as the size and shape of the magnet 120. The measured sensor
values, sensor position data, and magnet calibration data are
provided as inputs to the estimation processor 152 (see FIG. 15A)
in step 204A.
[0751] In an exemplary embodiment, the initial estimate of the
location .alpha. is provided by the neural network 154 (see FIG.
15A) based on the measured sensor values derived in step 202. As
previously discussed, the neural network 154 may require minimum
values from the magnetic sensors 108-114 to assure a reliable
initial estimate. The neural network 154 provides the initial
estimate of magnet location and orientation.
[0752] In step 210, the estimation processor 152 (see FIG. 15A)
calculates predicted sensor values. As described above, this
requires a measurement .DELTA..sub.ij (predicted) for each
combination of the 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 values (i.e.,
.DELTA..sub.ij (predicted)) with the measured sensor values (i.e.,
.DELTA..sub.ij (measured)). In decision 216, the estimation
processor 152 determines whether the predicted and measured sensor
values match within a desired degree of tolerance. If the predicted
sensor values and the measured sensor values are not a close match,
the result of decision 216 is NO. In that event, the estimation
processor 152 calculates a new estimate of the magnet location
.alpha. and orientation in step 218. Following the calculation of a
new estimated location .alpha. 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 magnet location
and orientation. The estimation processor 152 continues this
iterative process of adjusting the estimated location .alpha. of
the magnet 120 and orientation and comparing predicted sensor
values with measured sensor values until a close match is achieved.
When a close match between the predicted sensor values and the
measured sensor values is achieved, the result of decision 216 is
YES. In that event, in step 220A the detector system 100 displays
the magnet location .alpha. and orientation on the display 106 (see
FIGS. 15A, 15B, and 16). In addition, the detector system 100 may
display a confidence value indicative of a degree of confidence
with which the location .alpha. and orientation of the magnet 120
have been determined. The calculation of a confidence value based
on statistical data is well known in the art and need not be
described in detail herein. Following the display of location and
orientation data in step 220A, the detector system 100 returns to
step 202 and repeats the process on a new set of measured sensor
values. If cost function is too high, a close match may not be
achieved in decision 216. Such conditions may occur, for example,
in the presence of extraneous magnetic fields. In practice, it has
been determined that close matches have a cost function in the
range of 1-2 while the minimum cost function for an inaccurate
local minimal are orders of magnitude greater. If a close match
cannot be achieved (i.e., the cost function is too great), the
detector system 100 can start the measurement process anew with a
new estimated location or generate an error message indicating an
unacceptably high cost function.
[0753] The flowchart of FIG. 18B illustrates the steps performed by
the calibration processor 158 if automatic recalibration is
implemented within the detector system 100. In this implementation,
following the completion of step 220A, the system 100 may
optionally move to step 224, illustrated in FIG. 18B, wherein the
calibration processor 158 obtains the position data from the
digitizing arm 180 (see FIG. 15C) indicating the present location
of the detector system 100. Given the new location of the detector
system 100 and the known location .alpha. of the magnet 120, the
calibration processor 158 calculates the magnetic field resulting
from the magnet and subtracts the effects of the magnet from the
current measurements in step 226. As a result of this process, the
remaining residual values measured by the magnetic sensors 108-114
(see FIG. 15A) are due to the effects of the Earth's magnetic
field, including localized perturbations.
[0754] In step 228, this residual value is used to rezero the
detector system 100 to compensate for the effects of the Earth's
magnetic field at the new location. Following the recalibration
process, the detector system 100 returns to step 202, shown in FIG.
18A, to perform additional measurement cycles with the detector
system 100 at the new location and recalibrated for operation at
the new location.
[0755] 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 embodiment, the calibration processor 158 will perform
the recalibration process only if the detector system 100 has been
moved by a predetermined amount. This prevents the unnecessary
recalibration when the detector system 100 has not been moved.
[0756] The iterative estimation process is described above using
the difference in magnetic strength B provided by different pairs
of magnetic sensors 108-114. Alternatively, the detector system 100
can use the measured field gradient values G. In this embodiment,
equation (2) may be fit to the measured values, in a manner as
described above with respect to the iterative process to fit the
measurements of B. With respect to the flowchart of FIG. 18A, the
step 202 provides gradient values with respect to pairs of the
magnetic sensors 108-114. For example, a magnetic gradient
measurement 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 108-112,
respectively. In step 204A, the estimation processor 152 determines
an initial estimate of the magnet location and orientation, and, in
step 210, calculates predicted sensor values using equation (2). In
step 212, the measured sensor values are compared with the
predicted sensor values using conventional techniques, such as the
cost functions described above. The iterative process continues
until the measured sensor values and the predicted sensor values
match within the predetermined degree of tolerance.
[0757] In yet another alternative technique, the detector system
100 utilizes the measurement data and solves equation (2) for a
directly. The direct solution approach utilizes 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 for the location .alpha. and m directly.
This assumes that the magnitude, but not the direction, of m is
known. In practice, the magnitude m is known because 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 -
sign. The additional magnetic sensor, which need only measure the
magnetic field strength B, is used to determine the sign of the
mathematical function. In addition, combinations of these various
techniques may be used by the detector system 100 to determine the
location .alpha. of the magnet 120.
[0758] 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 multi-detector array formed by the
magnetic sensors 108-114. As is known to those of ordinary skill in
the art, Kalman filters are statistical predictive filters that use
statistical signal processing and optimal estimation. Numerous
textbooks, such as "Tracking And Data Association," by Y.
Bar-Shalom and R. E. Fortmann, Academic Press, Boston, 1988,
provide details on the theory and operation of Kalman filters. In
addition to the individual techniques described above, it is
possible to use any or all of these techniques in a combination,
such as a sum of cost functions for each sensor type. For example,
the differences between .DELTA.ij (predicted) and .DELTA.ij
(measured) can be required to match within a certain tolerance. If
the multiple mathematical techniques are unable to identify a
solution for which all difference values meet that tolerance, then
an error can be signaled to the operator using the display 106 (see
FIG. 15A). Assuming the errors in each sensor measurement are
independent and small, the uncertainty in the estimate of the
location .alpha. can be calculated using, for example, Cramer-Rao
bounds. Thus, a degree of redundancy between measurement techniques
can be advantageously implemented by the detector system 100. Such
redundancy is highly desirable for biomedical applications.
[0759] FIG. 13 illustrates the operation of the detector system 100
for a specific configuration of the magnetic sensors 108-114.
However, the techniques described above may be generalized to
virtually any fixed configuration of sensors. A minimum of one
gradient sensor or eight magnetic field sensors is required to
measure G(s) and B(s), respectively, assuming that the strength of
the magnetic dipole m is known. The magnetic sensors can be
configured relatively arbitrarily and thus may be readily
positioned at locations within the housing 102 (see FIG. 13) based
on instrument design and/or other signal or noise
considerations.
[0760] The magnetic sensors 108-114 may be calibrated using the
known strength of the Earth's magnetic field. In the absence of any
inhomogeneous fields (i.e., away from any strong magnetic dipoles)
the X sensor element of all sensors 108-114 can be read at the same
time. Similarly, all Y sensor elements and Z sensor elements can be
read at the same time. In any configuration, the sum of the squares
of the average readings of the magnetic field strength for each
orthogonal direction (i.e., B.sub.x, B.sub.y, and B.sub.z) should
be constant. The constant value of the Earth's magnetic field can
be used to determine the appropriate calibration factors for each
magnetic sensor using conventional algebraic and least squares
fitting methods.
[0761] An alternative calibration technique uses a small magnet of
known strength placed in one or more locations relative to the
magnetic sensors 108-114. Measurements are performed at each of the
one or more locations to determine the appropriate calibration
factors for each magnetic sensor. Other techniques, such as the use
of an electromagnetic cage, Helmholtz cage, or the like, may also
be used to calibrate the magnetic sensors 108-114.
[0762] The display 106 (see FIG. 13) provides graphical display of
the position of the magnet 120 with respect to the housing 102.
FIGS. 19A to 19D illustrate some of the different techniques used
by the detector system 100 to indicate the location .alpha. of the
magnet 120 (see FIG. 14). In the embodiment illustrated in FIG.
19A, the display 106 uses a circle 250 and a pair of orthogonal
lines 252a and 252b to indicate the location .alpha. of the magnet
120 relative to the housing 102. The orthogonal lines 252a and 252b
provide a visual indicator to the caregiver to assist in
determining when the magnet 120 is centered under the detector
system 100.
[0763] In an alternative embodiment, illustrated in FIG. 19B, a
fixed indicator 254, such as orthogonal lines 254a and 254b, form
cross-hairs over the center of the display 106. The circle 250, or
other indicator, is used to provide a visual indication of the
location .alpha. of the magnet 120 relative to the housing 102. The
circle 250 is centered in the cross-hairs in the center of the
display 106 when the magnet 120 is centered directly beneath the
detector system 100.
[0764] In yet another embodiment, shown in FIG. 19C, the display
106 provides a different indicator, such as an arrow 260, to
provide a visual indication of the location .alpha. of the magnet
120. The arrow 260 may also be used to indicate the orientation of
the magnet 120.
[0765] The depth of the magnet 120 beneath the surface of the
patient can be indicated on the display 106 in a variety of
fashions. For example, a portion 106a of the display 106 can
provide a visual indication of the depth of the magnet 120 using a
bar graph, such as illustrated in FIG. 19D. However, the depth
indicator portion 106a of the display 106 can also provide a
numerical read-out of the depth of the magnet 120 in absolute
units, such as centimeters, or in relative units.
[0766] Although the internal display 106 and external display are
two-dimensional display devices, it is possible to display the
magnet 120 with shading and graphical features to create the
appearance of a three-dimensional object. Conventional display
technology used in video games and other computer applications may
be readily applied to the system 100 so that the magnet 120 appears
like a three-dimensional arrow to show the location and direction
of the magnetic dipole or a donut to simulate the shape of the
magnet with an arrow extending therefrom. Techniques used for such
three-dimensional graphic representations are well known in the art
and need not be described in greater detail.
[0767] In addition to displaying the magnet 120 as a
three-dimensional graphic image, the system 100 can display the
magnet from any perspective. For example, FIG. 17B illustrates the
location of the magnet as viewed from the top surface of the
patient, thus illustrating the location of the magnet in the X-Y
plane. However, in some circumstances, it is desirable to view the
magnet from a different perspective, such as the Y-Z plane. This
perspective allows the user to see movement of the magnet 120 as it
moves up and down (i.e., movement on the Z axis) within the
patient. The user-selectable display perspective is particularly
useful in applications, such as image-guided surgery, where the
user must be able to visualize the movement of the intragastric
device in any plane. For example, it is important to see
directional movement in all three dimensions when inserting a
cardiac catheter. There are known technologies to permit the
display of the magnet 120 from any perspective. For example,
MICROSOFT.RTM. WINDOWS.RTM. includes functions that allow the user
to select the display perspective using a mouse, keyboard or other
input device.
[0768] Thus, the detector system 100 determines the location
.alpha. of the magnet 120 in a three-dimensional space and provides
an easy-to-read visual indication of the location of the magnet,
including a depth indication, as well as the orientation of the
magnetic dipole. While the housing 102 is illustrated as a
rectangular housing, with the magnetic sensors 108-114 distributed
equidistantly within the housing 102, the rectangular shape was
chosen for its ease in grasping by the caregiver. However, the
housing 102 can have any shape or size. Furthermore, the display
106, while illustrated as a liquid crystal display, can be any
convenient two-dimensional display, such as a dot matrix display or
the like. Thus, the embodiments are not limited by the specific
size or shape of the housing 102 or by the specific type of display
102. In addition, the detector system 100 can operate
satisfactorily with a variety of different magnetic sensors. Thus,
the system is not limited by the specific number or type of
magnetic sensors employed in the detector system 100.
[0769] Various techniques have been described above to detect the
three dimensional position and angular orientation of a single
magnet. However, the principles of the embodiments may be extended
to the detection of multiple magnets. The system 100 can detect the
position of two intragastric devices, such as illustrated in FIG.
20, where a first peripherally inserted central catheter (PICC) 300
is inserted in one arm of the patient and has a magnet 302
associated with a terminal portion thereof. A second PICC 304 is
inserted through another arm of the patient and includes a magnet
306 associated with a terminal portion thereof. Those 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 may be located using the techniques
described herein. Accordingly, the embodiments are not limited by
the specific type of medical tube (e.g., catheter) or device.
[0770] As previously described, the position and orientation of a
single magnet may be described in three dimensional space by five
parameters. Similarly, the position and orientation of the magnet
306 are also characterized by the same five parameters, although
corresponding parameters will likely have different values. Thus,
the position and orientation of the magnets 302 and 306 may be
characterized by a total of ten unknown parameters. In addition,
the contribution of the Earth's magnetic field in the x, y, and z,
directions is unknown. Thus, the model used by the detector system
100 for two magnets has thirteen unknowns and requires thirteen
independent measurements. In an exemplary embodiment of the
detector system, illustrated in FIG. 21, five magnetic sensors,
located at positions S.sub.1-S.sub.5, each having three
orthogonally oriented sensing elements, provide a set of fifteen
magnetic sensing elements. This is sufficient to detect the
position and orientation of the magnets 302 and 306.
[0771] As illustrated in FIG. 21, the magnet 302 is positioned at a
location .alpha..sub.1. As is known in the art, the magnet 302 has
a magnetic dipole that is represented by the vector m.sub.1.
Similarly, the magnet 306 is positioned at a location .alpha..sub.2
and has a magnetic dipole that is represented by the vector
m.sub.2. The vectors m.sub.1 and m.sub.2 represent the strength and
orientation of the magnetic dipoles of the magnets 302 and 306,
respectively.
[0772] The magnetic sensors, positioned at locations
S.sub.1-S.sub.5 will detect the total magnetic field generated by
both the magnet 302 and the magnet 306. Thus, the vector sensed at
each of the magnetic sensors at locations S.sub.1-S.sub.5 will be
the vector combination of the magnetic dipoles m.sub.1 and m.sub.2.
However, the system 100 knows the strength of the magnetic dipoles
m.sub.1 and m.sub.2 as well as the position and orientation of each
of the sensors at locations S.sub.1-S.sub.5. Given this
information, as well as the 15 separate measurements, the system
can accurately detect the location and orientation of the magnets
302 and 306. The measurement techniques, using the equations
described above, can be applied to two magnets. Although the
process described herein can locate two magnets, the principles of
can be further extended to more magnets. In the example above,
thirteen parameters characterize the Earth's magnetic field (three
parameters) and the two magnets 302 and 306 (five parameters each).
A third magnet (not shown) can be characterized by the same five
parameters discussed above. Thus, eighteen independent sensors are
needed to characterize three magnets, twenty-three sensors are
required to characterize four magnets and so forth.
[0773] The initial estimated location of the magnets 302 and 306
may also be determined using the neural network 154 (see FIG. 15A)
or other techniques described herein. As will be described in
greater detail below, the system 100 can include an array of
magnetic sensors (see FIG. 16). In this embodiment, the estimation
processor 152 can select a subset of sensors having measured
magnetic field strength values above a predetermined threshold. The
initial position of the magnets may be based on the values from the
magnetic sensors whose readings are above the predetermined
threshold.
[0774] In addition, the system 100 may perform an iterative
process, as described above, to determine the location and
orientation of the magnets 302 and 306. The process of optimization
for minimizing the error (or cost) function for multiple magnets
may be readily ascertained based on the foregoing description. For
the sake of brevity, that description will not be repeated
herein.
[0775] If a single magnet is associated with an intragastric
device, it is possible to determine the position and angular
orientation of the magnet and thus the intragastric device in the
manner described above. The techniques described above are adequate
to detect five degrees of freedom of the magnet and the
intragastric device associated therewith. However, those skilled in
the art will appreciate that a dipole magnet is symmetrical about
its axis of magnetization. Thus, the intragastric device may be
rotated along the axis of magnetization and the magnet will produce
the same magnetic field. Thus, the system described above cannot
determine the angular rotation of the intragastric device.
[0776] In another embodiment, the magnets 302 and 306 are both
associated with a single intragastric device. As illustrated in
FIG. 22, the magnets 302 and 306 are oriented such that their axes
of magnetization are not aligned with each other. In the example
illustrated in FIG. 22, the axis of magnetization of the magnet 302
is orthogonal to the axis of magnetization of the magnet 306. Given
the knowledge of the strength of the magnetic dipoles m.sub.1 and
m.sub.2, and the orientation of the axis of magnetization and the
physical location of the magnet 302 with respect to the magnet 306,
the system 100 can thereby detect a sixth degree of freedom of the
intragastric device. This is illustrated in FIG. 22 as a rotational
displacement .omega.. The techniques to determine the location and
orientation of the magnets 302 and 306 are identical to that
described above. However, given the additional knowledge of the
fixed orientation of the axes of magnetization and the physical
position of the magnet 302 with respect to the magnet 306, it is
possible to detect rotational displacement 10 of the intragastric
device. For example, the intragastric device may be an endoscope
that may be guided by the image shown on the display 106 (see FIG.
15A) or on an external display. The system 100 can advantageously
calculate six degrees of freedom (x, y, z, .theta., .phi., and
.omega.) of the intragastric device associated with the magnets 302
and 306.
[0777] As previously described, a large number of magnetic sensors
may be disposed to form a sensor array, as illustrated in FIG. 16.
The housing 102 may be sufficiently large (e.g., 9 inches.times.12
inches). In this embodiment, the housing 102 may remain fixed in a
stationary position on the measurement surface of the patient. As
the magnet 120 (see FIG. 14) or the magnets 302 and 306 (see FIG.
20) are positioned in proximity with the housing 102, one or more
of the sensors will detect the presence of the magnetic field. As
described above, a sufficient number of magnetic sensors must
detect the magnetic field and provide data in order to accurately
characterize the location and orientation of the magnet. As
described above, a sufficient number of magnetic sensors must
detect the magnetic field and provide data in order to accurately
characterize the location and orientation of the magnet.
[0778] FIG. 16 illustrates an array of sixteen magnetic sensors
uniformly distributed within the housing at locations
S.sub.1-S.sub.16. As previously described, each of the magnetic
sensors may comprise individual magnetic sensing elements
positioned in three orthogonal dimensions, which may conveniently
be characterized as x, y, and z. The orientation of sensors along
x, y, and z axes provides a convenient means for which to describe
the magnetic sensors. However, the principles of the embodiments do
not require a specific orientation of any of the sensors at the
locations S.sub.1-S.sub.16 nor, indeed, do the sensors need to be
uniformly distributed at the locations S.sub.1-S.sub.16. However,
proper operation of the system 100 does require that the position
and orientation of each of the magnetic sensors and magnetic
sensing elements be known.
[0779] As described above, a small detector array may be moved with
respect to the patient so as to track the insertion of an
intragastric device in the associated magnet. As the magnetic
sensors are moved, the effects of the Earth's magnetic field may
change. Thus, recalibration is required as the sensors are moved
with respect to the patient. The advantage of the large array
illustrated in FIG. 16 is that the housing 102 need not be moved
with respect to the patient. Thus, the effects of the Earth's
magnetic field need only be measured and compensated for a single
time.
[0780] As previously described, the initial position of a magnet
may be determined using the sensor array of FIG. 16 using the
detected magnetic field from four sensors that have the largest
values or values above a predetermined threshold. For example,
assume that the initial position of the magnet is unknown, that the
magnetic sensors at locations S.sub.5, S.sub.6, S.sub.9, and
S.sub.10 all have detected values above a predetermined threshold
or have values greater than those detected by the sensors at other
locations. As an initial estimate, the estimation processor 152
(see FIG. 15A) may assume that the magnet 120 (see FIG. 14) is
located in a position equidistant from the magnetic sensors at the
locations S.sub.5, S.sub.6, S.sub.9, and S.sub.10. Alternatively,
the position within the boundaries defined by these locations
S.sub.5, S.sub.6, S.sub.9, and S.sub.10 may be weighted based on
the value detected by each of the sensors at those locations. For
example, the sensor at location S S.sub.6 may have the highest
value of the sensors at locations S.sub.5, S.sub.6, S.sub.9, and
S.sub.10. Accordingly, the estimation processor 152 may calculate
an initial position for the magnet 120 that is closer to the
location S S.sub.6 rather than equidistant from each of the
locations S.sub.5, S.sub.6, S.sub.9, and S.sub.10. Other weighting
functions may also be used by the estimation processor 152.
[0781] In yet another alternative embodiment, the values detected
by the sensors at locations S.sub.5, S.sub.6, S.sub.9, and S.sub.10
may be provided to the neural network 154 and processed in a manner
described above. Thus, the system 100 offers a variety of
techniques to determine the initial estimated location of the
magnet 120. Through the iterative process described above, the
location and orientation of one or more magnets may readily be
detected and tracked by the system 100.
Examples
Component Integration into Device
[0782] FIG. 23 depicts a balloon 1100 of one embodiment
incorporating a pellet 1110 in an enclosed volume of the
intragastric balloon. The pellet 1110 may be an electromagnetic
sensor, a magnetic sensor, an acoustic sensor, a voltaic sensor, a
pH sensor, and/or other sensors or markers described herein. The
pellet 1110 can be loose or attached to a wall of the intragastric
balloon. FIG. 24 depicts a balloon 1200 of one embodiment
incorporating buttons 1210 attached to opposite sides of the
intragastric balloon. The buttons 1210 may be electromagnetic,
emagnetic, acoustic, voltaic, pH, and/or other buttons, sensors or
markers described herein. FIG. 25A depicts a cross section of a
valve system 1300 including a septum plug 1310, head unit 1312,
ring stop 1314, tube septum 1316, and retaining ring 1318. The
retaining ring may include electromagnetic, magnetic, acoustic,
voltaic, pH, and/or other sensors or markers. FIG. 25B is a top
view of the valve system, depicted in 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 an intragastric
balloon 1320. FIG. 26 depicts a gel cap 1400 containing an
intragastric balloon of FIGS. 25A-C in uninflated form. The gel cap
containing the uninflated balloon is engaged via the valve system
of the intragastric balloon to a dual catheter system comprising a
2FR tube 1410 and a 4FR tube 1412 via a press-fit connecting
structure 1414 incorporating a magnetized component, e.g., a needle
(not depicted).
Acoustic Tracking and Visualization Subcomponent
[0783] Various embodiments may implement acoustic tracking and
visualization functionality into devices and systems described
above. As used herein, "visualization" is used broadly to refer to
locating, characterizing, or otherwise identifying an item of
interest in the body in a number of ways, including by ultrasonic
and other acoustic wave data such as wave strength, wave
orientation, temporal characteristics of the wave, the effects of
the wave on a sensor, and other attributes of an ultrasound or
acoustic wave that may be used to facilitate tracking, locating,
identifying, and characterizing an item of interest, as well as
audio, visual, tactile, or other output based on the ultrasound
data that characterizes the item of interest. As used herein,
"acoustic" refers to using mechanical waves in gases, liquids or
solids and covers the use of such techniques as vibrations, sounds,
ultrasounds and infrasounds. While the acoustic embodiments are
described primarily in the context of ultrasounds, it is understood
that the embodiments may also be implemented with other acoustic
techniques, such as those mentioned above, and others not
explicitly mentioned. Thus, the ultrasound techniques described
herein may also be implemented in other acoustic type embodiments.
Due to the non-invasive nature of an acoustic-based device,
physicians may desire to determine, or confirm, the location and
orientation of the device prior to inflation or during the course
of treatment. Thus, acoustic-related devices and methods for
determining and confirming the location, orientation and/or state
of an intragastric device at all phases of administration are
disclosed. Such acoustic-based devices and techniques include
ultrasound-related means, which include but are not limited to
ultrasonography or ultrasonic imaging, "very directional" Doppler
systems, Doppler imaging systems, and systems related to
intravascular ultrasound techniques.
[0784] Ultrasound is an oscillating sound pressure wave with a
frequency greater than the upper limit of the human hearing range.
Ultrasound is thus not separated from `normal` (audible) sound by
differences in physical properties, only by the fact that humans
cannot hear it. Although this limit varies from person to person,
it is approximately 20 kilohertz (20,000 hertz) in healthy, young
adults. Ultrasound devices operate with frequencies from 20 kHz up
to several gigahertz.
[0785] Diagnostic sonography (ultrasonography) is an
ultrasound-based diagnostic imaging technique used for visualizing
internal body structures including tendons, muscles, joints,
vessels and internal organs for possible pathology or lesions. 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 too high for humans to hear.
Ultrasound images (sonograms) are made by sending a pulse of
ultrasound into tissue using an ultrasound transducer (probe). The
sound reflects and echoes off parts of the tissue; this echo is
recorded and displayed as an image to the operator. The techniques
employed for imaging tissue and organs using ultrasound can be
adapted for imaging the intragastric device or devices of the
embodiments
[0786] Many different types of images can be formed using
ultrasound. The most well-known type is a B-mode image, which
displays a two-dimensional cross-section of the tissue being
imaged. Other types of image can display a three-dimensional
region, enabling precise location of the intragastric device within
the gastric system. In certain embodiments, application of
ultrasound can also be used to rupture the device, facilitating
passage of the deflated device out of the body at the end of its
useful life.
[0787] Compared to other prominent methods of medical imaging,
ultrasonography has several advantages. It provides images in
real-time (rather than after an acquisition or processing delay),
it is portable and can be brought to a sick patient's bedside, it
is substantially lower in cost, and it does not use harmful
ionizing radiation. Each of these features is particularly
advantageous for locating or tracking an intragastric device.
[0788] Typical diagnostic sonographic scanners operate in the
frequency range of 2 to 18 megahertz, though frequencies up to
50-100 megahertz have been used in biomicroscopy. The choice of
frequency is a trade-off between spatial resolution of the image
and imaging depth: lower frequencies produce less resolution but
image deeper into the body. Higher frequency sound waves have a
smaller wavelength and thus are capable of reflecting or scattering
from smaller structures. Higher frequency sound waves also have a
larger attenuation coefficient and thus are more readily absorbed
in tissue, limiting the depth of penetration of the sound wave into
the body. Different frequencies can be employed, depending upon the
condition of the intragastric device at the time of imaging. For
example, an uninflated intragastric device in compacted form may
benefit from use of a higher imaging wavelength (e.g., 7-18 MHz)
due to the smaller cross section, especially when imaging in the
region of the throat, wherein the device would be expected to be
close to the surface of the body, while a lower imaging wavelength
(e.g., 1-6 MHz) may be desirable for the intragastric device in a
larger inflated form in the stomach, where the distance to the
surface of the skin may be further, wherein a lower axial and
lateral resolution but greater penetration is observed.
[0789] Ultrasonography can use a hand-held probe (called a
transducer) that is placed directly on and moved over the patient.
Sonography is effective for imaging soft tissues of the body.
Superficial structures such as muscles, tendons, testes, breast,
thyroid and parathyroid glands, and the neonatal brain are imaged
at a higher frequency (7-18 MHz), which provides better axial and
lateral resolution. Deeper structures such as liver and kidney are
imaged at a lower frequency 1-6 MHz with lower axial and lateral
resolution but greater penetration.
[0790] In ultrasound, a sound wave is typically produced by a
piezoelectric transducer or a capacitive micromachined transducer,
encased in a housing which can take a number of forms. Strong,
short electrical pulses from the ultrasound machine make the
transducer ring at the desired frequency. The frequencies can be
anywhere between 2 MHz or lower and 18 MHz or higher. The sound is
focused either by the shape of the transducer, a lens in front of
the transducer, or a complex set of control pulses from the
ultrasound scanner machine (beamforming). This focusing produces an
arc-shaped sound wave from the face of the transducer. The wave
travels into the body and comes into focus at a desired depth.
[0791] Transducers focus their beam with physical lenses or use
phased array techniques to enable the sonographic machine to change
the direction and depth of focus. Almost all piezoelectric
transducers are made of ceramic. Materials on the face of the
transducer enable the sound to be transmitted efficiently into the
body (e.g., a rubbery coating, a form of impedance matching). In
addition, a water-based gel is typically placed between the
patient's skin and the probe. The techniques of the embodiments can
be applied to administration of the gastric device to a patient
with an empty stomach, or to a patient with a stomach partially
filled with liquid and/or solid gastric contents.
[0792] The sound wave is partially reflected from the layers
between different tissues, or from the interface between the device
in compacted form and the surrounding tissue, or the interface
between the device in inflated form and the surrounding tissue or
gastric fluids or content. Specifically, sound is reflected
anywhere there are density changes, such that some of the
reflections return to the transducer. The return of the sound wave
to the transducer results in the same process that it took to send
the sound wave, except in reverse. The return sound wave vibrates
the transducer, the transducer turns the vibrations into electrical
pulses that travel to the ultrasonic scanner where they are
processed and transformed into a digital image. The sonographic
scanner determines from each received echo how long it took the
echo to be received from when the sound was transmitted, and how
strong the echo was. The focal length for the phased array can also
be determined, enabling a sharp image of that echo at that depth.
The ultrasonic imaging energy is delivered as a pulse with a
specific carrier frequency. Moving objects change this frequency on
reflection, so that it is only a matter of electronics to have
simultaneous Doppler sonography enabling movement to be imaged. The
received image is then digitally displayed.
[0793] Ultrasonography (sonography) uses a probe containing
multiple acoustic transducers to send pulses of sound into a
material. Whenever a sound wave encounters a material with a
different density (acoustical impedance), as in a compact or
inflated intragastric device, part of the sound wave is reflected
back to the probe and is detected as an echo. The time it takes for
the echo to travel back to the probe is measured and used to
calculate the depth of the tissue interface causing the echo. The
greater the difference between acoustic impedances, the larger the
echo is. If the pulse hits gases or solids, the density difference
is so great that most of the acoustic energy is reflected and it
becomes impossible to see deeper. This feature is advantageous in
the imaging of an inflated intragastric device.
[0794] The frequencies used for imaging are generally in the range
of 1 to 18 MHz. Higher frequencies have a correspondingly smaller
wavelength, and can be used to make sonograms with smaller details.
However, the attenuation of the sound wave is increased at higher
frequencies, so in order to have better penetration of deeper
tissues, a lower frequency (3-5 MHz) is used.
[0795] Seeing deep into the body with sonography is very difficult.
Some acoustic energy is lost every time an echo is formed, but most
of it (approximately) is lost from acoustic absorption. The speed
of sound varies as it travels through different materials, and is
dependent on the acoustical impedance of the material. However, the
sonographic instrument assumes that the acoustic velocity is
constant at 1540 m/s. An effect of this assumption is that in a
real body with non-uniform tissues, the beam becomes somewhat
de-focused and image resolution is reduced. However, in the various
embodiments, the profile of the device in its different forms
(compacted, undergoing inflation, inflated, undergoing deflation,
deflated) is generally readily ascertained despite the lower image
resolution.
[0796] To generate a two-dimensional (2D) image, the ultrasonic
beam is swept. A transducer may be swept mechanically by rotating
or swinging. Or a one dimensional phased array transducer may be
used to sweep the beam electronically. The received data is
processed and used to construct the image. The image is then a 2D
representation of the slice into the body. A 2D image may be
acceptable for determining the passage of the device longitudinally
through the gastrointestinal tract. Once in place, it may be
desirable to image the device in the stomach in three dimensions.
3D images can be generated by acquiring a series of adjacent 2D
images. A 2D phased array transducer that can sweep the beam in 3D
can be employed, as is commonly used in cardiac imaging. Doppler
ultrasonography is used to image motion. The different detected
speeds are represented in color for ease of interpretation. Colors
may alternatively be used to represent the amplitudes of the
received echoes. Such ultrasonography can be advantageously
employed to image the device as it moves down the esophagus.
[0797] Several modes of ultrasound used in medical imaging can be
employed in various embodiments. A-mode (amplitude mode) is the
simplest type of ultrasound. A single transducer scans a line
through the body with the echoes plotted on screen as a function of
depth. A-mode ultrasound also allows for pinpoint accurate focus of
a destructive wave energy, e.g., for use in deflating an inflated
intragastric device. In B-mode (brightness mode) ultrasound, a
linear array of transducers simultaneously scans a plane through
the body that can be viewed as a two-dimensional image on screen.
This mode is more commonly known as 2D mode now. A C-mode image is
formed in a plane normal to a B-mode image. A gate that selects
data from a specific depth from an A-mode line is used; then the
transducer is moved in the 2D plane to sample the entire region at
this fixed depth. When the transducer traverses the area in a
spiral, an area of 100 cm2 can be scanned in around 10 seconds. In
M-mode (motion mode) ultrasound, pulses are emitted in quick
succession--each time, either an A-mode or B-mode image is taken.
Over time, this is analogous to recording a video in ultrasound. As
the boundaries of the intragastric device produce reflections move
relative to the probe, this can be used to determine the velocity
of the intragastric device. Doppler mode makes use of the Doppler
effect in measuring and visualizing moving objects such as the
intragastric device. Velocity information can be presented as a
color-coded overlay on top of a B-mode image. Doppler information
can be continuously sampled along a line through the body, and all
velocities detected at each time point are presented (on a time
line). In pulsed wave (PW) Doppler, Doppler information is sampled
from only a small sample volume (defined in 2D image), and
presented on a timeline. Duplex mode is used to refer to the
simultaneous presentation of 2D and (usually) PW Doppler
information. Color Doppler can be referred to as Triplex mode. In
the pulse inversion mode, two successive pulses with opposite sign
are emitted and then subtracted from each other. This means that
any linearly responding constituent will disappear while gases with
non-linear compressibility stand out. Pulse inversion may also be
used in a similar manner as in harmonic mode, wherein a deep
penetrating fundamental frequency is emitted into the body and a
harmonic overtone is detected. This way noise and artifacts due to
reverberation and aberration are greatly reduced. Penetration depth
can be gained with improved lateral resolution. An additional
expansion or additional technique of ultrasound is biplanar
ultrasound, in which the probe has two 2D planes that are
perpendicular to each other, providing more efficient localization
and detection. An omniplane probe is one that can rotate
180.degree. to obtain multiple images. In 3D ultrasound, many 2D
planes are digitally added together to create a 3-dimensional image
of the object.
[0798] In contrast-enhanced ultrasound, microbubble contrast agents
enhance the ultrasound waves, resulting in increased contrast. In a
similar fashion, the intragastric device can advantageously 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.sub.6, and halocarbons such as C.sub.2F.sub.6, C.sub.3F.sub.8,
C.sub.4F.sub.10, C.sub.4F.sub.8, C.sub.3F.sub.6, CF.sub.4, and
CClF.sub.2--CF.sub.3.
[0799] Sonography can be enhanced with Doppler measurements, which
employ the Doppler Effect to assess whether structures such as the
intragastric device are moving towards or away from the probe, and
the structure's relative velocity. By calculating the frequency
shift of a particular sample volume, for example flow in an artery
or a jet of blood flow over a heart valve, its speed and direction
can be determined and visualized. This is particularly useful in
cardiovascular studies (sonography of the vascular system and
heart) and essential in many areas such as determining reverse
blood flow in the liver vasculature in portal hypertension. The
Doppler information is displayed graphically using spectral
Doppler, or as an image using color Doppler (directional Doppler)
or power Doppler (non-directional Doppler). This Doppler shift
falls in the audible range and is often presented audibly using
stereo speakers: this produces a very distinctive, although
synthetic, pulsating sound. Most modern sonographic machines use
pulsed Doppler to measure velocity. Pulsed wave machines transmit
and receive series of pulses. The frequency shift of each pulse is
ignored; however the relative phase changes of the pulses are used
to obtain the frequency shift (since frequency is the rate of
change of phase). The major advantages of pulsed Doppler over
continuous wave is that distance information is obtained (the time
between the transmitted and received pulses can be converted into a
distance with knowledge of the speed of sound) and gain correction
is applied. The disadvantage of pulsed Doppler is that the
measurements can suffer from aliasing. The terminology "Doppler
ultrasound" or "Doppler sonography" has been accepted to apply to
both pulsed and continuous Doppler systems despite the different
mechanisms by which the velocity is measured. There are no
standards for the display of color Doppler. A common convention is
to use red to indicate flow toward the transducer and blue away
from the transducer, or to display a red shift representing longer
waves of echoes (scattered) from the target.
[0800] Ultrasonography offers a number of advantages for imaging
the intragastric device in vivo. Ultrasonography images solid
surfaces very well and is particularly useful for delineating the
interfaces between solid and fluid-filled spaces, enabling the
imaging of the device in both a solid, compacted form as well as an
inflated form or even a deflated form. The method enables live
images to be obtained, showing motion as well as position of the
intragastric device. The method has no known long-term side effects
and rarely causes any discomfort to the patient. The equipment is
widely available and comparatively flexible. Small, easily carried
scanners are available such that examinations can be performed in a
physician's office or in a clinic setting. The technology is also
relatively inexpensive compared to other methods, such as CAT
imaging or magnetic resonance imaging. Spatial resolution is better
in high frequency ultrasound transducers than it is in most other
imaging modalities, enabling accurate tracking of the intragastric
device.
[0801] It is known that there might be difficulties imaging tissue
structures deep in the body, especially in obese patients, using
ultrasound. Body habitus has a large influence on image quality.
Image quality and accuracy of diagnosis is limited with obese
patients, overlying subcutaneous fat attenuates the sound beam and
a lower frequency transducer is required (with lower resolution).
However, the device in solid, compacted form provides satisfactory
imaging contrast. The device in inflated form, especially when
containing nitrogen, SF6, or other halocarbons, exhibits excellent
contrast, unlike tissue structures in vivo, enabling ease of
imaging even in the morbidly obese.
[0802] In some embodiments, an ultrasound sensor comprises a
non-contact sensor. An ultrasonic level or sensor or sensing system
requires no contact with the target. In the medical industries this
is an advantage over inline sensors that may contaminate or
otherwise interfere with the marker or item of interest. In some
embodiments, the sensor is a microphone.
[0803] In some embodiments, a pulsed wave system is used. The
principle behind a pulsed-ultrasonic technology is that the
transmit signal consists of short bursts of ultrasonic energy.
After each burst, the sensor electronics looks for a return signal
within a small window of time corresponding to the time it takes
for the energy to pass through the medium of interest. Only a
signal received during this window will qualify for additional
signal processing. In some embodiments a continuous wave system is
used. In the pulsed, continuous, or other wave systems, the sensor
may be a microphone that receives the return wave signal.
[0804] In some embodiments, a marker may transmit ultrasound
signals. For instance, Ultrasound Identification (USID) may be used
to automatically track and identify the location of intragastric
devices in real time using simple, inexpensive nodes (badges/tags)
attached to or embedded in the ultrasound devices, which then
transmit an ultrasound signal to communicate their location to
ultrasound sensors, such as microphones.
[0805] A computing system may be implemented in the ultrasound
locating system. The computing system comprises hardware and
software that receives data from the ultrasound sensor and
calculates information related to the location, orientation, and/or
state of an intragastric device according to certain algorithms. In
some embodiments, the hardware may comprise a central processing
unit, memory, an analog to digital converter, analog circuitry, a
display. In some embodiments, the software proceeds through a
number of steps including calibration, initialization, prediction,
estimation, measuring magnetic sensor data, calculating various
desired outputs including location, orientation, size,
configuration, etc. in accordance with the techniques discussed
herein.
[0806] The processor's output relating to the location, orientation
and/or state of an intragastric device may be communicated to a
user in a number of manners. In some embodiments, the output is
shown visually on a display.
[0807] In some embodiments, the processor's output related to an
intragastric device's location, orientation, and/or state is
audibly communicated to a user through a speaker.
[0808] In some embodiments, the processor's output related to an
intragastric device's location, orientation, and/or state is
communicated to a user through a combination of methods. For
instance, the system may employ a visual graphical display with
audible alerts sent through speakers.
[0809] In some embodiments, the ultrasound locating system is
calibrated before use. The ultrasound marker and the sensor are
positioned in pre-planned locations and orientations to verify the
output signal is within an expected range. In some embodiments, the
ultrasound locating systems are calibrated or otherwise verified
using a human patient simulator, or dummy, to test the ultrasound
locating system as an ultrasound marker travels through the
simulator. In some embodiments, the ultrasound locating system is
checked for stray signals from nearby acoustic interferences.
[0810] The ultrasound sensor may be used in conjunction with the
marker or markers in a variety of embodiments to locate or
otherwise characterize an ingested intragastric device. In some
embodiments, an off-the-shelf intragastric device, such as a
swallowable, inflatable balloon, may be used without modification
with any ultrasound markers. With that device, an ultrasound sensor
that pulses sound waves and senses their return signal with a
microphone may be used outside the body. The device could be
swallowed in a deflated state and would then inflate or be inflated
once inside the stomach. The ultrasound sensor may be used to
locate or otherwise characterize the device by pulsing the device
and receiving the return signals, in accordance with the techniques
discussed above.
[0811] The devices once ingested may be located using the
ultrasound intragastric locating system. In some embodiments, the
sensor may locate the device by pulsing in various locations and
analyzing the return signal. For instance, a return signal
corresponding to a body organ without the device may be
pre-determined by correlating a return wave signal to a location on
the body before the device is swallowed. This could produce an
ultrasound map of the organ or body without any device. Then, after
swallowing the device, and by running the sensor over the body, if
a different signal is returned for a corresponding location in the
body, then the location of the device is thus identified. This may
be implemented in accordance with the techniques discussed
above.
[0812] The orientation of the devices once ingested may be
ascertained using the ultrasound intragastric locating system. In
some embodiments, the sensor may identify the orientation of the
intragastric device by pulsing and sensing at various locations of
the device and analyzing the return signals. For instance, before
ingestion by a patient, the device may be pulsed at various
orientations such that a pre-determined database exists of known
correlations between return wave signatures and orientation of the
device. This may be done for the device in the deflated, inflated,
or other states. Then, after ingestion, the device may be pulsed
and the return signals compared to the pre-determined database to
determine the orientation of the device in accordance with the
techniques discussed above.
[0813] Further, the various sizes and configurations of the devices
once ingested may be characterized using the ultrasound
intragastric locating system in accordance with the techniques
discussed above. For instance, inflation of a balloon, or the
inflation or configuration of multiple balloons, may be
characterized and assessed. In some embodiments, the sensor may
characterize the device or devices by pulsing and sensing at
various locations of the device and analyzing the return signals.
For instance, the deflated device would return a different pulsed
signature than the inflated device. In such a manner, the device
may be characterized as either inflated, deflated, or in some other
state. The inflated device could further be characterized before
ingestion by a patient such that the return signal signature is
pre-determined and serves as a guidepost for assessing the state of
the device. In some embodiments, the ultrasound locating system may
be used in conjunction with a deflating system to characterize the
deflation process.
[0814] The timing and other attributes of the various methods of
administration can be characterized using the disclosed ultrasound
intragastric locating system and techniques. Whether the device is
administered using endoscopic techniques or orally, the progress of
the device as it makes its way to the stomach can be tracked with
the ultrasound locating system. For instance, the effects of
swallowing the device with hard gelatin or water or other
consumables may be characterized by tracking the location and
orientation as it is ingested. In some embodiments, the endoscope
employed to deliver the intragastric device incorporates an
ultrasound emitting device at a preselected distance from the
intragastric device to be deployed. The ultrasound transmittal can
enable precise positioning of the intragastric balloon, as well as
monitoring of the inflation process by changes in the emitted
ultrasound due to proximal inflation of the intragastric
device.
[0815] In some embodiments, the ultrasound locating system may
characterize an intragastric device that has 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.
[0816] Using the speed of sound, a distance can be computed from
the time between transmission and reception. The time between
transmission of the ultrasonic pulse and reception of the echo is
given by: t=2d/U, or d=Ut/2, (53) where U is the speed of sound in
the medium of interest, and d is the diameter of the device. If
transmission occurs in two orthogonal directions, two dimensions of
the intragastric device can be determined, and thus the area of the
device can be computed. Assuming the device is an ellipse, the
equation for the area of an ellipse using the major (a) and minor
(b) axes is as follows:
A=.pi.ab=(.pi.U.sup.2t.sub.1t.sub.2)/16
[0817] If the interior of an inflated device is clear, a clear echo
signal is obtained and the time of flight of the ultrasound pulse
is obtained in the clear area to determine device area. To detect
the presence of matter, foreign or otherwise, in the device, two
methods may be used. First, the orthogonal signal, that is the
amplitude of the scattered ultrasonic pulse in the orthogonal
direction, is compared with the original pulse echo return. And
second, the amount of false return in the original pulse echo may
even determine the ratio of solid to liquid matter in the analyzed
cross section of the device.
[0818] The intragastric device may include two orthogonal
ultrasonic transmitter/receiver ("transceiver") modules. One
transceiver is an anterior/posterior (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 is capable of
distinguishing between device echoes and the empty device interior.
The microprocessor is also capable of preparing a signal for
transmission. The microprocessor is in electrical communication
with a computer. In some embodiments, the computer and the
microprocessor are incorporated into the same component. In at
least one embodiment, the computer may be a look up table, capable
of determining the semi-major axis, the semi-minor axis, and the
scatter associated with the device.
[0819] The intragastric device may also include a transmitter
capable of transmitting the signals from the device to a location
outside of the body. The transmitter can include an antenna for
transmission, or an antenna in the band (not shown) can be in
electrical communication with the transmitter. The device may also
include a module either containing a battery or capable of powering
the intragastric device electronics inductively. External to the
patient may be an antenna for receiving the transmitted signals and
a receiver in operative communication with the antenna. A computer
may be included that has software capable of decoding and
processing the signals transmitted by the transmitter and received
by the receiver. The computer software is capable of measuring the
time of flight of horizontal and vertical ultrasonic pulses to
determine the length and width of the intragastric device, and
combining the length and width to find the area. It should be noted
that from the scatter of the horizontal into the vertical receiver
and the scatter of the vertical into the horizontal receiver, the
presence of any material in the device can be determined.
[0820] The various ultrasound markers and their acoustic properties
may be implemented in the ultrasound intragastric device locating
system with ultrasound sensors or detectors. The ultrasound markers
comprise any substance, material, or object, to which the
ultrasound sensors or detectors are responsive. As mentioned, an
ultrasound "marker" as used herein therefore includes the
intragastric device itself, such that an off-the-shelf, unmodified
intragastric device may already contain materials that are
responsive to or otherwise may be used with the ultrasound locating
system disclosed herein.
[0821] In some embodiments, the marker is a node attached to and/or
embedded in and/or otherwise coupled to the intragastric device.
Such a node may be, for example, a badge or tag that is responsive
to applied ultrasound energy. The node may also emit or transmit an
ultrasound signal to communicate its location to microphone
sensors. The node may be incorporated with the intragastric device
in various arrangements.
Acoustic Location
[0822] Referring now to FIGS. 27 and 28, a system for locating or
otherwise characterizing an intragastric device using ultrasound is
illustrated in accordance with at least one embodiment of the
present invention. The system 10B of FIG. 27 is used for measuring
a characteristic of the device, such as size, using an external
tuned circuit and a passive coil embedded in or on the device. The
system 10B includes a first coiled conductor 12 (or internal coil)
positioned within an intragastric device 14 (shown in more detail
in FIG. 28). The phrases "internal coil" and "inner coil" are also
used herein to denote the first coiled conductor 12. The system
further includes a circuit external to the device and patient that
includes a tunable frequency generator 16, a spectrum analyzer 18,
and a second coiled conductor 20. The phrases "external coil" and
"outer coil" are also used herein to denote the second coiled
conductor 20. The frequency generator may be a variable frequency
oscillator, for example. The phrase "frequency generator" is used
to denote any type of electrical or electronic device that produces
repetitive electrical or electronic signals. For example, the
frequency generator may be an electronic device capable of
generating repeating sine waves. The phrase "spectrum analyzer" is
used to denote any electrical or electronic device capable of
measuring the frequency and amplitude of a signal.
[0823] The system further includes appropriate capacitance,
inductance, and resistance to allow resonance both when a patient
is absent and when the patient is present, as will be described in
detail below. For example, the system shown in FIG. 27 includes a
variable capacitor 22 that can be tuned to achieve resonance.
Rather than providing a variable capacitor, in some embodiments,
the capacitor can be of fixed value and a variable inductor can be
included.
[0824] The system 10B may also include a device 24 for controlling
heating within the interior coil 12, shown in FIG. 28. As seen in
FIG. 28, the device 24, for example a resistor, is in electrical
communication with the internal coil. In some embodiments, two
electrical leads attached to the two-terminal resistor can be
extended out from the intragastric device, thereby allowing a
measurement to be taken. That is, the first terminal of the
resistor can be in electrical communication with a first end of a
first electrical lead, and the second terminal of the resistor can
be in electrical communication with a first end of a second
electrical lead. The second ends of the first and second electrical
leads can extend outward, external to the intragastric device
14.
[0825] In at least one embodiment, the electrical leads are
accessible via an access port on the patient's body, as seen in
FIG. 29. FIG. 29 depicts the intragastric device 14 with internal
coil 12, having an inflatable section 26, a solid substrate 28, and
placement tabs 30. As seen, electrical leads 32 extend from the
injection port 34 to the internal coil 12 to allow measurement of
the current in the coil. In some embodiments, these leads can be
conductively connected to the external circuit such that the
external circuit includes the intragastric device 14 and its
internal coil in the tuned circuit.
[0826] It should be noted that in the above-described embodiments,
no battery or radiofrequency (RF) module is needed because the
current in the intragastric device 14 is a result of induction.
[0827] The system may further include a computer 35B, depicted in
FIG. 27, having software capable of performing calculations based
on the current in the first coiled conductor and the resonant
frequency in the external circuit in order to determine the size of
the intragastric device 14. The derivations, calculations, and
theory of operation of the system are presented below.
[0828] Two embodiments of the present invention utilize induction
to calculate the size, orientation or other characteristic of the
intragastric device 14. The first embodiment using induction to be
considered is when the inner coil and the outer coil are placed
concentrically and coaxially relative one another, as shown
schematically in FIG. 30A. Such an embodiment occurs when the
external coil is placed around the patient's body such that the
inner 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)*the length (d) of the
solenoid. So, the number of turns of the outer solenoid in FIG. 30A
is given by the equation N.sub.1=n.sub.1*d.sub.1. It is assumed
that the external coil is excited with the following current:
I=I.sub.0 sin .omega.t, (1)
[0829] where .omega.=the angular frequency of the current source
and I.sub.0 is the maximum current of the current source. Then, the
magnetic field B for a relatively long coil is given by the
relation:
B=.mu.N.sub.1I.sub.0sin(.omega.t)/d.sub.1, (2)
[0830] where N.sub.1 is the number of turns in the coil, and
d.sub.1 is the length of the coil. The magnetic flux from the
larger external coil subtended by the intragastric device 14
is:
.PHI.=A.sub.2B=A.sub.2.mu.N.sub.1I.sub.0sin(.omega.t)/d.sub.1,
(3)
[0831] where .mu. is the magnetic susceptibility of the material
contained within the area A.sub.2 of the inner coil, B is the
magnetic field density, and N.sub.1 is the number of turns in the
coil. The electromotive force (emf) generated by coil 1 in coil 2
is given by the relation:
E=d.PHI./dt=-A.sub.2B=A.sub.2.mu.N.sub.1.omega..sub.1I.sub.0(cos
.omega.t)/d.sub.1 (4)
[0832] The voltage induced in the entire intragastric device 14 is
given by the relation:
E.sub.T=N.sub.2E=-A.sub.2.mu.N.sub.1N.sub.2.omega..sub.1I.sub.0cos(.omeg-
a..tau.)/d.sub.1 (5)
[0833] The self inductance (L) of a coil is defined as:
L=N.PHI./i=NA.mu.N/1=N.sup.2A.mu./d.sub.1 (6)
[0834] The self induced emf in the coil is then
V=-LdI/dt=-.omega.N.sup.2A.mu.I.sub.0cos(.omega.t)/d.sub.1 (7)
[0835] The mutual inductance (M) of the two coils is defined as
M.sub.21=N.sub.2.PHI..sub.21i.sub.1, (8)
[0836] where the current in coil 1 generates a flux in coil 2.
N.sub.2.PHI..sub.21=N.sub.2B.sub.1.pi.R.sub.2.sup.2, (9)
and also
N.sub.2.PHI..sub.21=N.sub.2N.sub.1.pi..mu..sub.0R.sub.2.sup.2.sub.i1/2R.-
sub.1, (10)
[0837] Thus the mutual inductance for the device and the external
coil can be given by
M.sub.21=N.sub.2N.sub.1.pi..mu..sub.0R.sub.21.sup.2/2R.sub.1
(11)
[0838] It should be noted that although the magnetic field
generated by the larger coil is essentially constant through the
smaller coil, this is not true of the field induced by the smaller
coil in the larger. But the mutual inductance of the larger coil
upon the smaller is equal to that of the smaller coil upon the
larger.
[0839] Continuing with the derivation, the voltage of a circuit is
the sum of the voltages resulting from the resistance (VR),
capacitance (VC), and inductance (VL) such that
V=V.sub.R+V.sub.C+V.sub.L, (12)
[0840] or as a function of time in integro-differential form,
v(t)=I.sub.1R+L.sub.1dI.sub.1/dt+1/C.intg.I.sub.1dt, (13)
[0841] or expressed completely as a differential equation (14):
1 L 1 v ( t ) t = 2 I 1 t 2 + R L 1 I 1 t + 1 L 1 C I 1 . ( 14 )
##EQU00004##
[0842] If the variable frequency oscillator applies an excitation
of
v(t)=V.sub.0 sin(.omega.t) (15)
[0843] to the external coil and associated resistor and capacitor,
then equation (14) can be written as
V 0 .omega. L 1 v ( t ) t = 2 I 1 t 2 + ( 1 .tau. 0 ) I 1 t R +
.omega. 0 2 I 1 , where ( 16 ) .tau. 0 = L 1 R ( 17 )
##EQU00005##
[0844] The tuned (or resonant) circuit including the external loop
has a natural frequency given by:
.omega..sub.n= {square root over (1/(LC))} (18)
[0845] The quality factor, or Q, of a resonant circuit is given
by:
Q=.omega..sub.nL/R= {square root over (1/(LC))}L/R=1/R {square root
over (L/C)} (19)
[0846] The bandwidth (.omega.2-.omega.1) of the frequency plot
(i.e. the width at half maximum response as measured by the
spectrum analyzer) is given by:
.omega..sub.2-.omega..sub.1=.omega..sub.n/Q=R/L.sub.1=1/.tau..sub.0
(20)
[0847] If the induced emf in the LAGB coil is known, then
V=N.sub.2-A.sub.2B=A.sub.2.mu.N.sub.1I.sub.0.omega./d.sub.1(cos
.omega.t) (21)
[0848] Considering the external tuned circuit without the LAGB
included, then:
dV/dt=Ld.sup.2I/dt.sup.2+RdI/dt+1/CI, (22)
[0849] which is the general equation for a series RLC circuit.
So,
1/LdV/dt=d.sup.2I/dt.sup.2+(1/.tau.)dI/dt+.omega..sub.0.sup.2I,
(23)
where
.tau.=L/R, (24)
and
.omega..sub.n= {square root over (1(L-C))} (25)
[0850] The proportional half power frequencies are given by the
relationship
.DELTA..omega..sub.0/.omega..sub.n=1/2Q=1/.tau..omega.)=R/L {square
root over (1/LC)}=R {square root over (C/L)} (26)
[0851] Now, an inductive circuit (which is a single conductive loop
with no 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,
then:
V.sub.1=L.sub.1d.sup.2I.sub.1/dt.sup.2+Md.sup.2I.sub.2/dt.sup.2+I.sub.1R-
.sub.1+1/C.intg.I.sub.1dt (27)
[0852] and because there is applied voltage in the device, and
because the resistance is small in the device,
V.sub.2=0=L.sub.2d.sup.2I.sub.2/dt.sup.2+Md.sup.2I.sub.1/dt.sup.2
(28)
[0853] Because we observe only the current parameters in the
external coil circuit, the current in the LAGB can be eliminated,
leaving:
d.sup.2I.sub.2/dt.sup.2=-M/L.sub.2d.sup.2I.sub.1/dt.sup.2, (29)
[0854] then substituting into equation (27) gives
V.sub.1=L.sub.1d.sup.2I.sub.1/dt.sup.2+M-M/L.sub.2d.sup.2I.sub.1/dt.sup.-
2+I.sub.1R.sub.1+1/C.intg.I.sub.1dt. (30)
[0855] Taking the derivative of equation (30):
V t = ( ( L 1 L 2 - M 2 ) L 2 ) 2 I 1 t 2 + R I t + 1 / C I , ( 31
) ##EQU00006##
[0856] which equals
L 2 ( L 1 L 2 - M 2 ) V t = 2 I 1 t 2 + R L 2 ( L 1 L 2 - M 2 ) I t
L 2 C ( L 1 L 2 - M 2 ) I 1 , ( 32 ) ##EQU00007##
[0857] which equals
L.sub.2/(L.sub.1L.sub.2-M.sup.2)dV/dt=d.sup.2I/dt.sup.2+(1/.tau.)dI/dt+.-
omega..sub.0.sup.2I. (33)
[0858] The resonance frequency of the external coil changes in the
presence of the LAGB, as does the bandwidth of the frequency, as
shown below:
.omega..sub.0.sup.2=L.sub.2/C(L.sub.1L.sub.2-M.sup.2), (34)
and where
.tau.=(L.sub.1L.sub.2-M.sup.2)/RL.sub.2 (35)
[0859] Comparing the square of resonance frequency of the external
coil in isolation and when concentric to the LAGB, the following
ratio is obtained:
.omega. no_lap _band 2 .omega. lap_band 2 = 1 L 1 C L 2 C ( L 1 L 2
- M 2 ) = ( L 1 L 2 - M 2 ) ( L 1 L 2 ) = 1 - M 2 ( L 1 L 2 ) ( 36
) ##EQU00008##
[0860] where .omega..sub.no.sub.--.sub.lap.sub.--.sub.band is the
natural frequency with no lap band or intragastric device 14 coil
in the circuit and .omega..sub.lap.sub.--.sub.band is the natural
frequency with the lap band or intragastric device 14 coil in the
circuit. Equation (36) assumes that the orientation of the external
coil in relation to the LAGB is such that the resonance frequency
is less in the presence of the LAGB. The ratio of the bandwidth is
given by
Q=.omega..sub.nL/R= {square root over (1/(LC))}L/R=1/R {square root
over (L/C)} (37)
[0861] The values of L.sub.1, L.sub.2, and M depend on the geometry
of the coils. As stated above, the first embodiment is directed
toward a configuration in which the inner coil and the outer coil
are placed concentrically and coaxially, as in FIG. 4A. In such an
embodiment,
M=.pi..mu.N.sub.1N.sub.2R.sub.2.sup.2/2R.sub.1=.mu.N.sub.1N.sub.2A.sub.2-
/2R.sub.1, (38)
L.sub.1=N.sub.1.sup.2A.sub.1.mu./d.sub.1, (39)
and
L.sub.2N.sub.2.sup.2A.sub.2.mu./d.sub.2, (40)
[0862] where R.sub.1 and R.sub.2 are the radii of the two coils,
d.sub.1 and d.sub.2 are the lengths of the two coils, and A.sub.1
and A.sub.2 are the respective areas enclosed by the coils.
[0863] Based on equations (38)-(40) for M, L1, L2,
M.sup.2L.sub.1L.sub.2=.pi..mu..sup.2N.sub.1.sup.2N.sub.2.sup.2A.sup.2.su-
b.2d.sub.1d.sub.2/4N.sub.1.sup.2N.sub.2.sup.2A.sub.1.sup.2A.sub.2.mu..sup.-
2=.pi.A.sub.2d.sub.1d.sub.2/4A.sub.1.sup.2 (41)
[0864] Substituting into equation (36) results in
.omega. no_lap _band 2 .omega. lap_band 2 = 1 L C L 2 C ( L 1 L 2 -
M 2 ) = ( L 1 L 2 - M 2 ) ( L 1 L 2 ) = 1 - .pi. A 2 d 1 d 2 4 A 1
2 ( 42 ) ##EQU00009##
[0865] Solving for the area A2 of the inner coil results in
A 2 = ( 1 - .omega. no_lap _band 2 .omega. lap_band 2 ) ( 4 A 1 2
.pi. d 1 d 2 ) ( 43 ) ##EQU00010##
[0866] The second embodiment using induction to be considered is
when the inner coil 12 and the outer coil 20 are placed in a
coaxial non-concentric arrangement relative to one another, as
shown schematically in FIG. 30B. There is an impedance Z, shown at
21, between the coils. Such an embodiment occurs when the external
coil is placed underneath or above, rather than around, the
patient's body.
[0867] As stated earlier, the values of L1, L2, and M depend on the
geometry of the coils. With the geometry of the second embodiment,
namely of two coaxial non-concentric coils, L1, L2, and M are as
follows:
M=.mu.N.sub.1N.sub.2A.sub.1A.sub.2/2.pi.(R.sub.1.sup.2+z.sup.2).sup.3/2,
(44)
and
L.sub.1=N.sub.1.sup.2A.sub.1.mu./d.sub.1, (45)
and
L.sub.2=N.sub.2.sup.2A.sub.2.mu./d.sub.2 (46)
[0868] Based on equations (44)-(46) for M, L1, L2,
M.sup.2/(L.sub.1L.sub.2)=.mu..sup.2N.sup.2.sub.1N.sup.2.sub.2A.sub.1.sup-
.2A.sub.2.sup.2d.sub.1d.sub.2/4.sub.1.pi..sup.2(R.sub.1.sup.2+z.sup.2).sup-
.3N.sub.1.sup.2N.sub.2.sup.2A.sub.1A.sub.2.mu..sup.2=A.sub.1A.sub.2d.sub.1-
d.sub.2/4.pi..sup.2(R.sub.1.sup.2+z.sup.2).sup.3 (47)
[0869] Substituting into equation (36) results in
.omega. no_lap _band 2 .omega. lap_band 2 = 1 L C L 2 C ( L 1 L 2 -
M 2 ) = ( L 1 L 2 - M 2 ) ( L 1 L 2 ) = 1 - A 1 A 2 d 1 d 2 4 .pi.
2 ( R 1 2 + z 2 ) 3 ( 48 ) ##EQU00011##
[0870] Solving for the area A2 of the inner coil results in
A 2 = ( 1 - .omega. no_lap _band 2 .omega. lap_band 2 ) ( 4 .pi. 2
( R 1 2 + z 2 ) 3 A 1 d 1 d 2 ) ( 49 ) ##EQU00012##
[0871] The area of the concentric coaxial embodiment of equation
(43) and the non-concentric coaxial embodiment of equation (49) can
be summarized with the following equation:
A 2 = k ( 1 - .omega. no_lap _band 2 .omega. lap_band 2 ) ,
##EQU00013##
[0872] where k depends on the geometry of the coils. Thus, the area
is proportional to the absolute value of one minus the ratio of the
squares of the maximum resonant frequencies, as measured by the
spectrum analyzer.
.DELTA..omega..sub.0/.omega..sub.n=1/2Q=1/.tau..omega. (51)
[0873] Thus, the change in resonance frequency peak and the change
in bandwidth can both be used to determine the product of the area
and the magnetic susceptibility of the intragastric device 14 or
marker. In both embodiments of the induction method, the external
coil can be adjusted in both height and orientation relative to the
device coil to give maximum resonance frequency variation from
isolation to insure proper relative position. The use of high
magnetic susceptibility fluid in the device or marker ensures that
only the device or marker area is measured rather than include the
stomach tissue.
[0874] As stated earlier, the system may include a computer for
calculating the area of the intragastric device 14 or marker. A
person of ordinary skill in the art would readily understand how to
write software that calculates the area of the inner coil, as
presented in equations (43) and (49) above, based on the
foregoing.
[0875] In order to adjust the external coil to produce a maximum
resonance frequency, some embodiments of the present invention
include a coil holder to which the external coil is secured.
Referring now to FIG. 31A, one embodiment of a coil holder for a
concentric, coaxial induction embodiment is shown. The coil holder
is used for orienting the external coil with the internal coil.
Because the above calculations are based on the orientation between
the two coils, using a coil holder can simplify the setup of the
system by making stationary the external coil. As seen in FIG. 31A,
the coil holder 36 can simply be an arm moveably engaged to a
vertical mount 37. It is important that the coil holder 36 can be
raised and lowered vertically. It is also important that the coil
holder 36 can be tilted, for example about a point 38 on the coil
holder. In this manner, the external coil 20 can be placed
concentrically and coaxially about the internal coil 12 within the
patient. There are numerous other possible embodiments of the coil
holder.
[0876] Referring now to FIG. 31B, another embodiment of a coil
holder is shown. Specifically, FIG. 31B depicts a coil holder for a
non-concentric, coaxial induction embodiment. As seen in FIG. 31B,
the coil holder 36 can simply be a small table-like device placed
under the seat of a chair 39. It is important that the coil holder
36 can be tilted, as before, thereby allowing the external coil 20
to be aligned with the internal coil within the patient to align.
In such an embodiment, the patient sits down on a chair 39 and the
coil holder 36 underneath the chair is oriented until the resonant
frequency is achieved. There are numerous other possible
embodiments of the coil holder. In some embodiments, the coil may
be placed above the patient, rather than underneath (not
depicted).
[0877] Referring now to FIG. 32, a method 40 of characterizing an
intragastric device or marker thereon is shown, in accordance with
at least one embodiment of the present invention. The method 40
includes the step 42 of providing a system for characterizing an
intragastric device or marker thereon. Embodiments of such a system
are described above. The method further includes the step 44 of
tuning the circuit external to the device or marker to a first
resonant frequency in the absence of a patient. This allows the
practitioner to tune and measure the circuit without the effects of
the coil in the marker. The first resonant frequency measured is
recorded in step 46 of the method. The method further includes the
step 48 of positioning the external coil near the patient. As
described above, the external coil can be placed near the patient
in two ways: concentrically and coaxially, and non-concentrically
and coaxially. The coil is either placed around the patient at the
approximate level of the device or marker, or underneath the
patient. The method further includes the step 50 of providing a
marker for the patient to swallow.
[0878] The measured characteristic of the device, such as the area,
is based on the spike that occurs in the resonant frequency after
the patient has swallowed the marker. The marker can be water with
a solution of non-toxic paramagnetic material such as magnetic
resonance imaging (MRI) contrast material. In some embodiments, the
marker can simply be water. In many cases, the method is sensitive
enough to detect the device or marker size or other characteristic
without ingesting of the MRI contrast material or with a very
dilute concentration. The method further includes the step 52 of
tuning the circuit external to the device or marker to a second
resonant frequency in the presence of the patient. In some
embodiments of the method, the external coil can be moved so as to
obtain the greatest change in resonance frequency of the external
circuit. For example, the external coil can be moved up and down,
side to side, and can be tilted so that it is aligned with the
internal coil. Finally, the method includes the step 54 of
calculating the size, orientation or other characteristic of the
marker or device based on the difference between the first resonant
frequency and the second resonant frequency. From the change of
resonance frequency of the external tuned circuit, the area of the
device or marker is calculated, knowing the magnetic susceptibility
of the MRI contrast material.
[0879] Referring now to FIGS. 33A-36, a setup and method of
equipment verification using a gastric magnetic susceptibility
phantom. FIG. 33A depicts a top view of the basic setup of the
phantom for equipment verification. The setup includes a
peristaltic pump 60 with longitudinal axis 63 (shown in FIG. 33B),
with a lumen 64, tissue 66, and three test laparoscopically
adjustable gastric markers 68, such as gastric bands. It should be
noted that more markers 68 could be used, depending on the accuracy
desired.
[0880] The peristaltic pump is filled with a magnetic contrast
material and the pump is set to a speed consistent with the speed
of human swallowing. As shown in FIG. 33B, a side view of the
embodiment shown in FIG. 33A, the test laparoscopically adjustable
gastric markers are positioned about the pump 60 at three
positions, P1, P2, and P3. The first, second, and third markers are
offset from one another along the longitudinal axis 63 of the
pump.
[0881] Referring now to FIG. 34, the adjustable outer coil 70 is
moved such that it is positioned about the markers 68. The
resonance frequency of each of the markers 68 positioned about the
pump is measured. The resonance frequencies are measured while the
magnetic material passes through the phantom into the receptor 72
and back through the pump again. The values of the resonance
frequencies are detected by the pickup coil 74 and transmitted to
external electronics 76 for further calculations. The maximum
deviation of the resonance frequency is determined from a spectrum
analyzer.
[0882] The above technique does not give an image of the
intragastric device or surrounding anatomy inside the body.
However, the data collected can be displayed graphically, as shown
in FIG. 35. As seen in FIG. 35, the change in frequency can be
graphically correlated to geometric characteristics, such as areas
A1, A2, and A3 of the markers placed at positions P1, P2, and P3,
respectively. As such, a practitioner can be assured that the
external coil is working properly by comparing known good values of
the A1, A2, and A3 versus the values that were measured during the
verification procedure.
[0883] It should be noted that the external frequency generating
apparatus described earlier can be modified to scan across the
gastric lumen using appropriate radiofrequency excitation, thereby
mimicking a rudimentary flow sensing magnetic resonance imaging
apparatus. Such an apparatus would provide an image, using
appropriate frequency domain software.
[0884] The method of determining the size of a gastric lumen using
a gastric magnetic susceptibility phantom is shown in FIG. 36. The
method includes the step 82 of filling a peristaltic pump with
water or a water solution containing a magnetic resonance imaging
contrast material. The method further includes the step 84 of
disposing a first, second, and third marker or device, as described
earlier with an internal coil, about the peristaltic pump. The
first, second, and third markers are offset from one another along
the longitudinal axis of the pump. The method further includes the
step 86 of setting the pump to a speed approximately equal to the
speed of human swallowing. The method further includes the step 88
of pumping the contrast material through the pump. The method
further includes the step 90 of positioning the external coil 70 of
FIG. 34 about the first, second, and third markers in turn and
determining the maximum deviation of the resonant frequency of the
each of the first, second, and third markers from the spectrum
analyzer while contrast material is pumped through the pump. The
method further includes the step 92 of calculating the area of each
of the first, second, and third markers based on their resonant
frequencies.
[0885] It should be noted that the steps in the method described in
FIG. 36 need not be performed in the order shown, and as such, the
method should not be limited to a particular order. Rather, a
person of ordinary skill in the art will recognize that the method
will perform equally well if, for example, the pump is set to a
certain speed prior to filling it with the water solution.
[0886] Referring now to FIGS. 37-40, a system for characterizing an
intragastric device, such as measuring the size of the device, is
illustrated in accordance with at least one embodiment of the
present invention. FIG. 37 is similar to FIG. 29. However, instead
of an internal coil, the embodiment depicted in FIG. 37 has two
ultrasonic modules placed in the device that allow the system to
measure the size and composition of the marker and/or device using
time of flight ultrasound technology.
[0887] The time between transmission of the ultrasonic pulse and
reception of the echo is given by:
t=2d/U, (52)
or
d=Ut/2, (53)
where U is the speed of sound in the medium, typically water, and d
is the diameter of the device or marker of interest.
[0888] If the speed of sound is known, a dimension can be computed
from the time between transmission and reception. If transmission
occurs in two orthogonal directions, two dimensions of the marker
can be determined, and thus the area of the marker can be computed.
Assuming the lumen is an ellipse, the equation for the area of an
ellipse using the major (a) and minor (b) axes is as follows:
A=.pi.ab=(.pi.U.sup.2t.sub.1t.sub.2)/16 (54)
[0889] The marker may be differentiated from the gastric tissue by
instructing the patient to drink water, thus flushing the gastric
area. If the marker is clear, a clear echo signal is obtained and
the time of flight of the ultrasound pulse is obtained in the clear
area to determine marker area.
[0890] To detect the presence of persistent solid mater, two
methods are used. First, the orthogonal signal, that is the
amplitude of the scattered ultrasonic pulse in the orthogonal
direction, is compared with the original pulse echo return. And
second, the amount of false return in the original pulse echo may
even determine the ratio of solid to liquid matter in the cross
section of the area encompassed by the marker.
[0891] Referring now to FIG. 37, the intragastric device 14
includes two orthogonal ultrasonic transmitter/receiver
("transceiver) modules 100A, 102A. Transceiver 100A is an
anterior/posterior (a/p) ultrasonic module, and transceiver 102A is
a lateral ultrasonic module.
[0892] The device 14 further includes a microprocessor 104A that
measures the time of flight from each transceiver module. The
microprocessor is capable of distinguishing between tissue echoes
and an empty marker. The microprocessor is also capable of
preparing a signal for transmission. The microprocessor is in
electrical communication with a computer 105. In some embodiments,
the computer and the microprocessor are incorporated into the same
component. In at least one embodiment, the computer may be a look
up table, capable of determining the semi-major axis, the
semi-minor axis, and the scatter associated with the lumen.
[0893] The intragastric device 14 also includes a transmitter 106A
capable of transmitting the signals from the marker to a location
outside of the body. The transmitter 106A can include an antenna
for transmission, or an antenna in the band (not shown) can be in
electrical communication with the transmitter. The device 14 also
includes a module 108A either containing a battery or capable of
powering the laparoscopically adjustable gastric band electronics
inductively.
[0894] External to the patient is an antenna 110A for receiving the
transmitted signals and a receiver 112 in operative communication
with the antenna. As before, a computer 35B may be included that
has software capable of decoding and processing the signals
transmitted by the transmitter 106A and received by the receiver
112. The computer software is capable of measuring the time of
flight of horizontal and vertical ultrasonic pulses to determine
the length and width of the device 14 and/or marker, and combining
the length and width to find the area. It should be noted that from
the scatter of the horizontal into the vertical receiver and the
scatter of the vertical into the horizontal receiver, the material
in the area of interest can be determined.
[0895] The ultrasonic system can be calibrated in a manner similar
to that described above with regards to FIGS. 33A-34. The above
technique does not give an image of the device 14 or marker or
internal anatomy. However, the data collected can be displayed in a
graphical manner, as shown in FIG. 38. As seen in FIG. 38, the
lateral and horizontal times of flight can be graphically
correlated to the areas A1, A2, and A3 of the marker or device 14
placed at positions P1, P2, and P3, respectively.
[0896] 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 positioned on the outer side of the device, as in FIG. 37.
[0897] FIG. 39 depicts a pulse timing diagram depicting the time of
flight using ultrasonic modules. Here, it is assumed that the
device 14 or marker is a gastric band about a lumen. As seen in
FIG. 39, the time of flight can be determined based on the time to
cross the gastric band bladder, the time to cross the gastric
tissue, and the time to cross the gastric lumen.
[0898] FIG. 40 is a graphical representation of the data collected
for both the ultrasonic embodiment 120A and the induction
embodiment 130A. The ultrasonic embodiment 120A is able to detect
any solid mass 122 within the lumen. In the induction embodiment
130A, the area 132 from the induction embodiment is depicted as
well as the area 134 from the adjustable gastric band tab
circumference minus the area from the induction area.
[0899] In some embodiments the ultrasound marker is a liquid,
solid, or combination thereof. The various materials may be
contained in a sac in or on the intragastric device. The properties
of the liquid may be tuned such that the acoustic signature is
easily identified.
[0900] The above techniques may be used with an ultrasound marker
and applied to the volume-occupying subcomponent when the
volume-occupying subcomponent is in a creased or folded state such
that when the volume-occupying subcomponent is in its deflated
state the marker has a characteristic ultrasound visualization or
signature, and when the volume-occupying subcomponent is inflated
the marker has another characteristic ultrasound visualization or
signature. Alternatively, the ultrasound marker may be applied or
incorporated into the volume-occupying subcomponent so as to
facilitate identification and location of the various subcomponents
of the device, such as a valve, head, or weight. The ultrasound
marker may be printed or painted onto a surface of the
volume-occupying subcomponent or between layers of the material
forming the volume-occupying subcomponent. Alternatively, an
acoustically-responsive coating may be used as an ultrasound marker
to assist with identifying and/or locating the volume-occupying
subcomponent. Alternatively, the ultrasound marker may be applied
to an elastomeric sleeve that covers all or part of the
volume-occupying subcomponent.
[0901] In another embodiment, the volume-occupying subcomponent
incorporates a subcomponent that changes mechanically upon
inflation of the volume-occupying subcomponent, which mechanical
change can be determined using the ultrasound visualization
equipment. For example, a mechanical portion of the
volume-occupying subcomponent containing an ultrasound
visualization marker may elongate upon an increase in pressure in
the volume-occupying subcomponent.
[0902] Alternatively, an ultrasound marker may be formed using a
mesh, for example a metallic mesh, located between layers of the
material from which the volume-occupying subcomponent is
constructed. The pattern or patterns formed by the imbedded
ultrasound marker will appear when the volume-occupying
subcomponent is in an inflated, deployed state.
[0903] In some embodiments, an ultrasound sensor comprises a
non-contact sensor. An ultrasonic level or sensor or sensing system
requires no contact with the target. In the medical industries this
is an advantage over inline sensors that may contaminate or
otherwise interfere with the marker or item of interest. In some
embodiments, the sensor is a microphone.
[0904] In some embodiments, a pulsed wave system is used. The
principle behind a pulsed-ultrasonic technology is that the
transmit signal consists of short bursts of ultrasonic energy.
After each burst, the sensor electronics looks for a return signal
within a small window of time corresponding to the time it takes
for the energy to pass through the medium of interest. Only a
signal received during this window will qualify for additional
signal processing. In some embodiments a continuous wave system is
used. In the pulsed, continuous, or other wave systems, the sensor
may be a microphone that receives the return wave signal.
[0905] In some embodiments, a marker may transmit ultrasound
signals. For instance, Ultrasound Identification (USID) may be used
to automatically track and identify the location of intragastric
devices in real time using simple, inexpensive nodes (badges/tags)
attached to or embedded in the ultrasound devices, which then
transmit an ultrasound signal to communicate their location to
ultrasound sensors, such as microphones.
[0906] A computing system may be implemented in the ultrasound
locating system. The computing system comprises hardware and
software that receives data from the ultrasound sensor and
calculates information related to the location, orientation, and/or
state of an intragastric device according to certain algorithms. In
some embodiments, the hardware may comprise a central processing
unit, memory, an analog to digital converter, analog circuitry, a
display. In some embodiments, the software proceeds through a
number of steps including calibration, initialization, prediction,
estimation, measuring magnetic sensor data, calculating various
desired outputs including location, orientation, size,
configuration, etc. in accordance with the techniques discussed
herein.
[0907] The processor's output relating to the location, orientation
and/or state of an intragastric device may be communicated to a
user in a number of manners. In some embodiments, the output is
shown visually on a display.
[0908] In some embodiments, the processor's output related to an
intragastric device's location, orientation, and/or state is
audibly communicated to a user through a speaker.
[0909] In some embodiments, the processor's output related to an
intragastric device's location, orientation, and/or state is
communicated to a user through a combination of methods. For
instance, the system may employ a visual graphical display with
audible alerts sent through speakers.
[0910] In some embodiments, the ultrasound locating system is
calibrated before use. The ultrasound marker and the sensor are
positioned in pre-planned locations and orientations to verify the
output signal is within an expected range. In some embodiments, the
ultrasound locating systems are calibrated or otherwise verified
using a human patient simulator, or dummy, to test the ultrasound
locating system as a ultrasound marker travels through the
simulator. In some embodiments, the ultrasound locating system is
checked for stray signals from nearby acoustic interferences.
[0911] The ultrasound sensor may be used in conjunction with the
marker or markers in a variety of embodiments to locate or
otherwise characterize an ingested intragastric device. In some
embodiments, an off-the-shelf intragastric device, such as a
swallowable, inflatable balloon, may be used without modification
with any ultrasound markers. With that device, an ultrasound sensor
that pulses sound waves and senses their return signal with a
microphone may be used outside the body. The device could be
swallowed in a deflated state and would then inflate once inside
the stomach. The ultrasound sensor may be used to locate or
otherwise characterize the device by pulsing the device and
receiving the return signals, in accordance with the techniques
discussed above.
[0912] The devices once ingested may be located using the
ultrasound intragastric locating system. In some embodiments, the
sensor may locate the device by pulsing in various locations and
analyzing the return signal. For instance, a return signal
corresponding to a body organ without the device may be
pre-determined by correlating a return wave signal to a location on
the body before the device is swallowed. This could produce an
ultrasound map of the organ or body without any device. Then, after
swallowing the device, and by running the sensor over the body, if
a different signal is returned for a corresponding location in the
body, then the location of the device is thus identified. This may
be implemented in accordance with the techniques discussed
above.
[0913] The orientation of the devices once ingested may be
ascertained using the ultrasound intragastric locating system. In
some embodiments, the sensor may identify the orientation of the
intragastric device by pulsing and sensing at various locations of
the device and analyzing the return signals. For instance, before
ingestion by a patient, the device may be pulsed at various
orientations such that a pre-determined database exists of known
correlations between return wave signatures and orientation of the
device. This may be done for the device in the deflated, inflated,
or other states. Then, after ingestion, the device may be pulsed
and the return signals compared to the pre-determined database to
determine the orientation of the device in accordance with the
techniques discussed above.
[0914] Further, the various sizes and configurations of the devices
once ingested may be characterized using the ultrasound
intragastric locating system in accordance with the techniques
discussed above. For instance, inflation of a balloon, or the
inflation or configuration of multiple balloons, may be
characterized and assessed. In some embodiments, the sensor may
characterize the device or devices by pulsing and sensing at
various locations of the device and analyzing the return signals.
For instance, the deflated device would return a different pulsed
signature than the inflated device. In such a manner, the device
may be characterized as either inflated, deflated, or in some other
state. The inflated device could further be characterized before
ingestion by a patient such that the return signal signature is
pre-determined and serves as a guidepost for assessing the state of
the device. In some embodiments, the ultrasound locating system may
be used in conjunction with a deflating system to characterize the
deflation process.
[0915] The timing and other attributes of the various methods of
administration can be characterized using the disclosed ultrasound
intragastric locating system and techniques. Whether the device is
administered using endoscopic techniques or orally, the progress of
the device as it makes its way to the stomach can be tracked with
the ultrasound locating system. For instance, the effects of
swallowing the device with hard gelatin or water or other
consumables may be characterized by tracking the location and
orientation as it is ingested.
[0916] In some embodiments, the ultrasound locating system may
characterize an intragastric device that has 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.
[0917] Using the speed of sound, a distance can be computed from
the time between transmission and reception. The time between
transmission of the ultrasonic pulse and reception of the echo is
given by: t=2d/U, or d=Ut/2, (53) where U is the speed of sound in
the medium of interest, and d is the diameter of the device. If
transmission occurs in two orthogonal directions, two dimensions of
the intragastric device can be determined, and thus the area of the
device can be computed. Assuming the device is an ellipse, the
equation for the area of an ellipse using the major (a) and minor
(b) axes is as follows:
A=.pi.ab=(.pi.U.sup.2t.sub.1t.sub.2)/16
[0918] If the interior of an inflated device is clear, a clear echo
signal is obtained and the time of flight of the ultrasound pulse
is obtained in the clear area to determine device area. To detect
the presence of matter, foreign or otherwise, in the device, two
methods may be used. First, the orthogonal signal, that is the
amplitude of the scattered ultrasonic pulse in the orthogonal
direction, is compared with the original pulse echo return. And
second, the amount of false return in the original pulse echo may
even determine the ratio of solid to liquid matter in the analyzed
cross section of the device.
[0919] The intragastric device may include two orthogonal
ultrasonic transmitter/receiver ("transceiver") modules. One
transceiver is an anterior/posterior (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 is capable of
distinguishing between device echoes and the empty device interior.
The microprocessor is also capable of preparing a signal for
transmission. The microprocessor is in electrical communication
with a computer. In some embodiments, the computer and the
microprocessor are incorporated into the same component. In at
least one embodiment, the computer may be a look up table, capable
of determining the semi-major axis, the semi-minor axis, and the
scatter associated with the device.
[0920] The intragastric device may also include a transmitter
capable of transmitting the signals from the device to a location
outside of the body. The transmitter can include an antenna for
transmission, or an antenna in the band (not shown) can be in
electrical communication with the transmitter. The device may also
include a module either containing a battery or capable of powering
the intragastric device electronics inductively. External to the
patient may be an antenna for receiving the transmitted signals and
a receiver in operative communication with the antenna. A computer
may be included that has software capable of decoding and
processing the signals transmitted by the transmitter and received
by the receiver. The computer software is capable of measuring the
time of flight of horizontal and vertical ultrasonic pulses to
determine the length and width of the intragastric device, and
combining the length and width to find the area. It should be noted
that from the scatter of the horizontal into the vertical receiver
and the scatter of the vertical into the horizontal receiver, the
presence of any material in the device can be determined.
[0921] In some embodiments, the ultrasonic system can be
calibrated. The data collected can be displayed in a graphical
manner with the lateral and horizontal times of flight graphically
correlated to various areas of the intragastric devices.
[0922] In some embodiments, the intragastric device has an inner
side and an outer side where the inner side being closer to the
intragastric device interior than the outer side, the two
ultrasonic modules being positioned on the outer side of the
intragastric device. The time of flight can be determined based on
the time to cross the intragastric device.
Voltaic Tracking and Visualization Subcomponent
[0923] Tracking and visualization functionality can be incorporated
into devices and systems described above. As used herein,
"visualization" is used broadly to refer to identifying an item of
interest in the body in a number of ways, including by providing a
sensor or marker to produce a voltage in response to the gastric
environment encountered by the voltage sensor or marker. Due to the
non-invasive nature of the present device, physicians may desire to
determine, or confirm, the location and orientation of the device
prior to inflation, during the course of treatment, or after
deflation. Accordingly, intragastric devices are provided that
incorporate voltaic sensing components configured for enabling
determining and confirming the location, orientation and/or state
of an intragastric device at all phases of administration.
[0924] In some embodiments, a voltaic tracking and visualization
subcomponent may be implemented in other embodiments described
herein. For example, as described above, FIG. 10C depicts an
embodiment of a voltage sensor that may be implemented with the
catheter of FIG. 10A. This is merely one example and other
embodiments may implement a voltaic sensor as well. Certain voltaic
sensor embodiments are described below which may be implemented in
or with the sensor of FIG. 10C or other systems described
herein.
[0925] In some embodiments, an ingestible event marker (i.e., an
IEM) and/or a personal signal receiver are implemented with an
intragastric device. Embodiments of the IEM include an identifier,
which may or may not be present in a physiologically acceptable
carrier. The identifier is characterized by being activated upon
contact with a target internal physiological site of a body (e.g.,
a specific target environment, including a target chemical
environment, target physical environment etc.), such as digestive
tract internal target site, including the stomach. The personal
signal receiver is configured to be associated with a physiological
location, e.g., inside of or on the body, and to receive a signal
from the IEM. During use, the IEM broadcasts or otherwise
communicates a signal which is received by the personal signal
receiver and which may be indicative of the location of the sensor.
For instance, the signal generated ma be indicative of the voltaic
sensor being located in the stomach. Where 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.
[0926] Embodiments include ingestible event marker compositions
having an identifier stably associated therewith. The identifier of
the IEM compositions is one that generates (i.e., emits) a
detectable signal upon contact of the identifier with a target
physiological sight. The identifiers of the present compositions
may vary depending on the particular embodiment and intended
application of the composition so long as they are activated (i.e.,
turned on) upon contact with a target physiological location, e.g.,
stomach. As such, the identifier may be an identifier that emits a
signal when it contacts a target body (i.e., physiological) site.
The identifier may be any component or device that is capable of
providing a detectable signal following activation, e.g., upon
contact with the target site. In certain embodiments, the
identifier emits a signal once the composition comes into contact
with a physiological target site, e.g., as summarized above.
[0927] 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: a location in
the gastrointestinal tract, such as the mouth, esophagus, stomach,
small intestine, large intestine, etc. In certain embodiments, the
identifier is configured to be activated upon contact with fluid in
the target site, regardless of the particular composition of the
target site. In some embodiments, the identifier is configured to
be activated only upon contact with a target site or region of
interest, such as the stomach, in order to, for example, confirm
the location of the intragastric device.
[0928] The signal obtained from the identifier may be a generic
signal, e.g., a signal that merely identifies that the composition
has contacted the target site, or a unique signal, e.g., a signal
which in some way uniquely identifies that a particular ingestible
event marker from a group or plurality of different markers in a
batch has contacted a target physiological site. In yet other
embodiments, the identifier emits a signal that uniquely identifies
that particular identifier. Accordingly, in certain embodiments the
identifier emits a unique signal that distinguishes one class of
identifier from other types of identifiers. In certain embodiments,
the identifier emits a unique signal that distinguishes that
identifier from other identifiers. In certain embodiments, the
identifier emits a signal that is unique, i.e., distinguishable,
from a signal emitted by any other identifier ever produced, where
such a signal may be viewed as a universally unique signal (e.g.,
analogous to a human fingerprint which is distinct from any other
fingerprint of any other individual and therefore uniquely
identifies an individual on a universal level). In one embodiment,
the signal may either directly convey information about a given
event, or provide an identifying code, which may be used to
retrieve information about the event from a database, i.e., a
database linking identifying codes with compositions.
[0929] The identifier may generate a variety of different types of
signals, including but not limited to: voltaic, RF signals,
magnetic signals, conductive (near field) signals, acoustic
signals, etc. The transmission time of the identifier may vary,
where in certain embodiments the transmission time may range from
about 0.1 .mu.sec to about 48 hours or longer, e.g., from about 0.1
.mu.sec to about 24 hours or longer, such as from about 0.1 .mu.sec
to about 4 hours or longer, such as from about 1 sec to about 4
hours, including about 1 minute to about 10 minutes. Depending on
the given embodiment, the identifier may transmit a signal once or
transmit a signal two or more times, such that the signal may be
viewed as a redundant signal.
[0930] In certain embodiments, the identifier is dimensioned to be
orally ingestible, e.g., either by itself or upon combination with
a physiologically acceptable carrier component of the composition,
such as a swallowable catheter or balloon. As such, in certain
embodiments, the identifier element is dimensioned to have a width
ranging from about 0.05 to about 2 or more mm, e.g., from about
0.05 mm to about 1 mm, such as from about 0.1 mm to about 0.2 mm; a
length ranging from about 0.05 to about 2 or more mm, e.g., from
about 0.05 mm to about 1 mm, such as from about 0.1 mm to about 0.2
mm and a height ranging from about 0.05 to about 2 or more mm,
e.g., from about 0.1 mm to about 1 mm, such as from about 0.05 mm
to about 0.3 mm, including from about 0.1 mm to about 0.2 mm. In
certain embodiments the identifier is 1 mm.sup.3 or smaller, such
as 0.1 mm.sup.3 or smaller, including 0.2 mm.sup.3 or smaller. The
identifier element may take a variety of different configurations,
such as but not limited to: a chip configuration, a cylinder
configuration, a spherical configuration, a disc configuration,
etc, where a particular configuration may be selected based on
intended application, method of manufacture, etc.
[0931] In certain embodiments, the identifier may be one that is
programmable following manufacture. For example, the signal
generated by the identifier may be determined after the identifier
is produced, where the identifier may be field programmable, mass
programmable, fuse programmable, and even reprogrammable. Such
embodiments are of interest where uncoded identifiers are first
produced and following incorporation into a composition are then
coded to emit an identifying signal for that composition. Any
convenient programming technology may be employed. In certain
embodiments, the programming technology employed is RFID
technology. RFID smart tag technology of interest that may be
employed in the subject identifiers includes, but is not limited
to: that described in U.S. Pat. Nos. 7,035,877; 7,035,818;
7,032,822; 7,031,946, as well as published application no.
20050131281, and the like, the disclosures of which are herein
incorporated by reference in their entirety. With RFID or other
smart tag technology, a manufacturer/vendor may associate a unique
ID code with a given identifier, even after the identifier has been
incorporated into the composition. In certain embodiments, each
individual or entity involved in the handling of the composition
prior to use may introduce information into the identifier, e.g.,
in the form of programming with respect to the signal emitted by
the identifier, e.g., as described in U.S. Pat. No. 7,031,946 the
disclosure of which is herein incorporated by reference in its
entirety.
[0932] The identifier of certain embodiments includes a memory
element, where the memory element may vary with respect to its
capacity. In certain embodiments, the memory element has a capacity
ranging from about 1 bit to 1 gigabyte or more, such as 1 bit to 1
megabyte, including from about 1 bit to about 128 bit. The
particular capacity employed may vary depending on the application,
e.g., whether the signal is a generic signal or coded signal, and
where the signal may or may not be annotated with some additional
information, e.g., name of active agent associated with the
identifier, etc.
[0933] Identifier components of some embodiments have: (a) an
activation component; and (b) a signal generation component, where
the signal generation component is activated by the activation
component to produce an identifying signal, e.g., as described
above.
[0934] The activation component is a component that activates the
signal generation element of the identifier to provide a signal,
e.g., by emission or upon interrogation, following contact of the
composition with a target physiological site of interest, such as
the stomach. Activation of the identifier may be achieved in a
number of different ways, where such approaches include, but are
not limited to: battery completion, battery connection, etc.
[0935] Embodiments of activation elements based on battery
completion formats employ a battery that includes, when completed,
a cathode, an anode, and an electrolyte, where the electrolyte is
made up, at least in part, by fluid present at the target
physiologic site (e.g. stomach fluid present in the stomach, where
the stomach is the target physiological site). For example, when a
stomach fluid activated IEM is ingested, it may travel, for
instance with a swallowable catheter and/or an intragastric device,
through the esophagus and proceed to enter the stomach. The cathode
and anode provided on the IEM do not constitute a full battery.
However, when the cathode and anode are exposed to stomach fluid,
the stomach fluid acts as the electrolyte component of the battery
and completes the battery. Therefore, as the IEM contacts the
target site, a power source is provided which activates the
identifier. The data signal is then transmitted.
[0936] In certain embodiments, the battery that is employed is one
that comprises two dissimilar electrochemical materials which
constitute the two electrodes (e.g., anode and cathode) of the
battery. When the electrode materials are exposed and come in
contact with the body fluid, such as stomach acid or other types of
fluid, a potential difference (i.e., voltage), is generated between
the electrodes as a result of the respective oxidation and
reduction reactions that occur the two electrode materials. The two
dissimilar materials in an electrolyte are at different potentials.
As an example, copper and zinc when put into a cell have different
potentials. Similarly, gold and magnesium have different
potentials.
[0937] 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 iodide, chloride, bromide,
sulfate, formate, (other anions possible); or Fe3+ salts such as
orthophosphate, pyrophosphate, (other anions possible); or Oxygen
or hydrogen on platinum, gold or other catalytic surfaces.
Intercalation compounds may also be used. For the anode, materials
include graphite with Li, K, Ca, Na, Mg, and for the cathode
materials include vanadium oxide and manganese oxide.
[0938] Certain high energy anode material such as Li, Na, and other
alkali metals are unstable in their pure form in the presence of
water or oxygen. These may however be used in an aqueous
environment if stabilized. One example of this stabilization is the
so-called "protected lithium anode" developed by Polyplus
Corporation (Berkeley, Calif.), where a polymer film is deposited
on the surface of lithium metal to protect it from rapid oxidation
and allow its use in aqueous environment or air ambient. (Polyplus
has IP pending on this). (.dagger . . . dagger.) Dissolved oxygen
can also serve as a cathode. In this case, the dissolved oxygen in
the bodily fluids would be reduced to OH-- at a suitable catalytic
surface such at Pt or gold. Other catalysts are also possible. Also
of interest dissolved hydrogen in a hydrogen reduction
reaction.
[0939] In certain embodiments, one or both of the metals may be
doped with a non-metal, e.g., to enhance the voltage output of the
battery. Non-metals that may be used as doping agents in certain
embodiments include, but are not limited to: sulfur, iodine and the
like.
[0940] In certain embodiments, the electrode materials are cuprous
iodine (CuI) or cuprous chloride as the cathode and magnesium (Mg)
metal or magnesium alloy as the anode. Embodiments of the present
invention use electrode materials that are not harmful to the human
body. In certain of these embodiments, the battery power source may
be viewed as a power source that exploits electrochemical reaction
in an ionic solution such as gastric fluid, blood, or other bodily
fluids and some tissues.
[0941] FIG. 41 provides a diagrammatic representation of an
identifier 30M according to an embodiment of the invention. First
and second electrode materials 32M and 33M are in an ionic solution
39M (e.g., stomach fluid). This configuration creates a low voltage
(V-) and a high voltage (V+) as applied to an electronic circuit
40M. The two outputs of that electronic circuit 40M are electrodes
41M and 42M, which are the signal-transmission electrodes. In an
alternate embodiment, the signal generation element 30M includes a
single electrode. In an alternative embodiment, a coil for
communication may be provided. In certain embodiments, a structure,
e.g., membrane, larger than the chip which defines a path for the
current to travel is provided.
[0942] Referring to FIG. 41, electrodes 32M and 33M can be made of
any two materials appropriate to the environment in which the
identifier 30M will be operating. The active materials are any pair
of materials with different electrochemical potentials. For
instance, in some embodiments where ionic solution 39M comprises
stomach acids, electrodes 32M and 33M may be made of a noble metal
(e.g., gold, silver, platinum, palladium or the like) so that they
do not corrode prematurely. Alternatively, the electrodes can be
fabricated of aluminum or any other conductive material whose
survival time in the applicable ionic solution is long enough to
allow identifier 30M to perform its intended function. Suitable
materials are not restricted to metals, and in certain embodiments
the paired materials are chosen from metals and non-metals, e.g., a
pair made up of a metal (such as Mg) and a salt (such as CuI). With
respect to the active electrode materials, any pairing of
substances--metals, salts, or intercalation compounds--with
suitably different electrochemical potentials (voltage) and low
interfacial resistance are suitable.
[0943] In certain embodiments, the IEMs are characterized by
including series battery structures, where these series battery
structures may be configured to substantially reduce, if not
eliminate, shorting between electrode elements of different battery
structures of the series. As the batteries of the present invention
are series batteries, the batteries include two or more individual
battery structures or units, where the number of battery structures
that may be present in a given series battery of the invention may
be two or more, three or more, four or more, five or more, etc., as
desired for a given application of the battery. Each individual
battery structure includes at least one anode and at least one
cathode, where the anode and the cathode are present on a surface
of a solid support, where the support for each of the anode and
cathode may be the same or different.
[0944] Aspects of the series batteries include configurations that
substantially reduce, if not eliminate, shorting between two or
more of the batteries of a given series. This elimination of
shorting is provided despite the small area that is occupied by the
two or more batteries of the series, e.g., where the battery units
are present on the surface of a solid support. Embodiments of the
subject series batteries include configurations in which the
resistance between electrodes of two different battery structures
of the series battery is much higher than the resistance between
electrodes within a given battery structure. In certain
embodiments, the ratio of the ionic resistance between electrodes
of two different battery structures as compared to electrodes
(i.e., anode and cathode) within a single battery structure is
about 1.5.times. or more, such as about 5.times. or more, including
about 10.times. or more.
[0945] Depending on a particular series battery configuration,
shorting between batteries can be reduced, if not eliminated, using
a variety of different approaches. Certain approaches that can be
employed are reviewed in greater detail below, where the below
approaches may or may not be used in combination, depending on the
particular battery configuration of interest.
[0946] In certain embodiments, two or more battery structures are
provided in series, where each battery structure includes a chamber
having an anode and cathode positioned inside the chamber, e.g., on
the same internal wall or different internal walls. The chamber has
a volume that may vary, and in certain embodiments ranges from
about 10.sup.-12 to about 10.sup.-5 L, such as from about
10.sup.-11 to about 10.sup.-7 L and including from about 10.sup.-10
to about 10.sup.-8 L. In certain embodiments, the chamber may
include an amount of a dried conductive medium, e.g., as described
in PCT Application Serial No. PCT/US07/82563, the disclosure of
which is herein incorporated by reference in its entirety.
[0947] In certain embodiments, a given chamber includes at least
one fluid entry port and at least one fluid exit port, so that
liquid, e.g., stomach fluid, can enter the chamber when the
composition in which the battery is present reaches the target site
of interest and gas can exit the chamber upon entry of the liquid.
While the dimensions of the fluid entry and exit ports may vary, in
certain embodiments the ports have a diameter ranging from about
0.01 .mu.m to about 2 mm, such as from about 5 .mu.m to about 500
.mu.m.
[0948] The ports of a given chamber are positioned relative to
ports of other chambers to provide for efficient entry of fluid
into and exit of gas from the chamber, and are also positioned to
provide for substantially no, if any, shorting between two or more
different chambers of the series battery. As such, location of the
ports is chosen in view of both the battery structure itself and
its physical relation to other battery structures of the series
battery. Any configuration of fluid ports may be chosen, so long as
the configuration provides the desired resistance ratio, e.g., as
described above.
[0949] FIG. 58 provides an overhead view of a series battery
according to one embodiment. In FIG. 58, a series battery 150 is
made up of two different battery structures 151A and 151B present
on a surface 152X of a solid support 153. The battery structure
151A includes cathode 154A and anode 155A while the structure 151B
includes cathode 154B and anode 155B. As illustrated, the cathodes
and anodes of each battery structure are present in a chamber
defined by boundary 156A and 156B. Present in the wall 156A of
structure 151A are ports 157A and 158A, which provide for fluid
entry and exit from the chamber. Ports 157A and 158A of structure
151A are positioned relative to ports 157B and 158B of structure
151B so that the potential for shorting between the electrodes of
structures 151A and 151B is substantially, if not completely
eliminated. In the configuration shown in FIG. 28, ports 157A and
158A are positioned on opposing walls of boundary 156A and ports
157B and 158B are positioned on opposing walls of boundary 156B.
Furthermore, ports 157A and 158A are present on opposing walls of
their boundary element 156A with respect to the positioning of
ports 157B and 158B in boundary element 156B.
[0950] FIG. 59 provides an overhead view of a series battery
according to an embodiment. In FIG. 59, series battery 160A is made
up of two different battery structures 161A and 161B present on
surface 162 of solid support 163. Battery structure 161A includes
cathode 164A and anode 165A while structure 161B includes cathode
164B and anode 165B. The structure illustrated in FIG. 59 differs
from that shown in FIG. 58 as the battery structures are stacked
next to each other. As illustrated, the cathodes and anodes of each
battery structure are present in a chamber defined by boundary 166A
and 166B. Present in the wall 166A of structure 161A are ports 167A
and 168A, which provide for fluid entry and exit from the chamber.
Ports 167A and 168A of structure 161A are positioned relative to
ports 167B and 168B of structure 161B so that the potential for
shorting between the electrodes of structures 161A and 161B is
substantially, if not completely eliminated.
[0951] In addition to, or instead of, locating fluid ports to
provide for the desired resistance ratio, the fluid ports may be
modified to provide the desired resistance between battery
structures. For example, the port may include a selective
semi-permeable membrane. Any convenient semi-permeable membrane may
be employed. The semi-permeable membrane may comprise 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 material. The pore size of the membrane may vary
depending on the particular configuration, where in certain
embodiments the membrane have a pore size (MW cutoff of about 1000
d or less, such as about 500 d or less, including about 250 d or
less, e.g., about 100 d or less, such as about 50 d or less). In
certain embodiments, the membrane is a water only permeable
membrane, such that water, but little if any other fluid
constituents at the target site, pass through the membrane to reach
to the dried conductive medium precursor of the identifier.
[0952] In certain embodiments, the solid support 153, 163 is a
circuitry support element. The circuitry support element may take
any convenient configuration, and in certain embodiments is an
integrated circuit (IC) chip. The surface upon which the electrode
elements are positioned may be the top surface, bottom surface or
some other surface, e.g., side surface, as desired, where in
certain embodiments the surface upon which the electrode elements
are at least partially present is a top surface of an IC chip.
[0953] In certain embodiments, the series batteries have a small
form factor. Batteries may be about 20 mm.sup.3 or smaller, e.g.,
about 10 mm.sup.3 or smaller, such as 1.0 mm.sup.3 or smaller,
including 0.1 mm.sup.3 or smaller, including 0.02 mm.sup.3 or
smaller. In certain embodiments, the battery element is dimensioned
to have a width ranging from about 0.01 mm to about 100 mm, e.g.,
from about 0.1 mm to about 20 mm, including from about 0.5 mm to
about 2 mm; a length ranging from about 0.01 mm to about 100 mm,
e.g., from about 0.1 mm to about 20 mm, including from about 0.5 mm
to about 2 mm, and a height ranging from about 0.01 mm to about 10
mm, e.g., from about 0.05 mm to about 2 mm, including from about
0.1 mm to about 0.5 mm.
[0954] Series battery embodiments includes those further described
in U.S. Provisional Application Ser. No. 60/889,871, the disclosure
of which is herein incorporated by reference in its entirety. The
signal generation component of the identifier element is a
structure that, upon activation by the activation component, emits
a detectable signal, e.g., that can be received by a receiver,
e.g., as described in greater detail below. The signal generation
component of certain embodiments can be any convenient component or
element that is capable of producing a detectable signal and/or
modulating transduced broadcast power, upon activation by the
activation component. Detectable signals of interest include, but
are not limited to: conductive signals, acoustic signals, etc. The
signals emitted by the signal generator may be generic or unique
signals, where representative types of signals of interest include,
but are not limited to: frequency shift coded signals; amplitude
modulation signals; frequency modulation signals; etc.
[0955] In certain embodiments, the signal generation element
includes circuitry which produces or generates the signal. The type
of circuitry chosen may depend, at least in part, on the driving
power that is supplied by the power source of the identifier. For
example, where the driving power is 1.2 volts or above, standard
CMOS circuitry may be employed. In other embodiments where the
driving power ranges from about 0.7 to about 1.2 V, sub-threshold
circuit designs may be employed. For driving powers of about 0.7 V
or less, zero-threshold transistor designs may be employed. In some
embodiments, the power source may be the voltage produced by
contact of the voltaic sensor with the gastric environment, as
discussed in further detail herein.
[0956] In certain embodiments, 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, which is
assigned an address and which can control the VCO with a control
voltage. This digital control circuit can be embedded onto a chip
that includes the activation component and oscillator. Using
amplitude modulation or phase shift keying to encode the address,
an identifying signal is transmitted.
[0957] The signal generation component may include a distinct
transmitter component that serves to transmit the generated signal
to a remote receiver, which may be internal or external to the
patient. The transmitter component, when present, may take a number
of different configurations, e.g., depending on the type of signal
that is generated and is to be emitted. In certain embodiments, the
transmitter component is made up of one or more electrodes. In
certain embodiments, the transmitter component is made up of one or
more wires, e.g., in the form of antenna(e). In certain
embodiments, the transmitter component is made up of one or more
coils. As such, the signal transmitter may include a variety of
different transmitters, e.g., electrodes, antennas (e.g., in the
form of wires) coils, etc. In certain embodiments, the signal is
transmitted either by one or two electrodes or by one or two wires
(a two-electrode transmitter is a dipole; a one electrode
transmitter forms a monopole). In certain embodiments, the
transmitter only requires one diode drop of power. In some
embodiments, the transmitter unit uses an electric dipole or
electric monopole antenna to transmit signals. In certain
embodiments, the identifier employs a conductive near-field mode of
communication in which the body itself is employed as a conductive
medium. In such embodiments, the signal is not a magnetic signal or
high frequency (RF) signal.
[0958] FIG. 42 shows the detail of one implementation of an
electronic circuit that can be employed in an identifier according
to some embodiments. On the left side are the two battery
electrodes, a first metal 32M and a second metal 33M. These metals,
when in contact with an electrolyte, form a battery that provides
power to an oscillator 61M, in this case shown as a schematic. The
metal 32M provides a low voltage, (ground) to the oscillator 61M.
Metal 33M provides a high voltage (V-high) to the oscillator 61M.
As the oscillator 61M becomes operative, it generates a clock
signal 62M and an inverted clock signal 63M, which are opposites of
each other. These two clock signals go into the counter 64M which
simply counts the number of clock cycles and stores the count in a
number of registers. In the example shown here, an 8 bit counter is
employed. Thus, the output of counter 64M begins with a value of
"00000000," changes to "00000001" at the first clock cycle, and
continues up to "11111111." The 8-bit output of counter 64M is
coupled to the input of an address multiplexer (mux) 65M. In one
embodiment, mux 65M contains an address interpreter, which can be
hard-wired in the circuit, and generates a control voltage to
control the oscillator 61M. Mux 65M uses the output of counter 64M
to reproduce the address in a serial bit stream, which is further
fed to the signal-transmission driving circuit. Mux 65M can also be
used to control the duty-cycle of the signal transmission. In one
embodiment, mux 65M turns on signal transmission only one sixteenth
of the time, using the clock counts generated by counter 64M. Such
a low duty cycle conserves power and also allows other devices to
transmit without jamming their signals. The address of a given chip
can be 8 bits, 16 bits or 32 bits.
[0959] According to one embodiment, mux 65M produces a control
voltage, which encodes the address serially and is used to vary the
output frequency of oscillator 61M. By example, when the control
voltage is low, that is, when the serial address bit is at a 0, a 1
megahertz signal is generated by the oscillator. When the control
voltage is high, that is, when the address bit is a 1, a 2
megahertz signal is generated the oscillator. Alternately, this can
be 10 megahertz and 20 megahertz, or a phase shift keying approach
where the device is limited to modulating the phase. The purpose of
mux 65M is to control the frequency of the oscillator or an AC
alternative embodiment of the amplified signal of oscillation.
[0960] The outputs of mux 65M are coupled to electrode drive 66M
which can drive the electrodes to impose a differential potential
to the solution, drive an oscillating current through a coil to
generate a magnetic signal, or drive a single electrode to push or
pull charge to or from the solution.
[0961] In this manner, the device broadcasts the sequence of 0's
and 1's which constitute the address stored in mux 65M. That
address would be broadcast repeatedly, and would continue
broadcasting until metal 32M or metal 33M is consumed and dissolved
in the solution, when the battery no longer operates.
[0962] Other configurations for the signal generation component are
of course possible. Other configurations of interest include, but
are not limited to: those described in PCT application serial no.
PCT/US2006/016370 and provisional application Ser. No. 60/807,060
filed on Jul. 11, 2006, the disclosure of each of which is herein
incorporated by reference.
[0963] In certain embodiments, the activation component includes a
power storage element. For example, a duty cycle configuration may
be employed, e.g., where slow energy production from a battery is
stored in a power storage element, e.g., in a capacitor, which then
provides a burst of power that is deployed to the signal generation
component. In certain embodiments, the activation component
includes a timing element which modulates, e.g., delays, delivery
of power to the signal generation element, e.g., so signals from
different compositions, e.g., different IEMs, that are administered
at substantially the same time are produced at different times and
are therefore distinguishable.
[0964] In certain embodiments, the components or functional blocks
of the identifiers of the ingestible event markers are present on
integrated circuits, where the integrated circuits include a number
of distinct functional blocks, i.e., modules. Within a given
identifier, at least some of, e.g., two or more, up to an including
all of, the functional blocks, e.g., power source, transmitter,
etc., may be present in a single integrated circuit in the
receiver. By single integrated circuit is meant a single circuit
structure that includes all of the different functional blocks. As
such, the integrated circuit is a monolithic integrated circuit
(also known as IC, microcircuit, microchip, silicon chip, computer
chip or chip) that is a miniaturized electronic circuit (which may
include semiconductor devices, as well as passive components) that
has been manufactured in the surface of a thin substrate of
semiconductor material. The integrated circuits of certain
embodiments of the present invention may be hybrid integrated
circuits, which are miniaturized electronic circuits constructed of
individual semiconductor devices, as well as passive components,
bonded to a substrate or circuit board.
[0965] Embodiments of the present invention provide a low-power,
miniature, ingestible marker that includes an integrated circuit
(IC) which automatically activates itself after the marker contacts
a patient's body fluid, transmits a predetermined signal based on
locally generated power, and de-activates itself after a certain
period of time. In these embodiments, as described above, the IEM
uses the patient's body fluid, such as the stomach acid, to form a
voltaic cell. Furthermore, the IEM uses a special circuit that
changes the impedance of a closed circuit which forms the voltaic
cell, thereby creating an external signal by modulating the
amplitude and waveform of the current that flows through the
patient's tissue and body fluid. As described in more detail below,
such a circuit configuration allows the circuitry to operate at a
low voltage while generating a signal that is sufficiently strong
to be detected by a receiver in contact with the patient's
body.
[0966] An IEM's IC can be packaged with an integrated voltaic cell
which can be manufactured on the same substrate as the IC circuit.
This wafer level integration significantly reduces the chip and
simplifies the manufacturing process. As a result, each IEM's cost
can be considerably lowered. In one embodiment, the anode and
cathode electrode materials are fabricated on each side of the
substrate, whereby the IC logic is situated between the two
electrodes. In one embodiment, the logic circuit is situated in a
location chosen to minimize the area overlapping vertically with
the anode or cathode electrode.
[0967] FIG. 43 illustrates an exemplary device configuration of the
IEM IC in accordance with one embodiment. In one embodiment, the IC
chip's substrate 204A is coupled to the anode (S1) of the voltaic
cell, which can be a layer of Magnesium (Mg) 206A coated on the
backside of substrate 204A. On the opposite side of substrate 204A
is a layer of cathode (S2) material 202A, which in this example is
Copper Chloride (CuCl). The electrodes 202A and 206A, and the body
fluid which serves as an electrolyte fluid, form the voltaic cell.
The IEM IC circuitry, which is fabricated on substrate 204A, is the
"external" circuit that forms a return circuit for the voltaic
cell. Essentially, 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, e.g., on a
personal health receiver as described in greater detail below, in
contact with the body fluid can detect this current change and
receive the encoded messages.
[0968] Note that the two electrodes S1 and S2 of the voltaic cell
also serve as the transmission electrodes for the IC. This
configuration significantly reduces the complexity of the IC chip.
Furthermore, since a fluid-metal interface often exhibits high
impedances, using a separate pair of electrodes which are different
from the voltaic-cell electrodes can introduce additional high
impedance to the circuit, thereby reducing the transmission
efficiency and increasing power consumption. Therefore, using the
voltaic-cell electrodes for transmission also improves the
power-efficiency of the IC circuitry.
[0969] The IC of the IEM functions as an ingestible transmitter
that transmits a unique identification code once powered on. This
IC can be packaged within a pharmaceutically acceptable vehicle,
e.g., as described above. When the IEM is swallowed and inside the
stomach, the integrated voltaic cell, or battery, uses the stomach
acid as the battery electrolyte to power up the main chip and
commences broadcasting or otherwise electrically communicating
thereafter. Furthermore, several pills can be ingested and transmit
at the same time. During operation, a unique identification code,
e.g., using BPSK modulation, is broadcasted. This broadcast can be
received and demodulated by a receiver, e.g., a sensor interface
unit. The receiver can decode and store the identification code
with a time stamp.
[0970] In one embodiment, a IEM IC includes an impedance-detection
circuitry. This circuitry is configured to detect the impedance
between the anode and cathode electrodes. When the electrodes are
not submerged in an electrolyte fluid, e.g., stomach acid, the
impedance between the electrodes is high and the IC is not
activated. When the electrodes are in contact with the electrolyte
fluid and the impedance-detection circuit detects the drop in
impedance, the IC is then activated.
[0971] Some embodiments allow the voltaic sensor to operate at low
voltages. In general, the IC can operate with a power supply at
0.8-2 V. In one embodiment, the IC is configured to operate with a
power supply at approximately 1.0-1.6 V. In addition, the voltaic
cell exhibits an internal impedance of 200-10K Ohm. In one
embodiment, the voltaic cell exhibits an internal impedance of
approximately 500-5K Ohm. The IC also provides an ultra stable
carrier clock frequency, thereby facilitating error-resistant
communications.
[0972] In one embodiment, an IC includes three parts of circuitry.
The first part is an impedance-detection circuitry that uses the
battery as the power supply. The second part is the main circuit
that broadcasts the messages. The impedance detection circuit can
hold the main circuit at substantially zero power consumption
before the battery detects an impedance lower than 10K Ohms. When
the impedance drops to approximately 10K Ohms, the main circuit is
activated and the impedance detection circuit can decouple itself
from the battery. The third part is a watchdog circuitry designed
to protect the patient's safety when hazardous situation
occurs.
[0973] FIG. 44 presents an exemplary schematic diagram illustrating
the design of a IEM IC in accordance with one embodiment of the
present invention. In general, the IEM chip has a battery section
302A and an IC circuitry 304A. Battery section 302A includes the
voltaic-cell electrodes, which when coupled with electrolyte fluid
form a voltaic cell. The two battery electrodes are coupled to the
high-voltage rail (VCC) and ground for the IC circuitry,
respectively. IC circuitry 304A includes a transmission switch
transistor 306A, a recharge transistor 308A, a recharge-protection
diode 310A, a recharge capacitor 316A, a local oscillator 314A, and
control logic 312A. Local oscillator 314A produces one or more
carrier frequencies which is used by control logic 312A to issue a
transmission command (labeled as "broadcast") to turn on and off
transmission switch transistor 306A. For example, oscillator 316A
can produce a 20 KHz signal, based on which control logic 312A can
generate a binary-phase shift keying (BPSK)-encoded message.
Control logic 312A then switches on and off transistor 306A to
transmit these messages.
[0974] When transistor 312A is turned on, a low-impedance external
return circuit is provided between the two voltaic-cell electrodes.
Consequently, the current flowing through the patient's body is
also increased. When transistor 312A is turned off, the external
return circuit between the two voltaic-cell electrodes exhibits a
high impedance. Correspondingly, the current flowing through the
patient's body is significantly lower. Note that the current draw
of the rest of the circuitry, e.g., the oscillator 314A and control
logic 312A, is sufficiently low so that there is a significant
difference in the body current between the broadcast period and the
silence period.
[0975] When transistor 306A is turned on, the two voltaic-cell
electrodes are effectively shorted. As a result, the voltage
provided by the electrodes is significantly 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 a silence
period, i.e., when transistor 306A remains off. When transistor
306A turns on which causes the voltage between the battery
electrodes to drop, diode 310A prevents the charges stored in
capacitor 316A from flowing back to the battery electrodes. In one
embodiment, diode 310A is a Schottky diode to ensure a fast
switching time.
[0976] It is possible that, during the transmission period,
oscillator 314A and/or control logic 312A have depleted the charges
stored in capacitor 316A, causing VCC to drop below a certain
threshold. For example, the voltage provided by recharge capacitor
316A may drop below the voltage provided by the voltaic cell. The
difference between these two voltages may not be large enough to
turn on Schottky diode 310A. In this case, control logic 312A can
issue a recharge signal to turn on recharge switching transistor
308A, which couples the battery voltage to capacitor 316A and
recharges capacitor 316A.
[0977] In one embodiment, the communication between the IEM IC and
the receiver is simplex. That is, the IEM IC only transmits signals
without receiving any signals. The communication is performed via
direct coupling between the IC electrodes and the receiver
circuitry through the patient's body tissue and fluids. The
transmission is performed at two frequencies, for example, one at
10 kHz and the other at 20 kHz. Other numbers of frequencies and
frequency values are also possible. In general, different
data-packet formats can be used with the present inventive system.
In one embodiment, the transmitted data packet is 40-bit long, of
which 16 bits are used as a synchronization/preamble pattern. The
rest 24 bits carry a payload that encodes the IEM's identifier. In
one embodiment, the payload can also include a forward error
correction (FEC) code so that the transmission is more robust. In
one embodiment, a data bit occupies 16 cycles of the carrier clock.
The bits are BPSK encoded. Other encoding schemes are also
possible. In a further embodiment, the 16-bit
synchronization/preamble pattern include 12 bits for
synchronization and 4 bits as a preamble.
[0978] FIG. 45 illustrates an exemplary transmission sequence for a
bit pattern of "0010" in accordance with one embodiment of the
present invention. Each bit is represented by 16 clock cycles.
Depending on the battery configuration, it might be desirable to
limit drive transistor 306A's duty cycle to maintain sufficient
power to the oscillator. In one embodiment, the "on" state of drive
transistor 306A is maintained to be substantially equal to or less
than 25 .mu.s. Thus, during the 20 kHz transmission where a clock
cycle is 50 .mu.s, the driver is on for 25 us and off for 25 .mu.s.
During the 10 kHz transmission, the driver is on for 25 us and off
for 75 .mu.s. A logical "0" transmission begins with the rising
edge of a data-clock cycle, and lasts for 16 clock cycles.
Correspondingly, a logical "1" transmission begins with the falling
edge of a data-clock cycle, and also lasts for 16 cycles. Note that
other duty-cycle configuration and encoding schemes are also
possible.
[0979] FIG. 46 presents an exemplary waveform for 20 kHz
transmission of a sequence "10101" in accordance with one
embodiment of the present invention. Note that for purposes of
illustration, each logical bit occupies 3 clock cycles, instead of
16 cycles. FIG. 47 presents an exemplary waveform of 10 kHz
transmission of a sequence "10101" in accordance with one
embodiment of the present invention. Note that each logical bit is
also shortened to 3 clock cycles.
[0980] In certain embodiments, the operation of the IEM can be
divided into the following four periods: storage, holding 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, the broadcast is
disabled for the oscillator clock signal to stabilize. In one
embodiment, during the broadcast period, a packet is transmitted
256 times. During each transmission, the transmission driver
transistor operates to transmit a packet and is then turned off for
a period of time. When the transmitter driver transistor is off,
the rest of the IEM IC remains powered on. In one embodiment, the
average duty cycle during the entire broadcast period is maintained
at approximately 3.9%. Other values of the average duty cycle are
also possible. During the power-down period, the IEM IC is powered
down gracefully. Broadcast is turned off completely.
[0981] FIG. 48 presents an exemplary state diagram illustrating the
operation of a IC in accordance with one embodiment. During
operation, the system first enters a storage period 702, when an
impedance detection circuit operates to detect the impedance
between the two battery electrodes. Meantime, the IC is power-gated
off. After the impedance detection circuit detects a low impedance,
for example an impedance of approximately 10 kOhm, the circuit
releases the IEM IC from the power-gated-off state.
Correspondingly, the system enters a holding period 704. During
holding period 704, the chip's 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 broadcasted twice in one cycle, one at 10 kHz and one
at 20 kHz, with a cycle pattern of ON (10 KHz) for 32 ms-OFF for
768 ms-ON (20 KHz) for 64 ms-OFF for 1536 ms. Each cycle is
approximately 2.4 seconds, and the system finishes 256 cycles in
approximately 10 minutes. Note that, at each frequency, the chip's
transmission duty cycle is maintained at approximately 3.9%. During
the remaining 96.1% of the time, the recharge capacitor is
recharged. Subsequently, the system enters a power-down state 708,
when the oscillator is stopped and the chip is power-gated down.
Note that if, for some reason, the chip keeps broadcasting
continuously before the end of the 10-minute broadcast period, the
system resets the chip's power supply and the broadcast process is
started again. Such situation may occur when, for example, the
stomach's conductivity suddenly drops so low that the oscillator
and its generated clocks cannot function properly.
[0982] In some embodiments, operation parameters for an IC may be
the following: the operating temperature may be from 20 to 45
degrees Celsius; the storage temperature may be from 0 to 60
degrees Celsius; the storage humidity may be from 20% to 90%
relative humidity; the human body conductivity/pH value may be from
0.01/4 to 1000/11 Sm.sup.-1/pH.
[0983] In some embodiments, an IEM circuit may have the following
DC parameters: the power supply for the main chip ("Vcc") except
the impedance detection circuit, and the output driver may be from
1.0-1.8 volts and typically about 1.6 volts; the DC current for the
chip during recharging ("I(s2)") may be from 8-12 uA and typically
about 1.6 uA; the battery voltage ("V(s2)") may be from 1.0-1.8
volts and typically 1.6 volts; the output driver's ON-resistance
("Zon") (function of "Vbattery") may be from 7-55 Ohms and
typically 11 Ohms; the output driver's OFF-resistance ("Zoff") may
be from about 75K-500 k Ohms and typically 100K ohms; the Battery
voltage when fully wetted ("Vbattery") may be from about 1.0-1.8
volts and typically about 1.6 volts; the solution's conductivity
for the chip to function properly ("Rbattery") may be from about
500-5K ohms and typically about 1K-3K ohms.
[0984] In some embodiments, an IEM circuit may have the following
AC parameters (note that for actual chip design the targeted value
can have +/-5% to +/-10% over temperature, power supply voltage,
and transistor's threshold voltage range): the oscillator's
frequency ("f_osc") may be from 256-384 kHz and typically about 320
kHz; the low broadcast frequency ("f1_broadcast") may be from about
8-12 kHz and typically about 10 kHz; the high broadcast frequency
("f2_broadcast") may be from about 16-24 kHz and typically about 20
kHz; the holding time before enabling chip to do broadcasting at
power-on ("T_brdcsten") may be from about 8-12 seconds and
typically about 10 seconds; the time for broadcasting
("T_brdcstoff") may be from about 8-12 minutes and typically about
10 minutes.
[0985] An IEM chip's physical size can be between 0.1 mm.sup.2 and
10 mm.sup.2. Because of the special IC configuration, embodiments
of the present invention can provide an IEM chip that is
sufficiently small to be included to most types of pills. For
example, a IEM IC chip can have a size less than 2.times.2
mm.sup.2. In one embodiment, the IC chip can be 1.times.1 mm.sup.2
or smaller. In one embodiment, the chip is 1 mm.times.1 mm. The
bottom side of the chip's substrate serves as the S1 electrode, and
the S2 is a pad fabricated on the top side of the substrate. The
pad's size can be between 2500 .mu.m.sup.2 and 0.25 mm.sup.2. In
one embodiment, the pad is approximately 85 .mu.m.times.85
.mu.m.
[0986] Although the previous description discloses a chip
configuration that uses the same electrodes for battery and signal
transmission, in certain embodiments separate electrodes are
employed for power generation and signal transmission.
[0987] FIG. 49 illustrates one exemplary IEM chip configuration
where two separate electrodes are used for battery and signal
transmission, respectively. A ground electrode 802 is fabricated on
the bottom side of a substrate 800. On the top side of substrate
800 is a battery electrode 804 and a transmission electrode 806.
Also fabricated on substrate 800 is a circuitry region 808. During
operation, the battery formed by electrodes 802 and 804 provides a
power supply to the circuitry within region 808. The circuitry
drives transmission electrodes 806 and 802, and produces a current
change in the patient's body. It is possible that the current
flowing from transmission electrode 806 to ground electrode 802 may
flow below the circuitry region 808, causing changes to the
electrical potentials in the circuit elements. Such potential
changes can cause undesirable latch-ups in the transistors within
circuitry region 808.
[0988] One approach to avoid such latch-ups is to separate the
transmission-electrode region and the circuitry regions so that
there is minimum lateral current flow that would change the
potential under the circuits. For example, the substrate contacts
can be located in regions that can divert current flow from the
circuitry area.
[0989] FIG. 50 illustrates an exemplary chip configuration that
minimizes circuit latch-ups in accordance with one embodiment of
the present invention. As shown in FIG. 50, it is possible to place
substrate contact regions at the four corners of the substrate. As
a result, the electrode current flowing toward the substrate is
diverted to the four corners, away from the circuitry region which
is in the middle. Similarly, special layout design scan be used for
the merged-electrode chip configurations.
[0990] FIG. 51 illustrates an exemplary layout that minimizes
latch-ups in a IEM chip. As shown in FIG. 51, on the bottom of a
substrate 1000 is a Mg electrode 1002. On the top side of substrate
1000 is a CuCl electrode 1006. Electrodes 1002 and 1006 serve as
both battery electrodes and transmission electrodes. Below CuCl
electrode 1006 are a number of transmission driver circuitry
regions 1004, which are located at the peripheral of the layout. A
control-logic circuitry region 1008 is located at the center of the
chip. This way, the current flowing from the transmission drivers
toward the Mg electrode 1002 is diverted away from the
control-logic circuitry region 1008, thereby avoiding any latch-ups
in the transistors.
[0991] FIG. 52 is an exploded view of an embodiment of an IEM that
may be used with the voltaic sensor. In FIG. 52, an IEM 1200
includes silicon dioxide substrate 1201, e.g., having a thickness
of 300 .mu.m. On the bottom surface is an electrode layer of
Magnesium 1202, e.g., having a thickness of 8 .mu.m. Positioned
between Mg electrode layer 1202 and bottom surface of substrate
1201 is titanium layer 1203, e.g., having a thickness of 1000
Angstroms. Positioned on upper surface of substrate 1201 is
electrode layer (CuCl) 1204, e.g., having a thickness of 6 .mu.m.
Positioned between upper electrode layer 1204 and substrate 1201 is
titanium layer 1205, e.g., having a thickness of 1000 Angstroms,
and gold layer 1206, e.g., have a thickness of 5 .mu.m.
[0992] While the signal generation and emission protocol above has
been described in terms of activation and transmission occurring at
substantially the same time, e.g., following contact with target
site and/or environment, in certain embodiments the activation of
the IEM and transmission of the signal can be separate events,
i.e., that may occur at distinct times separated by some duration.
For example, an IEM may include a conducting medium that provides
for activation prior to ingestion. In certain embodiments, the IEM
is encapsulated in a fluid, electrolyte sponge, or other conducting
media such that it can be activated externally prior to digestion.
In these embodiments, the receiver is configured to detect a
transmitted signal only when the signal is transmitted from the
target site of interest. For example, the system may be configured
so that transmission will only occur upon contact with body tissue
insuring proper event marking. For example, activation can occur
with handling of the IEM. Pressure sensitive membranes that break
with handling or contact may be employed, where braking causes
electrolyte material to enable connection of the battery elements.
Alternatively, degradation of the gel capsule in the stomach can
also release stored electrolyte and activate the IEM. Encapsulating
the IEM in a sponge (composed of conducting material which retains
water close to the IEM) allows for activation to occur in the
presence of small amounts of liquid. This configuration counteracts
poor transmission performance in the absence of conducting
fluids.
[0993] Note that other layout designs are also possible. In
addition, silicon-over-insulator (SOI) fabrication techniques can
be used to insulate the logic-control circuitry region from the
conductive substrate, so that the transmission current cannot
interfere with the control circuit.
[0994] In certain embodiments, the identifier compositions are
disrupted upon administration to a subject. As such, in certain
embodiments, the compositions are physically broken, e.g.,
dissolved, degraded, eroded, etc., following delivery to a body,
e.g., via ingestion, injection, etc. The compositions of these
embodiments are distinguished from devices that are configured to
be ingested and survive transit through the gastrointestinal tract
substantially, if not completely, intact.
[0995] In certain embodiments, the identifiers do not include an
imaging system, e.g., camera or other visualization or imaging
element, or components thereof, e.g., CCD element, illumination
element, etc. In certain embodiments, the identifiers do not
include a sensing element, e.g., for sensing a physiological
parameter, beyond the activator which detects contact with the
targeted physiological site. In certain embodiments, the
identifiers do not include a propulsion element. In certain
embodiments, the identifiers do not include a sampling element,
such as a fluid retrieval element. In certain embodiments, the
identifiers do not include an actuatable active agent delivery
element, such as an element that retains an active agent with the
composition until a signal is received that causes the delivery
element to release the active agent.
[0996] The identifiers may be fabricated using any convenient
processing technology. In certain embodiments, planar processing
protocols are employed to fabricate power sources having surface
electrodes, where the surface electrodes include at least an anode
and cathode at least partially on the same surface of a circuitry
support element. In certain embodiments, planar processing
protocols are employed in a wafer bonding protocol to produce a
battery source. Planar processing techniques, such as
Micro-Electro-Mechanical Systems (MEMS) fabrication techniques,
including surface micromachining and bulk micromachining
techniques, may be employed. Deposition techniques that may be
employed in certain embodiments of fabricating the structures
include, but are not limited to: electrodeposition (e.g.,
electroplating), cathodic arc deposition, plasma spray, sputtering,
e-beam evaporation, physical vapor deposition, chemical vapor
deposition, plasma enhanced chemical vapor deposition, etc.
Material removal techniques include, but are not limited to:
reactive ion etching, anisotropic chemical etching, isotropic
chemical etching, planarization, e.g., via chemical mechanical
polishing, laser ablation, electronic discharge machining (EDM),
etc. Also of interest are lithographic protocols. Of interest in
certain embodiments is the use of planar processing protocols, in
which structures are built up and/or removed from a surface or
surfaces of an initially planar substrate using a variety of
different material removal and deposition protocols applied to the
substrate in a sequential manner. Illustrative fabrication methods
of interest are described in greater detail in PCT application
serial no. PCT/US2006/016370, the disclosure of which is herein
incorporated by reference in its entirety.
[0997] In certain fabrication protocols, a sacrificial layer is
used. For example, in certain three-dimensional embodiments, such
as ones described in greater detail below, where gaps or spaces are
desired, sacrificial layers may be employed during fabrication,
where such layers are removed in whole or in part prior to use of
the battery. Sacrificial layer materials of interest include, but
are not limited to, photoresists which can be hard baked to make
them stable processing. The photoresist sacrificial layer can be
removed using any convenient protocol, e.g., with acetone, once the
deposition of the top electrode is complete. Other materials that
can be used as a sacrificial layer include, but are not limited to,
a silicon nitride, silicon dioxide, benzocyclobutene or tungsten.
Other methods of removing the sacrificial layer include but are not
limited to gas phase removal, dry etch removal and hydrogen
peroxide.
[0998] In some embodiments, planar processing, e.g., MEMS,
fabrication protocols are employed to fabricate batteries that
include an anode and cathode that are at least partially present on
the same surface of a circuitry support element. By "at least
partially present on the same surface of a circuitry support
element" is meant that at least a portion of a cathode and at least
a portion of anode are present on the same surface of a circuitry
support element, where both electrodes may be entirely present on
the surface of the circuitry support element, one electrode may be
wholly present on a surface and the other electrode only partially
present on surface, e.g., where the other electrode includes a
portion that is present on a different surface than the surface on
which the first electrode is positioned, and where 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 a variety of ways. The circuitry
support element may take any convenient configuration, and in
certain embodiments is an integrated circuit (IC) chip. The surface
upon which the electrode elements are positioned may be the top
surface, bottom surface or some other surface, e.g., side surface,
as desired, where in certain embodiments the surface upon which the
electrode elements are at least partially present is a top surface
of an IC chip.
[0999] Using MEMS fabrication techniques, batteries of some
embodiments can be manufactured to be a very small size, e.g., as
reviewed above. The electrodes of the batteries can be deposited in
a variety of thicknesses, e.g., ranging from about 0.001 to about
1000 .mu.m, such as from about 0.5 to about 10 .mu.m. Where gaps
are present between electrodes, the gaps may have a width ranging
from about 0.001 to about 1000 .mu.m, such as from about 1 to about
10 .mu.m.
[1000] In one embodiment two cathodes are deposited on the surface
of a chip with an anode separating the two cathodes. A dielectric
layer is deposited in between the electrodes and the circuit chip
with circuit contacts penetrating the chip surface. This
configuration allows multiple batteries to be put into series which
provides for a greater voltage to be applied to the circuit chip
upon activation of the battery by contact with the target site.
FIG. 60 shows a planar, inter-digitated battery layout. The
dielectric material 9 is deposited on the circuit chip 5 which
contains the circuit contacts 7. The anode 3 separates the first
cathode 1 from the second cathode 2. Embodiments employing this
configuration include ones in which batteries are in series (e.g.,
as described above), which provides for higher voltages that may be
used by the circuit upon contact with the target physiological
site. In certain embodiments, this configuration also provides for
low battery impedance because the electrodes are placed so closely
together. This embodiment is characterized in that both the cathode
and anode elements are wholly present on the same surface of the
chip.
[1001] In some embodiments, at least one of the anode and cathode
elements is partially present on the same surface as the other
electrode, but also partially present on another surface, e.g.,
side, bottom, etc., of the chip. For example, the anode may be
present on a small portion of 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 remainder of the top
surface of the circuit chip, and a small gap is provided between
the cathode and the anode. In one aspect, a large cathode plate
covers a majority of the top surface of the circuit chip while the
anode covers the bottom surface of the circuit chip and wraps
around the side to the top surface. Both electrodes, e.g., plates,
can be connected to the circuit chip via a circuit contact through
the dielectric layer on the top surface of the chip.
[1002] FIG. 61 shows the dielectric material 9 covering the circuit
chip 5. Cathode 1 is deposited over a majority of the top surface
of the dielectric material 9. The anode 3 is deposited over the
remainder of the top surface as well as the side and bottom
surfaces of the circuit chip 5 saving a separation between the
cathode 1 and anode 3 on the top. In certain embodiments, the
separation ranges from about 0.001 to about 1000 .mu.m, such as
from about 0.1 to about 100 .mu.m, e.g., about 2.0 .mu.m. In
certain embodiments, the circuit chip 5 may be flipped during
fabrication in order to deposit the anode 3 on the bottom surface
of the chip 5. Circuit contacts 7 for both the anode 3 and cathode
1 are provided on the top surface of the circuit chip 5, traveling
down through the dielectric 9. This configuration provides a very
large electrode area since it utilizes both the top and bottom of
the circuit chip 5 as well as one of the sides.
[1003] In another embodiment, a cathode is positioned on a top
surface of a circuit chip, e.g., present as a layer that has been
deposited over a dielectric on the top surface of the circuit chip.
During fabrication, a sacrificial layer is then deposited on top of
the cathode layer. An anode layer is then deposited on top of the
sacrificial layer. The sacrificial layer can then be removed
leaving a gap which provides an area for target site fluids, e.g.,
electrolytic stomach fluids, to contact the anode and cathode.
Using this embodiment, additional electrode layers can be stacked
on top of one another after depositing another sacrificial layer on
top of the anode. In doing so, the implantable on-chip battery can
be put into series, e.g., where a vertical series configuration is
desired.
[1004] FIG. 62 shows dielectric layer 9 disposed on top of circuit
chip 5. The cathode 1 is deposited on top of dielectric layer 9 and
through to the circuit contact 7. A sacrificial layer (not shown)
is deposited on top of the cathode 1 to provide a base for the
anodes 3 to be deposited. Once the sacrificial layer is deposited,
its surface can be etched to provide a rougher surface. Therefore,
when the anodes 3 are deposited onto the sacrificial layer, the
bottom of the anodes 3 will conform to a rough surface. The
sacrificial layer could also be deposited using cathodic arc, which
would deposit it in a rough and porous manner. Multiple anodes 3
can be deposited in multiple sizes to provide multiple voltages to
the chip circuit 5. Once the anodes 3 are deposited, the
sacrificial layer can be removed to create a gap, where in certain
embodiments the gap ranges from about 0.001 to about 1000 .mu.m,
such as from about 0.1 to about 100 .mu.m, and including from about
1 to about 10 .mu.m. In certain embodiments, the gab between the
anodes 3 and the cathode 1 is chosen to provide a battery with
desired impedances and different currents. The areas of the anodes
3 can also be manufactured to provide different voltages to the
circuit chip 5, as desired. Therefore, the anodes 3 can be
manufactured to provide multiple voltages with multiple impedances
and currents for the same chip, with minimal use of chip space.
[1005] In some embodiments, a cathode layer is deposited over the
dielectric on the surface of the chip, and multiple anodes are
deposited over different areas of the cathode. A sacrificial layer
is deposited to separate the anodes from the cathode during
fabrication, and upon removal produces a gap between the common
cathode and two or more anodes positioned over the cathode. As
shown in FIG. 63, the anode 3 may be anchored to the outer area of
the circuit chip 5. It is at that point 4 where the circuit contact
for the anode 3 may be placed. FIG. 63 differs from FIG. 62 in that
only two anodes 3 are deposited above the cathode 1. The two anodes
3 are also different sizes, and therefore provide different surface
areas. The anodes 3 can be manufactured to meet the requirements of
the application. If multiple voltages are desired, the anodes 3 can
be manufactured out of different materials. If multiple currents
are desired, the anodes 3 can be deposited in multiple sizes. If
multiple impedances are desired, the anodes 3 can be deposited with
different sized gaps between the anodes 3 and the cathode 1.
[1006] In some embodiments, two anode plates are present on the
surface of the circuit chip with a cathode circuit contact
deposited in the middle of the surface. The cathode is then
attached to the circuit contact in a way such that it hangs over
the anodes, thereby forming a gap between the cathode and anode.
FIG. 64 shows another embodiment of the implantable on-chip
capacitor that utilizes the space above the circuit chip 5. An
insulating layer 171 is formed on the surface of the circuit chip
5. The circuit contact for the cathode 1 is formed at the center of
the chip with anodes 3 formed at either side leaving a gap between
the circuit contact and the anodes 3. During fabrication, a
sacrificial layer is then deposited on top of the anodes 3 to form
a base for the cathode 1. Once the cathode 1 is deposited, the
sacrificial layer is removed providing a space for the liquid to
enter.
[1007] In some embodiments, a cathode is present on the surface of
the circuit chip with an anode positioned in a manner sufficient to
provide an open chamber above and at least partially around the
cathode. Openings are provided that allow electrolytic fluid to
flow into the chamber, which produces a current path between the
anode and the cathode. Multiple openings may be provided as
desired, e.g., in order to ensure that no air gets trapped inside
of the chamber. In FIG. 65, the anode 3 surrounds the cathode 1
creating a chamber 173 into which an electrolytic fluid will enter.
An insulating layer 11 separates the cathode 1 from the circuit
chip 5. Upon contact with the target site, the electrolytic fluid
will enter the chamber 173 through the openings 175. The openings
175 may be situated in opposite corners of the chamber 173 to make
sure that no air gets trapped inside. The configuration of FIG. 65
may be desirable in certain instances. For instances when there may
not be an abundant amount of electrolytic fluid present in the
stomach, the implantable on-chip battery can be fabricated to
contain the fluid it comes in contact with around the electrodes,
e.g., as shown in FIG. 65. By doing so the battery would be assured
of having a continuous reaction whereas, if it were open, the fluid
may enter and exit the reaction area and cause the battery to
stop.
[1008] Where a given battery unit includes a chamber, e.g., as
shown in FIG. 65, surface coating to modulate fluid flow into and
out of the chamber may be employed, as desired. In certain
embodiments, the surface of a portion of the chamber, e.g., an
interior surface of the chamber, may be modified to provide for
desired fluid flow properties. For example, the surface energy of
one or more surfaces of the chamber and fluid ports may be modified
to provide for enhanced fluid flow into the chamber. For example,
the surface energy of one or more surfaces of the chamber may be
increased, such that the surface becomes more hydrophilic. A
variety of different surface energy modification protocols may be
employed, where the particular protocol chosen may depend on the
particular composition of the barrier and the desired surface
energy properties. For example, if one wishes to increase the
surface energy of a given surface, the surface may be subjected to
plasma treatment, contacted with a surface energy modification such
as surface modifying polymer solutions described in, e.g., U.S.
Pat. Nos. 5,948,227 and 6,042,710, the disclosure of each of which
is incorporated herein in its entirety for all purposes. In certain
embodiments, a hydrophilic substance may be employed to attract and
retain the electrolytic fluid within the chamber, e.g., as
described in PCT application serial no. PCT/US07/82563, the
disclosure of which is herein incorporated by reference in its
entirety.
[1009] In certain embodiments, one or more surfaces of the battery,
e.g., interior surfaces of a chamber, are modified to modulate gas
bubble formation and positioning on the surface. For example,
activation of a battery may result in bubble production, e.g.,
hydrogen gas bubble production. Surface modification may be
employed so that bubbles produced during activation, e.g., on the
active cathode, are drawn from the cathode to another location,
e.g., away from the cathode, outside of the chamber, etc.
[1010] The above embodiments are examples of planar processing
protocol produced batteries in which at least one anode and at
least one cathode are present on the same surface of a circuitry
support element. The above description is in no way limiting, as
other embodiments may be produced which have the above common
characteristic.
[1011] In some embodiments, planar processing protocols are
employed in a wafer bonding protocol to produce a battery source.
In certain of such embodiments, a dielectric can be deposited on a
circuit chip. A cathode layer can then be deposited on top of the
dielectric. An anode can be deposited on a separate support wafer.
The anode may then be bonded to the bottom of the circuit chip at
which point the support wafer can be etched out to allow the anode
surface to come in contact with the electrolytic fluid. As such,
another fabrication technique that can be used in making the
implantable on-chip battery is wafer bonding.
[1012] The implantable on-chip battery can be manufactured using
two wafers, such as in the embodiment of FIG. 66. The circuit chip
5 provides the base for the cathode 1, which is deposited on top of
a dielectric 9. This composes the first wafer assembly 179. The
second wafer assembly 178 is comprised 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 away exposing areas of the anode
3. The amount of the support wafer 177 that is etched away is
dependent on the areas that are desired for the anode 3. This
fabrication method can be useful for the implantable on-chip
battery because if more circuitry is desired it can be placed in
the support wafer 177.
[1013] These embodiments discussed above and others can be altered
to switch a cathode with an anode and vice versa, providing yet
additional disclosed configurations of the invention. Additional
planar process fabricated embodiments of interest include those
described in U.S. Provisional Application Ser. No. 60/889,868; the
disclosure of which is herein incorporated by reference in its
entirety.
[1014] In addition to the identifier component described above, the
ingestible event markers may be present in (i.e., combined with) a
physiologically acceptable carrier component, e.g., a composition
or vehicle that aids in ingestion of the identifier and/or protects
the identifier until it reaches the target site of interest. By
"physiologically acceptable carrier component" it is meant a
composition, which may be a solid or fluid (e.g., liquid), which is
ingestible. Such markers may be incorporated into an intragastric
locating system in any of the manners described herein, for example
by incorporation into a catheter, with the intragastric device such
as the balloon, with an intermediate device coupling the catheter
to the intragastric device, or others. The markers may be
configured to release from any structure of the intragastric
locating system, for example after location has been confirmed.
Such markers may be implemented in a physiologically acceptable
carrier component to assist in passage, disposal, etc. of the
marker.
[1015] Common carriers and excipients, such as corn starch or
gelatin, lactose, dextrose, sucrose, microcrystalline cellulose,
kaolin, mannitol, dicalcium phosphate, sodium chloride, and alginic
acid are of interest. Disintegrators commonly used in the
formulations of the invention include croscarmellose,
microcrystalline cellulose, corn starch, sodium starch glycolate
and alginic acid.
[1016] A liquid composition may comprise a suspension or solution
of the compound or pharmaceutically acceptable salt in a suitable
liquid carrier(s), for example, ethanol, glycerine, sorbitol,
non-aqueous solvent such as polyethylene glycol, oils or water,
with a suspending agent, preservative, surfactant, wetting agent,
flavoring or coloring agent. Alternatively, a liquid formulation
can be prepared from a reconstitutable powder. For example, a
powder containing active compound, suspending agent, sucrose and a
sweetener can be reconstituted with water to form a suspension; and
a syrup can be prepared from a powder containing active ingredient,
sucrose and a sweetener.
[1017] A composition in the form of a tablet or pill can be
prepared using any suitable pharmaceutical carrier(s) routinely
used for preparing solid compositions. Examples of such carriers
include magnesium stearate, starch, lactose, sucrose,
microcrystalline cellulose and binders, for example,
polyvinylpyrrolidone. The tablet can also be provided with a color
film coating, or color included as part of the carrier(s). In
addition, active compound can be formulated in a controlled release
dosage form as a tablet comprising a hydrophilic or hydrophobic
matrix.
[1018] "Controlled release", "sustained release", and similar terms
are used to denote a mode of active agent delivery that occurs when
the active agent is released from the delivery vehicle at an
ascertainable and controllable rate over a period of time, rather
than dispersed immediately upon application or injection.
Controlled or sustained release may extend for hours, days or
months, and may vary as a function of numerous factors. For the
pharmaceutical composition of the present invention, the rate of
release will depend on the type of the excipient selected and the
concentration of the excipient in the composition. Another
determinant of the rate of release is the rate of hydrolysis of the
linkages between and within the units of the polyorthoester. The
rate of hydrolysis in turn may be controlled by the composition of
the polyorthoester and the number of hydrolysable bonds in the
polyorthoester. Other factors determining the rate of release of an
active agent from the present pharmaceutical composition include
particle size, acidity of the medium (either internal or external
to the matrix) and physical and chemical properties of the active
agent in the matrix.
[1019] A composition in the form of a capsule can be prepared using
routine encapsulation procedures, for example, by incorporation of
active compound and excipients into a hard gelatin capsule.
Alternatively, a semi-solid matrix of active compound and high
molecular weight polyethylene glycol can be prepared and filled
into a hard gelatin capsule; or a solution of active compound in
polyethylene glycol or a suspension in edible oil, for example,
liquid paraffin or fractionated coconut oil can be prepared and
filled into a soft gelatin capsule.
[1020] Tablet binders that can be included are acacia,
methylcellulose, sodium carboxymethylcellulose,
poly-vinylpyrrolidone (Povidone), hydroxypropyl methyl-cellulose,
sucrose, starch and ethylcellulose. Lubricants that can be used
include magnesium stearate or other metallic stearates, stearic
acid, silicone fluid, talc, waxes, oils and colloidal silica.
[1021] Flavoring agents such as peppermint, oil of wintergreen,
cherry flavoring or the like can also be used. Additionally, it may
be desirable to add a coloring agent 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 to a user that the intragastric balloon has deflated, as
described herein.
[1022] Other components suitable for use in the formulations of the
present invention can be found in Remington's Pharmaceutical
Sciences, Mace Publishing Company, Philadelphia, Pa., 17th ed.
(1985).
[1023] The locating systems may include signal receivers configured
to receive a signal from the identifier of the IEM, i.e., to
receive a signal emitted by the IEM upon contact of the IEM with
the target physiological site following ingestion of the IEM. The
signal receiver may vary significantly depending on the nature of
the signal that is generated by the signal generation element,
e.g., as reviewed below. As such, the signal receiver may be
configured to receive a variety of different types of signals,
including but not limited to: RF signals, magnetic signals,
conductive (near field) signals, acoustic signals, etc., as
indicated above.
[1024] In certain embodiments, the receiver is configured to
receive a signal conductively from another component, e.g., the
identifier of an IEM, such that the two components use the body of
the patient as a communication medium. As such, the signal that is
transferred between identifier of the IEM and the receiver travels
through the body, and requires the body as the conduction medium.
The identifier emitted signal may be transmitted through and
received from the skin and other body tissues of the subject body
in the form of electrical alternating current (a.c.) voltage
signals that are conducted through the body tissues. As a result,
such embodiments do not require any additional cable or hard wire
connection, or even a radio link connection for transmitting the
sensor data from the autonomous sensor units to the central
transmitting and receiving unit and other components of the system,
since the sensor data are directly exchanged via the skin and other
body tissues of the subject. This communication protocol has the
advantage that the receivers may be adaptably arranged at any
desired location on the body of the subject, whereby the receivers
are automatically connected to the required electrical conductor
for achieving the signal transmission, i.e., the signal
transmission is carried out through the electrical conductor
provided by the skin and other body tissues of the subject. Where
the receivers include sensing elements (see below), one may have a
plurality of receiver/sensor elements distributed throughout the
body and communicating with each other via this body conductive
medium protocol. Such a body-based data transmission additionally
has the advantage that the transmitting power required therefore is
extremely small. This avoids the generation of interference in the
electrical operation of other devices, and also helps to prevent
the unintended interception or tapping and surveillance of the
sensitive medical data. The resulting very low power consumption is
additionally advantageous for achieving the goal of a long-term
monitoring, especially in applications having a limited power
supply.
[1025] The signal receiver is configured to receive a signal from
an identification element of an IEM. As such, the signal receiver
is configured so that it can recognize a signal emitted from an
identifier of an IEM. In certain embodiments, the signal detection
component is one that is activated upon detection of a signal
emitted from an identifier. In certain embodiments, the signal
receiver is capable of (i.e., configured to) simultaneously
detecting multiple pharma-informatics enabled compositions, e.g., 2
or more, 5 or more, 10 or more, etc.
[1026] The signal receiver may include a variety of different types
of signal receiver elements, where the nature of the receiver
element necessarily varies depending on the nature of the signal
produced by the signal generation element. In certain embodiments,
the signal receiver may include one or more electrodes (e.g., 2 or
more electrodes, 3 or more electrodes, includes multiple, e.g., 2
or more, 3 or more, 4 or more pairs of electrodes, etc.) for
detecting signal emitted by the signal generation element. In
certain embodiments, the receiver device will be provided with two
electrodes that are dispersed at a distance, e.g., a distance that
allows the electrodes to detect a differential voltage. This
distance may vary, and in certain embodiments ranges from about 0.1
to about 5 cm, such as from about 0.5 to about 2.5 cm, e.g., about
1 cm. In certain embodiments, the first electrode is in contact
with an electrically conductive body element, e.g., blood, and the
second electrode is in contact with an electrically insulative body
element relative to said conductive body element, e.g., adipose
tissue (fat). In an alternative embodiment, a receiver that
utilizes a single electrode is employed. In certain embodiments,
the signal detection component may include one or more coils for
detecting signal emitted by the signal generation element. In
certain embodiments, the signal detection component includes an
acoustic detection element for detecting signal emitted by the
signal generation element. In certain embodiments, multiple pairs
of electrodes (e.g., as reviewed above) are provided, for example
to increase detection probability of the signal.
[1027] The signal receivers of interest include both external and
implantable signal receivers. In external embodiments, the signal
receiver is ex vivo, by which is meant that the receiver is present
outside of the body during use. Where the receiver is implanted,
the signal receiver is in vivo. The signal receiver is configured
to be stably associated with the body, e.g., either in vivo or ex
vivo, at least during the time that it receives the emitted signal
from the IEM.
[1028] In the broadest sense, receivers of the invention may be
either mobile or immobile relative to the patient for which they
are configured to operate. Mobile embodiments of the signal
receiver include ones that are sized to be stably associated with a
living subject in a manner that does not substantially impact
movement of the living subject. As such, embodiments the signal
receiver have dimensions that, when employed with a subject, such
as a human subject, will not cause the subject to experience any
difference in its ability to move. In these embodiments, the
receiver is dimensioned such that its size does not hinder the
ability of the subject to physically move.
[1029] In certain embodiments, the signal receivers can be
configured to have a very small size. Where the signal receiver has
a small size, in certain embodiments the signal receiver occupies a
volume of space of about 5 cm.sup.3 or less, such as about 3
cm.sup.3 or less, including about 1 cm.sup.3 or less. In certain
embodiments, the desired functionality of the signal receiver is
achieved with one rechargeable battery.
[1030] In addition to receiving a signal from an identifier of an
ingestible event marker, the signal receiver may further include
one or more distinct physiological parameter sensing abilities. By
physiological parameter sensing ability is meant a capability of
sensing a physiological parameter or biomarker, such as, but not
limited to: chemical composition of fluid,
[1031] In certain embodiments, the signal receiver includes a set
of 2 or more electrodes that provide for dual functions of signal
receiving and sensing. For example, in addition to receiving
signal, the electrodes can also serve additional sensing
functions.
[1032] In certain embodiments, a signal receiver that may be viewed
as an autonomous sensor unit is included. In certain of these
embodiments, the sensor unit includes a sensor and a pair of
transmit/receive electrodes that are adapted to be arranged on the
skin or body surface of the subject. The receiver may further
include a central transmitting and receiving unit which is adapted
to be arranged on the body of the subject, and a portable data
recording unit. The autonomous sensor units are adapted to acquire
sensor data from the body of the subject that may be indicative of
the location of the marker, i.e., medical and/or physical data such
as one or more of pulse rate, blood oxygen content, blood glucose
content, other blood composition data, blood pressure data,
electrocardiogram data, electroencephalogram data, respiration rate
data, perspiration data, body temperature data, activity, motion,
electrode impedance, and the like. In addition, the component
includes the ability to receive a signal from an internal device,
e.g., the identifier of an IEM. The transmit/receive electrodes of
each autonomous sensor unit are adapted to transmit the acquired
sensor data into the body of the subject, so that these sensor data
are transmitted via the skin and/or other body tissues of the
subject to a central transmitting and receiving unit, such as the
sensor interface units described above with respect to the
electromagnetic locating systems. Other signals, such as monitoring
signals and polling signals can be transmitted from the central
transmitting and receiving unit through the body tissues of the
subject to the sensor unit, where these signals are picked up by
the transmit/receive electrodes of the respective sensor unit.
[1033] Additional elements that may be present in the signal
receiver include, but are not limited to: a signal demodulator,
e.g., for decoding the signal emitted from ingestible event marker;
a signal transmitter, e.g., for sending a signal from the signal
receiver to an external location; a data storage element, e.g., for
storing data regarding a received signal, physiological parameter
data, medical record data, etc.; a clock element, e.g., for
associated a specific time with an event, such as receipt of a
signal; a pre-amplifier; a microprocessor, e.g., for coordinating
one or more of the different functionalities of the signal
receiver.
[1034] Aspects of implantable versions of the signal receiver will
have a biologically compatible enclosure, two or more sense
electrodes, a power source, which could either be a primary cell or
rechargeable battery, or one that is powered by broadcast
inductively to a coil. The signal receiver may also have circuitry
that includes a demodulator to decode the transmitted signal, some
storage to record events, a clock, and a way to transmit outside
the body. The clock and transmit functionality may, in certain
embodiments, be omitted. The transmitter could be an RF link or
conductive link to transfer information from local data storage to
an external data storage device.
[1035] The demodulator component, when present, may be any
convenient demodulator configured to demodulate the signal emitted
from the identifier of the pharma-informatics enabled
pharmaceutical composition. In certain embodiments, the demodulator
is an in-vivo transmission decoder that allows for accurate signal
decoding of a low-level signal, even in the presence of significant
noise, using a small-scale chip which consumes very low power. In
one embodiment, the in-vivo transmission decoder is designed to
decode signals which were modulated using binary phase shift keying
(BPSK). The signal can then be demodulated using a Costas loop. The
binary code is recovered by applying a symbol recovery technique to
the Costas loop output. In some embodiments, the in-vivo
transmission decoder can include an automatic gain control (AGC)
block. The AGC block can determine the strongest frequency
component and signal power of the incoming signal. The strongest
frequency of the signal can be used to adjust filters and
voltage-controlled oscillators in other parts of the algorithm.
This can help the receiver to actively adjust to variations of the
incoming signal frequency and drift of the incoming signal
frequency. By measuring the signal power, the AGC block can then
calculate and apply the gain necessary to normalize the signal
power to a predetermined value. This gain can further be adjusted
by reading the signal power at the Costas loop. In one embodiment,
the in-vivo transmission decoder can actively adjust the sampling
rate of the incoming signal to adjust to 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 a set threshold during the
decoding 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 to be as low as possible, the algorithm
saves power. Further aspects of such in-vivo transmission decoders
are provided in U.S. Provisional Application Ser. No. 60/866,581
titled "In-Vivo Transmission Decoder," the disclosure of which
application is herein incorporated by reference in its
entirety.
[1036] In certain embodiments, the components or functional blocks
of the present receivers are present on integrated circuits, where
the integrated circuits include a number of distinct functional
blocks, i.e., modules. Within a given receiver, at least some of,
e.g., two or more, up to an including all of, the functional blocks
may be present in a single integrated circuit in the receiver. By
single integrated circuit is meant a single circuit structure that
includes all of the different functional blocks. As such, the
integrated circuit is a monolithic integrated circuit (also known
as IC, microcircuit, microchip, silicon chip, computer chip or
chip) that is a miniaturized electronic circuit (which may include
semiconductor devices, as well as passive components) that has been
manufactured in the surface of a thin substrate of semiconductor
material. The integrated circuits of certain embodiments of the
present invention may be hybrid integrated circuits, which are
miniaturized electronic circuits constructed of individual
semiconductor devices, as well as passive components, bonded to a
substrate or circuit board.
[1037] FIG. 53 provides a schematic representation of a functional
block diagram according to an embodiment of the invention. In FIG.
53, a receiver 10C includes first and second electrodes 11C &
12C respectively, which are separated by distance X and serve as an
antenna to receive a signal generated by an identifier. The
distance X may vary, and in certain embodiments ranges from about
0.5 to about 5 cm, such as from about 0.5 to about 1.5 cm, e.g.,
about 1 cm. Amplifier 13C detects the differential signal across
the electrodes. The detected signal then goes into the demodulator
14C. Also shown is memory 15C to store the demodulated data. Clock
16C which writes to that memory which time-stamps the events.
Transmit circuit (Tx) (16) transfers data from the memory out to
the external receiver (not shown). There is also a power source 17C
which powers all the microelectronics. In the embodiment depicted,
also present is a microprocessor 18C, which coordinates the
function between all these blocks. Finally, a coil 19C wound around
the perimeter provides for RF transmission out. As summarized
above, all of the different functional blocks shown in the
embodiment of FIG. 53 could be on the same integrated circuit.
[1038] Another embodiment is depicted in FIG. 54. In FIG. 54, the
main portion of the receiver 20C includes all of the
functionalities listed above and electrode 21C. Also shown is
electrode 22C which is at the end of wire 23C. This configuration
provides for sufficient distance between e.sub.0 and e.sub.1 to
serve as an effective receiver and yet minimizes the overall size
of the receiver 20C.
[1039] In some embodiments, the signal receivers may be external.
Where the signal receivers are external, they may be configured in
any convenient manner. External configuration may include any of
the elements described above with respect to implantable
embodiments, as desired. As such, external receivers may include
circuits as depicted in FIG. 53, and described above. Accordingly,
elements as described above, such as signal receivers,
transmitters, memory, processors, demodulators, etc., may be
present in external receivers of the invention, as desired. For
example, functional diagrams of circuitry that may be present in
external receivers of the invention are shown in FIGS. 55A and
55B.
[1040] FIG. 55A provides a functional block diagram of a receiver
70C according to one embodiment, where the receiver includes an
external interface block 71C, where the external interface block
may include a wireless communication element (e.g., antenna),
serial port, conductive interface, etc. Also present is signal
receiver circuitry block 72C. Also present is receiver electrodes
functional block 73C. FIG. 55B provides a view of a circuit 74C
found in a receiver according to an embodiment of the invention.
Circuit 74C includes external interface 75C, memory 76C, digital
signal processor (DSP) 77C and real time clock (RTC) 78C. Also
shown is analog to digital converter (ADC) 79C, pre-amplifier 80C,
optional reference (common mode cancellation circuit) 81C and
electrodes 82C.
[1041] In certain external embodiments, the receiver may be
configured to be in contact with or associated with a patient only
temporarily, i.e., transiently, for example while the ingestible
event marker is actually being ingested. For example, the receiver
may be configured as an external device having two finger
electrodes or handgrips. Upon ingestion of the IEM, the patient or
a healthcare provider touches the electrodes or grabs the handgrips
completely to produce a conductive circuit with the receiver. Upon
emission of the signal from the IEM, e.g., when the IEM contacts
the stomach, the signal emitted by the identifier of the IEM is
picked up by the receiver. At this point, the receiver may provide
an indication to the patient or healthcare provider, e.g., in the
form of an audible or visual signal, that the signal from the IEM
has been received. As indicated above, in certain external
embodiments, the receiver is configured to be in contact with or
associated with a patient only temporarily, i.e., transiently, for
example while the intragastric device, ingestible marker, etc., is
actually being ingested.
[1042] In some embodiments, the marker may be ingested by the
subject using any convenient means capable of producing the desired
result, where the administration route depends, at least in part,
on the particular format of the composition, e.g., as reviewed
above, and involves ingesting the ingestible event marker, e.g., by
swallowing the IEM composition along with an intragastric device
and/or the swallowable catheter. Depending on the particular
application, the methods may include ingesting an event marker by
itself or in conjunction with another composition of matter such as
an intragastric device. Once the ingestible event marker reaches
the target physiological site, the identifier of the IEM emits a
detectable signal, e.g., as reviewed above. A signal receiver may
handle received data (e.g., in the form of a signal emitted from an
ingestible event marker) in various ways. In some embodiments, the
signal receiver simply retransmits the data to an external device
(e.g., using wires that extend through the catheter, by using
conventional RF communications, or others), e.g., immediately or
following some period of time, in which case the data is stored in
a storage element of the receiver. Accordingly, in certain
embodiments, the signal receiver stores the received data for
subsequent retransmission to an external device or for use in
processing of subsequent data (e.g., detecting a change in some
parameter over time). For instance, an implanted collector may
include conventional RF circuitry (operating, e.g., in the 405 MHz
medical device band) with which a practitioner can communicate,
e.g., using a data retrieval device, such as a wand as is known in
the art. In other embodiments, the signal receiver processes the
received data to determine whether to take some action such as
operating an effector that is under its control, activating a
visible or audible alarm, transmitting a control signal to an
effector located elsewhere in the body, or the like. The signal
receivers may perform any combination of these and/or other
operations using received data.
[1043] 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 where the balloon has a voltaic
sensor 5630 therein. The capsule 5610 and catheter 5620 may be any
of the embodiments described herein. The sensor 5630 may be any of
the embodiments of an ingestible event marker as described herein.
The sensor 5630 is shown located at the end of the capsule 5610
opposite from the coupling with the catheter 5620. However, this is
merely one example and the sensor 630 may be in a any suitable
location, either inside or outside the capsule 5610.
[1044] FIG. 57 is a side view of an embodiment of an intragastric
balloon system 5700 including a balloon 5710 and catheter 5720 with
an anode 5750 and a cathode 5740 having specific pH coatings 5760.
The pH coatings 5760 may be chosen so as to control the exposure of
the anode and cathode to the gastric environment, such as the
gastric fluid. The catheter 5720 may have wires 5720 to communicate
electrical signals received by the system, such as voltage. The
wires 5720 may, for example, electrically couple with the sensor
interface units, as described herein.
[1045] FIG. 67 illustrates use with a patient of an embodiment of a
voltaic locating system 6700 having an event marker. The system
6700 includes a balloon capsule 6710 exposed to gastric fluid
inside the stomach of the patient. The capsule 6710 may be ingested
in any of the manners described herein. The capsule 6710 is coupled
with a balloon catheter 6720. In some embodiments, the catheter
6720 is coupled with the ingestible event marker. In some
embodiments, the capsule 6710 is coupled with the marker. In some
embodiments, the balloon system 5600 of FIG. 56 may be implemented
with the system 6700 shown in FIG. 67. As further shown in FIG. 67,
the system 6700 may further include a signal receiver 6730, which
may be external to the patient's body. In some embodiments, the
receiver 6730 is located near the patient's stomach. The system
6700 may also include a mobile device 6740, such as a smartphone or
tablet, that communicates with the receiver 6730.
[1046] FIG. 68 illustrates use with a patient of an embodiment of a
voltaic locating system 6800 having an anode and cathode. The
system 6800 may include a balloon capsule 6810 exposed to gastric
fluid in the stomach of the patient. The capsule 6810 may be
ingested in any of the manners described herein. The capsule 6810
is electrically coupled with wires inside of a balloon catheter
6820. In some embodiments, the catheter 6820 includes an anode and
cathode at its distal end near the balloon 6810. The anode and
cathode may provide the voltage signal to confirm placement in the
stomach once the anode and cathode contact the gastric fluid, as
described herein. The system 6800 may also include a voltage lead
6830 in electrical communication with the cathode and anode. The
voltage lead may couple the anode and cathode to a signal receiver
6840 that measures the voltage. The receiver 6840 may report to a
user of the system 6800 when the voltage level has reached a
predetermined threshold, for example a voltage level indicative of
the gastric environment of the stomach.
pH Based Tracking and Visualization Subcomponent
[1047] Tracking and visualization functionality can be incorporated
into devices and systems described above. As used herein,
"visualization" is used broadly to refer to identifying an item of
interest in the body in a number of ways, including by measuring
the pH levels encountered by the intragastric device or by portions
thereof. Due to the non-invasive nature of the present device,
physicians may desire to determine, or confirm, the location and
orientation of the device prior to inflation, during the course of
treatment, or after deflation. Accordingly, intragastric devices
are provided that incorporate pH sensing components configured for
enabling determining and confirming the location, orientation
and/or state of an intragastric device at all phases of
administration.
[1048] A variety of pH measuring systems may be used to indicate
the pH level along the alimentary canal encountered by an
intragastric device. FIG. 69A depicts an embodiment of an
intragastric device 10A (shown in FIG. 69B) inside a patient with
an external controller 86, as well as a separate display unit 87
option, demonstrated during use with a patient. As shown, the
external controller 86 may be integrated with the device. FIG. 69A
also shows an embodiment where the controller 86 may plug into a
separate display unit 87 for a larger or more sophisticated
display.
[1049] FIG. 69B depicts an embodiment of the intragastric device
10A with a wireless external display 88. As shown, the external
display 88 could be used with the intragastric device 10A or
accessory therewith where wireless communication is being utilized.
While monitoring the data, the physician could alter the
orientation, location, etc. of the intragastric device, to ensure
it is within an ideal position and orientation, etc. The device 10A
could have the ability to collect and analyze the data with an
algorithm to determine whether the device was in the ideal
position, orientation, etc.
[1050] In some embodiments, the intragastric device and/or
accessories therewith includes a sensor or sensors to be used with
the intragastric device or procedure to monitor one or more
parameters, such as pH, inside the alimentary canal, including the
esophagus, stomach and/or intestines. FIG. 69C depicts a side view
of an embodiment of pH sensors 28B of an intragastric system 20B
located on an intragastric device 16B, such as a balloon, within a
cross-section of a stomach. In some embodiments, the sensors 28B
would be adapted to accurately monitor pH with fine resolution, low
hysteresis and would be adapted for tissue contact. The sensors
could have a very small surface contact area or could have a wider
surface contact area.
[1051] The system 20B may include an instrument that is separate
from the intragastric device 16B and may be constructed with a
shaft for placement down the esophagus and possibly an arm for
manipulation. The system may further include an accessory that is
attached to or contacting the intragastric device 16B and may be
removed after the device is placed.
[1052] In some embodiments, the sensors 28B are used as a guide
during placement of the intragastric device 16B to monitor
placement, performance, adjustments or other data as needed. The
sensor 28B is used when placing the intragastric device or
performing a bariatric surgical procedure that induces weight loss
by a variety of weight loss mechanisms. The sensors could be used
to ensure that the intragastric device is placed in the proper
location. The weight loss mechanism may include space occupying
devices such as an inflatable intragastric balloon, as shown in
FIG. 69C, or other similar devices described herein, where the
sensors may be used, for example, to ensure proper fill volumes are
achieved to lose weight. The intragastric device 16B equipped with
sensors 28B may also gather placement or adjustment data to
customize the placement and/or fit to the patient for improved long
term performance.
[1053] Whether a wired or wireless sensor 28B is used, the external
display may have the capability to gather and record data regarding
the ambient pH level surrounding the intragastric device 16B. In
some embodiments, the external display may be on the controller 86,
the external display 87 and/or the wireless external display 88
shown in FIGS. 69A-B. The external display may also contain the
ability to perform analysis of the collected data for further
diagnostic capabilities. The external display may have the
capability to gather the data and display it in a variety of
presentations. It may display raw data, averages, or it could
analyze the data and diagnose a generalized state as being
appropriate or inappropriate. For example, an inappropriate state
might be displayed with a red light while an appropriate state
might be indicated with a green light. Similarly, the external
display could be shown in a lighted bar graph where a more
appropriate state is indicated by more bars and a less appropriate
state is indicated by less bars. Where a wired sensor is used, the
external display 87 (FIG. 69A) could be connected and integrated
into the system 20B for reading the parametric data. Where a
wireless sensor is used, the wireless external display 88 (FIG.
69B) could be wirelessly connected to the system 20B.
[1054] In some embodiments, the intragastric device 16B or portions
thereof could contain an array of the sensors 28B that are
positioned on top of or integrated into a thin, flexible sheet or
element. This element could take a variety of shapes including a
strip, disk, frusto-cone, sphere, a portion of any of these or
other. Where an array of sensors 28B is used, the display may show
a 2D or 3D color plot or graphical representation of the pH mapping
across the sensor array. A variety of visual displays could be used
to represent the state of the device 16B condition.
[1055] In some embodiments, multiple sensor arrays could be located
on a single arm 24 or multiple arms 24. The single arm 24 could
take the form of a loop, a curved wire, a spiral, cylinder, cone or
multiples of these, or other shapes and multiples, to cover a
region of interest. The arm or arms 24 could articulate to allow
for manipulation for ideal positioning of the device 16B during the
introduction into the body. In some embodiments, the sensors 28B
may be incorporated with an instrument with a narrow cross-section
to allow it to fit down the working channel of a gastroscope.
Alternatively, it may require a larger sizing for additional
features such as articulating arms, but could be sized small enough
to fit down the esophagus next to the gastroscope, and long enough
for proper manipulation outside the body. Where there are expanding
or articulating features, the device 16B or accessory may have
adequate ability to collapse into a long narrow profile to
facilitate placement down the esophagus. The device 16B may also be
smooth and contoured to reduce the potential for tissue
irritation.
[1056] The sensor 28B could be in indirect contact with the patient
such as being outside of a sizing balloon or outside of a tube
where the alimentary canal contacts the balloon or tube. The
sensors 28B or device 16B could be reusable or disposable. After
the device 16B placement, adjustment, or procedure was completed,
the sensors 28B or instrument used to place the device 16B, such as
a catheter, could be removed.
[1057] An instrument or accessory used to place the device 16B
could be made of many different materials or combinations of
materials. For an instrument, the materials would be acid resistant
for transient contact with the stomach for single or repeat use.
For a device accessory that is intended to remain on the device
16B, the accessory may need more acid resistant properties.
Elements of the device 16B could be made of Nitinol, shape memory
plastics, shape memory gels, stainless steel, superalloys,
titanium, silicone, elastomers, teflons, polyurethanes,
polynorborenes, styrene butadiene co-polymers, cross-linked
polyethylenes, cross-linked polycyclooctenes, polyethers,
polyacrylates, polyamides, polysiloxanes, polyether amides,
polyether esters, and urethane-butadiene co-polymers, other
polymers, or combinations of the above, or other suitable materials
or materials as described elsewhere herein.
[1058] In some embodiments, the system 20B could contain wireless
or wired sensors 28B. Where wired sensors 28B are used on the
instrument 20, the wires used to transmit data could be contained
inside a shaft 22B, and data could be sent directly from the sensor
28B to the display, for example a small display on the controller
86 or larger display unit 87 in FIG. 69A, for monitoring, or to a
microprocessor for analysis and then to the display. The
microprocessor or external display could be integrated directly
into the system 20B, or the system 20B could plug into a separate
and larger external display 87 (shown in FIG. 69A).
[1059] Where wireless sensors 28B are used with the system 20B, an
external display, such as wireless external display 88 shown in
FIG. 69B, may be used to remotely send and receive signals via
telemetry from the sensor 28B. The external display 88 may display
the data for monitoring or could contain a microprocessor for
analysis and then display the data.
[1060] In one embodiment, a wireless or wired sensor 28B may be
used on the system 20B to communicate with a separate external
display unit, whether a small display on the controller 86, the
larger wired display 87, or the wireless display 88. It may be
desirable to control the sensor 28B from the external display unit.
The external display unit may send a command to the sensor 28B to
query it to start gathering data. The external display unit may
also send a separate or simultaneous command to send data. The
sensor 28B may receive the command from the external display unit
and then transmit or respond to collect and/or send data. When
sufficient data was received, a command may be sent from the
external display unit to the sensor 28B to tell the sensor 28B to
stop gathering and/or sending data.
[1061] In addition, the sensor 28B and or memory module of the
system 20B may be communicatively coupled with a transmitter, a
receiver, or both, to allow communication of data or other
information with outside receivers and transmitters. The
transmitter may transmit signals received from the sensor, or
signal data stored in the memory module.
[1062] In some embodiments, the sensors 28B may assist with placing
the intragastric device 16B. The device 16B may be placed down the
esophagus and then filled through a fill tube with saline, air or
other fluid or method as described herein to the appropriate
volume. With this system 20B, the sensor 28B could be placed
between the balloon 16 and the surrounding anatomy to measure the
pH level. The system 20B could be used for adjusting the device 16B
at a later time, by filling or removing fluid in the device 16B to
customize the fit for each patient over time. In some cases, it may
be necessary to increase the device 16B fill volume to increase
weight loss. It may also be necessary to remove fluid from the
device 16B to reduce intolerance where a balloon, for example, was
overfilled at the time of placement. Since the device 16B is free
to move and rotate within the stomach, it could be monitoring
orientation as well.
[1063] The sensors 28B could be used to gather important patient
data to understand performance, positioning, patient status or
whether an adjustment needs to be performed for the adjustable
intragastric device 16B, or whether the device 16B needs to be
replaced or resized. The sensed pH could detect whether the device
was not in an ideal condition, and display this information to the
external display 86.
[1064] Appropriate algorithm(s) may determine and/or control ideal
parameter condition(s), or such condition(s) could be based on a
parameter range. For example, the data could be collected from the
sensor 28B for a fixed time period. A microprocessor in the
external controller 86 or display 87, 88 could then calculate the
average over time, the minimum, the maximum, the standard deviation
or the variation in standard deviation over time, or other suitable
analysis. Based on the analysis, the microprocessor may determine
whether the intragastric device 16B was in the ideal position or
adjustment state.
[1065] FIG. 70A is a schematic side view of a person with a pH
monitor 18B which may be incorporated with an intragastric device
within the esophagus. FIG. 70A illustrates how physiological
parameter data such as pH can be relayed by the monitor 18B, which
is positioned within the esophagus 30E, to a radiofrequency
receiver or radioreceiver 32B located outside the body of a person
40P. As is illustrated in FIG. 70A, more than one monitor 18B can
be incorporated with an intragastric device (not shown in FIG. 70A)
so that data can be obtained from a plurality of locations.
Further, the monitor 18B may be any pH sensor discussed herein, for
example sensor 28B with respect to FIGS. 69A-69C.
[1066] In certain embodiments, this transmission of data is
accomplished via radio telemetry in real time. The radioreceiver
32B receives physiological parameter data within 12 seconds after
it is measured by the monitor 18B. After reception of this data,
the radioreceiver 32B apparatus can record, manipulate, interpret
and/or display the data, using technology well known to those
skilled in the art. In certain embodiments, the patient can wear
the receiver 32 and recorder on, for example, a belt, bracelet, arm
or leg band, or necklace during the period of pH analysis.
[1067] In certain embodiments, the monitor 18B can record and
compress physiological parameter data, such as pH level, as it is
gathered, rather than transmit the data in real time. Following an
assessment period, or at intervals therein, an external transceiver
can be used to download pulses of condensed data. Transmission of
data can be initiated at predetermined intervals or by an
activation signal sent from the external transceiver or other
activating device to the monitor 18B, as will be understood by
those of skill in the art. In this manner, a tabletop transceiver
can be utilized, either at the patient's home, or in the
physician's office or other clinical site.
[1068] In other embodiments, the monitor 18B can record, compress,
and store physiological parameter data as it is gathered, using a
memory chip and microprocessor. The person 40P can excrete the
monitor 18B in his or her stool, and the monitor 18B can be
retrieved. Subsequently, data stored in the monitor 18B can be
downloaded into an external data retrieval device, which can be a
computer or other analysis machine located outside the patient's
body. This downloading can be accomplished by IR or RF transmission
in response to an activation signal, using magnetic field or
radiofrequency technology well known to those skilled in the
art.
[1069] FIG. 70B is a schematic view of one embodiment of an
electrical circuit for the pH monitor 18B. FIG. 70B illustrates a
simplified circuit for the monitor 18B of a physiological parameter
such as pH level. This monitor 18B may also be referred to as a
"probe" or "pill" and may be incorporated with the intragastric
devices described herein. In the particular embodiment illustrated
in FIG. 70B, pH is the physiological parameter to be sensed, and it
is detected by a transducer 110C, which comprises a pH sensor and
preferably also a reference sensor. In the present invention, a
monitoring transducer can be any transducer that senses a
physiological parameter and furnishes a signal one of whose
electrical characteristics, such as current or voltage, is
proportional to the measured physiological parameter.
[1070] Although a pH sensor is described here, those skilled in the
art will appreciate that a sensor of any of a variety of other
physiological parameters, such as pressure or temperature, can be
detected and monitored. Sometimes, temperature and/or pressure will
be sensed and transduced together with pH, in order to adjust or
calibrate the pH readings and make them more accurate, or to supply
additional data helpful in the analysis of the patient's condition.
In addition, the concentration of ions or other solutes present in
body fluids can be detected and analyzed using this invention. For
example, ions such as sodium, potassium, calcium, magnesium,
chloride, bicarbonate, or phosphate may be measured. Other solutes
whose concentrations in body fluids are of importance and may be
measured by the present invention include, among others, glucose,
bilirubin (total, conjugated, or unconjugated), creatinine, blood
urea nitrogen, urinary nitrogen, renin, and angiotensin. Any
combination of two or more of the preceding parameters may be
sensed by the transducer 110C. For any physiological parameter
sensed and transduced by means of a transducer, a reference sensor
may or may not be required.
[1071] FIG. 70B also illustrates a radiofrequency transmitter
circuit 112C and a power source 114C. The radio frequency
transmitter circuit 112C can comprise an antenna (or antenna coil),
and the antenna can be at least in part external to the monitor
18B. Alternatively, the antenna, if present, can be entirely
self-contained within the monitor 18B. As an alternative to RF
transmission, a signal which is indicative of the monitored
parameter can be propagated through the patient's tissue from an
electrical contact on the probe to a conductive dermal electrode or
other conductor in contact with the patient.
[1072] When located within the monitor 18B, the power source 114C
can be a battery or capacitor or any other device that is capable
of storing an electrical charge at least temporarily. In a battery
powered embodiment, battery life can be extended by disconnecting
the battery from other circuit components thereby limiting
parasitic current drain. This can be accomplished in a variety of
ways, such as by including a magnetically activated switch in the
monitor 18B. This switch can be used to connect or disconnect the
battery as needed. By packaging the monitor 18B with an adjacent
permanent magnet, the switch can be opened thereby disconnecting
the battery and the shelf life of the device can thus be extended.
Removing the monitor 18B from the packaging (and the adjacent
permanent magnet) closes the switch and causes the battery to
become connected and supply power to the monitor 18B.
[1073] In some embodiments, the source of power to the monitor 18B
can be external to the monitor 18B. For example, the monitor 18B
can derive power from an external electromagnetic radiofrequency
(RF) source, as occurs with passive RF telemetry techniques, such
as RF coupling, that are well known to those skilled in the art.
The monitor 18B can be energized by a time-varying RF wave that is
transmitted by an external transceiver 32, also known as an
"interrogator," which can also serve as a reader of data from the
monitor 18B. When the RF field passes through an antenna coil
located within 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 in the monitor 18B is
transmitted back to the interrogator 32 (FIG. 70A), in a process
often referred to as "backscattering." By detecting the
backscattering signal, the data stored in the monitor 18B can be
fully transferred.
[1074] Other possible sources of power for the monitor 18B include
light, body heat, and the potential difference in voltage that can
be generated in body fluids and detected by electrodes made of
varying materials. The harnessing of such power sources for
biotelemetry purposes is well described in R. Stuart Mackay:
Bio-Medical Telemetry, Sensing and Transmitting Biological
Information from Animals and Man, 2d ed., IEEE Press, New York,
1993, whose section entitled "Electronics: Power Sources" is hereby
incorporated herein by reference in its entirety.
[1075] FIG. 70C is a schematic view of an embodiment of a pH
monitor circuit, wherein the circuit also includes a microprocessor
116. In some embodiments, the microprocessor 116 can perform one or
more functions, including temporary storage or memory of data,
reception of input signal from the transducer, and transformation
between analog and digital signals, among other functions that will
be apparent to those skilled in the art. The transducer 110C,
radiofrequency transmitter 112C, and power source 114C are also
present. Many other circuitry components that can help to generate,
amplify, modify, or clarify the electrical signal can be used in
other embodiments of the monitor. Such components include buffers,
amplifiers, signal offset controls, signal gain controls, low pass
filters, output voltage clamps, and analog-to-digital converters,
among others. Numerous possible circuitry features of a portable pH
monitoring device, all of which can be used in the present
invention, are well described in U.S. Pat. No. 4,748,562 by Miller,
et al., the disclosure of which is incorporated herein by reference
in its entirety.
[1076] In certain embodiments, the monitor 18B further comprises a
digital recorder or memory chip (not illustrated), which records
the transduced physiological parameter data. This recorder or
memory chip will allow temporary storage of this data accumulated
over time.
[1077] Shown in FIGS. 71A-71H are various views of various
embodiments of intragastric systems and apparatuses that use a
chemical-property indicating medium to detect pH level. In some
embodiments, an intragastric apparatus may comprise a detection
indicator and a housing. The detection indicator may be configured
to change from a first visual indication to a second visual
indication upon contact with a fluid based on a characteristic of
the fluid, such as acidity. The housing may comprise an interior
chamber configured to receive the fluid and to provide contact
between the fluid and the detection indicator. The housing may
further be configured to removably engage a lumen inserted into a
patient to receive the fluid from the patient through the lumen. In
some embodiments, a first opening of the removable housing is
engaged to a proximal end of a lumen inserted into a patient. A
transfer of a fluid sample from a distal end of the lumen, through
the lumen, and into the removable housing through the first opening
may be caused such that the fluid sample contacts a detection
indicator coupled with the removable housing. A visual comparison
of the detection indicator with a reference indicator, coupled to
the removable housing, may then be performed to determine a
characteristic of the fluid sample. The first opening of the
removable housing, may be removed from the proximal end of the
lumen.
[1078] In some embodiments, the intragastric tube or the guide
element may incorporate a chemical-property indicating medium to
facilitate verification that the intragastric tube and/or
intragastric devices thereon have been inserted properly into the
patient's stomach. The fluids present in a patient's stomach have
an acidic pH below 5.0. By exposing the indicating medium to the
fluids surrounding the distal end of the intragastric tube, the
indicating medium enables the user to verify that the pH of those
fluids is below 5.0, thus confirming correct insertion of the
intragastric tube in the proper location, orientation, state, etc.
If the indicating medium is incorporated in the intragastric tube,
the fluids surrounding the distal end of the tube may be aspirated
through the tube and into contact with the medium, the condition of
which may then be observed by the user. If the indicating medium is
incorporated in the guide element, the fluids surrounding the
distal end of the tube will come in contact with the medium without
additional overt action by the user, although the guide element
must subsequently be withdrawn from the patient so that the
condition of the medium may be observed. The indicator may
generally be used to obtain a measurement of the gastric pH.
[1079] Shown in FIG. 71A is a side view of an example embodiment of
an intragastric tube 810 in which a chemical-property indicating
medium is incorporated near the proximal end section 114D thereof.
FIG. 71B is a cross section view of the example embodiment tube 810
taken along section lines 44-44 of FIG. 3A.
[1080] As shown in FIGS. 71A-71B, the intragastric tube 810 may
comprise a generally tubular proximal end section 114D having an
interior wall 814 forming at least one lumen 146D. If plural lumina
are provided in tube 810, the lumen 146D may be the one adapted for
use in aspirating fluid near the distal end of the tube. The
intragastric tube 810 may include a section 812 for housing a
chemical property indicating medium 820. Section 812 may be
enlarged, compared to the diameter of other sections of the
intragastric tube. A channel 822 is preferably provided in which
the chemical property indicating medium 820 is captured. Several
openings 816 are preferably provided between the main bore of lumen
146D and the channel 822 to allow communication of fluid between
the lumen 146D and the channel 822. The openings 816, channel 822,
and medium 820 are preferably adapted such that when fluid is
present in lumen 146D, it inundates channel 822 and exposes medium
820.
[1081] In some embodiments, the medium 820 furnishes a visual
indication of a chemical property, such as pH, which may, for
example, be manifested as a change in color, reflectivity, or the
like. Section 812 may be clear or translucent to allow the medium
820 to be viewed externally. The shape of section 812 may act as a
magnifying lens to allow a small medium to be easily viewed. Any
appropriate chemical-property indicating medium, including but not
limited to litmus, pH indicating strips, paper, cloth, or any other
substrate impregnated with or bearing a pH indicator, or the like,
may be used to implement medium 820. The position and size of
section 812 is preferably selected such that the condition of the
indicator strip is visually apparent when fluids are initially
aspirated through lumen 146D so that the user need not take any
additional steps in order to confirm correct insertion of the
intragastric tube in the patient's stomach.
[1082] Shown in FIG. 71C a side view of an additional example
embodiment of an intragastric tube 830 in which a chemical-property
indicating medium is incorporated near the proximal end section
114D thereof. There is shown in FIG. 71D a side view of an
additional example embodiment of an intragastric tube 840 in which
a chemical-property indicating medium is incorporated near the
proximal end section 114D thereof. FIG. 71E is a cross section view
of the embodiment 830 taken along the section lines 47-47 thereof.
FIG. 71F is a cross section view of the embodiment 840 taken along
the section lines 48-48 thereof.
[1083] As shown in FIGS. 71C-71F, in some embodiments each of
intragastric tubes 830 and 840 comprises a generally tubular
proximal end section 114D having an interior wall 814 forming at
least one lumen 146D. If plural lumina are provided in tube 830 or
840, the lumen 146D may be the one adapted for use in aspirating
fluid near the distal end of the tube. Intragastric tube 830 may
comprise a chemical-property indicating medium applied to the
interior wall 814 in the form of a plurality of indicating elements
832 spaced circumferentially along the interior wall 814.
Intragastric tube 840 may comprise a chemical-property indicating
medium applied to the interior wall 814 in the form of an
indicating element 842 that covers the circumference of the
interior wall 814. These particular configurations of the
indicating elements 832 and 842 are examples. Other configurations
could also be used.
[1084] In some embodiments, the indicating elements 832 and 842 may
be formed using any suitable chemical-property indicating medium or
substance, including but not limited to a coating, litmus,
pH-indicating strips, paper, cloth, or the like. For example, the
medium may be formed as a coating or gelatin bearing
phenolphthalein. The term medium is also intended to refer to any
indicating substance, regardless of whether or not the indicating
chemical or component is carried in or on a substrate, matrix, or
similar carrier. Other indicating media could also be used. If the
medium is integrated with a substrate such as a paper strip, such
substrate may be applied to the interior wall 814 using an
appropriate adhesive or fastening technology, which may include
infrared or ultrasonic bonding. The positions and sizes of the
indicating elements 832 and 842 are preferably selected such that
the condition of the indicating elements is visually apparent when
fluids are initially aspirated through lumen 146D, so that the user
need not take any additional steps in order to confirm correct
insertion of the intragastric tube in the patient's stomach. In
some applications, aspirated fluid that contacts the indicating
medium may be reintroduced into the patient or may otherwise come
in contact with the patient.
[1085] In some embodiments, the indicating medium is attached or
adherent to the interior wall 814, to prevent particles or
fragments of the indicating medium itself from being inadvertently
introduced into the patient through the intragastric tube or
otherwise contacting the patient. In some embodiments, an
indicating medium is preferably selected for bio-compatibility to
avoid any potentially toxic effects.
[1086] Shown in FIG. 71G is a side view of an additional example
embodiment of a intragastric tube 850 in which a chemical-property
indicating medium is incorporated near the proximal end section
114D thereof. As shown in FIG. 71G, a plurality of distinct
indicating elements, such as 852, 854, and 856 are provided, each
having a medium for visually and distinctly indicating a different
chemical property or a different value of a chemical property. The
indicating elements 852, 854, and 856 may, for example, change
appearance to indicate different pH thresholds have been sensed, or
may change appearance to indicate the presence or absence of
specific chemicals, proteins, or other detectable components in the
fluid aspirated from the vicinity of the distal end of the
intragastric tube. This would give a measurement of gastric pH, as
well as verify proper placement, orientation, state, etc. of the
intragastric tube and/or device. The activated appearance of each
of the indicating elements 852, 854, 856 may be visually
distinctive. For example, they may appear as distinguishably
different colors, thereby minimizing ambiguity as to which
indicators are activated. Although the indicating elements are
shown in the shape of dots, any suitable shape could also be used,
and the elements may be provided in any practical size and number.
Any suitable indicating media could be used to implement the
indicating elements 852, 854, and 856, such as those described in
connection with the embodiments 830 and 840 of FIGS. 71C-71D.
[1087] Shown in FIG. 71H is a side view of an additional example
embodiment of a intragastric tube 860 in which a chemical-property
indicating medium is incorporated near the proximal end section
114D thereof. As shown in FIG. 71H, a plurality of distinct
indicating elements, such as 862, 864, and 866 are provided, each
having a medium for visually and distinctly indicating a different
chemical property or a different value of a chemical property, and
each having a different shape, size, or other characteristic so
that there is no ambiguity as to which indicators are activated.
The indicating elements 862, 864, and 866 may, for example, change
appearance to indicate different pH thresholds have been sensed, or
may change appearance to indicate the presence or absence of
specific chemicals, proteins, or other detectable components in the
fluid aspirated from the vicinity of the distal end of the
intragastric tube. The shape, size, or other characteristics of the
indicating elements may be selected to correspond to the property
indicated. In some embodiments, the indicating elements 862, 864,
and 866 may be designed to change appearance when fluid pH crosses
specific pH thresholds of 4.0, 5.0, and 3.0, respectively, and the
indicating elements may be formed as recognizable characters,
symbols, or glyphs corresponding to these thresholds. Other
distinctive shapes and forms and other schemes defining
correspondence between the visual distinctiveness of the indicating
element and the property being sensed could also be used. The
activated appearance of each of the indicating elements 862, 864,
866 may be visually distinctive in ways in addition to their shape,
for example, they may appear as distinguishably different colors,
to further minimize ambiguity as to which indicators are activated.
Any suitable indicating media could be used to implement the
indicating elements 862, 864, and 866, such as those described in
connection with the embodiments 830 and 840 of FIGS. 71C and 71D,
respectively.
[1088] FIG. 72 shows a further embodiment of an intragastric device
19B with a space filler 22A and a sensor 22C, such as a pH sensor,
with delivery means for implanting and retrieving the device and
sensor. In some embodiments, the sensor 22C comprises a pH sensor
element for sensing a pH of a stomach of the patient, wherein the
pH sensor element may further comprise a transmitter for wirelessly
transmitting the sensed pH to a receiver outside a body of the
patient. The sensed pH or the change of the sensed pH may be
analyzed for assessing the intragastric device 19B location,
orientation, state, performance, etc. FIG. 72 depicts an embodiment
of the intragastric device 19B with the space filler 22A secured to
and in tandem to the sensor 22C. In some embodiments, the space
filler 22A is secured to and in parallel with the sensor 22C. In
some embodiments, the space filler 22A and the sensor 22C of the
intragastric device 19B are configured to be in tandem inside a
stomach pouch.
[1089] In some embodiments, there may be two or more space fillers
22A. In some embodiments, the sensor 22C may also be a second space
filler. In some embodiments, the two or more space fillers are in
tandem to each other. In some embodiments, the two or more space
fillers are parallel to each other. In some embodiments, the second
space filler is enclosed entirely or partially within the first
space filler 22A.
[1090] In some embodiments, at least a portion of one or both of
two space fillers is made of a biodegradable material and one or
both have a sensor 22C for measuring the property of the content
surrounding, in or near the space filler or fillers, wherein the
property includes pH. In some embodiments, more than two space
fillers 22A and/or sensors 22C are incorporated in, on, or
otherwise with, the intragastric device 19B.
[1091] In some embodiments, a catheter sheath 25 or delivery device
for the intragastric device 19B passes through the esophagus 24 and
cardiac notch into the stomach 40Z of a patient. Once it is
delivered to the stomach, the space filler or fillers 22A and/or
sensor 22C are inflated. As shown in FIG. 72, in some embodiments
the intragastric device 19B comprises a plurality of connecting
members 36Z between the first space filler 22A and the second space
filler or sensor 22C, wherein the first space filler 22A is
connected to an infusing tubing 23 via a sealed inlet.
[1092] In some embodiments, capsule technology may be incorporated
with the intragastric device to sense pH level. FIG. 73A is a
schematic illustration of an embodiment of a capsule device that
may be incorporated with an intragastric device to sense pH level.
FIG. 73B is a schematic illustration of a system that may be
incorporated with an intragastric device for measuring pH having
two capsules connected to each other.
[1093] Referring to FIG. 73A, an embodiment of a capsule device and
its components are illustrated. As shown, the capsule device
comprises a pH electrode 8B which is positioned at the capsule
device to allow direct contact with the environment surrounding the
capsule device. The pH electrode 8B is further in electrical
contact with a reference electrode 9B. Additionally, the capsule
device comprises a means which can be connected with the
transmitter 5B for transmitting the pH measurement data to a
recording and/or analyzing unit.
[1094] In some embodiments, the capsule device contains a fixing
means 10B which preferably comprises an evacuable well and a pin.
The device may be fixed to an intragastric device via the fixing
means, which may be mechanical, chemical or other means for
attaching and fixing the capsule to the device.
[1095] In some embodiments, the capsule device may have a pH sensor
used in conjunction with an imaging system. The pH level may
indicate a likely position, orientation, location, etc. and the
imaging system may be used to confirm or provide verification of
the position, etc. In some embodiments, the capsule device may
comprise an optical window 1B and an imaging system for obtaining
images from inside of the esophagus. The imaging system may include
an illumination source 2B, such as a white LED, an imaging camera
3B, which detects the images and an optical system 4B which focuses
the images onto the imaging camera 3B. The illumination source 2B
may illuminate the inner portions 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,
that provides power to the electrical elements of the capsule
device.
[1096] Reference is now made to FIG. 73B which schematically
illustrates a plurality of connected capsules 11B and 12B in
accordance with an embodiment of the invention. The plurality of
capsules may be connected by, for example, a thread, tube, cable,
wire or flexible narrow shaft 13B. According to some embodiments
more than one connecting wire or shaft may be used to connect two
or more capsules. The connecting wire 13B may physically and/or
electrically connect the two or more capsules and may be of any
suitable lengths from a few millimeters to a centimeter or more.
The flexible connection between the two capsules may make the
capsules more flyable and maneuverable in an esophagus than would
be a single rigid or partially flexible capsule device of the same
size or mass. In some embodiments, the first capsule 11B may
contain the components necessary for pH measurement and the
component for fixing the capsule device to, in or on the
intragastric device, wherein the second capsule 12B may also
contain components necessary for pH measurement and/or the
component for fixing the capsule device to, in or on the
intragastric device. In some embodiments, more than two capsules
are used, where each may be used for pH sensing and/or fixation. In
some embodiments, the first capsule 11B may contain the components
necessary for pH measurement and a component for fixing the capsule
device to the mural surface of the stomach, wherein the second
capsule 12B may contain the components necessary for imaging the
stomach and/or intragastric device.
[1097] FIG. 74 illustrates an embodiment of a capsule system 2C
with one or more pH sensors 61D, for incorporation with an
intragastric device, having two hard capsule-like units 11E, 11F
and a soft flexible tube 12D connecting the capsule units. The
capsule-type system 2C comprises a first capsule 11E and a second
capsule 11F as two capsule-like hard units of different diameters
and a soft flexible tube 12D connecting the capsules and having a
diameter less than the diameter of the two capsules 11E, 11F, and
has a structure in which the two capsules 11E, 11F are connected by
the tube.
[1098] The capsule-type system 2C may have a structure in which one
or more sensors 61D, such as a pH sensor, are provided, for
example, in the first capsule 11E. The sensor or sensors 61D are
secured to the outer member of the capsule, such as the transparent
cover 15D, so that a sensing zone of the sensor 61D is exposed to
the outside, and the inside of the capsule is maintained in a
water-tight state.
[1099] Data such as chemical parameters (e.g., pH value) of body
fluids are obtained from the sensing zones. The data obtained are
temporarily accumulated in a memory (not shown in the figures)
located inside the capsule and then transmitted by a
transmission-receiving circuit and antenna to a receiver such as an
external unit located outside the body.
[1100] In some embodiments, a pH sensor 61D may be used in
conjunction with an imaging system. For example, in the first
capsule 11E, the cylindrical peripheral portion of the hard capsule
frame may be water-tight sealed with a dome-like hard transparent
cover 15D via a seal member. An image pickup device and an
illumination device may be housed inside the first capsule. In some
embodiments, an objective lens 16D constituting the image pickup
device may be mounted on a light-shielding lens frame 17D and
disposed opposite the transparent cover 15D in the central portion
of the internal space covered with the dome-like transparent cover
15D. An image pickup element, for example, a CMOS image pickup
device, may be disposed in the image forming position of the
objective lens. In some embodiments, white LEDs 19D are disposed as
illumination devices in a plurality of places around the lens frame
17D, and the light emitted by the white LEDs 19D passes through the
transparent cover 15D and illuminates the space outside thereof. An
elastic resin cover 28D may be on an external part of the second
capsule 11F. In some embodiments, the image pickup device may be
used to verify the location, orientation, state, etc. of an
intragastric device after the pH sensor 61D indicates a particular
pH level.
[1101] The pH Sensor may be integrated with the intragastric
locating system in a number of manners. For example, as shown in
FIG. 23, the balloon 1100 may incorporate a pellet 1110 that is a
pH sensor pellet. The pellet can be loose or attached to a wall of
the intragastric balloon 1100. As another example, as shown in FIG.
24, the balloon 1200 of one embodiment may incorporate buttons 1210
as pH sensor buttons that are attached to opposite sides of the
intragastric balloon 1200. As another example, as shown in
cross-section in FIG. 25A, the valve system 1300 may include the
retaining ring 1318 containing a pH sensor. FIG. 25B is a top view
of the valve system 1300 that may contain the pH sensor, depicted
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 contain the pH
sensor. As another example, FIG. 26 depicts a gel cap 1400
containing the intragastric balloon of FIGS. 25A-C in uninflated
form that may contain the pH sensor. The gel cap containing the
uninflated balloon is engaged via the valve system of the
intragastric balloon to a dual catheter system comprising a 2FR
tube 1410 and a 4FR tube 1412 via a press-fit connecting structure
1414 which may incorporate a pH sensor, e.g., a needle (not
depicted).
[1102] The preceding examples, and/or any other embodiments of the
device, may be used in a variety of manners. FIG. 75 is a flowchart
of an embodiment of a method 1100 for using pH detection to locate
and/or characterize an intragastric device. The method 1100 may
include block 1110 where 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. 1A-10. The method 1100 may
further include block 1120 where the intragastric device is
inserted into a patient. The intragastric device may be inserted
into a patient in any of the manners described herein, for instance
by swallowing a balloon, by inserting a catheter with a balloon,
etc.
[1103] The method 1100 may further include block 1130 where the
ambient pH level is sensed. The ambient pH level may be the pH
level of the surrounding fluids in the alimentary canal encountered
by the device. For instance, the pH level of the esophagus and/or
stomach may be sensed as the device travels through the respective
portions of the canal. The method may further include block 1140
where the data relating to the pH level is transmitted to a
computer. By computer it is meant to include any device that
receives the signal that includes the data, for instance a
receiver. In some embodiments, the data is sent wirelessly to a
receiver. In some embodiments, the data is sent by wire from a
wired sensor to a connected computer or receiver. Any of the
examples and/or embodiments discussed herein may also be used in
block 1140 to transmit the pH data.
[1104] The method 1100 may further include block 1150 where the pH
data is analyzed. The pH data may be analyzed by any of the methods
discussed herein, for instance by visual reading on a display, by
numerical analysis, and/or others. In some embodiments, the pH data
is analyzed by a computer. In some embodiments, the pH data is
analyzed by a doctor or technician.
[1105] Finally, the method 1100 may further include block 1160
where the location, orientation, state, etc. of the intragastric
device is determined based on the pH data. In some embodiments,
analysis of the pH data indicates a likely location, orientation,
state, etc. of the device. For instance, a lower pH level may
indicate that the device is in the stomach and a higher pH level
may indicate that the device is in the esophagus. Such information
may be useful, for example, in determining whether to inflate a
balloon.
Commercial Systems
[1106] In some embodiments, commercial systems may be incorporated
into the present disclosure to provide pH sensing. One such
commercial system is the BRAVO.RTM. pH Monitoring System by Given
Imaging. The BRAVO.RTM. pH monitoring system is a catheter-free
ambulatory pH test that utilizes a small pH capsule to transmit pH
data up to 96 hours. While the system is useful for pH measurement
and monitoring of gastric reflux to assist clinicians diagnose
gastroesophageal reflux disease (GERD), the system may also be
incorporated into embodiments of the present disclosure for
verifying the location, orientation, state, etc. of an intragastric
device inside the body.
[1107] In some embodiments, a system using two main components for
pH sensing is implemented. The first main component is a small pH
capsule about the size of a gelcap that is incorporated in, on, or
otherwise with, the intragastric device, and transmits data to a
receiver. The second main component is the pager-sized receiver
that receives pH data from the capsule. Data from the receiver may
be uploaded to pH analysis software using infrared technology. The
capsule may be integrated with the intragastric device in a number
of ways. Further, multiple capsules may be incorporated with the
intragastric device in various locations. In some embodiments,
capsules are placed on opposing sides of the intragastric device,
such as top/bottom, front/back, and left/right. Individual readings
from each sensor can provide indications of the orientation of the
device, in addition to location, state, etc.
[1108] Another commercial system which may be incorporated into
some embodiments is the VersaFlex.TM. System from Sierra Scientific
Instruments in Los Angeles, Calif. The system has a probe, such as
a pH sensor, inserted into the gastric lumen and connected to a pH
recording device, such as the Digitrapper from Sierra Scientific
Instruments, Los Angeles, Calif. The probes are small and flexible
to ensure maximum comfort for the patient. The probes are available
in single or dual channel configurations. The tubing may be, 1.5 mm
(4 Fr) diameter tubing with smooth surfaces to eliminate the large
"bump" typically found at the sensor tip. They may further have
optimal stiffness for easier intubation that softens at body
temperature for greater patient comfort. The dual channel
configuration features two sensors spaced 5 cm apart. Because pH
probes must be soaked and calibrated prior to any procedure, a
calibration kit is provided containing disposable tubes with pH
buffers, providing a convenient solution to streamline
pre-procedure tasks. The calibration kit can contain, for example,
pH7 and pH4 buffers as well as deionized water for rinsing.
[1109] FIG. 76 is a perspective view of an embodiment of a suitcase
kit 3800 for the intragastric locating systems of the present
disclosure. The kit 3800 may include any of the tracking systems
discussed herein, for example the system 1501 or 1601. The kit 3800
provides a collapsible and portable assembly for transporting the
various systems. The kit 3800 includes a case 3810. The case 3810
may be similar to a standard suitcase with a handle for easy
carrying. The case 3810 includes a top portion 3815 and a bottom
portion 3820. The top portion 3815 is rotatably attached to the
bottom portion 3820 such that the top portion 3815 may rotate to
open and close. The top portion 3815 includes a display 3825 that
may be electrically connected with other features of the
system.
[1110] The bottom portion 3820 may define a cavity 3830 therein.
The cavity 3820 may include space for storing the various
components of the various systems. For instance, the components of
the systems 1501 or 1601 may be stored in the cavity 3820. By
closing the top portion 3815, the contents of the cavity 3830 may
be protected from theft or the elements. The bottom portion 3820
may further include a set of vertical supports 3835 and horizontal
supports 3840. The supports 3835, 3840 may be coupled together to
allow them to rotate relative to each other and stow with the
bottom portion 3820. As shown, the supports 3835, 3840 are extended
such that the case 3810 is elevated. The supports 3835, 3840 may be
rotatably coupled at joints 3842, which may be a pin or bushing to
allow rotation.
[1111] FIG. 77 is a perspective view of an embodiment of a backpack
kit 3900 for the intragastric locating systems of the present
disclosure. The kit 3900 may include any of the tracking systems
discussed herein, for example the system 1501 or 1601. As shown,
the kit 390 includes a case 3910. The case 3910 may store various
components of the various systems and allow for easy movement of
those components to and from different kits 3900. The case 3910 is
shown hanging on a support member 3908 by straps 3915. The straps
3915 may allow for securing the case 3910 to the member 3908. The
straps 3915 may also be sued to carry the case 3910 like a typical
backpack.
[1112] The support members 3908 are coupled with a support surface
3920. The surface 3920 provides an elevated platform on which to
place items while performing procedures with the systems. The
surface 3920 supports a display 3925. The display 3925 may be used
to show the identifiers indicating the locations of the various
sensors. The surface 3920 also includes a foldable end portion
3930. The end portion 3930 is shown in the down position. It may
also rotate up to provide more area for the surface 3920. The
surface 3920 and end portion 3920 are supported on a frame 3935.
The frame 3935 may include compartments for storing items, such as
patient records or components for the system such as disposable
catheters. In some embodiments, the frame 3935 includes a drawer
for storing items. The frame 3935 is supported by a mount 3940
having wheels 3942 that allow the kit 3900 to be easily moved by
rolling on the wheels 3942.
Film Permeability
[1113] A variety of different composite films were tested for
permeability of gases as measured by CO.sub.2 diffusion at
37.degree. C., and for suitability for use as materials for wall or
other components of the intragastric devices of various
embodiments. As shown in the data of Table 3, the permeability of
varying composite wall constructions were evaluated and determined
by their resistance to CO.sub.2 diffusion rates, where the smaller
the permeability test result, the higher barrier to gas diffusion
the film provides. As noted, the permeability of the film and
degree of barrier the film provides to gas diffusion was derived
using CO.sub.2 at 37.degree. C., one of the most permeable gasses.
This can be used as a surrogate to other gas diffusion rates where
generally CO.sub.2 is 3 to 5 times faster in diffusion across a
membrane than oxygen, and nitrogen is 0.2 to 0.4 times faster than
the oxygen transmission rate when these are evaluated at 25.degree.
C. As Table 3 indicates, permeability of the film is also affected
by orientation of the film (which layer is exposed to the CO.sub.2
gas first), and Relative Humidity. The walls were tested under
conditions of low relative humidity (0%, representative of
conditions inside the balloon upon fill) and high relative humidity
(100%, representative of in vivo conditions). In certain
embodiments, a composite wall having a permeability of <10
cc/m.sup.2/day is generally preferred; however, depending upon the
desired effect of inflation and re-inflation by in vivo gasses such
as CO.sub.2, a higher permeability of >10 cc/m.sup.2/day in in
vivo conditions can be desirable. For example, each of the films in
the table can be suitable for use in various selected embodiments,
such that the resulting balloon wall has a permeability to CO.sub.2
of even greater than >10 cc/m.sup.2/day, e.g., >50
cc/m.sup.2/day, >100 cc/m.sup.2/day, >200 cc/m.sup.2/day,
>300 cc/m.sup.2/day, >400 cc/m.sup.2/day, >500
cc/m.sup.2/day, >750 cc/m.sup.2/day, >1000 cc/m.sup.2/day,
>1500 cc/m.sup.2/day, >2000 cc/m.sup.2/day, >2500
cc/m.sup.2/day, >3000 cc/m.sup.2/day, >3500 cc/m.sup.2/day,
or even >4000 cc/m.sup.2/day. In selected embodiments, it is
generally preferred to have a permeability of from about 1, 2, 3,
4, 5, 6, 7, 8, 9, or 10 cc/m.sup.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.sup.2/day. In Table 3 and elsewhere herein, various films are
listed. When the film comprises two or more layers, a "/" is used
to indicate a layer of one material adjacent to another layer,
optionally with intervening layers or materials. For example,
"A/B/C" would refer to a film comprising a layer of A adjacent to a
layer of B, and the layer of B adjacent to a layer of C on an
opposite side of layer B from the side adjacent to layer A, with or
without intervening layers or materials (e.g., tie layers,
adhesives, surface preparations, surface treatments, or the like).
Referring to the first entry of Table 3, "PE/EVOH/PE" refers to a
film comprising a first layer of polyethylene adjacent to a layer
of ethylene vinyl alcohol, and the layer of ethylene vinyl alcohol
adjacent to a second layer of polyethylene on an opposite side of
the ethylene vinyl alcohol to that adjacent to the first layer of
polyethylene.
TABLE-US-00004 TABLE 3 Innermost Layer Permeability Film (CO.sub.2
Test Results Thickness Exposed (cc/m2/day) Film (in) Layer) RH % (1
ATM/37.degree. C.) PE/EVOH/PE 0.002 .+-. 0.001 PE 0 10.8 70% Nylon
6,66, 0.003 Nylon 6,66 0 2.4 30% MXD6/ EVOH/PVDC/ 70% Nylon 6,66,
30% MXD6/ LLDPE + LDPE 70% Nylon 6,66, 0.003 Nylon 6,66 95 .+-. 5
51.0 30% MXD6/ EVOH/PVDC/ 70% Nylon 6,66, 30% MXD6/ LLDPE + LDPE
70% Nylon 6,66, 0.003 LDPE 95 .+-. 5 3.3 30% MXD6/ EVOH/PVDC/ 70%
Nylon 6,66, 30% MXD6/ LLDPE + LDPE 70% Nylon 6,66, 0.002 LDPE 0
43.0 30% MXD6/PVDC/ 70% Nylon 6,66, 30% MXD6/ LLDPE + LDPE 70%
Nylon 6,66, 0.003 LDPE 0 50.0 30% MXD6/PVDC/ 70% Nylon 6,66, 30%
MXD6/ LLDPE + LDPE 70% Nylon 6,66, 0.002 LDPE 95 .+-. 5 41.0 30%
MXD6/PVDC/ 70% Nylon 6,66, 30% MXD6/ LLDPE + LDPE 70% Nylon 6,66,
0.003 LDPE 95 .+-. 5 49.0 30% MXD6/PVDC/70% Nylon 6,66,30% MXD6/LLD
PE + LDPE Bi-axially Oriented 0.00125 LDPE 0 15.4 PP/EVOH/PE
Bi-axially Oriented 0.00175 PE 0 8.2 PP/EVOH/PE Bi-axially Oriented
0.00125 PE 95 .+-. 5 282.6 PP/EVOH/PE Bi-axially Oriented 0.00125
PE 95 .+-. 5 1088.0 PP/EVOH/PE Bi-axially Oriented 0.00175 PE 95
.+-. 5 235.4 PP/EVOH/PE Cast PP 0.002 .+-. 0.001 NA 0 772.0 Cast
PP/PE/EVOH/PE 0.0025 PE 0 7.2 Cast PP/PE/EVOH/PE 0.0025 PE 0 10.1
Cast PP/PE/EVOH/PE 0.0025 PE 95 .+-. 5 169.3 Cast PP/PE/EVOH/PE
0.0025 PE 95 .+-. 5 18.5 Coextruded 0.00125 PE 0 8.1 PE/EVOH/PE
Coextruded 0.0015 PE 0 4.9 PE/EVOH/PE Coextruded 0.002 .+-. 0.001
PE 0 12.4 PET/SiOx/PE CoExtrude- 0.0025 HDPE 0 1.7 LLDPE/HDPE/EVOH/
HDPE HDPE/HDPE/PVdC/ 0.003 HDPE 0 5.0 EVOH/HDPE/ LLDPE + LDPE
HDPE/HDPE/PVdC/ 0.003 HDPE 95 .+-. 5 6.8 EVOH/HDPE/ LLDPE + LDPE
HDPE/HDPE/PVdC/ 0.003 LDPE 0 4.4 EVOH/HDPE/ LLDPE + LDPE
HDPE/HDPE/PVdC/ 0.003 LDPE 95 .+-. 5 52.0 EVOH/HDPE/ LLDPE + LDPE
HDPE/HDPE/PVdC/ 0.003 LDPE 0 74.0 HDPE/HDPE/ LLDPE + LDPE
HDPE/HDPE/PVdC/ 0.003 LDPE 0 47.0 HDPE/HDPE/ LLDPE + LDPE
HDPE/HDPE/PVdC/ 0.003 LDPE 95 .+-. 5 68.0 HDPE/HDPE/ LLDPE + LDPE
HDPE/HDPE/PVdC/ 0.003 LDPE 95 .+-. 5 44.0 HDPE/HDPE/ LLDPE + LDPE
Kurarister .TM. C, 3 mil 0.003 UNK 0 3.2 Nylon12/ 0.003 LLDPE +
LDPE 0 52.0 PvDC/Nylon 12/LLDPE + LDPE Nylon12/ 0.003 LLDPE + LDPE
95 .+-. 5 56.0 PvDC/Nylon 12/LLDPE + LDPE MPI Supernyl 0.0022 LLDPE
0 3.3 LLDPE 40 .mu.m MPI Supernyl 0.0022 LLDPE 95 .+-. 5 5.8 LLDPE
40 .mu.m MPI Supernyl 0.0026 LLDPE 0 4.2 LLDPE 50 .mu.m MPI
Supernyl 0.0026 LLDPE 95 .+-. 5 7.5 LLDPE 50 .mu.m Nylon12/ 0.003
LLDPE + LDPE 0 59.3 PvDC/Nylon 12/LLDPE + LDPE Nylon12/PVDC/ 0.003
LLDPE + LDPE 95 .+-. 5 29.5 Nylon12/ LLDPE + LDPE Nylon12/PVDC/
0.003 LLDPE + LDPE 0 73.2 Nylon12/ LLDPE + LDPE - Thermoformed
Nylon12/PVDC/ 0.0024 LLDPE + LDPE 0 77.0 Nylon12/ LLDPE + LDPE
Nylon12/PVDC/ 0.0024 LLDPE + LDPE 95 .+-. 5 68.0 Nylon12/ LLDPE +
LDPE Nylon12/PVdC/ 0.003 LDPE 0 58.0 Nylon12/LDPE-Cast
Nylon12/Nylon Tie/ 0.003 LDPE 95 .+-. 5 54.0 EVA/PVdC/Adhesive/
Nylon12/Nylon Tie/ LDPE-Cast Nylon12/PVdC/ 0.0035 LDPE 0 14.9
Nylon12/LDPE Nylon12/ 0.004 LDPE 0 34.0 PVdC/Nylon12/ LDPE Nylon12/
0.0035 LDPE 95 .+-. 5 24.9 PVdC/Nylon12/ LDPE Nylon12/ 0.0035 LDPE
95 .+-. 5 41.3 PVdC/Nylon12/ LDPE Nylon12/ 0.004 LDPE 95 .+-. 5
31.7 PVdC/Nylon12/ LDPE Nylon 6,66/ 0.0024 LDPE 0 54.0
PVDC/Nylon6,66/ LLDPE + LDPE Nylon 6,66/ 0.0024 LDPE 95 .+-. 5 56.0
PVDC/Nylon6,66/ LLDPE + LDPE Nylon 6,66/ 0.0032 LDPE 0 5.5
EVOH/PVDC/ Nylon 6,66/LDPE Nylon 6,66/ 0.0032 LDPE 95 .+-. 5 6.4
EVOH/PVDC/ Nylon 6,66/LDPE Nylon 6,66/ 0.0032 Nylon 6,66 95 .+-. 5
49.9 EVOH/PVDC/ Nylon 6,66/LDPE Nylon 6,66/ 0.0027 LDPE 0 57.0
PVDC/Nylon6,66/ LLDPE + LDPE Nylon 6,66/ 0.003 LDPE 0 41.0
PVDC/Nylon6,66/ LLDPE + LDPE Nylon 6,66/ 0.0027 LDPE 95 .+-. 5 55.0
PVDC/Nylon6,66/ LLDPE + LDPE Nylon 6,66/ 0.003 LDPE 95 .+-. 5 46.0
PVDC/Nylon6,66/ LLDPE + LDPE Multi-layer Nylon 12/ 0.0035 LDPE 0
3203.5 LLDPE + LDPE Multi-layer Nylon 12/ 0.004 LDPE 0 2725.5 LLDPE
+ LDPE Multi-layer Nylon 12/ 0.0045 LDPE 0 2553.6 LLDPE + LDPE
Multi-layer Nylon 12/ 0.0035 LDPE 95 .+-. 5 2539.3 LLDPE + LDPE
Multi-layer Nylon 12/ 0.004 LDPE 95 .+-. 5 2527.8 LLDPE + LDPE
Multi-layer Nylon 12/ 0.0045 LDPE 0 1522.6 LLDPE + LDPE + Parylene
Multi-layer Nylon 12/ 0.0045 LDPE 95 .+-. 5 1275.5 LLDPE + LDPE +
Parylene NYLON- 0.003 LLDPE 95 .+-. 5 83.0 SIOX/HDPE/ LLDPE NYLON-
0.003 LLDPE 0 70.0 SIOX/HDPE/LLDPE Nylon-SIOX/LLDPE 0.0015 LLDPE 0
134.0 Nylon-SIOX/LLDPE 0.0015 LLDPE 95 .+-. 5 82.0 OPP Co-extrude
with 0.002 mPE 0 5.9 mPE/EVOH/mPE OPP Laminated to 0.0025 mPE 0 4.7
mPE/EVOH/mPE OPP Laminated to 0.003 mPE 0 3.4 mPE/EVOH/mPE OPP
Laminated to 0.0025 mPE 95 + 5 294.3 mPE/EVOH/mPE OPP SIOX/LLDPE
0.002 LLDPE 0 540.5 OPP SIOX/LLDPE 0.002 LLDPE 0 1081.0 OPP
SIOX/LLDPE 0.002 LLDPE 95 + 5 565.0 OPP SIOX/LLDPE 0.002 LLDPE 95 +
5 594.5 OPP/mPE/ 0.0021 mPE 0 5.0 EVOH/mPE OPP/mPE/ 0.0021 mPE 95 +
5 437.1 EVOH/mPE OPP/PE/ 0.0025 OPP 0 8.5 EVOH/PE OPP/PE/ 0.0025
OPP 95 + 5 11.6 EVOH/PE OPP/PE/ 0.00175 PE 0 8.1 EVOH/PE OPP/PE/
0.0025 PE 0 8.9 EVOH/PE OPP/PE/ 0.0025 PE 0 18.6 EVOH/PE OPP/PE/
0.0025 PE 95 + 5 259.0 EVOH/PE OPP/PE/ 0.0025 PE 95 + 5 556.1
EVOH/PE OPP/PVDC/mPE 0.0017 mPE 0 74.2 OPP/PVDC/mPE 0.0017 mPE 95 +
5 84.6 OPP-SIOX/LLDPE 0.002 .+-. 0.001 LLDPE 95 + 5 1159.7 Oriented
PA 0.002 .+-. 0.001 NA 0 750.9 Oriented PP 0.002 .+-. 0.001 NA 0
726.0 PA/EVOH/ 0.0022 LLDPE 0 5.0 PA/LLDPE PA/EVOH/ 0.0022 LLDPE 0
3.1 PA/LLDPE PA/EVOH/ 0.0022 LLDPE 95 .+-. 5 10.8 PA/LLDPE
PE/EVOH/PE 0.002 .+-. 0.001 PE 0 9.2 PET 0.001 PE 0 524.7
SiOx-PET/EVOH/PE 0.002 PE 0 1.4 SiOx-PET/MPE/ 0.0016 mPE 0 1.0
EVOH/mPE Si-Ox-PET/PE/ 0.00125 PE 0 1.7 EVOH/PE Si-Ox-PET/PE/
0.0015 PE 0 1.6 EVOH/PE Si-Ox-PET/PE/ 0.0015 PE 0 5.4 EVOH/PE
Si-Ox-PET/PE/ 0.002 PE 0 1.5 EVOH/PE
Si-Ox-PET/PE/ 0.002 PE 0 1.8 EVOH/PE Si-Ox-PET/PE/ 0.002 PE 95 .+-.
5 22.6 EVOH/PE
Animal Studies
[1114] Two different composite walls were tested: a material
(Nylon12/PvDC/Nylon 12/LLDPE+LDPE) with high barrier material
characteristics and a material with low barrier characteristics
(multi-layer Nylon12/LLDPE+LDPE). A series of experiments were
performed using a mixture of 75% N.sub.2 and 25% CO.sub.2 as the
balloon initial fill. As shown in the data of Table 4, each of the
balloons maintained pressure over the duration tested, but gained
substantially in volume. Considering the composite walls studied
are not a metal canister (volume and pressure change due to
material stretch) there was a significant change in the number of
overall gas molecules inside the balloon from the initial gas fill.
Since the internal balloon environment started with CO.sub.2 and
nitrogen, most likely additional CO.sub.2 entered due to the
environment the balloon was subjected to (N.sub.2 and CO.sub.2
headspace) but also most likely other gases available in the air as
well as water vapor also diffused within the balloon wall.
TABLE-US-00005 TABLE 4 % CO.sub.2 in Starting balloon Measured
Balloon #, implant Estd. Explant Explant (meas. w/ % CO.sub.2 in %
gas Wall pressure Volume Volume Pressure CO.sub.2 stomach Final
gain Pig # Composition (PSI) at implant (cc) (PSI) meter) gas (%)
Vol. (calc.) 1 1, Barrier 1.0 277 360 1.1 22% 10% 385 23.5 Material
(Nylon/Saran) 1 2, Barrier 1.09 282 340 0.7 19.63% 10% 358 15
Material (Nylon/Saran) 2 3, Non- 1.15 283 330 1.2 26.57% 8% 320
14.5 Barrier Material (Nylon) 2 4, Non- 1.07 281 323 0.96 31% 8%
316 12.4 Barrier Material (Nylon)
[1115] Volume gains were higher for the barrier material composite
walls than for the non-barrier walls. An analysis of gas in the
balloons after explants (Tables 5a and 5b) showed gains in oxygen,
hydrogen, and argon in addition to the nitrogen and carbon dioxide
that was already present in the balloon at initial inflation. The
balloons, both with a good barrier composite wall (table 5a) and a
poor barrier composite wall (table 5b) both gained in overall
volume while maintaining pressure after 30 days in vivo. Explant
results of the balloon with a composite wall containing a good
barrier material (#2, table 5a) showed a slightly higher increase
in carbon dioxide than the wall without a barrier material (#3,
table 5b). It is unlikely that nitrogen diffused in or out of the
balloon due to its inertness as well as the external gastric
environment most likely matched the internal concentration of
nitrogen such that there was no (or an insignificant) diffusion
gradient for the nitrogen gas.
TABLE-US-00006 TABLE 5a Gas % v/v, by MS Detection Limit Nitrogen
64.04 0.01 Oxygen 7.63 0.01 Argon 0.60 0.01 Carbon Dioxide 19.63
0.01 Hydrogen 8.10 0.01 Helium not detected 0.01 Methane not
detected 0.01
TABLE-US-00007 TABLE 5b Gas % v/v, by MS Detection Limit Nitrogen
62.33 0.01 Oxygen 9.27 0.01 Argon 0.7 0.01 Carbon Dioxide 26.57
0.01 Hydrogen 1.13 0.01 Helium not detected 0.01 Methane not
detected 0.01
[1116] The data show that when it is desirable to minimize volume
gain over the useful life of the device, a non-barrier composite
wall material may be more desirable than a barrier wall. This
observation is contrary to conventional wisdom that seeks to
maintain the initial fill of gas in the balloon by maximizing
barrier properties of the intragastric balloon wall.
Simulated Gastric Environment
[1117] Balloons constructed with non-barrier film composite walls
were tested (multi-layer Nylon 12/LLDPE+LDPE) in a simulated
gastric environment (tank containing a 1.2 pH HCl solution with
NaCl and pepsin at 40.degree. C. with a variable N.sub.2/CO.sub.2
headspace; samples were taken at peak CO.sub.2 at 50% and trough
CO.sub.2 at 0% in the tank). The balloons were initially filled
with either pure N.sub.2 or a mixture of N.sub.2 (75%) and CO.sub.2
(25%), and pressure, volume, and gas gain were monitored over time.
The balloon filled with pure nitrogen exhibited significantly
higher gain of CO.sub.2 when compared to the balloon filled with
the N.sub.2/CO.sub.2 mixture. When a volume gain (as manifested in
a gain of CO.sub.2 gas) is desired, pure nitrogen as the initial
fill gas in connection with a non-barrier film is desirable. Data
for the experiments is provided in Table 6.
TABLE-US-00008 TABLE 6 (Day 2) Volume Volume Pressure Balloon
Pressure Volume Volume Volume Pressure 9:00 (Day 5) (Day 5) (Day 5)
(Day 5) Experiment Material Sample Internal Gas (Day 0) (Day 0)
(Day 1) (Day 2) (Day 2) AM 9:00am 7:00 PM 7:00 PM 7:00 PM End of
Cycle .fwdarw. 50% CO.sub.2 50% CO.sub.2 % Gas Gain 50% CO.sub.2 0%
CO.sub.2 0% CO.sub.2 % Gas Gain N2 or T = 0 T = 0 T = 1 T = 2 T = 2
T = 2 T = 5 T = 5 T = 5 T = 5 # OGB # # N2/CO2 (psi) (cc) (cc) (cc)
(psi) (%) (cc) (cc) (psi) (%) 1 Non-Barrier 1 N2 1.12 304 312 314
1.84 7.4% 323 319 2.50 12.3% Film 3 1.12 300 310 313 1.81 8.2% 319
314 2.53 12.3% 4 1.09 294 309 311 1.79 9.5% 321 313 2.56 14.1% 5
1.10 300 312 314 1.82 8.6% 324 318 2.70 14.3% 6 1.10 309 317 320
1.68 6.9% 329 328 2.58 13.9% avg. 1.11 301 312 314 1.79 8.1% 323
318 2.57 13.4% 2 1B N2/CO2 1.10 318 328 326 1.15 2.1% 329 324 1.37
2.6% 2B (75%/25%) 1.00 295 301 299 1.04 1.2% 302 297 1.28 1.8% 4B
1.10 292 300 295 1.18 1.1% 299 293 1.25 1.0% 5B 1.08 294 306 303
1.22 2.9% 305 302 1.16 2.4% 6B 1.07 293 300 293 1.18 0.5% 298 295
1.26 1.4% avg. 1.07 298 307 303 1.15 1.6% 307 302 1.26 1.8% Volume
Volume Pressure (Day 6) Pressure (Day 6) Volume Pressure (Day 6)
(Day 7) (Day 7) CO.sub.2 % Volume Balloon 8:00 (Day 6) 8:00 (Day 6)
(Day 6) 7:00 8:00 8:00 (Day 7) (Day 7) Experiment # Material Sample
# Internal Gas AM 8:00 AM AM 7:00 PM 7:00 PM PM AM AM 8:00AM 7:00
PM End of Cycle .fwdarw. 50% CO.sub.2 50% CO.sub.2 % Gas Gain* 0%
CO.sub.2 0% CO.sub.2 % Gas Gain 50% CO.sub.2 50% CO.sub.2 % Gas
Gain* 0% CO.sub.2 T = 6 T = 6 T = 6 T = 6 T = 6 T = 6 T = 7 T = 7 T
= 7 T = 7 (cc) (psi) (%) (cc) (psi) (%) (cc) (psi) (%) (cc) 1
Non-Barrier 1 N.sub.2 323 3.03 16.0% balloon cut during test Film 3
320 3.01 16.3% 318 2.84 14.9% 322 3.02 16.8% 319 4 322 3.04 18.7%
321 2.87 17.7% 322 3.05 18.8% 320 5 322 3.19 17.7% 322 2.98 16.7%
325 3.15 18.3% 323 6 330 3.12 17.0% 329 2.89 15.6% 331 3.08 17.0%
329 avg. 323 3.08 17.1% 323 2.90 16.2% 325 3.08 17.7% 323 2 1B
N.sub.2/CO.sub.2 329 1.82 5.7% 329 1.48 4.2% 327 1.63 4.4% 326 2B
(75%/25%) 300 1.61 4.0% 301 1.38 3.2% 300 1.57 3.8% 299 4B 299 1.64
4.2% 298 1.46 3.1% 299 1.61 4.0% 296 5B 304 1.55 4.6% 306 1.33 4.1%
303 1.45 3.9% 303 6B 299 1.62 4.0% 298 1.41 2.8% 300 1.60 4.1% 297
avg. 306 1.65 4.5% 306 1.41 3.5% 306 1.57 4.1% 304 Volume Pressure
CO.sub.2 % Volume Volume Pressure CO.sub.2 % (Day 8) (Day 8) (Day
8) (Day 8) Pressure CO.sub.2 % (Day 9) Pressure Balloon (Day 7)
(Day 7) 8:00 8:00 8:00 7:00 (Day 8) (Day 8) 8:00 (Day 9) Experiment
# Material Sample # Internal Gas 7:00 PM 7:00 PM AM AM AM PM 7:00
PM 7:00 PM AM 8:00 AM End of Cycle .fwdarw. 50% CO.sub.2 % Gas Gain
0% CO.sub.2 0% CO.sub.2 % Gas Gain 50% CO.sub.2 50% CO.sub.2 T = 7
T = 8 T = 8 T = 8 T = 8 T = 8 T = 8 T = 9 T = 9 T = 7 (%) (cc)
(psi) (%) (cc) (psi) (%) (cc) (psi) 1 Non-Barrier 1 N.sub.2 Film 3
2.90 15.5% 322 3.01 16.8% 318 2.88 15.1% 323 2.96 4 2.92 17.7% 323
2.99 18.8% 322 2.87 17.9% 323 3.00 5 2.91 16.7% 325 3.07 17.9% 325
2.96 17.4% 323 3.01 6 2.88 15.6% 332 3.03 17.1% 330 2.88 15.8% 332
2.91 avg. 2.90 16.3% 326 3.03 17.6% 324 2.90 16.6% 325 2.97 2 1B
N.sub.2/CO.sub.2 1.42 3.3% 329 1.43 4.0% 325 1.30 2.5% 327 1.28 2B
(75%/25%) 1.37 2.7% 301 1.42 3.4% 314 1.28 5.8% 301 1.35 4B 1.37
2.3% 299 1.29 2.6% 300 1.32 3.0% 298 1.45 5B 1.23 2.9% 306 1.32
4.0% 304 1.23 3.2% 307 1.35 6B 1.42 2.6% 299 1.43 3.1% 299 1.34
2.7% 299 1.39 avg. 1.36 2.8% 307 1.38 3.4% 308 1.29 3.4% 306 1.36
Volume Pressure Balloon CO.sub.2 % Volume Pressure CO.sub.2 %
Volume Pressure CO.sub.2 % (Day 14) (Day 14) CO.sub.2 % Internal
(Day 9) (Day 12) (Day 12) (Day 12) (Day 13) (Day 13) (Day 13) 8:00
8:00 (Day 14) Experiment # Material Sample # Gas 8:00 AM 8:00AM
8:00 AM 8:00 AM 8:00 AM 8:00 AM 8:00 AM AM AM 8:00 AM End of Cycle
.fwdarw. % Gas Gain* 50% CO2 50% CO2 % Gas Gain* 50% CO2 50% CO2 %
Gas Gain* T = 9 T = 8 T = 8 T = 8 T = 9 T = 9 T = 9 T = 10 T = 10 T
= 10 (%) (cc) (psi) (%) (cc) (psi) (%) (cc) (psi) (%) 1 Non-Barrier
1 N.sub.2 Film 3 16.8% 323 3.00 17.0% 325 3.37 19.2% 323 3.25 18.1%
4 18.8% 322 3.25 19.7% 326 3.36 21.2% 327 3.21 20.7% 5 17.1% 325
3.27 18.8% 327 3.38 19.8% 326 3.36 19.5% 6 16.5% 330 3.25 17.6% 333
3.30 18.5% 334 3.30 18.8% avg. 17.3% 325 3.19 18.3% 328 3.35 19.7%
328 3.28 19.3% 2 1B N.sub.2/CO.sub.2 2.9% 326 1.62 4.2% 330 1.68
5.3% 329 1.68 5.1% 2B (75%/25%) 3.1% 302 1.62 4.5% 304 1.69 5.3%
302 1.48 3.9% 4B 3.1% 298 1.42 3.0% 300 1.56 4.1% 299 1.43 3.3% 5B
4.4% 305 1.66 5.3% 309 1.69 6.3% 307 1.57 5.3% 6B 3.0% 298 1.58
3.6% 298 1.70 4.1% 300 1.66 4.4% avg. 3.3% 306 1.58 4.1% 308 1.66
5.0% 307 1.56 4.4%
[1118] Balloons constructed with various composite walls, a barrier
material Nylon12/PvDC/Nylon12/LLDPE+LDPE) and a non-barrier
material (multi-layer Nylon12/LLDPE+LDPE) were tested in a
simulated gastric environment (tank containing a 1.2 pH HCl
solution with NaCl and pepsin at 40.degree. C. with a variable
N.sub.2/CO.sub.2 headspace (75%/25% to 100%/0%)). The balloons were
initially filled with a mixture of N.sub.2 (75%) and CO.sub.2
(25%). Pressure for the balloons fabricated from CO.sub.2 barrier
materials maintained pressure and volume over the time period
tested, whereas the balloons fabricated from CO.sub.2 non-barrier
materials exhibited substantial pressure gain over the same time
period, with a smaller volume gain. Results are presented in Table
7
TABLE-US-00009 TABLE 7 Balloon Volume Pressure Volume Pressure
Volume Pressure Volume Pressure Volume Pressure Volume Pressure
Internal (Day 0) (Day 0) (Day 1) (Day 1) (Day 2) (Day 2) (Day 3)
(Day 3) (Day 4) (Day 4) (Day 5) (Day 5) Exp. Material Sample Gas
(cc) (psi) (cc) (psi) (cc) (psi) (cc) (psi) (cc) (psi) (cc) (psi) 1
Barrier 1 N.sub.2/CO.sub.2 280 1.05 286 1.05 289 1.08 292 1.07 2
(75%/ 279 1.03 284 1.01 287 1.03 292 1.04 avg. 25%) 280 1.04 285
1.03 288 1.06 292 1.06 2 Barrier 1 N.sub.2/CO.sub.2 279 1.06 283
0.97 284 1.14 287 1.01 2 (75%/ 278 1.07 282 1.04 286 1.13 287 1.02
avg. 25%) 279 1.07 283 1.01 285 1.14 287 1.02 3 Barrier 1
N.sub.2/CO.sub.2 280 1.05 287 1.05 285 1.09 287 1.05 2 (75%/ 278
1.02 280 0.97 285 1.05 286 1.00 avg. 25%) 279 1.04 284 1.01 285
1.07 287 1.03 4 Barrier 1 N.sub.2/CO.sub.2 296 1.14 303 1.28 308
1.35 309 1.36 2 (75%/ 295 1.05 303 1.18 306 1.39 306 1.29 avg. 25%)
296 1.10 303 1.23 307 1.37 308 1.33 5 Non- 1 N.sub.2/CO.sub.2 304
1.12 313 2.26 320 2.44 322 2.51 Barrier 2 (75%/ 292 1.11 312 2.37
315 2.59 315 2.58 avg. 25%) 298 1.12 313 2.32 318 2.52 319 2.55 6
Non- 1 N.sub.2/CO.sub.2 298 1.15 308 2.34 311 2.48 312 2.59 Barrier
2 (75%/ 294 1.14 301 2.15 306 2.39 308 2.51 avg. 25%) 296 1.15 305
2.25 309 2.44 310 2.55 7 Non- 1 N.sub.2/CO.sub.2 297 1.14 307 2.17
310 2.43 308 2.45 Barrier 2 (75%/ 302 1.15 312 2.22 315 2.43 316
2.54 avg. 25%) 300 1.15 310 2.20 313 2.43 312 2.50 8 Barrier 1
N.sub.2/CO.sub.2 298 1.11 303 1.28 305 1.39 305 1.36 2 (75%/ 302
1.12 303 1.28 303 1.34 306 1.31 avg. 25%) 300 1.12 303 1.28 304
1.37 306 1.34 9 Barrier 1 N.sub.2/CO.sub.2 294 1.18 301 1.24 303
1.30 304 1.29 2 (75%/ 291 1.13 298 1.24 298 1.35 299 1.33 avg. 25%)
293 1.16 300 1.24 301 1.33 302 1.31
[1119] Balloons constructed with composite walls with high CO.sub.2
barrier properties (Experiments 1, 2, and 3) (Nylon12/PvDC/Nylon
12/LLDPE+LDPE) and walls having a higher permeability to CO.sub.2
(Experiments 4, 5, and 6) consisting of multi-layer
Nylon12/LLDPE+LDPE were exposed to a stimulated gastric
environment. The simulated gastric environment comprised a tank
containing a 1.2 pH HCl solution with NaCl and pepsin at 40.degree.
C. The headspace in the tank was cycled from a gas mixture
comprising 75% N.sub.2/25% CO.sub.2 headspace to one comprising
100% N.sub.2/0% CO.sub.2. The balloons were initially filled with
various mixtures of N.sub.2 and CO.sub.2, and volume was monitored.
Data regarding volume changes are provided in Table 8. The balloons
constructed using walls having a higher permeability to CO.sub.2
gained substantially in volume compared to those with high CO.sub.2
barrier properties. For the balloons constructed using walls having
a higher permeability to CO.sub.2, those with higher ratios of
N.sub.2 to CO.sub.2 as initial fill gas gained less volume than
those with lower ratios of N.sub.2 to CO.sub.2. The data
demonstrate that permeation of CO.sub.2 into balloons fabricated
with walls having a higher permeability to CO.sub.2 occurs quickly
in the gastric environment, and that this process can be employed
to assist with inflation in the early stages of implant.
TABLE-US-00010 TABLE 8 Volume Pressure Volume Pressure Volume
Pressure Volume Pressure (Day 1) (Day 1) (Day 2) (Day 2) (Day 2)
(Day 2) (Day 3) (Day 3) Balloon 5:00 PM 5:00 PM 8:00 AM 8:00 AM
8:30 PM 8:30 PM 8 AM 8 AM Experiment Material Sample Internal Gas
(cc) (psi) (cc) (psi) (cc) (psi) (cc) (psi) 1 Barrier 1 N2/CO2 298
1.07 301 1.08 301 1.11 301 1.13 2 (92%/8%) 293 1.02 293 1.06 295
1.06 302 1.10 3 285 1.00 287 1.05 284 1.03 289 1.07 avg. 296 1.05
297 1.07 298 1.09 302 1.12 2 Barrier 1 N2/CO2 286 1.09 287 1.09 287
1.13 287 1.12 2 (90%/10%) 291 1.09 294 1.14 294 1.13 296 1.17 3 293
1.08 298 1.13 297 1.15 300 1.19 avg. 290 1.09 304 1.20 293 1.14 294
1.16 3 Barrier 1 N2/CO2 290 1.10 295 1.15 294 1.17 297 1.21 2
(85%/15%) 290 1.02 290 1.03 290 1.08 294 1.10 3 299 1.16 304 1.20
302 1.27 308 1.27 avg. 293 1.09 293 1.09 295 1.17 300 1.19 4 Non- 1
N2/CO2 290 1.04 298 1.54 296 1.48 297 1.72 Barrier 2 (92%/8%) 292
1.07 300 1.60 298 1.55 302 1.81 3 291 1.09 301 1.68 296 1.65 301
1.80 avg. 291 1.07 299 1.57 297 1.56 300 1.78 5 Non- 1 N2/CO2 283
1.07 293 1.64 291 1.56 294 1.80 Barrier 2 (90%/10%) 287 1.05 295
1.60 295 1.50 295 1.67 3 290 1.00 300 1.48 298 1.44 301 1.65 avg.
287 1.04 294 1.62 293 1.53 297 1.71 6 Non- 1 N2/CO2 287 1.06 297
1.76 295 1.76 300 1.99 Barrier 2 (85%/15%) 298 1.07 307 1.66 305
1.69 312 1.93 3 290 1.13 304 1.78 302 1.80 305 2.03 avg. 292 1.09
302 1.71 300 1.73 306 1.98
Human Gastric Environment
[1120] Balloons constructed with non-barrier film composite walls
were tested in vivo in 10 patients in a clinical study for 30 days.
The balloon wall comprised multi-layer Nylon 12/LLDPE+LDPE. One
balloon per patient was administered. Balloons were filled with a
mixed gas to approximately 245 cc with an average starting balloon
pressure of 1.01 psi above atmosphere. The initial fill gas was 95%
Nitrogen and 5% CO.sub.2. At the end of 30 days, balloons remained
full and firm, although ending pressure and volumes could not be
discerned visually/endoscopically. Of the 10 balloons retrieved, 10
balloons had internal gas samples obtained, and 8 provided
meaningful data. Table 9 provides the data retrieved from the
balloons. The end gas samples are reflective of the gastric
environment and are averaged as follows: 82.4% N.sub.2, 10.6%
O.sub.2, 5.9% CO.sub.2, and 0.84% Ar. Thus, the internal balloon
environment reflects that of the average gastric environment gas
concentrations. Data for the experiments is provided in Table
9.
TABLE-US-00011 TABLE 9 Starting Balloon Ending Balloon Gas Gas
Concentration Patient # Concentration (% v/v, by MS) Patient # [N2]
[CO.sub.2] [N2] [O.sub.2] [CO.sub.2] [Ar] 1 95.00 5.00 81.19 10.20
7.60 0.86 2 95.00 5.00 81.24 12.90 4.85 0.86 3 95.00 5.00 82.41
10.80 5.65 0.85 4 95.00 5.00 82.07 11.20 5.70 0.82 5 95.00 5.00
82.87 10.05 6.00 0.82 6 95.00 5.00 82.54 11.50 4.80 0.88 7 95.00
5.00 Erroneous Sample 8 95.00 5.00 81.76 10.20 7.00 0.82 9 95.00
5.00 Erroneous Sample 10 95.00 5.00 84.95 8.20 5.80 0.81 Avg. 82.38
10.63 5.93 0.84 Std Dev 1.20 1.36 0.97 0.03 Max 84.95 12.90 7.60
0.88 Min 81.19 8.20 4.80 0.81
[1121] In certain embodiments wherein it is desirable to maintain
the starting pressure and volume of the device, this can be
accomplished by matching the internal balloon environment at
implant (i.e., the fill gases) closely to 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 concentration of argon and
other in vivo gases can be considered inconsequential to the total
volume/pressure, and may be omitted for convenience or included as
desirable. To encourage inflation of the balloon in vivo, the
starting concentrations of oxygen and/or carbon dioxide can be
reduced.
[1122] Experiments were conducted to determine pressure in various
balloons over time for different initial fill gases. In reference
to FIG. 43, the initial fill gases included the following (vol. %):
100% SF.sub.6; 100% N.sub.2; 50% SF.sub.6 in combination with 50%
N.sub.2; 25% SF.sub.6 in combination with 75% N.sub.2; and 18-20%
SF.sub.6 in combination with 78-80% N.sub.2. One type of balloon
tested included a composite polymeric wall including a layer of 3.5
mil polyethylene and a layer of nylon. Another type of balloon
tested included an ethylene vinyl alcohol layer in the composite
polymeric wall. As shown by the data presented in FIG. 43, the
balloons including 100% N.sub.2 as the fill gas exhibited slight
increase in pressure over approximately the first 2-4 weeks of the
test, followed by a loss of pressure over time. The balloon
including an ethylene vinyl alcohol layer was able to maintain
pressure at a level equal to or greater than to the initial fill
pressure for approximately four months, while the balloon including
a polyethylene/nylon wall was able to maintain such a pressure for
approximately 1 month. Balloons including 100% SF.sub.6 exhibited
substantial increase in pressure over the first approx. 2 to 3
months, at which time the pressure tended to level off for the
duration of the test. By adding N.sub.2 to the SF.sub.6, the
pressure at which leveling occurred was lowered. A mixture of
approx. 18-20% SF.sub.6 with the remainder N.sub.2 exhibited a
modest rise in pressure over approx. one month followed by
substantially level maintenance of pressure over an approx. 4 month
period of time.
[1123] The present invention has been described above with
reference to specific embodiments. However, other embodiments than
the above described are equally possible within the scope of the
invention. Different method steps than those described above may be
provided within the scope of the invention. The different features
and steps of the invention may be combined in other combinations
than those described. The scope of the invention is only limited by
the appended patent claims.
[1124] All references cited herein are incorporated herein by
reference in their entirety. To the extent publications and patents
or patent applications incorporated by reference contradict the
disclosure contained in the specification, the specification is
intended to supersede and/or take precedence over any such
contradictory material.
[1125] To the extent publications and patents or patent
applications incorporated by reference herein contradict the
disclosure contained in the specification, the specification is
intended to supersede and/or take precedence over any such
contradictory material.
[1126] Unless otherwise defined, all terms (including technical and
scientific terms) are to be given their ordinary and customary
meaning to a person of ordinary skill in the art, and are not to be
limited to a special or customized meaning unless expressly so
defined herein.
[1127] Terms and phrases used in this application, and variations
thereof, unless otherwise expressly stated, should be construed as
open ended as opposed to limiting. As examples of the foregoing,
the term `including` should be read to mean `including, without
limitation` or the like; the term `comprising` as used herein is
synonymous with `including,` `containing,` or `characterized by,`
and is inclusive or open-ended and does not exclude additional,
unrecited elements or method steps; the term `example` is used to
provide exemplary instances of the item in discussion, not an
exhaustive or limiting list thereof; adjectives such as `known`,
`normal`, `standard`, and terms of similar meaning should not be
construed as limiting the item described to a given time period or
to an item available as of a given time, but instead should be read
to encompass known, normal, or standard technologies that may be
available or known now or at any time in the future; and use of
terms like `preferably,` `preferred,` `desired,` or `desirable,`
and words of similar meaning should not be understood as implying
that certain features are critical, essential, or even important to
the structure or function of the invention, but instead as merely
intended to highlight alternative or additional features that may
or may not be utilized in a particular embodiment of the invention.
Likewise, a group of items linked with the conjunction `and` should
not be read as requiring that each and every one of those items be
present in the grouping, but rather should be read as `and/or`
unless expressly stated otherwise. Similarly, a group of items
linked with the conjunction `or` should not be read as requiring
mutual exclusivity among that group, but rather should be read as
`and/or` unless expressly stated otherwise. In addition, as used in
this application, the articles `a` and `an` should be construed as
referring to one or more than one (i.e., to at least one) of the
grammatical objects of the article. By way of example, `an element`
means one element or more than one element.
[1128] The presence in some instances of broadening words and
phrases such as `one or more`, `at least`, `but not limited to`, or
other like phrases shall not be read to mean that the narrower case
is intended or required in instances where such broadening phrases
may be absent.
[1129] All numbers expressing quantities of ingredients, reaction
conditions, and so forth used in the specification are to be
understood as being modified in all instances by the term `about.`
Accordingly, unless indicated to the contrary, the numerical
parameters set forth herein are approximations that may vary
depending upon the desired properties sought to be obtained. At the
very least, and not as an attempt to limit the application of the
doctrine of equivalents to the scope of any claims in any
application claiming priority to the present application, each
numerical parameter should be construed in light of the number of
significant digits and ordinary rounding approaches. Where a range
of values is provided, it is understood that the upper and lower
limit, and each intervening value between the upper and lower limit
of the range is encompassed within the embodiments.
[1130] Furthermore, although the foregoing has been described in
some detail by way of illustrations and examples for purposes of
clarity and understanding, it is apparent to those skilled in the
art that certain changes and modifications may be practiced.
Therefore, the description and examples should not be construed as
limiting the scope of the invention to the specific embodiments and
examples described herein, but rather to also cover all
modification and alternatives coming with the true scope and spirit
of the invention.
* * * * *