Abstract:
In one aspect, an ingestible, electrical device, comprises one or more electrodes comprising a biocompatible conducting material and a biocompatible insulating material; a generator connected to the one or more electrodes; and an outer casing enclosing the one or more electrodes and the generator, the outer casing configured to dissolve in an aqueous environment of the organism; wherein the one or more electrodes have a first form factor when enclosed in the outer casing and a second form factor following a dissolution of the outer casing, the first form factor is a form factor that is collapsed an increased amount relative to an amount that the second form factor is collapsed, and the second form factor is a form factor that is collapsed a decreased amount relative to an amount that the first form factor is collapsed.

Description:
CLAIM OF PRIORITY 
       [0001]    This application is a divisional application and claims the benefit of priority under 35 U.S.C. §121 to U.S. patent application Ser. No. 14/397,749, filed on Oct. 29, 2014, which is a U.S. National Stage Application under 35 U.S.C. §371 of and claims priority to International Application Number PCT/US2013/038787, filed on Apr. 30, 2013, which claims the benefit of priority under 35 U.S.C. §119(e) to provisional U.S. Patent Application No. 61/687,720, filed on Apr. 30, 2012, the entire contents of each of which are hereby incorporated by reference. 
     
    
     FIELD OF USE 
       [0002]    The present disclosure relates generally to an ingestible, electrical device, and specifically to an electrical device that stimulates tissues of a gastrointestinal tract of an organism. 
       BACKGROUND 
       [0003]    In gastric bypass surgery, a surgeon reduces the volume of the stomach by suturing off a large section of the stomach. A portion of the small intestine is then resected, and the remaining organ structure is ligated to the stomach. The result of this therapy is that the amount of food that patients may consume at one time is restricted and the allowed time for nutrient absorption is dramatically reduced. Although effective, this procedure produces debilitating and dangerous side effects such as malnutrition and death. 
       SUMMARY 
       [0004]    The present disclosure describes apparatus and methods relating to an ingestible, electrical device that stimulates tissues of a gastrointestinal tract of an organism. The device includes a stimulation electrode that provides a current, a voltage, or both to the tissue of the organism and a component for generating the current, the voltage, or both. 
         [0005]    In one aspect of the present disclosure, an ingestible, electrical device, comprises one or more electrodes comprising a biocompatible conducting material and a biocompatible insulating material; a generator connected to the one or more electrodes, with the generator being configured to deliver one or more of a current or a voltage across the one or more electrodes to stimulate one or more internal cells of an organism that ingests the ingestible, electrical device; and an outer casing enclosing the one or more electrodes and the generator, the outer casing configured to dissolve in an aqueous environment of the organism; wherein the one or more electrodes have a first form factor when enclosed in the outer casing and a second form factor following a dissolution of the outer casing, wherein the first form factor is a form factor that is collapsed an increased amount relative to an amount of that the second form factor is collapsed, and wherein the second form factor is a form factor that is collapsed a decreased amount relative to an amount that the first form factor is collapsed. 
         [0006]    Implementations of the disclosure can include one or more of the following features. The one or more electrodes may include a complementary anode cathode pair. The biocompatible conducting material may include at least one of a bioinert metal or a conducting polymer. The bioinert metal may include at least one of copper, gold, magnesium, silver, platinum, or zinc. The biocompatible insulating material may include a bioexcretable copolymer. The bioexcretable copolymer comprises at least one of polyester, polyanhydride, polyamide, polyether, polyphosphoester, polyorthoester, poly(ε-caprolactone) (PCL), or poly(ethylene glycol) (PEG). In some implementations, the generator includes a water-activated battery comprising one or more biocompatible materials. In some implementations, the generator includes a receiver coil and a rectifying circuit, each of the receiver coil and the rectifying circuit comprising one or more of a biodegradable material and a bioinert metal, the receiver coil configured to receive a near-field radio frequency signal, and the rectifying circuit configured to convert energy from the near-field radio frequency signal into the one or more of the current or the voltage. In some implementations, the generator includes one or more fuel cells. The generator may be configured to provide up to 0.1 mA of current for up to 90 minutes. The outer casing comprises at least one of gelatin, synthetic alphahydroxy polymer, crosslinked carbohydrate, polyester, polyanhydride, polyamide, polyether, polyphosphoester, polyorthoester, poly(□-caprolactone) (PCL), or poly(ethylene glycol) (PEG). A timing of the dissolution of the outer casing may be based on a thickness of and a degree of crosslinking within a material of the outer casing. The ingestible, electrical device may be an electrical device that stimulates one or more internal cells of a gastrointestinal tract of the organism. The first form factor of the one or more electrodes may be formed by configuring the one or more electrodes into a planar geometry and straining the one or more electrodes equibiaxially during deposition of the bioinert metal to promote thin film metallic buckling of the one or more electrodes. 
         [0007]    In another aspect of the present disclosure, a method performed by an ingestible, electrical device, comprises following a dissolution of an outer casing of the ingestible, electrical device, expanding a form factor of one or more electrodes included in the ingestible, electrical device; wherein at least one of the one or more electrodes comprises a biocompatible conducting material and a biocompatible insulating material; and wherein the dissolution occurs in an organism that ingests the ingestible, electrical device; activating, based on exposure to an aqueous environment in the organism, a generator of the ingestible, electrical device, the generator being connected to the one or more electrodes; following activation of the generator, delivering one or more of a current or a voltage across the one or more electrodes of the ingestible, electrical device; stimulating, based on delivery of the one or more of the current or the voltage, one or more internal cells of the organism that ingests the ingestible, electrical device; and ceasing to deliver the one or more of the current or the voltage across the one or more electrodes after a predetermined time; wherein the ingestible, electrical device may be configured to break down following a cease in delivery of the one or more of the current or the voltage. 
         [0008]    Implementations of the disclosure can include one or more of the following features. The method includes causing, based on stimulating, a decrease in an amount of intestinal motility in the organism relative to an amount of intestinal motility in the organism prior to stimulation. The ingestible, electrical device may be an electrical device that stimulates one or more internal cells of a gastrointestinal tract of the organism. The biocompatible conducting material may include at least one of a bioinert metal or a conducting polymer. The bioinert metal may include at least one of copper, gold, magnesium, silver, platinum, or zinc. The biocompatible insulating material may include a bioexcretable copolymer. The bioexcretable copolymer may include at least one of polyester, polyanhydride, polyamide, polyether, polyphosphoester, polyorthoester, poly(-caprolactone) (PCL) or poly(ethylene glycol) (PEG). In some implementations, the generator includes a water-activated battery comprising biocompatible materials. In some implementations, the generator includes a receiver coil and a rectifying circuit, each of the receiver coil and the rectifying circuit comprising one or more of a biodegradable material and a bioinert metal, the receiver coil configured to receive a near-field radio frequency signal, and the rectifying circuit configured to convert energy from the near-field radio frequency signal into the one or more of the current or the voltage. In some implementations, the generator includes one or more fuel cells. The generator may be configured to provide up to 0.1 mA of current for up to 90 minutes. The outer casing may include at least one of a gelatin material, a synthetic alphahydroxy polymer, a crosslinked carbohydrate, polyester, polyanhydride, polyamide, polyether, polyphosphoester, polyorthoester, poly(-caprolactone) (PCL), or poly(ethylene glycol) (PEG). A timing of the dissolution of the outer casing may be based on a thickness of and a degree of crosslinking within a material of the outer casing. 
         [0009]    In yet another aspect of the present disclosure, a gastroelectrical stimulation (GES) device, comprises one or more electrodes comprising gold deposited on a poly(ε-caprolactone) (PCL) and poly(ethylene glycol) (PEG) copolymer, the one or more electrodes configured to stimulate one or more internal cells of an organism that ingests the GES device to cause a decrease in an amount of intestinal motility in the organism relative to an amount of intestinal motility in the organism prior to stimulation; a water-activated battery comprising one or more biocompatible materials, the water-activated battery connected to the one or more electrodes, with the water-activated battery being configured to deliver a current of up to 0.1 mA for up to 90 minutes across the one or more electrodes to stimulate the one or more internal cells of the organism that ingests the GES device; and an outer casing comprising gelatin material in a capsule form, the outer casing enclosing the one or more electrodes and the water-activated battery, the outer casing configured to dissolve in an aqueous environment of the organism, with a timing of a dissolution of the outer casing based on a thickness and a degree of crosslinking within the gelatin material; wherein the electrodes have a first form factor when enclosed in the outer casing and a second form factor following the dissolution of the outer casing, wherein the first form factor is a form factor with an decreased amount of expansion relative to an amount of expansion of the second form factor, and wherein the second form factor is a form factor with an increased amount of expansion relative to an amount of expansion of the first form factor. 
         [0010]    The details of one or more implementations are set forth in the accompanying drawings and the description below. Other features, objects, and advantages will be apparent from the description, the drawings, and the claims. 
     
    
     
       BRIEF DESCRIPTION OF THE FIGURES 
         [0011]      FIG. 1  shows an example of an ingestible, electrical device in a condensed geometry packaged into an orally ingestible capsule. 
           [0012]      FIG. 2  shows the ingestible, electrical device of  FIG. 1  in an expanded geometry with deployed electrodes. 
           [0013]      FIG. 3  shows an ingestible, electrical device during different stages of operation. 
           [0014]      FIG. 4  shows a progression of an ingestible, electrical device through a gastrointestinal tract of an organism. 
           [0015]      FIG. 5  is a flowchart of operations performed by an ingestible, electrical device. 
           [0016]      FIG. 6  shows an ingestible, electrical device during different stages of fabrication. 
       
    
    
     DETAILED DESCRIPTION 
       [0017]    An ingestible, electrical device consistent with this disclosure may provide GES that can be administered orally. The ingestible, electrical device may include a stimulation electrode and a generator. The generator provides a current, a voltage, or both to the stimulation electrode to stimulate tissues of a gastrointestinal (GI) tract of an organism. In this context, stimulate includes a change in local properties based on a delivery of a voltage or a current. The device poses minimal risk to an organism, especially in the context of consuming the device for chronic management of obesity. While this disclosure describes an ingestible, electrical device in the context of coordinated simulation for obesity treatment, the apparatus and methods described in the present disclosure could also be used to treat a wide range of food metabolism pathologies. 
         [0018]    The ingestible, electrical device may be fabricated into a form factor that can be delivered orally and easily swallowed. The ingestible, electrical device may be fabricated from materials that are biodegradable and endogenous to an organism that ingests the device. Biodegradable devices reduce the risk associated with permanent devices including possible build-up and obstruction in the GI tract. Additionally, finite device lifetimes limit the potential toxicity profile associated with ingesting multiple devices over a sustained period of time. 
         [0019]      FIG. 1  shows an example of an ingestible, electrical device  100  in a condensed (consolidated, compressed, or collapsed) geometry packaged into an orally ingestible capsule. When packaged in an outer casing  101 , the device  100  may take the approximate shape of a rectangular prism with a length of 2 cm, a width of 0.8 cm, and a height of 0.8 cm, which is approximately the size of a large pill to be taken orally. The device  100  includes non-toxic materials that can be absorbed, metabolized, or excreted by an organism, e.g., a human or other animal, that ingests the device  100 .  FIG. 1  will be described in conjunction with  FIG. 2 , which shows the ingestible, electrical device  100  in an expanded (or swollen) geometry with deployed electrodes  102 ,  104 ,  106 , and  108 . In addition to the electrodes  102 ,  104 ,  106 , and  108 , the device  100  includes a generator  110 . 
         [0020]    The outer casing  101  encloses the device components, such as the electrodes  102 ,  104 ,  106 , and  108 , and the generator  110 . The outer casing  101  may protect the device components as the device  100  passes through a stomach and into a small intestine of an organism to ensure that the device  100  is not subjected to caustic environments. The outer casing may serve as a time protective retainer that keeps the electrodes  102 ,  104 ,  106 , and  108  in the condensed geometry until it reaches an area of interest within the GI tract of the organism. The material of the outer casing  101  can be engineered to dissolve within a precisely defined time line. After dissolution, the outer casing  101  can be absorbed and metabolized by the organism, or excreted by the organism with other non-absorbed device components. 
         [0021]    The outer casing  101  of the device  100  may include, for example, gelatin in a capsule form similar to those commonly used in existing oral pill formulations. The timing of the device expansion or swelling is controlled by engineering the thickness and degree of crosslinking within the gelatin layer. The outer casing  101  may include other suitable materials such as synthetic alpha-hydroxy polymers, crosslinked carbohydrates, polyesters, polyanhydride, polyamides, polyethers, polyphosphoesters, polyorthoesters, poly(ε-caprolactone) (PCL), or poly(ethylene glycol) (PEG). 
         [0022]    The electrodes  102 ,  104 ,  106 , and  108  have a condensed geometry when packaged in the outer casing  101  as shown in  FIG. 1 , and have an expanded or swollen geometry following dissolution of the outer casing  101  as shown in  FIG. 2 . The electrodes  102 ,  104 ,  106 , and  108  may include conducting materials  102   a,    104   a,    106   a,  and  108   a  such as bioinert metals or conducting polymers. Examples of bioinert metals include copper, gold, magnesium, silver, platinum, and zinc. 
         [0023]    The electrodes  102 ,  104 ,  106 , and  108  may be shape-memory electrodes fabricated from insulating materials  102   b,    104   b,    106   b,  and  108   b  such as copolymers based on poly(ε-caprolactone) (PCL), poly(ethylene glycol) (PEG), or a combination. PCL and PEG copolymers are thermally actuated to deploy the electrodes  102 ,  104 ,  106 , and  108  through expansion. PCL is biodegradable, and PEG is bioexcretable. PCL and PEG have both been extensively utilized in medical devices that have been FDA-approved for various applications as surgical materials, drug delivery systems, and scaffolds for tissue regeneration. The electrodes  102 ,  104 ,  106 , and  108  may include other suitable insulating materials such as polyesters, polyanhydride, polyamides, polyethers, polyphosphoesters, polyorthoesters, or a combination. Poly(ester amide) networks are both elastomeric and biodegradable. Biodegradable shape-memory elastomer electrodes synthesized from poly(ester amide) networks can be actuated through rubbery-glassy transitions via hydration to deploy the electrodes  102 ,  104 ,  106 , and  108  through swelling. Another example of a suitable material for the electrodes  102 ,  104 ,  106 , and  108  may include a superabsorbent polymer such as a hydrogel. In this example, the electrodes  102 ,  104 ,  106 , and  108  may deploy by swelling due to hydrolysis. Other mechanisms for deployment of the electrodes  102 ,  104 ,  106 , and  108  may be based on environmental factors such as changes in potential hydrogen (pH), changes in temperature, and other environmental factors. 
         [0024]    The generator  110  is connected to the electrodes  102 ,  104 ,  106 , and  108  to provide a current, a voltage, or both to the electrodes  102 ,  104 ,  106 , and  108 . The generator  110  may be composed of non-toxic biomaterials that can be absorbed as nutrients or excreted as waste. The generator  110  may be an on-board power supply for autonomous power generation or electronically active structures that are able to harvest externally applied energy which can be converted into electric current, voltage, or both for tissue stimulation. For example, the device  100  can be powered internally through a biocompatible or biodegradable battery or externally through near-field radiofrequency power transfer. The generator  110  may be configured to provide, for example, up to 0.1 mA of current for up to 90 minutes. The current or voltage may be programmed into arbitrary wave forms including constant, pulsed, and sinusoidal stimulation patterns. The current or voltage can be alternating or direct. 
         [0025]    In some implementations, the generator  110  may be a water-activated biodegradable battery. The low currents and voltages and limited stimulation times of the device  100  allow for incorporation of a small battery to serve as an on-board power supply. The geometry of the battery may be a high-aspect ratio cylinder similar to an oral pill. The battery may be stored in a dry state and coated in a biodegradable poly(L-lactide-co-glycolide) (PLGA) film that is semi-permeable to water. Battery operation is activated once water permeates the PLGA film and wets the aqueous cell. The initiation of battery function is engineered by controlling water permeation in the PLGA casing. Water permeability is controlled through PLGA composition and film geometry. Other suitable material compositions may be used in addition, or as an alternative, to the PLGA film. 
         [0026]    The battery may include a cathode, an anode, and a separator. The cathode may be fabricated from a compound based on sodium and manganese oxide. These cathode materials are able to shuttle sodium ions in aqueous cells with sufficient efficiencies. These cathode materials may be biocompatible. The anode of the battery may be fabricated from activated carbon. Activated carbon is non-toxic and may absorb toxins to replace liver function. The separator may be fabricated from microporous poly(L-lactide). The microporous structure may be achieved by phase inversion via rapid precipitation. The cathode and the anode of the battery are connected to the electrodes  102 ,  104 ,  106 , and  108 . 
         [0027]    In some implementations, the generator  110  may power the device is through external radiofrequency stimulation. The generator  110  may include a receiver coil and a rectifying circuit. The receiver coil receives a near-field radio frequency signal, e.g., an AC signal, that may be provided by a pack of external coils. The rectifying circuit converts the energy from the near-field radio frequency signal into electric current, e.g., a DC current, or voltage that is used for GES. The receiver coil and the rectifying circuit may include electronically active biodegradable materials, bioinert metals, or a combination. The generator  110  may be devices other than those described above. For example, the generator  110  may be one or more fuel cells that provide power to the device  100 . 
         [0028]      FIG. 3  shows an ingestible, electrical device, e.g., the device  100  of  FIG. 1  and  FIG. 2 , during different stages (a)-(d) of operation.  FIG. 3  will be described in conjunction with  FIG. 4 , which shows a progression of the device  100  through a gastrointestinal (GI) tract  400  of an organism during the different stages (a)-(d) of operation. The device  100  progresses through the GI tract  400  in a consolidated form factor via natural digestion. The device  100  can be selectively deployed and activated anywhere within the GI tract  400  through careful selection of materials and design of a geometry of the device  100 . For example, rapidly dissolvable packaging materials may be suitable for device deployment in a section of the small intestines  404 , e.g., the duodenum, while more slowly degrading materials may be suitable for device deployment in a section of the large intestines  406  such as the colon. 
         [0029]    In stage (a), the components of the device  100  are enclosed in and protected by the outer casing  101 , and the device  100  is inactive. In this context, inactive refers to not being functional as in the case when the generator  110  is not supplying power to the electrodes  102 ,  104 ,  106 , and  108  of the device  100 . The device  100  may be in stage (a) while the device  100  is passing through a stomach  402  and into a small intestine  404  of the organism. The outer casing  101  can be engineered to dissolve within a precisely defined time line. Precisely timed dissolution of the outer casing  101  liberates the device  100  in a predetermined location with the GI track  400 . 
         [0030]    The device  100  progresses to stage (b) after the device  100  passes through the stomach  402  and into the small intestine  404  of the organism. The outer casing  101  may have completely dissolved after passing through the stomach  404 . After dissolution of the outer casing  101 , the components of the device  100  are exposed to high salinity aqueous environments with elevated temperatures within the small intestine  404  of the organism. 
         [0031]    At stage (c), elevated temperatures and hydration initiate shape change routines in the electrodes  102 ,  104 ,  106 , and  108 . The electrodes  102 ,  104 ,  106 , and  108  deploy by expanding, unfurling, or swelling. Water diffuses across a polymeric casing of the generator  110  and initiates activation of the generator  110 . In the case where the generator  110  is a water-activated battery, hydration of the battery initiates activation of the wet cell. The battery transitions from an inactive dehydrated state into an active wet-cell battery. The generator  110  delivers a current, a voltage, or both  302  across complementary cathode anode electrode pairs, e.g., electrodes  102  and  104 , or electrodes  106  and  108 . Complementary cathode anode electrode pairs form intimate contact with the soft tissues in the small intestines  404  to stimulate the gastric tissues at the predetermined location of interest. GES may occur for approximately 60 to 120 minutes. In some implementations, the device  100  may continue to progress through the small intestines  404  during GES. In some implementations, the electrodes  102 ,  103 ,  106 , and  108  may stabilize and anchor the device  100  and retard passage of the device  100  through the GI tract  400  during GES. 
         [0032]    After stimulation, the device  100  ceases to function. The device  100 , including the electrodes  102 ,  104 ,  106 , and  108 , and the generator  110 , may degrade, or break down, and may lose mechanical resiliency at stage (d) as it progresses toward the end of the large intestine  406  of the GI tract  400 . The materials of the device  100  are absorbed or metabolized, or passed through the remainder of the GI tract  400  through active digestive motion and eventually excreted. The materials of the device  100  are selected such that they can be completely bioabsorbed by the organism or efficiently secreted without any negative health impacts. 
         [0033]      FIG. 5  is a flowchart of operations performed by an ingestible, electrical device. As described above, the process  500  includes expanding a form factor of one or more electrodes included in the device ( 502 ), activating a generator of the device based on exposure to an aqueous environment in the organism ( 504 ), and delivering a current, a voltage, or both across the electrodes of the device following activation of the generator ( 506 ). Based on delivery of the current, the voltage, or both across the electrodes, the device stimulates one or more internal cells of the organism ( 508 ), which may cause a decrease in an amount of intestinal motility in the organism relative to an amount of intestinal motility in the organism prior to stimulation. After a predetermined time of stimulation, the device ceases to deliver the current or the voltage across the electrodes. Following a cease in the delivery of the current or the voltage, the device is configured to degrade or break down. 
         [0034]      FIG. 6  shows an ingestible, electrical device during different stages of fabrication. The device may be fabricated entirely from non-toxic materials, biodegradable materials, or a combination of both. In some implementations, the device components are fabricated using materials that have been incorporated into FDA-approved medical devices. In some implementations, the device components are fabricated using materials that may be used in dietary supplements or other oral treatments such as detoxification. 
         [0035]    In the example of  FIG. 6 , insulating materials  602 , e.g., biodegradable shape-memory polymers synthesized from PCL and PEG composites, are injection molded at stage (a) into a final complex 3D geometry, as shown in stage (b). The form factor of the insulating materials  602  is programmed into a planar geometry at stage (c) to facilitate electrode integration. Materials such as poly(ester) amides can be integrated with an electrically conducting material  604 , e.g., a thin gold film. Gold is a bioinert metal that has been used in many medical devices and should pose no risk as a material that is consumed orally. Other suitable conducting materials include other bioinert metals, such as silver and platinum, and conducting polymers. Electrodes  603  are fabricated by thermal deposition or evaporation of the conducting material  604  and patterned using shadow masks at stage (d). At stage (e), the electrodes  603  may be processed into serpentine geometries to enable high density packaging into an outer gelatin capsule. For example, the insulating materials  602  in the planar form factor may be strained equibiaxially during deposition of the conducting material  604  in order to induce thin film buckling. Evaporating rigid films on pre-strained substrates can produce micron-scale buckling features. These corrugated features may help maintain electrical conductivity during deformation of the biodegradable elastomeric electrodes  602  during both packaging and deployment, e.g., during flexion and hydration-induced swelling in the GI tract. The electrodes  603  are connected to a generator  605 . 
         [0036]    A number of implementations have been described. Nevertheless, various modifications can be made without departing from the spirit and scope of the processes and techniques described herein. In addition, the processes depicted in the figures do not require the particular order shown, or sequential order, to achieve desirable results. In addition, other steps can be provided, or steps can be eliminated, from the described processes, and other components can be added to, or removed from, the describe apparatus and systems. Accordingly, other embodiments are within the scope of the following claims.