Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/07—Endoradiosondes
• • A—HUMAN NECESSITIES
  • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
  • A23P—SHAPING OR WORKING OF FOODSTUFFS, NOT FULLY COVERED BY A SINGLE OTHER SUBCLASS
  • A23P20/00—Coating of foodstuffs; Coatings therefor; Making laminated, multi-layered, stuffed or hollow foodstuffs
  • A23P20/20—Making of laminated, multi-layered, stuffed or hollow foodstuffs, e.g. by wrapping in preformed edible dough sheets or in edible food containers
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/06—Devices, other than using radiation, for detecting or locating foreign bodies ; Determining position of diagnostic devices within or on the body of the patient
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/07—Endoradiosondes
  • A61B5/073—Intestinal transmitters
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/42—Detecting, measuring or recording for evaluating the gastrointestinal, the endocrine or the exocrine systems
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/48—Other medical applications
  • A61B5/4833—Assessment of subject's compliance to treatment
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/48—Other medical applications
  • A61B5/4836—Diagnosis combined with treatment in closed-loop systems or methods
  • A61B5/4839—Diagnosis combined with treatment in closed-loop systems or methods combined with drug delivery
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/68—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
  • A61B5/6846—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive
  • A61B5/6847—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive mounted on an invasive device
  • A61B5/6861—Capsules, e.g. for swallowing or implanting
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/68—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
  • A61B5/6846—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive
  • A61B5/6867—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive specially adapted to be attached or implanted in a specific body part
  • A61B5/6871—Stomach
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/68—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
  • A61B5/6846—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive
  • A61B5/6867—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive specially adapted to be attached or implanted in a specific body part
  • A61B5/6873—Intestine
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
  • A61J3/00—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
  • A61J3/007—Marking tablets or the like
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
  • A61J3/00—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
  • A61J3/06—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms into the form of pills, lozenges or dragees
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
  • A61K9/0097—Micromachined devices; Microelectromechanical systems [MEMS]; Devices obtained by lithographic treatment of silicon; Devices comprising chips
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
  • A61K9/4816—Wall or shell material
  • A61K9/4825—Proteins, e.g. gelatin
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
  • A61K9/4833—Encapsulating processes; Filling of capsules
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
  • G01N33/15—Medicinal preparations ; Physical properties thereof, e.g. dissolubility
• • G—PHYSICS
  • G05—CONTROLLING; REGULATING
  • G05F—SYSTEMS FOR REGULATING ELECTRIC OR MAGNETIC VARIABLES
  • G05F1/00—Automatic systems in which deviations of an electric quantity from one or more predetermined values are detected at the output of the system and fed back to a device within the system to restore the detected quantity to its predetermined value or values, i.e. retroactive systems
• • H—ELECTRICITY
  • H01—ELECTRIC ELEMENTS
  • H01M—PROCESSES OR MEANS, e.g. BATTERIES, FOR THE DIRECT CONVERSION OF CHEMICAL ENERGY INTO ELECTRICAL ENERGY
  • H01M6/00—Primary cells; Manufacture thereof
• • H—ELECTRICITY
  • H05—ELECTRIC TECHNIQUES NOT OTHERWISE PROVIDED FOR
  • H05K—PRINTED CIRCUITS; CASINGS OR CONSTRUCTIONAL DETAILS OF ELECTRIC APPARATUS; MANUFACTURE OF ASSEMBLAGES OF ELECTRICAL COMPONENTS
  • H05K13/00—Apparatus or processes specially adapted for manufacturing or adjusting assemblages of electric components
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/0002—Remote monitoring of patients using telemetry, e.g. transmission of vital signals via a communication network
  • A61B5/0031—Implanted circuitry
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
  • A61J2200/00—General characteristics or adaptations
  • A61J2200/30—Compliance analysis for taking medication
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
  • A61J2205/00—General identification or selection means
  • A61J2205/60—General identification or selection means using magnetic or electronic identifications, e.g. chips, RFID, electronic tags
• • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
  • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
  • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
  • Y10S128/00—Surgery
  • Y10S128/903—Radio telemetry
• • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
  • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
  • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
  • Y10T29/00—Metal working
  • Y10T29/49—Method of mechanical manufacture
  • Y10T29/49002—Electrical device making
  • Y10T29/49108—Electric battery cell making
• • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
  • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
  • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
  • Y10T29/00—Metal working
  • Y10T29/49—Method of mechanical manufacture
  • Y10T29/49002—Electrical device making
  • Y10T29/49117—Conductor or circuit manufacturing
  • Y10T29/49124—On flat or curved insulated base, e.g., printed circuit, etc.

Definitions

• Examples of such ingestible devices are ingestible electronic capsules which collect data as they pass through the body, and transmit the data to an external receiver system.
• An example of this type of electronic capsule is disclosed in U.S. Patent No. 5,604,531 lddan et al., which describes what is called an in vivo video camera.
• the swallowable capsule includes a camera system and an optical system for imaging an area of interest onto the camera system.
• the transmitter transmits the video output of the camera system and the reception system receives the transmitted video output.
• U.S. Patent No. 7,009,634 also issued to lddan et al discloses an ingestible imaging device that obtains images from within body lumens or cavities.
• the electronic circuit components of the device are enclosed by an inert indigestible housing (e.g. glass housing) that passes through the body internally.
• U.S. Patent No. 6,800,060 issued to Marshall discloses an ingestible data recorder capsule medical device.
• the electronic circuits of the disclosed device e.g. sensor, recorder, etc.
• the electronic circuits are housed in a capsule made of inert materials, and therefore ingestible and passable through the digestive tract without being consumed by the body.
• the electronic circuits are protected in a housing or capsule that prevents damage to the device's electronic circuits during the process of ingestion and elimination in the human body.
• RFID tags for use in drug ingestion monitoring applications.
• the RFID tags disclosed in this application are simple antenna structures that are configured to break down during transit through the body.
• the present invention provides for robust ingestible circuitry, where the components of the ingestible circuitry are ingestible, and in some instances digestible.
• the ingestible circuitry is made up of ingestible, and even digestible, components, the ingestible circuitry results in little, if any, unwanted side effects, even when employed in chronic situations.
• the ingestible circuitry is particularly suited for use in signal identifiers, e.g., as may be found in ingestible event markers (IEMs), which include pharma-informatics enabled compositions.
• Embodiments of ingestible circuitry of the invention include a solid support of an ingestible material, which support has on a surface thereof one or more electronic components.
• Components that may be present on the surface of the support may vary, and include but are not limited to: logic and/or memory elements, e.g., in the form of an integrated circuit; a power device, e.g., battery, fuel cell or capacitor; an effector, e.g., sensor, stimulator, etc.; a signal transmission element, e.g., in the form of an antenna, electrode, coil, etc.; a passive element, e.g., an inductor, resistor, etc.
• the one or more components on the surface of the support may be laid out in any convenient configuration. Where two or more components are present on the surface of the solid support, interconnects may be provided. All of the components and the support of the ingestible circuitry are ingestible, and in certain instances digestible. BRIEF DESCRIPTION OF THE FIGURES
• FIG. 1 shows diagrammatically an ingestible identifier that includes ingestible circuitry in accordance with the invention.
• FIGS. 2A to 2D provide views of assembly of an ingestible identifier that includes ingestible circuitry in accordance with the invention.
• FIGS. 3A and 3B provide views of assembly of an ingestible identifier that includes ingestible circuitry in accordance with the invention.
• FIG. 4 provides a view of assembly of an ingestible identifier that includes ingestible circuitry in accordance with the invention.
• FIG. 5 provides a view of assembly of an ingestible identifier that includes ingestible circuitry in accordance with the invention.
• FIGS. 6A and 6B provide views of assembly of an ingestible identifier that includes ingestible circuitry in accordance with the invention.
• FIGS. 7A to 7B provide views of a bifurcated laminate process employed to fabricate devices according to one embodiment of the invention.
• the present invention provides for ingestible circuitry, where the components of the circuitry are ingestible, and in some instances digestible. As the ingestible circuitry is made up of ingestible, and even digestible, components, the ingestible circuitry results in little, if any, unwanted side effects, even when employed in chronic situations.
• Embodiments of ingestible circuitry of the invention include a solid support of an ingestible material, which support has on a surface thereof one or more electronic components.
• Components that may be present on the surface of the support may vary, and include but are not limited to: logic and/or memory elements, e.g., in the form of an integrated circuit; a power device, e.g., battery, fuel cell or capacitor; an effector, e.g., sensor, stimulator, etc.; a signal transmission element, e.g., in the form of an antenna, electrode, coil, etc.; a passive element, e.g., an inductor, resistor, etc.
• the one or more components on the surface of the support may be laid out in any convenient configuration. Where two or more components are present on the surface of the solid support, interconnects may be provided.
• the ingestible circuitry is particularly suited for use in signal identifiers, e.g., as may be found in ingestible event markers and pharma-informatics enabled compositions.
• One example includes use of the ingestible circuitry in association with a specific pharmaceutical product, such as a pill, to determine when a patient takes the pharmaceutical product. As the pill is consumed, the ingestible circuit is activated and generates a signal that is detected thereby signifying that the pharmaceutical product has been taken by a patient.
• Ingestible circuitry of the invention includes a solid support fabricated from an ingestible material, and one or more electronic components displayed on a surface thereof. Where two or more components are present on a given solid support, conductive interconnecting elements are also present that electrically couple the two or more components. A variety of different types of components may be present on the support, as reviewed in greater detail below. In addition, one or more optional elements, such as a protective layer, etc., may be provided.
• Ingestible circuitry of the invention can be a standalone unit or it can be incorporated into another structure, e.g., an ingestible identifier, such as may be found in an ingestible event marker, including a pharma-informatics enabled pharmaceutical composition.
• an ingestible identifier such as may be found in an ingestible event marker, including a pharma-informatics enabled pharmaceutical composition.
• circuitry of the invention is ingestible, where the disparate components of the circuitry are fabricated from ingestible materials.
• one or more of the ingestible materials of the circuits are digestible materials.
• the amounts of the materials are below chronic ingestion limits if the circuitry is present in a device that is going to be ingested chronically. If the circuitry is incorporated into a device that is going to be ingested less frequently, materials may be chosen based on the anticipated dosage schedule.
• elements of the ingestible circuitry of the invention include a solid support, one or more electronic components, and interconnects, among other elements.
• the solid support is the structure on which all of the components are present.
• the solid support is fabricated from an ingestible material, where the material is a dielectric or insulating material. It can be fabricated from a variety of materials. Materials that provide mechanical strength and may be employed as an insoluble component of the solid support include, but are not limited to: Ethyl cellulose (e.g. Hercules Aqualon or Dow Ethocel), cellulose acetate, Agar, Gelatin.
• Insoluble materials of interest include ethylcellulose, a copolymer of acrylic acid and methacrylic acid esters, having from about 5 to 10% functional quaternary ammonium groups, polyethylene, polyamide, polyvinylchloride, polyvinyl acetate and any mixtures thereof.
• Fillers such as, starch, glucose, lactose, inorganic salts such as sodium or potassium chloride, carbonates, bicarbonates, sulfates, nitrates, silicates (e.g., magnesium silicate) and alkali metals phosphates and oxides (e.g., titanium dioxide, magnesium oxide), may also be present.
• Soluble materials that may be employed, e.g., as disintegrating agents, in the solid support include, but are not limited to: Hydroxypropyl cellulose, hydroxyethylcellulose, carboxymethylcellulose, croscarmellose, hypromellose, hydroxypropyl methyl cellulose, methyl cellulose, Polysaccharides (starch, different sugars); Polyvinyl alcohol; Gums (guar, xanthan, acacia); Alginates (sodium or calcium alginate); povidone; etc.
• Plasticizing agents e.g., Dibutyl sebacate, triacetin, triethyl citrate, polyethylene glycol, polyethylene oxide.
• Soluble materials of interest include proteins, polysaccharides, polyacrylates, hydrogels, polyvinyl alcohol, polyvinyl pyrrolidone, and derivatives of such polymers.
• plasticizers may be present, where plasticizers make it easier to process and modulate the strength so that it is not stiff and brittle.
• surfactants are also of interest.
• Environmentally sensitive materials may also be present in the support, such as environmentally sensitive polymers, e.g., temperature sensitive polymers, ph sensitive polymers (e.g., Polymethacrylates (e.g.
• the support is fabricated from a foodstuff which has suitable properties.
• Foodstuffs of interest include, but are not limited to: soy, whey, wheat glutein, rice starch, tapioca starch, rice paper, nori, corn chips, potato, pasta, filo, fruit roll-ups, haw flakes, crackers, gelatin and gummy.
• the solid supports can be fabricated via any convenient protocol, such as through deposition via a number of methods such as solvent cast, or melt extrusion.
• Also present in ingestible circuitry is one or more conductive elements which serve to interconnect two or more distinct components on a surface(s) of the support.
• this conductive element e.g., interconnect or wire
• this conductive element is a thin layer or strip of a homogenous conductive and ingestible material, such as gold, silver, graphite, titanium, copper, etc.
• the material making up the conductive element may be any material whose total amount is below chronic ingestion limits (i.e., how often one is ingesting the ingestible device) where the conductivity is within a desired range. Table 1 below provides examples of ranges.
• the conductive elements can be deposited on a surface of the support to provide interconnection between two or more components as a homogeneous layer, for example a layer of gold.
• Any convenient deposition protocol may be employed, such as but not limited to: evaporation, plating, electrolysis plating, galvanic deposition, screen or ink jet printing, or other thin layer deposition techniques.
• a lamination method may be employed, where various elements are positioned as sheets.
• a decal transfer process may be employed, where each of the distinct elements is on a separate backing layer. The distinct elements are transferred to the solid support, and then the backing layer is removed. With each of the above protocols, a patterning technique may be employed.
• the choice of patterning technique will depend on the choice of deposition process and the dimensional control required of the final pattern, for example evaporation or plating is very compatible with photo lithography.
• laser patterning might be employed, e.g., where a layer is deposited and the unwanted portions are cut out.
• purely additive techniques such as ink jet or screen printing, are employed.
• the conductive element can be a heterogenous material that is a paste or an ink.
• a suspension of a conductive filler of the conductive materials e.g., gold, silver, graphite, etc.
• an ingestible binder material such as a polymer, a thermoset or thermoplastic polymer
• This heterogenous material can contain other polymeric components such as plasticizers, surfactants to make the ink and the paste flow better, be more processable etc.
• the conductive element is an isotropic conductive film, e.g., a film of inert particles, such as of a material like glass, that have been coated with a conductive material, e.g., a metal.
• Electrical connection between the conductive element and components on the support may be achieved in a number of different ways.
• interconnects and various components may be positioned on a surface of the solid support, and a layer of conductive material that covers the disparate components and conductive elements can be deposited in a manner that provides the desired connection.
• a layer of conductive material that covers the disparate components and conductive elements can be deposited in a manner that provides the desired connection.
• ingestible conductive glues, pastes and adhesives may be employed.
• of interest is the use of a combination of two (or more) glues, where one of the glues provides for desired conductive properties and one of the glues provides mechanical strength.
• mechanical attachment protocols such as pressing different components together, e.g., where the components have suitable shape interfaces that make it easier for them to bond under mechanical force, pressure, and temperature, may be employed.
• laser welding, sonic welding, etc. The components can be immobilized relative to a surface of the solid support by mechanically holding the components on to the solid support, e.g., via deposition of a conductive overlay, as reviewed above, by way of a glue, such as a thermoplastic glue that physically holds items in place or thermosetting glue that is cross linked.
• the ingestible circuitry of the invention also includes one or more electronic components.
• Electrical components of interest include, but are not limited to: logic and/or memory elements, e.g., in the form of an integrated circuit; a power device, e.g., battery, fuel cell or capacitor; an effector, e.g., sensor, stimulator, etc.; a signal transmission element, e.g., in the form of an antenna, electrode, coil, etc.; a passive element, e.g., an inductor, resistor, etc.
• the various components may be produced on a surface of a solid support using a variety of different protocols. For example, where the components are electrode elements that make up a battery which is activated upon contact with stomach fluid, e.g., as described below, the battery components can be deposited directly onto the solid support.
• a magnesium layer can be evaporated onto a surface of the solid support, where the solid support is fabricated from a material(s) that withstands the temperature and pressure that occurs during that deposition process.
• the different components of the electrodes can be deposited onto a conductor layer that is then attached to the solid support.
• a conductor layer For example, one can have a thin sheet of gold, and a layer of CuCI can be deposited onto the gold, with the resultant product being attached to the solid support.
• the different layers can also be deposited via an ink or a paste.
• a structure of CuCI deposited on gold can be broken up into small particles, and an ink material can be fabricated from the particles.
• the resultant ink material can be used to either print or silk screen the desired electrode pattern onto the solid support.
• protocols that employ screen printing or ink jet printing techniques.
• an unpatterned slurry is deposited.
• "roll-to- roll" or "continuous web” protocols are employed.
• the ingestible circuitry includes a coating layer.
• the purpose of this coating layer can vary, e.g., to protect the circuitry, the chip and/or the battery, or any components during processing, during storage, or even during ingestion.
• this coating layer can vary, e.g., to protect the circuitry, the chip and/or the battery, or any components during processing, during storage, or even during ingestion.
• a coating on top of the circuitry that is ingestible but does not dissolve until the device is finished doing its transmission may be provided.
• coatings that are designed to protect the ingestible circuitry during storage, but dissolve immediately during use.
• coatings that dissolve upon contact with an aqueous fluid e.g., stomach fluid.
• protective processing coatings that are employed to allow the use of processing steps that would otherwise damage certain components of the device.
• the product needs to be diced. However, the dicing process can scratch off the battery material, and also there might be liquid involved which would cause the battery materials to discharge or dissolve.
• a protective coating on the battery that prevents mechanical or liquid contact with the battery component during processing can be employed. Another purpose of the edible coatings would be to control the activation of the device.
• an edible coating that sits on the battery electrodes and takes a certain period of time, e.g., five minutes, to dissolve upon contact with stomach fluid may be employed.
• the coating can also be an environmentally sensitive coating, e.g., a temperature or pH sensitive coating, or other chemically sensitive coating that provides for dissolution in a controlled fashion and allows one to activate the device when desired. Coatings that survive the stomach but dissolve in the intestine are also of interest, e.g., where one desires to delay activation until the device leaves the stomach.
• An example of such a coating is a polymer that is insoluble at low pH, but becomes soluble at a higher pH.
• pharmaceutical formulation protective coatings e.g., a gel cap liquid protective coating that prevents the circuit from being activated by liquid of the gel cap.
• Another component present in certain embodiments of the ingestible circuit is an activation mechanism, e.g., where the activation mechanism is distinct from the power source (e.g., battery).
• an alternative activation element is a patch of circuit that closes upon contact with fluid and activates the device.
• Another example is the reactive removal of a patch of the circuit that, before it is removed, keeps the circuit from operating.
• ingestible circuitry devices in accordance with the invention may be fabricated in a variety of different ways. Any of a variety of different protocols may be employed in manufacturing the circuitry structures and components thereof. For example, molding, deposition and material removal, e.g., planar processing techniques, such as Micro-Electro-Mechanical Systems (MEMS) fabrication techniques, including surface micromachining and bulk micromachining techniques, may be employed.
• MEMS Micro-Electro-Mechanical Systems
• Deposition techniques that may be employed in certain embodiments of fabricating the structures include, but are not limited to: electroplating, cathodic arc deposition, plasma spray, screen or ink jet printing, sputtering, e-beam evaporation, physical vapor deposition, chemical vapor deposition, plasma enhanced chemical vapor deposition, etc.
• Material removal techniques included, but are not limited to: reactive ion etching, anisotropic chemical etching, isotropic chemical etching, sacrificial lift-off etching, planarization, e.g., via chemical mechanical polishing, laser ablation, electronic discharge machining (EDM), etc. Also of interest are lithographic protocols.
• 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 nos. PCT/US2006/016370; PCT/ US2007/022257; PCT/US2007/082563; PCT/US2008/052845; PCT/ US2008/053999; and PCT/US2008/077753; the disclosures of which are herein incorporated by reference.
• a bifurcated laminate process for preparing a device made up of ingestible circuitry.
• a laminate component is made separate from a circuitry component, allowing greater freedom in terms of processing protocols than may be employed to fabricate the disparate components together, since protocols may be employed to fabricate a first component that cannot be used to fabricate the other, and vice versa.
• the circuitry and laminate components are combined into a single device following separate fabrication of the two components. To combine the two components, any convenient protocol may be employed.
• the circuitry component is fixed into receiving feature of the laminate component, and fixed in place with a suitable adhesive, such as a conductive adhesive.
• FIG. 7A an initial laminate sheet which includes battery elements and a virtual dipole element (e.g., skirt) of an ingestible event marker is shown being prepared using a "continuous web” or "roll-to-roll process”.
• a virtual dipole element e.g., skirt
• the initial laminate sheet is characterized by having exposed battery layers, e.g., upper and lower exposed battery layers, and includes a first battery layer 708, e.g., CuCI layer (e.g., produced by evaporation, electrodeposition, slurry deposition, silkscreen, or inkjet, etc.), a second virtual dipole layer 710 positioned on top of the battery layer (i.e., skirt), a third current collector layer 712, e.g., Au, Cu, or graphite, etc., which may be a sheet or printed on the skirt, on top of the virtual dipole layer, and a fourth battery layer 714, e.g., Mg foil.
• a first battery layer 708 e.g., CuCI layer (e.g., produced by evaporation, electrodeposition, slurry deposition, silkscreen, or inkjet, etc.)
• a second virtual dipole layer 710 positioned on top of the battery layer (i.e., skirt)
• one or more of the layers can be made separately before lamination, so each process need not be compatible with all the layers e.g., current collector can be graphite-based, made with a high temperature process, which may be incompatible with processes and/or materials used to fabricate the other layers. Layers may be glued together with edible, cellulose adhesive or other safe pressure sensitive adhesives (including but not limited to, silicon materials, etc.).
• the circuitry component may be fabricated using any convenient protocol, e.g., as summarized above.
• a hole or passage 720 configured to receive the circuitry component
• circuitry component 722 e.g., integrated circuit (IC)
• IC integrated circuit
• conductive adhesives may be employed, e.g., a polymer filled with conductive particles or a reactive (2-part) glue.
• the conductivity of the adhesive may be moderate.
• the adhesive can be covered with a final layer of insulating adhesive.
• a pre-punched lower laminate is employed.
• the IC is placed onto a pre-punch hole, where prior to placement, the sheet may be covered with a pressure sensitive adhesive material that is removed prior to chip placement during punching but is removed prior to chip placement.
• a second laminate is applied over the top of the chips and then opened, e.g., with a laser, over the chips and the top conductor (e.g., battery material) is additively applied, e.g., by screen printing.
• a final non-conductive layer, such as treated paper or plastic, is used in a roll-to-roll process after this step to isolate the two sides of the battery before the IEMs are finally punched out of the roll for assembly into tablets or capsules.
• a disc shaped device 740 e.g., shown by dashed lines in FIG. 7B, is punched out to produce the desired IEM.
• Ingestible circuitry of the invention finds use in a variety of different types of devices.
• One example of a device that can include ingestible circuitry of the invention is an ingestible identifier.
• Ingestible identifiers are described in PCT application serial no. PCT/US2006/016370 published as WO/2006/116718; PCT application serial no. PCT/US2007/082563 published as WO/2008/052136; PCT application serial no. PCT/US2007/024225 published as WO/2008/063626; PCT application serial no. PCT/US2007/022257 published as WO/2008/066617; PCT application serial no.
• PCT/US2008/052845 published as WO/2008/095183; PCT application serial no. PCT/US2008/053999 published as WO/2008/101 107; PCT application serial no. PCT/US2008/056296 published as WO/2008/1 12577; PCT application serial no. PCT/US2008/056299 published as WO/2008/1 12578; PCT application serial no. PCT/US2008/077753 published as WO2009/042812; PCT application serial no. PCT/US2008/085048 published as WO 2009/070773; and PCT application serial no. PCT/US2009/36231 ; as well as pending United States application serial nos. 12/126,792 and 12/126,798; the disclosures of which are incorporated herein by reference.
• An example of such an ingestible identifier is an identifier that includes battery.
• the battery includes, when completed, a cathode, an anode, and an electrolyte, where the electrolyte component is provided by a physiological fluid, e.g., stomach acid.
• a physiological fluid e.g., stomach acid.
• the stomach fluid acts as the electrolyte component of the battery. Completion of the battery powers the circuitry of the identifier which, in turn broadcasts a detectable signal.
• Identifiers of interest include two dissimilar electrochemical materials which constitute the two electrodes (e.g., anode and cathode) of the battery.
• the electrode materials When the electrode materials are exposed and come into contact with the body fluid, such as stomach acid or other types of fluid (either alone or in combination with a dried conductive medium precursor), a potential difference, that is, a voltage, is generated between the electrodes as a result of the respective oxidation and reduction reactions incurred to the two electrode materials.
• a voltaic cell, or battery can thereby be produced.
• such batteries are configured such that when the two dissimilar materials are exposed to the target site, e.g., the stomach, the digestive tract, etc., during the physical and chemical erosion of the composition in which the signal generation element is present, a voltage is generated.
• the two dissimilar materials in an electrolyte are at different potentials.
• copper and zinc when put into a cell have different potentials.
• gold and magnesium have different potentials.
• a potential difference between the two dissimilar materials is generated.
• 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.
• FIG. 1 provides a diagrammatic representation of an ingestible identifier 10 having a battery that is completed by stomach fluid.
• First and second electrode materials (12 and 13) are present in an ionic solution 16 (which may be made up of target site fluid alone or target site fluid combined with a dried conductive medium precursor).
• This configuration creates a low voltage (V-) and a high voltage (V+) as applied to an electronic circuit 14.
• V- low voltage
• V+ high voltage
• the polarity of the electrodes are determined by the connection needs of the electronic circuit 14 and the design as illustrated is just one embodiment. Thus, it will be apparent to one skilled in the art that the scope of the present invention includes reversal of the polarity of the electrodes, such that electrode 13 represents the low voltage and electrode 12 represents high voltage.
• the two outputs of that electronic circuit 14 are EO 11 and E1 15, which are the signal-transmission electrodes on the top surface.
• Electrodes 12 and 13 can be made of any two materials appropriate to the environment in which the identifier 10 will be operating.
• the active materials are any pair of materials with different electrochemical potentials, as long as they are ingestible, e.g., as described above.
• electrodes 12 and 13 may be made of a noble metal (e.g., gold, silver, platinum, palladium or the like) so that they do not corrode prematurely.
• 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 CuCI or CuI).
• any pairing of substances - metals, salts, or intercalation compounds - with suitably different electrochemical potentials (voltage) and low interfacial resistance are suitable.
• t Protected anodes 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, CA), 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).
• ttDissolved oxygen can also serve as a cathode.
• the dissolved oxygen in the bodily fluids would be reduced to OH- at a suitable catalytic surface such at Pt or gold.
• a suitable catalytic surface such at Pt or gold.
• dissolved hydrogen in a hydrogen reduction reaction dissolved hydrogen in a hydrogen reduction reaction.
• 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.
• the electrode materials are cuprous iodine (CuI) or cuprous chloride as the cathode and magnesium (Mg) metal or magnesium alloy as the anode.
• CuI cuprous iodine
• Mg magnesium
• Embodiments of the present invention use electrode materials that are not harmful to the human body.
• the batteries have a small form factor. Batteries may be about 20 mm 3 or smaller, e.g., about 10 mm 3 or smaller, such as 1.0 mm 3 or smaller, including 0.1 mm 3 or smaller, including 0.02 mm 3 or smaller.
• 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.
• the ingestible identifier 10 uses the voltage potential difference to power up electronic circuit 14.
• the electronic circuit 14 modulates conductance to create a unique and identifiable current signature.
• the battery has a laminate structure.
• a laminate process may be employed to fabricate ingestible circuitry in accordance with the invention.
• FIGS. 2A to 2D An example of such a laminate process is illustrated in FIGS. 2A to 2D.
• structure 21 is made up of circular metallic foil 22, e.g., gold, and has patterned areas of an electrode material, such as CuCI, patterned on its surface in the form of four distinct quadrants 24.
• the CuCI regions 24 may be produced on the surface of the foil via any convenient protocol, such as evaporation.
• area 26 which lacks electrode material and is configured to receive an integrated circuit.
• FIG. 1 In FIG.
• structure 21 placed onto solid support 23, which support is made of an ingestible material, e.g., as described above.
• Structure 21 may be placed onto support 23 in a manner such that the two components are stably associated with each other, e.g., by press-fitting the structure 21 onto support
• FIGS. 2A and 2B illustrate a protocol in which structure 21 is produced before placement on support 23, in another embodiment the metallic foil 22 is first placed on support 23. Following placement of metallic foil 22 on support 23, the patterned areas of electrode material
• FIG. 2C integrated circuit 25 is positioned in area 26 and connected to metallic foil 22.
• a cover layer 27 e.g., fabricated from the same material as the support
• electrode cutout areas 28 is stably positioned (e.g., with an ingestible adhesive) over structure 21 to produce a final ingestible circuit device that includes a solid support, an integrated circuit and four distinct surface electrodes.
• the metallic foil layer 22 serves as the conductive interconnect between the different electronic components, i.e., the integrated circuit and electrodes, that are positioned on the surface of the support.
• FIG. 3A illustrates another embodiment of a laminate process that may be employed to construct an ingestible circuit device of the invention.
• structure 30 has been produced by first providing a release layer 31 on a backing layer 32.
• Metallic layer (e.g., gold) 33 has been deposited on the surface of release layer 31.
• electrode material 34 e.g., CuCI
• insulating layer 35 is positioned over electrode layer 34, which insulating layer may have cutout regions (not shown), e.g., as described in connection with the description of FIGS. 2A to 2D.
• FIG. 3B an integrated circuit 36 having a layer of a second electrode material 37, e.g., Mg, on a surface thereof, is positioned in ingestible support 38.
• the release layer 31 and backing layer 32 are removed from structure 30, providing exposed metallic layer 33.
• This exposed metallic layer 33 is then positioned over circuit 36 and support 38 to yield the final desired device.
• FIG. 4 illustrates a transfer protocol that may be employed to fabricate ingestible circuits in accordance with the invention.
• a circuit structure 40 that includes integrated circuit 41 connected to five different electrodes 42 via interconnecting conductive lines 43 is first produced on a removable backing 44.
• circuit structure 40 After production of circuit structure 40, backing 44 is removed and the circuit structure 44 is positioned on the surface of ingestible support 45.
• the protocol illustrated in FIG. 4 may be employed in processes where parameters of circuit structure production (e.g., chemicals, temperatures, pressures) are incompatible with the solid support material.
• FIG. 5 illustrates a variation in which a conductive ink is employed to provide conductive interconnects between different components of an ingestible circuit device.
• ingestible support 51 has displayed on its surface four different electrodes (made up of electrode material) 52. Positioned at a center region of support 51 are four contact pads 53. Interconnecting each electrode to a contact pad is a line of conductive ink material 54.
• an integrated circuit is bonded to pads 53 and then a layer of protection material is positioned over the surface leaving exposed electrode elements, analogous to that shown in FIG. 2D.
• laser patterning may be employed during fabrication of ingestible circuits of the invention, e.g., as illustrated in FIGS. 6A and 6B.
• a blanket (i.e., non-patterned) layer of metal 61 is deposited on a surface of an ingestible support 62.
• integrated circuit 63 Positioned on a portion of metal layer 61 is integrated circuit 63.
• laser patterning is employed to remove portions of metal layer 61 to produce antenna structure 64 and 65 on surface of support 62.
• Ingestible identifiers that include ingestible circuitry of the invention find use in a variety of different applications.
• IEMs ingestible event markers
• PCT/US2006/016370 published as WO/2006/1 16718
• PCT application serial no. PCT/US2007/082563 published as WO/2008/052136
• PCT application serial no. PCT/US2007/024225 published as WO/2008/063626
• PCT application serial no. PCT/US2007/022257 published as WO/2008/066617
• PCT application serial no. PCT/US2008/052845 published as WO/2008/095183
• Therapeutic applications of ingestible identifiers are embodiments where, at least in some instances, the identifier is associated with a pharmaceutical composition.
• Medical embodiments of the present invention provide the clinician an important new tool in their therapeutic armamentarium: automatic detection and identification of pharmaceutical agents actually delivered into the body.
• the applications of this new information device and system are multi-fold. Applications include, but are not limited to: (1 ) monitoring patient compliance with prescribed therapeutic regimens; (2) tailoring therapeutic regimens based on patient compliance; (3) monitoring patient compliance in clinical trials; (4) monitoring usage of controlled substances; and the like. Each of these different illustrative applications is reviewed in greater detail in PCT application serial no.
• PCT/US2008/056299 published as WO/2008/1 12578
• PCT application serial no. PCT/US2008/077753 published as WO2009/042812
• PCT application serial no. PCT/US2008/085048 published as WO 2009/070773
• PCT application serial no. PCT/US2009/36231 as well as pending United States application serial nos. 12/126,792 and 12/126,798; the disclosures of which are incorporated herein by reference.

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