Evaluation of gastrointestinal function using portable electroviscerography systems and methods of using the same

Information

  • Patent Grant
  • 8583227
  • Patent Number
    8,583,227
  • Date Filed
    Friday, September 23, 2011
    13 years ago
  • Date Issued
    Tuesday, November 12, 2013
    11 years ago
Abstract
Portable electroviscerography systems are provided. Aspects of the systems include a body-associated receiver and an ingestible identifier unit, both of which are configured to detect visceral electrical signals. The system communicates with an extra-corporeal data processor configured to receive data from the body-associated receiver and generate and electroviscerogram from the received data. Also provided are methods of producing electroviscerograms using systems of the present invention.
Description
FIELD OF THE INVENTION

The present invention is related to electronic systems and, more specifically, to electronic systems for determining electrical signals generated by a subject.


INTRODUCTION

Gastrointestinal disorders are responsible for a variety of different medical conditions. One type of gastrointestinal disorder is gastric motility disorders. Gastric motility disorders can include gastric dysrhythmias (such as bradygastria and tachygastria), gastroparesis and gastric outlet obstruction. Gastric motility disorders may arise from multiple different causes, such as autonomic neuropathy secondary to diabetes, prior abdominal surgery, various diseases such as autoimmune disorders, drug side effects, etc. Symptoms of gastric motility disorders may vary, and may include nausea, vomiting, bloating and abdominal discomfort. The symptoms may be mild, or may develop into chronic, severe, or even debilitating conditions, which adversely affect the physical and/or mental well-being of an individual.


Another type of gastrointestinal disorder is gastroesophageal reflux disease (GERD), which is characterized by chronic symptoms or mucosal damage produced by the abnormal reflux in the esophagus. DeVault K R, Castell D O (1999). “Updated guidelines for the diagnosis and treatment of gastoesophageal reflux disease. The Practice Parameters Committee of the American College of Gastroenterology”. Am. J. Gastroenterol. 94 (6): 1434-42. GERD may arise from transient or permanent changes in the barrier between the esophagus and the stomach. These changes can arise from incompetence of the lower esophageal sphincter, transient lower esophageal sphincter relaxation, impaired expulsion of gastric reflux from the esophagus, or a hiatus hernia.


A variety of different tests associated with gastrointestinal disorders exists. One type of test that has been developed for evaluating gastromotility is the Gastric Emptying Scintigraphy (GES) test. GES is considered the gold-standard diagnostic test for gastroparesis. Other tests that may be employed for gastric motility disorders include barium studies, ultrasound, CAT scan, magnetic resonance imaging (MRI), endoscopy, manometry, and electrogastrograms.


An electrogastrogram (EGG) is a graphic produced by an electrogastrograph, which records the myoelectrical signals which travel through the stomach muscles and control the contractions of the stomach muscles. An electrogastroenterogram (or gastroenterogram) is analogous to an electrogastrogram, with the exception that electric signals arising from both the stomach and the intestines are employed.


To obtain electrogastrograms and electrogastroenterograms, sensors (such as electrodes) are applied to the skin surface of a patient and employed to detect electrical signals indicative of muscular activity of the gastrointestinal system, or region of interest thereof.


The problem with systems currently being used that employ skin surface readings is that the electrical signals associated with abdominal muscular activity are hard to distinguish from electrical signals indicative of muscular activity of the gastrointestinal system. Therefore what is needed is a system and method for accurately reading and detecting electrical signals indicative of muscular activity of the gastrointestinal system.


SUMMARY

In accordance with the teaching of the present invention, systems and methods are disclosed for capturing electrical signals associated with muscular activity of the gastrointestinal system. The systems and method disclosed herein can be used with electroviscerography systems and methods of evaluating gastrointestinal function in a subject. Aspects of the system include an ingestible identifier marker and a body-associated receiver configured to detect electrical signals. The system is configured to receive data from the identifier unit or marker. The information can be used to generate an electroviscerogram from the received data. Also provided are methods of producing electroviscerograms using the markers and receivers according to the present invention.





BRIEF DESCRIPTION OF THE FIGURES


FIG. 1 is an illustrative example of a receiver unit attached to a subject and an identifier unit ingested by the subject.



FIG. 2A is a cross-sectional side view of the identifier unit of FIG. 1 in accordance with the teachings of the present invention.



FIG. 2B is a top view of the identifier unit of FIG. 2A.



FIG. 3 is a functional component block diagram of the integrated circuit of the identifier unit of FIG. 2A.



FIG. 4 is a functional component block diagram of the detection unit of the integrated circuit of FIG. 3.



FIG. 5 is a functional component block diagram of the receiver unit of FIG. 1.



FIG. 6 is a block diagram representation of the receiver unit of FIG. 1.



FIG. 7 shows a system for creating an array of identifier units using a receiver to coordinate position.





DETAILED DESCRIPTION

Referring FIG. 1, a subject is shown with a portion of an electroviscerography system that collects data about the subject in accordance with the teaching of the present invention. The electroviscerography system includes a body-associated receiver unit 20 and an identifier unit 22. An extra-corporeal data processor 24 communicates with the receiver unit 20. The extra-corporeal data processor 24 may take a variety of configurations, such as a computer with a built-in or peripheral monitor (such as may be found in a bedside monitor or a health information system), a personal digital assistant (PDA), a smart phone, a messaging device, etc. To provide data to the extra-corporeal data processor 24, the receiver unit 20 may be configured to re-transmit data of a received signal to the location external to said subject. Alternatively, the receiver may be configured to be interrogated by an external interrogation device to provide data of a received signal to an external location. Any convenient data transmission protocol may be employed, including both wired and wireless data transmission protocols.


The electroviscerography systems of the invention are systems configured to produce electroviscerograms. Electroviscerograms refer to any usable manifestation of data, such as graphical reports that can be used to evaluate gastrointestinal function in a subject. Gastrointestinal information includes one or more parameters that provide information about the myoelectrical activity of a visceral organ or the gastrointestinal system or a portion thereof. Visceral organs of a subject are the soft internal organs of the body, especially those contained within the abdominal and thoracic cavities. Of interest are organs involved in motility, such as organs of the gastrointestinal tract. The term “gastrointestinal” relates to the stomach and intestines. The phrase “gastrointestinal system” refers collectively to the stomach, small and large intestine, as well as related structures, such as esophagus, etc. As such, electroviscerograms produced by systems of the invention include electroenterograms and electrogastrograms. Additional visceral organs of interest include organs of the urinary tract, such as the bladder, etc.


According to one aspect of the present invention, the subject ingests the identifier unit 22 in order to activate the identifier unit 22. As shown in the current example of FIG. 1, the identifier unit 22 is at an advanced ingested stage. The receiver unit 20 is shown secured to the subject at a desired location. The location of the receiver unit 20 can be determined by the medical requirements and the system design. The receiver unit 20 employed in accordance with the aspects of the present invention are those that are configured to be associated with a body location (either inside of or on a surface of a body) and to detect electrical signals from one or more visceral organs of the body, such as the gastrointestinal tract or a portion thereof, such as the stomach, small intestine, large intestine, etc. It is also within the scope of the present invention, as detailed below, to have the receiver unit 20 attached to the clothing of the subject with just electrode leads/wires secured to the skin of the subject.


Referring now to FIGS. 2A and 2B, identifier unit 22 includes an integrated circuit component 30, an upper electrode 32, a lower electrode 34, and a signal amplification element 36. According to the teachings of the present invention, the upper and lower electrodes 32 and 34, respectively, may have any convenient shape, e.g., square, disc, etc. The signal amplification element 36 is a planar disc structure, where the edge of the signal amplification element 36 extends beyond the edge of the upper electrode 32 and the lower electrode 34. In the depicted embodiment, the radius of the signal amplification element 36 is longer than the radius of the upper electrode 32 and the lower electrode 34, e.g., by 1 mm or more, such as by 10 mm or more.


The distance that the edge of the signal amplification element 36 may extend beyond the edge of electrodes 32 and 34 may vary, and in certain embodiments is 0.05 mm or more, e.g., 0.1 mm or more, including 1.0 mm or more, such as 5.0 mm or more and including 10 mm or more, where the distance may not exceed 100 mm in certain embodiments. The upper electrode 32 and lower electrode 34 are configured such that upon contact with a conducting fluid, such as stomach fluid, a voltage potential is created and current flows through the integrated circuit 30 to cause one or more functional blocks in the integrated circuit 30 to produce a unique current signature when the identifier unit 22 is operating in the broadcast mode. The voltage potential created between the upper electrode 32 and the lower electrode 34 is created through a chemical reaction between materials that make-up the electrodes 32/34 and the surrounding conducting fluid. In the broadcast mode, current paths 50 are formed between upper electrode 32 and lower electrode 34 through the conducting fluid surrounding the identifier unit 22.


Referring now to FIG. 3, the integrated circuit 30 includes a control unit 38 electrically coupled to a detection unit 40 and a sensing unit 41. In broadcast mode, the control unit 38 of the integrated circuit 30 controls the conductance between the upper and lower electrodes 32 and 34 respectively. Through controlling the conductance, the identifier unit 22 is able to produce a unique current signature and has encoded therein data gathered by the identifier unit 22 during the detection mode. In the detection mode the detection unit 40 detects the myoelectrical activity of the visceral organs or the gastrointestinal system or a portion thereof. Myoelectric signals have frequencies ranging from a few hertz to about 300 Hz, and voltages ranging from approximately 10 microvolts to 1 millivolt. Depending on the embodiment, the target physiological site or location of activation of the identifier unit 22 may vary. 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. Identifiers may be configured to be activated upon contact with fluid at the target site, e.g., stomach fluid, regardless of the particular composition of the target site. Where desired, the identifier may be configured to be activated by interrogation, following contact of the composition with a target physiological site. The identifier unit 22 may be configured to be activated at a target site, wherein the target site is reached after a specified period of time.


The sensing unit 41 includes circuitry for sensing and detection of various parameters associated with the environment. For example, the sensing unit 41 may be a temperature sensing or a pH sensing unit or a combination thereof. Other physiological parameter sensing sensors may be included.


Referring now to FIG. 4, the detection unit 40 includes power/signal lines 40a and 40b for powering the circuitry that detects the myoelectrical activity of the visceral organs when the identifier unit 22 is operating in detection mode. The myoelectric currents are typically lower frequency current sources. The power lines 40a and 40b are electrically coupled to a zener diode 42 and capacitor 44 for power supply control. Additionally, the power lines 40a and 40b are electrically coupled in parallel to capacitors 46 and 48 and amplifier 50 for detection and filtering of the electrical signals associated with the myoelectrical activity of the visceral organs. More specifically, the signal passes through amplifier 50. The amplified signal is passed to the bandpass filter unit 52. At the filter unit 52 removes the high frequency portion of the signals so that the myoelectrical activity and the associated signals are left. The filtered information is passed to a peak detection unit 54. The peak detection unit 54 is used to determine if a signal is associated with a true myoelectric activity as well as the proximity of the activity to the identifier unit 22, all which can be determined by the peak power or spike that occur. The peak detection unit 54 is able to adjust the reference or base-line values using the desired detection parameters. If there is a peak in voltage potential that exceeds the threshold value set by the peak detection unit 54, then the peak spike signal is passed to a pattern recognition unit 56 to determine the nature and type of myoelectric signal. The output of the pattern recognition unit 56 is received by a signal acknowledgement module 58, an IPG filter 60, a physiological parameter filter 62, and a second physiological parameter filter 64. Each filter 60, 62, and 64 are set to determine and allow only a specific type of detected electrical activity to pass through each filter's defined range. For example, if the information detected and collected by the identifier unit 22 is low frequency myoelectric current and then only one of the three filters 60, 62, and 64 will be passed the information to the connector 39. Any number of filters can be added to the detection unit 40 depending on the parameters are being evaluated. For example, one filter may be added to allow only information related pH to pass to the control unit 38. Once the information is passed through one of the filters on the detection unit 40, then the data or information is sent to the control unit 38 where it is encoded as part of the unique current signature that the control unit 38 produces. This unique current signature is detected and decoded by the receiver units of the system.


According to some aspects of the present invention, the identifier unit 22 is physiologically sized, by which is meant that it, alone or in combination with other vehicles, is compatible with ingestion. In certain aspects, the identifier unit may be associated with a carrier such as an active pharmaceutical agent or other vehicle. For example, physiologic sized identifier units may have a size of 10 mm3 or smaller, such as 5 mm3 or smaller, including 1 mm3 or smaller. In other instances, the identifier unit 22 may be sized to remain in the stomach following ingestion, at least until the identifier unit 22 is broken up by the digestive action of the stomach. In these instances, the identifier unit 22 may be configured to have a surface area of 1 cm2 or greater, such as 10 cm2 or greater.


The receiver unit 20 and the identifier unit 22 are configured to detect electrical or magnetic field signals. The processor 24 can be used or configured to receive data from receiver unit 20 via any communication means, including wireless and wired methods. The processor 24 can generate an electroviscerogram from the received data. The receiver unit 20 of interest includes those 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, the receiver unit 20 may 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 some instances, the receiver unit 20 is dimensioned such that its size does not hinder the ability of the subject to physically move. Where desired, the receiver unit 20 has a small size and may occupy a volume of space of 5 cm3 or less, such as 3 cm3 or less, including 1 cm3 or less. In some instances, the receiver has a chip size limit ranging from 10 mm2 to 2 cm2.


Referring now to FIG. 5, the receiver unit 20 includes a processing unit 70 positioned in a housing 72. The processing unit 70 is electrically coupled to and connected to electrodes 74. A coil 76 is wrapped around the hosing 72 and electrically coupled to the processing unit 70. The coil 76 is wound around the perimeter and provides for signal transmission from the receiver unit 20 device to an extra-corporeal data processor 24 of FIG. 1. In the current example, the receiver unit 20 includes two electrodes. However, in accordance with another aspect of the present invention, the receiver unit 20 may include additional electrodes and the scope of the present invention is not limited by the number electrodes. Thus, in one configuration of interest, the receiver unit 20 includes one or more electrodes (such as two or more electrodes, three or more electrodes, and/or includes multiple, such as two or more, three or more, four or more pairs of electrodes, etc.) for detecting electrical signals emitted by the visceral organ of interest as well as detection of the current signature from the identifier unit 22. In one configuration of interest, the receiver unit 20 includes two electrodes that are dispersed at a distance “X” from each other, which distance may be one that allows the electrodes to detect a differential voltage. This distance may vary, and may range from 0.1 to 5 cm, such as from 0.5 to 2.5 cm. The electrodes may also serve as an antenna to receive a signature current associated with an identifier unit or marker.


The receiver unit 20 may include a variety of different types of signal receiver elements and processing protocols, as long as the receiver unit 20 is configured to detect the desired visceral electrical signals. Additionally, the receiver unit of interest may be both external and implantable.


Referring now to FIG. 6, the processing unit 70 includes an amplifier 80 that detects the differential voltage potential across the electrodes 74 of FIG. 5. This voltage potential difference represents the myoelectric signal across the electrodes. The potential is sent to the amplifier 80 through leads 82 that are electrically connected to the electrodes 74 of FIG. 5 via the amplifier. The detected signal then goes into the demodulator 84. Also shown is a memory unit 85 to store the demodulated data, received signal, physiological parameter data, as well as medical record data. A clock 86 writes to the memory unit 85 in order to time-stamp the events. A transmit unit 89 transfers data from the memory unit 85 to the extra-corporeal data processor unit 24 of FIG. 1. The processing unit 70 also includes a power source 87 electrically coupled to a microprocessor 88. The microprocessor 88 coordinates the function between the various functional blocks as well as power management.


According to various aspects of the present invention, the system of the invention may include a single receiver unit or multiple receiver units. For systems that include a single receiver unit, the receiver unit may include three or more distinct electrodes, and may be configured to be positioned in an abdominal or xyphoid region of the subject. The receiver unit of such systems may be positioned at any convenient location, such as the front of a torso, the back of a torso, etc., as desired. In systems that have multiple receiver units, each receiver may have a single electrode and such receivers may be in communication with one another to create an array of receiver units.


Aspects of implantable versions of the receiver unit will have a biologically compatible enclosure, one or more sense electrodes, a power source, which could either be a primary cell or rechargeable battery, or one that is powered by broadcasting inductively to a coil. For the external signal receivers, embodiments include structures that have electrodes opposed to the skin. The communication may be wireless or performed over one or more conductive media, e.g., wires, optical fibers, etc. Where desired, the same electrodes may be used for receiving and transmitting signals.


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 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.


Signal receivers of interest include, but are not limited to, those receivers disclosed in: PCT application serial no. PCT/US2006/016370 published as WO 2006/116718; PCT application serial No. PCT/2007/24225 published as WO 2008/063626; PCT application serial no. PCT/US2008/52845 published as WO/2008/095183; the disclosures of which applications are herein incorporated by reference.


In accordance with other aspects of the present invention, the system may include two or more (such as three or more, including four or more) receiver units. In such systems, the two or more body-associated receivers may be adaptively arranged at any desired location on the body of the subject. For example, all of the body-associated signal receivers may be present on the same side of a body, such as the front torso of a body, or they may be present on opposite sides of a body, such as the front and back of the torso of a body.


In addition to the one or more body-associated signal receivers, systems of the invention may include an extra-corporeal data processor configured to receive data from the body-associated receiver and generate an electroviscerogram from the received data. The extra-corporeal data processor unit 24 may receive the electrical signal data directly from the receiver unit, or via a data relay device (such as a device that receives data from the receiver unit and then forwards the received data to an extra-corporeal data processor). The extra-corporeal data processor unit 24 may be configured to receive the data via any convenient wired or wireless protocol, as desired. Extra-corporeal data processors of interest are those that can receive the electrical signal data and process the data to produce an electroviscerogram. The produced electroviscerograms may be output to a user by any convenient medium, such as writing the electroviscerograms on paper, displaying an electroviscerogram to a user via a graphical user interface, and the like. Extra-corporeal data processors of the systems of the invention may take a variety of configurations, such as a computer with a built-in or peripheral monitor (for example as embodied in a bedside monitor or a health information system), a personal digital assistant (PDA), a smart phone, a messaging device, etc.


In some instances, the identifier unit identifier is environmentally sensitive. By environmentally sensitive is meant that the identifier is configured to be activated when the identifier comes into contact with one or more conditions to which the identifier is designed to respond. Environmental conditions to which identifiers of interest may be configured to respond include temperature, pressure, pH, analyte presence, etc. In some instances, the identifiers are pH sensitive, by which is meant that the identifiers are configured to respond to predetermined pH conditions, such as acidic or alkaline conditions. For example, an identifier may be configured to respond (for example by activation and emission of a signal) when it contacts fluid having an acidic pH (such as pH 6.5 or less, such as pH 6 or less) or fluid having an alkaline pH (such as pH of 7.5 or higher, such as pH of 8 or higher). As environmentally sensitive identifiers are responsive to a predetermined condition or set of two or more conditions to which they are exposed, they are configured to activate and emit a signal upon contact with the predetermined condition or set of conditions.


Depending on the needs of a particular application, the current detected by the receiver unit from the identifier unit may be generic, such that it merely identifies that the identifier has contacted the target site. Alternatively, the signal may be represent information about the myoelectric activity as detected by the identifier unit. As such, the identifier may be one that, when employed with a batch of dosages, emits a signal which cannot be distinguished from the signal emitted by the identifier of any other dosage member of the batch. Alternatively, each member of the batch may have an identifier that emits a unique signal, at least with respect to all the other identifiers of the members of the batch. In these instances, each identifier of the batch emits a signal that uniquely identifies that particular identifier in the batch, at least relative to all the other identifiers of the batch. The identifier may emit a unique signal that is a universally unique signal (where such a signal may be 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). 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 (for example a database linking identifying codes with compositions).


The identifier may generate a variety of different types of signals, including but not limited to: current signatures produced through controlling conductance, RF signals, magnetic signals, conductive (near field) signals, acoustic signals, etc. The transmission time of the identifier may vary, where in certain instances the transmission time may range from 0.1 μsec to 48 hours or longer, such as from 0.1 μsec to 24 hours or longer, such as from 0.1 μsec to 4 hours or longer, such as from 1 sec to 4 hours, including from 1 minute to 10 minutes. Depending on the given embodiment, the identifier may produce a unique current signature once. Alternatively, the identifier may be configured to produce a unique current signature with the same information (identical signals), two or more times, where the collection of discrete identical signals may be collectively referred to as a redundant signal.


In some instances, the identifier marker may be configured to remain at a location of the gastrointestinal tract once it reaches that location. For example, the marker may include a muco-adhesive element that, upon contact with an internal location of the gastrointestinal tract, will cause the marker to remain at that location. An example of use of such an embodiment is where multiple identifier units that include a muco-adhesive element are administered to a subject. The markers will adhere to different positions of the stomach and will emit signals from different locations. The multiple different signals may be employed to produce a map of the stomach, which may be monitored over time. Where desired, the map may be monitored in response to different states, such as mealtimes, fasting, etc.


The identifiers 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, such as the stomach. Identifier may include an activation component, such as a battery that is completed by stomach acid, and a transmission element. Examples of different types of identifiers of interest include; but are not limited to, those identifiers 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/2008/101107; PCT application serial no. PCT/US2008/056296 published as WO/2008/112577; PCT application serial no. PCT/US2008/056299 published as WO/2008/112578; and PCT application serial no. PCT/US2008/077753; and U.S. patent application Ser. No. 12/564,017 filed on Sep. 21, 2009, the disclosures of which are herein incorporated by reference.


In addition to the identifier component described above, the identifier units employed in methods of the invention may be associated with a vehicle component. Vehicle components may include one or more constituents, including but not limited to fillers, binders, disintegrants, coloring agents, etc. Vehicle components of interest are further reviewed in PCT Application Serial No. US2006/016370 published as WO 2006/116718, the disclosure of which is herein incorporated by reference. Additional disclosure of components that can be present in compositions of the invention can be found in Remington's Pharmaceutical Sciences, Mace Publishing Company, Philadelphia, Pa., 17th ed. (1985). The identifier unit may be configured in a variety of different formats. Formats of interest include solid formats, such as tablets, powders, coated granules, filled capsules, etc.


Depending on the particular method, the identifier unit may not include a pharmaceutically active agent. As such, the identifier and any vehicle component or components that make up the identifier unit do not include an active agent. In yet other embodiments, the identifier unit includes an active agent. As used herein, the term “active agent” includes any compound that produces a physiological result, for example a beneficial or useful result, upon contact with a living organism, such as a human. Active agents are distinguishable from vehicle components such as fillers, binders, coloring agents, etc. The active agent may be any molecule that is capable of modulating a biological process in a living subject. In some instances, the active agent may be a substance used in the diagnosis, treatment, or prevention of a disease or as a component of a medication. Broad categories of active agents of interest include, but are not limited to: cardiovascular agents; pain-relief agents, e.g., analgesics, anesthetics, anti-inflammatory agents, etc.; nerve-acting agents; chemotherapeutic (such as anti-neoplastic) agents; etc. Active agents of interest are further disclosed in PCT Application Serial No. US2006/016370 published as WO 2006/116718, the disclosure of which is herein incorporated by reference.


A given identifier unit may include a single identifier, or two or more identifiers. The identifiers may be arranged in a variety of different configurations with respect to the other components of the marker. Where the marker includes a tablet as a vehicle, the identifier or identifiers may be arranged on a surface of the tablet vehicle. In some instances, the marker is made up of two or more identifiers present in an ingestible container. For example, multiple identifier unit identifiers may be present in a capsule fabricated from a material that dissolves upon contact with stomach fluid. Materials of interest from which the carrier components may be fabricated include physiologically acceptable polymeric materials that are used in conventional pharmaceutical capsule dosages. The materials may be clear or opaque, and may be colored as desired. Of interest are both rigid and elastic materials. Suitable polymers from which carrier components of the invention may be fabricated include, but are not limited to: polyvinyl alcohol (PVA); natural and synthetic polysaccharides, including pullulan, carrageenan, xanthan, chitosan agar gums, and cellulosic materials, such as carboxymethylcellulose, hydroxypropylmethylcellulose (HPMC), methylcellulose, hydroxyethylcellulose, hydroxyethyl methylcellulose, hydroxypropylcellulose; polyethylene glycols (PEGs), polyethylene oxides (PEOs), mixtures of PEGs and PEOs; acrylic and methacrylic acid based polymers, such as EUDRAGIT E™, EUDRAGIT L™ and/or EUDRAGIT S™ methacrylic acid polymers), EUDRAGIT RL™ and/or EUDRAGIT RS™ ammonium methacrylate copolymers; povidone (polyvinyl pyrrolidone), polyglycolysed glycerides (such as GELUCIRE 44/14™, GELUCIRE 50/02™, GELUCIRE 50/13™ and GELUCIRE 53/10™ polymers); carboxyvinyl polymers (such as CARBOPOL™ polymers); polyoxyethylene-polyoxypropylene copolymers (such as POLOXAMER188™ polymer); and the like. The capsule components may be fabricated using any convenient protocol, including molding, etc. Fabrication protocols of interest include, but are not limited to, those described in U.S. Pat. Nos. 5,705,189; 4,576,284; 4,591,475; 4,655,840; 4,738,724; 4,738,817 and 4,790,881; the disclosures of which are herein incorporated by reference. Alternatively, the capsule component may be obtained from a commercial vendor, such as Qualicaps Inc., Whitsett N.C.


Methods of producing an electroviscerogram for a subject are also provided. As reviewed above, an electroviscerogram is any usable manifestation of data, such as a graphical report (which may be written onto a physical medium or displayed on a monitor, etc.), that provides information about the myoelectrical activity of a visceral organ or organs of a subject. Visceral organs of interest include organs involved in motility, such as organs of the gastrointestinal tract, for example the stomach and intestines. As such, electroviscerograms produced by systems of the invention include electroenterograms and electrogastrograms. Additional visceral organs of interest include organs of the urinary tract, such as the bladder, etc.


In practicing methods of the invention, electrical signals generated by the visceral organ of interest (for example myoelectric signals), such as the stomach or intestine, are detected with the one or more body-associated signal receivers of the system, as described above. The resultant detected electrical signal data are then forwarded to the extra-corporeal data processor, which receives the data and generates the desired electroviscerogram from the received data. A given method may include detecting electrical signals for a given period of time, such as one hour or longer, two hours or longer, twelve hours or longer, one day or longer, two days or longer, one week or longer, two weeks or longer, one month longer, six months or longer, including one year or longer. As the systems of the invention are portable, the data may be detected and recorded continuously over these periods of time, as desired.


Depending on the particular application, the body-associated signal receiver may be positioned in a variety of different configurations relative to the organ of interest. For example, where a single body-associated signal receiver is employed, the methods may include initially positioning or implanting the single receiver at a location proximal to the organ of interest. Where the organ of interest is the stomach, the single receiver may be positioned at an abdominal or xyphoid region, as desired. With other systems that include two or more signal receivers, the receivers may be positioned at a variety of body locations. For example, the methods may include positioning two or more distinct receivers at distinct abdominal locations (for example to provide for triangulate location capability of an identifier unit as it passes through the gastrointestinal tract), or positioning one receiver at a front abdominal location and a second receiver at a back location. This latter configuration is representative of instances where the receivers are placed on opposite sides of a target organ, e.g., to measure impedance through the organ. Measuring impedance through the stomach finds interest as an independent way to evaluate gastric motility, which may be used in combination with electroviscerograms of the invention or independently thereof. For example, the measured impedance through the stomach will change depending on whether the stomach is full or empty. By correlating impedance with time following food intake, a measure of gastric motility can be readily produced.


In some instances, the identifier unit identifier is environmentally sensitive. By environmentally sensitive is meant that the identifier is configured to be activated when the identifier comes into contact with one or more conditions to which the identifier is designed to respond. Environmental conditions to which identifiers of interest may be configured to respond include temperature, pressure, pH, analyte presence, etc. In some instances, the identifiers are pH sensitive, by which is meant that the identifiers are configured to respond to predetermined pH conditions, such as acidic or alkaline conditions. For example, an identifier may be configured to respond (for example by activation and emission of a signal) when it contacts fluid having an acidic pH (such as pH 6.5 or less, such as pH 6 or less) or fluid having an alkaline pH (such as pH of 7.5 or higher, such as pH of 8 or higher). As environmentally sensitive identifiers are responsive to a predetermined condition or set of two or more conditions to which they are exposed, they are configured to activate and emit a signal upon contact with the predetermined condition or set of conditions.


For pH sensitive identifier units of the invention, pH sensitivity may be imparted to the markers using a number of different approaches. For example, the markers may include a pH sensor element, which element is configured to detect the pH of a given environment in which the marker may be placed and activate the identifier in response thereto. One example of an identifier having an integrated pH sensor is an identifier that includes an integrated circuit and three disparate electrode elements, two of which act as part of the partial power source and part of the broadcast mode while the third is used in operation during the detection mode components of the battery which is produced upon contact of the identifier with a conductive medium and the third of which (e.g., fabricated from platinum or other suitable material) serves as a counter electrode for each of the battery electrodes. The integrated circuit further includes a bandgap reference. During operation, when the identifier contacts a suitable conductive medium, such as stomach fluid, the battery electrodes provide operating voltage for the integrated circuit, including the clock component of the integrated circuit. The identifier emits a signal or signals representing temperature from the bandgap reference on the circuit and battery electrode voltages. Also transmitted from the identifier is a signal or signals providing the voltage on the reference electrode with respect to each battery electrode (for example battery electrode 1 v. Pt reference electrode and battery electrode 2 v. Pt reference electrode), where these voltages are related to pH of the environment and temperature. These signals may be transmitted as a digital signal or a frequency or a duty cycle. With such an identifier, the transmitted signal or signals are then processed, e.g., by a body-associated receiver and/or an extra-corporeal data processor, to covert the signals representing temperature and battery/reference electrode voltages into pH values, e.g., by using lookup tables or appropriate algorithms. Another approach that may be employed to impart pH sensitivity to a given marker is to include a pH sensitive coating covering activation components (such as battery elements) of the identifier, where the pH sensitive coating only dissolves to expose the activation components when the desired pH conditions are present. pH sensitive coatings of interest include, but are not limited to: cellulose acetate pthalate, EUDRAGIT L™, EUDRAGIT S™, EUDRAGIT FS™, and other pthalate salts of cellulose derivatives. Additional marker configurations that can be employed to obtained environmental sensitivity include, but are not limited to, configurations described in PCT application serial no. PCT/US2007/082563 published as WO 2008/052136, the disclosure of which is herein incorporated by reference.


In some instances, pH sensitivity is provided by an identifier unit that emits a different signal depending on the particular pH of the environment to which it is exposed. For example, an identifier may include three electrodes, one of which is coated with a pH sensitive coating which only dissolves to expose the electrode at a certain pH. In this type of identifier, a first signal will be transmitted by the uncoated electrodes and a second signal distinguishable from the first will be transmitted by the electrodes when the coating on the coated electrode is removed, e.g., by dissolution. In yet another example, the identifier may include a chemical agent that is released upon exposure to a particular pH, for example by include the agent in a chamber that is sealed with a pH sensitive coating. Upon removal of the pH sensitive coating, the agent is released and modifies the identifier emitted signal.


Yet another way to provide pH sensitivity to an identifier is to provide an element, such as a trip wire, whose conductivity is modified depending on the pH of the environment of the identifier. For example, an identifier may include a conductive trace or wire that dissolves when the identifier is exposed to a certain pH. The pH sensitivity of this element may be provided by material (for example, Mg, Zn or other metal that dissolves in acidic conditions) of the element and/or a suitable coating. When the element is present, a first signal is emitted by the identifier and when the element dissolves or is otherwise compromised, a second signal is emitted by the identifier. Alternatively, an identifier may include a conductive trace or wire that is produced when the identifier is exposed to a certain pH. For example, a trace of CuCl will convert to Cu metal upon exposure to acidic conditions to product a conductive element. Again, the material may be covered by an appropriate coating which imparts pH sensitivity to the identifier. When the conductive element is not present, a first signal is emitted by the identifier and when the element is produced, a second signal is emitted by the identifier.


A given method may include administering a single identifier unit to a subject, or two or more identifier units, such as first, second and even third or more identifier units. As such, a given method may include administration of a single identifier unit. Alternatively, a given method may include administration of two or more, such as three or more, four or more, five or more, ten or more, fifteen or more, twenty or more, etc., identifier units to a subject. Where multiple identifier units are employed in a given method, they may be administered to a subject at the same time or at different times.


As indicated above, identifier units employed may be environmentally sensitive. In some instances where two or more environmentally sensitive identifier units are employed, the identifier units may be responsive to different environmental conditions. As such, a given method may include administering to a subject a first environmentally sensitive marker that is responsive to a first environmental condition (such as acidic conditions) and a second environmentally sensitive marker that is response to a second environmental condition (such as alkaline conditions). In such instances, the markers may be sensitive to a variety of different types of environmental conditions, such as pH.


Administration of markers may be coordinated with administration of liquid and/or foods, as desired. For example, subjects may be instructed to ingest the markers with food, including specific types of foods or meals, with liquids or during fasting, at different times of the day, etc., as desired, to obtain information that is coupled with other types of relevant information, such as caloric intake, time of day, etc.


Following administration of the one or more identifier units to a subject, as reviewed above, one or more signals emitted from the one or more identifier units are detected by a body-associated receiver of the system. The current detection is carried out through the skin and other body tissues of the subject. In some instances, the receiver is configured to simultaneously detect multiple unique current signatures each from a respective identifier unit, such as an ingestible event marker or an ionic emission module. The number of different unique current signatures from the respective number of identifier units may be 2 or more, 5 or more, 10 or more that may be emitted from different identifier units.


To provide data to the extra-corporeal data processor, the signal receiver may be configured to retransmit data of a received signal to the location external to said subject. Alternatively, the signal receiver may be configured to be interrogated by an external interrogation device to provide data of a received signal to an external location. The particular protocol employed in this evaluation may vary depending on the particular function being determined. In some instances, the evaluation protocol is one that is based on detection of a signal that is indicative of the identifier unit coming into a contact with a predetermined environmental condition of interest. For example, an evaluation protocol may be one that is based on detection of a particular pH at a particular physiological location, such as a low pH in the stomach or esophagus, which may be used in determining the presence of GERD (as reviewed in greater detail below). In these types of evaluation protocols, a single identifier unit may be employed, or multiple identifier units may be employed. For example, a set of two or more identifier units that emit differently coded signals may be employed, where the two markers are configured to emit signals at different locations.


Alternatively, each identifier unit may be configured to emit its signal at a different physiological target site, e.g., where each identifier unit is configured to be activated at a different target physiological site. For example, a first identifier unit may be activated in the mouth, a second identifier unit may be activated in the esophagus, a third identifier unit may be activated in the small intestine and a fourth identifier unit may be activated in the large intestine. Such an identifier unit set may be employed in a diagnostic application to determine function of the digestive system, such as motility through the digestive tract, gastric emptying, and the like. For example, by noting when each identifier unit emits its respective signal, a plot of signal vs. time may be generated from which information regarding digestive tract functioning may be obtained.


Instead of using a signal indicative of contact of the identifier unit with a predetermined environmental condition (such as a pH value), the evaluation protocol that is employed may monitor detected signal relative to time and location following administration. Such information may be employed to determine various aspects of gastrointestinal function, such as total GI transit time or transit times specific for portions of the gastrointestinal tract, such as gastric emptying times, small bowel transit time, total colonic transit time, and the like.


A given evaluation protocol may be one that employs data obtained solely from identifier unit 22, or may be one that employs data obtained from identifier units and one or more other types of data, such as physiologic data (including but not limited to electrogastrogram, temperature, heart rate, blood pressure, etc.), non-physiologic patient specific data (including, but not limited to gender, age, height, weight, medication history, feeding history, exercise history, etc.), environmental data (including but not limited air temperature, pressure, etc.), and the signals obtained from the body-associated signal receivers configured to obtain an electroviscerogram, such as an electroenterogram, including an electrogastrogram. The particular protocol employed to obtain the electroviscerogram may vary. For example, the particular protocol may solely employ data representing electrical signals generated by the organ of interest, i.e., organ specific myoelectric data. Alternatively, the particular protocol may employ organ specific myoelectric data and additional types of data, as reviewed above. A given protocol may include comparing data with reference, i.e., control, data to identify deviations from a norm. Another approach would be to combine data relevant to a pH with data that is relevant to myoelectric activity thereby providing the physician with powerful tools for diagnostics and decision making. A given protocol may include use of noise cancellation algorithms, as desired.


Where identifier units are employed, a given protocol may employ the signal of the identifier unit in a number of different ways, as desired. For example, the signal emitted by the identifier unit may be employed as an independent calibration of the obtained electroviscerogram. In some instances, the system employed in a given method uses an identifier unit configured to emit a signal that varies in frequency with respect to time from administration and activation. In these embodiments, changes in frequency of signal emitted by the identifier unit may be designed to reinforce or cancel out an organ of interest's myoelectric signals, such as stomach waves. For example, an identifier unit may be configured to emit signals that vary from high to low frequency as it traverses the gastrointestinal tract. Data obtained from the body-associated receiver may then be used to generate a map of both high and low frequency signals. The high frequency signals may be employed as a map of the location of the identifier unit with respect to time as it transits the gastrointestinal tract, while the low frequency signals can be employed in generating the electrogastrogram, with only those signals that resonate with the organ's myoelectric waves being employed so as to enhance the signal to noise ratio.


As discussed above with respect to FIG. 3, in yet other systems according to another aspect of the present invention, the identifier unit may itself record myoelectric signals of interest, and transmit data that includes information about these myoelectric signals to the body-associated receiver or receivers of the system. For example, the identifier unit can be configured to include a functional block which detects the myoelectric signals of interest and then transmits resultant detected myoelectric data to the one or more body-associated receiver units of the system.


A given method may include generating a clinically diagnostic score as desired, where the score may take the form of a single value or be more detailed with respect to values for one or more parameters of interest (for example, where the score is provided in the form of a report card). Using appropriate algorithms, the electroviscerograms of the invention may be combined with one or more additional data streams in order to provide this score. The methods of the invention may be employed with a variety of different types of subjects.


Referring now to FIG. 7, a schematic of a method which is employed to determine gastrointestinal transit time in a patient or subject is shown. The patient is provided three different identifier unit capsules 92, one to be taken in the morning, one to be taken in the afternoon and one to be taken in the evening. Each capsule 92 includes a set of multiple distinct identifier units that are configured to emit a signal when they reach a different portion of the gastrointestinal tract 94, such as the set of markers described above. Following administration, each capsule 92 dissolves in the stomach of the gastrointestinal tract 94 and becomes activated as active capsule 92a, each of which produces a unique current signature. The identifier unit emits a current signature as it reaches its predetermined location. The information encoded in the current signal is recorded by a receiver unit 96. The receiver unit 96 then wirelessly forwards the data to an extracorporeal data processor 98, such as a PDA or a laptop computer. The processor 98 performs an evaluation protocol on the received data to output transit time results (such as total transit time, colonic transit time, etc.) to a user (for example by displaying a graphical user interface on a monitor). The graph shown to the user via the PDA or laptop computer is a graph showing the percent emptying of the stomach as a function of time.


The methods of the invention may be employed with a variety of different types of subjects, including “mammals,” carnivores (such as dogs and cats), rodentia (such as mice, guinea pigs and rats), and primates (such as humans, chimpanzees and monkeys).


The methods and systems of the invention find use in a variety of different applications in which generation of an electroviscerogram, such as an electroenterogram, like an electrogastrogram, is desired. Applications of interest include those in which electroenterograms of the invention are employed to evaluate gastrointestinal function. For example, electrogastrograms of the invention find use in the determination of stomach motility, gastric cycles, gastrointestinal transit times, stomach volume, etc. Applications of interest include use of electroviscerograms of the invention in the diagnosis and/or monitoring of gastrointestinal conditions in a subject. Gastrointestinal disorders that may be assessed in a subject using electrogastrograms of the invention include, but are not limited to: gastric motility conditions, such as gastroparesis. One application of interest is the assessment of a gastric motility condition in a subject, where assessment includes both diagnosis of the presence of a gastric motility condition in a subject as well as monitoring the progress of treatment of a subject for a gastric motility condition (for example to determine whether a given treatment protocol is having a desired therapeutic affect on the gastric motility condition of interest).


One gastric motility condition whose assessment may be achieved using methods of the invention is gastroparesis. Gastroparesis, also known as delayed gastric emptying, is a medical condition consisting of a partial paralysis of the stomach, resulting in food remaining in the stomach for a longer period of time than normal. Gastroparesis may occur when the vagus nerve is damaged and the muscles of the stomach and intestines do not work normally. Food then moves slowly or stops moving through the digestive tract. Symptoms associated with gastroparesis include vomiting, bloating, abdominal pain or discomfort and early satiety.


Subjects of interest include those at least suspected of suffering from gastroparesis, such as through the use of one or more symptoms of gastroparesis. In assessing gastroparesis in an individual, an identifier unit emits a controlled current signature as it is activated. As the identifier unit enters the gastrointestinal tract, a receiver unit's movement and position may be monitored as a function of time. For example, by plotting location as a function of time, one can readily determine when the identifier unit passes from the stomach into the small intestine after ingestion of the identifier unit, and thereby make a determination of gastric emptying time. Alternatively, a set of two or more identifier units may be employed, which markers are responsive to different environmental conditions. For example, one may administer a first identifier unit that is responsive to acidic conditions and a second identifier unit that is responsive to alkaline conditions. If these markers are administered at the same time and then the signal detection time of each is recorded, a measure of gastric emptying time can readily be made by comparing when the signals from the acidic pH and alkaline pH responsive markers are obtained. For example, the time from administration to detection of the signal from the acidic pH responsive marker may be subtracted from the time from administration to detection of the signal from the alkaline pH responsive marker in order to obtain a measure of gastric emptying time. Where desired, plots of a given parameter (such as location, pH, pressure, etc.) as a function of time may be prepared and compared to a suitable control plot (in other words reference) to obtain the desired measure of gastric emptying.


Methods of evaluating gastroparesis that may be readily modified to employ identifier units as described in the present application include, but are not limited to, those described in United States Published Application Nos. 20080287833; 20080161643; 20080064938 and 20040162501; as well as U.S. Pat. Nos. 7,160,258 and 7,141,016; the disclosures of which applications are herein incorporated by reference.


Where desired, methods of invention may be employed in conjunction with one or more additional methods of diagnosing gastroparesis. For example, methods of invention may be employed as a first determination or screen of whether or not a subject suffers from gastroparesis. If the results of this first determination are positive, one or more additional tests may be performed to confirm the presence of gastroparesis. Additional gastroparesis diagnostic tests with which the present methods may be used in conjunction include, but are not limited to: diagnostic tests based on symptoms and physical examination; diagnostic tests in which isotopic marker compositions are ingested and monitored, upper gastrointestinal endoscopy tests; antro-duodenal motility tests which measure the pressure that is generated by the contractions of the stomach and intestinal muscles; electrogastrograms (EGG) which record the electrical signals that travel through the stomach muscles and control the muscles' contractions; etc.


Where desired, methods of the invention may further include treating a subject for gastroparesis when the methods identify the subject as suffering from gastroparesis. Of interest are medications that treat gastroparesis by stimulating the stomach to contract more normally. Specific medications of interest include, but are not limited to: metoclopramide, domperidone, erythromycin, octreotide, etc. Where desired, surgery may be employed, such as surgery that creates a larger opening between the stomach and the small intestine in order to facilitate the process of emptying the stomach. Additional treatment protocols of interest include, but are not limited to those described in United States Published Application Nos. 20060029614; 20050164925; 20050106167; 20050090554; 20030059374 and 20020143030; the disclosures of which are herein incorporated by reference.


Other gastric motility disorders in which the methods of the invention find use include, but are not limited to: gastric dysrhythmias, such as bradygastria and tachygastria, and gastric outlet obstruction, pelvic floor dysfunction, chronic constipation, and GI conditions that are manifestations of diabetes and/or autonomic neuropathy. Other types of conditions in which electrogastrograms of the invention find use in the assessment thereof include, but are not limited to: other intestinal disorders, bladder disorders, Children with Angelman Syndrome, as well as endometriosis. Applications in which electrogastrograms of the invention find use are further reviewed in U.S. Pat. Nos. 5,704,368 and 6,351,665; as well as United States Published Application No. 20050215917; the disclosures of which are herein incorporated by reference. As described above, when methods of the invention are employed to assess such conditions, the methods may further include confirming diagnoses with one or more additional tests and/or treating the subject for the diagnosed condition with one or more treatment protocols.


In addition, electroviscerograms of the invention may find use in assessing physiological responses to various stimuli. In some instances, electrogastrograms of the invention may be employed to evaluate an individual's response to different types of foods. For example, observed electrogastrograms vary between high caloric content foods and low caloric content foods. Various in observed electrogastrograms may therefore be used to assess an individual's diet, e.g., where one wishes to monitor a subject's compliance with a dietary regimen.


Another type of gastrointestinal condition with which the subject methods find use is GERD, as well as related conditions, such as functional dyspepsia. Subjects of interest for these applications include those at least suspected of suffering from GERD. For assessment of GERD, one or more identifier units may be administered to a subject, where the identifier units are pH sensitive and are configured to emit a signal from which the pH at a given physiological site may be determined. Upon receipt of the signal or signals, an assessment of GERD may be obtained. For example, when a patient suffering from GERD is on a given treatment protocol, the methods of invention may be used to identify low gastric pH despite the treatment protocol that the patient is receiving. This result may be used to justify alteration of the treatment protocol in some manner. Alternatively, an identifier unit configured to provide a signal from which lower esophageal pH may be determined can be employed. With such an environmentally responsive identifier unit, low pH detected in the lower esophagus may be employed as a diagnostic marker of GERD.


Where desired, the methods of invention may be employed in conjunction with one or more additional GERD diagnostic methods. GERD diagnostic methods of interest include, but are not limited to: barium swallow X-rays, esophageal manometry, 24-hour esophageal pH monitoring and Esophagogastroduodenoscopy (EGD). The methods of invention may further include treating an individual for GERD following assessment of GERD by methods of the invention. Pharmacologic treatment protocols of interest include, but are not limited to: proton pump inhibitors (such as omeprazole, pantoprazole, lansoprazole, and rabeprazole); gastric H2 receptor blockers (such as ranitidine, famotidine and cimetidine); antacids; alginic acid; prokinetics (such as cisapride; sucralfate; 5-HT4 receptor agonists, such as mosapride citrate; etc.


It is to be understood that this invention is not limited to particular embodiments described, as such may vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting, since the scope of the present invention will be limited only by the appended claims.


Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limit of that range and any other stated or intervening value in that stated range, is encompassed within the invention. The upper and lower limits of these smaller ranges may independently be included in the smaller ranges and are also encompassed within the invention, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the invention.


Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although any methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the present invention, representative illustrative methods and materials are now described.


All publications and patents cited in this specification are herein incorporated by reference as if each individual publication or patent were specifically and individually indicated to be incorporated by reference and are incorporated herein by reference to disclose and describe the methods and/or materials in connection with which the publications are cited. The citation of any publication is for its disclosure prior to the filing date and should not be construed as an admission that the present invention is not entitled to antedate such publication by virtue of prior invention. Further, the dates of publication provided may be different from the actual publication dates which may need to be independently confirmed.


It is noted that, as used herein and in the appended claims, the singular forms “a”, “an”, and “the” include plural referents unless the context clearly dictates otherwise. It is further noted that the claims may be drafted to exclude any optional element. As such, this statement is intended to serve as antecedent basis for use of such exclusive terminology as “solely,” “only” and the like in connection with the recitation of claim elements, or use of a “negative” limitation.


Certain ranges have been presented herein with numerical values being preceded by the term “about.” The term “about” is used herein to provide literal support for the exact number that it precedes, as well as a number that is near to or approximately the number that the term precedes. In determining whether a number is near to or approximately a specifically recited number, the near or approximating unrecited number may be a number which, in the context in which it is presented, provides the substantial equivalent of the specifically recited number.


As will be apparent to those of skill in the art upon reading this disclosure, each of the individual embodiments described and illustrated herein has discrete components and features which may be readily separated from or combined with the features of any of the other several embodiments without departing from the scope or spirit of the present invention. Any recited method can be carried out in the order of events recited or in any other order which is logically possible.


Although the foregoing invention has been described in some detail by way of illustration and example for purposes of clarity of understanding, it is readily apparent to those of ordinary skill in the art in light of the teachings of this invention that certain changes and modifications may be made thereto without departing from the spirit or scope of the appended claims.

Claims
  • 1. A system for detection of myoelectric activity, the system comprising: an ingestible identifier comprising: a housing including a first electrode and a second electrode secured thereto;a control unit electrically coupled to the first and second electrodes, wherein the control unit changes conductance between the first and second electrodes; anda detection unit electrically coupled to the first and second electrodes, wherein the detection unit reads a surrounding environment to collect information, wherein electrochemical reactions between the first electrode and the surrounding environment and the second electrode and the surrounding environment respectively produce a voltage potential that powers the ingestible identifier such that the control unit switches the ingestible identifier between broadcast mode and detection mode; anda second ingestible identifier configured to communicate with the ingestible identifier such that when the second ingestible identifier is in the broadcast mode the ingestible identifier is in the detection mode thereby allowing the ingestible identifiers to communicate.
  • 2. The system of claim 1, wherein the information is encoded in a unique current signature produced by the ingestible identifier, wherein the information comprises identification information to indicate activation of the ingestible identifier.
  • 3. The system of claim 2, wherein the information encoded in the ingestible identifier's unique current signature represents data gathered during the detection mode.
  • 4. The system of claim 1, further comprising a receiver unit configured to communicate with at least one of the ingestible identifier or the second ingestible identifier.
  • 5. The system of claim 4, wherein the receiver unit comprises a detection module capable of detecting low frequency current signals produced by a voltage potential and capable of detecting high frequency current signals produced by the ingestible identifier or the second ingestible identifier.
  • 6. The system of claim 1, wherein the ingestible identifier further comprises a temperature sensing unit responsive to and capable of recording the surrounding temperature.
  • 7. The system of claim 1, wherein the ingestible identifier includes a sensor capable of measuring the surrounding temperature.
  • 8. The system of claim 1, wherein the ingestible identifier includes a sensor capable of measuring the surrounding pH level.
  • 9. The system of claim 1, wherein the ingestible identifier measures acidic conditions and the second ingestible identifier measures alkaline conditions.
  • 10. The system of claim 4, wherein the system further comprises an extra-corporeal data processor configured to receive data from the receiver unit and generate an electroviscerogram from the received data.
  • 11. The system of claim 1, wherein the ingestible identifier includes a disc secured to the housing, wherein the disk is non-conducting, and wherein during the detection mode the ingestible identifier records data associated with myoelectric activity and during the broadcast mode the ingestible identifier produces a unique current signature including the data.
  • 12. The system of claim 1, wherein during the detection mode the ingestible identifier detects and records data associated an implantable device and during the broadcast mode the ingestible identifier produces a unique current signature encoded with the data.
  • 13. A system for creating an electroviscerogram for a subject based on detected myoelectric activity, the system comprising: an ingestible identifier system with each ingestible identifier having at least two electrodes secured thereto for detection of a change in voltage potential associated with myoelectric information of the subject, the ingestible identifier system comprising:an ingestible identifier comprising: a housing including a first electrode and a second electrode secured thereto,a control unit electrically coupled to the first and second electrodes, wherein the control unit changes conductance between the first and second electrodes;a detection unit electrically coupled to the first and second electrodes, wherein the detection unit reads a surrounding environment to collect information, wherein electrochemical reactions between the first electrode and the surrounding environment and the second electrode and the surrounding environment respectively produce the voltage potential that powers the ingestible identifier such that the control unit switches the ingestible identifier between broadcast mode and detection mode; anda processing unit for receiving the detected myoelectric information and providing an encoded message;a transmission module secured to the housing and electrically coupled to the processing unit, wherein the transmission module receives the encoded message from the processing unit; anda second ingestible identifier configured to communicate with the ingestible identifier such that when the second ingestible identifier is in the detection mode, the ingestible identifier is in the broadcast mode thereby allowing the ingestible identifiers to communicate; and
  • 14. The system of claim 13, wherein the ingestible identifier further comprises: a non-conducting membrane positioned between the first and second electrodes and secured to the housing.
  • 15. The system of claim 13, wherein the ingestible identifier operated in the detection mode to gather information associated with an implanted pulse generator, and wherein during the broadcast mode the ingestible identifier produces a unique current signature containing the information associated with the implanted pulse generator.
  • 16. The system of claim 13, wherein the ingestible identifier comprises a sensor that detects a physiological parameter and combines data associated with the physiological parameters with the data associated with myoelectric information and during the broadcast mode the ingestible identifier produces a unique current signature containing the combined information.
CROSS REFERENCE

Pursuant to 35 U.S.C. §119 (e), this application claims priority to the filing dates of U.S. Provisional Application Ser. Nos. 61/121,878 filed on Dec. 11, 2008, and U.S. Provisional Application Ser. Nos. 61/121,881 filed on Dec. 11, 2008, each of the disclosures of which is herein incorporated by reference in their entirety.

US Referenced Citations (781)
Number Name Date Kind
3589943 Grubb et al. Jun 1971 A
3607788 Adolph Sep 1971 A
3642008 Bolduc Feb 1972 A
3679480 Brown et al. Jul 1972 A
3682160 Murata Aug 1972 A
3719183 Schwartz Mar 1973 A
3799802 Schneble, Jr. et al. Mar 1974 A
3828766 Krasnow Aug 1974 A
3837339 Aisenberg et al. Sep 1974 A
3893111 Cotter Jul 1975 A
3944064 Bashaw et al. Mar 1976 A
3967202 Batz Jun 1976 A
3989050 Buchalter Nov 1976 A
4017856 Wiegand Apr 1977 A
4055178 Harrigan Oct 1977 A
4077397 Ellis Mar 1978 A
4077398 Ellis Mar 1978 A
4082087 Howson Apr 1978 A
4090752 Long May 1978 A
4106348 Auphan Aug 1978 A
4129125 Lester Dec 1978 A
4166453 McClelland Sep 1979 A
4239046 Ong Dec 1980 A
4251795 Shibasaki et al. Feb 1981 A
4269189 Abraham May 1981 A
4331654 Morris May 1982 A
4345588 Widder et al. Aug 1982 A
4418697 Tama Dec 1983 A
4425117 Hugemann et al. Jan 1984 A
4494950 Fischell Jan 1985 A
4559950 Vaughan Dec 1985 A
4564363 Bagnall et al. Jan 1986 A
4578061 Lemelson Mar 1986 A
4635641 Hoffman Jan 1987 A
4654165 Eisenberg Mar 1987 A
4663250 Ong et al. May 1987 A
4669479 Dunseath Jun 1987 A
4681111 Silvian Jul 1987 A
4725997 Urquhart et al. Feb 1988 A
4763659 Dunseath Aug 1988 A
4767627 Caldwell et al. Aug 1988 A
4784162 Ricks Nov 1988 A
4793825 Benjamin et al. Dec 1988 A
4844076 Lesho Jul 1989 A
4896261 Nolan Jan 1990 A
4975230 Pinkhasov Dec 1990 A
4987897 Funke Jan 1991 A
5016634 Vock et al. May 1991 A
5079006 Urquhart Jan 1992 A
5167626 Casper Dec 1992 A
5176626 Soehendra Jan 1993 A
5261402 DiSabito Nov 1993 A
5263481 Axelgaard et al. Nov 1993 A
5279607 Schentag et al. Jan 1994 A
5281287 Lloyd Jan 1994 A
5283136 Peled et al. Feb 1994 A
5305745 Zacouto Apr 1994 A
5318557 Gross Jun 1994 A
5394882 Mawhinney Mar 1995 A
5395366 D'Andrea et al. Mar 1995 A
5436091 Shackle et al. Jul 1995 A
5443461 Atkinson et al. Aug 1995 A
5443843 Curatolo et al. Aug 1995 A
5458141 Neil et al. Oct 1995 A
5485841 Watkin et al. Jan 1996 A
5511548 Riazzi et al. Apr 1996 A
5567210 Bates et al. Oct 1996 A
5596302 Mastrocola et al. Jan 1997 A
5600548 Nguyen et al. Feb 1997 A
5634466 Gruner Jun 1997 A
5634468 Platt Jun 1997 A
5645063 Straka et al. Jul 1997 A
5705189 Lehmann et al. Jan 1998 A
5720771 Snell Feb 1998 A
5738708 Peachey et al. Apr 1998 A
5740811 Hedberg Apr 1998 A
5757326 Koyama et al. May 1998 A
5792048 Schaefer Aug 1998 A
5802467 Salazar Sep 1998 A
5833716 Bar-Or Nov 1998 A
5845265 Woolston Dec 1998 A
5862803 Besson Jan 1999 A
5862808 Albarello Jan 1999 A
5868136 Fox Feb 1999 A
5921925 Cartmell et al. Jul 1999 A
5925030 Gross et al. Jul 1999 A
5925066 Kroll et al. Jul 1999 A
5957854 Besson Sep 1999 A
5963132 Yoakum et al. Oct 1999 A
5974124 Schlueter, Jr. et al. Oct 1999 A
5981166 Mandecki Nov 1999 A
5999846 Pardey et al. Dec 1999 A
6023631 Cartmell et al. Feb 2000 A
6038464 Axelgaard et al. Mar 2000 A
6042710 Dubrow Mar 2000 A
6047203 Sackner Apr 2000 A
6076016 Feierbach et al. Jun 2000 A
6081734 Batz Jun 2000 A
6083248 Thompson Jul 2000 A
6091975 Daddona et al. Jul 2000 A
6095985 Raymond et al. Aug 2000 A
6115636 Ryan Sep 2000 A
6122351 Schlueter, Jr. et al. Sep 2000 A
6141592 Pauly Oct 2000 A
6200265 Walsh et al. Mar 2001 B1
6204764 Maloney Mar 2001 B1
6206702 Hayden et al. Mar 2001 B1
6217744 Crosby Apr 2001 B1
6231593 Meserol May 2001 B1
6245057 Sieben et al. Jun 2001 B1
6269058 Yamanoi et al. Jul 2001 B1
6275476 Wood Aug 2001 B1
6285897 Kilcoyne et al. Sep 2001 B1
6287252 Lugo Sep 2001 B1
6288629 Cofino et al. Sep 2001 B1
6289238 Besson Sep 2001 B1
6315719 Rode et al. Nov 2001 B1
6342774 Kreisinger et al. Jan 2002 B1
6358202 Arent Mar 2002 B1
6364834 Reuss Apr 2002 B1
6366206 Ishikawa et al. Apr 2002 B1
6368190 Easter et al. Apr 2002 B1
6371927 Brune Apr 2002 B1
6374670 Spelman Apr 2002 B1
6380858 Yarin et al. Apr 2002 B1
6394997 Lemelson May 2002 B1
6409674 Brockway et al. Jun 2002 B1
6426863 Munshi Jul 2002 B1
6432292 Pinto et al. Aug 2002 B1
6440069 Raymond et al. Aug 2002 B1
6441747 Khair Aug 2002 B1
6453199 Kobozev Sep 2002 B1
6477424 Thompson et al. Nov 2002 B1
6494829 New et al. Dec 2002 B1
6496705 Ng et al. Dec 2002 B1
6526315 Inagawa Feb 2003 B1
6531026 Takeichi et al. Mar 2003 B1
6544174 West Apr 2003 B2
6564079 Cory May 2003 B1
6572636 Hagen et al. Jun 2003 B1
6577893 Besson Jun 2003 B1
6579231 Phipps Jun 2003 B1
6595929 Stivoric Jul 2003 B2
6605038 Teller Aug 2003 B1
6609018 Cory Aug 2003 B2
6612984 Kerr Sep 2003 B1
6632175 Marshall Oct 2003 B1
6632216 Houzego et al. Oct 2003 B2
6635279 Kolter et al. Oct 2003 B2
6643541 Mok et al. Nov 2003 B2
6654638 Sweeney Nov 2003 B1
6663846 McCombs Dec 2003 B1
6673474 Yamamoto Jan 2004 B2
6680923 Leon Jan 2004 B1
6689117 Sweeney et al. Feb 2004 B2
6694161 Mehrotra Feb 2004 B2
6704602 Berg et al. Mar 2004 B2
6720923 Hayward et al. Apr 2004 B1
6738671 Christophersom et al. May 2004 B2
6740033 Olejniczak et al. May 2004 B1
6745082 Axelgaard et al. Jun 2004 B2
6755783 Cosentino Jun 2004 B2
6757523 Fry Jun 2004 B2
6759968 Zierolf Jul 2004 B2
6800060 Marshall Oct 2004 B2
6801137 Eggers et al. Oct 2004 B2
6814706 Barton et al. Nov 2004 B2
6822554 Vrijens et al. Nov 2004 B2
6836862 Erekson et al. Dec 2004 B1
6839659 Tarassenko et al. Jan 2005 B2
6840904 Goldberg Jan 2005 B2
6845272 Thomsen Jan 2005 B1
6864780 Doi Mar 2005 B2
6879810 Bouet Apr 2005 B2
6882881 Lesser et al. Apr 2005 B1
6897788 Khair et al. May 2005 B2
6909878 Haller Jun 2005 B2
6922592 Thompson et al. Jul 2005 B2
6928370 Anuzis et al. Aug 2005 B2
6929636 Von Alten Aug 2005 B1
6937150 Medema Aug 2005 B2
6942616 Kerr Sep 2005 B2
6951536 Yokoi Oct 2005 B2
6957107 Rogers et al. Oct 2005 B2
6959929 Pugnet et al. Nov 2005 B2
6968153 Heinonen Nov 2005 B1
6987965 Ng et al. Jan 2006 B2
6990082 Zehavi et al. Jan 2006 B1
7002476 Rapchak Feb 2006 B2
7004395 Koenck Feb 2006 B2
7009634 Iddan et al. Mar 2006 B2
7009946 Kardach Mar 2006 B1
7013162 Gorsuch Mar 2006 B2
7016648 Haller Mar 2006 B2
7020508 Stivoric Mar 2006 B2
7024248 Penner et al. Apr 2006 B2
7031745 Shen Apr 2006 B2
7031857 Tarassenko et al. Apr 2006 B2
7039453 Mullick May 2006 B2
7044911 Drinan et al. May 2006 B2
7046649 Awater et al. May 2006 B2
7118531 Krill Oct 2006 B2
7127300 Mazar et al. Oct 2006 B2
7146228 Nielsen Dec 2006 B2
7146449 Do et al. Dec 2006 B2
7149581 Goedeke et al. Dec 2006 B2
7154071 Sattler et al. Dec 2006 B2
7155232 Godfrey et al. Dec 2006 B2
7160258 Imran Jan 2007 B2
7161484 Tsoukalis Jan 2007 B2
7164942 Avrahami Jan 2007 B2
7171166 Ng et al. Jan 2007 B2
7171177 Park et al. Jan 2007 B2
7171259 Rytky Jan 2007 B2
7176784 Gilbert et al. Feb 2007 B2
7187960 Abreu Mar 2007 B2
7188767 Penuela Mar 2007 B2
7194038 Inkinen Mar 2007 B1
7206630 Tarler Apr 2007 B1
7209790 Thompson et al. Apr 2007 B2
7215660 Perlman May 2007 B2
7215991 Besson May 2007 B2
7218967 Bergelson May 2007 B2
7231451 Law Jun 2007 B2
7243118 Lou Jul 2007 B2
7246521 Kim Jul 2007 B2
7249212 Do Jul 2007 B2
7252792 Perrault Aug 2007 B2
7253716 Lovoi et al. Aug 2007 B2
7261690 Teller Aug 2007 B2
7270633 Goscha Sep 2007 B1
7273454 Raymond et al. Sep 2007 B2
7285090 Stivoric et al. Oct 2007 B2
7289855 Nghiem Oct 2007 B2
7291497 Holmes Nov 2007 B2
7292139 Mazar et al. Nov 2007 B2
7294105 Islam Nov 2007 B1
7313163 Liu Dec 2007 B2
7317378 Jarvis et al. Jan 2008 B2
7318808 Tarassenko et al. Jan 2008 B2
7336929 Yasuda Feb 2008 B2
7342895 Serpa Mar 2008 B2
7346380 Axelgaard et al. Mar 2008 B2
7349722 Witkowski et al. Mar 2008 B2
7352998 Palin Apr 2008 B2
7353258 Washburn Apr 2008 B2
7357891 Yang et al. Apr 2008 B2
7359674 Markki Apr 2008 B2
7366558 Virtanen et al. Apr 2008 B2
7368190 Heller et al. May 2008 B2
7368191 Andelman et al. May 2008 B2
7373196 Ryu et al. May 2008 B2
7375739 Robbins May 2008 B2
7376435 McGowan May 2008 B2
7382263 Danowski et al. Jun 2008 B2
7387607 Holt Jun 2008 B2
7388903 Godfrey et al. Jun 2008 B2
7389088 Kim Jun 2008 B2
7392015 Farlow Jun 2008 B1
7395106 Ryu et al. Jul 2008 B2
7396330 Banet Jul 2008 B2
7404968 Abrams et al. Jul 2008 B2
7413544 Kerr Aug 2008 B2
7414534 Kroll et al. Aug 2008 B1
7414543 Rye et al. Aug 2008 B2
8224667 Rye et al. Aug 2008 B1
7424268 Diener Sep 2008 B2
7424319 Muehlsteff Sep 2008 B2
7427266 Ayer et al. Sep 2008 B2
7471665 Perlman Dec 2008 B2
7499674 Salokannel Mar 2009 B2
7502643 Farringdon et al. Mar 2009 B2
7505795 Lim et al. Mar 2009 B1
7510121 Koenck Mar 2009 B2
7512448 Malick Mar 2009 B2
7515043 Welch Apr 2009 B2
7519416 Sula et al. Apr 2009 B2
7523756 Minai Apr 2009 B2
7525426 Edelstein Apr 2009 B2
7539533 Tran May 2009 B2
7542878 Nanikashvili Jun 2009 B2
7551590 Haller Jun 2009 B2
7554452 Cole Jun 2009 B2
7575005 Mumford Aug 2009 B2
7616111 Covannon Nov 2009 B2
7617001 Penner et al. Nov 2009 B2
7639473 Hsu et al. Dec 2009 B2
7640802 King et al. Jan 2010 B2
7647112 Tracey Jan 2010 B2
7647185 Tarassenko et al. Jan 2010 B2
7653031 Godfrey et al. Jan 2010 B2
7668437 Yamada et al. Feb 2010 B1
7672703 Yeo et al. Mar 2010 B2
7672714 Kuo Mar 2010 B2
7673679 Harrison et al. Mar 2010 B2
7678043 Gilad Mar 2010 B2
7689437 Teller et al. Mar 2010 B1
7697994 VanDanacker et al. Apr 2010 B2
7720036 Sadri May 2010 B2
7729776 Von Arx et al. Jun 2010 B2
7733224 Tran Jun 2010 B2
7736318 Cosentino Jun 2010 B2
7756587 Penner et al. Jul 2010 B2
7796043 Euliano et al. Sep 2010 B2
7797033 D'Andrea et al. Sep 2010 B2
7809399 Lu Oct 2010 B2
7844341 Von Arx et al. Nov 2010 B2
7904133 Gehman et al. Mar 2011 B2
8073707 Teller et al. Dec 2011 B2
8083128 Dembo et al. Dec 2011 B2
8123576 Kim Feb 2012 B2
8180425 Selvitelli et al. May 2012 B2
8200320 Kovacs Jun 2012 B2
8214007 Baker et al. Jul 2012 B2
8238998 Park Aug 2012 B2
8249686 Libbus et al. Aug 2012 B2
8258962 Robertson et al. Sep 2012 B2
8285356 Bly et al. Oct 2012 B2
8290574 Feild et al. Oct 2012 B2
8301232 Albert et al. Oct 2012 B2
8308640 Baldus et al. Nov 2012 B2
8315687 Cross et al. Nov 2012 B2
8369936 Farringdon et al. Feb 2013 B2
8386009 Lindberg et al. Feb 2013 B2
20010027331 Thompson Oct 2001 A1
20010044588 Mault Nov 2001 A1
20010051766 Gazdzinski Dec 2001 A1
20020002326 Causey, III Jan 2002 A1
20020026111 Ackerman Feb 2002 A1
20020032385 Raymond et al. Mar 2002 A1
20020040278 Anuzis et al. Apr 2002 A1
20020077620 Sweeney et al. Jun 2002 A1
20020132226 Nair Sep 2002 A1
20020192159 Reitberg Dec 2002 A1
20020193669 Glukhovsky Dec 2002 A1
20020193846 Pool et al. Dec 2002 A1
20020198470 Imran et al. Dec 2002 A1
20030017826 Fishman Jan 2003 A1
20030023150 Yokoi et al. Jan 2003 A1
20030028226 Thompson Feb 2003 A1
20030063522 Sagar Apr 2003 A1
20030065536 Hansen Apr 2003 A1
20030076179 Branch et al. Apr 2003 A1
20030083559 Thompson May 2003 A1
20030126593 Mault Jul 2003 A1
20030130714 Nielsen et al. Jul 2003 A1
20030135128 Suffin et al. Jul 2003 A1
20030135392 Vrijens et al. Jul 2003 A1
20030152622 Louie-Helm et al. Aug 2003 A1
20030158466 Lynn et al. Aug 2003 A1
20030158756 Abramson Aug 2003 A1
20030162556 Libes Aug 2003 A1
20030167000 Mullick et al. Sep 2003 A1
20030171791 KenKnight Sep 2003 A1
20030171898 Tarassenko et al. Sep 2003 A1
20030181788 Yokoi et al. Sep 2003 A1
20030181815 Ebner et al. Sep 2003 A1
20030185286 Yuen Oct 2003 A1
20030187337 Tarassenko et al. Oct 2003 A1
20030187338 Say et al. Oct 2003 A1
20030195403 Berner et al. Oct 2003 A1
20030213495 Fujita et al. Nov 2003 A1
20030214579 Iddan Nov 2003 A1
20030216622 Meron et al. Nov 2003 A1
20030216625 Phipps Nov 2003 A1
20030216666 Ericson et al. Nov 2003 A1
20030216729 Marchitto Nov 2003 A1
20040008123 Carrender et al. Jan 2004 A1
20040018476 LaDue Jan 2004 A1
20040019172 Yang et al. Jan 2004 A1
20040034295 Salganicoff Feb 2004 A1
20040049245 Gass Mar 2004 A1
20040073095 Causey et al. Apr 2004 A1
20040073454 Urquhart et al. Apr 2004 A1
20040077995 Ferek-Petric Apr 2004 A1
20040082982 Gord et al. Apr 2004 A1
20040087839 Raymond et al. May 2004 A1
20040092801 Drakulic May 2004 A1
20040106859 Say et al. Jun 2004 A1
20040115517 Fukada et al. Jun 2004 A1
20040121015 Chidlaw et al. Jun 2004 A1
20040148140 Tarassenko et al. Jul 2004 A1
20040153007 Harris Aug 2004 A1
20040162501 Imran Aug 2004 A1
20040167226 Serafini Aug 2004 A1
20040167801 Say et al. Aug 2004 A1
20040193020 Chiba Sep 2004 A1
20040193029 Glukhovsky Sep 2004 A1
20040193446 Mayer et al. Sep 2004 A1
20040199222 Sun et al. Oct 2004 A1
20040215084 Shimizu et al. Oct 2004 A1
20040218683 Batra Nov 2004 A1
20040220643 Schmidt Nov 2004 A1
20040224644 Wu Nov 2004 A1
20040225199 Evanyk Nov 2004 A1
20040253304 Gross et al. Dec 2004 A1
20040260154 Sidelnik Dec 2004 A1
20050017841 Doi Jan 2005 A1
20050020887 Goldberg Jan 2005 A1
20050021103 DiLorenzo Jan 2005 A1
20050021370 Riff Jan 2005 A1
20050024198 Ward Feb 2005 A1
20050027205 Tarassenko et al. Feb 2005 A1
20050038321 Fujita et al. Feb 2005 A1
20050043634 Yokoi et al. Feb 2005 A1
20050043894 Fernandez Feb 2005 A1
20050054897 Hashimoto et al. Mar 2005 A1
20050062644 Leci Mar 2005 A1
20050065407 Nakamura et al. Mar 2005 A1
20050070778 Lackey Mar 2005 A1
20050090753 Goor et al. Apr 2005 A1
20050096514 Starkebaum May 2005 A1
20050096562 Delalic et al. May 2005 A1
20050101843 Quinn May 2005 A1
20050101872 Sattler May 2005 A1
20050115561 Stahmann et al. Jun 2005 A1
20050116820 Goldreich Jun 2005 A1
20050117389 Worledge Jun 2005 A1
20050121322 Say et al. Jun 2005 A1
20050131281 Ayer et al. Jun 2005 A1
20050137480 Alt et al. Jun 2005 A1
20050143623 Kojima Jun 2005 A1
20050148883 Boesen Jul 2005 A1
20050151625 Lai Jul 2005 A1
20050154428 Bruinsma Jul 2005 A1
20050156709 Gilbert et al. Jul 2005 A1
20050165323 Montgomery Jul 2005 A1
20050177069 Takizawa Aug 2005 A1
20050182389 LaPorte Aug 2005 A1
20050187789 Hatlestad et al. Aug 2005 A1
20050192489 Marshall Sep 2005 A1
20050197680 DelMain et al. Sep 2005 A1
20050228268 Cole Oct 2005 A1
20050234307 Heinonen Oct 2005 A1
20050240305 Bogash et al. Oct 2005 A1
20050245794 Dinsmoor Nov 2005 A1
20050245839 Stivoric et al. Nov 2005 A1
20050259768 Yang et al. Nov 2005 A1
20050261559 Mumford Nov 2005 A1
20050267556 Shuros et al. Dec 2005 A1
20050267756 Schultz et al. Dec 2005 A1
20050277912 John Dec 2005 A1
20050277999 Strother et al. Dec 2005 A1
20050285746 Sengupta Dec 2005 A1
20050288594 Lewkowicz et al. Dec 2005 A1
20060001496 Abrosimov et al. Jan 2006 A1
20060028727 Moon et al. Feb 2006 A1
20060036134 Tarassenko et al. Feb 2006 A1
20060058602 Kwiatkowski et al. Mar 2006 A1
20060061472 Lovoi et al. Mar 2006 A1
20060065713 Kingery Mar 2006 A1
20060068006 Begleiter Mar 2006 A1
20060074283 Henderson Apr 2006 A1
20060078765 Yang et al. Apr 2006 A1
20060095091 Drew May 2006 A1
20060095093 Bettesh et al. May 2006 A1
20060100533 Han May 2006 A1
20060109058 Keating May 2006 A1
20060110962 Powell May 2006 A1
20060122474 Teller et al. Jun 2006 A1
20060122667 Chavan et al. Jun 2006 A1
20060136266 Tarassenko et al. Jun 2006 A1
20060142648 Banet Jun 2006 A1
20060145876 Kimura Jul 2006 A1
20060148254 McLean Jul 2006 A1
20060149339 Burnes Jul 2006 A1
20060155174 Glukhovsky et al. Jul 2006 A1
20060155183 Kroecker Jul 2006 A1
20060158820 Takiguchi Jul 2006 A1
20060161225 Sormann et al. Jul 2006 A1
20060179949 Kim Aug 2006 A1
20060183992 Kawashima Aug 2006 A1
20060183993 Horn Aug 2006 A1
20060184092 Atanasoska et al. Aug 2006 A1
20060204738 Dubrow et al. Sep 2006 A1
20060210626 Spaeder Sep 2006 A1
20060216603 Choi Sep 2006 A1
20060218011 Walker Sep 2006 A1
20060229053 Sivard Oct 2006 A1
20060235489 Drew Oct 2006 A1
20060243288 Kim et al. Nov 2006 A1
20060247505 Siddiqui Nov 2006 A1
20060253005 Drinan Nov 2006 A1
20060265246 Hoag Nov 2006 A1
20060270346 Ibrahim Nov 2006 A1
20060273882 Posamentier Dec 2006 A1
20060276702 McGinnis Dec 2006 A1
20060280227 Pinkney Dec 2006 A1
20060282001 Noel Dec 2006 A1
20060289640 Mercure Dec 2006 A1
20060293607 Alt Dec 2006 A1
20070002038 Suzuki Jan 2007 A1
20070006636 King et al. Jan 2007 A1
20070008113 Spoonhower et al. Jan 2007 A1
20070016089 Fischell et al. Jan 2007 A1
20070027386 Such Feb 2007 A1
20070027388 Chou Feb 2007 A1
20070038054 Zhou Feb 2007 A1
20070049339 Barak et al. Mar 2007 A1
20070055098 Shimizu et al. Mar 2007 A1
20070060797 Ball Mar 2007 A1
20070060800 Drinan et al. Mar 2007 A1
20070073353 Rooney et al. Mar 2007 A1
20070096765 Kagan May 2007 A1
20070106346 Bergelson May 2007 A1
20070123772 Euliano May 2007 A1
20070129622 Bourget Jun 2007 A1
20070130287 Kumar Jun 2007 A1
20070135691 Zingelewicz et al. Jun 2007 A1
20070135803 Belson Jun 2007 A1
20070142721 Berner et al. Jun 2007 A1
20070156016 Betesh Jul 2007 A1
20070162089 Mosesov Jul 2007 A1
20070162090 Penner Jul 2007 A1
20070167495 Brown et al. Jul 2007 A1
20070167848 Kuo et al. Jul 2007 A1
20070173701 Al-Ali Jul 2007 A1
20070179347 Tarassenko et al. Aug 2007 A1
20070179371 Peyser et al. Aug 2007 A1
20070185393 Zhou Aug 2007 A1
20070191002 Ge Aug 2007 A1
20070196456 Stevens Aug 2007 A1
20070207793 Myer Sep 2007 A1
20070208233 Kovacs Sep 2007 A1
20070213659 Trovato et al. Sep 2007 A1
20070237719 Jones Oct 2007 A1
20070244370 Kuo et al. Oct 2007 A1
20070255198 Leong et al. Nov 2007 A1
20070255330 Lee Nov 2007 A1
20070270672 Hayter Nov 2007 A1
20070279217 Venkatraman Dec 2007 A1
20070282174 Sabatino Dec 2007 A1
20070282177 Pilz Dec 2007 A1
20070299480 Hill Dec 2007 A1
20080014866 Lipowski Jan 2008 A1
20080015421 Penner Jan 2008 A1
20080020037 Robertson et al. Jan 2008 A1
20080021519 DeGeest Jan 2008 A1
20080021521 Shah Jan 2008 A1
20080027679 Shklarski Jan 2008 A1
20080033273 Zhou Feb 2008 A1
20080039700 Drinan et al. Feb 2008 A1
20080045843 Tsuji et al. Feb 2008 A1
20080046038 Hill Feb 2008 A1
20080051647 Wu et al. Feb 2008 A1
20080051667 Goldreich Feb 2008 A1
20080051767 Rossing et al. Feb 2008 A1
20080058614 Banet Mar 2008 A1
20080062856 Feher Mar 2008 A1
20080065168 Bitton et al. Mar 2008 A1
20080074307 Boric-Lubecke Mar 2008 A1
20080077015 Boric-Lubecke Mar 2008 A1
20080077028 Schaldach et al. Mar 2008 A1
20080077188 Denker et al. Mar 2008 A1
20080091089 Guillory et al. Apr 2008 A1
20080091114 Min Apr 2008 A1
20080097549 Colbaugh Apr 2008 A1
20080097917 Dicks et al. Apr 2008 A1
20080103440 Ferren et al. May 2008 A1
20080114224 Bandy et al. May 2008 A1
20080119705 Patel May 2008 A1
20080119716 Boric-Lubecke May 2008 A1
20080121825 Trovato et al. May 2008 A1
20080137566 Marholev Jun 2008 A1
20080140403 Hughes et al. Jun 2008 A1
20080146871 Arneson et al. Jun 2008 A1
20080146889 Young Jun 2008 A1
20080146892 LeBoeuf Jun 2008 A1
20080154104 Lamego Jun 2008 A1
20080166992 Ricordi Jul 2008 A1
20080175898 Jones et al. Jul 2008 A1
20080183245 Van Oort Jul 2008 A1
20080188837 Belsky et al. Aug 2008 A1
20080194912 Trovato et al. Aug 2008 A1
20080208009 Shklarski Aug 2008 A1
20080214901 Gehman Sep 2008 A1
20080214985 Yanaki Sep 2008 A1
20080243020 Chou Oct 2008 A1
20080249360 Li Oct 2008 A1
20080262320 Schaefer et al. Oct 2008 A1
20080262336 Ryu Oct 2008 A1
20080269664 Trovato et al. Oct 2008 A1
20080275312 Mosesov Nov 2008 A1
20080281636 Jung et al. Nov 2008 A1
20080284599 Zdeblick et al. Nov 2008 A1
20080288026 Cross et al. Nov 2008 A1
20080294020 Sapounas Nov 2008 A1
20080299197 Toneguzzo et al. Dec 2008 A1
20080300572 Rankers Dec 2008 A1
20080303638 Nguyen Dec 2008 A1
20080306357 Korman Dec 2008 A1
20080306359 Zdeblick et al. Dec 2008 A1
20080306360 Robertson et al. Dec 2008 A1
20080311852 Hansen Dec 2008 A1
20080312522 Rowlandson Dec 2008 A1
20080316020 Robertson Dec 2008 A1
20090009330 Sakama et al. Jan 2009 A1
20090009332 Nunez et al. Jan 2009 A1
20090024045 Prakash Jan 2009 A1
20090030293 Cooper et al. Jan 2009 A1
20090030297 Miller Jan 2009 A1
20090034209 Joo Feb 2009 A1
20090043171 Rule Feb 2009 A1
20090048498 Riskey Feb 2009 A1
20090062634 Say et al. Mar 2009 A1
20090062670 Sterling Mar 2009 A1
20090069642 Gao Mar 2009 A1
20090069655 Say et al. Mar 2009 A1
20090069656 Say et al. Mar 2009 A1
20090069657 Say et al. Mar 2009 A1
20090069658 Say et al. Mar 2009 A1
20090076340 Libbus et al. Mar 2009 A1
20090076343 James Mar 2009 A1
20090076397 Libbus et al. Mar 2009 A1
20090082645 Hafezi et al. Mar 2009 A1
20090087483 Sison Apr 2009 A1
20090088618 Ameson Apr 2009 A1
20090099435 Say et al. Apr 2009 A1
20090105561 Boyden et al. Apr 2009 A1
20090110148 Zhang Apr 2009 A1
20090112626 Talbot Apr 2009 A1
20090124871 Arshak May 2009 A1
20090131774 Sweitzer May 2009 A1
20090135886 Robertson et al. May 2009 A1
20090157113 Marcotte Jun 2009 A1
20090157358 Kim Jun 2009 A1
20090161602 Matsumoto Jun 2009 A1
20090163789 Say et al. Jun 2009 A1
20090171180 Pering Jul 2009 A1
20090173628 Say et al. Jul 2009 A1
20090177055 Say et al. Jul 2009 A1
20090177056 Say et al. Jul 2009 A1
20090177057 Say et al. Jul 2009 A1
20090177058 Say et al. Jul 2009 A1
20090177059 Say et al. Jul 2009 A1
20090177060 Say et al. Jul 2009 A1
20090177061 Say et al. Jul 2009 A1
20090177062 Say et al. Jul 2009 A1
20090177063 Say et al. Jul 2009 A1
20090177064 Say et al. Jul 2009 A1
20090177065 Say et al. Jul 2009 A1
20090177066 Say et al. Jul 2009 A1
20090182206 Najafi Jul 2009 A1
20090182212 Say et al. Jul 2009 A1
20090182213 Say et al. Jul 2009 A1
20090182214 Say et al. Jul 2009 A1
20090182215 Say et al. Jul 2009 A1
20090182388 Von Arx Jul 2009 A1
20090187088 Say et al. Jul 2009 A1
20090187089 Say et al. Jul 2009 A1
20090187090 Say et al. Jul 2009 A1
20090187091 Say et al. Jul 2009 A1
20090187092 Say et al. Jul 2009 A1
20090187093 Say et al. Jul 2009 A1
20090187094 Say et al. Jul 2009 A1
20090187095 Say et al. Jul 2009 A1
20090187381 King et al. Jul 2009 A1
20090192351 Nishino Jul 2009 A1
20090192368 Say et al. Jul 2009 A1
20090192369 Say et al. Jul 2009 A1
20090192370 Say et al. Jul 2009 A1
20090192371 Say et al. Jul 2009 A1
20090192372 Say et al. Jul 2009 A1
20090192373 Say et al. Jul 2009 A1
20090192374 Say et al. Jul 2009 A1
20090192375 Say et al. Jul 2009 A1
20090192376 Say et al. Jul 2009 A1
20090192377 Say et al. Jul 2009 A1
20090192378 Say et al. Jul 2009 A1
20090192379 Say et al. Jul 2009 A1
20090198115 Say et al. Aug 2009 A1
20090198116 Say et al. Aug 2009 A1
20090198175 Say et al. Aug 2009 A1
20090203964 Shimizu et al. Aug 2009 A1
20090203971 Sciarappa Aug 2009 A1
20090203972 Heneghan Aug 2009 A1
20090203978 Say et al. Aug 2009 A1
20090204265 Hackett Aug 2009 A1
20090210164 Say et al. Aug 2009 A1
20090216101 Say et al. Aug 2009 A1
20090216102 Say et al. Aug 2009 A1
20090227204 Robertson et al. Sep 2009 A1
20090227876 Tran Sep 2009 A1
20090227940 Say et al. Sep 2009 A1
20090227941 Say et al. Sep 2009 A1
20090227988 Wood et al. Sep 2009 A1
20090228214 Say et al. Sep 2009 A1
20090231125 Baldus Sep 2009 A1
20090234200 Husheer Sep 2009 A1
20090243833 Huang Oct 2009 A1
20090253960 Takenaka et al. Oct 2009 A1
20090256702 Robertson Oct 2009 A1
20090264714 Chou Oct 2009 A1
20090264964 Abrahamson Oct 2009 A1
20090265186 Tarassenko et al. Oct 2009 A1
20090273467 Elixmann Nov 2009 A1
20090281539 Selig Nov 2009 A1
20090292194 Libbus et al. Nov 2009 A1
20090295548 Ronkka Dec 2009 A1
20090296677 Mahany Dec 2009 A1
20090303920 Mahany Dec 2009 A1
20090306633 Trovato et al. Dec 2009 A1
20090312619 Say et al. Dec 2009 A1
20090318761 Rabinovitz Dec 2009 A1
20090318779 Tran Dec 2009 A1
20090318783 Rohde Dec 2009 A1
20090318793 Datta Dec 2009 A1
20100001841 Cardullo Jan 2010 A1
20100006585 Flowers et al. Jan 2010 A1
20100010330 Rankers Jan 2010 A1
20100049004 Edman et al. Feb 2010 A1
20100049006 Magar Feb 2010 A1
20100049012 Dijksman et al. Feb 2010 A1
20100049069 Tarassenko et al. Feb 2010 A1
20100056878 Partin Mar 2010 A1
20100056891 Say et al. Mar 2010 A1
20100056939 Tarassenko et al. Mar 2010 A1
20100057041 Hayter Mar 2010 A1
20100062709 Kato Mar 2010 A1
20100063438 Bengtsson Mar 2010 A1
20100063841 D'Ambrosia et al. Mar 2010 A1
20100069002 Rong Mar 2010 A1
20100069717 Hafezi et al. Mar 2010 A1
20100081894 Zdeblick et al. Apr 2010 A1
20100099967 Say et al. Apr 2010 A1
20100099968 Say et al. Apr 2010 A1
20100099969 Say et al. Apr 2010 A1
20100100077 Rush Apr 2010 A1
20100100078 Say et al. Apr 2010 A1
20100106001 Say et al. Apr 2010 A1
20100118853 Godfrey May 2010 A1
20100139672 Kroll et al. Jun 2010 A1
20100160742 Seidl et al. Jun 2010 A1
20100168659 Say et al. Jul 2010 A1
20100179398 Say et al. Jul 2010 A1
20100185055 Robertson Jul 2010 A1
20100191073 Tarassenko et al. Jul 2010 A1
20100210299 Gorbachov Aug 2010 A1
20100222652 Cho Sep 2010 A1
20100228113 Solosko Sep 2010 A1
20100234706 Gilland Sep 2010 A1
20100234715 Shin Sep 2010 A1
20100234914 Shen Sep 2010 A1
20100245091 Singh Sep 2010 A1
20100249881 Corndorf Sep 2010 A1
20100256461 Mohamedali Oct 2010 A1
20100259543 Tarassenko et al. Oct 2010 A1
20100268048 Say et al. Oct 2010 A1
20100268049 Say et al. Oct 2010 A1
20100268050 Say et al. Oct 2010 A1
20100274111 Say et al. Oct 2010 A1
20100280345 Say et al. Nov 2010 A1
20100280346 Say et al. Nov 2010 A1
20100295694 Kauffman et al. Nov 2010 A1
20100298668 Hafezi et al. Nov 2010 A1
20100298730 Tarassenko et al. Nov 2010 A1
20100299155 Findlay et al. Nov 2010 A1
20100312188 Robertson et al. Dec 2010 A1
20100312580 Tarassenko et al. Dec 2010 A1
20100332443 Gartenberg Dec 2010 A1
20110009715 O'Reilly et al. Jan 2011 A1
20110040203 Savage et al. Feb 2011 A1
20110050431 Hood et al. Mar 2011 A1
20110054265 Hafezi et al. Mar 2011 A1
20110065983 Hafezi et al. Mar 2011 A1
20110077660 Janik et al. Mar 2011 A1
20110105864 Robertson et al. May 2011 A1
20110124983 Kroll et al. May 2011 A1
20110144470 Mazar et al. Jun 2011 A1
20110224912 Bhavaraju et al. Sep 2011 A1
20110230732 Edman et al. Sep 2011 A1
20110279963 Kumar et al. Nov 2011 A1
20120029309 Paquet et al. Feb 2012 A1
20120062371 Radivojevic et al. Mar 2012 A1
20120101396 Solosko et al. Apr 2012 A1
20120197144 Christ et al. Aug 2012 A1
20120265544 Hwang et al. Oct 2012 A1
20120310070 Kumar et al. Dec 2012 A1
20120316413 Liu et al. Dec 2012 A1
20130030259 Thomsen et al. Jan 2013 A1
20130060115 Gehman et al. Mar 2013 A1
Foreign Referenced Citations (147)
Number Date Country
1991868 Jul 2007 CN
101005470 Jul 2007 CN
201076456 Jun 2008 CN
1246356 Oct 2002 EP
15434054 May 2005 EP
1702553 Sep 2006 EP
1789128 May 2007 EP
2143369 Jan 2010 EP
2432862 Jun 2007 GB
61017949 Jan 1986 JP
05-228128 Sep 1993 JP
10-14898 Jan 1998 JP
2000-506410 May 2000 JP
2002291684 Oct 2002 JP
2004-7187 Jan 2004 JP
2004134384 Apr 2004 JP
2005-073886 Mar 2005 JP
2005-087552 Apr 2005 JP
2005-304880 Apr 2005 JP
2005-532841 Nov 2005 JP
2005-532849 Nov 2005 JP
2006509574 Mar 2006 JP
2006-177699 Jul 2006 JP
2006-187611 Jul 2006 JP
2006278091 Oct 2006 JP
2007-313340 Dec 2007 JP
2009-061236 Mar 2009 JP
20020015907 Mar 2002 KR
20020061744 Jul 2002 KR
927471 Nov 2009 KR
553735 Sep 2003 TW
200724094 Jul 2007 TW
8802237 Apr 1988 WO
WO9221307 Dec 1992 WO
WO9308734 May 1993 WO
WO9319667 Oct 1993 WO
WO9843537 Oct 1998 WO
WO9937290 Jul 1999 WO
WO9959465 Nov 1999 WO
WO0033246 Jun 2000 WO
WO0100085 Jan 2001 WO
WO0147466 Jul 2001 WO
WO0149364 Jul 2001 WO
WO0174011 Oct 2001 WO
WO0180731 Nov 2001 WO
WO0204406 Jan 2002 WO
WO0245489 Jun 2002 WO
WO02058330 Jul 2002 WO
WO02062276 Aug 2002 WO
WO02087681 Nov 2002 WO
WO03050643 Jun 2003 WO
WO03068061 Aug 2003 WO
WO2004014225 Feb 2004 WO
WO2004019172 Mar 2004 WO
WO2004039256 May 2004 WO
WO2004066833 Aug 2004 WO
WO2004066834 Aug 2004 WO
WO2004066903 Aug 2004 WO
WO2004068748 Aug 2004 WO
WO2004068881 Aug 2004 WO
WO2004075751 Sep 2004 WO
WO2004109316 Dec 2004 WO
WO2005011237 Feb 2005 WO
WO2005020023 Mar 2005 WO
WO2005024687 Mar 2005 WO
WO2005047837 May 2005 WO
WO2005051166 Jun 2005 WO
WO2005110238 Nov 2005 WO
WO2006021932 Mar 2006 WO
WO2006027586 Mar 2006 WO
WO2006035351 Apr 2006 WO
WO2006055892 May 2006 WO
WO2006055956 May 2006 WO
WO2006075016 Jul 2006 WO
WO2006100620 Sep 2006 WO
WO2006104843 Oct 2006 WO
WO2006109072 Oct 2006 WO
WO 2006116718 Nov 2006 WO
WO2006116718 Nov 2006 WO
WO2006119345 Nov 2006 WO
WO2006127355 Nov 2006 WO
WO2007001724 Jan 2007 WO
WO2007001742 Jan 2007 WO
WO2007013952 Feb 2007 WO
WO2007014084 Feb 2007 WO
WO2007014527 Feb 2007 WO
WO2007021496 Feb 2007 WO
WO2007027660 Mar 2007 WO
WO2007028035 Mar 2007 WO
WO2007036687 Apr 2007 WO
WO2007036741 Apr 2007 WO
WO2007036746 Apr 2007 WO
WO2007040878 Apr 2007 WO
WO2007071180 Jun 2007 WO
WO2007096810 Aug 2007 WO
WO2007101141 Sep 2007 WO
WO2007120946 Oct 2007 WO
WO2007127316 Nov 2007 WO
WO2007127879 Nov 2007 WO
WO2007128165 Nov 2007 WO
WO2007130491 Nov 2007 WO
WO2007143535 Dec 2007 WO
WO2007149546 Dec 2007 WO
WO2008008281 Jan 2008 WO
WO2008030482 Mar 2008 WO
WO2008052136 May 2008 WO
WO2008063626 May 2008 WO
WO2008066617 Jun 2008 WO
WO2008076464 Jun 2008 WO
WO2008089232 Jul 2008 WO
WO2008091683 Jul 2008 WO
WO2008095183 Aug 2008 WO
WO2008097652 Aug 2008 WO
WO2008101107 Aug 2008 WO
WO2008112577 Sep 2008 WO
WO2008112578 Sep 2008 WO
WO2008120156 Oct 2008 WO
WO2008133394 Nov 2008 WO
WO2008134185 Nov 2008 WO
WO2008150633 Dec 2008 WO
WO2009001108 Dec 2008 WO
WO2009006615 Jan 2009 WO
WO2009029453 Mar 2009 WO
WO2009036334 Mar 2009 WO
WO2009051829 Apr 2009 WO
WO2009051830 Apr 2009 WO
WO2009063377 May 2009 WO
WO2009081348 Jul 2009 WO
WO2009111664 Sep 2009 WO
WO2009146082 Dec 2009 WO
WO2010000085 Jan 2010 WO
WO2010009100 Jan 2010 WO
WO2010011833 Jan 2010 WO
WO2010019778 Feb 2010 WO
WO2010057049 May 2010 WO
WO2010080765 Jul 2010 WO
WO2010080843 Jul 2010 WO
WO2010107563 Sep 2010 WO
WO2010132331 Nov 2010 WO
WO2010135516 Nov 2010 WO
WO2011068963 Jun 2011 WO
WO2011159336 Dec 2011 WO
WO2011159337 Dec 2011 WO
WO2011159338 Dec 2011 WO
WO2011159339 Dec 2011 WO
WO2012104657 Aug 2012 WO
WO2012158190 Nov 2012 WO
Non-Patent Literature Citations (90)
Entry
Barrie, Heidelberg pH capsule gastric analysis. Texbook of Natural Medicine, (1992), Pizzorno, Murray & Barrie.
Carlson et al., “Evaluation of a non-invasive respiratory monitoring system for sleeping subjects” Physiological Measurement (1999) 20(1): 53.
Heydari et al., “Analysis of the PLL jitter due to power/ground and substrate noise”; IEEE Transactions on Circuits and Systems (2004) 51(12): 2404-16.
Intromedic, MicroCam Innovative Capsule Endoscope Pamphlet. (2006) 8 pp (http://www.intromedic.com/en/product/productinfo.asp).
MacKay et al., “Radio Telemetering from within the Body Inside Information is Revealed by Tiny Transmitters that can be Swallowed or Implanted in Man or Animal Science” (1991) 1196-1202; 134; American Association for the Advancement of Science, Washington D.C.
Mackay et al., “Endoradiosonde” Nature, (1957) 1239-1240, 179 Nature Publishing Group.
McKenzie et al., “Validation of a new telemetric core temperature monitor” J. Therm. Biol. (2004) 29(7-8):605-11.
Minimitter Co. Inc. “Actiheart” Traditional 510(k) Summary. Sep. 27, 2005.
Minimitter Co. Inc. Noninvasive technology to help your studies succeed. Mini Mitter.com Mar. 31, 2009.
Mini Mitter Co, Inc. 510(k) Premarket Notification Mini-Logger for Diagnostic Spirometer. 9-21 (1999).
Mini Mitter Co, Inc. 510(k) Premarket Notification for VitalSense. Apr. 22, 2004.
Minimitter Co. Inc. VitalSense Integrated Physiological Monitoring System. Product Description. (2005).
Minimitter Co. Inc. VitalSense Wireless Vital Signs Monitoring. Temperatures.com Mar. 31, 2009.
Mohaverian et al., “Estimation of gastric residence time of the Heidelberg capsule in humans: effect of varying food composition” Gastroenterology (1985) 89:(2): 392-7.
Sanduleanu et al., “Octave tunable, highly linear, RC-ring oscillator with differential fine-coarse tuning, quadrature outputs and amplitude control for fiber optic transceivers” (2002) IEEE MTT-S International Microwave Symposium Digest 545-8.
Tajalli et al., “Improving the power-delay performance in subthreshold source-coupled logic circuits” Integrated Circuit and System Design. Power and Timing Modeling, Optimization and Simulation, Springer Berlin Heidelberg (2008) 21-30.
Tatbul et al., “Confidence-based data management for personal area sensor networks” ACM International Conference Proceeding Series (2004) 72.
Xiaoming et al., “A telemedicine system for wireless home healthcare based on bluetooth and the internet” Telemedicine Journal and e-health (2004) 10(S2): S110-6.
Yang et al., “Fast-switching frequency synthesizer with a discriminator-aided phase detector” IEEE Journal of Solid-State Circuits (2000) 35(10): 1445-52.
Yao et al., “Low Power Digital Communication in Implantable Devices Using Volume Conduction of Biological Tissues” Proceedings of the 28th IEEE, EMBS Annual International Conference, Aug. 30-Sep. 3, 2006.
Zimmerman, “Personal Area Networks: Near-field intrabody communication” IBM Systems Journal (1996) 35 (3-4):609-17.
Zworkin, “A Radio Pill” Nature, (1957) 898, 179 Nature Publishing Group.
Li, P-Y, et al. “An electrochemical intraocular drug delivery device”, Sensors and Actuators A 143 (2008) p. 41-48.
NPL—AntennaBasics.pdf, Radio Antennae, http://www.erikdeman.de/html/sail018h.htm; (2008) 3pp.
Santini, J.T. et al, “Microchips as controlled drug delivery-devices”, Agnew. Chem. Int. Ed. (2000), vol. 39, p. 2396-2407.
Shawgo, R.S. et al. “BioMEMS from drug delivery”, Current Opinion in Solid State and Material Science 6 (2002), p. 329-334.
Soper, S.A. et al. “Bio-Mems Technologies and Applications”, Chapter 12, “MEMS for Drug Delivery”, p. 325-346 (2007).
Tierney, M.J. et al “Electroreleasing Composite Membranes for Delivery of Insulin and other Biomacromolecules”, J. Electrochem. Soc., vol. 137, No. 6, Jun. 1990, p. 2005-2006.
Description of ePatch Technology Platform for ECG and EMG, located it http://www.madebydelta.com/imported/images/DELTA—Web/documents/ME/ePatch—ECG—EMG.pdf, Dated Sep. 2, 2010.
AADE, “AADE 37th Annual Meeting San Antonio Aug. 4-7, 2010” American Association of Diabetes Educators Aug. 2010; http://www.diabeteseducator.org/annualmeeting/2010/index.html; 2 pp.
Arshak et al., A Review and Adaptation of Methods of Object Tracking to Telemetry Capsules IC-Med; Jan. 2007 vol. 1, No. 1, Issue 1, 12pp.
“ASGE Technology Status Evaluation Report: wireless capsule endoscopy” American Soc. for Gastrointestinal Endoscopy; Apr. 2006 vol. 63, No. 4; 7 pp.
Aydin et al., “Design and implementation considerations for an advanced wireless interface in miniturized integrated sensor Microsystems” Sch. of Eng. & Electron, Edinburgh Univ., UK; Sep. 2003; Abstract Only.
Bohidar et al., “Dielectric Behavior of Gelatin Solutions and Gels” Colloid Polym Sci (1998) 276:81-86.
Brock, “Smart Medicine: The Application of Auto-ID Technology to Healthcare” Auto-ID Labs (2002) http://www.autoidlabs.org/uploads/media/MIT-AUTOID-WH-010.pdf.
Coury, L. “Conductance Measurement Part 1: Theory”; Current Separations, 18:3 (1999) p. 91-96.
Delvaux et al., “Capsule endoscopy: Technique and indications” Clinical Gastoenterology; Oct. 2008 vol. 22, Issue 5, 1 pp. (Abstract Only).
Dhar et al., “Electroless nickel plated contacts on porous silicon” Appl. Phys. Lett. 68 (10) pp. 1392-1393 (1996).
Eldek A., “Design of double dipole antenna with enhanced usable bandwidth for wideband phased array applications” Progress in Electromagnetics Research PIER 59, 1-15 (2006).
Fawaz et al., “Enhanced Telemetry System using CP-QPSK Band—Pass Modulation Technique Suitable for Smart Pill Medical Application” IFIP IEEE Dubai Conference Apr. 2008; http://www.asic.fh-offenburg.de/downloads/ePille/IFIP—IEEE Dubai—Conference.pdf.
Ferguson et al., “Dialectric Constant Studies III Aqueous Gelatin Solutions” J. Chem. Phys. 2, 94 (1934) p. 94-98.
Furse C. M., “Dipole Antennas” J. Webster (ed). Wiley Encyclopedia of Electrical and Electronics Engineering (1999) p. 575-581.
Gaglani S. “Put Your Phone, or Skin, on Vibrate” MedGadget; Mar. 2012 http://medgadget.com/2012/03/put-your-phone-or-skin-on-vibrate.html 8pp.
Gilson, D.R. “Molecular dynamics simulation of dipole interactions”, Department of Physics, Hull University, Dec. 2002, p. 1-43.
Given Imaging, “Agile Patency Brochure” (2006) http://www.inclino.no/documents/AgilePatencyBrochure—Global—GMB-0118-01.pdf; 4pp.
Gonzalez-Guillaumin et al., “Ingestible capsule for impedance and pH monitoring in the esophagus” IEEE Trans Biomed Eng; Dec. 2007 54(12) 1pp. (Abstract Only).
Greene, “Edible RFID microchip monitor can tell if you take your medicine” Bloomberg Businessweek; Mar. 2010 2 pp.; http://www.businessweek.com/idg/2010-03-31/edible-rfid-microchip-monitor-can-tell-if-you-take-your-medicine.html.
Halthion Medical Technologies “Providing Ambulatory Medical Devices Which Monitor, Measure and Record” webpage. Online website: http://www.halthion.com/; downloaded May 30, 2012.
Hoeksma, J. “New ‘smart pill’ to track adherence” E-Health-Insider May 2010 http://www.e-health-insider.com/news/5910/new—‘smart—pill’—monitors—medicines.
Hoover et al., “Rx for health: Engineers design pill that signals it has been swallowed” University of Florida News; Mar. 2010 2pp.; http://news.ufl.edu/2010/03/31/antenna-pill-2/.
ISFET—Ion Sensitive Field-Effect Transistor; Microsens S.A. pdf document. Office Action dated Jun. 13, 2011 for U.S. Appl. No. 12/238,345; 4pp.
International Foundation for Functional Gastrointestinal Disorders—IFFGD (2012) “Diagnosis and Tests for GERD” Online article last updated Aug. 22, 2012; Downloaded Dec. 14, 2012 at http://www.aboutgerd.org/site/about-gerd/diagnosis/.
Jimbo et al., “Gastric-fluid-utilized micro battery for micro medical devices” The Sixth International Workshop on Micro and Nanotechnology for Power Geneartion and Energy Conservation Applications, (2006) pp. 97-100.
Jung, S. “Dissolvable ‘Transient Electronics’ Will Be Good for Your Body and the Environment” MedGadget; Oct. 1, 2012; Onlne website: http://medgadget.com/2012/10/dissolvable-transient-electronics-will-be-good-for-your-body-and-the-environment.html; downloaded Oct. 24, 2012; 4 pp.
Juvenile Diabetes Research Foundation International (JDRF), “Artificial Pancreas Project” Jun. 2010; http://www.artificialpancreasproject.com/; 3 pp.
Kamada K., “Electrophoretic deposition assisted by soluble anode” Materials Letters 57 (2003) 2348-2351.
Lifescan, “OneTouch UltraLink™” http://www.lifescan.com/products/meters/ultralink; Jul. 2010 2 pp.
Medtronic, “CareLink Therapy Management Software for Diabetes” Jul. 2010; https://carelink.minimed.com/patient/entry.jsp?bhcp=1; 1 pp.
Medtronic, “Carelink™ USB” (2008) http://www.medtronicdiabetes.com/pdf/carelink—usb—factsheet.pdf 2pp.
Medtronic “The New MiniMed Paradigm® REAL-Time Revel™ System” Aug. 2010 http://www.medtronicdiabetes.com/products/index.html; 2 pp.
Medtronic, “Mini Med Paradigm® Revel™ Insulin Pump” Jul. 2010 http://www.medtronicdiabetes.com/products/insulinpumps/index.html; 2 pp.
Medtronic, Mini Med Paradigm™ Veo™ System: Factsheet (2010). http://www.medtronic-diabetes.com.au/downloads/Paradigm%20Veo%20Factsheet.pdf ; 4 pp.
Melanson, “Walkers swallow RFID pills for science” Engadget; Jul. 2008; http://www.engadget.com/2008/07/29/walkers-swallow-rfid-pills-for-science/.
MMS “What is Impedance?” (2012) Online article downloaded on Dec. 13, 2012 from http://www.mmsinternational.com/int/781/gastroenterology-impedance-ph-measurement-product-ohmega-video.
O'Brien et al., “The Production and Characterization of Chemically Reactive Porous Coatings of Zirconium Via Unbalanced Magnetron Sputtering” Surface and Coatings Technology (1996) 86-87; 200-206.
Owano, N., “Study proposes smart sutures with sensors for wounds” Phys.Org. Aug. 2012. http://phys.org/news/2012-08-smart-sutures-sensors-wounds.html.
Park, “Medtronic to Buy MiniMed for $3.7 Billion” (2001) HomeCare; http://homecaremag.com/mag/medical—medtronic—buy—minimed/; 2 pp.
Platt, D., “Modulation and Deviation” AE6EO, Foothills Amateur Radio Society; Oct. 26, 2007; 61 pp.
“RFID “pill” monitors marchers” RFID News; Jul. 2008 http://www.rfidnews.org/2008/07/23/rfid-pill-monitors-marchers/.
Rolison et al., “Electrically conductive oxide aerogels: new materials in electrochemistry” J. Mater. Chem. (2001) 1, 963-980.
Roulstone, et al., “Studies on Polymer Latex Films: I. A study of latex film morphology” Polymer International 24 (1991) pp. 87-94.
“SensiVida minimally invasive clinical systems” Investor Presentation Oct. 2009 28pp; http://www.sensividamedtech.com/SensiVidaGeneralOctober09.pdf.
Shin et al., “A Simple Route to Metal Nanodots and Nanoporous Metal Films”; Nano Letters, vol. 2, No. 9 (2002) pp. 933-936.
Shrivas et al., “A New Platform for Bioelectronics-Electronic Pill”, Cummins College, (2010).; http://www.cumminscollege.org/downloads/electronics—and—telecommunication/Newsletters/Current%20Newsletters.pdf; First cited in third party client search conducted by Patent Eagle Search May 18, 2010.
“Smartlife awarded patent for knitted transducer” Innovation in Textiles News: http://www.innovationintextiles.com/articles/208.php; 2pp. Aug. 2009.
“The SmartPill Wireless Motility Capsule” Smartpill, The Measure of GI Health; May 2010 http://www.smartpillcorp.com/index.cfm?pagepath=Products/The—SmartPill—Capsule&id=17814.
Solanas et al., “RFID Technology for the Health Care Sector” Recent Patents on Electrical Engineering (2008) 1, 22-31.
Swedberg, “University Team Sees Ingestible RFID Tag as a Boon to Clinical Trials” RFID Journal Apr. 27, 2010; http://www.rfidjournal.com/article/view/7560/1 3pp.
U.S. Appl. No. 12/238,345, filed Sep. 25, 2008, Hooman et al., Non-Final Office Action mailed Jun. 13, 2011 22pp.
Walkey, “MOSFET Structure and Processing”; 97.398* Physical Electronics Lecture 20; Office Action dated Jun. 13, 2011 for U.S. Appl. No. 12/238,345; 24 pp.
Watson, et al., “Determination of the relationship between the pH and conductivity of gastric juice” Physiol Meas. 17 (1996) pp. 21-27.
Wongmanerod et al., “Determination of pore size distribution and surface area of thin porous silicon layers by spectroscopic ellipsometry” Applied Surface Science 172 (2001) 117-125.
“PALO Bluetooth Baseband” PALO Bluetooth Resource Center (2002) Retrieved from Internet Dec. 12, 2012 at URL: http://palowireless.com/bluearticles/baseband.asp; first cited in Office Action dated Jan. 17, 2013 for EP08853901.0.
Trutag, Technologies, Inc., Spectral Microtags for Authentication and Anti-Counterfeiting; “Product Authentication and Brand Protection Solutions”; http://www.trutags.com/; downloaded Feb. 12, 2013; 1 pp.
Baskiyar, S. “A Real-time Fault Tolerant Intra-body Network” Dept. of Comp. Sci & Soft Eng; Auburn University; Proceedings of the 27th Annual IEEE Conference; 0742-1303/02 (2002) IEEE; 6 pp.
Hotz “The Really Smart Phone” The Wall Street Journal, What They Know (2011); 6 pp.; http://online.wsj.com/article/SB10001424052748704547604576263261679848814.html?mod=djemTECH—t.
Lin et al., “Do Physiological Data Relate to Traditional Usability Indexes?” Proceedings of OZCHI 2005, Canberra, Australia (2005) 10 pp.
Mandryk et al., “A physiological approach for continuously modeling user emotion in interactive play environments” Proceedings of Measuring Behavior (2008) (Maastrichtm the Netherlandsm Aug. 26-29) 2 pp.
Mandryk et al., “Objectively Evaluating Entertainment Technology” Simon Fraser University; CHI (2004) ACM 1-58113-703-6/0410004; 2 pp.
Winter, J. et al. “The material properties of gelatin gels”; USA Ballistic Research Laboratories, Mar. (1975), p. 1-157.
Related Publications (1)
Number Date Country
20120016211 A1 Jan 2012 US
Provisional Applications (2)
Number Date Country
61121878 Dec 2008 US
61121881 Dec 2008 US
Continuations (1)
Number Date Country
Parent 12665022 US
Child 13243759 US