Method, program and apparatus for determining location of ingestible capsule - Patents.com

Abstract

11. A method for determining a location of an ingestible capsule within a digestive tract of a subject mammal, the method comprising: providing an ingestible capsule to the subject mammal for ingestion, the ingestible capsule comprising a housing, a power source, a TCD gas sensor, and a VOC gas sensor; recording readings of the ingestible capsule as a function of time, the readings comprising TCD gas sensor readings and VOC gas sensor readings; and processing the recorded readings, the processing comprising determining a timing of gastroduodenal transition, the determining the timing comprising detecting a gastroduodenal transition indicator in the recorded readings, the determining the timing comprising detecting a VOC gas sensor reading. 12. The method of claim 11, wherein the ingestible capsule comprises a housing, a power source, a TCD gas sensor, and a VOC gas sensor.

Description

[Technical field]

[0001] The present invention relates to sensors useful in ingestible sensor capsules for medical and health applications in the gastrointestinal (GI) tract of mammals, including humans, and in particular to recording sensor readings from ingestible capsules and determining the location within the GI tract at the time of the reading. [Background technology]

[0002] A gas sensor capsule such as that disclosed in EP3497437A1 contains a gas sensor within an ingestible capsule whereby readings can be obtained from within the gastrointestinal (GI) tract of a mammal and from which analyte gas concentration readings can be determined.

[0003] A process for determining the type and concentration of specific gases in a multi-gas mixture based on readings taken from within the GI tract by a gas sensor mounted in an ingestible capsule is disclosed in EP 3 619 526 A1.

[0004] There are numerous reports that these gas components are associated with different diseases, conditions, etc., and that there is a likely link between gas and intestinal health, and therefore overall health.

[0005] However, to correlate gas constituents with different diseases, conditions, etc., it is desirable to know or be able to accurately predict the location of the capsule in the GI tract at the moment the gas sensor reading is taken. A particular gas or gas concentration expected in one part of the GI tract may be an indicator of a disease or condition elsewhere in the GI tract.

[0006] Furthermore, gut health is increasingly recognized as a contributor to overall health. Motility of ingestible capsules (with or without associated gas content measurements) provides important information for the assessment of gut health. Summary of the Invention

[0007] A method for determining a location of an ingestible capsule within a gastrointestinal (GI) tract of a subject mammal comprising: providing an ingestible capsule to the subject mammal for ingestion, the ingestible capsule comprising a housing, a power source, a TCD gas sensor, and a VOC gas sensor; recording readings of the ingestible capsule as a function of time, the readings including a TCD gas sensor reading and a VOC gas sensor reading; recording and processing the recorded readings to determine a first transition event timing, the first transition event timing being indicative of a timing of gastroduodenal transition by the ingestible capsule. and determining a second transition event timing is timing of a transition across the ileocecal junction by the ingestible capsule, the second transition event timing comprising detecting an ileocecal junction indicator in a second subset of the recorded readings, the second subset comprising recorded TCD gas sensor readings.

[0008] Motility diagnosis relies on understanding key metrics within the transit of an ingestible capsule through the GI tract. Key metrics include gastric emptying time (GET), small bowel transit time (SBTT), large bowel transit time (LBTT), and whole bowel transit time (WGTT). Any one or combination of a number of these metrics can be beneficial to a physician in assessing the health of a human subject and / or diagnosing a disease or condition.

[0009] Additionally, readings from the gas sensor may be used to determine the constituent gases and their concentrations in the gas mixture at the location of the ingestible capsule. Determining the location of the capsule in terms of which organ in the GI tract it is located within at the time of the gas sensor reading adds context to the determination of the constituent gases and their concentrations, which may be beneficial to a physician in assessing the subject's human health and / or diagnosing a disease or condition.

[0010] Furthermore, data collected by sensors on the capsule for specific medical or more general bowel health data collection purposes has improved information value if associated with an indication of the capsule's location within the intestine at the instance of data collection.

[0011] Gut health is a major component of the health of humans and other mammals, and is very difficult to analyze because it is difficult to obtain readings from within the gut or to accurately assess gut health parameters based on readings from outside the gut.

[0012] Embodiments provide a mechanism for obtaining sensor readings from within the GI tract and determining the location of the sensor at the instance of said reading.

[0013] The embodiments provide a mechanism for obtaining timing information for an article's passage through the GI tract and through specific regions of the GI tract, which is itself an artifact useful in gut health and gut-related medical applications.

[0014] Embodiments provide a mechanism for obtaining and recording readings from a sensor mounted on an ingestible capsule, and for processing the readings to determine the location of the capsule within the GI tract at the time of the reading. Such processing may be performed within the capsule or at a remote device that receives data (directly or indirectly) from the capsule.

[0015] The embodiments utilize sensor readings to determine the location of the capsule in the GI tract. However, the embodiments do not rely on converting the readings into measurements of constituent gas concentrations. Patterns and features in the sensor output itself (i.e., raw readings) can be utilized as markers / indicators to determine which physical event has occurred (i.e., which intestinal section or junction the capsule has passed through). Thus, issues regarding accuracy of calibration and the ability to derive accurate and precise measurements of gas concentrations can be avoided in the process of positioning the capsule. Of course, gas concentrations are interesting as companion information, but the gas concentrations themselves are necessary for determining motility information. For example, while gastric emptying is undoubtedly related to changes in CO2 concentration, it is not necessary to know the actual CO2 concentration around the capsule (if the readings are analyzed) to determine whether gastric emptying has occurred. One or more indicators in the sensor readings, which may be caused by changes in CO2 or by other physical changes related to gastric emptying, are detected and combined (if the readings are analyzed) to determine whether gastric emptying has occurred or not.

[0016] Optionally, the ingestible capsule includes an environmental sensor, and the readings include environmental sensor readings, and either determining the first transition event timing further includes comparing one or more of the environmental temperature sensor readings at or near the timing of the detected gastroduodenal transition indicator to a baseline environmental temperature value and determining whether the timing of the detected gastroduodenal transition indicator is associated with the first transition event timing based on a result of the comparison, or detecting the gastroduodenal transition indicator includes adjusting a TCD gas sensor reading in accordance with each concurrent environmental temperature sensor reading and detecting a gastroduodenal transition indicator in the adjusted TCD gas sensor reading.

[0017] Optionally, the gastroduodenal transition indicator is a spike, step change, or inflection in the TCD gas sensor reading from the recorded readings, and the timing of the gastroduodenal transition indicator is determined to be associated with the first transition event timing if the environmental temperature value was within a predetermined threshold distance of the baseline environmental temperature value for a predetermined period of time prior to the timing of the gastroduodenal transition indicator.

[0018] Optionally, the VOC gas sensor includes a heating element and is configured to pulse the heating element, and the VOC gas sensor readings are each taken at the same point in the phase of a respective pulse of the heating element.

[0019] Optionally, the ingestible capsule further comprises a primary transceiver comprising an antenna, and the method further comprises transmitting, by the antenna, a reading of the ingestible capsule to a receiver device external to the target mammal configured to record the reading.

[0020] Optionally, the ingestible capsule further comprises a directional coupler in series with the antenna to form a reflectometer, and the ingestible capsule readings include the reflectometer readings, and the first subset includes the reflectometer readings.

[0021] Optionally, the ingestible capsule further comprises a directional coupler in the primary transceiver in series with the antenna to form a reflectometer.

[0022] Optionally, the ingestible capsule further comprises a diode detector forming part of a reflectometer, the diode detector configured to receive a reflected signal from the antenna via the directional coupler and to measure an amplitude of the reflected signal.

[0023] Optionally, the ingestible capsule further comprises a quadrature demodulator forming part of the reflectometer, the quadrature demodulator configured to receive a reflected signal from the antenna via the directional coupler and extract phase information of the reflected signal relative to a carrier signal, the carrier signal being a carrier signal for transmitting data from the ingestible capsule to a receiver device.

[0024] Optionally, the ingestible capsule comprises an antenna impedance control mechanism comprising a variable capacitor configured to vary the impedance of the antenna and a controller, wherein the reflectometer and the antenna impedance control mechanism form a closed or feedback loop, and the controller is configured to receive measurements of the amplitude of the reflected signal from the diode detector and execute a control algorithm to generate an antenna impedance control signal that sets the capacitance of the variable capacitor to vary the impedance of the antenna so as to reduce the amplitude of the reflected signal.

[0025] Optionally, the closed loop or feedback loop further comprises a quadrature demodulator, and phase information extracted by the quadrature demodulator is output to a controller, the controller being configured to generate an antenna impedance control signal using the amplitude information and the phase information.

[0026] Optionally, the recorded readings of the gas sensor capsule are: a reflected signal amplitude reading measured by a diode detector; A readout of the phase information of the reflected signal extracted by the quadrature demodulator; one or more antenna reflectivity related readings of an antenna impedance control signal; A first subset of the recorded readings from which a first transition event timing is determined comprises antenna reflectivity related readings, and / or a second subset of the recorded readings from which a second transition event timing is determined comprises antenna reflectivity related readings.

[0027] Optionally, the reflectometer further comprises a diode detector, and the antenna reflectivity related reading is a measurement by the diode detector of the amplitude of a reflected signal from the antenna.

[0028] Optionally, determining the first transition event timing further includes detecting a gastroduodenal transition indicator in the antenna reflectivity related readings from the first subset, and determining that a first transition event has occurred and its timing based on the gastroduodenal junction indicator detected in the antenna reflectivity related readings from the first subset.

[0029] Optionally, the method further includes detecting a gastroduodenal transition indicator in the TCD gas sensor readings from the first subset as a first gastroduodenal transition indicator, detecting a gastroduodenal transition indicator in the antenna reflectivity associated readings from the first subset within a predetermined time range of the detected first gastroduodenal transition indicator as a second gastroduodenal transition indicator, and determining that a first transition event has occurred and the timing thereof based on the detection of the first and second gastroduodenal transition indicators.

[0030] Optionally, the ingestible capsule further comprises an accelerometer, and the readings of the ingestible capsule include accelerometer readings, and the first subset includes the accelerometer readings.

[0031] Optionally, determining the first transition event timing further includes detecting a gastroduodenal transition indicator in the accelerometer readings from the first subset, and determining that a first transition event occurred and its timing based on the gastroduodenal transition indicator detected in the accelerometer readings from the first subset.

[0032] Optionally, the first subset includes antenna reflectivity related readings, and determining the first transition event timing further includes detecting a gastroduodenal transition indicator in the antenna reflectivity related readings from the first subset, and determining that the first transition event occurred and its timing based on the gastroduodenal transition indicator detected in the antenna reflectivity related readings from the first subset.

[0033] Optionally, the method includes detecting a gastroduodenal transition indicator in the TCD gas sensor readings from the first subset as a first gastroduodenal transition indicator, detecting a gastroduodenal transition indicator in the antenna reflectivity associated readings from the first subset within a predetermined time range of the detected first gastroduodenal transition indicator as a second gastroduodenal transition indicator, and determining that a first transition event has occurred and the timing thereof based on detecting the first and second gastroduodenal transition indicators.

[0034] Optionally, the method further includes detecting a gastroduodenal junction indicator in the TCD gas sensor readings from the first subset as a first gastroduodenal junction indicator, detecting a gastroduodenal junction indicator in the accelerometer readings from the first subset within a predetermined time range of the detected first gastroduodenal transition indicator as a second gastroduodenal transition indicator, and determining that a first transition event has occurred and its timing based on the detection of the first and second gastroduodenal transition indicators.

[0035] Optionally, the method includes detecting a gastroduodenal transition indicator in the TCD gas sensor readings from the first subset as a first gastroduodenal transition indicator; calculating a confidence score representing a likelihood that the detected gastroduodenal transition indicator in the TCD gas sensor readings was caused by the ingestible capsule crossing the gastroduodenal junction; comparing the calculated confidence score to a threshold; and determining that a first transition event occurred and its timing based on a timing of the detected gastroduodenal transition indicator if the confidence score meets the threshold. , if the confidence score does not meet a threshold, assigning the detected gastroduodenal transition indicator from the TCD gas sensor readings as a first gastroduodenal transition indicator, detecting whether a second gastroduodenal transition indicator is present in the readings from a first subset other than the TCD gas sensor readings and within a predetermined time range of the first gastroduodenal transition indicator, and if the second gastroduodenal transition indicator is detected, determining that a first transition event has occurred and its timing based on the timing of the first gastroduodenal transition indicator.

[0036] Optionally, detecting whether a second gastroduodenal transition indicator is present in readings from a first subset other than the TCD gas sensor readings and within a predetermined time range of the first gastroduodenal transition indicator comprises: first detecting whether a second gastroduodenal transition indicator is present in antenna reflectivity related readings from the first subset within a predetermined time range of the first gastroduodenal transition indicator; determining that a first transition event has occurred and the timing thereof based on a timing of the first gastroduodenal transition indicator if the second gastroduodenal transition indicator is detected in the antenna reflectivity related readings from the first subset; and determining that a first transition event has occurred and its timing based on a timing of the first gastroduodenal transition indicator if the second gastroduodenal transition indicator is detected in the accelerometer readings from the first subset within the predetermined time range of the first gastroduodenal transition indicator. and if the second gastroduodenal transition indicator is not detected in the accelerometer readings from the first subset within the predetermined time range of the first gastroduodenal transition indicator, issuing a notification requesting manual review and continuing to monitor the first subset for another instance of the first gastroduodenal transition indicator.

[0037] Optionally, the accelerometer readings provide readings of an orientation of the ingestible capsule relative to a reference frame having a fixed relationship to the gravity vector, and detecting a gastroduodenal transition indicator in the accelerometer readings includes recording the orientation of the ingestible capsule provided by the first accelerometer reading as a reference orientation, and repeating chronologically for each successive accelerometer reading to determine whether the orientation of the ingestible capsule provided by the respective accelerometer reading exceeds a threshold angular displacement from the reference orientation, and if the threshold angular displacement is not met, proceeding to the next accelerometer reading without changing the reference orientation, and if the threshold angular displacement is met, changing the reference orientation to align with the orientation of the ingestible capsule provided by the respective accelerometer reading, and the gastroduodenal transition indicator in the accelerometer readings is an increase in the rate of change of the reference orientation.

[0038] Optionally, the accelerometer readings provide readings of an orientation of the ingestible capsule relative to a frame of reference in a fixed relationship to the gravity vector, and detecting a gastroduodenal transition indicator in the accelerometer readings includes: for each of three orthogonal axes in a fixed spatial relationship to the ingestible capsule derivable from the orientation readings, repeatedly in a chronological order for each successive accelerometer reading, calculating a change in the orthogonal axis relative to the gravity vector from a preceding accelerometer reading as a scalar value, applying a low pass filter to the calculated changes, and recording the cumulative filtered calculated changes, and the gastroduodenal transition indicator in the accelerometer readings is a step change in a rate of increase of the cumulative filtered calculated changes.

[0039] Optionally, the ingestible capsule includes an environmental sensor, and the readings include environmental sensor readings, the environmental sensor being an environmental temperature sensor, an environmental relative humidity sensor, or an environmental temperature sensor and an environmental humidity sensor, and processing the recorded readings includes determining an excretion event timing by detecting a change in the environmental sensor readings between an internal environmental condition and an external environmental condition of the target mammal at the location of the target mammal, and the excretion event timing is a timing of excretion of the ingestible capsule by the target mammal.

[0040] Optionally, the ingestible capsule includes an environmental sensor, the readings include environmental sensor readings, the environmental sensor being an environmental temperature sensor, an environmental relative humidity sensor, or an environmental temperature sensor and an environmental humidity sensor, and processing the recorded readings includes determining an ingestion event timing by detecting a change in the environmental sensor readings between internal environmental conditions and external environmental conditions of the target mammal at the location of the target mammal, the ingestion event timing being a timing of ingestion of the ingestible capsule by the target mammal.

[0041] An embodiment includes an apparatus for determining a location of an ingestible capsule in a gastrointestinal (GI) tract of a target mammal, the apparatus comprising: an ingestible capsule ingestible by the target mammal, the ingestible capsule comprising a housing, a power source, a TCD gas sensor, and a VOC gas sensor; a receiver device configured to determine a location at a location external to the target mammal to receive readings from the ingestible capsule at a location internal to the target mammal and record readings of the ingestible capsule as a function of time including a period during which the ingestible capsule is in the gastrointestinal (GI) tract of the target mammal, the readings including TCD gas sensor readings and VOC gas sensor readings; and a processor configured to process the recorded readings by a process. and determining a first transition event timing, the first transition event timing being a timing of gastroduodenal transition by the ingestible capsule, where determining the first transition event timing comprises detecting a gastroduodenal transition indicator in a first subset of the recorded readings, where the first subset comprises the recorded TCD gas sensor readings; and determining a second transition event timing, the second transition event timing being a timing of transition across the ileocecal junction by the ingestible capsule, where determining the second transition event timing comprises detecting an ileocecal junction transition indicator in a second subset of the recorded readings, where the second subset comprises the VOC gas sensor readings.

[0042] Optionally, the receiver device and the processing device are the same computing device. Alternatively, the receiver device is a first device and the processing device is a second device, which is a different computing device than the first device and is configured to access the readings recorded by the first device. The processing device may be referred to as a remote computer elsewhere in this disclosure. The receiver device may be a smartphone that runs an application for one or more of storing, processing, and transmitting data received from the capsule 10. The receiver device may be a dedicated device configured for one or more of storing, processing, and transmitting data received from the capsule 10.

[0043] Optionally, the ingestible capsule further comprises a secondary transceiver, which is operable in a listening phase of the ingestible capsule in which the primary transceiver, sensor, and on-board processor of the ingestible capsule are powered off, and the secondary transceiver is configured to receive an encoded activation control signal from the encoded activation control signal transmitting device during the listening mode and respond by terminating the listening phase and initiating a live phase of the ingestible capsule in which the primary transceiver, sensor, and on-board processor and memory are powered on and readings are recorded and optionally transmitted to the receiver device.

[0044] Optionally, the secondary transceiver is an NFC transceiver and the encoded activation control signal is an NFC signal.

[0045] Optionally, the receiver device is a transmitting device for the coded activation control signal, the receiver device being a smartphone or tablet computer running an application that causes the smartphone or tablet computer to generate and transmit the coded activation control signal, receive recorded readings transmitted from the capsule by the primary transceiver, and optionally process and transmit them.

[0046] Embodiments may include a computer program for determining a location of an ingestible capsule within a gastrointestinal (GI) tract of a subject mammal, the ingestible capsule being ingestible by the subject mammal and including a housing, a power source, a TCD gas sensor, and a VOC gas sensor, the computer program being executable by a computing device including a processor and a memory, which upon execution causes the computing device to perform a process, the process including: accessing recorded readings of the ingestible capsule as a function of time including a period during which the ingestible capsule is in the gastrointestinal (GI) tract of the subject mammal, the readings including TCD gas sensor readings and VOC gas sensor readings; and processing the recorded readings, the processing including: determining a first transition event timing, the first transition event timing being a timing of gastro-duodenal transition by the ingestible capsule, determining the first transition event timing comprising detecting a gastro-duodenal transition indicator in a first subset of the recorded readings, the first subset comprising the recorded TCD gas sensor readings; and determining a second transition event timing, the second transition event timing being a timing of transition across the ileocecal junction by the ingestible capsule, the determining the second transition event timing comprising detecting an ileocecal junction indicator in a second subset of the recorded readings, the second subset comprising the VOC gas sensor readings.

[0047] Another aspect of the embodiment includes a method for determining a position of an ingestible capsule in a gastrointestinal (GI) tract of a subject mammal, the method including providing an ingestible capsule to the subject mammal for ingestion, the ingestible capsule including a housing, a power source, a TCD gas sensor, and a VOC gas sensor; recording readings of the ingestible capsule as a function of time, the readings including TCD gas sensor readings and VOC gas sensor readings; and processing the recorded readings, the processing including determining a first transition event timing, the first transition event timing being a timing of gastroduodenal transition by the ingestible capsule, the determining the first transition event timing including detecting a gastroduodenal transition indicator in a first subset of the recorded readings, the first subset including the recorded TCD gas sensor readings. Such an embodiment may also include one or more of the optional features described above. Such an embodiment may further include determining a second transition event timing, the second transition event timing being a timing of transition across the ileocecal junction by the ingestible capsule, where determining the second transition event timing includes detecting an ileocecal junction indicator in a second subset of the recorded readings, the second subset including the VOC gas sensor readings.

[0048] Another aspect of the embodiment includes a method for determining a location of an ingestible capsule in a gastrointestinal (GI) tract of a subject mammal, the method including providing an ingestible capsule to a subject mammal for ingestion, the ingestible capsule including a housing, a power source, a TCD gas sensor, and a VOC gas sensor; recording readings of the ingestible capsule as a function of time, the readings including TCD gas sensor readings and VOC gas sensor readings; and processing the recorded readings, the processing including determining a transition event timing, the transition event timing being a timing of a transition by the ingestible capsule across an ileocecal junction, the determining the transition event timing including detecting an ileocecal junction indicator in a subset of the recorded readings, the subset including a VOC gas sensor reading. Such an embodiment may also include one or more of the optional features described above. Such an embodiment may further include determining a first transition event timing, the first transition event timing being a timing of gastroduodenal transition by the ingestible capsule, and determining the first transition event timing includes detecting a gastroduodenal transition indicator in a first subset of the recorded readings, the first subset including the recorded TCD gas sensor readings.

[0049] Embodiments may include an ingestible capsule that is ingestible by a target mammal, the ingestible capsule comprising a housing, a power source, a primary transceiver including an antenna, a processor and memory configured to record readings from one or more sensors of the ingestible capsule and store the recorded readings for transmission by the primary transceiver to a receiver device, and a directional coupler in series with the antenna to form a reflectometer, the one or more sensors including a reflectometer.

[0050] Optionally, the ingestible capsule further comprises a diode detector, the diode detector forming part of a reflectometer, the diode detector configured to receive a reflected signal from the antenna via the directional coupler and measure an amplitude of the reflected signal, and the recorded readings include a measurement of the amplitude of the reflected signal.

[0051] Optionally, the ingestible capsule further comprises a quadrature demodulator forming part of the reflectometer, the quadrature demodulator configured to receive a reflected signal from the antenna via the directional coupler and extract phase information of the reflected signal relative to a carrier signal, the carrier signal being a carrier signal for transmitting data from the ingestible capsule to a receiver device.

[0052] Optionally, the ingestible capsule comprises an antenna impedance control mechanism comprising a variable capacitor configured to vary the impedance of the antenna and a controller, wherein the reflectometer and the antenna impedance control mechanism form a closed or feedback loop, and the controller is configured to receive measurements of the amplitude of the reflected signal from the diode detector and execute a control algorithm to generate an antenna impedance control signal that sets the capacitance of the variable capacitor to vary the impedance of the antenna so as to reduce the amplitude of the reflected signal.

[0053] Optionally, the closed loop or feedback loop further comprises a quadrature demodulator, and phase information extracted by the quadrature demodulator is output to a controller, the controller being configured to generate an antenna impedance control signal using the amplitude information and the phase information.

[0054] Optionally, the recorded readings of the gas sensor capsule comprise an antenna reflectivity related reading of one or more of: a reading of the amplitude of the reflected signal measured by a diode detector, a reading of phase information of the reflected signal extracted by a quadrature demodulator, and an antenna impedance control signal.

[0055] Optionally, the processor is configured to detect that the ingestible capsule is located in one of the stomach, small intestine, and large intestine of the subject mammal based on a spike or step change in the antenna reflectivity-related reading and / or based on a level of the physical quantity represented by the antenna reflectivity-related reading.

[0056] Optionally, the ingestible capsule further comprises one or more gas sensors, wherein the one or more sensors comprises one or more gas sensors.

[0057] Embodiments include a system comprising an ingestible capsule and a receiver device configured to receive recorded readings transmitted by a primary receiver antenna, process the recorded readings to identify spikes or step changes in the antenna reflectivity-related readings, and / or detect that the ingestible capsule is located in one of the stomach, small intestine, and large intestine of a target mammal at the timing of an identified spike or step change in the recorded reading or a particular recorded reading based on the level of a physical quantity represented by a particular antenna reflectivity-related reading. [Brief description of the drawings]

[0058] The embodiments will be described with reference to the accompanying drawings.

[0059] [Figure 1A] FIG. 1 is a schematic diagram of an ingestible capsule. [Figure 1B] FIG. 2 is a cross-sectional view of an ingestible capsule. [Figure 1C] FIG. 1 is a schematic diagram of a system. [Figure 2A] 1 illustrates the system during the live phase of an ingestible capsule. [Figure 2B] 1 illustrates a system that includes an ingestible capsule. [Figure 2C] A receiver device and a relay device are illustrated. [Figure 2D]1 illustrates an example user interface of a receiver device. [Figure 3A] FIG. 2 is a schematic diagram of the electronic configuration of the ingestible capsule. [Figure 3B] FIG. 2 is a schematic diagram of a primary transceiver. [Figure 4] 1 is a flow chart of a method for determining the location of an ingestible capsule in the GI tract. [Diagram 5] 1 is a flow chart of a method for determining the location of an ingestible capsule in the GI tract. [Figure 6] 1 is a plot of thermal conductivity versus time and associated component gas concentrations. [Figure 7A] 1 is a plot of capsule readings versus time. [Figure 7B] 1 is a plot of capsule readings versus time. [Figure 7C] 1 is a plot of environmental temperature readings and environmental humidity readings versus time. [Figure 8A-8E] 1 is a plot of sensor readings and determined gas concentrations versus time. [Figure 9A-9D] 1 is a plot of recorded capsule readings versus time. [Figure 10] 1 is a flow chart of a method for determining the timing of a gastroduodenal transition event. [Figure 11A] Illustrates the relationship between sensors, algorithms, and processing results. [Figure 11B] 1 shows an example data visualization marked with transit time metrics. [Figures 12A-12D] The processing algorithm is illustrated. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0060] Figures 1A and 1B show an ingestible capsule 10. A system including the ingestible capsule 10 of Figures 1A and 1B during the live phase of the ingestible capsule 10 (i.e., while the ingestible capsule 10 is taking readings from within the GI tract of a subject mammal 40) is shown in Figure 2A. A schematic diagram of an exemplary arrangement of electronic components within the ingestible capsule 10 as illustrated in Figures 1A and 1B is shown in Figure 3A.

[0061] As shown in FIGS. 1A and B, capsule 10 consists of a housing, such as a gas-impermeable shell 11 having an opening covered by a gas-permeable membrane 12 .

[0062] System Architecture As shown in Fig. 1C, in addition to the capsule 10, the system further comprises a receiver device 30 that receives data transmitted by the capsule from within the GI tract of the subject mammal during the live phase. Concurrently or subsequently, the receiver device 30 processes the received data and may also upload some or all of the received data to a remote processing device, such as a cloud-based service, for further processing. The remote computer may be a cloud resource, or a standalone computer at a clinician facility where the subject is a patient, or a server (whether cloud-based or not) of a service provider where the clinician is a subscriber / customer / service user.

[0063] The receiver device 30 may be a dedicated device (designed to store and optionally process data received from the capsule 10) or may be a general-purpose device such as a smartphone. The smartphone may run an app (downloaded to the smartphone prior to capsule ingestion) for storing and optionally processing data received from the capsule 10. In particular, the capsule 10 may be equipped with a Bluetooth transceiver and the receiver device 30 may be a Bluetooth-enabled tablet, smartphone, or personal computer.

[0064] Optionally, the system may further comprise a remote processing device 20, such as a server forming part of a cloud computing environment or some other distributed processing environment. The remote processing device 20 may be a server provided by or on behalf of a clinical center where the subject 40 is a patient and which is responsible for interpreting the results (i.e., data transmission payload) generated by the capsule 10 and reporting them to the subject 40.

[0065] Capsule Components By way of example, the capsule shown in FIG. 1C houses as sensor hardware an environmental sensor 14 in the form of a temperature sensor 14a and / or a humidity sensor 14b, a gas sensor in the form of a TCD gas sensor 131 and a VOC gas sensor 132, an accelerometer 19, and a reflectometer. An embodiment may include any single sensor or combination of those individual sensors. Alternatively or additionally, an embodiment may include one or more sensors not shown in FIG. 1C, such as a spectrophotometer, a surface acoustic wave sensor, and / or a bulk acoustic resonator array. The reflectometer includes a primary transceiver and associated circuitry.

[0066] Communication Between the Capsule and the Receiver Device During the live phase of the capsule connection between the capsule 10 and the receiver device 30, communication takes place via a data transmitter on the capsule, which may be part of a wireless transceiver, for example a Bluetooth transceiver, which may operate according to the standard Bluetooth transmission protocol or according to the Bluetooth low energy transmission protocol. Other operable communication technologies include LoRa, wifi, and 433MHz radio.

[0067] Optionally, there may be multiple wireless transceivers on the capsule 10, such as a Bluetooth or primary transceiver and an NFC or secondary transceiver. A single integrated chip may provide both transceivers, thereby eliminating the need to duplicate certain parts of the circuitry. However, the single integrated chip includes two separate antennas, one for Bluetooth communication (e.g., 2.4Ghz) and one for NFC communication (e.g., 13.6MHz). The capsule 10 may include two separate wireless communication mechanisms, each configured to at least one of transmit and receive data to a smartphone or tablet within communication range. The wireless communication mechanisms may be a primary wireless communication mechanism or a Bluetooth wireless communication mechanism, and a secondary wireless communication mechanism or an NFC wireless communication mechanism.

[0068] For example, the smartphone or tablet may execute an application that manages data communication with the capsule 10, and may in particular be configured to store, process and / or transmit data from the capsule 10. The same application may facilitate communication with a communication mechanism on the capsule 10, for example by encoding one or more signals transmitted from the smartphone or tablet with a code, the capsule 10 being pre-configured to accept said code as a key to unlock functionality. That is, the capsule 10 is pre-configured to only respond to received signals that are encoded with a code. The code is unique to a particular capsule instance.

[0069] Primary Transceiver When capsule 10 includes two wireless transceivers, the first wireless transceiver may be configured as a primary transceiver that may use Bluetooth or 433 MHz wireless communication protocols. The primary transceiver is configured to transmit a data transmission payload to receiver device 30 during the live phase of capsule 10. The data transmission payload may include readings, metrics representative of the readings, timing or reports of motility event indicators, and / or determinations that motility events have occurred and reports of their timing, as described elsewhere. The primary transceiver is active during the passage of capsule 10 through the GI tract of subject mammal 40, and is thus configured to transmit signals including a data transmission payload from within the GI tract of subject mammal 40 to receiver device 30 external to the subject mammal. Thus, when this disclosure refers to a data transceiver or data transmitter, or transmitter, it is assumed that it is the primary wireless transceiver being discussed (i.e., a Bluetooth transceiver or a 433 MHz transceiver), unless specifically referred to as a secondary transceiver or an NFC wireless transceiver.

[0070] Secondary Transceiver The second wireless transceiver is a secondary wireless transceiver that may use the NFC communication protocol. The secondary transceiver is only for specific activation control signaling, such as to initiate the active mode of the capsule 10 during the unpacking phase or otherwise before ingestion of the capsule 10. The secondary transceiver is not active during the live phase of the capsule 10, i.e., during its passage through the GI tract of the target mammal. The secondary transceiver does not contribute to the transmission of data transmission payloads from the capsule 10 to the receiver device 30. The secondary transceiver may not need to perform any transmission, i.e., the secondary transceiver may only need to receive an activation control signal from a smartphone or tablet running an application. However, the NFC protocol may require a two-way exchange of signals, such as a handshake or binding process, to enable said activation control signal to be transmitted from the smartphone or tablet and received by the capsule 10. Nevertheless, because the secondary transceiver is inactive while the capsule 10 is passing through the GI tract of the target mammal, unlike the primary transceiver, the secondary transceiver does not need to be configured to transmit signals from within the GI tract of the target mammal 40 to a receiver device 30 external to the target mammal.

[0071] Optionally, the secondary transceiver may be configured to receive an encoded activation control signal from a smartphone or tablet (tablet in this context meaning a tablet computer) running an application configured to manage the interaction between the smartphone or tablet and the capsule 10, which initiates a live phase of the capsule 10 during which the capsule sensors take readings and the readings themselves, or metrics and / or reports based on the readings, are transmitted from the capsule 10 to the smartphone or table via the primary wireless data transceiver. Thus, the secondary wireless data transceiver is active in a listening phase preceding the live phase of the capsule. The primary wireless data transceiver is inactive (i.e. does not consume any power) during the listening phase. When the encoded activation control signal is received (and the capsule 10 is powered on in response thereto), the listening phase ends and the secondary wireless data transceiver becomes inactive. The primary wireless data transceiver is active during the live phase.

[0072] To conserve battery power, the capsule 10 operates in a standby or listening mode during the time between release from manufacture and the start of the live phase, during which readings are recorded by on-board sensors and transmitted from the capsule. The standby or listening mode is an extremely low power mode. The live phase of the capsule is initiated prior to ingestion by the subject mammal. The mechanism for exiting the standby or listening mode and entering the live phase includes a reed switch coupled to a magnet on the packaging, which is triggered by the release of the capsule from the packaging and, upon triggering, powers up the processor, the sensor, and the primary transceiver (i.e., initiates the live phase). An alternative mechanism is based on near field communication, NFC. In the alternative mechanism, the capsule 10 is maintained in a standby or listening mode (in the specific example of NFC, this is the sense mode) before being released to the subject. In the listening mode, the on-board microcontroller (i.e., the processor) enters the live phase when an electromagnetic field is detected with an appropriately coded activation control message. A tablet computer or mobile phone with NFC capabilities, running an application configured for managing interaction with and processing of data received from the capsule 10, can generate an appropriately encoded activation control message. In particular, the backend server may link a user account to a particular capsule instance, such that when that user logs into the application and selects to activate the capsule, the application performs a lookup to the backend server to determine how the activation control message should be encoded. In other words, optionally, the encoding is unique for each capsule. Alternatively, the encoding may be uniform across a batch of capsules or across all capsules.

[0073] The NFC transceiver may be on the same integrated chip as the primary transceiver. The NFC transceiver may be positioned near the housing at the end of the capsule to facilitate communication with a tablet computer or mobile phone.

[0074] Further Exemplary System Architectures As shown in Figure 2A, in addition to the capsule, the system further comprises a receiver device 30 that receives the data transmitted by the capsule from within the GI tract of the subject mammal during the live phase. Concurrently or subsequently, the receiver device 30 uploads the recorded readings to a remote computer 20 for processing. The remote computer may be a cloud resource, or may be a stand-alone computer at a clinician facility where the subject is a patient, or may be a server (whether cloud-based or not) of a service provider where the clinician is a subscriber / customer / service user.

[0075] FIG. 2B illustrates a further example of the system. The system comprises an ingestible capsule 10, a receiver device 30, a charger 32 for the receiver device, a communication cable 34 for connecting the receiver device to a relay device 50, and a remote computer 20 accessible via the cloud. The ingestible capsule 10 is provided to the patient in a sealed package. For example, during the live phase, the ingestible capsule transmits sensor readings to the receiver device 30 via a 433 MHz transceiver. The receiver device 30 is mounted on a belt worn by the patient and also comprises a 433 MHz transceiver. The receiver device 30 is rechargeable via the charger 32. The user interface comprises a button and an LED display. The receiver device 30 can be connected to the relay device 50, for example, via a USB-C connection. Firmware and midware on the receiver device 30 can be updated via the relay device 50. The relay device 50 can be a tablet with an application and can also be rechargeable. The relay device 50 is configured to be held by the clinician, thereby associating data uploaded from the receiver device with a patient ID before being transmitted for processing by the remote computer 20. Once the capsule's live phase is over, the receiver device is returned by the patient to the clinician, and readings transmitted by the capsule 10 during the live phase are associated with patient data and uploaded to the relay device 50 for transfer to the remote computer 20 for processing. The remote computer 20 analyzes the received data to detect indicators and determine timing of motility events including gastro-duodenal transition, ileocecal junction transition, ingestion, and elimination. An external magnetic clip may keep the capsule in a powered-down state during storage and transport (which may be magnetically coupled to a reed switch in the capsule 10 prior to unpacking).Alternatively, the capsule 10 may be in a very low power mode in which the secondary NFC transceiver is in listening mode and configured to receive an encoded NFC control signal from an NFC-enabled receiver device 30, such as a smartphone or tablet running an application for managing data communication with the capsule 10, the received signal powering up the capsule 10 and initiating the live phase of the capsule 10.

[0076] 1C, the Bluetooth-enabled capsule may communicate directly with a smartphone or tablet running an application for managing data communications with the capsule 10, the smartphone being operable as a receiver device, as disclosed herein, via the application. As discussed elsewhere in this disclosure, the capsule 10 may further comprise an NFC communication mechanism for communicating with the smartphone or tablet as a secondary transceiver.

[0077] Pairing or coupling The primary wireless data transmitter may be a Bluetooth transmitter, a Wifi transmitter, a radio transmitter, or another form of wireless data transmitter. The primary wireless transmitter may be configured to transmit in the 433 MHz band. In either case, the primary wireless data transmitter may be provided as part of the primary wireless data transceiver. For example, the primary wireless data transceiver may receive signals at least when performing pairing or any other form of coupling to the receiving device 30. The capsule 10 may be configured to enter wireless pairing or coupling mode immediately at the start of the live phase (i.e., first full power on), where the subject or another user is instructed (either via an instruction manual or via an application running on the receiving device itself) to pair or couple the capsule 10, and in particular the primary wireless transceiver of the capsule 10, with the receiving device 30 before ingesting the capsule 10. However, embodiments may be configured such that pairing or coupling is not required, for example, the capsule 10 may be configured to broadcast data to the receiving device with a data transmission technique that is independent of the pairing or coupling state. The pairing or coupling establishes a data communication connection or path for the transmission of a data transmission payload from capsule 10 to receiver device 30 by the primary data transceiver.

[0078] The data transmission payload is data transmitted from capsule 10 to receiver device 30 either during a pre-excretion transmission routine, a post-excretion transmission routine, or both. The data transmission payload may comprise one or more of raw readings from sensors or pseudo sensors on capsule 10, metrics calculated by on-board processing of the raw readings, and motility event indicators identified by on-board processing of the raw readings.

[0079] Primary Transreceiver Post-Excretion Data Transmission Routine There are two main data transmission routines, and the ingestible capsule may be configured to use either or both data transmission routines depending on the implementation details (i.e., use case). In the post-excretion data transmission model, signals from the sensors are received at the processor hardware 151 (also utilizing the storage capabilities of the memory hardware 152) and processed on the capsule 10 to identify and record motility indicators (and optionally other characteristics of the sensor output or sensor readings of interest or groups of sensor readings of interest), and the recorded motility indicators (and optionally other characteristics, metrics, and readings or groups of readings of interest, such as peak H2, area under a plot of H2 against time) are stored on the memory hardware 152 as a data transmission payload. Other characteristics and readings or groups of readings of interest may include, for example, maximum or minimum readings from a particular sensor, or maximum or minimum readings from a metric calculated by combining the sensors. The maximum or minimum reading may be a local maximum reading or a local minimum reading, where local is defined, for example, by a predefined timing or motility event determined to have occurred by the capsule 10 itself. A specific example is a maximum or minimum H2 concentration, which is a metric calculated from the gas sensor readings by appropriately calibrated processor hardware.

[0080] In a post-excretion data transmission routine, after the excretion of the capsule 10 from the GI tract is detected (e.g., by the temperature sensor 14a signal and / or the accelerometer 19 signal), a data transmission payload is transmitted by the wireless transceiver. Metrics further include peak H2 level or value, timing of peak H2, and total H2 (area under the curve). Such metrics may be calculated by the on-board processor hardware 151 during transit through the subject's GI tract and transmitted from the capsule 10 to a receiver device in a post-excretion transmission, as part of a report or by other methods.

[0081] In the post-excretion data transmission routine, transmission may occur via a Bluetooth transmission mode that is independent of pairing status. That is, for example, if the Bluetooth transceiver is paired to the receiver device 30, it transmits a data transmission payload to the paired receiver device, and if the Bluetooth transceiver is not paired, it broadcasts a data transmission payload to the receiver device 30 in an inquiry mode (sometimes called a discovery mode or a beacon mode) without pairing. The Bluetooth protocol has an inquiry mode in which a device broadcasts a unique identifier, name, and other information. The data transmission payload, or portions thereof, may comprise or be included with such other information. In particular, the data transmission payload may be prioritized or otherwise filtered by the processor hardware 151, such that information deemed particularly important, such as an indication that an excretion has occurred (knowing that the capsule 10 has been excreted is important for clinical reasons), and potentially information such as the timing of determined motility events, is transferred from the capsule 10 in preference to other information.

[0082] Following the inquiry mode transmission, the transceiver again attempts to pair, connect, or otherwise couple with the receiving device and, if successful, attempts to transmit the remainder of the data transmission payload. Of course, the pairing, connection, or coupling may have been performed initially prior to ingestion, such that after excretion the Bluetooth transceiver attempts to re-pair, re-connect, or re-couple with the receiver device 30. This description uses Bluetooth as an example transmission protocol, but it should be noted that the same techniques may be applied to different transmission protocols.

[0083] If there is a data transmission payload pending transmission from capsule 10 after the broadcast of its unique identifier, name, and other information during the Bluetooth inquiry mode, capsule 10 may be configured to initiate or re-initiate a data communication connection (i.e., pairing or re-pairing) with receiver device 30. If the initiation or re-initiation of the communication connection is successful, any pending transmission of said data transmission payload from capsule 10 is effected while the data communication connection remains active.

[0084] The Bluetooth, primary, transceiver 18, or any other primary wireless data transceiver 18, may be configured to automatically reconnect following an initial (i.e., pre-input) connection to the receiver device 30. The receiver device 30 may run an app or web app to guide the subject on how to ingest the capsule 10, notify the subject that an excretion event has been determined, and optionally notify the subject that a data transmission payload has been successfully transmitted to the receiver device 30 so that the capsule 10 can be cleaned. It should be noted that the terms pairing, connecting, and coupling are interchangeable herein and each refers to the establishment of a wireless connection between two devices for wireless data transfer.

[0085] It should be noted that the data transmission payload may be transmitted throughout the capsule 10's passage through the GI tract, depending on the pairing, coupling, or connection to the receiver device 30. However, since the safety of the capsule 10 depends on the capsule 10 being excreted, confirmation that the capsule has determined that an excretion event has occurred is particularly important information. Thus, information representative of the determination of the occurrence of an excretion event (i.e., a report thereof) takes priority and may be transmitted in a broadcast or inquiry mode, with the remaining data transmission payload being transmitted after a connection between the wireless data transmitter 18 and the receiver device 30 has been established.

[0086] In Bluetooth inquiry mode, data can be transmitted to receiver device 30, or any Bluetooth receiver device within range of capsule 10, without pairing. Primary transceiver 18 can operate in Bluetooth inquiry mode or Bluetooth low energy mode. Capsule 10 may store and transmit readings of a data transmission payload readings from one or more sensors representing a predetermined period on either side of an identified motility indicator, for example, only the gas sensor signal, or for all sensors. Such readings may be used to add confidence to the identified motility indicator in terms of determining whether a motility event has occurred and / or may provide other information useful in a health or clinical context.

[0087] More generally, the data transmitted according to the post-excretion data transmission routine may be any of the data transmission payloads that have not yet been transmitted. For example, the primary transceiver 18 may be configured to transmit the data transmission payload to the paired receiver device while still in the GI tract (this element of the transmission is referred to herein as the pre-excretion data transmission routine). However, due to issues such as signal attenuation, noise, power issues, temporary pairing failure, or if pairing was not initially performed, or for any other reason, some or all of the data transmission payload may be pending transmission at the time of excretion. In that case, the remaining data transmission payload is transmitted according to the post-excretion data transmission routine after the excretion is detected. Note that downsampling of the data transmission payload may be performed prior to transmission via the post-excretion data transmission routine. Additionally, note that some elements of the data transmission payload may be blocked from being transmitted via the post-excretion data transmission routine. For example, the bandwidth and time to transmit may also be limited, so that sensor readings may be excluded from the data transmitted according to the post-excretion data transmission routine, although motility event indicators and diagnostic indicators themselves may be included.

[0088] Primary Transreceiver Post-Excretion Data Transmission Routine In the pre-elimination data transmission technique, the sensor signal is transmitted continuously (despite errors, failures, and other unintended interruptions) by the primary transceiver 18. In the pre-elimination data transmission routine, process hardware 151 coordinates receipt of signals from the sensor and storage in memory hardware 152 for transmission by the wireless transceiver 18.

[0089] In the example of the Bluetooth primary transceiver 18, in the pre-elimination transmission routine, the transceiver may be operated according to a long-range Bluetooth transmission procedure, such as BTLE Coded PHY, or a coded-phy Bluetooth transmission procedure. Approximately 10 dB of signal power enhancement is achievable via the BTLE Coded PHY Bluetooth transmission procedure.

[0090] During the data transmission phase of the ingestible capsule 10 (i.e., while the ingestible capsule 10 is in use, i.e., in the GI tract of the subject mammal 40, and taking and transmitting readings, the data transmission phase of the ingestible capsule 10 is a post-excretion short burst in a post-excretion data transmission routine and continuous in a pre-excretion data transmission routine), the wireless transmitter 18 transmits the readings to the receiver device 30, which may be a dedicated device for receiving and storing the readings (and optionally with a user interface) or may be a multi-function device such as a mobile phone (such as a smartphone). The mobile phone may execute an application that processes some or all of the data transmission payload to generate a motility report or a diagnosis of a medical condition based on the motility indicators and diagnostic indicators contained in or derivable from the data transmission payload. Alternatively, the application may be configured to transmit the data transmission payload to a server or another processing device to generate a motility report or a diagnosis based on the data transmission payload. The subject mammal does not need to remain within a particular range of the remote computer 20 during the live phase. The capsule 10 with Bluetooth transceiver 18 may communicate directly with the user's smartphone, thereby eliminating the need for a dedicated receiver device (the smartphone takes on the role of receiver device 30). The receiver device 30 (whether a dedicated device, a mobile phone, or a tablet computer) may process the readings itself or may upload the readings to a remote computer 20 for processing (i.e., identifying motility indicators, determining motility event timing, and decomposing gas analytes). The uploading may be done continuously during the capsule's live phase, or the uploading may be done after the capsule's live phase has ended. The receiver device 30 may also store the readings, so that loss of connection between the receiver device 30 and the remote processing device is not critical.

[0091] Pretreatment The on-board processor 151 may apply one or more processing or pre-processing steps, as discussed in more detail below. Digitization of the readings may be performed by the sensor itself, by the processor 151, or by the wireless transceiver 18. The digitized readings are transmitted via the antenna 17. The capsule 10 readings are taken instantaneously and associated with the instantaneous time the readings were taken. For example, a timestamp may be associated with the readings by the microcontroller 15, the wireless transmitter 18, or at the receiver device 30 or remote computer 20. For example, if the readings are taken and transmitted by the wireless transmitter 18 approximately instantaneously (i.e., within a second or a few seconds), the time of receipt by the receiver device may be associated with the readings as a timestamp. The processing of the readings, discussed further below, depends somewhat on the relative timing of the readings (i.e., whereby simultaneous readings from different sensors may be identified as simultaneous), but accuracy on the level of a second, a few seconds, or tens of seconds is sufficient.

[0092] Combining Data Transmission Routines In the hybrid mode, the capsule 10 may combine two data transmission routines. For example, the capsule 10 may process the sensor readings on-board to identify motility markers (and optionally other readings or groups of readings of interest as well) for transmission in Bluetooth inquiry mode immediately after excretion. In addition, the capsule 10 may continuously transmit the sensor readings to a paired receiver device. Optionally, the continuous transmission may be the gas sensor signal alone, or the gas sensor signal and the temperature sensor signal required to calibrate the gas sensor signal. The gas sensor signal is particularly useful in providing health and clinical information, especially when combined with motility indicators provided by other sensors such as accelerometers, reflectometers, etc. The gas sensor signal may be downsampled or subjected to other compression techniques by the on-board processor before transmission. Optionally, the on-board processor hardware 151 may apply one or more filters, such as a high-pass or low-pass filter applied to the value itself or to its derivative with respect to time, so that only gas sensor signals that meet certain thresholds are included in the data transmission payload. A metric representative of the gas sensor signal, such as the peak of the derived H2 value or the area under a plot of the derived H2 value with respect to time, may be maintained and transmitted from the capsule 10.

[0093] For capsules 10 configured to perform data transmission during passage through the GI tract (i.e., pre-excretion data transmission routine), commercial bands (433 MHz, Bluetooth (2.4 Ghz), etc.) are used by the antenna 17 so that electromagnetic waves in this frequency range can safely penetrate the mammalian tissue 40. Bluetooth may also be used in such capsules, which may be long-range Bluetooth, especially if the subject's (human) BMI is above a threshold or if a high level of attenuation is expected for some other reason. Other commercial bands and protocols may be used in various applications, such as LoRa. Coding may be applied at the digitization stage to ensure that the data transmitted by the capsule 10 is distinguishable from data transmitted by other similar capsules 10. The transmitting antenna 17 may be, for example, a pseudo-patch type for transmitting data outside the body data acquisition system.

[0094] power supply The power source 16 is a battery or supercapacitor capable of powering the sensors and electronics, including the processor hardware 151 and the memory hardware 152. A lifespan of at least 48 hours may be set as a minimum requirement for the GI capsule. The number of silver oxide batteries in the power source 16 is configurable depending on the required lifespan and other specifications for the capsule. For example, long-range Bluetooth may consume more power than standard Bluetooth. The capsule may be configured to switch from long-range Bluetooth transmission to standard Bluetooth transmission when the energy stored in the battery (or batteries) falls below a certain threshold, and the on-board processor is configured to monitor the stored energy level.

[0095] Repeater FIG. 2C shows a receiver device 30 connected to a relay device 50. For example, the relay device 50 may be an in-clinic Android tablet used to pair capsule IDs, such as serial numbers, to patent information that is displayed on generated reports. The Android tablet is loaded with an application with a series of screens that walk the clinician through the capsule administration process, including instructing the patient to ingest the capsule. In some implementations, the timestamp of the instruction may be recorded as the ingestion event timing (e.g., if the ingestion is witnessed by the clinician). Alternatively, the ingestion event timing may be recorded via the subject's interaction with a button on the receiver device 30 (and as shown in FIGS. 2A-2D).

[0096] On-board components The capsule 10 includes internally a gas sensor 13, an environmental sensor 14, and a microcontroller 15. The environmental sensor 14 can be a temperature sensor 14a or a humidity sensor 14b, or can be a temperature sensor 14a and a humidity sensor 14b. The internal electronics can also include a power source 16, such as a silver oxide battery, an antenna 17, a wireless transmitter 18, and a reed switch. As shown in FIG. 3A, the gas sensor 13 includes a TCD gas sensor 131 and a VOC gas sensor 132.

[0097] The gas sensors 13 are each less than a few mm in size and are sensitive to specific gas components including oxygen, hydrogen, carbon dioxide, and methane. In practice, the VOC sensor 132 may be configured to provide a sensor-side reading and a driver or heater-side reading. The heater-side reading may be used to determine the thermal conductivity of the surrounding gas, whereby the heater-side reading of the VOC is a TCD reading. The sensor-side reading is used to determine the concentration of volatile organic compounds in the surrounding gas, which is a VOC reading. The TCD sensor 131 may be, for example, a heating element coupled to a thermopile output, where the thermopile temperature changes due to the energy transferred to the gas at the location of the capsule 10. The TCD sensor 131 measures the rate of heat diffusion from the heating element.

[0098] As shown in FIG. 6, the heater side of the VOC sensor (operating as a TCD sensor) and the sensor side of the TCD sensor have different operating ranges, so that the TCD readings from the two sensors collectively span a wider operating temperature range than either sensor individually. Both sensors have a heating element. The TCD sensor has a lower operating temperature but higher accuracy. The heater side of the VOC extends the operating range but has a lower accuracy of the TCD readings than the TCD sensor. The greater collective thermal range achieved by the two gas sensors 13 in concert allows for better resolution of analytes in the second processing branch. Since the thermal conductivity of the constituent gases in the gas mixture of the GI tract varies with temperature, by taking TCD readings at different operating temperatures, different gases can be resolved from one another. This is exploited in the second processing branch, which determines the identity and concentration of the constituent gases in the gas mixture surrounding the capsule 10.

[0099] The gas sensors 13 are contained in a portion of the capsule 10 that is sealed from the power source 16 and other electronic components. The exterior surface of this portion of the capsule is constructed with a selectively permeable membrane. For example, the gas sensors 13 include respective heaters that are activated to heat the sensing portion of each gas sensor 13 to a temperature at which a sensor reading is to be taken (i.e., a measurement temperature). The heaters may be pulsed such that the temperature of the sensing portion varies over time, so that a measurement temperature is taken for a period of time sufficient to make a reading, but without consuming the power required to continuously maintain the measurement temperature.

[0100] The gas sensor 13 is calibrated so that the gas sensor readings can be used to identify the composition and concentration of a particular gas. Calibration coefficients are collected in manufacturing and applied to the recorded readings at the processing stage (i.e., by a server, such as on the cloud). Otherwise, this calibration can be performed on the capsule 10, on the receiver device 30, or on any device that has access to the calibration coefficients and the recorded readings from the gas sensor 13. Such calibration relates to a branch of the process related to measuring the concentrations of the constituent gases in the gas mixture in the capsule 10. Context for the output of that branch of the process is provided by another branch of the process, which determines (or predicts within a given confidence level) the location of the capsule 10 in the GI tract where said gas mixture is found. In the location determination process branch, some calibration may also be required to find the gastroduodenal transition indicator, since food ingested at different temperatures changes the environmental temperature in the stomach, affecting the rate of thermal diffusion. For gas sensor readings taken after ingestion and before the gastroduodenal transition (i.e., while the capsule 10 is in the stomach), processing of the readings may include applying an adjustment to the TCD readings from either gas sensor to correct for changes in environmental temperature based on the environmental temperature reading by the environmental temperature sensor 14a. Since the TCD readings effectively measure the rate of heat loss to the surroundings, accuracy is improved by measuring the temperature of the surroundings rather than relying on assumptions (i.e., prior knowledge of the subject mammal's internal temperature). However, processing may rely on assumptions, for example, if the capsule 10 does not include an environmental temperature sensor 14a, or if there is some problem with the environmental temperature sensor readings, or, for example, if the level of accuracy provided by the assumptions is acceptable for the particular implementation. The stomach temperature may change, for example, based on the ingestion of liquids or food by the subject mammal, or physical activity performed by the subject mammal 40. Environmental temperature is a term used herein to refer to the temperature of the environment in which the capsule 10 is located, which is different from the operating temperature of the gas sensor 13.The sensitivity of the gas sensor 13 to different component gases varies according to the operating temperature of the sensor, and processing of the readings includes calibrating (also called adjusting or correcting) the readings from the gas sensor according to the concurrent operating temperature and, optionally, according to the concurrent environmental temperature.

[0101] In addition to the gas sensor 13 and the environmental sensor 14, the capsule electronics further includes a microcontroller 15, a power source 16, an antenna 17 or multiple antennas, a wireless transceiver 18 or multiple wireless transceivers, and optionally a reed switch (although if there are two wireless transceivers the reed switch may be omitted). The wireless transmitter 18 operates in conjunction with the primary transceiver antenna 17 to send data transmission payloads including readings from the sensors (collectively referring to the gas sensor 13 and the environmental sensor 14) to a receiver device 30 and / or a remote computer 20 for processing.

[0102] Assuming a pre-excretion data transmission routine, during the live phase of the ingestible capsule 10 (i.e. while the ingestible capsule 10 is in use, i.e. while it is in the GI tract of the subject mammal 40 and taking and transmitting readings), the wireless transmitter 18 of the primary transceiver transmits the readings to the receiver device 30, which may be a dedicated device for receiving and storing the readings (and optionally with a user interface) or may be a multi-function device such as a mobile phone (such as a smartphone) running an application that manages the smartphone's role in receiving, processing, and / or transmitting data from the capsule 10. The subject mammal 40 does not need to remain within a particular range of the remote computer 20 during the live phase. The receiver device 30 uploads the readings to the remote computer 20. The uploading may be done continuously during the capsule's live phase or the uploading may be done after the capsule's live phase has ended. In the case of continuous transmission, the receiver device 30 may also store the readings so that loss of connection between the receiver device 30 and the network is not significant. The receiver device 30 may apply one or more pre-processing steps. Digitization of the readings may be performed by the sensor itself, by the microcontroller 15, or by the wireless transmitter 18. The digitized readings are transmitted via antenna 17. Readings of the capsule 10 are taken instantaneously and associated with the instantaneous time the readings were taken. For example, a timestamp may be associated with the readings by the microcontroller 15, the wireless transmitter 18, or at the receiver device 30 or remote computer 20. For example, if the readings are taken and transmitted by the wireless transmitter 18 approximately instantaneously (i.e., within a second or a few seconds), the time of receipt by the receiver device may be associated with the readings as a timestamp.The processing of the readings, discussed further below, depends somewhat on the relative timing of the readings (i.e., whereby simultaneous readings from different sensors may be identified as simultaneous), but accuracy on the level of one second, a few seconds, or even tens of seconds is sufficient.

[0103] 3A illustrates the primary transceiver antenna 17 and directional coupler 171 as elements of the wireless transmitter 18 because the antenna is the physical means by which the wireless transmitter 18 transmits data to the receiver device 30. The wireless transmitter 18 is also configured to buffer the data for transmission. The wireless transmitter 18 may also be configured to encode the data with a code that is unique to the capsule 10 among a group of similar capsules 10.

[0104] The interconnections between the electronic components in FIG. 3A are shown as being through a central bus. This is one example of how power and data may be distributed between the components. Other circuit architectures may be implemented, for example all connections may be through a microcontroller 15 which coordinates the distribution of data and power between the components. The sensors (TCD sensor 131, VOC sensor 132, environmental sensor 14, accelerometer 19, and directional coupler 171) take readings under the direction of the microcontroller 15 which is powered by a power source 16 and transfers the readings to a wireless transmitter 18 for transmission via an antenna 17 to a receiver device.

[0105] The capsule dimensions may be less than 11.2 mm in diameter and less than 27.8 mm in length. The housing of the capsule 10 may be made of a biocompatible, non-digestible polymer. The housing may be smooth and non-sticky to allow passage of the capsule in the shortest possible time and to minimize the risk of any capsule retention.

[0106] Data Processing The processing may be performed in near real-time, allowing for latency caused by transmission and processing. Alternatively, the readings may be received by the receiver device 30 and stored for uploading and retrospective processing. Such retrospective processing may be performed by first analyzing the most recent readings (i.e., in reverse chronological order), so that the first event timing determined is time of ejection, the next is time of ICJ, then time of acquisition, then time of ingestion, or the analysis may be an analysis of readings in chronological order.

[0107] The remote computer 20 may process the readings, or the processing may be performed within the capsule 10, or by the receiver device 30. The processing may be performed by some combination of these devices. The processing may be considered to include two branches, a first (motility) branch for determining the location of the ingestible capsule 10 in the GI tract based on the readings, and an optional second (gas composition) branch for determining the constituent gases and their concentrations in the gas mixture at the location of the ingestible capsule 10. It is noted that the embodiments discussed herein are primarily concerned with the first (motility) branch, and a particular advantage of accurately determining the location of the ingestible capsule 10 in the GI tract is to provide context for the determination of the second (gas composition) branch. However, it is noted that the results of the first (motility) branch of the processing may provide useful information in the assessment of gut health even in the absence of the second (gas composition) branch of the processing, and may have other utilities beyond the second (gas composition) branch of the processing. Optionally, the determination of the second (gas composition) branch of the process may be utilized to add confidence to the determination of the first (motility) branch of the process.

[0108] Readings from a different sensor or pseudo sensor are used in the first (motility) branch and / or the second (gas composition) branch, as appropriate. For example, TCD gas sensor readings are utilized to detect gastroduodenal transit indicators in the first (motility) branch and the second (gas composition) branch, for example to determine the concentration of H2 at the location of the capsule 10. Readings from the VOC heater side are used in the second (gas composition) branch as a hotter TCD sensor to increase the temperature range over which TCD readings are obtained and thus the range of detectable H2 concentrations. As the VOC sensor side is sensitive to both O2 and H2 as well as other gases, these readings may be utilized in the second (gas composition) branch. Other gases include CH4 and SCFA. Optionally, the VOC sensor side readings are not used in the second (gas composition) branch, and the VOC sensor side readings are used only to detect the ileocecal junction indicator. Optionally, the VOC sensor side (i.e., the VOC sensing element) forms a resistor in a voltage divider network, the output of which is measured as a live reading on the VOC sensor side. A conversion may be applied in the capsule 10 and / or as part of the processing to convert the output of the voltage divider network to a resistance measurement from the sensing element. The VOC sensor side may be driven with a consistent (i.e., repeated) voltage pulse profile. The VOC sensor side readings may be taken synchronously with the voltage pulse profile such that there is no phase shift between the timing of the voltage pulses and the readings. The CH4 concentration is determined from the TCD gas sensor readings and / or the VOC heater side readings.

[0109] Primary transceiver configuration and antenna reflectivity related readings Commercial bands (such as 433 MHz and Bluetooth 2.4 GHz) are used by the primary transceiver antenna 17 because electromagnetic waves in this frequency range can safely penetrate mammalian tissue 40. Other commercial bands may be used. Coding may be applied in the digitization stage to ensure that the data transmitted by the capsule 10 is distinguishable from data transmitted by other similar capsules 10. The transmitting antenna 17 may be, for example, a pseudo-patch type for transmitting data outside the body data acquisition system. The power source 16 is a battery or supercapacitor capable of powering the sensors and electronic circuits. A life of at least 48 hours is required for the gastrointestinal capsule. A number of silver oxide batteries in the power source 16 can be configured depending on the required life and other specifications for the capsule.

[0110] The antenna 17 may be in series with a directional coupler 171. The directional coupler 171 and the antenna 17 are configured as a reflectometer. The reflectometer measures the amplitude of the reflected signal by a diode detector. The reflectometer amplitude measurement is a reading that represents the electromagnetic properties of the material in the vicinity of the capsule. For example, a good impedance match between the antenna and the environment surrounding the capsule 10 results in a low amplitude reflected signal and therefore a low amplitude measurement. A poor impedance match between the antenna and the environment surrounding the capsule 10 results in a high amplitude reflected signal and therefore a high amplitude measurement.

[0111] In the above example, the reflectometer measures the amplitude of the reflected signal at the primary transceiver antenna 17. Optionally, the reflectometer may be configured to measure the phase of the reflected signal. For example, the capsule 10 may include a quadrature demodulator to extract phase information from the reflected signal. The phase information provides a dimension in addition to the amplitude information representing the reflected signal. In a first example, the phase information from the reflected signal may indicate a step change in a change in the environment surrounding the capsule such that analysis of the phase information provides a motility event indicator. In a second example, described in more detail below, the phase information allows a determination to be made as to how to modify the antenna control signal to better match the antenna impedance to the impedance of the environment.

[0112] The quadrature demodulator converts the modulation of the reflectance signal into an imaginary signal and a real baseband signal. The quadrature demodulator is driven by a carrier frequency (the carrier frequency is the frequency of transmission by the primary transceiver) sine wave with a phase difference of 90 degrees, and produces two baseband signals that can be compared to produce phase information. Low pass filtering can be applied (to each of the imaginary and baseband signals) to filter out high frequency content at a frequency approximately twice the original baseband frequency.

[0113] The reflectometer readings (either amplitude and / or phase readings) provide the basis for distinguishing between gas, liquid and solid materials at the location of the capsule in the GI tract. The reflectometer readings (either amplitude and / or phase readings) provide the basis for distinguishing between different physical environments surrounding the capsule 10. The reflectometer readings enable the antenna 17 and directional coupler 171 to operate in cooperation as an environmental dielectric and impedance sensor.

[0114] Reflectometer Tunable Antenna FIG. 3B shows a specific example of a reflectometer. The capsule 10 is configured to transmit the capsule 10's data transmission payload captured via on-board sensors and pseudo sensors to the receiver device 30 via wireless signals. Since available energy is limited within the capsule 10, the capsule 10 may be configured to transmit the wireless signals in an energy efficient manner. The constrained volume and shape of the capsule 10, combined with the changing electromagnetic properties of the surrounding environment during passage through the GI tract of the subject mammal, means that impedance matching between the antenna 17 and the surrounding environment is difficult to achieve. Better impedance matching improves transmission efficiency. The transmitter 18 may be, for example, a transceiver control circuit including buffering data for transmission.

[0115] The transceiver shown in Figure 3B includes a tunable antenna 17. A reflected signal from the antenna 17 is generated during transmission, received at a directional coupler, and processed in a controller 181 to extract amplitude and / or phase information from the reflected signal.

[0116] The amplitude provides a measure of the amount of reflected energy. The phase information provides information about how the phase shifts between the transmitted and reflected signals. Either or both step changes can be caused by changes in the electromagnetic properties of the transmit environment, i.e., the environment in which the capsule 10 is located. Thus, reflectometer measurements (which is a collective term that applies to either or both of the amplitude and phase information) provide an indicator of the environment surrounding the capsule or changes in the environment surrounding the capsule by their absolute value (and via reference to calibration information such as a look-up table) and / or by the presence of step changes in their values ​​(in this case, no calibration information is required).

[0117] The antenna 17, directional coupler 171, controller 181, and variable capacitor 172 form a closed loop mechanism for measuring the efficiency of the antenna (where the amplitude of the reflected signal indicates efficiency, low amplitude indicates efficiency, and high amplitude indicates inefficiency) and generating a control signal to the variable capacitor 172 by the controller 181 to minimize the reflectivity of the antenna. Depending on how the reflectometer is configured, the controller 181 may be configured to incrementally change the control signal to the variable capacitor 172, compare the amplitude reading to the amplitude reading before the incremental change, and determine based on the comparison whether to reverse the direction of the incremental change. Otherwise, in a reflectometer that extracts phase information, the phase information itself may inform the controller 181 in which direction the control signal should be changed to reduce the amplitude reading.

[0118] The controller 181 is configured to generate a control signal for varying the capacitance of the variable capacitor 172, which changes the impedance of the antenna 17, based on the antenna reflectivity related readings. The control algorithm has the capability of determining a control signal output by the controller 181 for varying the capacitance of the variable capacitor 172 to change the impedance of the antenna 17 to reduce the amplitude of the reflected signal from the antenna 17. The controller 181 may empirically generate the control signal by periodically adjusting the control signal in a given direction, comparing pre- and post-adjustment of the reflectometer amplitude readings, changing the direction of adjustment for the next periodic adjustment if the reflectometer amplitude readings increase from the pre-adjustment value to the post-adjustment value, and maintaining the direction of adjustment for the next periodic adjustment if the antenna reflectivity related readings decrease from the pre-adjustment value to the post-adjustment value. The controller may deterministically generate the control signal based on the reflectometer phase information, where a particular phase reading range indicates that the controller should increase the control signal, a particular phase reading range indicates that the controller should decrease the control signal, and optionally a particular phase reading range indicates that the controller should maintain the control signal. The level of the control signal generated by the controller 181 is proportional or directly proportional to the capacitance of the variable capacitor 172 and therefore proportional to the impedance of the antenna 17. As described above, the antenna 17, the controller 181 and the variable capacitor 172 form a closed loop or feedback loop mechanism for impedance matching the antenna 17 to the surrounding environment (i.e., reducing the reflected signal amplitude), so logically the control signal generated by the controller 181 to set the capacitance of the variable capacitor is proportional to the impedance of the environment surrounding the capsule 10. Thus, the control signal itself can be recorded as an antenna reflectivity related reading that is representative or indicative of the environment surrounding the capsule 10.

[0119] The reflectometer, consisting of directional coupler 171, controller 181, variable capacitor 172, and antenna 17, forms a closed loop (i.e., feedback loop) to automatically adjust antenna 17 to increase transmission efficiency. Furthermore, as described above, the control signal from controller 181 to variable capacitor 172 is indicative of the impedance of antenna 17, and therefore the environment surrounding capsule 10, and thus the control signal itself can be sampled as an antenna reflectivity related reading for use in motility processing. The change in the control signal, or the absolute value of the control signal itself (combined with a calibrated look-up table), provides an indicator of the position of capsule 10 within the GI tract of the subject mammal.

[0120] Transmitter 18, in the context of Figure 3B, is a circuit that provides a transmission signal (i.e., a carrier wave having an encoded data transmission payload, any metadata required by the transmission protocol, etc.) Transmitter 18 may be a Bluetooth transmitter.

[0121] The readings of the ingestible capsule 10, including one or more of readings from the environmental sensor 14, the heater side 132b of the VOC gas sensor 132, the sensor side 132a of the VOC gas sensor 132, and the TCD gas sensor 131, may also include reflectometer readings. Thus, a change in capsule position within the GI tract causes a change in the antenna reflectivity related readings, thus providing an indicator that a transition event between two sections of the GI tract has occurred.

[0122] Ingestible capsule: Accelerometer The ingestible capsule 10 may further comprise an accelerometer 19. The accelerometer 19 may be a three-axis accelerometer. The rate of change of the angular position or orientation of the capsule 10 is dependent in part on the position within the GI tract, and thus the accelerometer readings provide an indicator that a transition event between two sections of the GI tract has occurred. The accelerometer readings may measure angular acceleration about three axes of rotation, which may be mutually orthogonal.

[0123] Off-board Processing The ingestible capsule 10 of Figs. 1A-3 is a data collection and data transmission device. As mentioned elsewhere in this disclosure, the collected data (i.e., readings) are uploaded to the remote computer 20 for processing via the receiver device 30, which may be an intermediary device for transmitting the readings to the remote computer, or may be directly connectable to the remote computer for uploading the readings to the remote computer. For example, the receiver device 30 may comprise a memory readable by the remote computer 20. The receiver device 30 provides a data connection, such as a wired connection, a network connection, or a plug socket connection, directly to the remote computer 20, or through a network such as the Internet, through which the readings are relayed to the remote computer 20. In this way, the capsule 10 need only be configured to establish a data connection with the receiver device 30, such that the subject mammal does not need to remain within a certain range of the remote computer 20 during the live phase, and the receiver device 30 may be a dedicated device for receiving and storing the readings (and optionally with a user interface) or may be a multi-function device, such as a mobile phone (e.g., a smartphone). The receiver device 30 uploads the readings to the remote computer 20. The uploading may be done continuously during the live phase of the capsule, or the uploading may be done after the live phase of the capsule has ended. In the case of continuous transmission, the receiver device 30 may also store the readings so that loss of connection between the receiver device 30 and the network is not significant.

[0124] Processing the recorded readings A method including obtaining readings and processing the readings is shown in Figures 4 and 5. The process can be considered to include two branches, a first (motility) branch for determining the location of the ingestible capsule 10 in the GI tract based on the readings, and a second (gas composition) branch for determining the constituent gases and their concentrations in the gas mixture at the location of the ingestible capsule 10. The second (gas composition) branch is optional and is an example of the usefulness of the results of the first (motility) branch of the process. This disclosure is primarily concerned with the first (motility) branch. The second (gas composition) branch can be performed in parallel with the first (motility) branch or delayed with respect to the first (motility) branch, as the second (gas composition) branch utilizes the determination of the first (motility) branch to detect a disease or condition. For example, the second (gas composition) branch includes processing the readings of the TCD gas sensor 131, the VOC gas sensor 132 to determine the component gases and their concentrations in the gas mixture at the location of the ingestible capsule 10, and using the determination of the process of the first (motility) branch to determine the location of the ingestible capsule 10. In this manner, the determined gases and concentrations can be determined to be pre-gastroduodenal transition after ingestion, or pre-ileal junction after gastroduodenal transition, or pre-ileal junction before voiding. However, it should be noted that the results of the first (motility) branch of the process can provide useful information in the assessment of gut health even in the absence of the second (gas composition) branch of the process and have other usefulness over the second (gas composition) branch of the process. Optionally, the determination of the second (gas composition) branch of the process may be utilized to add reliability to the determination of the first (motility) branch of the process.

[0125] The method may include storing and / or transmitting the TCD gas sensor readings and the VOC gas sensor readings from among the recorded readings as a function of time along with the determined timing of the first and second transition events (and optionally the ingestion and excretion events) for analysis. For example, the analysis may include a diagnosis of one or more conditions or diseases associated with the production of a particular constituent gas or concentration thereof at a particular location or section of the GI tract.

[0126] FIG. 4 illustrates a method of determining the location of the capsule 10 in terms of a section of the GI tract by providing an ingestible capsule 10 to a mammal for ingestion S100, recording readings from the capsule 10 S102, and determining a first transition event timing S104 and a second transition event timing S106.

[0127] FIG. 5 illustrates a particular example of the method of FIG. 4, further including determining ingestion event timing S103 and excretion event timing S107.

[0128] As described elsewhere, the readings may be processed chronologically or in reverse chronological order. Thus, the order in which the steps are performed in FIG. Time series processing: S100, S102, S104 and S104a, S106 and S106a, or Reverse chronological processing: S100, S102, S106 and S106a, S104 and S104a. Or in Figure 5: Time series processing: S100, S102, S103 and S103a, S104 and S104a, S106 and S106a, S107 and S107a, or Reverse chronological processing: S100, S102, S107 and S107a, S106 and S106a, S104 and S104a, S103 and S103a.

[0129] The binding for the readings analyzed to detect an indicator of an event is set by an already determined event. Thus, in case of chronological processing, in detecting an event indicator, the readings are analyzed sequentially from the determined timing of the preceding event (when detecting an ingestion, the preceding event is the start). In case of reverse chronological processing, when detecting an event indicator, the readings are analyzed sequentially backwards from the determined timing of the processing event (when detecting an excretion, the subsequent event is the end, which may be set by no more readings or by an object on the user interface). Thus, the processing may be as follows: Time series processing: S100, S102, S104 and S104a, S106 and S106a (pre-binding provided by S104) Reverse chronological processing: S100, S102, S106 and S106a, S104 and S104a (delay binding provided by S106) Or in Figure 5: Time series processing: S100, S102, S103 and S103a (pre-bound by the start event), S104 and S104a (pre-bound by S103), S106 and S106a (pre-bound by S104), S107 and S107a (pre-bound by S106), or Reverse chronological processing: S100, S102, S107 and S107a (late bound provided by end event), S106 and S106a (late bound provided by S107), S104 and S104a (late bound provided by S106), S103 and S103a (late bound provided by S104).

[0130] For simplicity and ease of understanding, the discussion of Figures 4 and 5 pertains to example time series processing where the rolling average progresses in a forward direction from a pre-bound starting point. However, the above provides guidance that enables the application of the present disclosure to reverse time series processing where the rolling average progresses in a reverse direction from a late-bound starting point.

[0131] start References to a start event refer to a power-on event of the capsule that initiates a live phase in which the capsule is active and readings are generated by the sensors and received by the receiver device, or the initiation of recording by pressing a button on the user interface of the receiver device 30 (allowing the capsule to already be powered). The live phase refers to the time when the capsule is powered on and readings are being recorded (i.e. stored or relayed) by the receiver device 30.

[0132] The initiating event may be an encoded activation control signal received by the secondary transceiver, which is the NFC transceiver in the capsule. The encoded activation control signal is transmitted by the NFC transceiver of the receiver device 30.

[0133] end References to an end event refer to the end of the live phase, which may refer to a power down event of the capsule that ends the live phase, or to the end of the live phase by pressing a button on the user interface of the receiver device 30.

[0134] intake At S100, an ingestible capsule 10 is provided to a target mammal 40 for ingestion. The ingestible capsule 10 may be as illustrated in any of FIGS. 1A-3 and includes, among other things, a housing 11, a power source 16, an environmental sensor 14, a TCD gas sensor 131, and a VOC gas sensor 132. The ingestible capsule 10 may be stored in a powered-down state in contact with the packaging, and separation of the ingestible capsule 10 from the packaging terminates the powered-down state and the capsule 10 enters a powered state. Entering the powered state may be an initiating event, or the initiating event may require the capsule to enter a powered state and a button press (or other interaction) with a user interface on the receiver device 30. Separation of the capsule 10 from the packaging may be an event that causes the capsule to power up and begin taking and transmitting readings by the capsule 10.

[0135] Ingestion is expected to occur shortly after entering the powered state, which is taken to mean within 15 minutes, 30 minutes, or 1 hour. The subject may be instructed via the application and / or via instructions on the packaging of capsule 10 to only activate the capsule when ready for ingestion (i.e., NFC activation via the application), thereby keeping the time between activation and ingestion to one minute or less.

[0136] Record the reading At S102, recording of readings begins. The readings are recorded by the receiver device 30, which either immediately relays the readings to the remote computer 20 for processing or stores them for later uploading to the remote computer 20. The readings include readings of the TCD gas sensor 131, readings of the sensor side of the VOC gas sensor 132a, and may also include one or more of environmental sensor readings, readings from the heater side of the VOC sensor 132b, antenna reflectivity related readings (i.e., readings from the antenna 17 and directional coupler 171), and readings from the accelerometer 19. The readings are recorded as a function of time. The time value assigned to each live reading may be assigned at the capsule 10, for example, by the microcontroller 15 and / or the wireless transmitter 18, may be assigned by the receiver device 30 based on the time of receipt of the respective reading from the capsule 10, and / or may be assigned by the remote computer 20 based on the time of receipt from the capsule 10 or from the receiver device 30. Alternatively or additionally, the time value assigned to each live reading may be based on the order of arrival. For example, if it is known that TCD gas sensor readings are taken every n seconds, then the mth reading will be taken m×n seconds (or m−1×n seconds, depending on the implementation) after the start event that starts the live phase. Note that the time values ​​may be relative to a baseline, such as the capsule 10 entering a powered state, rather than an absolute value of time based on calendar and time values.

[0137] Although these steps are shown sequentially in Figures 4 and 5, in practice the taking and recording of readings S102 may be performed while the processing steps S103-S107 are being performed (in the case of chronological processing, obviously for reverse chronological processing the live phase is ended before the processing steps are performed). Optionally, the processing may be performed after the recording of the readings S102 is completed and the capsule is expelled. The processing may be performed on the cloud. The processing may be performed on a server computing device connectable to the capsule 10 via an internet connection to the receiver device 30. The receiver device itself may perform some or all of the processing steps S103-S107.

[0138] Processing for determining motility event timing Steps S103 to S107 are processing steps and involve analysing the recorded readings to determine whether a particular event has occurred that allows for determining the position of the capsule 10 in the GI tract. The processing is not necessarily intended to determine the live or contemporaneous position of the capsule 10, but rather the position of the capsule 10 at the timing of the recorded readings. The position at the timing of a subset of readings is the intended output, not the position at the timing of the processing. For example, determining that the capsule was in a particular section of the GI tract at the timing when a series of readings were taken from the VOC gas sensor 132 or the TCD gas sensor 131. Or, for example, determining the timing of passing through a section of the GI tract, the section of the GI tract being itself an indicator of gut health.

[0139] Each of the determination steps of determining an ingestion event timing S103, determining a first transition event timing S104, determining a second transition event timing S106, and determining an excretion event timing S107 has a respective associated detection step. In general, the detection step involves processing and analyzing the recorded readings to identify indicators (i.e., markers) that indicate that an event associated with motility of the capsule 10 may have occurred. Each determination step involves, in addition to detection, applying a condition or some other logic to the detected indicator to determine (within a confidence level) that the indicator was caused by a motility event, and thus, a motility event may be determined to have occurred at (or around) the time of the detected indicator. Motility events include one or more of an ingestion event, a gastroduodenal transition, an ileocecal junction transition, and an excretion event. Gastrointestinal motility is defined by the movement of the digestive system and the movement of contents through the digestive system. The indicators are features in a plot of recorded readings from an associated sensor or pseudo sensor versus time. A feature may be a step, a bump, an inflection point, or a slope change. A particular indicator may be more specific, for example a condition may be more specific than an indicator that is simply a step, a bump, an inflection point, or a slope change.

[0140] An indicator may be detected in a reading from a first sensor. The indicator is associated with the hypothesis that the indicator was caused by an event associated with capsule motility. Confidence may be added to the hypothesis by obtaining readings from other sensors at (and around) the timing of the indicator and detecting a confirming indicator in those readings. For example, hydrogen (H2) levels vary throughout the GI tract, so H2 level readings may be used to add confidence to readings from other sensors. H2 level readings may be used as the basis for an ileocecal junction transition indicator. In particular, an ileocecal junction transition indicator may be detected by identifying an increase in the (sensor side) VOC gas sensor output above a predetermined threshold with a simultaneous increase in H2 levels above a predetermined threshold or a temporally adjacent increase in H2 levels above a predetermined threshold within a predetermined time distance to either side. Note that the H2 level is determined from the TCD gas sensor output and / or the heater side VOC sensor output.

[0141] Similarly, the CH4 level readings may be used as the basis for an ileocecal junction transition indicator. In particular, the ileocecal junction transition indicator may be detected by identifying an increase in the (sensor side) VOC gas sensor output above a predetermined threshold with a simultaneous increase in CH4 levels above a predetermined threshold, or a temporally adjacent increase in H2 levels above a predetermined threshold within a predetermined time distance to either side. Note that the CH4 level may be determined from the TCD gas sensor output and / or the heater side VOC sensor output.

[0142] Different subsets of the recorded readings may be analyzed to detect different indicators. The subsets may be partitioned according to timing and according to the sensor from which they were obtained. Partitioning by timing is discussed above with respect to early and late binding for time series and reverse time series processing.

[0143] It should be noted that the term sensor is used broadly to encompass not only the sensor itself (i.e., the TCD gas sensor 131, the sensor side of the VOC gas sensor 132a, and optionally the environmental sensor 14 and / or the accelerometer 19), but also components that provide readings and are not the sensor itself, such as the directional coupler 171 and the heater side of the VOC sensor 132b (these components may be referred to as pseudo-sensors). The term sensor encompasses the sensor itself and pseudo-sensors.

[0144] In S103a, the recorded readings from the environmental sensors 14 are analyzed to detect a change in the environment indicative of an ingestion event. In this context, the change may be a change in environmental temperature as indicated by the readings of the environmental temperature sensor 14a, or the change may be a change in environmental humidity as indicated by the readings of the environmental humidity sensor 14b. The detection is based on readings from both the environmental temperature sensor 14a and the environmental humidity sensor 14b to add confidence to each other or to account for unusual ambient humidity or temperature conditions that may reduce the change in one state upon ingestion (i.e., ingestion on a hot day may not record a significant temperature change, but in many circumstances will record a significant humidity change). In time series processing, the analysis may be an analysis of the environmental sensor readings forward from a starting event (such as powering on the capsule 10), with an upper time limit set by the determination of the ingestion event timing. That is, after a detected change in the environmental sensor readings is determined to be due to an ingestion event, no further analysis is performed to detect the ingestion event. In reverse chronological processing, the analysis may be environmental sensor readings in a reverse direction from the gastroduodenal transition event, with a lower temporal limit set by the determination of the ingestion event timing. That is, after a detected change in the environmental sensor readings is determined to be caused by an ingestion event, no further analysis is performed to detect the ingestion event. Regardless of the processing direction (where processing direction refers to chronological or reverse chronological), detecting the change in S103a may be performed sequentially by comparing one or more readings of the subject to a predetermined number of preceding readings, with a difference exceeding a threshold (i.e., 1 or 2 degrees Celsius or 1% or 2% relative humidity) being a detected change. Determining the ingestion event timing may include comparing the temperature or humidity of the subject reading to an expected temperature or humidity for the environment at the beginning of the GI tract of the subject mammal 40, with being within the threshold being a determination that the capsule 10 has been ingested. Alternatively, the condition may be that a predetermined number or more consecutive readings are within the expected temperature or humidity threshold for the environment at the beginning of the GI tract of the subject mammal.

[0145] Determining the timing of intake FIG. 12a shows an exemplary algorithm for determining ingestion timing. In S1201, a sudden change in the environmental sensor reading is detected as a potential ingestion indicator, exception catching and pre-ingestion filtering are applied, and in S1202, median filtering is applied. The algorithm automatically determines ingestion preferentially by checking whether the temperature at the start of the sudden change is within a predetermined range for room temperature in S1203. If the temperature is not within the predetermined range for room temperature, a check is performed for a patient marker in S1204 (i.e., the patient marker is an ingestion indicator provided by the patient via a user interface on the receiver device 30, such as a button press, or an ingestion indicator provided via an application running on a device at the hospital where the subject is a patient). Thus, if the result in S1204 is positive, the presence of the patient marker is sufficient to be used as an ingestion marker, and in S1206, the ingestion timing is considered to be the timing of the patient marker. If the patient marker is not present in S1204, the timing of the first reading of the sudden change is considered to be the ingestion timing in S1205. If the temperature at the start of the detected abrupt change is within the predetermined room temperature range in S1203, processing proceeds to S1207 where the next time the temperature first derivative is greater than 3 standard deviations is found and a check is made in S1208 as to whether the ambient temperature sensor readings indicate a rise into the predetermined range for the body temperature over the following 5 minutes. If not, flow returns to S1207. If so, flow proceeds to S1209 where the timing of the temperature rise is the determined intake timing.

[0146] Sensors, Algorithms, Processing FIG. 11a illustrates the relationship between sensors, algorithms, and processing results in one embodiment. Calibration data 1101, such as a look-up table for calibrating the VOC sensor to operate as a TCD sensor at different environmental temperatures, is combined with the heater side of the VOC sensor 132b to provide calibration parameters. Clinical data 1102 is the knowledge that changes in the VOC sensor heater side readings are related to changes in H2 concentration in the target gas mixture, which is fed to ICJ detection in S106 and S106a, and is itself an output data entity at 1103. Similar reference numbers are used for equivalent features in other figures, so a complete description of the features of FIG. 11a is disclosed by reference to the other figures herein. It should be noted that the intake algorithm performs steps S103 and S103a, the void detection algorithm performs steps S107 and S107a, the ICJ detection algorithm performs steps S106 and S106a, and the gastric emptying algorithm performs steps S104 and S104a. Step S1110 is to correct the TCD sensor readings to account for changes in environmental temperature. Step S1120 applies an algorithm to process the accelerometer data as described below in connection with the first technique, i.e., the angular shift technique. S1130 is an exemplary processing algorithm for antenna reflectivity related readings to determine changes in noise in its output signal. Other processing algorithms may be applied to the accelerometer and readings. Algorithms S1110, S1120, and S1130 may be considered pre-processing algorithms. The event timings determined by the algorithms are combined with each other to determine the event timings of intake, gastric emptying, ileocecal junction transition, and voiding. The event timings are in turn combined to determine transit time metrics including gastric emptying timing 1105, small intestine transit time 1106, colonic transit time 1107, and whole intestine transit time 1108. These are included in the output motility report 1104. The data visualization 1103 may be, for example, as illustrated in Figures 7A, 7B, 7C, 8, 9A, and 9B. Figure 11B shows an exemplary data visualization marked with the transit time metrics.

[0147] 7A and 7B show plots of capsule readings versus time since a start event (boot) of an ingestible capsule 10 being ingested by a human subject, traveling through the GI tract, and then excreted. Ingestion and excretion events are marked. In this example, the external temperature is much lower than the internal temperature of the human subject. The plots also show hydrogen readings, motility readings, and CO2 readings, and eating and bowel events are marked (these events are automatically detected or manually reported). The specific timings assigned to the ingestion and excretion events can be determined in several ways. FIG. 7C shows environmental temperature and humidity sensor readings versus time since a start event (boot) of an ingestible capsule 10 being ingested by a human subject, traveling through the GI tract, and then excreted. Ingestion and excretion indicators are detectable in FIG. 7C, the events are not marked as they are apparent from FIG. 7A. It should be noted that the specific timings assigned to the ingestion and excretion events may be determined in a number of ways, and the processing of the readings may be performed in a chronological or reverse chronological order. An example of an ingestion event: determining the average value of three adjacent environmental sensor readings progressively (i.e., sequentially) from a starting point that is the onset event (in the case of a chronological order) or the gastroduodenal transit timing (in the case of a reverse chronological order), determining when the average value begins or ends within a threshold distance of the expected post-ingestion environmental value (i.e., within 1 degree Celsius of the expected temperature, or within 1, 2, 5, or 10% of the expected humidity), and then determining that the ingestion event timing is between the three readings (e.g., the midpoint, the earliest point, or the most recent point). The number three is exemplary, and a different number for the number of samples in the rolling average may be selected, e.g., 5, 10, 12, or 20. Furthermore, the tolerance of 1 degree Celsius is configurable, and may be, e.g., 2 degrees, 3 degrees, etc.

[0148] In the above example, the ingestion event timing is determined by detection of an ingestion indicator (rise in environmental temperature reading) in the temperature sensor reading. The ingestion event timing is coincident with the ingestion indicator. The ingestion indicator (i.e., marker) may be detected in the antenna reflectance signal from the directional coupler, the indicator being a step change in the reading (this is specific to the embodiment in which the antenna 17 and directional coupler 19 operate as a reflectometer from which readings are taken). The ingestion event timing is coincident with the ingestion indicator in the antenna reflectance related reading. As a further example, the capsule may include a relative humidity sensor as a form of environmental sensor, and the ingestion indicator may be detected by processing the readings from said relative humidity sensor. The indicator is the earliest (post-start event) rise in relative humidity that falls within a predefined threshold of 100%, e.g., minus 5%, or minus 1%. A further ingestion indicator is a button press of an ingestion confirmation button on the user interface of the user device. An embodiment may combine one or more of the disclosed ingestion indicators to determine the ingestion event timing. For example, two or more of the disclosed ingestion indicators are detected with timing within a predetermined timing window of each other, for example, within one minute of each other, to determine an ingestion event timing.

[0149] Example of an excretion event: determining the average value of three adjacent environmental sensor readings progressively (i.e., sequentially) from a starting point that is an ICJ event (for time series) or an end event (for reverse time series), determining when the average value stops or starts to fall within a threshold distance of the expected environmental value before excretion (i.e., within 1 degree Celsius of the expected temperature, or within 1, 2, 5, or 10% of the expected humidity), and then determining that the excretion event timing is between the three readings (e.g., the midpoint, the earliest point, or the latest point). The number 3 is exemplary, and a different number for the number of samples in the rolling average can be selected, e.g., 5, 10, 12, or 20. Furthermore, the tolerance of 1 degree Celsius is configurable, and can be, e.g., 2 degrees, 3 degrees, etc. An excretion event can be confirmed or detected by an accelerometer reading indicating a free-fall event.

[0150] Note that in some cases, there may be no change in temperature upon ingestion or excretion. The process may include a backup algorithm that is implemented if the earliest environmental temperature reading at the start (assuming the capsule 10 has not yet been ingested) is within a threshold range of the expected temperature for the environment at the start of the GI tract of the subject mammal. The backup algorithm looks for other ingestion or excretion indicators in the recorded readings from other sensors (such as the accelerometer and / or other ingestion or excretion indicators mentioned above) that may indicate an excretion or ingestion event. Alternatively, if the environmental sensor 14 further comprises an environmental humidity sensor 14b, the relative humidity reading may be used as a fallback for temperature. A further example is a manual button press on the user interface of the device (such as the receiver unit 30). An embodiment may combine indicators in a hierarchical manner (i.e., look for an indicator in the temperature reading first and look for an indicator in readings from other sensors only if no indicator is found in the temperature reading) or may treat the indicators equally (i.e., look for any two simultaneous indicators). Other algorithms for determining timing may be implemented, for example, a confidence level may be ascribed to the detected indicator, and then only if the confidence level does not satisfy a threshold, readings from other sensors are processed to find concurrent indicators to improve the confidence. Note that in this specification humidity refers to relative humidity.

[0151] A particular defecation indicator used to add confidence to the defecation indicator (start of decline from body temperature) in the ambient temperature reading is a button press on a defecation button on the receiver device user interface, and a further defecation indicator is a communication loss at the receiver. For example, a communication loss at the timing of a recorded button press of the defecation button (i.e., within a predefined timing window) is an defecation indicator that may be used instead of or to add confidence to the defecation indicator in the ambient temperature reading to determine defecation event timing.

[0152] Excretion timing FIG. 12b shows an exemplary algorithm for determining the timing of a bowel movement. In S1210, a check is made as to whether the temperature at the timing of the termination event (which may be the capsule being turned off or a marker provided by the patient, such as pressing a button on the user interface on the receiver device 30), the environmental temperature sensor reading, is within the range of room temperature. If not within the range of room temperature in S1211, a check is made for bowel movement before and after the timing of the termination event. If not, then it is determined that no bowel movement has occurred yet, and the termination event is determined to be a connection dropout rather than an bowel movement event in S1212. In S1213, if there has been a bowel movement (where a bowel movement may be recorded by the patient, for example, by pressing a button on the user interface of the receiver device), the bowel movement event timing is the timing of the last received data packet. In S1214, the algorithm identifies the next time that the temperature first derivative is less than 3 standard deviations, and in S1215, a check is made as to whether the environmental temperature sensor reading indicates a drop below a predetermined range for the body temperature over the previous 5 minutes. If it does not indicate a drop below the predetermined range, flow returns to S1214. If it does indicate a drop below the predetermined range, flow proceeds to S1216, where the timing of the temperature drop is the determined timing for elimination.

[0153] Figure 2D illustrates a user interface on the receiver device 30 with a button for recording a bowel movement event by manually pressing the button. In Figure 2D, an example of 5 seconds is provided as the length of time the button is manually pressed to record a bowel movement. An LED display provides feedback to the patient that a bowel movement event is being recorded.

[0154] The layout of Figure 4 shows a chronological processing direction in which gastroduodenal event timing is determined first and used as a pre-bound (i.e., lower bound) for the earliest reading analyzed in detecting the ileocecal junction indicator. Processing may be performed in the reverse chronological direction, as indicated by the arrow in Figure 4, in which the ileocecal junction event timing is determined and used as a post-bound (i.e., upper bound) for the reading analyzed in detecting the gastroduodenal transition indicator.

[0155] gastric emptying In S104a, the recorded readings after the determined ingestion event timing are analyzed for gastroduodenal transition indicators, or in the reverse chronological processing case, the readings before the determined ileocecal junction transition event timing are analyzed. Thus, the recorded readings are analyzed by iteratively or repeatedly progressing in each processing direction up to the determined timing of the first transition event.

[0156] The first transition event is emptying or crossing the interface between the stomach and duodenum. The gastroduodenal indicator may be detected in a first subset of recorded readings, the first subset being temporally defined as described above. Further, the first subset may be constrained by sensor and includes readings from the TCD gas sensor 131. The first subset may further include antenna reflectivity related readings (i.e., readings from the antenna 17 and directional coupler 171) and / or the accelerometer 19.

[0157] The gastroduodenal transition indicator in the TCD gas sensor reading may be a spike, a step change, or an inflection point in the TCD gas sensor reading. A correction may be applied to the TCD gas sensor reading to account for changes in environmental temperature based on the recorded readings from the environmental temperature sensor 14a. The correction may be applied in the detection stage S104a, whereby the recorded readings themselves are corrected to account for changes in environmental temperature, and the gastroduodenal transition indicator is detected in the corrected reading. Alternatively, the gastroduodenal transition indicator may be detected in the raw readings (i.e., uncorrected readings), and then in the decision step S104, a check may be performed to determine whether the indicator is due to a change in environmental temperature, and if the indicator is not due to a change in environmental temperature, the gastroduodenal transition indicator is determined to be due to gastroduodenal transition by the capsule 10, or a further condition is applied to the decision (e.g., a recorded reading from another sensor is checked for a simultaneous indicator). Alternatively, the further condition may be a threshold or some other condition applied to the detected spike, step change, or inflection point itself.

[0158] The primary physical mechanism sensed in the TCD gas sensor reading in detecting the gastroduodenal transition indicator is as follows: Hydrochloric acid in the gastric juice leaving the stomach mixes with bicarbonate in the bile acids released from the pancreas. The bile acids serve to neutralize the pH of the fluid, and the by-product of this reaction is CO2. In this region of the GI tract, the ambient gases are primarily N2 and O2 with some trace amounts of CO2. The amount of CO2 produced in this reaction is significantly greater than the ambient trace amounts of CO2 due to swallowing exhaled air. It is therefore appropriate to simply use the output of the TCD sensor without calculating CO2. That is, the TCD gas sensor reading, after being corrected for changes in environmental temperature, provides the gastroduodenal transition indicator itself due to changes in thermal conductivity caused by changes in CO2 concentration across the two sides of the gastroduodenal transition. For motility purposes (i.e., to determine the position of the ingestible capsule 10), there is no particular need to calculate the actual CO2 concentration.

[0159] Since the TCD sensor 131 is affected by the temperature of the gas mixture at the location of the capsule, the temperature compensation process must account for changes in external environmental temperature changes, i.e., drinking cold water, exercising, eating, etc. Starting from the determined ingestion event timing, the first bump, step change or large inflection in the TCD gas sensor 131 reading plotted against time that is not associated with an environmental temperature change identifies the gastroduodenal transition.

[0160] 8a shows the recorded readings of the environmental temperature sensor 14a versus time (lines above the readings on the top graph) and the corrected TCD gas sensor readings versus time for an example of ingestion and progression of a capsule through the GI tract. The gastroduodenal transition indicator may be labeled gastric emptying and is indicated by a spike above a threshold height in the corrected TCD gas sensor reading. The height of the spike may be measured, for example, by its distance (e.g., as a percentage, as an absolute value, or as a number of standard deviations) from a trend line fitted to the readings up to that point.

[0161] Gas concentrations are examples of metrics that may be calculated by an on-board processor or a remote processing device based on raw data obtained from on-board sensors. For example, capsule 10 may be configured to calculate and convert one or more such metrics for transmission from capsule 10. The raw data may be discarded or stored for transmission from capsule 10. Optionally, metrics may be calculated by an on-board or off-board processor based on the calculated gas concentrations. An example of such a metric is peak H2, which may be determined at the timing of an excretion event and transmitted from capsule 10 in a data transmission payload from capsule 10 to receiver device 30.

[0162] FIG. 8B shows gastric emptying as seen in the TCD sensor output and CO2 readings. CO2 is produced when hydrochloric acid in the gastric juice leaves the stomach and mixes with bicarbonate in the bile acids released by the pancreas. This reaction also neutralizes the pH of the fluid. The embodiment uses the temperature compensated raw TCD sensor output rather than the calculated CO2 to detect this event because the temperature compensated raw TCD sensor output is much less noisy. The TCD sensor output is adjusted to compensate for temperature variations measured by the environmental temperature sensor 14a. An algorithm is used to remove drinking events and find the moment when CO2 increases by searching for a clear discontinuity in the TCD output between ingestion and the ICJ transition.

[0163] The process may include detecting a gastroduodenal transition indicator in the TCD gas sensor readings from a first subset of the recorded readings as a first gastroduodenal transition indicator, and calculating a confidence score representing the likelihood that the detected gastroduodenal transition indicator in the TCD gas sensor readings was caused by the ingestible capsule 10 crossing the gastroduodenal junction. The confidence score may be based, for example, on the height of the spike relative to a trend line, with more standard deviations above the trend line giving a higher confidence level. A probability distribution lookup table may be utilized to convert the height of the spike to a confidence score. The confidence score may be a likelihood percentage that the spike in the corrected TCD readings is caused by a first transition event, rather than being caused by noise or other random changes in the corrected TCD readings.

[0164] The processing may include comparing the calculated confidence score to a threshold; if the confidence score meets the threshold, determining that a first transition event has occurred and its timing based on the timing of the detected gastroduodenal transition indicator; if the confidence score does not meet the threshold, assigning the detected gastroduodenal transition indicator from the TCD gas sensor readings as a first gastroduodenal transition indicator; detecting whether a second gastroduodenal transition indicator is present in readings from a first subset other than the TCD gas sensor readings and is present simultaneously with the first gastroduodenal transition indicator; and if the second gastroduodenal transition indicator is detected, determining that a first transition event has occurred and its timing based on the timing of the first gastroduodenal transition indicator.

[0165] In practice, if the first gastroduodenal transition indicator does not meet the confidence score threshold, a further processing thread is initiated to detect further gastroduodenal transition indicators to add to the first confidence level. Readings recorded simultaneously with the first gastroduodenal transition indicator from other sensors or pseudo sensors are analyzed to identify one or more second gastroduodenal transition indicators. The time bound of the readings included in the analysis may be, for example, a predetermined time distance on either side of the first gastroduodenal transition indicator, for example, 1 second, 5 seconds, 10 seconds, 20 seconds, 30 seconds, 1 minute, 2 minutes, or 5 minutes. In attempting to identify one or more second gastroduodenal transition indicators, recorded readings from one or both of antenna reflectivity related readings (i.e., antenna 17 and directional coupler 171 are configured as a reflectometer that senses whether and how the dielectric of the environment surrounding capsule 10 changes) and accelerometer 19 (i.e., senses whether and how the rate of change of the capsule's orientation changes) may be analyzed.

[0166] As shown in FIG. 3A, the circuit includes a directional coupler 171 in series with the antenna 17, where the directional coupler 171 and the antenna 17 act as a reflectometer. A diode detector measures the amplitude of the reflected signal from the antenna. The diode detector measurement is an example of an antenna reflectivity related reading, which indicates the reflected energy from the antenna, i.e., the energy that was not radiated from the antenna 17 due to impedance mismatch. The reflectometer reading indicates the radiation efficiency of the antenna, which is affected by the dielectric of the material surrounding the capsule. In another example, the antenna reflectivity related reading is generated by a feedback loop that includes a controller that controls a variable capacitor that impedance matches the antenna to the surrounding environment. The control signal from the controller to the variable capacitor acts to impedance match the antenna to the surrounding environment, and thus represents or correlates to the electromagnetic properties of the environment surrounding the capsule).

[0167] Readings may be noisy and / or experience baseline shifts in the timing of gastroduodenal transition events, for example, increased noise and / or baseline shifts are detectable as transition indicators.

[0168] FIG. 9D shows antenna reflectance-related readings (labeled "Ant" for antenna) versus time (on the top plot on the lower of the two sets of axes), marked with gastric emptying events. Antenna 17 and directional coupler 171 function as a reflectometer to measure reflected energy from the antenna, i.e., energy that was not radiated from the antenna. This signal changes as the dielectric properties of the surroundings change, most notably as the capsule leaves the spongy, fluid-filled stomach and transitions to be surrounded by the tubular tissue of the small intestine. Shifts in antenna reflectance-related readings are observed to coincide with TCD markers, adding confidence as a secondary measure.

[0169] FIG. 9A is a plot of recorded readings (or processed versions thereof) versus time for several sensors and pseudo sensors in capsule 10. Gastric emptying (gastroduodenal transition) events are labeled. The top plot in the graph of FIG. 9A is the antenna reflectivity related readings versus time (labeled "Ant" for antenna). It can be seen that baseline shifts occur at times that coincide with spikes in the corrected TCD gas sensor readings. Thus, for example, if a confidence score representing the likelihood that a spike is caused by gastroduodenal transition does not meet a threshold, the antenna reflectivity related readings are analyzed to detect baseline shifts that coincide with the spikes. For example, baseline shifts can be detected by incrementally / sequentially comparing the average value of the last few (e.g., 5, 10, or 20) consecutive readings to the average value of the last few consecutive readings that precede (or follow in the case of reverse time series processing) the last few consecutive readings. A baseline shift can be indicated by a difference that exceeds a threshold, which can be an absolute value, a percentage, or determined relative to the standard deviation in the readings. Detecting a contemporaneous gastroduodenal indicator in the reflectometer output may be sufficient to confirm that the first gastroduodenal transition indicator is due to gastroduodenal transition of capsule 10, and therefore determine the timing of gastroduodenal transition. Alternatively, the combination of the two indicators may be evaluated via a probabilistic model to revise a confidence score and compare the revised confidence score to a threshold, the satisfaction of which determines that the first gastroduodenal transition indicator is due to gastroduodenal transition of capsule 10, and therefore determine the timing of gastroduodenal transition.

[0170] Accelerometer and Accelerometer Data Processing The exemplary accelerometer 19 measures roll about three mutually orthogonal axes. Readings from the accelerometer 19 may be a vector with a component per axis, with each component indicating the instantaneous angular acceleration about the corresponding axis, or the average acceleration about the corresponding axis over a period of time since the previous live reading. Alternatively, the readings may provide a three-dimensional orientation of the capsule. Processing of the readings from the accelerometer may be performed in the receiver device 30 or remote computer 20 to generate a representation (such as a plot versus time) of aggregated (i.e., all three axes) accelerometer readings from which markers (i.e., gastroduodenal transition indicators) can be identified. Such a plot or representation may be used to identify markers of other events, including evacuation events. In FIG. 9A, an "angular displacement" plot is generated. This is a plot of scalar angular displacement about all three axes accumulated over time, with a low pass filter applied to filter out small angular displacements.

[0171] FIG. 9C shows roll in each of three mutually orthogonal dimensions, with gastric emptying events marked, from which it can be seen that the change in accelerometer readings correlates in time with the change in the corrected TCD readings (i.e., can be used to add confidence to the detection of the gastroduodenal transition indicator in the temperature corrected TCD readings). The orientation of the capsule is measured using a three-axis accelerometer to track the gravity vector with respect to the capsule reference frame. The orientation of the capsule is measured using a three-axis accelerometer to track the gravity vector with respect to the capsule reference frame. Once the capsule leaves the stomach, it tends to undergo rapid changes in capsule orientation as it passes through the duodenum and small intestine. The "angular movement" simply accumulates the change in orientation over a hysteresis angle of 90 degrees. This algorithm tends to be robust to small changes in orientation experienced in the stomach, avoiding some of the complexities of other approaches.

[0172] The first technique for processing accelerometer data is sometimes called angular displacement. Angular displacement uses vector mathematics to calculate the angle between the gravity vector and the temporal vector. The temporal vector is pulled in the direction of the change in angle only when this angle exceeds a given threshold (currently 90 degrees). The change in the temporal vector is then accumulated, visualized in a representation where the marker is identifiable. In general, since the angle between the gravity vector and the temporal vector rarely exceeds the threshold in either direction, it is believed that this measure does not change much in the stomach (small anterior-posterior orientation changes in the stomach are effectively ignored by the inherent hysteresis of this algorithm), but accumulates significantly due to the larger and more continuous orientation changes of the capsule after entering the tortuous lumen of the small intestine. Thus, a step change in the accumulated angular displacement measure is a gastroduodenal transition indicator.

[0173] In an exemplary implementation of the angular movement, the accelerometer readings may provide a reading of the orientation of the ingestible capsule relative to a reference frame in a fixed relationship to the gravity vector. Processing the readings from the accelerometer may include recording the orientation of the ingestible capsule provided by the first accelerometer reading as a reference orientation, iterating over time for each successive accelerometer reading to determine whether the orientation of the ingestible capsule provided by the respective accelerometer reading is greater than a threshold angular displacement from the reference orientation, proceeding to the next accelerometer reading without changing the reference orientation if the threshold angular displacement is not met, and changing the reference orientation to align with the orientation of the ingestible capsule provided by the respective accelerometer reading if the threshold angular displacement is met. An indicator such as a gastroduodenal transition indicator may be a step change in the rate of change of the reference orientation.

[0174] 9B shows that a step change in the plot of angular movement is identifiable within a threshold period of the detected spike in the TCD gas sensor reading. Thus, the step change in the plot of angular movement increases confidence in the hypothesis that the detected spike in the TCD gas sensor reading is due to gastroduodenal transition. There are two nearly simultaneous gastroduodenal transition indicators, which allows the timing of one of the indicators (which may be preselected, for example, the TCD gas sensor reading) to be determined as the timing of the transition event.

[0175] A second technique for processing accelerometer data is sometimes called total roll. Total roll calculates the angle between the gravity vector and each of the capsule x-axis, y-axis, and z-axis, and represents this as a continuous measure that can accumulate beyond 360 degrees. For example, if the capsule x-axis is at an angle of 350 degrees and rotates an additional 20 degrees, the resulting angle is represented as 370 degrees instead of 10 degrees. This is useful when representing the readings as a plot where markers are identified, as it avoids the sudden angle changes associated with crossing the zero line. In this example, an actual change of 20 degrees is visualized instead of an artificial change of 340 degrees. In addition to this basic technique, low-pass filtering may be applied to filter the raw data to remove sensor noise. Additionally, angles are only calculated when the raw accelerometer data provides enough data to calculate a meaningful angle. An example where this is not the case is when the two accelerometer axis values ​​used to calculate the orientation angle about the third axis both approach zero. In this case, a meaningful angle cannot be determined because the calculation is dominated by the sensor noise.

[0176] The accelerometer readings provide readings of the orientation of the ingestible capsule relative to a frame of reference in a fixed relationship with the gravity vector. Exemplary processing of readings from the accelerometer may include: for each of three orthogonal axes in a fixed spatial relationship with the ingestible capsule derivable from the orientation readings, iterating over time for each successive accelerometer reading, calculating the change of the orthogonal axis relative to the gravity vector from the preceding accelerometer reading as a scalar value, applying a low pass filter to the calculated change, and recording the cumulative filtered calculated change. A marker that serves as a gastroduodenal transition indicator may be, for example, an increase (such as a spike or step change) in the rate of increase of the cumulative filtered calculated change.

[0177] FIG. 12D illustrates an exemplary algorithm for determining the timing of gastric emptying (i.e., gastroduodenal transition event timing). At S1230, a temperature corrected TCD reading is obtained, and at S1231, the search window is narrowed by using the determined ICJ event timing as a delay bind (in the example of reverse time series processing). Two indicators are detected in the readings. At S1232, the timing of the most recent positive peak in the second derivative of the temperature corrected TCD reading is detected as Marker 1, and at S1233, the timing of the largest step change in the reading is detected as Marker 2. At S1234, the timing of the two indicators is compared, and if they are within a predetermined threshold distance, such as within 30 minutes of each other, at S1235, the timing of Marker 2 is determined to be the timing of gastroduodenal transition of the capsule.

[0178] If the two indicators do not match, the accelerometer data is processed. At S1240, angular movement data is obtained and at S1241, the search window is narrowed as in S1231. At S1242, marker 3 is found as the timing of the most recent positive peak in the second derivative of the angular movement data. At S1243, a check is made as to whether the timings of marker 1 and marker 3 match within a predetermined threshold distance, such as within 30 minutes of each other, and if so, flow proceeds to S1244 where the timing of marker 1 is determined to be the timing of the gastroduodenal transition of the capsule. If marker 1 and marker 3 do not match, flow proceeds to S1245 where a check is made as to whether the timings of marker 2 and marker 3 match within a predetermined threshold distance, such as within 30 minutes of each other. If so, flow proceeds to S1246 where the timing of marker 2 is determined to be the timing of the gastroduodenal transition of the capsule. Otherwise, full roll data is obtained from the accelerometer readings at S1250. In S1251, a gastroduodenal transition indicator is detected as marker 4 by detecting a baseline shift or noise floor change in the accelerometer total roll data. In S1252, the timing of marker 4 is compared to the timing of markers 1, 2, and 3. If the timing of marker 4 is within a predetermined threshold distance, such as within 30 minutes, of any of the other markers, the timing of the other marker is determined to be the timing of gastroduodenal transition of the capsule in S1253. If marker 4 matches >1 of markers 1, 2, and 3, for example, the timing of the marker among 1, 2, and 3 that is closest to the timing of marker 4 may be determined to be the timing of gastroduodenal transition of the capsule. Otherwise, a predetermined hierarchy may be programmed as an algorithm, for example, such that marker 1 is prioritized over marker 2, which is prioritized over marker 3.

[0179] If no match is found in S1252, a reflectometer reading is taken in S1260 (marked as "directional coupler" due to the directional coupler 171 in series with antenna 17 forming the reflectometer). In S1261, processing is performed to detect the timing of baseline shift or noise floor change in the reflectometer reading as marker 5. In S1262, the timing of marker 5 is compared to the timing of markers 1, 2, 3, and 4. If the timing of marker 5 is within a predetermined threshold distance, such as within 30 minutes, of any of the other markers, the timing of the other marker is determined to be the timing of gastroduodenal transition of the capsule in S1253. If marker 5 matches >1 of markers 1, 2, 3, 4, for example, the timing of the marker among 1, 2, 3, and 4 that is closest to the timing of marker 4 may be determined to be the timing of gastroduodenal transition of the capsule. Otherwise, a predetermined hierarchy may be programmed into the algorithm, such that, for example, marker 1 is prioritized over marker 2, which is prioritized over marker 3, which is prioritized over marker 4.

[0180] In the case of time series processing, in S106a, the recorded readings after the determined first transition event timing are analyzed for the ileocecal junction indicator, or in the case of reverse time series processing, the readings before the determined elimination event timing are analyzed for the ileocecal junction indicator. Thus, the recorded readings from each determined event timing are analyzed by iteratively or repeatedly advancing the reading being analyzed up to the determined second transition event timing.

[0181] Determining the timing of the ileocecal junction transition A second transition event is the passage of the capsule 10 through the ileocecal junction. The ileocecal junction indicator may be detected in a second subset of the recorded readings, the second subset being defined in time as described above depending on time series or reverse time series processing. Additionally, the second subset may be constrained by sensor and include readings from the sensor side of the VOC gas sensor 132a.

[0182] The ileocecal junction indicator in the VOC gas sensor reading may be a spike, a step change, or an inflection point in the VOC gas sensor reading.

[0183] Determining the second transition event timing S106 involves applying one or more conditions to the detected ileocecal junction indicator to determine whether the ileocecal junction indicator can be attributed to (i.e., can predict the passage within a predetermined confidence level of) the capsule 10 crossing the ileocecal junction.

[0184] Transition prediction of the small intestine to large intestine transition is the second transition event timing determined. The change in gas environment between the small intestine and large intestine is significant because the bacterial population in the large intestine occurs at a significantly higher prevalence, promoting the production or increase of volatile substances and the decrease of O2 due to the fermentation of carbohydrates and proteins by the microbiota.

[0185] The VOC gas sensor output 132 from the sensor side 132a is sensitive to many different volatile analytes, with the largest response being due to H2 and O2. A significant drop on the VOC sensor is observed upon transition through the ileocecal valve. As the capsule passes through the GI tract, the environment becomes increasingly anaerobic as O2 is consumed by bacteria. FIG. 8C illustrates an indicator of the ICJ on a plot of the VOC sensor output and the determined H2 concentration. An indicator in the VOC sensor output can be identified in S106a by plotting the difference between the VOC sensor side reading and time while the sensor is heated and finding the most negative peak. This difference identifies the maximum point of change associated with the transition, but which does not occur at the beginning of the transition event. The beginning of the transition event can be found by an initial inflection point from the baseline in the first derivative. Thus, the indicator can be detected by the most negative peak and the event timing can be determined by the inflection point. The highest negative peak may be found retrospectively by analyzing VOC gas sensor readings from a predefined period (e.g., 1 hour, 2 hours, 4 hours, etc.) that follows the determined gastroduodenal transit event timing or precedes the determined elimination event timing (in the case of reverse time series processing). Alternatively, a threshold negative peak size may be determined and the first peak exceeding the threshold size is detected as the ileocecal junction transit indicator.

[0186] As shown in FIG. 8D, the ICJ indicator is also present in the determined H2 concentration percentage as a sudden increase in H2 when the capsule reaches the colon. H2 produced in the GI tract is a by-product of fermentation. Bacterial colonies are orders of magnitude larger in the colon than in the small intestine. Therefore, the determined H2 concentration can be used to add confidence to the ileocecal junction indicator of the VOC sensor output.

[0187] FIG. 8E illustrates a further fallback marker of ileocecal junction transition in the form of detected CO2 concentration. CO2 in the GI tract is produced as a by-product of fermentation. Bacterial colonies are orders of magnitude larger in the colon than in the small intestine. Thus, the determined CO2 concentration can be used to add confidence to the ileocecal junction indicator of the VOC sensor output.

[0188] FIG. 12C illustrates an exemplary algorithm for processing readings to determine ileocecal junction transition event timing. The inputs are the readings from the VOC sensor sensing side and the H2 reading (determined by the pre-processed output of the VOC sensor heater side). Steps S1220-S1223 narrow the search window for the ICJ indicator / marker between the determined time of the transition event and the time when the determined concentration of H2 in the gas mixture detected by the capsule gas sensor first reaches 10%. In S1224, the first and second derivatives of the VOC hot trace (which is the hottest point of the VOC sensor sensing side from the pulsed drive signal) are found, and in S1225, the timing of the last coincident peak of the first derivative (i.e., the most negative peak from the first derivative) is found. In S1226, the timing of the last coincident peak of the first derivative is used to delimit the search window of the second derivative by 30 minutes on either side of the last coincident peak time. In S1227, the timing of the peak of the second derivative of the VOC hot trace is found, and in S1228, the ileocecal junction transition event timing is determined to be the timing of the second derivative peak. In S107a, the recorded readings from the environmental sensor 14 are analyzed to detect a change in the environmental conditions (either one or both of the environmental temperature and the environmental relative humidity) indicative of an excretion event. In the case of time series processing, the analysis is an analysis of the environmental sensor readings from the determined timing of the second transition event onwards. If the detected change in the environmental temperature is determined to be due to an excretion event, no further analysis is performed to detect the excretion event. In the case of reverse time series processing, the analysis in S107a is an analysis of the readings from the termination event and before. For example, detecting the change in S107a may be performed sequentially by comparing one or more readings to a predetermined number of previous readings or processing readings, and a difference exceeding a threshold (i.e., 1 or 2 degrees Celsius) is the detected change. The change detected may be a change in temperature, a change in relative humidity, or both, depending on the geographic location and climatic considerations.Determining the excretion event timing S107 may include comparing the temperature of one or more readings to an expected temperature for the environment at the end of the GI tract of the target mammal 40, with a change above a threshold (in the case of reverse time series processing) or below a threshold (in the case of time series processing) being a determination that the capsule 10 has been excreted. Alternatively, the condition may be that a predetermined number or more consecutive readings are outside of a threshold range of an expected temperature for the environment at the end of the GI tract of the target mammal.

[0189] Determining the timing of excretory events Generally, a temperature drop upon defecation is a reliable signal. However, there are cases where no temperature drop is observed in the data. A defecation button press as illustrated in FIG. 2D may be used as a fallback, or additional sensor readings may be treated as fallbacks. Determining the defecation event timing S107 may include comparing the relative humidity of one or more readings to the expected relative humidity of the environment at the end of the GI tract of the target mammal 40, and a change higher than a threshold (in the case of reverse time series processing) or lower than a threshold (in the case of time series processing) is a determination that the capsule 10 has been defecate. Alternatively, the condition may be that a predetermined number or more consecutive readings are outside the expected relative humidity threshold for the environment at the end of the GI tract of the target mammal.

[0190] Note that in some cases, there may be no change in temperature at the time of excretion. The process may include a backup algorithm that is implemented if the earliest environmental temperature reading at the start (assuming that the capsule 10 has not yet been ingested) is within a threshold range of the expected temperature for the environment at the end of the subject mammal's GI tract (indicating that the subject is in an environment having at or near the expected GI tract temperature). The backup algorithm looks for markers in the recorded readings from other sensors that may indicate an excretion event. Since excretion is commonly associated with a physical fall, the markers may be indicators in the accelerometer readings. Alternatively or additionally, changes in relative humidity may be detected by the backup algorithm.

[0191] gastric emptying 10 is a flow chart of a method, device, and process for determining gastroduodenal transit event timing. Note that gastroduodenal transit events may be referred to as gastric emptying. Determining event timing may also be referred to as predicted timing of the event.

[0192] In S1002, the recorded readings from the environmental temperature sensor 14a and the TCD gas sensor 131 are combined to correct (i.e., adjust or calibrate) the TCD gas sensor readings to correct for changes in temperature at the location of the capsule 10. The effects of temperature changes at the location of the capsule 10 are thereby compensated for in the corrected TCD gas sensor readings, from which a first gastroduodenal indicator may be identified in S1004. This is an example of S104a discussed above. Assuming that the processing steps are performed while the capsule 10 is within the subject mammal, the recorded readings are continuously monitored for the gastroduodenal transition indicator. For example, monitoring of the gastroduodenal transition indicator may begin after an ingestion event timing is determined. If the processing is applied retrospectively, the recorded readings are processed sequentially from the ingestion event timing in an attempt to identify the gastroduodenal transition indicator. The gastroduodenal transition indicator may be a bump, step change, or inflection in a plot of the corrected TCD gas sensor readings versus time. The detection algorithm may apply low pass filtering to prevent bumps, step changes, or inflection points below a respective magnitude threshold from being detected as a gastroduodenal transition indicator.

[0193] Alternatively, retrospective reverse time series processing may be performed to detect the first gastroduodenal indicator in S1004, as described above.

[0194] In S1006, a confidence score is calculated for the detected indicator, as discussed above. For example, the hypothesis is that the detected indicator (in the corrected recorded TCD gas sensor readings) was caused by a gastroduodenal transition event of the capsule 10, and the null hypothesis is that the detected indicator was a random fluctuation in the readings caused by noise or physical effects in the stomach. The confidence score may be generated by knowing the probability distribution (e.g., normal distribution by knowing the standard distribution of the TCD gas sensor readings when in the stomach) and the size of the bump in the standard deviation. Similarly, the step change or inflection point magnitude for the standard deviation may be used to generate a probability score from the probability distribution. A threshold minimum confidence score may be applied in S1006, and if the calculated confidence score meets a threshold (e.g., 0.9, 0.92, 0.95, or 0.99), flow proceeds to S1016 and the timing of the detected transition indicator is determined to be the timing of a gastroduodenal transition event.

[0195] If the calculated confidence score does not meet the threshold, a second gastroduodenal transition indicator is determined. Alternatively, multiple transition indicators may be detected in S1004, for example, a first non-temperature related bump, step change, or inflection point may be detected as a first transition indicator, and a further non-temperature related bump, step change, or inflection point may be detected as an alternative first transition indicator. Here, the alternative first transition indicators are at different respective times than the first transition indicator, and therefore it must be determined which are due to a gastroduodenal transition event of the capsule and which are not due to a gastroduodenal transition event of the capsule. Note that the change in the TCD gas sensor readings during the gastroduodenal transition is caused by an increase in CO2 in the gas mixture surrounding the capsule. The embodiment may process the TCD gas sensor readings in raw form to detect the first transition indicator and the alternative first transition indicator, or the embodiment may process a pre-processed version of the TCD gas sensor readings that have been pre-processed to represent the CO2 concentration in the gas mixture, for example, based on a lookup to a calibration table stored in the device performing the detection. For example, if neither the first transition indicator nor the alternative first transition indicator (based on the assumption that the first transition indicator is the earliest indicator and the alternative transition indicator is slower and therefore the first transition indicator is false, i.e., not due to a gastroduodenal transition event) meets a confidence threshold, readings from one or more other sensors may be processed to detect an indicator simultaneously with either the first transition indicator or the alternative first transition indicator, where a simultaneous indicator in a reading from another sensor (i.e., a second gastroduodenal transition indicator) adds confidence to the respective transition detector. The other sensor may be, for example, an accelerometer, and an increase in the rate of orientation change is a second transition indicator. Alternatively, the other sensor may be a directional coupler (ie, a reflectometer) and a step change in the antenna reflectivity reading is the second indicator.A high variance in the antenna reflectance signal (i.e., reflectometer readings or variable capacitor control signal readings) is associated with presence in the intestine, so a step change or spike is an indicator that the capsule has undergone gastroduodenal transition. As a further example, another sensor may be a temperature sensor, where a large temperature change is associated with presence in the stomach, but the temperature of the small intestine is much more consistent. Thus, the end of the large temperature change may be considered a second gastroduodenal transition indicator. Using the same logic, a rapid temperature change at the timing of the first transition indicator may reduce the confidence of said transition indicator. As a metric for expressing the temperature change, the average rate of change over a rolling time window, e.g., a quantity such as 30 seconds, or 1 minute, may be used to express the amount of temperature change. An average rate of change over a preceding time window being less than a threshold is an indicator that gastroduodenal transition has occurred, thus adding confidence to a simultaneous or recent first transition indicator.

[0196] 10 shows a hierarchical procedure where first the antenna reflectivity related readings (i.e. the antenna 17 configured as a reflectometer and the directional coupler 171, or the control signal of the variable capacitor 172) are analyzed for the second gastroduodenal transition indicator, then the recorded readings from the accelerometer 19 are analyzed if there is no identifiable second gastroduodenal indicator in the recorded readings from the reflectometer. However, the method can be reversed, where the accelerometer readings are analyzed first, then the recorded readings from the reflectometer are analyzed if there is no identifiable second gastroduodenal indicator in the recorded readings from the accelerometer 19.

[0197] At S1008, the recorded readings from the reflectometer (comprised of antenna 17 and directional coupler 171) within a predetermined time range of the detected first gastroduodenal transition indicator are analyzed to detect or identify a second gastroduodenal transition indicator. Specifically, the second gastroduodenal transition indicator in the recorded readings from the reflectometer may be a baseline shift and / or a noise floor change. If either or both are detected, then the first gastroduodenal indicator detected in the recorded readings of the TCD gas sensor is confirmed at S1016 to be due to capsule 10 undergoing a gastroduodenal transition event.

[0198] At S1010a and S1010b, accelerometer 19 readings within a predetermined time range of a detected first gastroduodenal transition indicator are analyzed to detect or identify a second gastroduodenal transition indicator. The method may utilize one or both of steps S1010a and S1010b. At S1010a, an angular movement representation of the recorded readings of the accelerometer readings (described in detail above) is analyzed to detect or identify a second gastroduodenal transition indicator. In particular, the second gastroduodenal transition indicator may be a step change in cumulative angular movement. At S1010b, a total roll representation of the recorded readings of the accelerometer readings (described in detail above) is analyzed to detect or identify a second gastroduodenal transition indicator. In particular, the second gastroduodenal transition indicator may be a step change in the rate of increase of the total roll.

[0199] At S1012, a check is made whether a second gastroduodenal transition indicator is detected in the accelerometer readings. If a second gastroduodenal transition indicator is not detected, flow proceeds to S1014, where the first gastroduodenal transition indicator detected is not determined to be due to a capsule gastroduodenal transition event (although the first gastroduodenal transition indicator may be flagged for manual checking of the sensor output). Monitoring of the TCD gas sensor readings continues from the timing of the first gastroduodenal transition indicator detected to detect a new first gastroduodenal transition indicator at S1004, or in the case of reverse time series processing, continues in a reverse manner from the timing of the first gastroduodenal transition indicator detected.

[0200] At S1016, a label may be applied to the readings recorded at the determined timing of the gastroduodenal transition event, for example to add context to the readings from the gas sensor for further analysis by a medical professional. Alternatively or additionally, an alert or notification may be generated and sent to a recipient to inform them of the timing of the gastroduodenal transition event.

[0201] It will be understood by those skilled in the art that numerous variations and / or modifications may be made to the above-described embodiments without departing from the broad general scope of the present disclosure. The present embodiments are therefore to be considered in all respects as illustrative and not restrictive.

Claims

1. 1. An apparatus for determining the location of an ingestible capsule within the gastrointestinal (GI) tract of a mammalian subject, comprising: an ingestible capsule that is ingestible by a target mammal, the ingestible capsule comprising a housing, a power source, a TCD gas sensor, and a VOC gas sensor; means for recording readings of the ingestible capsule as a function of time, including the period during which the ingestible capsule is in the gastrointestinal (GI) tract of the target mammal, the readings including TCD gas sensor readings and VOC gas sensor readings, the means being the ingestible capsule or a receiver device at a location external to the target mammal configured to receive readings from the ingestible capsule at a location internal to the target mammal; a processing device configured to process the recorded readings by a process, the process comprising: determining a first transition event timing, the first transition event timing being a timing of gastroduodenal transition by the ingestible capsule, wherein determining the first transition event timing comprises detecting a gastroduodenal transition indicator in a first subset of the recorded readings, the first subset comprising the recorded TCD gas sensor readings; and determining a second transition event timing, the second transition event timing being a timing of transition across an ileocecal junction by the ingestible capsule, wherein determining the second transition event timing comprises detecting an ileocecal junction indicator in a second subset of the recorded readings, the second subset comprising the VOC gas sensor readings.

2. the ingestible capsule includes an environmental sensor, and the readings include environmental sensor readings; determining the first transition event timing further comprises comparing one or more of the environmental temperature sensor readings at or near the timing of a detected gastroduodenal transition indicator to a baseline environmental temperature value, and determining whether the timing of the detected gastroduodenal transition indicator is associated with the first transition event timing based on a result of the comparison; or 2. The device of claim 1, wherein detecting the gastroduodenal transition indicator comprises: adjusting the TCD gas sensor readings according to the respective concurrent ambient temperature sensor readings; and detecting the gastroduodenal transition indicator in the adjusted TCD gas sensor readings.

3. 3. The apparatus of claim 2, wherein the gastroduodenal transition indicator is a spike, step change, or inflection in the TCD gas sensor reading from the recorded readings, and the timing of the gastroduodenal transition indicator is determined to be associated with the first transition event timing if the environmental temperature value was within a predetermined threshold distance of a baseline environmental temperature value for a predetermined period of time preceding the timing of the gastroduodenal transition indicator.

4. the ingestible capsule further comprising a primary transceiver including an antenna, a directional coupler in series with the antenna to form a reflectometer, and a diode detector forming part of the reflectometer; the ingestible capsule is configured to transmit the readings of the ingestible capsule to the receiver device by the antenna; the diode detector is configured to receive a reflected signal from the antenna via the directional coupler and measure an amplitude of the reflected signal; The recorded readings of the gas sensor capsule are the amplitude reading of the reflected signal measured by the diode detector; a reading of the phase information of the reflected signal extracted by the quadrature demodulator; and Antenna impedance control signal, and one or more antenna reflectivity related readings of 2. The apparatus of claim 1, wherein a first subset of the recorded readings from which the timing of the first transition event is determined includes the antenna reflectivity related readings, and / or a second subset of the recorded readings from which the timing of the second transition event is determined includes the antenna reflectivity related readings.

5. the first subset includes the antenna reflectivity related readings, and determining the first transition event timing; detecting a gastroduodenal transition indicator in the antenna reflectivity-related readings from the first subset; determining that and when the first transition event occurred based on the gastroduodenal transition indicator detected in the antenna reflectivity-related readings from the first subset; The process comprises: detecting a gastroduodenal transition indicator in the TCD gas sensor readings from the first subset as a first gastroduodenal transition indicator; detecting a gastroduodenal transit indicator in the antenna reflectivity-related readings from the first subset within a predetermined time range of the detected first gastroduodenal transit indicator as a second gastroduodenal transit indicator; 5. The apparatus of claim 4, further comprising determining that and when the first transition event occurred based on detecting the first and second gastroduodenal transition indicators.

6. 10. The device of claim 1, wherein the ingestible capsule further comprises an accelerometer, the readings of the ingestible capsule include accelerometer readings, and the first subset includes accelerometer readings.

7. Determining the first transition event timing includes: detecting a gastroduodenal transition indicator in the accelerometer readings from the first subset; and determining that and timing of the first transition event occurred based on the gastroduodenal transition indicator detected in the accelerometer readings from the first subset.

8. The process comprises: detecting a gastroduodenal junction indicator in the TCD gas sensor readings from the first subset as a first gastroduodenal junction indicator; detecting a gastroduodenal junction indicator in the accelerometer readings from the first subset within a predetermined time range of the detected first gastroduodenal transition indicator as a second gastroduodenal transition indicator; 8. The apparatus of claim 7, further comprising determining that and when the first transition event occurred based on detecting the first and second gastroduodenal transition indicators.

9. the second subset includes the antenna reflectivity related readings, and determining the second transition event timing; detecting an ileocecal junction transition indicator in the antenna reflectivity-related readings from the second subset; and determining that and timing of the second transition event occurred based on the ileocecal junction transition indicator detected in the antenna reflectivity-related readings from the first subset.

10. the ileocecal junction transition indicator comprises an increase in a sensor-side VOC gas sensor reading with a concomitant increase in H2 concentration, the H2 concentration being derived from a TCD reading of the TCD gas sensor and / or a heater-side reading of the VOC gas sensor; or 10. The apparatus of claim 9, wherein the ileocecal junction transition indicator comprises an increase in a sensor-side VOC gas sensor reading accompanied by a simultaneous increase in a CH4 concentration, the CH4 concentration being derived from a TCD reading of the TCD gas sensor and / or a heater-side reading of the VOC gas sensor.

11. the ingestible capsule includes an environmental sensor, the readings include readings of the environmental sensor, the environmental sensor being an environmental temperature sensor, an environmental relative humidity sensor, or an environmental temperature sensor and an environmental humidity sensor; 10. The device of claim 1, wherein the process further comprises determining an excretion event timing by detecting an excretion indicator, the excretion indicator being a change in the environmental sensor reading between an internal environmental condition of the target mammal and an external environmental condition at the location of the target mammal, and the excretion event timing being the timing of excretion of the ingestible capsule by the target mammal.

12. the ingestible capsule includes an environmental sensor, the readings include readings of the environmental sensor, the environmental sensor being an environmental temperature sensor, an environmental relative humidity sensor, or an environmental temperature sensor and an environmental humidity sensor; 2. The device of claim 1, wherein the process further comprises determining an ingestion event timing by detecting an ingestion indicator, the ingestion indicator being a change in the environmental sensor reading between an internal environmental condition of the target mammal and an external environmental condition at the target mammal's location, and the ingestion event timing being the timing of ingestion of the ingestible capsule by the target mammal.

13. the ingestible capsule further comprises a secondary transceiver, the secondary transceiver operable in a listening phase of the ingestible capsule, during which the primary transceiver, sensor, and on-board processor of the ingestible capsule are powered down, the secondary transceiver configured to receive a coded activation control signal from a coded activation control signal transmitting device during the listening mode and respond by terminating the listening phase and initiating a live phase of the ingestible capsule, during which the primary transceiver, sensor, on-board processor, and memory are powered up, and the readings are recorded and optionally transmitted to a receiver device; the secondary transceiver is an NFC transceiver, and the encoded activation control signal is an NFC signal; and 2. The apparatus of claim 1, wherein the receiver device is a transmitting device for the encoded activation control signal, the receiver device being a smartphone or tablet computer running an application that causes the smartphone or tablet computer to generate and transmit the encoded activation control signal and to receive, optionally process and transmit, the recorded readings transmitted from the capsule by the primary transceiver.

14. 1. A method for determining the location of an ingestible capsule within the gastrointestinal (GI) tract of a mammalian subject, comprising: providing the ingestible capsule to the mammalian subject for ingestion, the ingestible capsule comprising a housing, a power source, a TCD gas sensor, and a VOC gas sensor; recording readings of the ingestible capsule as a function of time, the readings including TCD gas sensor readings and VOC gas sensor readings; processing the recorded readings, determining a first transition event timing, the first transition event timing being a timing of gastroduodenal transition by the ingestible capsule, wherein determining the first transition event timing comprises detecting a gastroduodenal transition indicator in a first subset of the recorded readings, the first subset comprising the recorded TCD gas sensor readings; determining a second transition event timing, the second transition event timing being a timing of transition across an ileocecal junction by the ingestible capsule, and determining the second transition event timing comprises detecting an ileocecal junction indicator in a second subset of the recorded readings, the second subset comprising the VOC gas sensor readings.

15. 1. A computer program for determining the location of an ingestible capsule within a gastrointestinal (GI) tract of a subject mammal, the ingestible capsule being ingestible by the subject mammal and comprising: a housing; a power source; a TCD gas sensor; and a VOC gas sensor; The computer program is executable by a computing device having a processor and a memory, and when executed causes the computing device to perform a process, the process comprising: accessing recorded readings of the ingestible capsule as a function of time, including a period of time the ingestible capsule is in the GI tract of the subject mammal, the readings including TCD gas sensor readings and VOC gas sensor readings; and processing the recorded readings, wherein processing comprises: determining a first transition event timing, the first transition event timing being a timing of gastroduodenal transition by the ingestible capsule, wherein determining the first transition event timing comprises detecting a gastroduodenal transition indicator in a first subset of the recorded readings, the first subset comprising the recorded TCD gas sensor readings; determining a second transition event timing, the second transition event timing being a timing of transition across the ileocecal junction by the ingestible capsule, and determining the second transition event timing comprises detecting an ileocecal junction indicator in a second subset of the recorded readings, the second subset comprising the VOC gas sensor readings.

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