Ingestible capsule with on-board sensor hardware

Abstract

Embodiments include an ingestible capsule configured to determine the occurrence of an ejection event in response to identifying an ejection marker from on-board sensor hardware, and to modify one or more settings of a wireless data transmitter in response to determining the occurrence of an ejection event, such that the wireless data transmitter initiates, resumes, increases wireless transmission power, or increases wireless transmission rate of a data transmission payload from the ingestible capsule.

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 processing signals from sensors contained in ingestible capsules and wirelessly transmitting the processed results. [Background technology]

[0002] Sensor capsules such as those disclosed in EP 3497437 house gas and other sensors in an ingestible capsule so that readings can be taken from within the gastrointestinal (GI) tract of a mammal, from which readings about the GI tract, such as motility reports and concentrations of analyte gases, can be determined.

[0003] EP 3619526 discloses a process for determining the type and concentration of a particular gas in a multi-gas mixture based on readings taken from within the GI tract by a gas sensor mounted in an ingestible capsule.

[0004] Numerous studies have shown a strong possibility of linking these gas components with various diseases and symptoms, as well as the relationship between gas and intestinal health and, ultimately, overall health.

[0005] However, it is desirable to know or be able to accurately predict the location of the capsule within the GI tract at the time the gas sensor reading is taken in order to correlate gas constituents with various diseases, conditions, and the like. A predicted gas or gas concentration at one location in the GI tract may be indicative of a disease or condition at another location in the GI tract. Additionally, it is desirable to monitor and report health indicators such as GI tract motility. Motility in this context refers to the progression of an ingestible object, such as an ingestible capsule, through the digestive tract, which may be expressed, for example, in terms of residence time in different GI tract regions.

[0006] Additionally, information regarding capsule motility (i.e., information describing the capsule's progression through the GI tract, for example, by determining the time it takes to pass through various GI tract organs) can be used to diagnose GI tract and intestinal conditions and assess health status.

[0007] Gut health is increasingly recognized as a contributor to overall health and wellness. Motility of ingestible capsules (with or without measurement of associated gas components) provides important information in the assessment of gut health.

[0008] Accurate prediction and determination of capsule position itself provides information as a record of capsule motility, which is a useful indicator of GI tract health and condition. Additionally, contemporaneous recording of signals from, or data extracted from, one or more other sensors can be combined with the motility record to provide further indicators of GI tract health and condition.

[0009] It is desirable to address limitations of the prior art regarding reliable transmission, storage, and / or processing of signals provided by sensors mounted in ingestible sensor capsules.

[0010] Essay writing An embodiment is an ingestible capsule comprising an ingestible, indigestible, biocompatible housing, further comprising within the housing: sensor hardware including a power source and a temperature sensor configured to output a temperature sensor signal representative of a temperature of an environment surrounding the ingestible capsule; processor hardware; memory hardware; and a wireless data transmitter, wherein while the ingestible capsule passes through the GI tract of a subject mammal, the processor hardware receives signals output by the sensor hardware, processes the received signals, and transmits some or all of the processed signals, or data extracted therefrom, to a data transmission processor. and wherein the processor hardware is configured to receive and monitor the temperature sensor signal to identify when the temperature sensor signal indicates that the ingestible capsule is no longer present in the GI tract of the subject mammal, to determine, in response to the identification, that an expulsion event has occurred, and to modify one or more settings of the wireless data transmitter to initiate, resume, increase wireless transmission power, or increase wireless transmission rate of the data transmission payload from the ingestible capsule by the wireless data transmitter.

[0011] Optionally, in response to determining that an ejection event has occurred, said data transmission payload transmitted from said capsule includes a report that said ejection event has been determined to have occurred.

[0012] Optionally, changing the setting causes the wireless data transceiver to transmit the report that the ejection event has been determined to have occurred to a receiving device in a broadcast or query mode, and to wirelessly connect to the receiving device, or to wirelessly reconnect following an initial connection prior to ingestion of the ingestible capsule, to transmit the remainder of the data transmission payload.

[0013] Optionally, the sensor hardware includes one or more gas sensors, wherein the signals output by the sensor hardware and processed by the processor hardware include gas sensor signals output by the one or more gas sensors, and the data transmission payload includes the processed gas sensor signals or data extracted therefrom.

[0014] Optionally, said one or more gas sensors comprise: one or more spectrophotometers; one or more surface acoustic wave sensors; one or more bulk acoustic resonator arrays; one or more VOC gas sensors; and one or more TCD gas sensors; Each of the one or more gas sensors is configured to generate a constituent gas sensor signal that forms a portion of the gas sensor signal.

[0015] Optionally, processing the received gas sensor signal includes identifying one or more motility event indicators in the received gas sensor signal and storing a representation of the identified motility indicators in the memory hardware as a data transmission payload.

[0016] Optionally, identifying the one or more motility event indicators includes monitoring the gas sensor signals received from each of the one or more gas sensors on a rolling basis over a period of time immediately preceding a predetermined time period and identifying spikes, step changes, or inflection points in the gas sensor signals as the motility indicators.

[0017] Optionally, the one or more gas sensors comprise one or more of a VOC gas sensor and a TCD gas sensor, and the gas sensor signal accordingly comprises one or more of a VOC gas sensor signal and a TCD gas sensor signal.

[0018] Optionally, the sensor hardware further comprises one or more of an accelerometer, a reflectometer formed by an antenna connected in series with a directional coupler, the antenna being the antenna of the data transmitter, the antenna being controlled by the processor to transmit an intermittent or continuous signal from which a reflectometer signal can be obtained, and in addition to identifying the motility event indicator within the gas sensor signal, the processor hardware is configured to store, in association with the motility event indicator within the data transmission payload, a representation of a signal received contemporaneously with the motility event indicator from one or more sensors within the housing, the accelerometer, or the reflectometer, that are different from the gas sensor that provides the signal from which the motility event indicator is detected.

[0019] Optionally, the representation of the signal is: recording said signal; recording said signal downsampled by retaining only one out of multiple readings; a dimensionality-reduced version of said signal; recording the identification markers identified by processing the signal; one or more of the following characteristic values ​​of the signal obtained by processing the signal, the characteristic value being an average value, a rate of change, a maximum value, a local maximum value, a minimum value, or a local minimum value.

[0020] Optionally, the ingestible capsule further comprises an accelerometer, and during passage through the GI tract, the processor hardware is configured to receive accelerometer signals output by the accelerometer, process the received accelerometer signals, and store the processed accelerometer signals, or a representation thereof, in the memory hardware as a data transmission payload.

[0021] Optionally, in response to identifying that the temperature represented by the temperature sensor signal has fallen below a predetermined temperature range for the target mammal, to determine the occurrence of the ejection event, the processor hardware is configured to determine whether the received accelerometer signal indicates that the ingestible capsule is experiencing a free fall event, and if it is determined that the received accelerometer signal indicates that the ingestible capsule is experiencing a free fall event, the processor hardware is configured to determine that the ejection event has occurred.

[0022] Optionally, said processor hardware is configured to process said temperature sensor signal and store said processed temperature signal, or data extracted therefrom, in said memory hardware as a data transmission payload.

[0023] Optionally, said wireless data transmitter is a Bluetooth transceiver.

[0024] Optionally, said wireless data transmitter is a Bluetooth transceiver configured to operate according to a Bluetooth Low Energy coded PHY transmission protocol.

[0025] Optionally, said Bluetooth transceiver comprises an integrated radio and microcontroller.

[0026] Optionally, in response to determining the occurrence of the ejection event, modifying one or more settings of the wireless data transmitter includes controlling the Bluetooth transceiver to transmit the data transmission payload stored in the memory hardware by broadcasting pending transmission data from the data transmission payload to the receiving device, regardless of whether the receiving device is paired with the Bluetooth transceiver.

[0027] Optionally, prior to determining the occurrence of the expulsion event, the Bluetooth transceiver is configured to pair with a Bluetooth compatible device external to the target mammal and transfer to the paired device data including or representative of one or more of the following: signal(s) from the sensor hardware, one or more motility indicators identified by processing signals from the sensor hardware, one or more diagnostic indicators identified by processing signals from the sensor hardware, information representative of remaining capacity of the power source, a metric calculated by processing a signal from a single sensor in the sensor hardware or combining signals from multiple sensors in the sensor hardware, a calculated gas concentration level of one or more component gases of a gas mixture present in the GI tract calculated by reference to predetermined calibration parameters stored in the memory hardware; and in the course of proceeding to determine the occurrence of the expulsion event, the processor hardware is configured to change a setting of the Bluetooth transceiver to transfer the data transmission payload to the same Bluetooth compatible device either by continuing the existing pairing, by re-pairing, or in the absence of pairing.

[0028] Optionally, the ingestible capsule is configured to operate in an ingestion detection mode in which, after an initiation event, the temperature sensor is activated, and the processor hardware is operative to monitor the temperature sensor signal to identify when the temperature represented by the temperature sensor signal reaches a predetermined internal temperature range of the subject mammal, and in response to said identification, determine that an ingestion event has occurred, record the ingestion event as a data transmission payload in the memory hardware, and begin collecting data during the transit through the GI tract.

[0029] An embodiment is an ingestible capsule, the ingestible capsule comprising: an ingestible, indigestible, biocompatible housing; Within the housing: Power supply and Sensor hardware; processor hardware; memory hardware; a Bluetooth transceiver; the processor hardware is configured to receive signals output by the sensor hardware while the ingestible capsule passes through the GI tract of the subject mammal; process the received signals by calculating a metric representative of the received signals or identifying a motility or diagnostic indicator in the received signals; and store the calculated metric or data representative of the motility or diagnostic indicator in the memory hardware as a data transmission payload, wherein the motility indicator and / or the diagnostic indicator is a predetermined pattern, range of values, spike, step change, inflection point, local maxima or minima, predetermined change, or sequence of changes in the signal(s) output by one or more sensors of the sensor hardware; and the Bluetooth transceiver is configured to transmit the data transmission payload from the ingestible capsule to a paired receiving device while the ingestible capsule passes through the GI tract of the subject mammal.

[0030] Embodiments may include an ingestible capsule comprising an ingestible, indigestible, biocompatible housing, further comprising within the housing a power source, sensor hardware, processor hardware, memory hardware, and a wireless data transmitter, wherein the ingestible capsule is configured to collect data during passage through the GI tract of a subject mammal after ingestion by the subject mammal, during which the processor hardware is configured to receive signals output by the sensor hardware, process the received signals, and store some or all of the processed signals, or data extracted therefrom, in the memory hardware as a data transmission payload, wherein the processor hardware is configured to receive and monitor the signals output by the sensor hardware to identify a transmission trigger event indicator, and in response to the identification, determine an occurrence of a transmission trigger event, and in response to determining the occurrence of the transmission trigger event, change one or more settings of the wireless data transmitter to start, resume, increase wireless transmission power, or increase wireless transmission rate of the data transmission payload from the capsule via the wireless data transmitter.

[0031] An embodiment is a method in an ingestible capsule adapted for ingestion by a target mammal, the ingestible capsule comprising an ingestible, indigestible, biocompatible housing, and within the housing, sensor hardware including a power source and a temperature sensor configured to output a temperature sensor signal representative of a temperature of an environment surrounding the ingestible capsule, processor hardware, memory hardware, and a wireless data transmitter, the method comprising: collecting data in the ingestible capsule after ingestion of the ingestible capsule by the target mammal during passage through the GI tract of the target mammal; receiving signals output by the sensor hardware during the passage through the GI tract of the target mammal; and processing the received signals. storing some or all of the processed signal, or data extracted therefrom, in the memory hardware as a data transmission payload; receiving and monitoring, in the processor hardware, the temperature sensor signal to identify when the temperature sensor signal indicates that the ingestible capsule is no longer present in the GI tract of the subject mammal; determining, in response to the identification, the occurrence of an expulsion event; and altering one or more settings of the wireless data transmitter to initiate, resume, increase wireless transmission power, or increase wireless transmission rate of the wireless data transmitter of the data transmission payload from the ingestible capsule in response to determining the occurrence of the expulsion event.

[0032] An embodiment is a method in an ingestible capsule, the ingestible capsule comprising: an ingestible, indigestible, biocompatible housing; Within the housing: Power supply and Sensor hardware; processor hardware; memory hardware; a Bluetooth transceiver; the method further comprising, after ingestion of the ingestible capsule by the subject mammal, and transmitting, in the Bluetooth transceiver, the data transmission payload from the ingestible capsule to a paired receiving device during transit through the GI tract of the subject mammal.

[0033] An embodiment is a method in an ingestible capsule, the ingestible capsule comprising: an ingestible, indigestible, biocompatible housing; Within the housing: Power supply and Sensor hardware; processor hardware; memory hardware; a wireless data transmitter; The method may include, after ingestion of the ingestible capsule by the subject mammal and during passage through the GI tract of the subject mammal, receiving, in the processor hardware, signals output by the sensor hardware; processing the received signals; and storing, in the memory hardware, some or all of the processed signals, or data extracted therefrom, as a data transmission payload; receiving and monitoring, in the processor hardware, the signals output by the sensor hardware to identify a transmission trigger event indicator; and, in response to the identification, determining an occurrence of a transmission trigger event; and, in response to determining an occurrence of the transmission trigger event, modifying one or more settings of the wireless data transmitter to start, resume, increase wireless transmission power, or increase wireless transmission rate wireless transmission of the data transmission payload from the capsule by the wireless data transmitter.

[0034] An embodiment is a computer program for execution by processor hardware in an ingestible capsule adapted for ingestion by a mammalian subject, the ingestible capsule comprising: an ingestible, indigestible, biocompatible housing; sensor hardware within the housing including a power source and a temperature sensor configured to output a temperature sensor signal representative of a temperature of an environment surrounding the ingestible capsule; the processor hardware; memory hardware; and a wireless data transmitter, the computer program, when executed by the processor hardware, causing the processor hardware to receive, after ingestion of the ingestible capsule by the mammalian subject, a signal output by the sensor hardware during passage of the ingestible capsule through the GI tract of the mammalian subject; and storing in the memory hardware some or all of the processed signal, or data extracted therefrom, as a data transmission payload; receiving and monitoring the temperature sensor signal to identify when the temperature sensor signal indicates that the ingestible capsule is no longer present in the GI tract of the subject mammal; determining, in response to the identification, the occurrence of an expulsion event; and, in response to determining the occurrence of the expulsion event, modifying one or more settings of the wireless data transmitter to initiate, resume, increase wireless transmission power, or increase wireless transmission rate of wireless transmission of the data transmission payload from the ingestible capsule by the wireless data transmitter.

[0035] An embodiment is a computer program for execution by processor hardware in an ingestible capsule, the ingestible capsule comprising an ingestible, indigestible, biocompatible housing, further comprising within the housing a power source, sensor hardware, the processor hardware, memory hardware, and a Bluetooth transceiver, the computer program, when executed by the processor hardware, causing the processor hardware to receive signals output by the sensor hardware during passage through the GI tract of a subject mammal following ingestion of the ingestible capsule by the subject mammal, and to calculate a metric representative of the received signals or to calculate a motility index or a diagnostic index in the received signals. and storing in the memory hardware as a data transmission payload data representative of the calculated metric or the motility index or the diagnostic index, wherein the motility index and / or the diagnostic index is a predetermined pattern, range of values, spike, step change, inflection point, local maximum or minimum, predetermined change, or sequence of change in a signal(s) output by one or more sensors of the sensor hardware; and transmitting in the Bluetooth transceiver from the ingestible capsule to a paired receiving device during the transit through the GI tract of the target mammal.

[0036] An embodiment is a computer program for execution by processor hardware in an ingestible capsule, the ingestible capsule comprising: an ingestible, indigestible, biocompatible housing; Within the housing: Power supply and Sensor hardware; the processor hardware; memory hardware; a wireless data transmitter; The computer program may include a computer program that, when executed by the processor hardware, causes the processor hardware to perform a method including receiving signals output by the sensor hardware while the ingestible capsule passes through the GI tract of the subject mammal; processing the received signals; storing some or all of the processed signals, or data extracted therefrom, in the memory hardware as a data transmission payload; receiving and monitoring the signals output by the sensor hardware to identify a transmission trigger event indicator; determining, in response to the identification, an occurrence of a transmission trigger event; and, in response to determining the occurrence of the transmission trigger event, modifying one or more settings of the wireless data transmitter to start, resume, increase wireless transmission power, or increase wireless transmission rate of wireless transmission of the data transmission payload from the capsule by the wireless data transmitter.

[0037] In the following, embodiments will be described by way of example only with reference to the accompanying drawings, in which: [Brief explanation of the drawings]

[0038] [Figure 1A] FIG. 1 is a schematic diagram of an ingestible capsule. [Figure 1B] FIG. 2 is a schematic diagram of the electronic components of the ingestible capsule. [Figure 1C] The system includes an ingestible capsule. [Figure 2] 1 shows a schematic diagram of the electronic components of the ingestible capsule. [Figure 3] The sensitivity to the component gases changes depending on the operating temperature. [Figure 4] 1 is a flow chart of a process according to an embodiment. [Figure 5] 1 is a flow chart of a process according to an embodiment. [Figure 6]1 illustrates data and processing operations in generating a motility report according to an embodiment. [Figure 7A] 1 shows plots of data generated by an embodiment. [Figure 7B] 1 shows plots of data generated by an embodiment. [Figure 7C] 1 shows plots of data generated by an embodiment. [Figure 8A] 1 shows plots of data generated by an embodiment. [Figure 8B] 1 shows plots of data generated by an embodiment. [Figure 8C] 1 shows plots of data generated by an embodiment. [Figure 8D] 1 shows plots of data generated by an embodiment. [Figure 9A] 1 shows plots of data generated by an embodiment. [Figure 9B] 1 shows plots of data generated by an embodiment. [Figure 9C] 1 shows plots of data generated by an embodiment. [Figure 9D] 1 shows plots of data generated by an embodiment. [Figure 10] 1 shows a flow of processing according to an embodiment. [Figure 11] 1 shows a flow of processing according to an embodiment. [Figure 12] 1 shows a flow of processing according to an embodiment. DETAILED DESCRIPTION OF THE INVENTION

[0039] Overview of ingestible capsules Figures 1A and 1B show an ingestible capsule 10. A system including the ingestible capsule 10 of Figures 1A and 1B is shown in Figure 1C 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).

[0040] 1A and 1B, a typical capsule 10 consists of a housing, such as a gas-impermeable shell 11, having an opening covered by a gas-permeable membrane 12. Membrane 111 separates an exposed interior cavity that is exposed to environmental gases that enter capsule 10 through membrane 12 from a sealed interior cavity that is not exposed to environmental gases.

[0041] 1C, in addition to the capsule, the system further comprises a receiving 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 receiving 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 the facility of a clinician where the subject is a patient, or a server (cloud-based or not) at a service provider where the clinician is a subscriber / customer / service user.

[0042] Optionally, the system may further comprise a remote processing device 20, such as a server forming part of a cloud computing environment or 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 responsible for interpreting the results (i.e., data transmission payload) generated by the capsule 10 and reporting them to the subject 40.

[0043] The connection between the capsule 10 and the receiving device 30 is 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 the Bluetooth Low Energy transmission protocol. Other available communication technologies include LoRa, Wi-Fi, and 433 MHz radio.

[0044] The capsule 10 contains inside it the gas sensor hardware 131, 132, the environmental sensor 14, as well as the processor hardware 151 and the memory hardware 152. The processor hardware 151 and the memory hardware 152 may be a microcontroller. The processor hardware 151 may be a microprocessor. The memory hardware 152 may be a non-volatile memory, and the data stored therein is accessible by the processor hardware 151. The processor hardware 151 processes data from the signals received from the gas sensor hardware and the environmental sensor (and optionally the reflectometer and the accelerometer), and stores the processed data in the memory hardware 152. The processed data or a part thereof is stored in the memory hardware 152 as a data transmission payload ready to be transmitted by the data transmitter 18 to the receiving device 30.

[0045] As an example, the capsule shown in Figure 1C houses, as sensor hardware, the environmental sensor 14 in the form of a temperature sensor 14a and / or a humidity sensor 14b, the gas sensors in the form of a TCD gas sensor 131 and a VOC gas sensor 132, an accelerometer 19, as well as a reflectometer. Embodiments may include any single or combination of those individual sensors. Alternatively or additionally, embodiments may include in the embodiment one or more sensors not shown in Figure 1C, such as a spectrophotometer, a surface acoustic wave sensor, and / or a bulk acoustic resonator array.

[0046] The environmental sensor 14 may be a temperature sensor 14a, or may be a temperature sensor 14a and a humidity sensor 14b. The gas sensor may be a TCD gas sensor 131, a VOC gas sensor 132, or both a TCD gas sensor 131 and a VOC gas sensor 132. As shown in FIG. 2, the internal electronics may also include a power source 16, such as a silver oxide battery, an antenna 17, and a wireless transceiver 18. The internal electronics may also include a reed switch. Other options for powering off the device (or otherwise not consuming power) during storage include a physical switch pressed through a flexible portion of the housing, or a photodetector and coupled field-effect transistor that latches on the microcontroller when exposed to light. The internal electronics may further include an accelerometer 19, from which accelerometer data (i.e., signals) are received and processed by processor hardware 151, then stored in memory hardware 152, and transmitted by data transmitter 18.

[0047] Gas sensors 131, 132 are each less than a few millimeters in size and sensitive to specific gas components, including oxygen, hydrogen, carbon dioxide, and methane. Indeed, VOC gas 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, and thus the heater-side reading of the VOC gas sensor is a TCD reading. The sensor-side reading is used to determine the concentration of volatile organic compounds in the surrounding gas, and is a VOC reading. TCD gas sensor 131 may be, for example, a heating element coupled to the output of a thermopile, and the thermopile's temperature, and therefore its output, varies with the energy transferred to the gas at the capsule 10. TCD gas sensor 131 measures the rate of heat diffusion from the heating element.

[0048] As shown in FIG. 3 , the heater side of the VOC gas sensor 132 (operating as a TCD sensor) and the sensor side of the TCD gas sensor 131 have different operating ranges, so that the TCD readings from the two sensors collectively span a wider operating temperature range than either sensor alone. Both sensors have heating elements. The TCD gas sensor 131 operates at a lower temperature but is highly accurate. The heater side of the VOC gas sensor 132 increases the operating range, but the accuracy of the TCD readings is lower than that of the TCD sensor. The greater overall thermal range achieved by the two gas sensors 13 in concert allows for better resolution of analytes when signals from the gas sensors are processed to resolve analytes. Because the thermal conductivity of component gases in the gas mixture in the GI tract varies with temperature, taking TCD readings at different operating temperatures allows different gases to be resolved from one another. This is exploited in the gas resolution processing branch to determine the identity and concentration of component gases in the gas mixture surrounding the capsule 10. The gas decomposition process may be performed on-board the gas capsule 10, in the receiving device 30, or in a remote processing device. The gas decomposition process is optional depending on the implementation.

[0049] The gas sensor 13 is housed in a portion of the capsule 10 that is sealed from the power source 16 and other electronic components by a membrane 111. This arrangement minimizes the volume of the sensing headspace (i.e., the sealed portion) and minimizes the risk of leaks caused by a perforated membrane that allows GI tract gases from the headspace to reach the power source. However, the membrane may be omitted because the power source may be configured so that exposure to GI tract gases does not adversely affect performance. That is, the membrane 111 is optional. The membrane 111 is permeable by electronic circuitry required to connect the components housed on either side. For example, wiring may pass through the membrane 111 in a sealed state. The exterior surface of the sealed portion of the capsule is constructed from a selectively permeable membrane. In this context, selectively permeable refers to a membrane that is impermeable to liquids but permeable to gases. Selectivity does not extend to allowing only some gases to pass through. For example, the gas sensors 13 include respective heaters that are driven to heat the sensing portion of each gas sensor 13 to a temperature at which a sensor reading is taken (i.e., a measurement temperature). The heaters may be driven in pulses such that there is a time-varying change in the temperature of the sensing portion such that the measurement temperature is obtained for a period sufficient to obtain a reading, but does not consume the power required to continuously maintain the measurement temperature.

[0050] The gas sensor 13 is calibrated, and gas sensor readings can be used to identify the composition and concentration of gases to which the gas sensor 13 is exposed. Calibration coefficients are collected during manufacturing and testing and applied to the recorded readings during the processing phase (i.e., by a server, such as on the cloud). Alternatively, this calibration can be performed in the capsule 10, in the receiving device 30, or in any device with access to the calibration coefficients and recorded readings from the gas sensor 13. Such calibration is related to the gas resolution processing branch, which is responsible for measuring the concentrations of the constituent gases in the gas mixture in the capsule 10. Context for the output from that processing branch is provided by the motility processing branch, which determines (or predicts, within a given confidence level) the location of the capsule 10 in the GI tract where that gas mixture will be found. The motility (or location) processing branch may also require some calibration when determining the gastroduodenal transit index, because food ingested at different temperatures changes the environmental temperature in the stomach, affecting the rate of heat diffusion. For gas sensor readings obtained after ingestion but before the gastroduodenal transition (i.e., while capsule 10 is in the stomach), processing of the readings may include applying an adjustment to the TCD reading from either gas sensor to correct for fluctuations in environmental temperature based on the environmental temperature reading from temperature sensor 14a. The TCD readings essentially measure the rate of heat loss to the surroundings, and therefore, measuring the ambient temperature rather than relying on assumptions (i.e., prior knowledge of the subject mammal's internal body temperature) improves accuracy. However, processing may rely on assumptions, for example, if there are issues with the temperature sensor readings or, for example, if the level of accuracy provided by the assumptions is acceptable in a particular embodiment. For example, gastric temperature may fluctuate based on the subject mammal's ingestion of liquids or food or physical activity engaged in by subject mammal 40. Environmental temperature is a term used herein to refer to the temperature of the environment in which capsule 10 is placed, as distinguished from the operating temperature of gas sensor 13.The sensitivity of the gas sensor 13 to different component gases varies depending on the operating temperature of the sensor, and processing of the readings includes calibrating (also called adjusting or correcting) the readings from the gas sensor depending on the contemporaneous operating temperature and, optionally, depending on the contemporaneous environmental temperature.

[0051] It should be noted that the motility processing branch and the gas decomposition processing branch are not independent of each other. Some motility indicators (i.e., features or characteristics of the sensor output signal used to determine the timing of motility events) may be found in a concentration reading of a single analyte gas in the gas mixture in the capsule, obtained by processing the output of one or more gas sensors 13.

[0052] In addition to the gas sensor 13 and temperature sensor 14a, the capsule electronics further include processor hardware 151, memory hardware 152, power supply 16, antenna 17, wireless transmitter 18, and optionally a reed switch. Wireless transmitter 18 operates in conjunction with antenna 17 to transmit readings from the sensors (collectively referring to gas sensor 13 and temperature sensor 14a, and optionally accelerometer 19 and reflectometer) to receiving device 30 for processing there or at a remote processing device with which the receiving device is in data communication; alternatively, processor hardware 151 processes signals received from the sensors to identify motility indicators (or otherwise extract information from the sensor readings).

[0053] The wireless transmitter 18 (also referred to as a data transmitter 18) may be provided as part of the wireless transceiver 18. The wireless transceiver 18 includes an antenna 17. Optionally, the wireless transceiver 18 also includes a directional coupler 171. The wireless transceiver 18 may transmit data according to the Bluetooth protocol, the Bluetooth Long Range (Coded PHY) protocol, the LoRa protocol, the wifi protocol, or using other transmission modes such as 433 MHz radio wave transmission.

[0054] In the example of Bluetooth wireless transceiver 18, in a transmit-before-emission technique, the transceiver may operate in accordance with a Bluetooth transmission procedure for a long-range or coded PHY, such as a BTLE coded PHY. Via the Bluetooth transmission procedure for a BTLE coded PHY, an increase in signal power of approximately 10 dB can be achieved.

[0055] 2, the antenna 17 and directional coupler 171 are shown as elements of the wireless transmitter 18 because the antenna is the physical means by which the wireless transmitter 18 transmits data to the receiving 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 population of similar capsules 10.

[0056] The interconnections between the electronic components in FIG. 3 may be via 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 via a microcontroller that coordinates the distribution of data and power between the components. The sensors (TCD sensor 131, VOC sensor 132, temperature sensor 14a, accelerometer 19, and directional coupler 171) take readings under the direction of the microcontroller, which is powered by power supply 16, and forward the readings (or processed results of the readings) to wireless transmitter 18 for transmission via antenna 17 to a receiving device. For example, processor hardware 151 and memory hardware 152 may be collectively referred to as a microcontroller.

[0057] 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, indigestible polymer. The housing may be smooth and non-sticky to allow for the shortest possible passage time and minimize the risk of capsule retention. Optionally, the ingestible capsule may be less than 32.3 mm in length and less than 11.6 mm in diameter.

[0058] Antenna 17 can be in series with directional coupler 171. Directional coupler 171 and antenna 17 are configured as a reflectometer. The reflectometer measures the amplitude of the signal reflected by a diode detector. The reflectometer reading is a reading that represents the electromagnetic properties of materials in the vicinity of the capsule. The reflectometer reading provides the basis for distinguishing between gas, liquid, and solid objects at the capsule's location in the GI tract. The reflectometer reading allows antenna 17 and directional coupler 171 to work in concert as an environmental dielectric sensor.

[0059] The readings of the ingestible capsule 10 include readings from one or more of the temperature sensor 14a, 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, and may also include reflectometer readings. Thus, a change in the position of the capsule within the GI tract causes a change in the reflectometer reading, thereby providing an indication that a transition event between two sections of the GI tract has occurred.

[0060] The ingestible capsule 10 may further include 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 its position within the GI tract, whereby the accelerometer readings provide an indication 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 orthogonal to one another.

[0061] Processor hardware, memory hardware The processor hardware and memory hardware may be separate components or may be part of the same single integrated chip. It should be noted that the processor hardware and memory hardware are selected according to the specific implementation requirements of each design or version of capsule 10, and constraints such as power consumption, cost, data throughput, and data transmission payload size may vary between designs or versions. The processor hardware may be a single processor or multiple interconnected processors.

[0062] Pairing The wireless data transmitter may be a Bluetooth transmitter, a Wi-Fi transmitter, a radio transmitter, or another form of wireless data transmitter. The radio transmitter may be configured to transmit in the 433 MHz band. In either case, the wireless data transmitter may be provided as part of a wireless data transceiver. For example, the wireless data transceiver may receive signals upon pairing or any other form of coupling with at least the receiving device 30. The capsule 10 may be configured to enter a wireless pairing or coupling mode immediately upon initiation (i.e., initial power-on), and the subject or another user may be instructed (via written instructions or via an application running on the receiving device itself) to pair or couple the capsule 10 with the receiving device 30 prior to ingestion of 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 using a data transmission technique that is independent of pairing or coupling status, as described in more detail below.

[0063] Data Transmission Technology There are two primary data transmission techniques, and the ingestible capsule can be configured to use either or both, depending on the implementation details (i.e., use case). In the post-ejection data transmission technique, signals from the sensors are received by processor hardware 151 (also utilizing the storage capabilities of memory hardware 152) and processed onboard capsule 10 to identify and record motility metrics (and optionally, sensor outputs or other characteristics of the sensor reading or group of sensor readings of interest). The recorded motility metrics (and optionally, other characteristics, metrics, and readings or groups of readings of interest, e.g., peak H2 values, area under an H2 plot versus time) are stored in memory hardware 152 as a data transmission payload. Other characteristics, readings or groups of readings of interest may include, for example, maximum or minimum readings from a particular sensor or from a metric calculated from a combination of sensors. The maximum or minimum reading may be a local maximum or minimum reading, where local is defined, for example, by a predetermined timing or a motility event determined to have occurred due to the capsule 10 itself. A specific example is a maximum or minimum H concentration, which is a metric calculated from gas sensor readings by appropriately calibrated processor hardware. The data transmission payload is transmitted by the wireless transceiver upon detection of capsule 10's expulsion from the GI tract (e.g., via the temperature sensor 14a signal and / or the accelerometer 19 signal). Further metrics may include peak H level or value, timing of peak H, and total H (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 receiving device in a post-expulsion transmission, as part of a report, or otherwise.

[0064] In the post-ejection data transmission technique, transmission may be via a Bluetooth transmission mode that is independent of pairing status. That is, for example, if the Bluetooth transceiver is paired with a receiving device, it transmits the data transmission payload to the paired receiving device; if the Bluetooth transceiver is not paired, it broadcasts the data transmission payload to the receiving device without pairing in an inquiry mode (which may also be called a discovery mode or a beacon mode). 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 include or be contained within such other information. In particular, the data transmission payload may be prioritized or otherwise filtered by the processor hardware 151 so that information deemed particularly important, such as an indication that ejection has occurred (knowing that the capsule 10 has been ejected is important for clinical reasons) and potential information such as the timing of determined motility events, is transferred from the capsule 10 in priority to other information. Following the inquiry mode transmission, the transceiver may again attempt to pair, connect, or otherwise couple with the receiving device and, if successful, transmit the remainder of the data transmission payload. Of course, such pairing, connecting, or coupling may first be performed prior to ingestion, and after ejection, the Bluetooth transceiver may attempt to re-pair, re-connect, or re-couple with the receiving device 30. Note that while this description uses Bluetooth as an example transmission protocol, the same techniques may be applied to different transmission protocols.

[0065] After the unique identifier, name, and other information are broadcast during the Bluetooth inquiry mode, if there is a data transmission payload pending transmission from the capsule 10, the capsule 10 may be configured to initiate or resume a data communication connection (i.e., pairing or re-pairing) with the receiving device 30. If the communication connection is successfully initiated or resumed, the transmission of the data transmission payload pending transmission from the capsule 10 is performed while the data communication connection remains active.

[0066] The Bluetooth transceiver 18, or any other wireless data transmitter 18, may be configured to automatically reconnect after an initial (i.e., pre-ingestion) connection to the receiving device 30. The receiving device 30 may run an app or web app to guide the subject on how to ingest the capsule 10, to notify the subject that an expulsion event has been determined, and, optionally, to notify the subject that the data transmission payload has been successfully transmitted to the receiving device 30 and that the capsule 10 may be expelled. Note that, as used herein, the terms pairing, connecting, and coupling are interchangeable and each refer to the establishment of a wireless connection between two devices for wireless data transfer.

[0067] It should be noted that the data transmission payload may be transmitted while the capsule 10 is transiting the GI tract, depending on its pairing, coupling, or connection with the receiving device 30. However, confirmation that an ejection event has been determined by the capsule is particularly important information since the safety of the capsule 10 depends on the ejection of the capsule 10. Therefore, information representing the determination of the occurrence of an ejection event (i.e., its report) takes priority and may be transmitted in a broadcast or query mode, while the remaining data transmission payload is transmitted after a connection between the wireless data transmitter 18 and the receiving device 30 is established.

[0068] In Bluetooth inquiry mode, data may be transmitted to receiving device 30 or any Bluetooth receiving device within range of capsule 10 without pairing. Wireless transceiver 18 can operate in Bluetooth inquiry mode or Bluetooth low energy mode. Capsule 10 may store and transmit data transmission payload readings from one or more sensors representing a predetermined period on either side of an identified motility indicator. For example, for only the gas sensor signal, or for all sensors. Such readings may be used to increase the reliability of the identified motility indicator with respect to determining whether a motility event has occurred and / or may provide other information useful in a health or clinical context.

[0069] More generally, the data transmitted according to the post-excretion data transmission technique can be any data transmission payload that has not yet been transmitted. For example, the wireless data transmitter 18 may be configured to transmit the data transmission payload to a paired receiving device while still in the GI tract (this transmission is referred to herein as a pre-excretion data transmission technique). However, due to issues such as signal attenuation, noise, power issues, temporary pairing failure, or if pairing was never performed in the first place, or for other reasons, some or all of the data transmission payload may be pending transmission at the time of expulsion. In that case, the remaining data transmission payload is transmitted according to the post-excretion data transmission technique once expulsion is detected. Note that downsampling of the data transmission payload may be performed before transmission via the post-excretion data transmission technique. Furthermore, note that some elements of the data transmission payload may be prevented from transmission via the post-excretion data transmission technique. For example, because bandwidth and time to transmit may be limited, sensor readings may be excluded from the data transmitted according to the post-excretion data transmission technique, while motility event indicators and diagnostic indicators themselves are included.

[0070] In the data-before-eject technique, the sensor signals are continuously transmitted by the wireless transceiver 18. In the data-before-eject technique, the process hardware 151 coordinates the reception of signals from the sensors and their storage in the memory hardware 152 for transmission by the wireless transceiver 18.

[0071] In the example of Bluetooth wireless transceiver 18, in a transmit-before-emission technique, the transceiver may operate in accordance with a Bluetooth transmission procedure for a long-range or coded PHY, such as a BTLE coded PHY. Via the Bluetooth transmission procedure for a BTLE coded PHY, an increase in signal power of approximately 10 dB can be achieved.

[0072] During the data transmission phase of the ingestible capsule 10 (i.e., a short burst after expulsion in post-expulsion data transmission techniques, or continuously while the ingestible capsule 10 is in use in the GI tract of the subject mammal 40 and taking and transmitting readings in pre-expulsion data transmission techniques), the wireless transmitter 18 transmits readings to the receiving device 30, which may be a dedicated device for receiving and storing readings (and optionally, including a user interface) or may be a multi-function device such as a mobile phone (e.g., a smartphone). The mobile phone may execute an application that processes some or all of the data transmission payload and generates a motility report or a diagnosis of a medical condition based on the motility 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 and generate a motility report or a diagnosis of a medical condition based on the data transmission payload. The subject mammal need not remain within a particular range of the remote computer 20 during the live phase. Capsule 10 equipped with Bluetooth transceiver 18 can communicate directly with the user's smartphone, thereby eliminating the need for a dedicated receiving device (the smartphone assumes the role of receiving device 30). Receiving device 30 (whether a dedicated device or a mobile phone or tablet computer) may process the readings itself or upload the readings to remote computer 20 for processing (i.e., identifying motility indicators, determining the timing of motility events, resolving gas analytes). Uploading may be continuous during the capsule's live phase or after the capsule's live phase has ended. Receiving device 30 can also store readings, so that loss of connectivity between receiving device 30 and the remote processing device is not significant.

[0073] The onboard processor 151 may apply one or more processing or pre-processing steps, as described in more detail below. Digitization of the readings is performed either by the sensor itself, by the processor 151, or by the wireless transceiver 18. The digitized readings are transmitted via the antenna 17. Capsule 10 readings are made at a point in time and are associated with the time they were made. For example, a timestamp may be associated with the readings by the microcontroller 15, the wireless transmitter 18, or by the receiving device 30 or remote computer 20. For example, if the readings are made and transmitted by the wireless transmitter 18 nearly instantaneously (i.e., within one or a few seconds), the time of receipt by the receiving device may be associated with the reading as a timestamp. The processing of the readings, as described further below, depends to some extent on the relative timing of the readings (i.e., allowing contemporaneous readings from different sensors to be distinguished as contemporaneous), but accuracy on the one-second, few-second, or ten-second level is sufficient.

[0074] In hybrid mode, the capsule 10 may combine two data transmission techniques. For example, the capsule 10 may process sensor readings onboard to identify motility markers (and optionally other readings or groups of readings of interest) and transmit them via Bluetooth interrogation mode immediately after ejection. Additionally, the capsule 10 may continuously transmit sensor readings to a paired receiving device. Optionally, the continuous transmission may be the gas sensor signal alone, or the gas sensor signal and a temperature sensor signal necessary for calibrating the gas sensor signal. The gas sensor signal is particularly important in providing health and clinical information, especially when combined with motility indicators provided by other sensors such as an accelerometer or reflectometer. The gas sensor signal may be downsampled or subjected to other compression techniques by the onboard processor before transmission. Optionally, the onboard processor hardware 151 may apply one or more filters, such as a high-pass or low-pass filter applied to the value itself or its derivative with respect to time, so that only gas sensor signals meeting a certain threshold 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 versus time, may be maintained and transmitted from the capsule 10.

[0075] For capsules 10 configured to transmit data during GI tract transit (i.e., pre-ejection data transmission technology), commercial bands (such as 433 MHz) are used by the antenna 17 because electromagnetic waves in this frequency range can safely penetrate mammalian tissue 40. Bluetooth can also be used in such capsules, and it can be long-range Bluetooth, especially if the subject's (human) BMI exceeds a threshold or if high levels of attenuation are expected for some other reason. Other commercial bands and protocols, such as LoRa, can be used in various applications. Encoding can be applied at the digitization stage to ensure that data transmitted by the capsule 10 can be distinguished from data transmitted by other similar capsules 10. The transmitting antenna 17 can be, for example, a pseudo-patch type for transmitting data external to the body data acquisition system.

[0076] The power source 16 is a battery or supercapacitor capable of powering the sensors and electronic circuitry, including the processor hardware 151 and 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 of 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 predetermined threshold, and the on-board processor is configured to monitor the stored energy level.

[0077] Data Processing Approach Broadly speaking, signal / reading / data processing can include any combination of three primary objectives: First (first branch or motility branch), assessing capsule motility through the GI tract by determining the timing of motility events, including ingestion, gastric emptying (gastroduodenal transition), ileocecal junction (ICJ) passage / transition, and ejection (thereby generating report data representative of capsule motility and / or altering internal capsule settings, such as data transmission settings, in response to the determination of the occurrence of motility events). Second (second branch or gas breakdown branch), determining the constituent gases and their concentrations in the gas mixture at the location of the ingestible capsule 10, either throughout its entire path through the GI tract or at one or more points. Third, diagnosing a medical condition by detecting or identifying predetermined diagnostic indicators in sensor hardware readings, where the diagnostic indicators are characteristic features of the signal output by an individual sensor, a combination of sensors, or a metric calculated by processing the signal output from a single sensor or combination of sensors. The diagnostic indicators are predefined based on discriminatory testing and related research. Conditions that may be diagnosed in this manner include, for example, small intestinal bacterial overgrowth (SIBO), constipation, and gastroparesis. It should be noted that the capsule 10 disclosed herein is directed to at least a first primary objective: a particular benefit of accurately determining the location of the ingestible capsule 10 within the GI tract is to provide context for the determination of constituent gases (i.e., analyte gases) and their concentrations. However, it should be noted that the results of the first branch of the process may provide useful information in assessing gut health even in the absence of the second branch of the process and may have other utility beyond the second branch of the process. Optionally, the determinations of the second branch of the process may be utilized to increase the reliability of the determinations in the first branch of the process. Furthermore, it should be noted that in either case, it is desirable to report to the receiving device that a determination of an expulsion motility event has occurred, since confirmation of expulsion notifies the subject and clinician that the capsule 10 is no longer present within the GI tract.

[0078] Readings from different sensors or pseudo-sensors (reflectometers may be referred to as sensors or pseudo-sensors) are used in the first branch, the second branch, and / or the third branch, as needed. For example, TCD gas sensor readings are used in the first branch to detect a gastroduodenal transit indicator, and in the second branch to determine, for example, the concentration of H at the location of the capsule 10. Readings from the VOC heater side are used in the second branch as a higher temperature TCD sensor to expand the temperature range over which TCD readings are obtained, thereby expanding the range of detectable H concentrations. The VOC sensor side is sensitive to O and H as well as other gases, and therefore these readings may be used in the second branch. Other gases include CH and SCFA. Optionally, readings from the VOC sensor side are not used in the second branch, and readings from the VOC sensor side are used only to detect the ileocecal junction transit indicator. Optionally, the VOC sensor side (i.e., the VOC sensing element) forms a resistor in a voltage divider circuit whose output is measured as the VOC sensor side reading. A conversion may be applied in the capsule 10 and / or as part of the processing to convert the output of the voltage divider circuit into a resistance measurement from the sensing element. The VOC sensor side may be driven with a constant (i.e., repeating) voltage pulse profile. The VOC sensor side reading may be taken synchronously with the voltage pulse profile so that there is no phase shift between the timing of the voltage pulse and the reading. The CH4 concentration is determined from the TCD gas sensor reading and / or the VOC heater side reading.

[0079] On-board sensors generate large amounts of data. Limitations such as the energy capacity of the power supply 16 mean that it may be preferable to process some of the data on-board the capsule 10 to extract (relatively small) data transmission payloads from the (relatively large) generated data. In addition to extraction, data processing techniques may summarize or otherwise represent the generated data to reduce the size of the data transmission payload. The processor hardware 151 may be configured to prioritize the content of the data transmission payload. In particular, data indicating that an ejection event has been determined and its timing may be given the highest priority (i.e., if data representing an ejection event is pending transmission, it will be transmitted in preference to the content of other data transmission payloads that are simultaneously pending transmission).

[0080] It will be appreciated that there is a wide range of possibilities between, at one extreme, transmitting all generated data from capsule 10 for processing (i.e., a high data transmission load and a low data processing load from the capsule's perspective) and, at the other extreme, performing advanced processing on-board to determine results with high certainty, including the timing of motility events, and even to diagnose specific health conditions or diseases, and transmitting only the processed results (i.e., a low data transmission load and a high data processing load from the capsule's perspective).

[0081] Embodiments can be configured during the design phase to combine data processing and data transmission in a manner that allows data processing to occur on-board or at the receiving device 30 or remote data processing device 20, depending on implementation requirements, to determine motility events and other intestinal health indicators such as gas component concentrations at one or more locations / timings in the GI tract, and to identify or detect diagnostic indicators.

[0082] It should be noted that the data transmission techniques detailed above may be considered orthogonal to the data processing approach, in the sense that whichever data transmission technique or combination of data transmission techniques is selected does not necessarily dictate the data processing approach. However, it should be understood that the data transmission capacity of each technique must be considered when determining how much processing to perform on-board capsule 10, and that performing on-board processing on capsule 10 generally reduces the size of the data transmission payload, provided that the processing results are included in the data transmission payload instead of the readings that were processed to produce the processing results.

[0083] In examples with large data transmission capacities, for example, when data is transmitted according to a pre-ejection data transmission technique or a pre-ejection data transmission technique, the raw sensor signal may be transmitted for processing off-board (i.e., not on the capsule) at the receiving device 30. The receiving device 30 or another processing device 20 connectable to the receiving device 30 (e.g., via a wired or wireless data transmission connection) may process the signal to identify motility indicators, determine the timing of motility events, and resolve the analyte gas from the gas sensor signal. The capsule 10 may transmit data using Bluetooth long-range mode (coded PHY).

[0084] Some processing of the sensor readings may continue to be performed onboard capsule 10, for example to identify or detect motility event indicators or diagnostic indicators, and the processed results may be added to a data transmission payload for transmission (in the first stage) according to a pre-ejection data transmission technique, which may be used as a fallback in case the data transmission payload is not successfully transmitted before ejection.

[0085] Further examples of on-board processing of sensor readings include processing signals from an accelerometer to calculate metrics representative of, for example, capsule sway or overall capsule motion. The calculated metrics may be calculated periodically (e.g., every 1, 2, 3, 5, 10 minutes) based on the accelerometer signal from the previous period, with the calculated metrics for each period being time-stamped and added to the data transmission payload.

[0086] The term signal may refer to an output signal produced by a sensor, while the term reading may refer to a particular measurement of a signal at or associated with a particular time point, which may be explicitly or implicitly included in or associated with the reading (e.g., if a reading is the 1000th reading in a series, and the readings are taken at a frequency of 1 Hz, and the timing of the first reading in the series is known, then the position of the reading in the series implicitly represents the timing). A timestamp or other timing indicator may be provided by processor hardware 151.

[0087] On-board processing may be performed in near real time, allowing for latency introduced by transfers between components and the processing itself. Alternatively, readings may be received by receiving device 30, processed there, and / or stored for later uploading and processing by remote processing device 20. Such post-processing may be performed by analyzing the most recent readings first (i.e., in reverse chronological order), so that the timing of events determined first is ejection, then ICJ, then GET, followed by ingestion. Alternatively, analysis may be in chronological order of readings. There may be other dependencies between indicators or markers in the data that constrain the order in which readings are processed.

[0088] Figure 4 shows an exemplary flow of processing tasks and data exchange in an embodiment of the post-ejection data transmission technique, in which signals from the sensors are received by on-board processor hardware 151 (also utilizing the storage capabilities of memory hardware 152) and processed in steps S100, S104a, S116a, and S107a to identify and record motility indicators onboard capsule 10 (and optionally, sensor outputs or other characteristics of the desired sensor readings or group of desired sensor readings are also processed), and the recorded motility indicators (and optionally, other characteristics, and the desired readings or group of readings) are stored in memory hardware 152 as a data transmission payload.

[0089] In the example of Figure 4, the suffix a in reference symbols S103a, S104a, S106a, and S107a represents the detection or identification of an indicator, and the corresponding unsuffixed number represents a determination that the event indicated by the corresponding numbered indicator has occurred. The timing of an ejection event is determined at S107, at which point capsule 10, or specifically Bluetooth transceiver 18, enters a beacon transmission mode and transmits data representing the detected motility indicators from steps S104a and S106a to receiving device 30. In receiving device 30 or a remote computer 20 in data communication therewith, the motility indicators from steps S104a and S106a are processed to determine the timing of a first transition event (gastroduodenal transition) at S104 and the timing of a second transition event at S106. Steps S104 and S106 are shown with dashed lines to indicate that they are not performed onboard the capsule, but rather in the receiving device or a remote computer connected thereto. The determination may be part of the same process as the detection, depending on the level of confidence required and whether there is a possibility of a false positive.

[0090] In the above example, a distinction is made between on-board processing required to identify or detect a motility event indicator and off-board processing that analyzes that indicator, and optionally contemporaneous readings from other sensors or pseudo sensors, to determine whether the indicator was caused by a motility event—for example, by calculating a confidence level and comparing that confidence level to a threshold. Note, however, that the determination may also be performed on-board the capsule. In particular, there may be on-board processing applied to the detected motility indicator (e.g., calculating the magnitude of a signal spike or signal slope), characterizing the motility indicator, comparing that characterization to a predetermined threshold, and determining that a motility event caused the motility indicator if that threshold is met.

[0091] It should be noted that if the capsule 10 is configured to operate according to the pre-ejection data transmission technique, the sensor signals are transmitted continuously by the wireless transceiver 18, and therefore steps S103a, S103, S104a, S104, S106a, S106, S107a, and S107 may all be performed outside the capsule in this case either by the receiving device 30 or by a remote processing device 20 in data communication with the receiving device 30.

[0092] A variation of the method of Figure 4 is shown in Figure 5, in which several recorded readings from S102, particularly gas sensor readings, are transferred from capsule 10 to receiving device 30 (and optionally to remote processing device 20) and processed to resolve the component gases of the gas mixture as the capsule moves through the GI tract. The gas sensor readings may be transmitted continuously (according to a pre-excretion data transmission technique) or may be transmitted during a beacon mode transmission after detection of an expulsion event in S107 (i.e., according to a post-excretion data transmission technique). The gas sensor readings transmitted for processing in S200 may be for the entire GI tract transit, or for a predetermined period on either side of one or more detected indicators, particularly gas sensor readings representing a predetermined period (e.g., 1 minute, 2 minutes, 5 minutes, 10 minutes, 15 minutes, or 30 minutes) on either side of the timing of a detected gastroduodenal transition indicator S104a and / or a detected ileocecal junction transition indicator S106a. For example, gas sensor readings from such periods may be useful in increasing the reliability of detected motility indicators and in determining whether the indicators are caused by motility events of the capsule passing through the GI tract. Furthermore, gas sensor readings from these periods may be particularly important in detecting health conditions and assessing the condition and health of the GI tract.

[0093] Monitoring Emission Events Steps S107a and S107 are performed onboard the capsule by onboard processor 151. If the temperature sensor readings monitored in S107a include a temperature reading, the change determined to be caused by an expulsion event in S107, presents the possibility of a false positive insofar as the capsule may experience a temperature drop in the stomach due to the subject's ingestion of a cold drink or other cold food. Such false positives can be avoided by the following technique. In the first technique, the timing of an ingestion event is determined onboard the capsule in S103, and the determined ingestion event starts a timer. The timer may be, for example, six hours. Step S107a, which processes the temperature sensor readings to detect changes that may be caused by expulsion, does not begin until after the timer expires. Thus, except in extremely rare circumstances, the capsule 10 has progressed through the stomach, and a temperature drop or other such change in the temperature sensor reading can be attributed to expulsion rather than the ingestion of a cold drink or food. This first technique presents difficulties, particularly in the case of gastroparesis patients, because time may not accurately predict capsule progression. In a second technique, both the detection in S106a of the ileocecal junction transition indicator and the determination of the ileocecal junction transition event S106 are performed on-board the capsule by processor 151. The step S107a of processing the temperature sensor readings to detect changes that may be caused by emptying is not initiated until after it has been determined that the ileocecal junction transition event has occurred. As a variation of the second technique, gastric emptying (i.e., the passage of capsule 10 from the stomach) may be detected on-board the capsule and used as an early boundary for the emptying monitoring in S107a. A third technique is a variation of the second technique. For example, detection of an ileocecal junction transition indicator in S106a can trigger S107a, which processes temperature sensor readings to detect changes that may be caused by expulsion, regardless of whether decision S106 is performed onboard or offboard. A variation of the third technique is to use another means to determine capsule 10's presence in the small or large intestine and trigger initiation of monitoring step S107a. For example, in a capsule including an accelerometer 19, a detected change in orientation or a metric representing the change in orientation can indicate movement through the intestine. Similarly, in a capsule including a reflectometer, a reflectometer signal falling within a predetermined range can be used to detect presence in the intestine and thereby initiate monitoring step S107a. In a further example where gas sensor signals are processed to calculate concentrations of component gases in a gas mixture entering the capsule's headspace, the calculated H2 level can fall within a predetermined range expected only in the large intestine, and thus, H2 level falling within that range triggers monitoring step S107a. In another example, the gas sensor may include a VOC gas sensor or some other means of detecting VOC concentration, and the detected VOC concentration being within a certain range is treated as a trigger to monitor step S107a.

[0094] Indicator detection and event determination A start event refers to a power-on event of the capsule that initiates the live phase in which the capsule is operational and readings are generated by the sensors and received by the receiving device, or the initiation of recording by pressing a button on the user interface of the receiving device 30 (so the capsule may already be powered on). The live phase refers to the period in which the capsule is powered on and readings are recorded (i.e., stored or relayed) by the receiving device 30.

[0095] Reference to an end event refers to the end of the live phase, which may be a power down event of the capsule that ends the live phase, or the end of the live phase due to a button press on the user interface of the receiving device 30.

[0096] In S100, an ingestible capsule 10 is provided to a target mammal 40 for ingestion. The ingestible capsule 10 is shown in any of FIGS. 1A, 1B, and 2 and includes, among other components, a housing 11, a power source 16, processor hardware 151, memory hardware 152, a temperature 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 packaging, and separation of the ingestible capsule 10 from the packaging terminates the powered-down state and causes the capsule 10 to enter a powered-on state. Entering the powered-on state may be an initiating event, or the initiating event may require the capsule to enter the powered-on state and a button press (or other interaction) on the user interface of the receiving device 30. Separation of the capsule 10 from the packaging may be the event that causes the capsule to power up and begin taking and processing readings by the capsule 10.

[0097] Ingestion is expected to occur shortly after initiation and may be detected by sensing an on-board sensor and processing the readings, or may be explicitly indicated by interaction of the subject 40 with the user interface of the receiving device 30.

[0098] At S102, recording of readings begins. Recording means saving for downstream processing and does not imply or indicate permanent storage. Particular readings may be retained or discarded after processing, depending on the configuration of the embodiment. Readings are recorded by capsule 10, for example, in memory hardware 151. Readings include readings from TCD gas sensor 131, sensor-side readings from VOC gas sensor 132a, and may also include one or more of temperature sensor readings, heater-side readings from VOC sensor 132b, readings from the reflectometer (i.e., antenna 17 and directional coupler 171), and readings from accelerometer 19. Readings may be recorded as a function of time, or time may be derivable from a position in a sequence. The temporal value assigned to each reading may be assigned at capsule 10 by, for example, microcontroller and / or wireless transmitter 18, by receiving device 30 based on the time of receipt of the respective reading from capsule 10, and / or by remote computer 20 based on the time of receipt from capsule 10 or receiving device 30. Alternatively or additionally, the temporal value assigned to each reading may be based on order of arrival. For example, if it is known that TCD gas sensor readings are taken every n seconds, then the mth reading would be timed m×n seconds (or m−1×n, depending on the implementation) after a start event that initiates the live phase. Note that the temporal values ​​may be relative to a baseline, such as capsule 10 entering a power-on state, rather than absolute values ​​based on calendar and time values.

[0099] Although the steps are shown sequentially in Figures 4 and 5, in practice, taking and recording readings S102 may be performed while processing steps S103-S107 are being performed. Optionally, some processing may be performed after recording readings S102 is completed and the capsule is ejected. As noted above, processing of the sensor signal may be performed on-board, on a receiving device such as a smartphone, or on a computer in data communication with the receiving device. Processing may be performed on the cloud. Processing may be performed on a server computing device connectable to the capsule 10 via an internet connection to the receiving device 30. The receiving device itself may perform some or all of processing steps S103-S107.

[0100] Each determination step, i.e., determining the timing of an ingestion event S103, determining the timing of a first transition event S104, determining the timing of a second transition event S106, and determining the timing of an expulsion event S107, has an associated detection step. Generally, the detection step involves processing and analyzing recorded readings to identify indicators (i.e., markers) that indicate that an event related to capsule 10 motility may have occurred. In addition to detection, each determination step involves 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 can 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 expulsion event. Gastrointestinal motility is defined by the movement of the digestive system and its contents. An indicator is a feature in a plot of recorded readings from an associated sensor or pseudo-sensor versus time. The feature may be a step, a bump, an inflection point, or a slope change. The particular indicator may be more specific, for example, a condition may be more specific than the indicator simply being a step, a bump, an inflection point, or a slope change. Embodiments may combine the detecting and determining steps into a single processing thread or processing event that accomplishes the determination.

[0101] An indicator may be detected in a reading from the first sensor. The indicator is associated with the hypothesis that the indicator was caused by an event related to 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 confirmatory indicators in those readings. For example, because hydrogen (H2) levels vary throughout the GI tract, H2 level readings may be used to increase the confidence of readings from other sensors. The H2 level reading may be used as a reference for the ileocecal junction transition indicator in S106a. The H2 level may be detected directly or may be derived, such as from a TCD gas sensor reading. 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 and an increase in the H2 level above a predetermined threshold on either side, either contemporaneously or adjacently within a predetermined time distance. Note that the H2 level is determined from the TCD gas sensor output and / or the heater-side VOC sensor output.

[0102] Similarly, the CH4 level reading may be used as a criterion for the ileocecal junction transition index. In particular, the ileocecal junction transition index may be detected by identifying an increase in the (sensor-side) VOC gas sensor output above a predetermined threshold and an increase in CH4 level above a predetermined threshold on either side, either contemporaneously or adjacently within a predetermined time distance. Note that the CH4 level may be determined from the TCD gas sensor output and / or the heater-side VOC sensor output.

[0103] An embodiment may be configured to perform detection of the ileocecal junction transition indicator S106a onboard the capsule, as its detection serves as a trigger to start monitoring the temperature sensor readings to detect changes therein in S107a.

[0104] Different subsets of the recorded readings can be analyzed to detect different indicators. The subsets can be divided according to timing and according to the sensor from which they were acquired. For example, a monitoring signal for detecting a particular indicator can be triggered by the detection of a preceding indicator. Because the indicators have a defined order, upper and / or lower limits for the timing of a particular indicator can be provided by the determined timing of the indicator(s) immediately adjacent in the defined order.

[0105] 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 acceleration sensor 19), but also components that provide readings but are not the sensor itself (these components may be referred to as pseudo-sensors), such as the directional coupler 171 and the heater side of the VOC sensor 132b. The term sensor encompasses the sensor itself and pseudo-sensors.

[0106] In S103a, the recorded readings from the temperature sensor 14a are analyzed to detect an environmental change indicative of an ingestion event. In this context, the change may be a change in environmental temperature indicated by a reading from the environmental temperature sensor 14a, or the change may be a change in environmental humidity indicated by a reading from the environmental humidity sensor 14b combined with a reading from the temperature sensor 14a. Detection may be based on readings from both the environmental temperature sensor 14a and the environmental humidity sensor 14b to increase reliability of one another or to account for unusual ambient humidity or temperature conditions that may reduce the change in one condition at the time of ingestion (i.e., ingestion on a hot day may not record a significant temperature change, but many situations record a significant humidity change). In on-board processing, the analysis may be of environmental sensor readings from a starting event (e.g., powering on the capsule 10), and the end of S103a is set by determining the timing of an ingestion event S103. That is, once it is determined that a detected change in the environmental sensor readings is caused by an ingestion event, no further processing to detect an ingestion event is performed. Detecting a change in S103a may be on a rolling basis by comparing one or more readings of interest with a predetermined number of preceding readings, with a difference exceeding a threshold (i.e., 1-2 degrees Celsius or 1 or 2% relative humidity) being a detected change. Determining the timing of an ingestion event may include comparing the temperature or humidity of the reading of interest to an expected temperature or humidity in the environment at the beginning of the GI tract of the subject mammal 40, where being within the threshold is 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 in the environment at the beginning of the GI tract of the subject mammal.

[0107] FIG. 6 illustrates exemplary relationships between sensors, algorithms, and processing results in an embodiment. Calibration data 1101, such as a lookup table for calibrating a VOC sensor operating as a TCD sensor at different ambient temperatures, is combined with the heater side of VOC sensor 132b to provide calibration parameters. Clinical data 1102, which is knowledge that changes in VOC sensor heater side readings are related to changes in H concentration in the gas mixture of interest, is fed to ICJ detection at S106 and S106a and is itself an output data entity at 1103. Similar reference numbers are used for equivalent features in other figures, and a complete description of the features in FIG. 6 is disclosed herein with reference to the other figures. Note that the intake algorithm performs steps S103 and S103a, the output 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. The algorithm may be executed on-board the processor, on a coupled receiving device, or on a remote computing device connected thereto. Step S1110 is correction of the TCD sensor readings to account for changes in environmental temperature. Step S1120 is applying an algorithm to process the accelerometer data, as described below in connection with the first technique or the angle of movement technique. Step S1130 is an exemplary processing algorithm for the reflectometer data to determine noise changes in its output signal. Other processing algorithms may be applied to the accelerometer and reflectometer data. Algorithms S1110, S1120, and S1130 may be considered pre-processing algorithms and may be executed on-board the capsule 10 to constrain the amount of data in the data transmission payload. The event timings determined by the algorithms are combined with each other to determine the event timings of one or more of ingestion, gastric emptying, ileocecal junction transition, and emptying. The event timings are then combined to determine transit time metrics including gastric emptying timing 1105, small bowel transit time 1106, colonic transit time 1107, and whole bowel transit time 1108.These are included in the motility report 1104. Data visualization 1103 is, for example, as shown in Figures 7A, 7B, 7C, 8, 9A, and 9B. GET 1105 is gastric emptying time, SITT 1106 is small intestinal transit time, CTT 1107 is colonic transit time, and WGTT 1108 is whole gut transit time. The MTT algorithm is a motility transit time algorithm.

[0108] 7A and 7B show plots of capsule readings versus time from a start event (activation) for an ingestible capsule 10 being ingested by a human subject, passing through the GI tract, and then being expelled. Ingestion and expulsion events are marked. In this example, the external temperature is significantly below the internal temperature of the human subject. The plots also show hydrogen readings, motility readings, and CO2 readings, with eating, drinking, and bowel movements events marked (these events may be automatically detected or manually reported). The specific timing assigned to ingestion and expulsion events may be determined in several ways. FIG. 7C shows environmental temperature and humidity sensor readings versus time from a start event (activation) for an ingestible capsule 10 being ingested by a human subject, passing through the GI tract, and then being expelled. Events are not marked because it is clear from FIG. 7A where ingestion and expulsion indicators are detectable in FIG. 7C. It should be noted that the specific timings assigned to the ingestion and expulsion events can be determined in a number of ways, and the processing of the readings can be performed on-board or off-board the capsule 10.

[0109] Ingestion Event Example: (For a time series) Starting from a starting point that is the initiation event, on a sequential (i.e., rolling) basis, determine the average of three adjacent environmental sensor readings, determine when that average begins or ends within a threshold distance (i.e., within 1 degree Celsius of the predicted temperature or within 1, 2, 5, or 10% of the predicted humidity) of the predicted environmental value after ingestion (i.e., the subject's average internal environment), and then determine the timing of the ingestion event to be between the three readings (e.g., the midpoint, the earliest point, or the latest point). The number 3 is exemplary; a different number of samples for the moving average can be selected, such as 5, 10, 12, or 20. Furthermore, the 1 degree Celsius tolerance is configurable, e.g., 2 degrees, 3 degrees, etc.

[0110] In the above example, the timing of the ingestion event is determined by detecting an ingestion indicator (an increase in the environmental temperature reading) in the temperature sensor readings. The timing of the ingestion event is contemporaneous with the ingestion indicator. The ingestion indicator (i.e., marker) may be detected in the antenna reflectivity signal from the directional coupler, where the indicator is a step change in the reading (this is specific to embodiments in which the antenna 17 and directional coupler 19 operate as a reflectometer from which readings are taken). The timing of the ingestion event is contemporaneous with the ingestion indicator in the reflectometer readings. As a further example, the capsule may include a relative humidity sensor 14b as a form of environmental sensor 14, and the ingestion indicator may be detected by processing the readings from the relative humidity sensor 14b. The indicator is the earliest increase in relative humidity (after the initiating event) to within a predetermined threshold of 100%, for example, plus or minus 5%, or plus or minus 1%. A further ingestion indicator is a button press of an ingestion confirmation button on the user interface of a user device, such as receiving device 30 (whether a smartphone or a device dedicated for this purpose). Embodiments may combine one or more of the disclosed ingestion indicators to determine the timing of an ingestion event, for example, by detecting two or more of the disclosed ingestion indicators within a predetermined timing window of each other, e.g., within one minute of each other, to determine the timing of an ingestion event.

[0111] Example of an ejection event: Starting from a starting point that is an ileocecal junction event determination, on a sequential (i.e., rolling) basis, determine the average of three adjacent temperature sensor readings, determine when the average is no longer within or begins to be within a threshold distance of the predicted environmental value before ejection (i.e., within 1 degree of the predicted temperature), and then determine that the timing of the ejection event is between the three readings (e.g., the midpoint, the earliest point, or the latest point). The number 3 is exemplary; a different number of samples for the moving average can be selected, such as 5, 10, 12, or 20. Furthermore, the tolerance of 1 degree Celsius is configurable, and can be, for example, 2 degrees, 3 degrees, etc. An ejection event may be confirmed or detected by an accelerometer reading indicating a free-fall event.

[0112] Note that in some cases, there may be no temperature change at the time of ingestion or excretion. The process may include a backup algorithm that runs 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 predicted temperature at the beginning of the subject mammal's GI tract. The backup algorithm looks for other ingestion or excretion indicators in recorded readings from other sensors (such as the accelerometer 19 or reflectometer, and / or other ingestion or excretion indicators described above) that may indicate an excretion or ingestion event. Alternatively, if the environmental sensor 14 further comprises an environmental humidity sensor 14b, a 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 receiving device 30). Embodiments may combine indicators in a hierarchical manner (i.e., first look for an indicator in the temperature reading, and only look for an indicator in readings from other sensors if the indicator in the temperature reading cannot be found), or may treat indicators equally (i.e., look for any two contemporaneous indicators). Other algorithms for determining timing may be implemented, for example, a confidence may be attributed to a detected indicator, and only if the confidence does not meet a threshold may readings from other sensors be processed to find contemporaneous indicators to improve the confidence. Note that in this specification humidity refers to relative humidity.

[0113] A specific ejection indicator that can be used to increase the reliability of the ejection indicator (start of decline from body temperature) in the ambient temperature reading is a button press of a defecation button on the user interface of the receiving device or a coupled smartphone.

[0114] At S104a, recorded readings after the determined timing of the ingestion event are analyzed for gastroduodenal transit index.

[0115] The first transition event is gastric emptying, or crossing the interface between the stomach and duodenum. The gastroduodenal indicator(s) may be detected in a first subset of recorded readings, the first subset being temporally defined by starting after an ingestion event. The first subset may further be constrained by sensors including readings from the TCD gas sensor 131. The first subset may further include readings from a reflectometer (i.e., antenna 17 and directional coupler 171) and / or an accelerometer 19.

[0116] The gastroduodenal transition indicator in the TCD gas sensor readings may be a spike, a step change, or an inflection point in the TCD gas sensor readings. A correction may be applied to the TCD gas sensor readings to account for changes in environmental temperature based on recorded readings from the environmental temperature sensor 14a. The correction may be applied in the detection step 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 readings. Alternatively, the gastroduodenal transition indicator may be detected in the raw readings (i.e., uncorrected readings), and then in the determining step S104a, a check is performed to determine whether the indicator is attributable to a change in environmental temperature. If not, the gastroduodenal transition indicator is determined to be caused by gastroduodenal transition by the capsule 10, or additional conditions are applied in the determination (e.g., recorded readings from another sensor are checked for a contemporaneous indicator). Alternatively, the further condition may be a threshold or some other condition applied to the detected spike, step change, or inflection point itself.

[0117] The primary physical mechanism detected in TCD gas sensor readings when detecting a gastroduodenal transition index is the mixing of hydrochloric acid in gastric juices exiting the stomach with bicarbonate in bile acids released by the pancreas. These bile acids function to neutralize the pH of the fluid, and a by-product of this reaction is CO2. In the GI tract region, ambient gases are primarily N2 and O2, with trace amounts of CO2. The amount of CO2 produced in this reaction significantly exceeds the trace amounts of CO2 present in the environment due to the swallowing of exhaled air. Therefore, it is appropriate to simply use the output of the TCD sensor without calculating CO2. In other words, when corrected for variations in environmental temperature, the TCD gas sensor reading itself provides a gastroduodenal transition index due to changes in thermal conductivity resulting from changes in CO2 concentration on 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.

[0118] Because the TCD sensor 131 is affected by the temperature of the gas mixture at the location of the capsule, a temperature correction process is necessary to account for external environmental temperature changes, i.e., changes such as drinking cold water, exercise, eating, etc. Starting from the determined timing of the ingestion event, 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.

[0119] 8A shows the recorded ambient temperature sensor 14a readings (top line of readings in the graph above) versus time and the corrected TCD gas sensor readings versus time for an example of a capsule being ingested and progressing through the GI tract. A gastroduodenal transition indicator, which may be labeled gastric emptying, 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, absolute value, or number of standard deviations) from a trendline fitted to the readings up to that point, or by its distance from the average value up to that point (the processor maintains the average value).

[0120] FIG. 8B shows gastric emptying visible in the TCD sensor output and CO2 readings. CO2 is produced when hydrochloric acid in gastric juice leaves the stomach and mixes with bicarbonate in bile acids released by the pancreas. This reaction also neutralizes the pH of the fluid. Embodiments detect this event using the temperature-corrected raw TCD sensor output rather than the calculated CO2 because it contains much less noise. The TCD sensor output is adjusted to compensate for temperature fluctuations measured by the environmental temperature sensor 14a. An algorithm is used to filter out drinking events and find the moment of CO2 increase by searching for a clear discontinuity in the TCD output between ingestion and ICJ transition.

[0121] The on-board S104a process may include detecting a gastroduodenal transition indicator in the TCD gas sensor readings in a first subset of the recorded readings as a first gastroduodenal transition indicator. Determining S104 (which may be performed off-board or on-board) may include calculating a confidence score representing the likelihood that the gastroduodenal transition indicator detected in the TCD gas sensor readings is caused by the ingestible capsule 10 passing through the gastroduodenal junction. The confidence score may be based, for example, on the height of the spike relative to a trendline, with a larger standard deviation above the trendline being given a higher confidence level. A probability distribution lookup table may be utilized to convert the spike height to a confidence score. The confidence score may be a percentage likelihood that the spike in the corrected TCD readings is caused by a first transition event, rather than being caused by noise or other random fluctuations in the corrected TCD readings.

[0122] The determination process S104 may include comparing the calculated confidence score with a threshold value; if the confidence score meets the threshold value, 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 value, 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 contemporaneously with the first gastroduodenal transition indicator in readings from a first subset other than the TCD gas sensor readings; 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.

[0123] In practice, a first gastroduodenal transition indicator that does not meet the confidence score threshold may initiate a further processing thread to detect additional gastroduodenal transition indicators to increase the reliability of the first indicator. Readings recorded contemporaneously with the first gastroduodenal transition indicator from other sensors or pseudo sensors are analyzed to identify one or more second gastroduodenal transition indicators. The temporal boundaries of the readings included in the analysis may be, for example, a predetermined temporal distance on either side of the first gastroduodenal transition indicator, e.g., 1 second, 5 seconds, 10 seconds, 20 seconds, 30 seconds, 1 minute, 2 minutes, or 5 minutes. Recorded readings from either or both the reflectometer (i.e., the antenna 17 and directional coupler 171 configured as a reflectometer that detects whether and how the dielectric of the environment surrounding the capsule 10 has changed) and the accelerometer 19 (i.e., that detects whether and how the rate of change in the capsule's orientation has changed) may be processed in an attempt to identify one or more second gastroduodenal transition indicators.

[0124] As shown in Figure 2, the circuit includes a directional coupler 171 connected in series with the antenna 17, which acts as a reflectometer. A diode detector measures the amplitude of the signal reflected from the antenna. The diode detector measurement is the reflectometer reading, which measures the energy reflected from the antenna, i.e., the energy not radiated from the antenna 17 due to impedance mismatch. The reflectometer reading measures the radiation efficiency of the antenna, which is affected by the dielectric of the material surrounding the capsule.

[0125] Readings may become noisy and / or experience baseline shifts in timing of gastroduodenal transit events, e.g., increased noise and / or baseline shifts may be detectable as transit indicators.

[0126] FIG. 9D shows reflectometer readings (labeled "Ant" for antenna) versus time (on the top plot below the two sets of axes), marked with gastric emptying events. Antenna 17 and directional coupler 171 function as a reflectometer, measuring energy reflected from the antenna, i.e., energy not radiated from the antenna. This signal fluctuates as the surrounding dielectric properties change, particularly as the capsule transitions from the hollow, fluid-filled stomach to being surrounded by the tubular tissue of the small intestine. Shifts in reflectometer readings are observed to coincide with TCD markers, enhancing its reliability as a secondary measurement.

[0127] FIG. 9A is a plot of recorded readings (or processed versions thereof) for multiple sensors and pseudo sensors within capsule 10 versus time. Gastric emptying (gastroduodenal transition) events are labeled. The top plot of the graph in FIG. 9A is the reflectometer readings (labeled with "Ant" for antenna) versus time. 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 the confidence score representing the likelihood that a spike is caused by gastroduodenal transition does not meet a threshold, the reflectometer readings are analyzed to detect baseline shifts consistent with the spikes. For example, baseline shifts may be detected by comparing, on a sequential / rolling basis, the average value of the most recent consecutive (e.g., 5, 10, or 20) readings to the average value of the number of readings preceding (or following, in the case of reverse time series processing) the most recent consecutive readings. A baseline shift may be indicated by a difference exceeding a threshold, where the threshold may be determined as an absolute value, a ratio, or relative to the standard deviation of the readings. Detecting a matching gastroduodenal indicator in the reflectometer output may be sufficient to confirm that the first gastroduodenal transition indicator is caused by gastroduodenal transition of capsule 10, thereby determining the timing of gastroduodenal transition. Alternatively, the combination of the two indicators may be evaluated via a probabilistic model to modify a confidence score and compare the modified confidence score to a threshold, where meeting the threshold determines that the first gastroduodenal transition indicator is caused by gastroduodenal transition of capsule 10, thereby determining the timing of gastroduodenal transition.

[0128] The exemplary accelerometer 19 measures rotation around three mutually orthogonal axes. Readings from the accelerometer 19 may be a vector with a component for each axis, with each component indicating either the instantaneous angular acceleration around the corresponding axis or the average acceleration around the corresponding axis over a period of time since the previous reading. Alternatively, the readings may provide a three-dimensional orientation of the capsule. Processing of the accelerometer readings may be performed onboard the capsule, in the receiving device 30, or on the remote computer 20 to generate a representation (e.g., a plot versus time) of aggregated (i.e., all three axes) accelerometer readings in which markers (i.e., gastroduodenal transition indicators) are identifiable. Such plots or representations may also be used to identify markers of other events, including emptying events. In FIG. 9A, a "travel angle" plot is generated. This is the accumulation of scalar angular displacements across all three axes versus time, with a low-pass filter applied to remove small angular displacements. Travel angle is an exemplary metric that may be periodically calculated to represent accelerometer data, and the periodically calculated values ​​are included in the data transmission payload in place of the relatively large data load of raw accelerometer data.

[0129] Figure 9C shows three mutually orthogonal rotations, marked with gastric emptying events, from which it can be seen that changes in accelerometer readings are temporally correlated with changes in corrected TCD readings (i.e., this can be used to increase the reliability of detecting gastroduodenal transition indicators in temperature-corrected TCD readings). The capsule's orientation is measured using a three-axis accelerometer to track the gravity vector with respect to the capsule's frame of reference. As the capsule exits the stomach, its orientation tends to change rapidly as it passes through the duodenum and small intestine. The "travel angle" simply accumulates the change in orientation over a 90-degree hysteresis angle. This processing technique tends to be robust to the small orientation changes experienced within the stomach and avoids some of the complexities of other approaches.

[0130] The first technique for processing accelerometer data can be called the displacement angle. Displacement angle uses vector mathematics to calculate the angle between the gravity vector and the temporal vector. The temporal vector is only attracted if this angle exceeds a predetermined threshold (currently 90 degrees). It is the accumulation of changes in the temporal vector that then causes the marker to be visualized in a discernible representation. What is generally observed is that this measurement does not change much within the stomach, since the angle between the gravity vector and the temporal vector rarely exceeds the threshold in any one direction (small back-and-forth orientation changes within the stomach are essentially ignored due to the inherent hysteresis of this algorithm), and once within the tortuous lumen of the small intestine, this measurement accumulates significantly due to larger and more continuous changes in the capsule's orientation. Thus, a step change in the accumulated displacement angle measurement is indicative of gastroduodenal transition and can be detected with the capsule onboard or offboard.

[0131] In an exemplary implementation of the movement angle, the acceleration sensor readings may provide a reading of the orientation of the ingestible capsule with respect to a reference frame fixed relative 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 through each successive accelerometer reading in time sequence to determine whether the orientation of the ingestible capsule provided by each accelerometer reading exceeds 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 match the orientation of the ingestible capsule provided by each accelerometer reading if the threshold angular displacement is met. An index such as a gastroduodenal transition index may be a step change in the rate of change of the reference orientation.

[0132] Figure 9B shows that a step change in the plot of the displacement angle is discernible within the threshold time of the spike detected in the TCD gas sensor reading. Thus, the step change in the plot of the displacement angle strengthens the hypothesis that the spike detected in the TCD gas sensor reading is due to gastroduodenal transition. There are two approximately contemporaneous gastroduodenal transition indicators, which allows the timing of one of the indicators (which may be preselected, e.g., the TCD gas sensor reading) to be determined as the timing of the transition event.

[0133] A second technique for processing accelerometer data can be called total rotation. Total rotation calculates the angle between the gravity vector and each of the capsule's x-, y-, and z-axes and represents this as a continuous measurement that can accumulate beyond 360 degrees. For example, if the capsule's x-axis is at an angle of 350 degrees and rotates an additional 20 degrees, the resulting angle is represented as 370 degrees rather than 10 degrees. This is useful when representing readings as a plot with identified markers, as it avoids the abrupt 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 approach, low-pass filtering can be applied to filter the raw data to remove sensor noise. Additionally, angles are calculated only when the raw accelerometer data provides enough data to calculate a meaningful angle. An example where this is not the case is when the values ​​of the two accelerometer axes 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 sensor noise.

[0134] The acceleration sensor readings provide readings of the orientation of the ingestible capsule with respect to a reference frame fixed relative to the gravity vector. Exemplary processing of the accelerometer readings may include: iterating over each successive accelerometer reading in a time series for each of three orthogonal axes in a fixed spatial relationship relative to the ingestible capsule that can be derived from the orientation readings, calculating the change in the orthogonal axis relative to the gravity vector from the previous accelerometer reading as a scalar value, applying a low-pass filter to the calculated change, and recording the cumulatively filtered calculated change. A marker that functions 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 cumulatively filtered calculated change.

[0135] For time series processing, in S106a, signals after the determined first transition event timing are analyzed for ileocecal junction transition index, or in some cases signals after the determined intake event timing are analyzed (e.g., if S104 is performed off-board and S106a is performed on-board).

[0136] The second transition event is the passage of the capsule 10 through the ileocecal junction. The ileocecal junction transition indicator (or indicators) may be detected in a second subset of the recorded readings, the second subset being temporally defined by the preceding determined event timing. Further, the second subset may be constrained by sensors including readings from the sensor side of the VOC gas sensor 132a.

[0137] The ileocecal junction transition indicator in the VOC gas sensor reading may be a spike, a step change, or an inflection point in the VOC gas sensor reading. A spike may be detectable by comparing the latest signal reading with the historical average, for example, a spike is defined when a predetermined number of adjacent readings exceed each other and the historical average by a predetermined threshold. An inflection point may be detectable by monitoring the slope and identifying when the second derivative (i.e., the rate of change of the slope) changes from positive to negative or vice versa. A step change may be detectable by comparing the latest signal reading with the historical average, for example, a spike is defined when a predetermined number of adjacent readings exceed the historical average by a predetermined threshold.

[0138] Determining the second transition event timing S106 applies one or more conditions to the detected ileocecal junction transition indicator to determine whether it is attributable to (i.e., predicts within a predetermined confidence level) the capsule 10 passing through the ileocecal junction. The detecting step S106a may be performed on-board and the determining step S106 may be performed off-board, or both may be performed on-board. If the detecting step S106a is performed on-board and the determining step S106 is performed off-board, the detected indicator or a characterization thereof is added to a data transmission payload, optionally along with contemporaneous readings from other sensors.

[0139] The timing of the second transition event was determined, which is the predicted transition from the small intestine to the large intestine. The change in gas environment between the small intestine and the large intestine is important because the bacterial population in the large intestine is significantly higher, which promotes the production or increase of volatile substances and causes a decrease in O2 through the fermentation of carbohydrates and proteins by the microbiota.

[0140] The VOC gas sensor output 132 from the sensor side 132a is sensitive to many different volatile analytes, with the largest responses due to H2 and O2. A significant decrease is observed on the VOC sensor as it passes through the ileocecal valve. As the capsule passes through the GI tract, the environment becomes increasingly anaerobic as O2 is consumed by bacteria. Figure 8C shows an indication of the ICJ in a plot of the VOC sensor output and the determined H2 concentration. An indication of 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 point of maximum change associated with the transition, but does not occur at the onset of the transition event. The onset of the transition event can be found by the first inflection point from the baseline in the first derivative. Thus, the indication can be detected by the most negative peak, and the timing of the event can be determined by the inflection point. The highest negative peak may be found by retrospectively analyzing VOC gas sensor readings from a predetermined time period (e.g., 1 hour, 2 hours, 4 hours, etc.) after the timing of the determined gastroduodenal transit event, or (in the case of reverse chronological processing) before the timing of the determined emptying event. Alternatively, a threshold negative peak size may be determined, and the first peak exceeding that threshold size may be detected as an indicator of the ileocecal junction transit.

[0141] As shown in Figure 8C, the determined H concentration percentage also contains an ICJ indicator, as a sudden rise in H when the capsule reaches the colon. H produced in the GI tract is a by-product of fermentation. Bacterial colonies are orders of magnitude more numerous in the colon than in the small intestine. Therefore, the determined H concentration may be used to enhance the reliability of the ileocecal junction transition indicator in the VOC sensor output. The H concentration may be directly sensed by a dedicated H gas sensor or may be derived from a gas sensor, for example, by taking TCD gas sensor readings at different operating temperature set points.

[0142] Figure 8D shows a further indicator 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 more abundant in the colon than in the small intestine. Therefore, the determined CO2 concentration may be used as an ileocecal junction transition indicator by itself or to enhance the reliability of another ileocecal junction transition indicator.

[0143] Generally, a temperature drop upon expulsion is a reliable signal. However, there are cases where no temperature drop is observed in the data. Determining the timing of the expulsion event S107 may include comparing the relative humidity of one or more readings to the predicted relative humidity at the end of the GI tract of the target mammal 40, with a change greater than (in the case of reverse time series processing) or less than (in the case of time series processing) a threshold value resulting in a determination that the capsule 10 has been expelled. Alternatively, the condition may be that a predetermined number or more consecutive readings are outside the threshold value of the predicted relative humidity at the end of the GI tract of the target mammal.

[0144] Note that in some cases, there may be no temperature change during ejection. The process may include a backup algorithm that runs if the earliest environmental temperature reading at start-up (assuming the capsule 10 has not yet been ingested) is within a threshold range of the predicted temperature at the end of the GI tract of the subject mammal (indicating that the subject is in an environment having a temperature at or near the predicted GI tract temperature). The backup algorithm looks for markers in recorded readings from other sensors that may indicate an ejection event. Because ejection is commonly associated with a physical fall, the marker may be an indicator in the accelerometer readings. Alternatively or additionally, changes in relative humidity may be detected by the backup algorithm.

[0145] The determination at S107 that an ejection event has occurred triggers a Bluetooth beacon transmission mode that transmits some or all of the data transmission payload that has not yet been transmitted. The receiving device 30 may be a dedicated receiving device or may be a general-purpose device such as a Bluetooth-enabled smartphone or tablet device.

[0146] 10 illustrates a method or process performed by ingestible capsule 10. For example, ingestible capsule 10 may include an ingestible, indigestible, biocompatible housing 11, and may further include within the housing a power source 16, sensor hardware including a temperature sensor 14a configured to output a temperature sensor signal representative of the temperature of the environment surrounding ingestible capsule 10, processor hardware 151, memory hardware 152, and a wireless data transmitter 18. Processor hardware 151 may be a CPU, processor, or microprocessor. Memory hardware 152 is a chip configured to store data. Memory hardware 152 and processor hardware 151 may be provided as part of a single integrated microcontroller chip.

[0147] The memory hardware 152 may store software, computer programs, or processing instructions that, when executed by the processor hardware 151, cause the processor hardware to perform the methods or processes illustrated in Figure 10. The software, computer programs, or processing instructions stored by the memory hardware may also cause the processor hardware 151 to perform other functions attributed to the processor hardware 151 elsewhere in this disclosure. The memory hardware 152 is an example of a computer-readable medium.

[0148] In S100, capsule 10 is ingested by target mammal 40. Target mammal 40 may be a human. After ingestion, in S102, capsule 10 is configured to collect data while passing through the GI tract of target mammal 40. Data is collected in capsule 10, particularly in memory hardware 152, by processor hardware 151 processing signals received from one or more sensors that form the sensor hardware of capsule 10.

[0149] In S102a, the processor hardware 151 is configured to receive signals output by the sensor hardware, process the received signals, and store some or all of the processed signals, or data extracted therefrom, in the memory hardware as a data transmission payload. The data transmission payload may include metrics representing signals from a single sensor or from multiple sensors. The data transmission payload may include one or more motility or diagnostic indicators, as described elsewhere in this disclosure. The data transmission payload may include a report of an event or series of events determined to have occurred based on one or more identified motility markers. The data transmission payload may also include information such as the remaining capacity of the power source 16.

[0150] In S107a, processor hardware 151 is configured to receive and monitor the temperature sensor signal to identify when the temperature sensor signal indicates that ingestible capsule 10 is no longer present within the GI tract of subject mammal 40. For example, processor hardware 151 may compare the temperature represented by the temperature sensor signal to determine when the temperature is no longer within a predetermined range of the GI tract of subject mammal 40. In particular, monitoring may begin following a determination by ingestible capsule 10 that it has exceeded the stomach of subject mammal 40, i.e., that a gastroduodenal transition event has occurred.

[0151] In S107, the processor hardware 151 is configured to determine that an emptying event has occurred. For example, the identifying step S107a may identify a drop in temperature represented by the temperature sensor signal, and in S107, the processor hardware 151 checks whether a gastroduodenal transition has already been determined to have occurred; if not, it determines that emptying has not occurred and continues with the monitoring and identifying step S107a; and if so, it determines that the identified drop in temperature represents an emptying event and that emptying has occurred. The capsule 10 may be configured in such a way that detecting a series of readings as an indication of capsule emptying necessarily also determines that emptying has occurred, and thus the timing of the indicator is the timing of emptying. In other words, the determining step S107 may be integrated into the processing of the detecting step S107a.

[0152] At S108, the microcontroller or other processor hardware 151 is configured to change one or more settings of the wireless data transmitter in response to determining the occurrence of an ejection event to cause the wireless data transmitter to begin, resume, or increase the rate of wireless transmission of the data transmission payload from the capsule. For example, the wireless data transmitter 18 may be a Bluetooth transceiver. For example, changing the setting may be to increase the rate of data transmission. Changing the setting may be to reconnect with a receiving device 30 external to the target mammal 40. The receiving device 30 may be a Bluetooth-enabled communication device such as a smartphone or tablet computer. Changing the setting may cause the wireless data transmitter 18 to transmit a report to the receiving device 30 in a broadcast or query mode that the ejection event has been determined to have occurred, and to wirelessly connect to the receiving device 30 to transmit the remainder of the data transmission payload, or to wirelessly reconnect following an initial connection prior to ingestion of the ingestible capsule.

[0153] Changing the transmission settings after detecting an emission may include increasing the transmission power. The rationale is as follows. After ejection, there is a final opportunity to acquire data from the capsule 10 before it is swept away. A complete data set is available, allowing for the calculation of all movement metrics as well as other items such as H2 peak time and total H2 (area under the curve) (potentially resulting in a smaller data transmission payload). · The absence of the capsule 10 remaining inside the body means that the radio power can be increased without exceeding the safety limit of the Specific Absorption Rate (SAR). The intestinal environment is likely to be more consistent than the patient's BMI and compliance.

[0154] 11 illustrates a method or process performed by ingestible capsule 10. For example, ingestible capsule 10 may include ingestible, indigestible, biocompatible housing 11, which may further include, within the housing, a power source 16, sensor hardware, processor hardware 151, memory hardware 152, and a Bluetooth transceiver 18 or wireless data transmitter 18 configured to transmit over a communication protocol other than Bluetooth, such as Wi-Fi. Processor hardware 151 may be a CPU, processor, or microprocessor. Memory hardware 152 is a chip configured to store data. Memory hardware 152 and processor hardware 151 may be provided as part of a single integrated microcontroller chip.

[0155] The memory hardware 152 may store software, computer programs, or processing instructions that, when executed by the processor hardware 151, cause the processor hardware to perform the methods or processes illustrated in Figure 11. The software, computer programs, or processing instructions stored by the memory hardware may also cause the processor hardware 151 to perform other functions attributed to the processor hardware 151 elsewhere in this disclosure. The memory hardware 152 is an example of a computer-readable medium.

[0156] In S100, capsule 10 is ingested by target mammal 40. Target mammal 40 may be a human. After ingestion, in S102, capsule 10 is configured to collect data while passing through the GI tract of target mammal 40. Data is collected in capsule 10, particularly in memory hardware 152, by processor hardware 151 processing signals received from one or more sensors that form the sensor hardware of capsule 10.

[0157] Processor hardware 151 executes one or both of steps S1021 and S102a. When both processes are executed, it may be that data generated by step S1021 is processed in step S102a, or data generated by step S102a is processed in step S1021, as indicated by the double arrow in FIG. 11 .

[0158] Steps S1021 and S102a represent different data processing functions that may be performed by processor hardware 151. Processor hardware 151 is configured to receive signals output by sensor hardware (i.e., signals or readings from one or more sensors) and process the received signals by S1021, which calculates a metric representative of the received signal(s), or by S102a, which identifies a motility or diagnostic indicator within the received signals. The metric may be a maximum, minimum, or local maximum or minimum bounded by one or more determined motility events. The metric may be calculated according to a calibration table or calibration parameters. A motility or diagnostic indicator refers to a predetermined pattern, range of values, spike, step change, inflection point, local maximum or minimum, predetermined change, or sequence of changes in the signal(s) output by one or more sensors of the sensor hardware. A motility indicator indicates that a motility event has occurred. Motility events include one or more of ingestion, emptiness, gastroduodenal transition, and ileocecal junction transition. A diagnostic indicator indicates that the subject mammal has a particular medical abnormality, e.g., a condition or disease. Examples include gastroparesis and small intestinal bacterial overgrowth. An indicator refers to a signature or other distinctive feature of a signal or reading from a sensor, whether motility or diagnostic. Further processing, such as comparison to a threshold or some other form of reliability testing, may be required (and performed by processor hardware 151 or in subsequent off-board processing) to determine whether the indicator is caused by a motility event or a medical condition, as appropriate.

[0159] In step S102a, capsule 10 stores the processing results as all or part of a data transmission payload in memory hardware 152, or optionally in a buffer in the Bluetooth transceiver. In S109, the data transmission payload is transmitted from Bluetooth transceiver 18 to target mammal 40 and to receiving device 30 external to capsule 10. At least a portion of the data transmission payload is transmitted while capsule 10 is still within the GI tract of target mammal 40. Optionally, a further portion may be transmitted after ejection, as illustrated in steps S107 and S108 of FIG. 10 and described in further detail above.

[0160] 12 illustrates a method or process performed by ingestible capsule 10. For example, ingestible capsule 10 may include ingestible, indigestible, biocompatible housing 11, which may further include, within the housing, a power source 16, sensor hardware, processor hardware 151, memory hardware 152, and a Bluetooth transceiver 18 or wireless data transmitter 18 configured to transmit over a communication protocol other than Bluetooth, such as Wi-Fi. Processor hardware 151 may be a CPU, processor, or microprocessor. Memory hardware 152 is a chip configured to store data. Memory hardware 152 and processor hardware 151 may be provided as part of a single integrated microcontroller chip.

[0161] The memory hardware 152 may store software, computer programs, or processing instructions that, when executed by the processor hardware 151, cause the processor hardware to perform the methods or processes illustrated in Figure 11. The software, computer programs, or processing instructions stored by the memory hardware may also cause the processor hardware 151 to perform other functions attributed to the processor hardware 151 elsewhere in this disclosure. The memory hardware 152 is an example of a computer-readable medium.

[0162] In S100, capsule 10 is ingested by target mammal 40. Target mammal 40 may be a human. After ingestion, in S102, capsule 10 is configured to collect data while passing through the GI tract of target mammal 40. Data is collected in capsule 10, particularly in memory hardware 152, by processor hardware 151 processing signals received from one or more sensors that form the sensor hardware of capsule 10.

[0163] The processor hardware 151 performs steps S102 and S102a as described above.

[0164] Steps S1200, S1201, and S1202 represent different data processing functions that may be performed by processor hardware 151. Processor hardware 151 is configured to receive signals (signals or readings from one or more sensors) output by sensor hardware and process the received signals, for example, by calculating a metric representative of the received signal(s) and / or by identifying a motility or diagnostic indicator within the received signal(s). The metric may be a maximum, minimum, or local maximum or minimum bounded by one or more determined motility events. The metric may be calculated according to a calibration table or calibration parameters. A motility or diagnostic indicator refers to a predetermined pattern, range of values, spike, step change, inflection point, local maximum or minimum, predetermined change, or sequence of changes in the signal(s) output by one or more sensors of the sensor hardware. The motility indicator indicates that a motility event has occurred. The motility event includes one or more of ingestion, emptiness, gastroduodenal transition, and ileocecal junction transition. A diagnostic indicator indicates that the subject mammal has a particular condition, e.g., a symptom or disease. Examples include gastroparesis and small intestinal bacterial overgrowth. An indicator refers to a signature or other distinctive feature of a signal or reading from a sensor, whether motility or diagnostic. Further processing, such as a comparison to a threshold or some other form of reliability testing, may be required (and performed by processor hardware 151 or in subsequent off-board processing) as appropriate in S1201 to determine whether the indicator is caused by a motility event or a medical condition.

[0165] In S1202, in response to determining the occurrence of a transmission trigger event in S1201, a setting of the wireless data transmitter is changed. For example, the wireless data transmitter 18 may be a Bluetooth transceiver. For example, changing the setting may be to increase the rate of data transmission. Changing the setting may be to reconnect with a receiving device 30 external to the target mammal 40. The receiving device 30 may be a Bluetooth-enabled communication device such as a smartphone or tablet computer. Changing the setting may cause the wireless data transmitter 18 to transmit a report to the receiving device 30 in a broadcast mode or a query mode that an ejection event has been determined to have occurred, and to wirelessly connect to the receiving device 30 to transmit the remainder of the data transmission payload, or to wirelessly reconnect following an initial connection prior to ingestion of the ingestible capsule.

[0166] Changing transmission settings after detecting an emission may include increasing transmit power, increasing signal strength, or otherwise actively changing settings to increase signal power.

Claims

1. An ingestible capsule comprising: an ingestible, indigestible, biocompatible housing; Within the housing: Power supply and sensor hardware including a temperature sensor configured to output a temperature sensor signal representative of a temperature of an environment surrounding the ingestible capsule; processor hardware; memory hardware; a wireless data transmitter; the processor hardware is configured to receive signals output by the sensor hardware, process the received signals, and store some or all of the processed signals, or data extracted therefrom, in the memory hardware as a data transmission payload while the ingestible capsule passes through the GI tract of the subject mammal; The ingestible capsule, wherein the processor hardware is configured to receive and monitor the temperature sensor signal to identify when the temperature sensor signal indicates that the ingestible capsule is no longer present in the GI tract of the target mammal, determine in response to the identification that an expulsion event has occurred, and modify one or more settings of the wireless data transmitter in response to determining the occurrence of the expulsion event to initiate, resume, increase wireless transmission power, or increase wireless transmission rate of the data transmission payload from the ingestible capsule by the wireless data transmitter.

2. 10. The ingestible capsule of claim 1, wherein the data transmission payload transmitted from the capsule in response to determining the occurrence of the ejection event includes a report that the occurrence of the ejection event has been determined.

3. 3. The ingestible capsule of claim 2, wherein changing the setting causes the wireless data transceiver to transmit the report that the ejection event has been determined to have occurred to a receiving device in a broadcast or query mode, and to wirelessly connect to the receiving device, or wirelessly reconnect following an initial connection before ingestion of the ingestible capsule, to transmit the remainder of the data transmission payload.

4. 2. The ingestible capsule of claim 1, wherein the sensor hardware includes one or more gas sensors, wherein the signals output by the sensor hardware and processed by the processor hardware include gas sensor signals output by the one or more gas sensors, and wherein the data transmission payload includes the processed gas sensor signals or data extracted therefrom.

5. the one or more gas sensors one or more spectrophotometers; one or more surface acoustic wave sensors; one or more bulk acoustic resonator arrays; one or more VOC gas sensors; and one or more TCD gas sensors; 5. The ingestible capsule of claim 4, wherein each of the one or more gas sensors is configured to generate a constituent gas sensor signal that forms a portion of the gas sensor signal.

6. 6. The ingestible capsule of claim 5, wherein processing the received gas sensor signal comprises identifying one or more motility event indicators in the received gas sensor signal and storing a representation of the identified motility indicators in the memory hardware as a data transmission payload.

7. 7. The ingestible capsule of claim 6, wherein identifying the one or more motility event indicators comprises monitoring the gas sensor signal received from each of the one or more gas sensors on a rolling basis over a proximate time period of a predetermined time period and identifying a spike, step change, or inflection point in the gas sensor signal as the motility indicator.

8. 8. The ingestible capsule of claim 7, wherein the one or more gas sensors comprise one or more of a VOC gas sensor and a TCD gas sensor, and the gas sensor signal accordingly comprises one or more of a VOC gas sensor signal and a TCD gas sensor signal.

9. the sensor hardware comprising: accelerometer, a reflectometer formed by an antenna connected in series with a directional coupler, the antenna being an antenna of the data transmitter, the antenna being controlled by the processor to transmit an intermittent or continuous signal from which a reflectometer signal can be obtained; In addition to identifying the motility event indicators in the gas sensor signal, the processor hardware: associated with the motility event indicator in the data transmission payload, a gas sensor different from the gas sensor providing the signal from which the motility event indicator is detected; the accelerometer; or 10. The ingestible capsule of claim 6 or any other preceding claim, configured to store a representation of signals received contemporaneously with the motility event indicator from one or more sensors within the housing, including the reflectometer.

10. The representation of the signal is recording said signal; recording said signal downsampled by retaining only one out of every multiple readings; a dimensionality-reduced version of said signal; recording the identification markers identified by processing the signal; 9. The ingestible capsule of claim 8, wherein a characteristic value of the signal is obtained by processing the signal, the characteristic value being one or more of the following characteristic values: an average value, a rate of change, a maximum value, a local maximum value, a minimum value, or a local minimum value.

11. 10. The ingestible capsule of any preceding claim, wherein the ingestible capsule further comprises an accelerometer, and wherein, during passage through the GI tract, the processor hardware is configured to receive accelerometer signals output by the accelerometer, process the received accelerometer signals, and store the processed accelerometer signals, or a representation thereof, in the memory hardware as a data transmission payload.

12. 12. The ingestible capsule of claim 11, wherein, in response to identifying that the temperature represented by the temperature sensor signal has fallen below a predetermined temperature range of the target mammal, to determine the occurrence of the ejection event, the processor hardware is configured to determine whether the received accelerometer signal indicates that the ingestible capsule is experiencing a free fall event, and if it is determined that the received accelerometer signal indicates that the ingestible capsule is experiencing a free fall event, the processor hardware is configured to determine that the ejection event has occurred.

13. 12. The ingestible capsule of claim 10 or 11, wherein the processor hardware is configured to process the temperature sensor signal and store the processed temperature signal or data extracted therefrom in the memory hardware as a data transmission payload.

14. 10. An ingestible capsule according to any preceding claim, wherein the wireless data transmitter is a Bluetooth transceiver.

15. 15. The ingestible capsule of claim 14, wherein the wireless data transmitter is a Bluetooth transceiver configured to operate according to a Bluetooth Low Energy coded PHY transmission protocol.

16. 16. An ingestible capsule according to any of claims 14 to 15, wherein the Bluetooth transceiver comprises an integrated radio and microcontroller.

17. 17. The ingestible capsule of claim 14, wherein in response to determining the occurrence of the ejection event, modifying one or more settings of the wireless data transmitter comprises controlling the Bluetooth transceiver to transmit the data transmission payload stored in the memory hardware by broadcasting pending transmission data from the data transmission payload to the receiving device, regardless of whether the receiving device is paired with the Bluetooth transceiver.

18. and, prior to determining the occurrence of the ejection event, the Bluetooth transceiver pairs with a Bluetooth compatible device external to the target mammal, and transmits to the paired device: signal(s) from said sensor hardware; one or more motility indicators identified by processing signals from the sensor hardware; one or more diagnostic indicators identified by processing signals from the sensor hardware; information indicating the remaining capacity of the power source; a metric calculated by processing a signal from a single sensor in the sensor hardware or by combining signals from multiple sensors in the sensor hardware; a calculated gas concentration level of one or more component gases of a gas mixture present in the GI tract, calculated by reference to predetermined calibration parameters stored in the memory hardware; 18. The ingestible capsule of any of claims 14 to 17, wherein in the course of determining the occurrence of the ejection event, the processor hardware is configured to change settings of the Bluetooth transceiver to forward the data transmission payload to the same Bluetooth compatible device either by continuing the existing pairing, by re-pairing, or in the absence of pairing.

19. 10. The ingestible capsule of any preceding claim, wherein the ingestible capsule is configured to operate in an ingestion detection mode in which, after an initiation event, the temperature sensor is activated, and the processor hardware is operative to monitor the temperature sensor signal to identify when the temperature represented by the temperature sensor signal reaches a predetermined internal temperature range of the target mammal, determine the occurrence of an ingestion event, record the ingestion event as a data transmission payload in the memory hardware, and begin collecting data during the transit through the GI tract.

20. An ingestible capsule comprising: an ingestible, indigestible, biocompatible housing; Within the housing: Power supply and Sensor hardware; processor hardware; memory hardware; a Bluetooth transceiver; the processor hardware is configured to: receive signals output by the sensor hardware while the ingestible capsule passes through the GI tract of the subject mammal; process the received signals by calculating a metric representative of the received signals or identifying a motility or diagnostic indicator in the received signals; and store the calculated metric or data representative of the motility or diagnostic indicator in the memory hardware as a data transmission payload, wherein the motility indicator and / or the diagnostic indicator is a predetermined pattern, range of values, spike, step change, inflection point, local maximum or minimum, predetermined change, or sequence of change in the signal(s) output by one or more sensors of the sensor hardware; The ingestible capsule, wherein the Bluetooth transceiver is configured to transmit the data transmission payload from the ingestible capsule to a paired receiving device during the transit through the GI tract of the subject mammal.

21. the sensor hardware including a temperature sensor configured to output a temperature sensor signal representative of a temperature of an environment surrounding the ingestible capsule; 21. The ingestible capsule of claim 20, wherein the processor hardware is configured to receive and monitor the temperature sensor signal to identify when the temperature sensor signal indicates that the ingestible capsule is no longer present in the GI tract of the target mammal, determine in response to the identification that an expulsion event has occurred, and modify one or more settings of the Bluetooth transceiver to resume wireless transmission of the data transmission payload from the capsule by the Bluetooth transceiver or increase the wireless transmission rate in response to determining the occurrence of the expulsion event.

22. 22. The ingestible capsule of claim 21, wherein the data transmission payload transmitted from the capsule in response to determining the occurrence of the ejection event includes a report that the occurrence of the ejection event has been determined.

23. 23. The ingestible capsule of claim 22, wherein the wireless data transceiver is configured to transmit the report of the determined occurrence of the ejection event to a receiving device in a broadcast or query mode, and to wirelessly connect to the receiving device, or wirelessly reconnect following an initial connection prior to ingestion of the ingestible capsule, to transmit the remainder of the data transmission payload.

24. 24. The ingestible capsule of claim 20, wherein the sensor hardware comprises one or more gas sensors, the signals output by the sensor hardware and processed by the processor hardware comprise gas sensor signals comprising constituent gas sensor signals output by each of the one or more individual gas sensors, and the data transmission payload comprises a metric representative of the gas sensor signals, or a motility indicator in the gas sensor signals, or a diagnostic indicator in the gas sensor signals.

25. the one or more gas sensors one or more spectrophotometers; one or more surface acoustic wave sensors; one or more H2 gas sensors; one or more CH4 gas sensors; one or more bulk acoustic resonator arrays; one or more VOC gas sensors; and one or more TCD gas sensors; 25. The ingestible capsule of any of claims 20 to 24, wherein each of the one or more gas sensors is configured to generate a constituent gas sensor signal that forms part of the gas sensor signal.

26. the sensor hardware comprising: further comprising an accelerometer; 26. The ingestible capsule of any of claims 20-25, wherein the signals output by the sensor hardware and processed by the processor hardware include accelerometer signals output by the accelerometer, and the data transmission payload includes metrics representative of the accelerometer signals or mobility or diagnostic indicators in the accelerometer signals.

27. a reflectometer formed by an antenna connected in series with a directional coupler, said antenna being an antenna of said Bluetooth transceiver, said antenna being controlled by said processor to transmit said data transmission payload via an intermittent or continuous signal from which a reflectometer signal can be obtained; 27. The ingestible capsule of any of claims 20-26, wherein the signal output by the sensor hardware and processed by the processor hardware comprises the reflectometer signal obtained from the reflectometer, and the data transmission payload comprises a metric representative of the reflectometer signal or a motility or diagnostic indicator in the reflectometer signal.

28. 28. The ingestible capsule of any of claims 20-27, wherein the ingestible capsule further comprises an accelerometer, and wherein during transit through the GI tract, the processor hardware is configured to receive accelerometer signals output by the accelerometer, process the received accelerometer signals by calculating metrics representative of the received accelerometer signals, and store the calculated metrics in the memory hardware as a data transmission payload.

29. 29. The ingestible capsule of any of claims 20-28, wherein the sensor hardware further comprises an accelerometer, and in response to identifying that the temperature represented by the temperature sensor signal has fallen below a predetermined temperature range of the target mammal, to determine the occurrence of the ejection event, the processor hardware is configured to determine whether an accelerometer signal received from the accelerometer indicates that the ingestible capsule is experiencing a free fall event, and if it is determined that the received accelerometer signal indicates that the ingestible capsule is experiencing a free fall event, the processor hardware is configured to determine that the ejection event has occurred.

30. 30. The ingestible capsule of any of claims 20 to 29, wherein the processor hardware is configured to process the temperature sensor signal and store the processed temperature signal or data extracted therefrom in the memory hardware as a data transmission payload.

31. 31. The ingestible capsule of any of claims 20 to 30, wherein the Bluetooth transceiver is configured to operate according to a Bluetooth Low Energy coded PHY transmission protocol.

32. 32. An ingestible capsule according to any of claims 20 to 31, wherein the Bluetooth transceiver comprises an integrated radio and microcontroller.

33. 33. The ingestible capsule of any of claims 20-32, wherein in response to determining the occurrence of the ejection event, modifying one or more settings of the wireless data transmitter comprises controlling the Bluetooth transceiver to transmit the data transmission payload stored in the memory hardware by broadcasting pending transmission data from the data transmission payload to the receiving device, regardless of whether the receiving device is paired with the Bluetooth transceiver.

34. and, prior to determining the occurrence of the ejection event, the Bluetooth transceiver pairs with a Bluetooth compatible device external to the target mammal, and transmits to the paired device: signal(s) from said sensor hardware; one or more motility indicators identified by processing signals from the sensor hardware; one or more diagnostic indicators identified by processing signals from the sensor hardware; information indicating the remaining capacity of the power source; a metric calculated by processing a signal from a single sensor in the sensor hardware or by combining signals from multiple sensors in the sensor hardware; a calculated gas concentration level of one or more component gases of a gas mixture present in the GI tract, calculated by reference to predetermined calibration parameters stored in the memory hardware; 34. The ingestible capsule of any of claims 20 to 33, wherein in the course of determining the occurrence of the ejection event, the processor hardware is configured to change settings of the Bluetooth transceiver to forward the data transmission payload to the same Bluetooth compatible device either by continuing the existing pairing, by re-pairing, or in the absence of pairing.

35. 35. The ingestible capsule of claim 34, wherein changing the settings of the Bluetooth transceiver includes increasing transmission power.

36. 36. The ingestible capsule of any of claims 20-35, wherein the ingestible capsule is configured to operate in an ingestion detection mode in which the temperature sensor is activated after an initiation event, and wherein the processor hardware is operative to monitor the temperature sensor signal to identify when the temperature represented by the temperature sensor signal reaches a predetermined internal temperature range of the subject mammal, and in response to said identification, determine that an ingestion event has occurred, record the ingestion event as a data transmission payload in the memory hardware, and begin collecting data during the transit through the GI tract.

37. An ingestible capsule comprising: an ingestible, indigestible, biocompatible housing; Within the housing: Power supply and Sensor hardware; processor hardware; memory hardware; a wireless data transmitter; the ingestible capsule is configured to collect data as it passes through the GI tract of the subject mammal after ingestion by the subject mammal, and during that passage, the processor hardware is configured to receive signals output by the sensor hardware, process the received signals, and store some or all of the processed signals, or data extracted therefrom, in the memory hardware as a data transmission payload; The ingestible capsule, wherein the processor hardware is configured to receive and monitor the signal output by the sensor hardware to identify a transmission trigger event indicator, determine in response to the identification that a transmission trigger event has occurred, and modify one or more settings of the wireless data transmitter in response to determining the occurrence of the transmission trigger event to initiate, resume, increase wireless transmission power, or increase wireless transmission rate of the data transmission payload from the capsule by the wireless data transmitter.

38. the transmission trigger event indicator is a motility event indicator associated with ingestion of the ingestible capsule, gastroduodenal transit of the ingestible capsule, ileocecal junction transit of the ingestible capsule, or expulsion of the ingestible capsule; or 38. The ingestible capsule of claim 37, wherein the transmission trigger event indicator is a diagnostic indicator associated with a clinical diagnosis of a medical condition.

39. 1. A method in an ingestible capsule adapted for ingestion by a target mammal, said ingestible capsule comprising: an ingestible, indigestible, biocompatible housing; Within the housing: Power supply and sensor hardware including a temperature sensor configured to output a temperature sensor signal representative of a temperature of an environment surrounding the ingestible capsule; processor hardware; memory hardware; a wireless data transmitter; The method comprises: collecting data in the ingestible capsule during transit through the GI tract of the subject mammal after ingestion of the ingestible capsule by the subject mammal; receiving signals output by the sensor hardware during the transit through the GI tract of the target mammal, processing the received signals, and storing some or all of the processed signals, or data extracted therefrom, in the memory hardware as a data transmission payload; The method includes, in the processor hardware, receiving and monitoring the temperature sensor signal to identify when the temperature sensor signal indicates that the ingestible capsule is no longer present in the GI tract of the target mammal; determining, in response to the identification, the occurrence of an expulsion event; and, in response to determining the occurrence of the expulsion event, altering one or more settings of the wireless data transmitter to initiate, resume, increase wireless transmission power, or increase wireless transmission rate of the data transmission payload from the ingestible capsule by the wireless data transmitter.

40. 40. The method of claim 39, wherein the data transmission payload transmitted from the capsule in response to determining the occurrence of the ejection event includes a report that the occurrence of the ejection event has been determined.

41. 41. The method of claim 40, wherein after changing the setting, the method includes transmitting, in the wireless data transceiver, the report that the occurrence of the ejection event has been determined to a receiving device in a broadcast or query mode, and wirelessly connecting to the receiving device or wirelessly reconnecting following an initial connection before ingestion of the ingestible capsule to transmit the remainder of the data transmission payload.

42. 40. The method of claim 39, wherein the sensor hardware includes one or more gas sensors, wherein the signals output by the sensor hardware and processed by the processor hardware include gas sensor signals output by the one or more gas sensors, and wherein the data transmission payload includes the processed gas sensor signals or data extracted therefrom.

43. the one or more gas sensors one or more spectrophotometers; one or more surface acoustic wave sensors; one or more bulk acoustic resonator arrays; one or more VOC gas sensors; and one or more TCD gas sensors; 43. The method of claim 42, wherein the method includes each of the one or more gas sensors generating a constituent gas sensor signal that forms a portion of the gas sensor signal during transit through the GI tract of the subject mammal.

44. 44. The method of claim 43, wherein the method includes processing the received gas sensor signal, the processing including identifying one or more motility event indicators in the received gas sensor signal and storing a representation of the identified motility indicators in the memory hardware as a data transmission payload.

45. 45. The method of claim 44, wherein identifying the one or more motility event indicators comprises monitoring the gas sensor signal received from each of the one or more gas sensors on a rolling basis over a period of time immediately preceding a predetermined time period and identifying a spike, step change, or inflection point in the gas sensor signal as the motility indicator.

46. 46. ​​The method of claim 45, wherein the one or more gas sensors comprise one or more of a VOC gas sensor and a TCD gas sensor, and the gas sensor signal accordingly comprises one or more of a VOC gas sensor signal and a TCD gas sensor signal.

47. the sensor hardware comprising: accelerometer, a reflectometer formed by an antenna connected in series with a directional coupler, the antenna being an antenna of the data transmitter, the antenna being controlled by the processor to transmit an intermittent or continuous signal from which a reflectometer signal can be obtained; In addition to identifying the motility event indicators in the gas sensor signal, the method further comprises: associated with the motility event indicator in the data transmission payload, a gas sensor different from the gas sensor providing the signal from which the motility event indicator is detected; the accelerometer; or 46. ​​A method according to claim 45 or any other of the preceding claims, comprising storing a representation of signals received contemporaneously with the motility event indicator from one or more sensors within the housing of the reflectometer.

48. The representation of the signal is recording said signal; recording said signal downsampled by retaining only one out of every multiple readings; a dimensionality-reduced version of said signal; recording the identification markers identified by processing the signal; 48. The method of claim 47, wherein the characteristic values ​​of the signal obtained by processing the signal are one or more of the following characteristic values: an average value, a rate of change, a maximum value, a local maximum value, a minimum value, or a local minimum value.

49. 49. The method of any of claims 39-48, wherein the ingestible capsule further comprises an accelerometer, and during transit through the GI tract, the method further comprising receiving, in the processor hardware, an accelerometer signal output by the accelerometer, processing the received accelerometer signal, and storing the processed accelerometer signal, or a representation thereof, in the memory hardware as a data transmission payload.

50. 50. The method of claim 49, wherein in response to identifying that the temperature represented by the temperature sensor signal has fallen below a predetermined temperature range of the target mammal, to determine the occurrence of the ejection event, the method further comprises, in the processor hardware, determining whether the received accelerometer signal indicates that the ingestible capsule is experiencing a free fall event, and determining that the ejection event has occurred if it is determined that the received accelerometer signal indicates that the ingestible capsule is experiencing a free fall event.

51. 51. The method of claim 49 or 50, wherein the method further comprises processing the temperature sensor signal in the processor hardware and storing the processed temperature signal or data extracted therefrom in the memory hardware as a data transmission payload.

52. 10. A method according to any preceding claim, wherein the wireless data transmitter is a Bluetooth transceiver.

53. 53. The method of claim 52, wherein the wireless data transmitter is a Bluetooth transceiver that transmits data comprising the data transmission payload according to a Bluetooth Low Energy coded PHY transmission protocol.

54. A method according to any one of claims 52 to 53, wherein the Bluetooth transceiver comprises an integrated radio and microcontroller.

55. 55. The method of any of claims 52 to 54, wherein modifying one or more settings of the wireless data transmitter in response to determining the occurrence of the ejection event comprises controlling the Bluetooth transceiver to transmit the data transmission payload stored in the memory hardware by broadcasting pending transmission data from the data transmission payload to the receiving device, regardless of whether the receiving device is paired with the Bluetooth transceiver.

56. The method comprises: and, prior to determining the occurrence of the ejection event, the Bluetooth transceiver pairs with a Bluetooth compatible device external to the target mammal, and transmits to the paired device: signal(s) from said sensor hardware; one or more motility indicators identified by processing signals from the sensor hardware; one or more diagnostic indicators identified by processing signals from the sensor hardware; information indicating the remaining capacity of the power source; a metric calculated by processing a signal from a single sensor in the sensor hardware or by combining signals from multiple sensors in the sensor hardware; a calculated gas concentration level of one or more component gases of the gas mixture present in the GI tract, calculated by referencing predetermined calibration parameters stored in the memory hardware; 56. A method as claimed in any one of claims 52 to 55, wherein in the course of determining the occurrence of the ejection event, the method includes changing a setting in the processor hardware of the Bluetooth transceiver to forward the data transmission payload to the same Bluetooth compatible device either by continuing the existing pairing, by re-pairing, or in the absence of pairing.

57. 10. The method of any preceding claim, wherein the method further comprises, after an initiation event, operating in an ingestion detection mode in which the temperature sensor is active; monitoring in the processor hardware the temperature sensor signal to identify when the temperature represented by the temperature sensor signal reaches a predetermined internal temperature range of the subject mammal; and, in response to said identification, determining the occurrence of the ingestion event; recording the ingestion event as a data transmission payload in the memory hardware; and commencing the collecting of data during the transit through the GI tract.

58. 1. A method in an ingestible capsule, the ingestible capsule comprising: an ingestible, indigestible, biocompatible housing; Within the housing: Power supply and Sensor hardware; processor hardware; memory hardware; a Bluetooth transceiver; the method comprising, after ingestion of the ingestible capsule by the subject mammal, receiving, in the processor hardware, signals output by the sensor hardware; processing the received signals by calculating a metric representative of the received signals or identifying a motility or diagnostic indicator in the received signals; and storing, in the memory hardware, the calculated metric or data representative of the motility or diagnostic indicator as a data transmission payload, wherein the motility and / or diagnostic indicator is a predetermined pattern, range of values, spike, step change, inflection point, local maximum or minimum, predetermined change, or sequence of change in the signal(s) output by one or more sensors of the sensor hardware; transmitting, in the Bluetooth transceiver, the data transmission payload from the ingestible capsule to a paired receiving device during the transit through the GI tract of the target mammal.

59. the sensor hardware includes a temperature sensor, the method including outputting, at the temperature sensor, a temperature sensor signal representative of a temperature of an environment surrounding the ingestible capsule; 59. The method of claim 58, wherein the method further comprises: in the processor hardware, receiving and monitoring the temperature sensor signal to identify when the temperature sensor signal indicates that the ingestible capsule is no longer present in the GI tract of the target mammal; determining, in response to the identification, the occurrence of an expulsion event; and, in response to determining the occurrence of the expulsion event, modifying one or more settings of the Bluetooth transceiver to initiate, resume, increase wireless transmission power, or increase wireless transmission rate of the data transmission payload from the ingestible capsule by the Bluetooth transceiver.

60. 60. The method of claim 59, wherein the data transmission payload transmitted from the capsule in response to determining the occurrence of the ejection event includes a report that the occurrence of the ejection event has been determined.

61. 61. The method of claim 60, further comprising transmitting, in the wireless data transceiver, the report that the occurrence of the ejection event has been determined to a receiving device in a broadcast or query mode, and wirelessly connecting to the receiving device or wirelessly reconnecting following an initial connection prior to ingestion of the ingestible capsule to transmit the remainder of the data transmission payload.

62. 62. The method of any of claims 58 to 61, wherein the sensor hardware includes one or more gas sensors, the signals output by the sensor hardware and processed by the processor hardware include gas sensor signals output by the one or more gas sensors, and the data transmission payload includes a metric representative of the gas sensor signal, or a motility indicator in the gas sensor signal, or a diagnostic indicator in the gas sensor signal.

63. the one or more gas sensors one or more spectrophotometers; one or more surface acoustic wave sensors; one or more H2 gas sensors; one or more CH4 gas sensors; one or more bulk acoustic resonator arrays; one or more VOC gas sensors; and one or more TCD gas sensors; 63. The method of any of claims 58-62, wherein the method comprises each of the one or more gas sensors generating a constituent gas sensor signal that forms part of the gas sensor signal during transit through the GI tract of the subject mammal.

64. the sensor hardware comprising: further comprising an accelerometer; 64. The method of any of claims 58 to 63, wherein the signals output by the sensor hardware and processed by the processor hardware comprise accelerometer signals output by the accelerometer, and wherein the data transmission payload comprises metrics representative of the accelerometer signals or mobility or diagnostic indicators in the accelerometer signals.

65. a reflectometer formed by an antenna connected in series with a directional coupler, said antenna being an antenna of said Bluetooth transceiver, said antenna being controlled by said processor to transmit said data transmission payload via an intermittent or continuous signal from which a reflectometer signal can be obtained; 65. The method of any of claims 58-64, wherein the signal output by the sensor hardware and processed by the processor hardware comprises the reflectometer signal obtained from the reflectometer, and wherein the data transmission payload comprises a metric representative of the reflectometer signal or a motility or diagnostic indicator in the reflectometer signal.

66. 66. The method of any of claims 58-65, wherein the ingestible capsule further comprises an accelerometer, the method comprising: receiving, in processor hardware, accelerometer signals output by the accelerometer while the ingestible capsule passes through the GI tract; processing the received accelerometer signals by calculating metrics representative of the received accelerometer signals; and storing the calculated metrics in the memory hardware as a data transmission payload.

67. 67. The method of any of claims 58-66, wherein the sensor hardware further comprises an accelerometer, and wherein the method, in the processor hardware, in response to identifying that the temperature represented by the temperature sensor signal has fallen below a predetermined temperature range of the target mammal, to determine the occurrence of the ejection event, includes determining whether an accelerometer signal received from the accelerometer indicates that the ingestible capsule is experiencing a free fall event, and determining that the ejection event has occurred if it is determined that the received accelerometer signal indicates that the ingestible capsule is experiencing a free fall event.

68. 68. The method of any of claims 58 to 67, further comprising: processing, in the processor hardware, the temperature sensor signal; and storing, in the memory hardware, the processed temperature signal or data extracted therefrom, as a data transmission payload.

69. A method according to any one of claims 58 to 68, wherein said Bluetooth transceiver is transmitting data comprising said data transmission payload in accordance with a Bluetooth Low Energy coded PHY transmission protocol.

70. A method according to any one of claims 58 to 69, wherein the Bluetooth transceiver comprises an integrated radio and microcontroller.

71. 71. The method of any of claims 58 to 70, wherein modifying one or more settings of the wireless data transmitter in response to determining the occurrence of the ejection event comprises controlling the Bluetooth transceiver to transmit the data transmission payload stored in the memory hardware by broadcasting pending transmission data from the data transmission payload to the receiving device, regardless of whether the receiving device is paired with the Bluetooth transceiver.

72. The method comprises: and, prior to determining the occurrence of the ejection event, the Bluetooth transceiver pairs with a Bluetooth compatible device external to the target mammal, and transmits to the paired device: signal(s) from said sensor hardware; one or more motility indicators identified by processing signals from the sensor hardware; one or more diagnostic indicators identified by processing signals from the sensor hardware; information indicating the remaining capacity of the power source; a metric calculated by processing a signal from a single sensor in the sensor hardware or by combining signals from multiple sensors in the sensor hardware; a calculated gas concentration level of one or more component gases of the gas mixture present in the GI tract, calculated by referencing predetermined calibration parameters stored in the memory hardware; 72. A method as claimed in any one of claims 58 to 71, wherein in the course of determining the occurrence of the ejection event, the method includes changing a setting of the Bluetooth transceiver in the processor hardware to forward the data transmission payload to the same Bluetooth compatible device either by continuing the existing pairing, by re-pairing, or in the absence of pairing.

73. 73. The method of claim 72, wherein changing a setting of the Bluetooth transceiver includes increasing a transmit power.

74. 74. The method of any of claims 58-73, wherein the method includes, after an initiation event, operating in an ingestion detection mode in which the temperature sensor is active; and the processor hardware operates to monitor the temperature sensor signal to identify when the temperature represented by the temperature sensor signal reaches a predetermined internal temperature range of the subject mammal; and in response to said identification, determine the occurrence of an ingestion event and record the ingestion event as a data transmission payload in the memory hardware; and commence said collecting of data during said transit through the GI tract.

75. 1. A method in an ingestible capsule, the ingestible capsule comprising: an ingestible, indigestible, biocompatible housing; Within the housing: Power supply and Sensor hardware; processor hardware; memory hardware; a wireless data transmitter; The method includes receiving, in the processor hardware, signals output by the sensor hardware during passage through the GI tract of the subject mammal after ingestion of the ingestible capsule by the subject mammal; processing the received signals; and storing some or all of the processed signals, or data extracted therefrom, in the memory hardware as a data transmission payload. The method includes, in the processor hardware, receiving and monitoring the signal output by the sensor hardware to identify a transmission trigger event indicator; determining, in response to the identification, an occurrence of a transmission trigger event; and, in response to determining the occurrence of the transmission trigger event, modifying one or more settings of the wireless data transmitter to initiate, resume, increase wireless transmission power, or increase wireless transmission rate of the data transmission payload from the capsule by the wireless data transmitter.

76. the transmission trigger event indicator is a motility event indicator associated with ingestion of the ingestible capsule, gastroduodenal transit of the ingestible capsule, ileocecal junction transit of the ingestible capsule, or expulsion of the ingestible capsule; or 76. The method of claim 75, wherein the transmission trigger event indicator is a diagnostic indicator associated with a clinical diagnosis of a medical condition.

77. A computer program which, when executed by a processor, causes the processor to carry out a method according to any one of claims 39 to 57.

78. 1. A computer program for execution by processor hardware in an ingestible capsule adapted for ingestion by a target mammal, said ingestible capsule comprising: an ingestible, indigestible, biocompatible housing; Within the housing: Power supply and sensor hardware including a temperature sensor configured to output a temperature sensor signal representative of a temperature of an environment surrounding the ingestible capsule; the processor hardware; memory hardware; a wireless data transmitter; When the computer program is executed by the processor hardware, the processor hardware receiving signals output by the sensor hardware during passage of the ingestible capsule through the GI tract of the subject mammal following ingestion of the ingestible capsule by the subject mammal; processing the received signals; and storing some or all of the processed signals, or data extracted therefrom, in the memory hardware as a data transmission payload; 1. The computer program product causing execution of a method comprising: receiving and monitoring the temperature sensor signal to identify when the temperature sensor signal indicates that the ingestible capsule is no longer present in the GI tract of the target mammal; determining, in response to the identification, the occurrence of an expulsion event; and altering one or more settings of the wireless data transmitter, in response to determining the occurrence of the expulsion event, to initiate, resume, increase wireless transmission power, or increase wireless transmission rate of the data transmission payload from the ingestible capsule by the wireless data transmitter.

79. 79. A non-transitory computer readable medium storing the computer program of claim 78.

80. A computer program which, when executed by a processor, causes the processor to carry out a method according to any of claims 58 to 74.

81. 1. A computer program for execution by processor hardware in an ingestible capsule, said ingestible capsule comprising: an ingestible, indigestible, biocompatible housing; Within the housing: Power supply and Sensor hardware; the processor hardware; memory hardware; a Bluetooth transceiver; When the computer program is executed by the processor hardware, the processor hardware receiving, in the processor hardware, signals output by the sensor hardware during transit through the GI tract of the subject mammal after ingestion of the ingestible capsule by the subject mammal; processing the received signals by calculating a metric representative of the received signals or identifying a motility or diagnostic indicator in the received signals; and storing, in the memory hardware, data representative of the calculated metric or the motility or diagnostic indicator as a data transmission payload, wherein the motility indicator and / or the diagnostic indicator is a predetermined pattern, range of values, spike, step change, inflection point, local maximum or minimum, predetermined change, or sequence of change in the signal(s) output by one or more sensors of the sensor hardware; transmitting, in the Bluetooth transceiver, the data transmission payload from the ingestible capsule to a paired receiving device during the transit through the GI tract of the target mammal.

82. 82. A non-transitory computer readable medium storing the computer program of claim 81.

83. A computer program which, when executed by a processor, causes the processor to carry out a method according to any of claims 75 to 76.

84. 1. A computer program for execution by processor hardware in an ingestible capsule, said ingestible capsule comprising: an ingestible, indigestible, biocompatible housing; Within the housing: Power supply and Sensor hardware; the processor hardware; memory hardware; a wireless data transmitter; The computer program, when executed by the processor hardware, causes the processor hardware to: receive signals output by the sensor hardware during passage of the ingestible capsule through the GI tract of the subject mammal; process the received signals; and store some or all of the processed signals, or data extracted therefrom, in the memory hardware as a data transmission payload. receiving and monitoring the signal output by the sensor hardware to identify a transmission trigger event indicator; determining, in response to the identification, an occurrence of a transmission trigger event; and, in response to determining the occurrence of the transmission trigger event, modifying one or more settings of the wireless data transmitter to initiate, resume, increase wireless transmission power, or increase wireless transmission rate of the data transmission payload from the capsule by the wireless data transmitter.

85. 85. A non-transitory computer readable medium storing the computer program of claim 84.

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