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WO2025175357A1 - Methods, programs, apparatus for obtaining health information from sensors in an ingestible capsule - Google Patents

Methods, programs, apparatus for obtaining health information from sensors in an ingestible capsule

Info

Publication number
WO2025175357A1
WO2025175357A1 PCT/AU2025/050151 AU2025050151W WO2025175357A1 WO 2025175357 A1 WO2025175357 A1 WO 2025175357A1 AU 2025050151 W AU2025050151 W AU 2025050151W WO 2025175357 A1 WO2025175357 A1 WO 2025175357A1
Authority
WO
WIPO (PCT)
Prior art keywords
ingestible capsule
capsule
tract
location
spectral analysis
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/AU2025/050151
Other languages
French (fr)
Inventor
James John
Malcolm Hebblewhite
Eduardo RATH ROHR
Kyle BEREAN
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Atmo Biosciences Ltd
Original Assignee
Atmo Biosciences Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from AU2024900450A external-priority patent/AU2024900450A0/en
Application filed by Atmo Biosciences Ltd filed Critical Atmo Biosciences Ltd
Publication of WO2025175357A1 publication Critical patent/WO2025175357A1/en
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

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Definitions

  • This invention relates to ingestible sensor capsules for medical and health applications in the gastrointestinal (GI) tract of mammals including humans, and specifically relates to recording sensor data within the ingestible capsule and determining a location within the GI tract based on the data.
  • GI gastrointestinal
  • Ingestible capsules housing sensors may be used to provide information about the health of a subject.
  • Gut health is increasingly identified as a contributor to overall health and wellness.
  • Motility of an ingestible capsule provides important information in the assessment of gut health. Determining location within the GI tract provides health information in itself, by providing information for GI tract motility reporting, and also provides context for sensor readings such as gas sensor readings.
  • WO2023/064996 explains techniques for using sensor data from on-board an ingestible capsule to determine capsule location.
  • a determination of the location of the ingestible capsule may be used to time the release of therapeutic matter from a releasable chamber in the capsule, so that the therapeutic matter can be delivered directly to a specific region of the GI tract.
  • Methods comprise following ingestion of an ingestible capsule by a subject, the ingestible capsule housing a motion sensor configured to generate a time series of motion sensor data representing motion of the ingestible capsule during passage through the GI tract of a subject, at data processing hardware communicably coupled to the motion sensor, performing a process comprising: generating a spectral analysis of the time series of motion sensor data generated by the motion sensor over a time period during passage of the ingestible capsule through the GI tract, using the spectral analysis to detect peristalsis at a location of the ingestible capsule within the GI tract at the time period.
  • An apparatus comprises: an ingestible capsule housing a motion sensor configured to generate a time series of motion sensor data representing motion of the ingestible capsule during passage through the GI tract of a subject; data processing hardware communicably coupled to the motion sensor, the data processing hardware being configured, following ingestion of the ingestible capsule by the subject, at data processing hardware communicably coupled to the motion sensor, to perform a process comprising: generating a spectral analysis of the time series of motion sensor data generated by the motion sensor over a time period during passage of the ingestible capsule through the GI tract, using the spectral analysis to detect peristalsis at a location of the ingestible capsule within the GI tract at the time period.
  • a computer program comprises processing instructions which, when executed by processor hardware communicably coupled to a motion sensor housed in an ingestible capsule and configured to to generate a time series of motion sensor data representing motion of the ingestible capsule during passage through the GI tract of a subject, causes the processor hardware to perform a process comprising, following ingestion of the ingestible capsule by the subject: generating a spectral analysis of the time series of motion sensor data generated by the motion sensor over a time period during passage of the ingestible capsule through the GI tract, using the spectral analysis to detect peristalsis at a location of the ingestible capsule within the GI tract at the time period.
  • motion sensors can be housed within the capsule and do not require exposure to the medium surrounding the capsule to generate readings.
  • Motion sensors are low cost, consume little power, and simplify capsule design since they do not rely upon direct exposure to the medium surrounding the capsule to generate readings.
  • the motion sensor may be an accelerometer or a gyroscope.
  • the process further comprises: determining the location of the capsule within the GI tract based on the detected peristalsis.
  • the process further comprises: generating and outputting to a receiver computing apparatus or message recipient a report including one or more from among: information extracted from the spectral analysis representing fluctuations, variations, or anomalies within spectral components; a metric or metrics calculated from the spectral analysis from among: centre frequency, frequency spread, power distribution, frequency gaps.
  • the one or more additional sensors comprise one or more from among:
  • one or more additional sensors external to the ingestible capsule are positioned externally on the skin of the subject, the one or more additional sensors being communicatively coupled to the ingestible capsule or to a receiver computing apparatus to which the ingestible capsule is communicatively coupled, one or more additional sensors configured to generate a time series of sensor data, and the process includes generating and outputting a report including one or more from among: the spectral analysis for the time period, and a result of processing the spectral analysis for the time period comprising information indicating a respiration rate, information indicating a detection of peristalsis, or information indicating a physical activity type being undertaken by the subject; additional sensor data readings from the same time period, and/or an outcome or processing the additional sensor data readings from the same time period such as a metric or identification of a motility marker, and/or information derived from additional sensor data readings from the same time period; wherein the one or more additional sensors comprises one or more from among:
  • a method comprises: following ingestion of an ingestible capsule by a subject, the ingestible capsule housing a motion sensor configured to generate a time series of motion sensor data representing motion of the ingestible capsule during passage through the GI tract of a subject, at data processing hardware communicably coupled to the motion sensor, performing a process comprising: generating a spectral analysis of the time series of motion sensor data generated by the motion sensor over a time period during passage of the ingestible capsule through the GI tract, extracting from the spectral analysis respiration information comprising an indication of respiration rate.
  • Apparatus comprises: an ingestible capsule housing a motion sensor configured to generate a time series of motion sensor data representing motion of the ingestible capsule during passage through the GI tract of a subject; data processing hardware communicably coupled to the motion sensor, the data processing hardware being configured, following ingestion of the ingestible capsule by the subject, at data processing hardware communicably coupled to the motion sensor, to perform a process comprising: generating a spectral analysis of the time series of motion sensor data generated by the motion sensor over a time period during passage of the ingestible capsule through the GI tract, extracting from the spectral analysis respiration information comprising an indication of respiration rate.
  • a computer program comprises processing instructions which, when executed by processor hardware communicably coupled to a motion sensor housed in an ingestible capsule and configured to to generate a time series of motion sensor data representing motion of the ingestible capsule during passage through the GI tract of a subject, causes the processor hardware to perform a process comprising, following ingestion of the ingestible capsule by the subject: generating a spectral analysis of the time series of motion sensor data generated by the motion sensor over a time period during passage of the ingestible capsule through the GI tract, extracting from the spectral analysis respiration information comprising an indication of respiration rate.
  • the extracted respiratory information comprises a measurement of a signal in one or more from a predefined set of respiration information frequency ranges or detection of a signal or signal characteristics in the spectral analysis indicating one or more from among:
  • the predefined set of respiration information frequency ranges includes a first respiration information frequency range indicating snoring, and a second respiration information frequency range indicating respiration.
  • the first respiration information frequency range is between 12 and 18 cpm.
  • the second respiration information frequency range is between 3600 and 18000cpm.
  • the ingestible capsule further comprises, or is operably coupled to a separate, one or more additional sensors, each additional sensor being configured to generate a time series of additional sensor data;
  • the additional sensor comprises a pulse oximetry sensor configured to generate a time series of pulse oximetry measurements representing concentration of oxygen in blood of the subject;
  • the method further comprises generating and outputting a report comprising the extracted respiration information for the time window and a contemporaneous extract from the time series of pulse oximetry measurements.
  • the report is generated and output by processor hardware and a wireless data transceiver on board the ingestible capsule.
  • the report is generated and output by a remote processing apparatus configured to receive data transmitted away from the ingestible capsule by a wireless data transceiver.
  • a method comprises: providing to a subject an ingestible capsule housing amotion sensor configured to generate a time series of motion sensor data representing motion of the ingestible capsule during passage through the GI tract; following ingestion of the ingestible capsule by the subject, at data processing hardware communicably coupled to the motion sensor, performing a process comprising: conducting a spectral analysis of the time series of motion sensor data generated by the motion sensor over a time period during passage of the ingestible capsule through the GI tract, using the spectral analysis to determine a physical activity being undertaken by the subject or to characterise a physical activity being undertaken by the subject.
  • An apparatus comprises: an ingestible capsule housing a motion sensor configured to generate a time series of motion sensor data representing motion of the ingestible capsule during passage through the GI tract of a subject; data processing hardware communicably coupled to the motion sensor, the data processing hardware being configured, following ingestion of the ingestible capsule by the subject, at data processing hardware communicably coupled to the motion sensor, to perform a process comprising: generating a spectral analysis of the time series of motion sensor data generated by the motion sensor over a time period during passage of the ingestible capsule through the GI tract, using the spectral analysis to determine a physical activity being undertaken by the subject or to characterise a physical activity being undertaken by the subject.
  • the sensing mechanism is a direct gas sensing mechanism comprising a VOC gas sensor, the direct gas sensing mechanism being housed within the capsule in a direct gas sensing portion sealed from other components of the ingestible capsule by a gas impermeable membrane and being exposed to a gas mixture in the environment external to the ingestible capsule via a gas permeable membrane in the housing at the location of the direct gas sensing portion, the output signal output by the sensing mechanism comprising VOC concentration readings of the VOC gas sensor.
  • the ingestible capsule comprises a microcontroller
  • the sampling mechanism includes the microcontroller; the microcontroller being configured to: during an identification phase, on a rolling basis, record a representation of the output signal for a most recent time period of duration t, and to process the recorded representation of the output signal for the most recent time period of duration t to identify presence of the one or more ileocecal junction transition indicators; the microcontroller being configured, upon identification of the presence of the one or more ileocecal junction transition indicators, to determine the sampling timing and based on the determined sampling timing to cause the sampling mechanism to open and close the sampling chamber to obtain a GI tract sample.
  • the sack rupturing actuator comprises a heating element arranged in contact with the fluid- filled sack and a supercapacitor configured to be trickle charged by the ingestible capsule power supply over a period of time beginning with ingestion of the ingestible capsule, and to be caused to release the charge to the heating element at the determined sampling timing under the control of the microcontroller to cause rupturing of the fluid-filled sack.
  • the sack rupturing actuator comprises a pre-sprung mechanical needle, wherein a microcontroller of the ingestible capsule is configured, at the determined sampling timing, to release the pre-sprung mechanical needle causing the pre-sprung mechanical needle to spring into the fluid- filled sack causing rupturing.
  • the sack rupturing actuator comprises a power source, a shape memory alloy wire, and a rupturing member, the power source being configured, at the determined sampling timing and under control of the microcontroller, to transfer energy to the shape memory alloy wire, to initiate a phase change at material level of the shape memory alloy wire and thereby to exert a force on the rupturing member to cause the rupturing member to come into contact with, and to rupture, the fluid-filled sack.
  • the sack rupturing actuator comprises a motor and a rupturing member, the microcontroller being configured, at the determined sampling timing, to power on the motor and thereby to exert a force on the rupturing member to cause the rupturing member to come into contact with, and to rupture, the fluid-filled sack.
  • the ingestible capsule includes an environmental sensor, and the readings include readings of the environmental sensor, the environmental sensor being an environmental temperature sensor, an environmental relative humidity sensor, or an environmental temperature sensor and an environmental humidity sensor; the processing the recorded readings including determining an excretion event timing by detecting an excretion indicator, the excretion indicator being a change in the environmental sensor readings between an internal environmental condition of the subject mammal and an external environmental condition at a location of the subject mammal, the excretion event timing being a timing of excretion of the ingestible capsule by the subject mammal.
  • the ingestible capsule comprising a wireless transceiver configured to transmit data transmission payload away from the ingestible capsule via Bluetooth, Bluetooth Long Range, and/or 433MHz radio transmission technique, the data transmission payload comprising one or more from among: a record of sampling timing; a record of excretion timing; a record of the one or more identified ileocecal junction transition indicators; a record of the one or more identified gastric-duodenal transition indicators; a record of an electrode signal indicating rupturing of the fluid-filled sack; a record of an electrode signal indicating a filled state of the sampling chamber; output signal output by the sensing mechanism; and a metric or metrics representing the output signal output by the sensing mechanism.
  • transmission of the data transmission payload by the wireless transceiver is triggered by one or more from among: determining that an excretion event has occurred; determining sampling timing; determining sampling timing and that a predefined delay after sampling timing has expired; receipt at a microcontroller of the ingestible capsule of an electrode signal indicating rupturing of the fluid-filled sack.
  • the sensing mechanism comprises a direct gas sensing mechanism and a non-contact sensing mechanism.
  • a method comprises: providing an ingestible capsule defined above to a subject mammal for ingestion; processing the output signal of the sensing mechanism to determine the sampling timing; causing the sampling mechanism to obtain a GI tract sample at the determined sampling timing.
  • a system comprises an ingestible capsule and a remote processing apparatus: the ingestible capsule, comprising: a housing, being a biocompatible indigestible housing including a sampling chamber; a power supply; a sampling mechanism; a wireless transceiver; and a sensing mechanism, the sensing mechanism being sensitive to an environment external to the housing; the ingestible capsule being configured for passage through a gastrointestinal, GI, tract of a subject mammal, during which passage: the sensing mechanism is configured to output an output signal varying according to GI tract environment external to the housing, wherein the sensing mechanism comprises one or more sensors from among: a VOC gas sensor; a TCD gas sensor; a reflectometer formed by a transmission antenna of the ingestible capsule connected in series with a directional coupler configured to measure a reflected signal from the transmission antenna; and a motion sensor; the sampling mechanism is configured to cause a sample of fluid or matter from the GI tract to be sealed in the sampling chamber at a sampling timing determined according to the output signal; where
  • FIG. 1 illustrates apparatus
  • Figures 3a and 3b illustrate schematically electronic components of ingestible capsules
  • Figure 4 illustrates schematically electronic components of an ingestible capsule
  • Figures 5a to 5c illustrate schematically electronic components of an ingestible capsule or a system including an ingestible capsule
  • Figure 6a illustrates a time series of accelerometer data
  • Figure 6b illustrates accelerometer data in the frequency domain
  • Figure 6c illustrates accelerometer data in the frequency domain
  • Figure 6d illustrates time series of sensor data from additional sensors and from an accelerometer
  • Figure 7 illustrates a reflectometer
  • Figure 8 illustrates time series sensor data from additional sensors and from an accelerometer
  • Figure 9 illustrates time series sensor data from additional sensors and from an accelerometer
  • Figure 10 illustrates schematically electronic components of an ingestible capsule
  • Figure 11 illustrates schematically electronic components of an ingestible capsule
  • Figure 12 illustrates a capsule with a sampling mechanism
  • Figure 13 illustrates a method
  • Figures la to Id illustrate methods.
  • Figure 2 illustrates an apparatus suitable for performing the methods.
  • Figures 3a and 3b are schematic illustrations of ingestible capsules 10.
  • the method of Figure la is a method for determining a location of an ingestible capsule 10 within the GI tract of a subject 40, illustrated in Figure 2.
  • the ingestible capsule 10 houses a motion sensor 19.
  • the motion sensor 19 is configured to generate a time series of motion sensor data representing acceleration, rotation, or positional changes experienced by the ingestible capsule 10 (otherwise referred to as raw accelerometer data).
  • the motion sensor 19 is fixed in position within the ingestible capsule 10 so that the ingestible capsule 10 and the motion sensor 19 experience the same acceleration, rotation, and positional changes.
  • Location within the GI tract may be an indication of presence in either the stomach, the small intestine, or the large intestine.
  • the location may be provided to a greater level of specificity, such as proximal or distal small intestine.
  • the method of Figure lb is a method for detecting respiratory events and/or for extracting information relating to respiratory activity. Steps S101 to S103 are common to the methods of Figures la to Id. In the method of Figure lb, step S104B is optional, as indicated by the dashed lines. Information derived from the location determinations at S104B may be included in a report also including the respiratory information extraction at S105, for example, for diagnostic purposes. Or it may be that the respiratory analysis such as at SI 05 is conducted in the absence of motility analysis such as at S104B.
  • the method of Figure 1c is a method for detecting an activity type of a patient, such as running, walking, resting.
  • steps S104B and S105 are optional, as indicated by the dashed lines.
  • Information derived from the location determinations at S104B may be included in a report also including the respiratory information extraction at S105 and the activity type determination at S106. Or it may be that the activity type determination at SI 06 is conducted in the absence of one or both of respiratory analysis such as at S105 and motility analysis such as at S104B.
  • Steps S104A to SI 06 may be referred to collectively as spectral analysis processing steps.
  • Each of S104Ato SI 06 utilises the result of the spectral analysis from SI 03 to extract information, detect events, or determine information.
  • the spectral analysis processing steps S104Ato SI 06 may be performed onboard the capsule or remotely (see Figure 2).
  • the results of the spectral analysis processing steps may be included in a report generated on-board the capsule 10 and transmitted away to a receiver computing apparatus 30, or may be included in a report generated by remote processing apparatus and transmitted to a recipient such as the subject or a clinician.
  • Steps S 104B to S 106 may be performed in combination with one another, or separately.
  • a single capsule 10 may be configured to perform any one of S104A to SI 06, all four of S104A to SI 06, or some combination thereof.
  • a system comprising an ingestible capsule 10 and remote processing apparatus may be configured to perform any one of S 104A to S 106, all four of S 104A to S 106, or some combination thereof.
  • apparatus arrangements for performing methods for determining location of the capsule 10 within the GI tract based on a spectral analysis of a time series of data generated by the motion sensor 19, such as illustrated by Figures la to Id, may comprise:
  • the remote processing apparatus may comprise only a receiver computing apparatus 30 in direct data communication with the ingestible capsule 10, or may comprise a receiver computing apparatus 30 in direct data communication with the ingestible capsule 10 and one or more further computing apparatus 20 to receive data from the receiver computing apparatus 30 over a network.
  • the receiver computing apparatus 30 and the further computing apparatus 20 are optional.
  • the receiver computing apparatus 30 may be a smart phone, a tablet, or some other personal computing device, or server computer, configured to pair, couple, or otherwise establish a direct data communication with a wireless data transceiver 18 of the ingestible capsule 10.
  • the further computing apparatus 20 may be a smart phone, a tablet, or some other personal computing device, server computer, or cloud computing device/service/infrastructure in network communication with the receiver computing apparatus 30.
  • the receiver computing apparatus 30 may be a personal device of the subject 30.
  • the further computing apparatus 20 may be a device of a clinical service provider, an ingestible capsule provider, or some other entity.
  • Data communications between the capsule 10 and the receiver computing apparatus 30 may be oneway, wherein raw motion sensor data is transmitted from the capsule 10 to the receiver computing apparatus 30 for processing (by the receiver computing apparatus 30 and/or the further computing apparatus 20), and no data flows in the reverse direction. Alternatively, a result of processing may be transmitted back to the capsule 10.
  • transmission from remote processing apparatus to the ingestible capsule 10 may be in response to determining at S 104B that a location of the capsule 10 within the GI tract is a target location for therapeutic matter being carried by the capsule 10 and thus the transmission is a trigger signal to trigger release of the therapeutic matter by the capsule 10.
  • Aprocess comprising the spectral analysis at S103, and the spectral analysis processing steps S104B to SI 06 may be performed on-board the ingestible capsule 10, may be performed by a receiver computing apparatus 30 in direct data communication with the ingestible capsule 10, or may be performed by further computing apparatus 20 in data communication with the receiver computing apparatus 30 over a network (such as the internet). The process may be performed by two or three of those elements in combination.
  • the apparatus arrangements of Figure 2 may also be referred to as systems.
  • the subject 40 is illustrated for context but is not intended to form part of an apparatus or system.
  • FIGS 3a and 3b schematically illustrate basic capsule arrangements.
  • the ingestible capsule 10 comprises at least a motion sensor 19 and a power source 16. Other components such as control circuitry may be present in the capsule 10 but are not illustrated.
  • the ingestible capsule 10 of Figure 3a includes data processing hardware 15 comprising processor hardware 151 such as a CPU for processing data, and a memory hardware 152 for storing data, in preparation for and during processing, and/or processing results.
  • the data processing hardware 15 is optional since the ingestible capsule 10 may comprise a wireless transceiver 18 to transmit the motion sensor data (and other sensor data generated by the capsule 10) away to remote apparatus (see Figure 2) for processing.
  • the ingestible capsule 10 may comprise data processing hardware 15 for on-board processing, and a wireless transceiver 18 to transmit a result of the on-board data processing to a remote apparatus for one or more from among further processing, storage, reporting, etc.
  • the spectral analysis step S 103 may be performed on-board the capsule 10, and the resultant frequency domain representation of the motion sensor data transmitted to the remote processing apparatus for the spectral analysis processing step or steps S104B-S106.
  • the ingestible capsule 10 illustrated in Figure 3a and in Figure 3b may further comprise additional sensor hardware such as an EMG 31, a pulse -oximetry sensor 32, or a gas sensor, which would be housed within a gas sensing headspace within a gas permeable membrane and sealed from the remainder of the components by an impermeable membrane.
  • additional sensor hardware such as an EMG 31, a pulse -oximetry sensor 32, or a gas sensor, which would be housed within a gas sensing headspace within a gas permeable membrane and sealed from the remainder of the components by an impermeable membrane.
  • the ingestible capsule 10 may be of an arrangement configured to release therapeutic matter into the GI tract at a timing based on a location determined at S104B by spectral analysis of a time series of data generated by the motion sensor 19.
  • the motion sensor 19 may be a gyroscope.
  • the motion sensor 19 may be an accelerometer.
  • the motion sensor 19 may comprise a gyroscope and an accelerometer.
  • the motion sensor 19 may be a tri -axis accelerometer.
  • the motion sensor 19 may be a 12 -bit tri-axis accelerometer.
  • the motion sensor 19 may be a single-axis accelerometer or a two-axis accelerometer.
  • the motion sensor 19 may comprise a piezo-film sensor, a surface MM capacitive sensor, a bulk capacitive sensor, and/or a piezo-electric electromechanical servo vibrational sensor.
  • the motion sensor 19 may comprise a fibre optic accelerometer, a Hall effect accelerometer, a magnetoresistive accelerometer, and/or a strain gauge accelerometer.
  • Methods for determining location of the capsule 10 within the GI tract based on a spectral analysis of a time series of data generated by the motion sensor 19, such as illustrated by Figure la, may be performed on-the-fly (during GI tract passage), or may be performed retrospectively (following GI tract passage).
  • Methods for extracting respiratory information from a spectral analysis of a time series of data generated by the motion sensor 19, such as illustrated by Figure lb, may be performed on-the-fly (during GI tract passage), or may be performed retrospectively (following GI tract passage).
  • Methods for determining an activity type of a subject 40 from a spectral analysis of a time series of data generated by the motion sensor 19, such as illustrated by Figure 1c, may be performed on-the-fly (during GI tract passage), or may be performed retrospectively (following GI tract passage).
  • the processing is retrospective insofar as the data being processed was generated by the motion sensor 19 in the past, but the processing is being performed more or less instantaneously after the end of a time period during which the time series represents to obtain a processing result representing the said time period, for example, a location of the capsule within the said time period.
  • On-the-fly processing may be useful in examples such as determining location in order to release therapeutic matter into a particular location within the GI tract. Such processing may be useful in order to reduce a data transmission overhead, so that rather than transmitting raw motion sensor data away from the capsule 10, it is only necessary to transmit results of a location determination for a time period or location determinations for a series of time periods. Or, for example, to transmit the spectral information resulting from the spectral analysis, that is, the frequency domain representation of the time series of motion sensor data, or a compressed or otherwise processed version thereof. Wherein processed or compressed may indicate that signals or components in one or more relevant frequency ranges are extracted and other signals or components discards. Relevant may be a predefined set of peristalsis indicator frequency ranges.
  • On-the-fly processing of the time series of motion sensor data to obtain a spectral analysis result at S 103 and a result of a spectral analysis processing step S 104B to S 106 may be performed on-board the capsule 10 by an arrangement such as illustrated in Figure 3a, or may be transmitted away from the capsule during passage through the GI tract for processing at a remote apparatus in an arrangement such as illustrated in Figure 3b.
  • Transmission of the raw motion sensor data (i.e. the time series of motion sensor data) from the capsule 10 to the remote apparatus may be during passage through the GI tract.
  • the wireless data transceiver 18 may pair or otherwise connect with the remote apparatus for transmission according to a protocol such as Bluetooth or Bluetooth Low Energy transmission protocol.
  • results of processing on-board the capsule may be transmitted to a remote apparatus via the same mechanism.
  • Results of processing on-board the capsule may be stored on the capsule for reporting by transmission to a remote apparatus after detection of excretion from the GI tract (by detecting a freefall event via the motion sensor 19 or by changes detected by temperature or relative humidity sensors, if included) triggering a burst of data transmission in an inquiry mode.
  • Retrospective processing which is taken to mean processing after passage through the GI tract, may be performed at a remote apparatus in an arrangement such as illustrated in Figures 2 and 3b.
  • the capsule 10 there may still be a wireless data transceiver 18 for transmitting away a result of the processing to a remote apparatus, and in the case of there being additional sensor hardware, it may be that data from the additional sensor hardware is transmitted away via the wireless data transceiver 18.
  • the additional sensor data may be processed on board the capsule 10 and a processing result transmitted away. It may be that no data is transmitted away from the ingestible capsule 10, for example if the processing result is a location determination at S104B used to determine a release timing of therapeutic matter, then the processing result does not necessarily need to be transmitted away from the capsule 10 (however it may be transmitted away for reporting purposes).
  • Retrospective processing may be useful in examples such as health reporting and diagnostics, when a clinician wishes to obtain a report on GI tract motility of a patient (comprising one or more from among whole gut transit time, small bowel residence time, large intestine residence time, gastric residence time, etc) based on the method of Figure la, on the respiratory activity or habits/pattems of a subject based on the method of Figure lb, or on the activity types of a subject based on the method of Figure 1c.
  • a report may include additional sensor data generated at each location within the GI tract.
  • additional sensor data may be generated by on-board gas sensors indicating gases present in the gas mixture surrounding the capsule 10 during its passage through the GI tract, noting that combining such sensor data with determinations of location from S104B in particular time windows enables a clinician to determine whether and to what extent gases indicative of disorders such as gastroparesis or SIBO are present.
  • on-the-fly processing could also be implemented.
  • Step S101 is common to the methods of Figures la to Id.
  • the ingestible capsule 10 ingested by a subject 40 may be a human subject.
  • the ingestible capsule 10 may be obtained by the subject from a clinician (that is, a medical professional) for obtaining information about the condition of the GI tract, respiratory patterns, or other health information about a subject. Further, the ingestible capsule 10 may be provided as a means to deliver therapeutic matter directly to a particular location in the GI tract of the subject.
  • the ingestible capsule 10 may be configured to power on upon removal from a package in which it is supplied, or upon receipt of a custom wireless signal from a dedicated application on a remote apparatus such as receiver computing apparatus 30.
  • the ingestible capsule 10 may include a secondary wireless transceiver, which may use an NFC communication protocol.
  • the secondary transceiver is for specific activation control signalling only, such as for initiating an active mode of the capsule 10 at an unpackaging stage or otherwise prior to ingestion of the capsule 10.
  • the secondary transceiver is not active during the live phase of the capsule 10, i.e. during passage through the GI tract of the subject mammal.
  • the secondary transceiver does not contribute to transmission of the data transmission payload from the capsule 10 to the receiver apparatus 30.
  • the secondary transceiver may be configured to receive an encoded activation control signal from a smartphone or tablet (e.g. the receiver computing apparatus 30) running an application configured for managing interactions between the smartphone or tablet (tablet in this context meaning tablet computer) and the capsule 10, which encoded activation control signal initiates a live phase of the capsule 10 during which capsule sensors take readings and the readings themselves or metrics and/or reports based on the readings are transmitted from the capsule 10 to the smartphone or table via the primary wireless data transceiver.
  • the secondary wireless data transceiver is active in a listening phase which precedes a live phase of the capsule.
  • the primary wireless data transceiver (and the other components such as the sensor hardware, processor hardware, etc) is inactive (i.e. consuming no power whatsoever) during the listening phase.
  • the listening phase ends and the secondary wireless data transceiver becomes inactive.
  • the primary wireless data transceiver is active during the live phase.
  • capsule 10 may operate in a standby or listening mode during the time between release from manufacturing and initiation of the live phase during which readings are recorded by the on-board sensors and transmitted away from the capsule.
  • the standby or listening mode is an extremely low power mode (for example, the sensors and the data processing hardware is inactive during the standby or listening mode).
  • a live phase of the capsule is initiated prior to ingestion by the subject 40.
  • a mechanism for ending the standby or listening mode and entering a live phase may include a reed switch coupled to a magnet on the packaging which is triggered by release of the capsule from the packaging and when triggered powers on the processor, sensors, and primary transceiver (i.e. initiates the live phase).
  • An alternative mechanism is based on Near Field Communication, NFC.
  • a back-end server may link a user account to a particular capsule instance, so that when that user is logged in to the application and selects to activate a capsule, the application performs a lookup to the back-end server to determine how to encode the activation control message.
  • the encoding is unique per capsule.
  • the encoding may be uniform across a batch of capsules or all capsules.
  • Step S102 is common to the methods of Figures la to Id.
  • the capsule 10 is in a live phase and so the motion sensor 19 is configured to take readings.
  • the motion sensor 19 is configured to take readings. For example, under control of control circuitry 15 on board the capsule 10 controlling power supply to the accelerometer and readings therefrom.
  • An exemplary motion sensor 19 is an accelerometer measuring roll about three mutually orthogonal axes.
  • the readings from the accelerometer 19 may be vectors with a component per axis, with each component indicating an instantaneous angular acceleration about the corresponding axis, or an average acceleration about the corresponding axis over the time period since the preceding live reading. Alternatively, the readings may give a three dimensional orientation of the capsule.
  • the motion sensor 19 may be a gyroscope or angular rate sensor.
  • the motion sensor 19 may be a magnetometer coupled to a magnet external to the subject. The magnet may be fixed to the subject or to a building or to an object.
  • Some pre-processing of the raw motion sensor data may be performed between SI 02 and S103 to prepare the motion sensor data for transform from the time domain to the frequency domain at SI 03.
  • Processing of the readings from the motion sensor 19 may be performed to generate a representation (such as a plot vs time) of aggregated (i.e. all three axes) motion sensor readings.
  • a representation such as a plot vs time
  • such a plot or representation may also be used to identify motility markers for events including an excretion event, gastric-duodenal transition, and ileocecal junction transition.
  • the capsule orientation may be measured using a triaxial accelerometer and tracking the gravity vector or another fixed vector (such as provided by an external magnet) with respect to the capsule frame of reference.
  • Readings from the motion sensor are a time series, so that there is a time value implicitly or explicitly associated with each reading.
  • readings may be time-stamped, and in the implicit case the readings are chronological and separated by a predefined time resolution step so that a timing can be inferred from a time of initiation of the live phase and a position of the reading within the chronological order.
  • the motion sensor 19 may be a tri-axis accelerometer generating a single time series of accelerometer data or one time series of accelerometer data per axis.
  • the process may include a pre-spectral analysis step between SI 02 and SI 03 comprising: combining the three time series into a single resultant time series representing pitch angle (or tilt angle) between a capsule reference axis in fixed relation to the capsule, and an earth reference axis in fixed relation to the earth.
  • the pre-spectral analysis step may comprise combining the three time series into a single resultant time series, for example by a vector addition, a summation of magnitudes, or an RSS combination. Spectral analysis at S 103 would then be performed on the single resultant time series.
  • the motion sensor data is accelerometer data comprising three contemporary time series each representing acceleration in a respective one of the three axes, and combining is performed in the frequency domain (as part of SI 03).
  • a preprocessing step may comprise discarding a time series representing an axis from which a predetermined number or proportion of readings are missing.
  • the time series of motion sensor data is a truncated time series insofar as it represents motion of the capsule 10 during a subset of the overall time during which it is resident in the GI tract of the subject.
  • the length of the time window determines the frequency resolution of the result of the spectral analysis.
  • the sampling frequency of the motion sensor readings i.e. the time separation between adjacent readings in the time series of motion sensor data
  • Motion sensor takes readings at a sampling rate f a .
  • Each motion sensor reading represents a motion sensor reading duration l/f a . This is the fundamental sampling rate of the data.
  • the size of the FFT (or other spectral analysis result) is N and the frequency resolution is f a /N.
  • the time series of motion sensor data may be divided into a series of time windows (either consecutive or sliding) each comprising M/f a , wherein M is a positive integer and is fixed or adaptive.
  • M/f a is a duration of time covered by a time window, wherein M is the number of readings in the time series data.
  • the time window may be a period of time having a length, for example, between 4 minutes 20 minutes, between 5 minutes and nineteen minutes, between six minutes and eighteen minutes, between seven minutes and seventeen minutes, between eight minutes and sixteen minutes.
  • the time window may have a length of ten minutes, that is, be between nine minutes and eleven minutes in length, or between eight minutes and twelve minutes in length, or between seven minutes and thirteen minutes in length, or between six minutes and fourteen minutes in length, or between five minutes and fifteen minutes in length.
  • the time window may be between fifteen minutes and twenty five minutes in length, between twenty five minutes and thirty five minutes in length, between thirty five minutes and forty five minutes in length, or between forty five minutes and fifty five minutes in length, or between fifty minutes and sixty five minutes in length.
  • the time window may be as short as one sample l/f a , or as long as all samples in the time series M, or any length in between.
  • Time window length may be fixed or adaptive. Applying an adaptive or variable time window duration function may provide greater spectral resolution at one time window and greater data loss immunity at another.
  • Figure 6a illustrates a time series of motion sensor data generated by an accelerometer and representing acceleration on the x axis relative to fixed gravitational vector g for a ten minute window 5 hours after ingestion of a sample ingestible capsule.
  • Step S103 Generate spectral analysis
  • Step S103 is common to the methods of Figures la to Id.
  • Step SI 03 comprises conducting a spectral analysis of the time series of motion sensor data generated by the motion sensor over a time period during passage of the ingestible capsule through the GI tract.
  • the motion sensor data is time-sampled.
  • data from the time series of motion sensor data belonging to a time window of duration T is extracted and processed at SI 03.
  • Figure 6a illustrates an exemplary data sample wherein T is ten minutes and the timing is five hours after ingestion of the capsule 10 by the subject 40.
  • spectral analysis may be performed on one or a series of such time windows.
  • the series of time windows may be contiguous, or they may be partially overlapping.
  • spectral analysis of a single time window may be sufficient to determine a capsule location at S104B, or spectral analysis of a series of time windows may be combined to determine a location of the capsule during the series of time windows, noting the relative loss in precision in the latter case.
  • Time windows may be of a fixed length or may be adaptive.
  • spectral analysis of a single time window may be sufficient to enable component signals caused by respiratory function to be identified and extracted.
  • spectral analysis of a series of time windows may be necessary to identify one or more patterns or events that can be attributed to respiratory function.
  • spectral analysis of a single time window may be sufficient to enable an activity type of a subject to be determined.
  • spectral analysis of a series of time windows may be necessary to identify one or more patterns or events that can be attributed to a particular activity type.
  • Spectral analysis at SI 03 comprises transforming the time series of motion sensor data from the time domain to the frequency domain.
  • An example of a process for performing the transform is a Fast Fourier Transform, FFT
  • a result of spectral analysis at SI 03 is a frequency domain representation of the motion sensor data from the time window.
  • the frequency domain representation may be a list, array, or another representation of signal magnitude in each of a series of component frequencies.
  • Figure 6b illustrates the result of a spectral analysis performed on the time series of motion sensor (accelerometer) data from Figure 6a.
  • the y-axis and z-axis data was also transformed to the frequency domain, but that the x-axis data had the greatest signal magnitude in the set of peristalsis indicator frequency ranges (which may, for example, be determined by a summation per axis of signal magnitudes in component frequencies falling within one or more frequency ranges in a predefined set of relevant frequency ranges (such as peristalsis indicator frequency ranges in the context of the method of Figure la), and a comparison of the summations to establish the greatest).
  • Figure 6b a peak in the frequency domain is observed at around 3 cycles per minute, which is within the frequency range indicating stomach peristalsis, as discussed below in relation to S104B.
  • the result of the spectral analysis is a measure of acceleration energy at each of a series of component frequencies.
  • Figure 6b is an illustration of underlying data, and in implementation the underlying data may remain as a data list or array without being rendered in illustrative form such as in Figure 6b.
  • the underlying data is rendered into illustrative form and the resulting rendered version (such as a graph, for example) is provided as an input to the machine learning algorithm.
  • the numerical list or array is provided as input to the machine learning algorithm.
  • Figure 6c illustrates the result of a spectral analysis performed on a further time series of data generated by the same capsule 10.
  • Figure 6c represents motion sensor data from an accelerometer at a ten minute time window 12 hours after ingestion.
  • the result of the spectral analysis is stored for use in the S104Bspectral analysis processing step S104B to S106.
  • the result of the spectral analysis is stored for reporting and other further processing.
  • the result of the spectral analysis may be transmitted away from the capsule 10 to the receiver computing apparatus 30 for reporting and other further processing, or may be discarded after completion of S104Bspectral analysis processing S104B to S106.
  • the result of the spectral analysis stored for use in the spectral analysis processing step S104B-S106 may comprise a representation of signal magnitude at every component frequency in the frequency domain to which the accelerometer data is transformed at SI 03.
  • data representing frequencies outside of a predefined set of relevant peristalsis indicator frequency ranges may be discarded.
  • power consumption on-board the capsule may be reduced by discarding some of the data at this stage.
  • respiration analysis S105 it may be that there is a single frequency range associated with respiration, but that also a frequency range associated with snoring is defined. These may be referred to as respiration information frequency ranges.
  • activity type determination S106 it may be that a predefined set of activity indicator frequency ranges are defined, including, for example, a frequency range indicating walking cadence at around 60cpm to 120cpm, and a frequency range indicating a running cadence at around 160cpm to 220cpm.
  • Using the spectral analysis to detect peristalsis SI 04a is an example of a spectral analysis processing step.
  • Using the spectral analysis to detect peristalsis S104a may include interrogating or otherwise processing the spectral analysis to identify signals indicative of peristalsis in one of the regions of the GI tract. Identifying a signal at a predefined minimum energy or magnitude in a frequency range indicating peristalsis (i.e. one of a predefined set of peristalsis indicator frequency ranges) may be a detection of peristalsis. Rather than a predefined minimum energy, it may be that a characteristic frequency is identified among the spectral analysis (i.e. a frequency component showing a strongest signal among the frequency components) and if the characteristic frequency is within one of a predefined set of peristalsis indicator frequency ranges, then peristalsis is detected.
  • a second peristalsis indicator frequency range being a frequency range indicating small intestine peristalsis
  • the third peristalsis indicator frequency range indicating large intestine peristalsis may be around 0.5 cycles per minute, around 1 cycle per minute, around 1.5 cycles per minute, or around 2 cycles per minute.
  • An exemplary frequency range is from 0.5 to 2 cycles per minute, or from 1 to 2 cycles per minute, or from 0.5 to 2.5 cycles per minute, or from 1 to 2 cycles per minute.
  • Further information may be derived from the spectral analysis, in particular where the process is repeated for a series of time periods. For example, fluctuations, variations, or anomalies within particular spectral components (frequency ranges of interest such as peristalsis indicator frequency ranges or respiration information frequency ranges or patterns, or physical activity type indicator frequency ranges) or of the characteristic frequency may be recorded and reported, either on-board the capsule 10, or in case the process is performed at a remote processing apparatus, then at the remote processing apparatus. Such further information may be valuable for health monitoring and diagnostic purposes.
  • An example of such further information is power distribution across the entire frequency range (or across the frequency ranges of interest) in one or a series of time periods.
  • An example of such further information is rhythm or distribution of a centre frequency across a series of time periods (optionally across the entire passage through the GI tract).
  • An example of such further information is the identification of gaps in the peristaltic wave, that is, is there a time period or time periods where signals in one of the peristalsis indicator frequency ranges is lower than chronologically adjacent time periods, or is not detectable whereas it is detectable in time periods before and after.
  • An example of such further information is a metric or metrics calculated from the spectral analysis from among: centre frequency, frequency spread, power distribution, frequency gaps. Any of these further information elements may be identified or measured on-board the capsule 10 or at a remote processing apparatus by processing the spectral analysis, and included in a report generated and output at SI 07.
  • Generating the further information from the spectral analysis is an example of a spectral analysis processing step.
  • Step S104B Determine location of the capsule within the GI tract
  • the method of Figure la includes S104B determining the location of the capsule within the GI tract at the time period represented by the time series of motion sensor data. Step S104B is optional in the methods of Figures lb and 1c.
  • Step S 104B comprises using the spectral analysis to determine a location of the ingestible capsule within the GI tract at the time period, based on the peristalsis detection at SI 04a.
  • the time period in question is the time period during which the motion sensor readings were taken that form the time series of motion sensor data on which spectral analysis is conducted at SI 03.
  • Absence of a signal may also contribute to a location determination. Therefore, it is feasible to determine location at SI 04b in the absence of a positive detections at SI 04a.
  • the ingestible capsule may be determined to be in the stomach by presence of a signal in the first peristalsis indicator frequency range.
  • the ingestible capsule may be determined to be in the small intestine by presence of a signal in the second peristalsis indicator frequency range.
  • the ingestible capsule may be determined to be in the large intestine by absence of a signal in the first peristalsis indicator frequency range and absence of a signal in the second peristalsis indicator frequency range.
  • the ingestible capsule may be determined to be in the large intestine by presence of a signal in the third peristalsis indicator frequency range.
  • spectral analysis steps S104A to S106 in addition to identifying primary or average frequencies, further information may be extracted from the spectral analysis result, such as instability at or around a specific frequency range. Instabilities may be the result of a health condition and hence may contribute to a diagnosis. Such further information may be included in a report to be transmitted away from the capsule 10, or in the case of remote processing may be included in a report to be output to a clinician, subject, or another recipient.
  • the spectral analysis shows a detectable spike at frequency components around 3cpm. This is an indication that magnitude(s) of the signal amplitudes (or a summation thereof) at the one or more frequency components within the first peristalsis indicator frequency range satisfies a threshold and that therefore at S104B a determination is made that, in the spectral analysis illustrated by Figure 6b, at the pertinent time window, the capsule 10 is located in the stomach.
  • the 2 nd harmonic at 6cpm is also detectable.
  • detection of a signal at the 2 nd harmonic may be used to confirm a detection at the first harmonic (the first harmonics being in the stated peristalsis indicator frequency ranges).
  • Figure 6d illustrates time series of additional sensor data.
  • Figure 6d illustrates that the two sample determinations based on the spectral analysis results in Figures 6b and 6c are correct.
  • Figure 6d further demonstrates the additional sensor data that may be generated by the capsule 10.
  • Figure 6d shows sensor data from a plurality of additional sensors: capsules 10 may have no additional sensors, one additional sensor, or some subset of the additional sensors generating the data shown in Figure 6d (which corresponds to a capsule 10 hardware arrangement such as is illustrated in Figure 4).
  • Other examples of additional sensors include pulse-oximetry sensors and EMG sensors, each of which may be housed within the ingestible capsule 10, or provided externally and affixed to a skin of the subject during GI tract passage of the ingestible capsule 10.
  • the determination at SI 04b may be based upon a spectral analysis result from a single spectral analysis representing a single time window.
  • the determination S104b may be based upon plural spectral analysis results each representing a different (and optionally distinct i.e. non-overlapping) time window.
  • a determination may be based upon meeting a minimum threshold amount of energy (or other measure of signal magnitude) at frequencies within the respective peristalsis indicator frequency range.
  • a minimum threshold amount of eneigy (or other measure of signal magnitude) needs to be met for a predefined proportion (such as three-quarters, two-thirds, etc) of a predefined number of time windows, in order to make a positive determination of location of the capsule 10 at the associated location.
  • the characteristic frequency from the spectral analysis results of n consecutive time windows is within a particular peristalsis indicator frequency range.
  • the minimum signal threshold to apply to a series of time periods may be, for example, a minimum summation of signal energy in the frequency range over the series of time periods, or a minimum proportion of individual time windows for which the signal in the frequency range exceeds a minimum for the individual time window. For example if an individual time window minimum is satisfied for 3 out of 4 time windows then that may result in the minimum signal threshold being satisfied, but if the individual time window minimum is only satisfied for 2 out of the 4 time windows then that may not be sufficient.
  • the determination may be a two-step process including first detecting S 104a a signal within the or each of the predefined set of frequency ranges, and second determining location SI 04b by comparing the detected signal with a predefined threshold minimum to determine whether the detected signal is strong enough for a positive determination of presence of the capsule 10 within the location associated with the respective frequency range.
  • a signal must exceed a threshold in order to be considered a detection, for example a threshold based on signal-to-noise ratio or signal-to-interference-plus-noise ratio.
  • a threshold based on signal-to-noise ratio or signal-to-interference-plus-noise ratio.
  • a pre-trained machine learning algorithm may process the result of the spectral analysis to determine the location of the ingestible capsule at the one or more time windows.
  • Figure lb illustrates a method in which the spectral analysis result is analysed to extract information relating to respiration and associated health parameters.
  • the process may include detecting signals in other relevant frequency ranges, for example, for health monitoring and diagnostics. Measurements representing signal amplitude or energy at one or a series of time windows in one or more from among a further set of frequency ranges may be calculated (either on-board or at a remote processing apparatus) and stored for reporting.
  • the further set of frequency ranges may be the respiration information frequency ranges referred to above, which is not to be interpreted as solely indicating respiration, but also allied rhythmic processes such as heart beat and snoring.
  • - a heart rate frequency range at around 50 to 120 cycles per minute
  • snoring frequency range at around 3600 to 18000 cycles per minute.
  • an application or messaging interface may be to provide the information to a clinician or to the subject.
  • the information extracted at SI 05 may be combined with contemporaneous readings from a pulse oximeter sensor 32, wherein combined is taken to mean reported in combination with (and aligned in terms of timings).
  • a report comprising an indication of time windows at which signals were or were not present in the respiration frequency ranges of interest, and the contemporaneous influence on pulse oximetry data, may be of particular interest to a clinician.
  • SI 04a and SI 04b with SI 05 enable a clinician to perform health monitoring or diagnostics in which, for example, influence of sleep or snoring on GI tract motility is analysed.
  • the method of Figure lb in which respiration information is extracted, may be used in a sleep study.
  • one or more of the following may be detected in the spectral analysis and such detections included in the extracted respiration information for reporting and output at SI 07:
  • Extracted respiration information may further include respiration rate and changes in rate.
  • the extracted respiration information may be combined (in a report) with contemporaneous readings from an onboard or external pulse oximetry sensor 32.
  • the extracted respiration information may be combined in a report with contemporaneous sensor data or information derived therefrom indicating movement and GI tract motility of the subject.
  • Extracted respiration information may be performed by pattern-matching based on a predefined set of frequency domain patterns each associated with a respiration pattern or respiration disorder.
  • a pattern matching algorithm may be executed on-board the capsule or at the remote processing apparatus.
  • the pattern may be in the spectral analysis for one time window or a series of time windows.
  • the pattern may comprise a marker, signature, or some other identifiable characteristic that facilitates matching by the pattern matching algorithm.
  • a classifier machine learning algorithm may be trained with training data comprising spectral analysis (from SI 03) for one or a series of time windows from patients known to have a particular respiratory condition, or to be exhibiting a particular respiratory pattern (normal breathing, disordered breathing), labelled with the condition or respiratory pattern as ground truth, training the machine learning algorithm to classify input representations of spectral analysis from SI 03 for one or a series of time windows to one of the respiratory conditions or respiratory pattern.
  • one or more metrics derived from the spectral analysis may be included as input to the machine learning algorithm or pattern matching algorithm, such as centre frequency variability. Equivalent functionality may be provided by a pattern matching algorithm. In either case the algorithm may be applied on the capsule or at the remote processing apparatus. Examples of respiratory conditions or patterns include:
  • the outcome of the pattern matching, the classifier machine learning algorithm, or the simplified alternative, may be included in a report to be output to a receive computing apparatus, to a message recipient, or to a particular storage location for later access by the subject or a clinician.
  • Further information may be derived from the spectral analysis, in particular where the process is repeated for a series of time periods. For example, fluctuations, variations, or anomalies within particular spectral components (frequency ranges of interest such as respiration information frequency ranges or fitting certain respiration patterns) or of frequencies in a heart rate range, may be recorded and reported, either on-board the capsule 10, or in case the process is performed at a remote processing apparatus, then at the remote processing apparatus. Such further information may be valuable for health monitoring and diagnostic purposes.
  • An example of such further information is power distribution across the entire frequency range (or within the frequency ranges of interest) in one or a series of time periods.
  • An example of such further information is rhythm or distribution of a centre frequency across a series of time periods (optionally across the entire passage through the GI tract).
  • Such further information is the identification of gaps in the respiration information frequency ranges, that is, is there a time period or time periods where signals in one of the respiration indicator frequency ranges is lower than chronologically adjacent time periods, or is not detectable whereas it is detectable in time periods before and after.
  • An example of such further information is a metric or metrics calculated from the spectral analysis from among: centre frequency, frequency spread, power distribution, frequency gaps. Any of these further information elements may be identified or measured on-board the capsule 10 or at a remote processing apparatus by processing the spectral analysis, and included in a report generated and output at SI 07.
  • Step SI 06 Physical activity analysis
  • Figure 1c illustrates a method in which the spectral analysis result is analysed to extract information relating to subject physical activity. Examples include strength training and gait analysis.
  • Cadence of subject gait may be an indicator of activity type in itself, for example a signal at a component frequency predefined as an indicator of walking (and optionally also associated with a contemporaneous net movement in the motion sensor data indicating movement) may lead to a determination of subject undertaking a walking activity. Likewise for running, albeit at a higher cadence.
  • the spectral analysis may provide information from which a characterisation of a physical activity can be made, such as distance travelled, steps taken, reps performed, cadence, active time vs resting time, intensity (based on power distribution or total power across the full frequency range).
  • Activity type may be determined on-board at S 106 and a signal comprising the result output to a receiver computing apparatus, which may be a smart watch.
  • the signal may be a trigger to the smart watch to start or finish activity tracking.
  • gait analysis may be used to detect sudden changes in gait, which may be a precursor to a fall.
  • the analysis at SI 06 may include comparing the gait of the subject at the time window to a preceding one or more time windows, and in the case of a sudden change, outputting a signal indicating the said change to a coupled smart watch or smart phone to warn of likelihood of a fall.
  • the said coupled smart watch or smart phone may be configured to relay the warning to a registered contact of the subject.
  • the capsule 10 may be signalled from the coupled smart watch or smart phone to begin gait analysis, initiate an execution of the method of figure 1c, and report either the spectral analysis result or a detection of any unusual gait information to the smart watch or smart phone.
  • the analysis at S106 may comprise, based on the spectral analysis, characterising the physical activity according to a characterisation model predefined for the specified type of physical activity. For example, in the context of weightlifting movements corresponding to repetitions may be identified in the spectral analysis data and counted as the characterisation. In the context of running or walking, signals within cadence ranges may be identified so that the characterisation includes cadence information. Furthermore, analysis of distribution of signals in the cadence range and variability may enable unusual gait to be detected and included in the characterisation. Likewise, periods of rest may be identified and included in the characterisation.
  • the process may further comprise outputting the generated report.
  • the outputting may comprise transmitting the report via a wireless transceiver (for example, via Bluetooth) to a paired receiver computing apparatus 30.
  • the report may be stored at the receiver computing apparatus 30, may be combined with further reports from the same ingestible capsule 10 (i.e. from the same GI tract passage), and may be relayed to a messaging recipient or uploaded to a remote computing apparatus for storage and optionally for further analysis.
  • a report is a message or other data artefact comprising payload data (the specified information) and optionally also metadata for the purposes of enabling the transmission of the report itself from one device to another.
  • those reports may be combined and treated as a single report for the purposes of data transmission.
  • a single set of messaging metadata may be combined with two or more such reports as payload data, to comprise a single combined report message.
  • Such a single combined report message may be generated at the capsule 10 and transmitted from the capsule 10 to the receiver computing apparatus 30 via Bluetooth.
  • Such a single combined report message may be generated at the receiver computing apparatus 30 and uploaded or otherwise sent to a remote computing apparatus or message recipient, either by combining individual reports generated by and received from the capsule 10 or by generating the individual reports at the receiver computing apparatus 30.
  • the methods of Figures la to Id may be performed on a repeated basis to monitor the relevant information (capsule location within GI tract, respiration, activity type) across a plurality of time windows.
  • the time windows need not run continuously.
  • the time windows may be contiguous.
  • the time windows may be partially overlapping.
  • the time windows may be separated by gaps of five, ten, fifteen, thirty, sixty minutes, for example.
  • the time windows themselves may be of the order of one minute, two minutes, five minutes, ten minutes, depending on the implementation.
  • the purpose of tracking the location may be to generate a motility report indicating a length of time the capsule 10 spent at each of plural locations within the GI tract such as stomach, small intestine, large intestine, or some combination thereof. Such information can be helpful in itself in gut health monitoring and diagnosis of conditions.
  • Said report may be augmented with additional sensor data for the same time window and/or with results of other spectral analysis processing steps S105 and/or S106.
  • the capsule 10 may comprise one or more additional sensors, such as illustrated in Figure 4 and Figures 5a to 5c. Wherein additional in this context is taken to mean a sensor beyond the motion sensor 19. Noting that there may be plural motion sensors 19 (an accelerometer and a gyroscope or magnetometer) so the additional sensor may also be a motion sensor.
  • the additional sensors may provide time series data that is also used in location determinations. Alternatively or additionally, the additional sensors may provide data for which the peristalsis detected at SI 04a or the locations determined at SI 04b provide context.
  • the capsule 10 may include one or more gas sensors, and there may be gases or gas concentrations that, if present in a particular location in the GI tract, are indicators of good gut health, poor gut health, or are diagnostic markers for conditions. Such conditions may include, for example, gastroparesis and SIBO.
  • Figure 4 illustrates an ingestible capsule 10 with a plurality of additional sensors. A single one from among the illustrated additional sensors may be included in a capsule 10, or some subset of those illustrated in Figure 4.
  • Figure 5a shows a particular selection, which includes the power source 16, motion sensor 19, wireless transceiver 18 comprising antenna 17 and directional coupler 171 to provide reflectometer readings, control circuitry 15 to control power supply to the other components and optionally also transfer of readings from the reflectometer and motion sensor 19 to the memory hardware 152, and processor hardware 151.
  • the sensors are a motion sensor 19 and reflectometer, so no direct exposure to the environment is required.
  • the arrangement of Figure 5a includes processor hardware 151.
  • Figure 5a may be configured to transmit raw motion sensor data away from the capsule 10 to remote processing apparatus for generating the spectral analysis result at SI 03 and S104Banalysing or otherwise processing the spectral analysis result at S104B, S105, or S106.
  • the processor hardware 151 may be included and one or both of performing the spectral analysis SI 03 and the spectral analysis processing S104B-S106 performed on-board the capsule 10.
  • the optional additional sensors in the capsule 10 may be one or some combination from among:
  • a gas sensor which in particular may be a TCD gas sensor 131 and/or a VOC gas sensor;
  • a reflectometer formed by an antenna 17 of the wireless data transceiver 18 and a directional coupler 171 (noting that one or more of these components may be present on the capsule for data communication purposes irrespective of reflectometer functionality.
  • the capsule 10 may include one or both of a TCD gas sensor 131 and a VOC gas sensor 132.
  • the gas sensors 13 are less than several mm in dimension each and are sensitive to particular gas constituents including oxygen, hydrogen, carbon dioxide and methane.
  • the VOC sensor 132 may be configured to give sensor side readings and driver or heater side readings.
  • the heater side readings may be used to determine thermal conductivity of a surrounding gas and thereby the heater side readings of the VOC are TCD readings.
  • the sensor side readings are used to determine concentrations of volatile organic compounds in the surrounding gases and are VOC readings.
  • the TCD sensor 131 may be, for example, a heating element coupled to a thermopile output, with the thermopile temperature varying due to energy conducted into the gas at the location of the capsule 10.
  • the TCD sensor 131 measures rate of heat diffusion away from the heating element.
  • the heater side of the VOC sensor (operating as a TCD sensor) and the sensor side of the TCD sensor have different operating ranges, so TCD readings from the two sensors collectively span a wider range of operating temperatures than either of the sensors individually. Both sensors have heating elements.
  • the TCD sensor has a low operating temperature but with a high precision.
  • the heater side of the VOC increases the operating range but has a lower precision for TCD readings than the TCD sensor.
  • the larger collective thermal range achieved by the two gas sensors 13 in concert enables better resolution of analytes in the second processing branch.
  • the thermal conductivity of constituent gases in the gas mixture of the GI tract varies with temperature and so by obtaining TCD readings at different operating temperatures the different gases can be resolved from each other. This may be leveraged in measuring concentrations of constituent gases in the gas mixture surrounding the capsule 10.
  • the capsule 10 may not include any gas sensors or may include only a single gas sensor.
  • the gas sensors are contained in a portion of the capsule 10 sealed from the power source 16 and other electronic components by a membrane 111.
  • the outer surface of this portion of the capsule may be composed of a selectively permeable membrane 11, or there may be an aperture allowing the gas mixture surrounding the capsule 10 to enter into the portion of the capsule 10 housing the gas sensors (and the temperature sensor 14a and relative humidity sensor 14b, where included).
  • the gas sensors include respective heaters which are driven to heat sensing portions of the respective gas sensors to temperatures at which sensor readings are obtained (i.e. a measurement temperature).
  • the heaters may be driven in pulses so that there is temporal variation in the sensing portion temperature and so that measurement temperatures are obtained for periods sufficient to take readings but without consuming the power that would be required to sustain the measurement temperature continuously.
  • the gas sensors may be calibrated, so that a gas sensor reading can be used to identify the composition and concentration of a particular gas.
  • Calibration coefficients are gathered in manufacturing and applied to the recorded readings at the processing stage (i.e. by a server such as on the cloud or on-board the capsule 10). Otherwise, this calibration could be performed on the capsule 10, at the receiver computing apparatus 30, or on any device having access to the calibration coefficients and the recorded readings from the gas sensors.
  • Such calibration relates to processing concerned with measuring the concentration of constituent gases in the gas mixture at the capsule 10. Context for the outputs of that processing may be provided by the determinations made at SI 04b providing a location of the capsule 10 within the GI tract at which said gas mixture is found.
  • the gas sensors may be used on a relative measure basis, where there is no formal pre -calibration and it is simply the variability in readings that is used.
  • the gas sensors could be calibrated on-the-fly using stomach data as a baseline. Additional sensor data may be processed to identify one or more motility markers to use as part of the determination at SI 04b. More detail on the detection and precise form of said motility markers is set out in PCT/AU2022/051270, to which reference may be made. A summary is presented below for ease of reference.
  • FIG. 5b illustrates a capsule arrangement in which the additional sensor hardware comprises an EMG 31.
  • the EMG 31 may be on-board the capsule 10 or may be separate from the capsule 10 but provided as part of a system comprising the capsule 10 and the EMG 31.
  • the capsule 10 may include an EMG (electromyographic) sensor comprising a pair of electrodes on an external surface of the ingestible capsule 10 at either end.
  • the EMG sensor measures electrical activity in a medium or on a surface by measuring a potential difference across the pair of electrodes.
  • the EMG sensor 31 may be separate from the capsule 10, and may comprise two or more electrodes affixed to the skin of the subject at locations corresponding to the GI tract.
  • the sensor data from the EMG sensor 31 may be processed on-board the capsule 10, or may be transmitted to the remote computing apparatus for processing.
  • the sensor data, or one or more results from the processing of the sensor data by a computing apparatus in receipt of the said sensor data may be transmitted to the wireless transceiver 18 of the capsule and then used by the on-board processor hardware 151.
  • the EMG sensor data may be used to add confidence to location determinations made from the results of the spectral analysis of the motion sensor data, or may be used in reporting to add context to results, or in diagnostics that utilise the location determination.
  • One or more from among: the motion sensor data; the spectral analysis result; location determinations; peristalsis detections; respiratory information; gait analysis information; activity type determination; the additional sensor data; and detected motility event timings; may be included in a report.
  • the reported data are contemporaneous, meaning that additional sensor data readings in a time series representing a time window are included in a report also comprising a spectral analysis result of the motion sensor data for the same time window, and/or an outcome or result of processing the said spectral analysis result.
  • the report may be compiled on-board the capsule 10 (by the memory hardware 152 and processor hardware 151) and transmitted away during passage through the GI tract or in a burst or inquiry mode following detection of excretion (for example by detecting a freefall event), or the report may be compiled by the remote computing apparatus. Or the report may be compiled on-board the capsule 10 and by the remote computing apparatus in combination.
  • Figure 5c illustrates a pulse-oximetry sensor 32 as additional sensor hardware.
  • the pulse-oximetry sensor 32 may be provided on-board the capsule 10 or as a separate part of a system also including the capsule 10.
  • the pulse -oximetry sensor may be finger-worn.
  • the capsule housing 11 may comprise a window or aperture via which LED light is transmitted and reflected light sensed.
  • the pulse-ox sensor 32 may comprise a light transmitter and sensor affixed to the exterior surface of the capsule housing 11.
  • Sensor data from the pulse-oximetry sensor may be included in a report generated by the capsule 10, or the capsule 10 in cooperation with the remote processing apparatus.
  • the report may be used by a clinician for diagnostic purposes.
  • influence of disordered respiration or other respiration events detected in the result of the spectral analysis may be combined with the pulse-oximetry data.
  • pulse-oximetry data from the small intestine may be particularly accurate due to the highly vascularized surfaces of the small intestine.
  • a first on-the-fly determination of location in the small intestine at SI 04b may be a trigger for the microcontroller 15 to turn on the pulse oximetry sensor 32 and start taking readings.
  • Figure 6d illustrates additional sensor data from a live phase of an ingestible capsule, that is, a powered- on phase of a capsule 10 within the GI tract of a subject.
  • An ingestion event (marked T) may be determined from the additional sensor data, for example the rise in relative humidity, or may be determined from a user interaction with a user interface on the receiver computing apparatus 30.
  • Hydrogen concentration measurements are a metric derivable from TCD gas sensor readings, appropriately calibrated. H2 levels or TCD gas sensor readings themselves may be used as a basis for a gastric-duodenal transition indicator (marked ‘GDJ’). H2 levels may be sensed directly or may be derived, such as derived from TCD gas sensor readings. C02 concentration measurements are derivable by appropriate calibration of the TCD gas sensor readings.
  • the ICJ indicator (marked ‘ICJ’) being a steep rise (i.e. positive gradient above a predefined threshold) in CO2 concentration.
  • PCT/AU2022/051270 at [0300] to [0303] explains in more detail how by operating the TCD gas sensor at different sensing temperatures, different gases may be resolved. Extra information may be added by driving the VOC gas sensor heater side to take TCD measurements therefrom.
  • the gastric-duodenal transition event may be detected in the TCD gas sensor readings as a spike, 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.
  • An ilCJ indicator may be detected by identifying an increase in (sensor side) VOC gas sensor output exceeding a predefined threshold.
  • ileocecal junction transition indicator may be detected by identifying an increase in a metric derived from VOC gas sensor output such as CO4 concentration (marked ‘fermentation’ in Figure 6d).
  • a further criterion may be applied such as presence of a contemporaneous, or temporally adjacent to within a predefined temporal distance either side, increase in measured H2 levels exceeding a predefined threshold. Noting that H2 levels are determined from the TCD gas sensor output and/or heater-side VOC sensor output.
  • the determination at SI 04b may be based on the spectral analysis from SI 03 and peristalsis detections at SI 04a alone, or in combination with data from the one or more additional sensors.
  • the data from the additional sensors may provide a motility marker being either an indication either of a location at which the capsule 10 is located (for example reflectometry measurements of the medium surrounding the capsule 10) or that a motility event has occurred (for example an inflection point, spike, or step change in concentration of a particular gas at a transition between two parts of the GI tract).
  • Figure 6d illustrates timings of three motility markers T (ingestion), ‘ICJ’ (ileocecal junction transition indicator), and ‘GDJ’ (gastric duodenal junction transition indicator).
  • Such motility markers from the additional sensor data may be used in a deterministic way at S 104B, for example it may be that a determination that the capsule 10 is in the small intestine at a time window based on the spectral analysis from S 103 can only be made if a gastric emptying event has been detected in the additional sensor data preceding that time window. Likewise, it may be that a determination that the capsule 10 is in the large intestine at a time window based on the spectral analysis from SI 03 can only be made if an ileocecal junction transition event has been detected in the additional sensor data preceding that time window.
  • the spectral analysis from SI 03 and the additional sensor data may be provided to a pretrained machine learning algorithm to classify capsule location at a particular time window.
  • processing of readings may include applying a moderation to TCD readings, from either gas sensor, in order to correct for variations in environmental temperature, based on environmental temperature readings by the environmental temperature sensor 14a.
  • TCD readings are effectively measuring rate of heat loss to surroundings, and so accuracy is improved by measuring the temperature of the surroundings rather than by relying on assumption (i.e.
  • Gastric temperature may vary based on, for example, ingestion of liquids or foodstuffs by the subject mammal, or physical activity undertaken by the subject mammal 40.
  • Environmental temperature is a term used in this document to refer to the temperature of the environment in which the capsule 10 is located, as distinct from operational temperatures of the gas sensors.
  • the sensitivity of the gas sensors to different constituent gases vary according to the operating temperature of the sensors and the processing of the readings includes calibrating (also referred to as moderating or correcting) readings from the gas sensors according to contemporaneous operating temperature and optionally also according to contemporaneous environmental temperature.
  • the capsule electronics further include a microcontroller 15 or some other form of control circuitry, a power source 16, an antenna 17 or plural antennae, a wireless transceiver 18 or plural wireless transceivers, and optionally a reed switch (though in the case of there being two wireless transceivers the reed switch may be omitted) or some other mechanism to initiate data recording.
  • the wireless transmitter 18 may operate in concert with the antenna 17 of the primary transceiver to transmit a data transmission payload including readings from the sensors (collectively referring to the gas sensors 13 and the environmental sensor 14) to a receiver apparatus 30 and/or a remote computer 20 for processing.
  • sensor data may be processed on-board and results transmitted away via the wireless transmitter 18.
  • Figure 4 illustrates the primary transceiver antenna 17 and directional coupler 171 as elements of the wireless transmitter 18, since the antenna is the physical means by which the wireless transmitter 18 transmits data to the receiver apparatus 30.
  • the wireless transmitter 18 is also configured to buffer data for transmission.
  • the wireless transmitter 18 may also be configured to encode the data with a code unique to the capsule 10 among a population of like capsules 10.
  • Figure 7 illustrates an exemplary reflectometer arrangement.
  • the capsule 10 includes a reflectometer comprising a transmission antenna 17 connected in series with a directional coupler 171 configured to measure a reflected signal from the transmission antenna 17, the output signal output by the sensing mechanism comprising accelerometer readings and/or reflectometer readings.
  • a reflectometer comprising a transmission antenna 17 connected in series with a directional coupler 171 configured to measure a reflected signal from the transmission antenna 17, the output signal output by the sensing mechanism comprising accelerometer readings and/or reflectometer readings.
  • the capsule 10 includes the reflectometer, and the ingestible capsule further comprises a diode detector and the diode detector forms a part of the reflectometer, the diode detector being configured to receive the reflected signal from the antenna and to measure an amplitude of the reflected signal, the reflectometer readings in the output signal comprising amplitude measurements of the reflected signal.
  • the ingestible capsule 10 further comprises a quadrature demodulator and the quadrature demodulator forms a part of the reflectometer, the quadrature demodulator being configured to receive the reflected signal from the antenna via the directional coupler and to extract phase information of the reflected signal relative to a carrier signal, the reflectometer readings in the output signal comprising the extracted phase information of the reflected signal.
  • the ingestible capsule 10 further comprises an antenna impedance control mechanism comprising a variable capacitor configured to vary impedance of the transmission antenna, and a controller, wherein the reflectometer and the antenna impedance control mechanism form a closed loop or feedback loop, and wherein the controller is configured to receive the measurements of the amplitude of the reflected signal from a diode detector and to execute a control algorithm to use the amplitude measurements to generate an antenna impedance control signal setting a capacitance of the variable capacitor 172 to vary impedance of the antenna to reduce amplitude of the reflected signal, wherein the reflectometer readings in the output signal comprise readings of the antenna impedance control signal.
  • an antenna impedance control mechanism comprising a variable capacitor configured to vary impedance of the transmission antenna
  • a controller wherein the reflectometer and the antenna impedance control mechanism form a closed loop or feedback loop, and wherein the controller is configured to receive the measurements of the amplitude of the reflected signal from a diode detector and to execute a control algorithm to use
  • the closed loop or feedback loop further comprises a quadrature demodulator, and wherein phase information is extracted by the quadrature demodulator and output to the controller, and wherein the controller is configured to use the amplitude information and the phase information to generate the antenna impedance control signal.
  • the additional sensor data comprises reflectometer readings, and a motility marker may be detected therein.
  • a motility marker may be detected therein.
  • an ileocecal junction transition indicator may be detected in readings from the reflectometer. Processing includes: processing the reflectometer readings to identify the presence of an ileocecal junction transition indicator in the reflectometer readings.
  • Figure 8 illustrates readings from a directional coupler 171 of a reflectometer and in particular illustrates step changes coinciding with the detected gastric duodenal transition indicator and the ileocecal junction transition indicator.
  • the presence of the step change may be detected to directly detect one or both transition events.
  • the antenna reflectance values themselves pre- or post- the transition events may be used as an indicator of capsule location.
  • Interconnections between electronic components may be via a central bus. This is one example of how power and data may be distributed between components.
  • Other circuitry architecture may be implemented, for example, all connections may be via the microcontroller 15 which coordinates distribution of data and power between components.
  • the sensors (the TCD sensor 131, the VOC sensor 132, the environmental sensor 14, the motion sensor 19, the EMG 31, the pulse-ox sensor 32, and/or the directional coupler 171) take readings under the instruction of the microcontroller 15, powered by the power source 16, and transfer the readings to the wireless transmitter 18 for transmission to the receiver apparatus via the antenna 17.
  • the dimension of the capsule may be less than 11.2 mm in diameter and 27.8 mm in length.
  • the housing of the capsule 10 may be made of indigestible polymer, which is biocompatible.
  • the housing may be smooth and non-sticky to allow its passage in the shortest possible time and to minimise risk of any capsule retention.
  • Detected motility markers described here may be utilised in determining release timing of therapeutic matter, or determining sampling timing.
  • Figure 9 shows time series of accelerometer readings as ‘roll’ in each of three mutually orthogonal dimensions and is marked with gastric emptying event, from which it can be seen that the change in accelerometer readings correlates temporally with a gastric emptying event. Therefore, accelerometer time series data may be utilised to provide an indicator of timing of a gastric-duodenal transition event which may be used to add confidence to a location determination at SI 04b.
  • the capsule orientation is measured using a triaxial accelerometer and tracking the gravity vector with respect the capsule frame of reference.
  • the capsule orientation is measured using a triaxial accelerometer and tracking the gravity vector with respect to the capsule frame of reference. When the capsule leaves the stomach it tends to experience rapid changes in its orientation as it transits through the duodenum and small intestine.
  • Metrics may be calculated from the raw readings, from which metrics one or more motility markers are detectable.
  • a first technique is “angle travelled”, which accumulates the orientation change in excess of a 90 degree hysteresis angle. This technique tends to be robust to small changes in orientation experienced in the stomach and avoids some of the complexities of other approaches.
  • Angle travelled uses vector mathematics to calculate the angle between the gravity vector and a temporary vector.
  • the temporary vector is pulled in the direction of the change in angle, only when this angle exceeds a given threshold (currently 90 Deg). It is then the accumulation of the change in the temporary vector that is visualized in the representation from which markers are identifiable.
  • this measure does not change much in the stomach since the angle between the gravity and temporary vectors rarely exceed the threshold in any one direction, (small back and forth orientation changes in the stomach are effectively ignored by the inherent hysteresis of this algorithm) and that once in the tortuous lumen of the small intestine, this measure accumulates significantly due to the larger, more continuous orientation changes of the capsule.
  • a step change in the cumulative angle travelled measure is a gastric-duodenal transition indicator.
  • the accelerometer readings may provide a reading of an orientation of the ingestible capsule relative to a frame of reference in fixed relation to a gravitational vector.
  • Processing of the readings from the accelerometer may comprise recording an orientation of the ingestible capsule given by a first accelerometer reading as a reference orientation, and repetitively in respect of each successive accelerometer reading chronologically: determining whether the orientation of the ingestible capsule given by the respective accelerometer reading is more than a threshold angular displacement from the reference orientation, and if the threshold angular displacement is not met, progressing to the next accelerometer reading without changing the reference orientation, and if the threshold angular displacement is met, changing the reference orientation to align with the orientation of the ingestible capsule given by the respective accelerometer reading.
  • An indicator such as the gastric -duodenal transition indicator, may be a step change in the rate of change of the reference orientation.
  • a second technique for processing accelerometer data may be referred to as total roll.
  • Total roll calculates the angle between the gravity vector and each of the capsule X, Y and Z axes and expresses this as a continuous measure that can accumulate beyond 360 Deg. For example, if the capsule x axis is at an angle of 350 Deg and rotates by a further 20 Deg, the resulting angle is expressed as 370 Deg rather than 10 Deg. This helps when representing the readings as a plot from which markers are identified since it avoids the sudden angle changes associated with crossing the zero line.
  • the accelerometer readings provide a reading of an orientation of the ingestible capsule relative to a frame of reference in fixed relation to a gravitational vector.
  • Exemplary processing of the readings from the accelerometer may comprise for each of three orthogonal axes in fixed spatial relation to the ingestible capsule derivable from the reading of the orientation, repetitively in respect of each successive accelerometer reading chronologically: calculating, as a scalar value, a change in the orthogonal axis relative to the gravitational vector from the preceding accelerometer reading; applying a low pass filter to the calculated changes; recording the cumulative filtered calculated changes.
  • a marker serving as a gastric-duodenal transition indicator may be, for example, an increase (such as a spike or step change) in the rate of increase in the cumulative filtered calculated changes.
  • Figures 10 & 11 illustrate schematically ingestible capsules configured to carry therapeutic matter into the GI tract of the subject and to release the therapeutic matter at a timing determined at least partially, or entirely, according the determination of location at SI 04b based on the spectral analysis at step SI 03 of the motion sensor data generated at S 102.
  • the motion sensor 19 functions as a sensing mechanism.
  • a release mechanism 20 includes a microcontroller 15, and a determination of release timing is made by the microcontroller according to determination of capsule location within the GI tract by on-board processing of the time series of motion sensor data generated at S102.
  • the processing hardware 152 may be a part of the microcontroller or distinct.
  • the microcontroller 15 comprises a memory 151 and a processor 152.
  • the microcontroller 15 is configured with midware or software to perform its functionality with respect to determining release timing of the therapeutic payload (based on the processor hardware 152 determining a location of the ingestible capsule within the GI tract as coincident with a target release location of therapeutic matter carried in carrying compartment 22).
  • the line around the release mechanism 20 is dashed to indicate that components therein do not necessarily perform functionality solely relating to the release mechanism 20 and may perform other functions.
  • the microcontroller 15 may perform functions including power and data distribution, data sampling, data processing, motility event indicator identification, release timing determination etc.
  • the processes of SI 03 onward from Figures la to Id is performed by the on-board processor hardware 152.
  • apparatus for determining location of the capsule within the GI tract includes remote processing apparatus, which comprises a receiver computing apparatus 30 and may also include a further computing apparatus 20.
  • the wireless transceiver may be configured to function as a reflectometer to provide additional sensor data as discussed above.
  • the wireless transceiver may be arranged as shown in Figure 7.
  • the capsule 10 may be configured to release therapeutic matter carried by the capsule 10 directly into the GI tract of the subject at a timing based on the determination of location at SI 04b.
  • the release timing may be immediately upon determination that the capsule 10 is located at a target release location of the therapeutic matter, or may be a predefined delay thereafter.
  • W02023087074 describes the configuration of an ingestible 10 with a therapeutic matter carrying compartment and release mechanism. Reference to that document could be made for a full description of those elements. A summary is provided herein for ease of reference, noting that further specific examples are provided in W02023087074.
  • An ingestible capsule 10 may comprise a housing 11, being a biocompatible indigestible housing including a therapeutic payload carrying compartment; a power supply; a release mechanism; and a sensing mechanism (comprising the accelerometer only or the accelerometer and the one or more additional sensors), the sensing mechanism being sensitive to the environment external to the housing.
  • the ingestible capsule being configured for passage through a gastrointestinal, GI, tract of a subject mammal (at S 101), during which passage: the sensing mechanism is configured to output an output signal varying according to the GI tract environment external to the housing, wherein the sensing mechanism comprises only an accelerometer or an accelerometer and one or more sensors from among: a VOC gas sensor; a TCD gas sensor; a reflectometer formed by a transmission antenna of the ingestible capsule connected in series with a directional coupler configured to measure a reflected signal from the transmission antenna.
  • the release mechanism is configured to cause a therapeutic payload to be released into the GI tract from the therapeutic payload carrying compartment at a release timing determined according to the output signal.
  • the output signal from the motion sensor (at SI 02) is processed by steps SI 03 to SI 04b of Figure la to determine a location of the capsule 10 within the GI tract (noting that there will be some latency between data generation and determination), and when the determined location coincides with a target location for the therapeutic matter (being a parameter stored by the memory of the capsule 10 or the remote processing apparatus) the therapeutic payload is caused to be released immediately or at a predetermined delay.
  • a target location for the therapeutic matter being a parameter stored by the memory of the capsule 10 or the remote processing apparatus
  • the therapeutic payload (the therapeutic matter) may be one or more from among: a drug, a pharmaceutical formulation, a pre-biotic substance, a faecal transplant, and/or a pro-biotic substance.
  • the components illustrated in Figures 10 and 11 also include a release mechanism 20. Regardless of functional form, the release mechanism 20 includes a release actuator 21 in physical communication with the therapeutic payload carrying compartment 22. Different release mechanism 20 configurations are illustrated in W02023087074 at Figures 3A to 3E.
  • Therapeutic payload may be drugs, prebiotics, probiotics, pharmaceuticals, faecal transplant matter, or other therapeutic matter configured for release into the GI tract for therapeutic effect.
  • the release actuator 21 is physically coupled to the releasable therapeutic payload carrying compartment, and in particular is physically coupled to a portion of the capsule housing at the therapeutic payload carrying compartment so that actuation of the actuator create an opening, aperture, or ruction, in the housing so that the therapeutic payload carrying compartment, and by extension the therapeutic payload itself, is exposed to the environment external to the capsule 10 and thus is released to the GI tract.
  • the electronic components of the capsule 10 are sealed from the therapeutic payload carrying compartment.
  • the capsule housing may contain the therapeutic payload carrying compartment within an open frame structure or via a portion having one or more apertures open to the environment external to the housing, with the therapeutic payload carrying compartment being closed via a valve or some other sealing member that is configured to be opened by the release actuator.
  • a kinked hose that is pulled by the release actuator to release the kink and to deploy the therapeutic payload to the environment external to the capsule 10.
  • the configuration of the release actuator and hose may be such that deployment of the therapeutic payload takes place over a period of time as the capsule 10 transits the colon.
  • the period of time may be between 30 minutes and an hour, between an hour and two hours, or more than two hours.
  • the therapeutic payload carrying compartment 22 may contain a balloon filled with the therapeutic matter, and optionally also further fluid such as liquid or gas or a combination thereof.
  • the release actuator 21 causes the balloon to burst, releasing the therapeutic payload from the balloon and into the subject GI tract via one or more apertures in the capsule housing. It is noted that the portion of the ingestible capsule 10 containing the balloon, and having one or more apertures, is sealed from the portion of the ingestible capsule 10 containing the electronic components (unless a component is specifically described as being in the therapeutic payload carrying compartment 22, for example if required as part of the release actuator 21).
  • the release actuator 21 may store potential energy, such as in a spring, which energy is released by the release actuator 21 in order to create the opening, aperture, perforation or ruction in the housing.
  • the housing is formed of a biocompatible indigestible polymer.
  • the polymer may be scored or otherwise formed to be thinner at the location of the portion physically coupled to the release actuator 21, so that the portion in question may be opened with a high degree of predictability.
  • a surrounding region may be formed thicker, in order to be stronger and thus to reduce likelihood of the opening, aperture, perforation or ruction in the housing extending beyond the coupled portion.
  • a headspace may be defined in the capsule 10 which is in fluid isolation from the remainder of the capsule interior but is in communication with the GI tract via an aperture in the capsule housing.
  • a perforable sealed (biocompatible, indigestible) film or foil contains a therapeutic payload, wherein the release actuator 21 is configured to perforate (i .e . rupture) the film or foil to release the payload to the GI tract via the aperture in the capsule housing.
  • the film or foil may be across or partially across the aperture, or may be otherwise in spatial communication with the aperture so that perforation of the foil causes release of the payload into the GI tract via the aperture.
  • the perforation of the foil or film may be by release of a spring pushing the foil or film against a perforating or puncturing member, or may be, for example, by rotation of a rotating member such as a motor that causes a peeling back, a puncturing, or a perforating of the foil or film.
  • the release actuator 21 may be any actuation mechanism arranged to cause the release of packaged therapeutic payload from the package and into the GI tract.
  • the therapeutic payload carrying compartment 22 may comprise a single compartment carrying all (i.e. the required dosage) of the therapeutic payload.
  • the therapeutic payload carrying compartment 22 may comprise a plurality of sub-compartments, wherein each sub-compartment carries a portion (i.e. a fraction) of the required dosage of the therapeutic payload.
  • the capsule 10 may be preset at time of manufacture, or configurable postmanufacture by a clinician (for example by sending a control signal from an external controller to the wireless transceiver 18 which, via the microcontroller 15 or otherwise, switches between two release modes), according to either of two release modes.
  • the intervals may be all of a predefined equal length (i.e. regular intervals) or may be of predefined unequal lengths (i.e. irregular intervals).
  • the release mechanism 21 may be controllable via the microcontroller 15 or otherwise to release the therapeutic matter at a single release timing or at plural distributed release timings.
  • the power source 16 of the elastic material membrane rupturing mechanism may be a supercapacitor configured to be trickle charged by the ingestible capsule power supply over a period of time beginning with an initiation event of the ingestible capsule, and to be caused to release the charge to the heating element at the determined release timing under the control of the microcontroller.
  • the supercapacitor and the heating element may be impedance matched, or impedance matched to within a defined tolerance.
  • the heating element may be a resistive heater element comprising one or more from among:
  • a release actuator may be an elastic material membrane rupturing mechanism including a power source 16 and a LASER diode focussed on the elastic material membrane, wherein a microcontroller of the ingestible capsule is configured at the determined release timing to activate the LASER diode to rupture the elastic material membrane, thereby unsealing the sealed chamber.
  • a release actuator may be an elastic material membrane rupturing mechanism including a pre-sprung mechanical needle, wherein a microcontroller of the ingestible capsule is configured, at the determined release timing, to release the pre-sprung mechanical needle causing the pre-sprung mechanical needle to spring into the elastic material membrane causing the elastic material membrane to rupture, thereby unsealing the sealed chamber.
  • a release actuator may be an elastic material membrane rupturing mechanism including the release mechanism comprises a microcontroller and a release actuator, and the therapeutic payload carrying compartment comprises a section of the ingestible capsule housing and a sealed chamber, an elastic material membrane defining at least a portion of a wall of the sealed chamber, within which sealed chamber a liquid diluent is sealed, the therapeutic payload being a lyophilized drug or other therapeutic matter in powdered, dehydrated, or other solid form, and being contained within the therapeutic matter carrying compartment in a space external to the sealed chamber and at least partially defined by the elastic material membrane, the section of the ingestible capsule housing comprising one or more apertures enabling fluid communication between the therapeutic payload carrying compartment and the exterior of the capsule, the one or more apertures being blocked by the elastic material membrane and unblocked following rupture of the elastic material membrane by an elastic material membrane rupturing mechanism at the determined release timing, the rupturing of the elastic material membrane allowing the liquid diluent to mix
  • the ingestible capsule 10 may comprise a sampling mechanism to obtain a GI tract sample.
  • the determination of timing is equivalent, so that references above to determining release timing may be applied here to the concept of determining sampling timing. The concept is the same: to identify a motility event and to determine sampling or release timing (as appropriate) accordingly.
  • the ingestible capsule 10 may comprise a chamber that is open to the surrounding environment in a first configuration, and closed to the surrounding environment in a second configuration.
  • the chamber is changed either from the first configuration (open) to the second configuration (closed), or from the second configuration (closed) to the first configuration (open) and returned to the second configuration (closed).
  • a miniaturised motor may drive a sealable door member.
  • the sampling may be passive, for example relying on gas flowing into the chamber. In the first configuration, there may an aperture allowing fluid to flow freely in and out of the chamber.
  • a semi-permeable membrane may remain in place, wherein the difference between the two configurations is that in the second, closed, configuration an impermeable membrane is coupled to the semi-permeable membrane to prevent fluids flowing across the membrane(s).
  • the sampling may be active, in which in the first configuration a protruding member is extended beyond the housing of the ingestible capsule 10 and, after a period of time, retracted into the housing and the chamber returned to the closed configuration.
  • the capsule housing 11 has two apertures or valved interfaces between the interior and exterior of the capsule 10: a one-way sampling valve 121 at a first end of the sampling chamber 126; and a drain aperture or drain valve 127 at a second opposing end of the sampling chamber 126.
  • a fluid-filled ballon or sack 123 At ingestion (i.e. at all times between manufacture of the capsule 10 and sampling) a fluid-filled ballon or sack 123 at least partially occupies the sampling chamber 126.
  • An elastic membrane 122 is in a stretched configuration (i.e. is storing elastic potential energy) between the fluid filled sack 123 and the interior surface of the capsule housing 11 which defines the sampling chamber 126.
  • the elastic membrane 122 is arranged (that is, positioned and composed of an appropriate material) to permit fluid from the fluid-filled sack 123 to exit the sampling chamber 126 via the aperture or drain valve 127, and to block a fluid path between the one-way sampling valve 121 and the aperture or drain valve 127. In other words, fluid entering the sampling chamber 126 via the one-way sampling valve 121 is prevented from leaving the sampling chamber by a combination of the one-way sampling valve 121 and the elastic membrane 122.
  • the trigger signal that initiates the sampling mechanism may be a determination by a microcontroller 15 or other processor hardware 151 on-board the capsule that a determined location of the capsule 10 within the GI tract matches a target sampling location (being a parameter pre-stored or signalled to the capsule 10).
  • capsule location within the GI tract may be determined by remote processing apparatus, which remote processing apparatus also stores an indication of target sampling location, so that a trigger signal sent to the capsule 10 is simply an instruction to initiate sampling, in the absence of any location information. Which is received by the data transceiver 18, and via a microcontroller or otherwise, triggers the sampling mechanism.
  • Determining capsule location to trigger sampling may be performed by the methods of Figure la to Id including capsule location determination SI 04b.
  • the location determination step SI 04b causing triggering of the sampling mechanism may be performed on-board the capsule 10 or may be performed remotely.
  • a microcontroller 15 may be in a listening mode for a trigger signal to trigger sampling (for example if location determination S104b is being performed at a remote processing apparatus), or the microcontroller 15 may store an indicator of a target sampling location, and may monitor location determinations may by one or more executions of SI 04b performed on-board the capsule to determine when the determined location at SI 04b matches the target sampling location. In either case, when the capsule 10 is determined to be at the target sampling location, the microcontroller 15 (which may be or include the on-board processor hardware 151 or other control circuitry) triggers a sack rupturing actuator 124.
  • the sack-rupturing actuator 124 is a heater in contact with the fluid-filled sack 123 configured to actuate by heating quickly and causing the sack 123 to rupture.
  • Other options include a miniaturised motor configured to actuate by driving a pin into the fluid-filled sack 123, or a laser light from a laser diode configured to actuate by focusing laser light onto a surface of the fluid-filled sack 123 to cause rupturing.
  • the heater, or heating element may be an SMT resistor; metallic resistive wire; nichrome; MEMS heater element.
  • a pre-sprung mechanical needle may be released at the determined sampling timing to cause a point of the needle to contact the fluid-filled sack and cause rupturing.
  • the sack rupturing actuator comprises a power source, a shape memory alloy wire, and a rupturing member, the power source being configured, at the determined sampling timing and under control of the microcontroller, to transfer energy to the shape memory alloy wire, to initiate a phase change at material level of the shape memory alloy wire and thereby to exert a force on the rupturing member to cause the rupturing member to come into contact with, and to rupture, the fluid- filled sack.
  • Electrodes on opposing sides of the sampling chamber may be included and used as a mechanism to measure how full the sampling chamber is.
  • the sack-rupturing mechanism 124 actuates to cause the sack 123 to rupture and thereby to cause the fluid from the sack 123 to flow from the sack 123 out of the sampling chamber 126 via the aperture or drain valve 127, and the elastic membrane 122 to become less stretched than in the stretched state and thereby to reduce pressure in the sampling chamber 126.
  • By becoming less stretched it is to be understood to mean that at least a portion of the elastic potential energy stored in the elastic membrane 122 is released. A pressure differential established between the sampling chamber
  • the GI tract fluid (i.e. the sample) obtained reduces the pressure differential which causes the one-way sampling valve 127 to close and so the GI tract fluid is then retained in the sampling chamber 126 by the closed one-way sampling valve
  • the fluid-filled sack is filled with water or a saline solution not harmful to the GI tracked.
  • Target sampling location may be stomach, small intestine, large intestine, cecum, proximal small intestine, distal small intestine.
  • the power source 16 of the capsule 10 may be a lithium cell or a supercapacitor.
  • the elastic membrane 122 is to encapsulate the GI tract fluid and so is selected to be biocompatible, elastic, and stable.
  • the fluid-filled sack 123 is to be burstable with heat and to be stable and biocompatible.
  • the capsule 10 also includes a motion sensor 19 for generating the motion sensor data at SI 02 leading to the location determination at SI 04b.
  • the capsule may also include a temperature sensor to take readings for the microcontroller 15 to determine when to switch the capsule from a sleep state to a live state (for example, wake every minute, take a reading, and if ⁇ 35 degrees Celsius, return to sleep).
  • the capsule may wake every minute and take a reading from the motion sensor 19, and return to sleep if no movement is detected by the motion sensor 19, and so the temperature sensor may be omitted.
  • Timing of the actuation of the sack rupturing member 123, or some other representation of sampling time, may be included in a report such as at SI 07 to be transmitted away from the capsule 10 via Bluetooth.
  • the capsule 10 may also be configured to monitor and feedback a filled state of the sampling chamber 126.
  • the fluid occupying the fluid filled sack 126 prior to rupturing may be liquid or gas.
  • the timing of the GI tract sampling by the sampling mechanism is based on a determination of capsule location, and sampling is triggered when the determined capsule location matches a target sampling location.
  • the location determination may be based upon spectral analysis SI 03 of motion sensor data generated at SI 02 and processed according to the process described above including detecting peristalsis SI 04a in the spectral analysis and determining location S 104b based on the peristalsis detection.
  • the location determination may be based upon a motility marker identified in a time series of data from a sensor.
  • the sensor may be a motion sensor 19.
  • the sensor may be a gas sensor, or a reflectometer.
  • the motility marker may be either an indication either of a location at which the capsule 10 is located (for example reflectometry measurements of the medium surrounding the capsule 10) or that a motility event has occurred (for example an inflection point, spike, or step change in concentration of a particular gas at a transition between two parts of the GI tract).
  • Figure 6d illustrates timings of three motility markers T (ingestion), ‘ICJ’ (ileocecal junction transition indicator), and ‘GDJ’ (gastric duodenal junction transition indicator). Processes for identifying motility markers in time series of data from sensors are described elsewhere in this document and may be applied in the context of the present discussion of determining location of the capsule to determine GI tract sampling timing.
  • a microcontroller 15 on the capsule 10 may be monitoring output signals from a sensor (sensing mechanism) such as a VOC gas sensor, a TCD gas sensor, a motion sensor, a reflectometer, to identify either or both of a gastric-duodenal transition indicator or an ileocecal junction transition indicator to trigger the sampling mechanism.
  • a sensor sensing mechanism
  • VOC gas sensor a VOC gas sensor
  • TCD gas sensor a motion sensor
  • reflectometer to identify either or both of a gastric-duodenal transition indicator or an ileocecal junction transition indicator to trigger the sampling mechanism.
  • Reporting of information away from the capsule by Bluetooth or 433 MHz transmission may include an indication of timing of the sampling, and/or one or more elements such as a record of sampling timing; a record of excretion timing; a record of the one or more identified ileocecal junction transition indicators; a record of the one or more identified gastric -duodenal transition indicators; a record of an electrode signal indicating rupturing of the fluid-filled sack; a record of an electrode signal indicating a filled state of the sampling chamber; output signal output by the sensing mechanism; and a metric or metrics representing the output signal output by the sensing mechanism
  • references to the sampling chamber being sealed are to imply releasably sealed, so that retrieval of the sample is possible by a technician or clinician. For example by perforating the membrane and syringing the content.
  • the ingestible capsule 10 includes a power source.
  • the power source may be a battery or may be a supercapacitor.
  • Figure 13 illustrates a method or process, in which steps in common with methods of Figures la to Id are assigned like reference signs.
  • the process of Figure 13 is performed by or in association with a capsule such as illustrated, for example, in Figures 3a, 3b, 4, 5a, 5b, 5c, but which also includes an onboard vibrating motor.
  • the on-board vibrating motor may be, for example, an eccentric mass rotating motor, or a linear vibratory motor, or any motor configured to cause the capsule to vibrate.
  • a vibration therapy initiation condition may be the large bowel residence condition.
  • a vibration therapy initiation condition may be partially based on the large bowel residence condition being satisfied, and partially based on another condition, such as energy remaining in the power source, absence of an override flag/switch.
  • the large bowel residence condition may be simply that the capsule is resident in the large bowel. Alternatively, the large bowel residence condition may be that the capsule has been resident in the large bowel for more than a threshold time period.
  • the threshold time period may be, for example, not less than one hour, not less than two hours, not less than three hours, not less than four hours, not less than five hours, not less than six hours, not less than eight hours, not less than ten hours, not less than twelve hours, not less than fourteen hours, not less than sixteen hours, not less than eighteen hours, not less than twenty hours, or not less than twenty four hours.
  • the threshold time period may be selected to be a value associated with the capsule progressing to the distal portion of the bowel.
  • the process of steps S 102 so S 113a is repeated (and may eventually be stopped by a termination event such as excretion or powering off of the capsule) . If the large bowel residence condition is met at SI 13a, the process continues to SI 13b and vibration is initiated. Optionally, the process of SI 02 to SI 04b may be performed repetitively until a termination event such as excretion or powering off of the capsule occurs.
  • the vibrating motor Upon initiation of vibration at SI 13b, the vibrating motor is powered on and the capsule is caused to vibrate. The intention is to stimulate a bowel movement.
  • the initiated vibration may be for a fixed time period or may continue indefinitely.
  • the initiated vibration may be pulsed, wherein the vibrating motor is powered on for a pulse period and then powered off for a rest period, on a repeated basis, for the vibration duration.
  • the vibration duration may be, for example, ten minutes, twenty minutes, thirty minutes, or one hour.
  • the pulse periods may be, for example, five seconds, ten seconds, twenty seconds, thirty seconds.
  • the rest periods may be, for example, five seconds, ten seconds, twenty seconds, thirty seconds.
  • Completion of the vibration duration may be followed by an enforced period of inactivity so that the vibration motor cannot be powered on again for, for example, one hour, two hours, three hours, or four hours.
  • the capsule may be configured to initiate only a finite number or vibration durations during GI tract passage, for example, one, two, three, four, or five.
  • Detection of an excretion event may cause the controller to power off the vibrating motor.
  • the initiation of the vibrating motor, or the switching from the powered off state to the powered on state during a vibration duration may be conditional upon the power source having a predefined amount of energy remaining.
  • the controller may be configured to guarantee the power source has sufficient energy at excretion to transmit a report away from the capsule to a receiver apparatus.
  • the vibrating motor may be configured to cause vibration in one spatial dimension, or in two or three mutually orthogonal spatial dimensions.
  • the controller may have a vibrating motor override flag or switch which, upon receipt of a predefined signal from a paired apparatus external to the body such as a smartphone or receiver apparatus paired with the capsule, prevents the vibrating motor being switched into a powered on state even if other conditions such as at S 113a are met.
  • the capsule since the capsule was only ingested one hour ago, it is still resident in the stomach and so is not passed in the bowel movement. Experience of the bowel movement may remove the motivation to initiate or conduct vibration therapy via the capsule, and so by allowing the subject to log the bowel movement on the paired apparatus (i.e. via an app or another user interface), a signal is transmitted to the capsule which switches the override flag or switch to a state preventing the vibrating motor from being powered on.
  • the default state of the override flag or switch may be a state which permits the powering on of the vibrating motor.
  • measurement of time series of motion sensor data such as at S 102 may be suspended during the vibration duration, or more specifically whenever the vibrating motor is in a powered on state.
  • the vibration caused by the vibrating motor may be extracted from the spectrograph generated at SI 03 prior to determination of location within the GI tract at SI 04b.
  • a method comprising: following ingestion of an ingestible capsule by a subject, the ingestible capsule housing a motion sensor configured to generate a time series of motion sensor data representing motion of the ingestible capsule during passage through the GI tract of a subject, at data processing hardware communicably coupled to the motion sensor, performing a process comprising: generating a spectral analysis of the time series of motion sensor data generated by the motion sensor over a time period during passage of the ingestible capsule through the GI tract, extracting from the spectral analysis respiration information comprising an indication of respiration rate.
  • Statement 2 The method of Statement 1, wherein the extracted respiratory information comprises a measurement of a signal in one or more from a predefined set of respiration information frequency ranges.
  • Statement 3 The method of Statement 2, wherein the predefined set of respiration information frequency ranges includes a first respiration information frequency range indicating snoring, and a second respiration information frequency range indicating respiration.
  • Statement 4 The method of Statement 3, wherein the first respiration information frequency range is between 12 and 18 cpm.
  • Statement 6 The method of any of Statements 1 to 5, wherein the ingestible capsule further comprises, or is operably coupled to a separate, one or more additional sensors, each additional sensor being configured to generate a time series of additional sensor data; the additional sensor comprises a pulse oximetry sensor configured to generate a time series of pulse oximetry measurements representing concentration of oxygen in blood of the subject; the method further comprises generating and outputting a report comprising the extracted respiration information for the time window and a contemporaneous extract from the time series of pulse oximetry measurements.
  • Statement 7 The method of Statement 6, wherein the report is generated and output by processor hardware and a wireless data transceiver on board the ingestible capsule.
  • Statement 8 The method of Statement 6, wherein the report is generated and output by a remote processing apparatus configured to receive data transmitted away from the ingestible capsule by a wireless data transceiver.
  • Statement 10 The method according to any of the preceding Statements, wherein the method comprises repeating the process for a series of time periods during passage of the ingestible capsule through the GI tract.
  • Statement 11 The method according to Statement 10, wherein the series of time periods are contiguous, or wherein the series of time windows are sliding so that adjacent time windows in the series partially overlap one another.
  • Statement 13 The method according to any of the preceding Statements, wherein the sensor hardware comprises a gyroscope and the sensor data comprises a time series of gyroscope data representing changes to a frame of reference of the ingestible capsule relative to a fixed frame of reference; extracting from the gyroscope data a long axis rotation time series representing rotation of the ingestible capsule about the long axis defined by the capsule housing; wherein the spectral analysis is generated from the long axis rotation time series.
  • the motion sensor is a three-axis accelerometer and the motion sensor data comprises three time series each representing acceleration in a respective one of the three axes
  • generating the spectral analysis comprises: transforming each of the three time series into respective single axis frequency domain representations; combining the three single axis frequency domain representations to obtain a combined frequency domain representation.
  • Statement 15 The method according to any of Statements 12 to 14, wherein combining the three single axis frequency domain representations comprises comparing magnitude of a signal in a taiget frequency range from each of the single axis frequency domain representations, and selecting the single axis frequency domain representation with the greatest magnitude signal in the target frequency range as the combined frequency domain representation.
  • Statement 16 The method according to any of Statements 12 to 14, wherein combining the three single axis frequency domain representations comprises, for each component frequency in the frequency domain, combining a component magnitude from each of the single axis frequency domain representations, the resulting combination per component frequency being the combined frequency domain representation.
  • Statement 17 The method according to Statement 16, wherein wherein the combining is a summation, or a root sum squared.
  • the ingestible capsule further comprises a wireless data transmitter to transmit the to transmit the time series of motion sensor data to a remote apparatus for processing, the data processing hardware being a component of the remote apparatus.
  • Statement 21 The method according to any of the preceding Statements, wherein the process further comprises: generating a report including information extracted from the spectral analysis representing fluctuations, variations, or anomalies within spectral components.
  • the ingestible capsule further comprises one or more additional sensors configured to generate a time series of sensor data
  • the process includes generating and outputting a report including one or more from among: the spectral analysis for the time period, and a result of processing the spectral analysis for the time period comprising information indicating a respiration rate, information indicating a detection of peristalsis, or information indicating a physical activity type being undertaken by the subject; additional sensor data readings from the same time period, and/or an outcome or processing the additional sensor data readings from the same time period such as a metric or identification of a motility marker, and/or information derived from additional sensor data readings from the same time period.
  • Statement 24b The method according to any of the preceding Statements, wherein the process includes determining the location of the capsule within the GI tract based on the detected peristalsis; the ingestible capsule further comprises a vibrating motor arranged, when in a powered on state, to vibrate within the capsule to cause vibration of the capsule housing, and the process further comprises, in response to the determined location of the ingestible capsule satisfying a vibration therapy initiation condition, causing the vibrating motor to switch from a powered off state to the powered on state.
  • Apparatus comprising : an ingestible capsule housing a motion sensor configured to generate a time series of motion sensor data representing motion of the ingestible capsule during passage through the GI tract of a subject; data processing hardware communicably coupled to the motion sensor, the data processing hardware being configured, following ingestion of the ingestible capsule by the subject, at data processing hardware communicably coupled to the motion sensor, to perform a process comprising: generating a spectral analysis of the time series of motion sensor data generated by the motion sensor over a time period during passage of the ingestible capsule through the GI tract, extracting from the spectral analysis respiration information comprising an indication of respiration rate.
  • Statement 26 The apparatus of Statement 25, wherein the extracted respiratory information comprises a measurement of a signal in one or more from a predefined set of respiration information frequency ranges.
  • Statement 27 The apparatus of Statement 26, wherein the predefined set of respiration information frequency ranges includes a first respiration information frequency range indicating snoring, and a second respiration information frequency range indicating respiration.
  • Statement 28 The apparatus of Statement 27, wherein the first respiration information frequency range is between 12 and 18 cpm.
  • Statement 29 The apparatus of Statement 28, wherein the second respiration information frequency range is between 3600 and 18000cpm.
  • Statement 30 The apparatus of any of Statements 25 to 29, wherein the ingestible capsule further comprises, or is operably coupled to a separate, one or more additional sensors, each additional sensor being configured to generate a time series of additional sensor data; the additional sensor comprises a pulse oximetry sensor configured to generate a time series of pulse oximetry measurements representing concentration of oxygen in blood of the subject; the method further comprises generating and outputting a report comprising the extracted respiration information for the time window and a contemporaneous extract from the time series of pulse oximetry measurements.
  • Statement 31 The apparatus of Statement 30 wherein the report is generated and output by processor hardware and a wireless data transceiver on board the ingestible capsule.
  • Statement 32 The apparatus of Statement 30, wherein the report is generated and output by a remote processing apparatus configured to receive data transmitted away from the ingestible capsule by a wireless data transceiver.
  • Statement 33 The apparatus according to any of Statements 25 to 32, wherein the motion sensor comprises an accelerometer and the time series of motion sensor data comprises a time series of accelerometer data; and/or the motion sensor comprises a gyroscope and the time series of motion sensor data comprises a time series of gyroscope data.
  • Statement 34 The apparatus according to any of Statements 25 to 33, wherein the process comprises repeating the process for a series of time periods during passage of the ingestible capsule through the GI tract.
  • Statement 35 The apparatus according to Statement 34, wherein the series of time periods are contiguous, or wherein the series of time windows are sliding so that adjacent time windows in the series partially overlap one another.
  • Statement 36 The apparatus according to any of Statements 25 to 35, wherein the motion sensor comprises a three-axis accelerometer and the motion sensor data comprises three time series each representing acceleration in a respective one of the three axes, and the process includes a pre-spectral analysis step comprising: combining the three time series into a single resultant time series ; wherein the spectral analysis is generated from the single resultant time series.
  • Statement 37 The apparatus according to any of Statements 25 to 36, wherein the sensor hardware comprises a gyroscope and the sensor data comprises a time series of gyroscope data representing changes to a frame of reference of the ingestible capsule relative to a fixed frame of reference; extracting from the gyroscope data a long axis rotation time series representing rotation of the ingestible capsule about the long axis defined by the capsule housing; wherein the spectral analysis is generated from the long axis rotation time series.
  • the sensor hardware comprises a gyroscope and the sensor data comprises a time series of gyroscope data representing changes to a frame of reference of the ingestible capsule relative to a fixed frame of reference; extracting from the gyroscope data a long axis rotation time series representing rotation of the ingestible capsule about the long axis defined by the capsule housing; wherein the spectral analysis is generated from the long axis rotation time series.
  • Statement 38 The apparatus according to any of Statements 25 to 37, wherein the motion sensor is a three-axis accelerometer and the motion sensor data comprises three time series each representing acceleration in a respective one of the three axes, and generating the spectral analysis comprises: transforming each of the three time series into respective single axis frequency domain representations; combining the three single axis frequency domain representations to obtain a combined frequency domain representation.
  • the motion sensor is a three-axis accelerometer and the motion sensor data comprises three time series each representing acceleration in a respective one of the three axes
  • generating the spectral analysis comprises: transforming each of the three time series into respective single axis frequency domain representations; combining the three single axis frequency domain representations to obtain a combined frequency domain representation.
  • Statement 39 The apparatus according to any of Statements 36 to 38, wherein combining the three single axis frequency domain representations comprises comparing magnitude of a signal in a taiget frequency range from each of the single axis frequency domain representations, and selecting the single axis frequency domain representation with the greatest magnitude signal in the target frequency range as the combined frequency domain representation.
  • Statement 40 The apparatus according to any of Statements 36 to 38, wherein combining the three single axis frequency domain representations comprises, for each component frequency in the frequency domain, combining a component magnitude from each of the single axis frequency domain representations, the resulting combination per component frequency being the combined frequency domain representation.
  • Statement 41 The apparatus according to Statement 40, wherein wherein the combining is a summation, or a root sum squared.
  • Statement 42 The apparatus according to any of Statements 25 to 41, wherein the spectral analysis is a value representing magnitude of a component at each of a series of component frequencies.
  • Statement 43 The apparatus according to any of Statements 25 to 42, wherein the ingestible capsule further comprises the data processing hardware.
  • Statement 44 The apparatus according to any of Statements 25 to 43, wherein the apparatus further comprises a remote computing apparatus; the ingestible capsule further comprises a wireless data transmitter to transmit the time series of motion sensor data to the remote computing apparatus for processing, the data processing hardware being a component of the remote computing apparatus.
  • Statement 45 The apparatus according to any of Statements 25 to 44, wherein the process further comprises: generating a report including information extracted from the spectral analysis representing fluctuations, variations, or anomalies within spectral components.
  • Statement 46 The apparatus according to any of Statements 25 to 45, wherein the ingestible capsule further comprises one or more additional sensors configured to generate a time series of sensor data, and the process includes generating and outputting a report including one or more from among: the spectral analysis for the time period, and a result of processing the spectral analysis for the time period comprising information indicating a respiration rate, information indicating a detection of peristalsis, or information indicating a physical activity type being undertaken by the subject; additional sensor data readings from the same time period, and/or an outcome or processing the additional sensor data readings from the same time period such as a metric or identification of a motility marker, and/or information derived from additional sensor data readings from the same time period.
  • Statement 48 The apparatus according to any of Statements 25 to 47, wherein the apparatus further comprises one or more additional sensors external to the ingestible capsule positioned externally on the skin of the subject, the one or more additional sensors being communicatively coupled to the ingestible capsule or to a remote computing apparatus to which the ingestible capsule is communicatively coupled, the one or more additional sensors being configured to generate a time series of sensor data, and the process includes generating and outputting a report including one or more from among: the spectral analysis for the time period, and a result of processing the spectral analysis for the time period comprising information indicating a respiration rate, information indicating a detection of peristalsis, or information indicating a physical activity type being undertaken by the subject; additional sensor data readings from the same time period, and/or an outcome or processing the additional sensor data readings from the same time period such as a metric or identification of a motility marker, and/or information derived from additional sensor data readings from the same time period; wherein the one or more additional
  • Statement 49 The apparatus according to any of Statements 25 to 48, wherein the process includes determining the location of the capsule within the GI tract based on the detected peristalsis; the ingestible capsule further comprises a vibrating motor arranged, when in a powered on state, to vibrate within the capsule to cause vibration of the capsule housing, and the process further comprises, in response to the determined location of the ingestible capsule satisfying a vibration therapy initiation condition, causing the vibrating motor to switch from a powered off state to the powered on state.

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Abstract

A method comprising following ingestion of an ingestible capsule by a subject, the ingestible capsule housing a motion sensor configured to generate a time series of motion sensor data representing motion of the ingestible capsule during passage through the GI tract of a subject, at data processing hardware communicably coupled to the motion sensor, performing a process comprising: generating a spectral analysis of the time series of motion sensor data generated by the motion sensor over a time period during passage of the ingestible capsule through the GI tract, using the spectral analysis to detect peristalsis at a location of the ingestible capsule within the GI tract at the time period.

Description

Methods, Programs, Apparatus for Obtaining Health Information from Sensors in an Ingestible Capsule
Technical Field
This invention relates to ingestible sensor capsules for medical and health applications in the gastrointestinal (GI) tract of mammals including humans, and specifically relates to recording sensor data within the ingestible capsule and determining a location within the GI tract based on the data.
Background
Ingestible capsules housing sensors may be used to provide information about the health of a subject.
Gut health is increasingly identified as a contributor to overall health and wellness. Motility of an ingestible capsule (with or without associated gas constituent measurements) provides important information in the assessment of gut health. Determining location within the GI tract provides health information in itself, by providing information for GI tract motility reporting, and also provides context for sensor readings such as gas sensor readings. WO2023/064996 explains techniques for using sensor data from on-board an ingestible capsule to determine capsule location.
Furthermore, as set out in W02023087074, a determination of the location of the ingestible capsule may be used to time the release of therapeutic matter from a releasable chamber in the capsule, so that the therapeutic matter can be delivered directly to a specific region of the GI tract.
It is desirable to find accurate and reliable techniques for detecting and reporting data and information indicative of GI tract health, or data and information from the GI tract indicative of general patient health.
It is desirable to take GI tract samples from a predefined target location for analysis ex-vivo in a lab or clinical environment.
Statements
Methods comprise following ingestion of an ingestible capsule by a subject, the ingestible capsule housing a motion sensor configured to generate a time series of motion sensor data representing motion of the ingestible capsule during passage through the GI tract of a subject, at data processing hardware communicably coupled to the motion sensor, performing a process comprising: generating a spectral analysis of the time series of motion sensor data generated by the motion sensor over a time period during passage of the ingestible capsule through the GI tract, using the spectral analysis to detect peristalsis at a location of the ingestible capsule within the GI tract at the time period.
An apparatus comprises: an ingestible capsule housing a motion sensor configured to generate a time series of motion sensor data representing motion of the ingestible capsule during passage through the GI tract of a subject; data processing hardware communicably coupled to the motion sensor, the data processing hardware being configured, following ingestion of the ingestible capsule by the subject, at data processing hardware communicably coupled to the motion sensor, to perform a process comprising: generating a spectral analysis of the time series of motion sensor data generated by the motion sensor over a time period during passage of the ingestible capsule through the GI tract, using the spectral analysis to detect peristalsis at a location of the ingestible capsule within the GI tract at the time period.
A computer program comprises processing instructions which, when executed by processor hardware communicably coupled to a motion sensor housed in an ingestible capsule and configured to to generate a time series of motion sensor data representing motion of the ingestible capsule during passage through the GI tract of a subject, causes the processor hardware to perform a process comprising, following ingestion of the ingestible capsule by the subject: generating a spectral analysis of the time series of motion sensor data generated by the motion sensor over a time period during passage of the ingestible capsule through the GI tract, using the spectral analysis to detect peristalsis at a location of the ingestible capsule within the GI tract at the time period.
Advantageously, the inventors have found that by transforming the motion sensor data into the frequency domain, it provides a much more robust basis for determining capsule location than the same data in the time domain. Advantageously, motion sensors can be housed within the capsule and do not require exposure to the medium surrounding the capsule to generate readings. Motion sensors are low cost, consume little power, and simplify capsule design since they do not rely upon direct exposure to the medium surrounding the capsule to generate readings. The motion sensor may be an accelerometer or a gyroscope.
Optionally, the process further comprises: determining the location of the capsule within the GI tract based on the detected peristalsis.
Optionally, the process further comprises: generating a report including information extracted from the spectral analysis at one or a set of predefined peristalsis indicator frequency ranges.
Optionally, the process further comprises: generating and outputting to a receiver computing apparatus or message recipient a report including one or more from among: information extracted from the spectral analysis representing fluctuations, variations, or anomalies within spectral components; a metric or metrics calculated from the spectral analysis from among: centre frequency, frequency spread, power distribution, frequency gaps.
Optionally, the ingestible capsule further comprises one or more additional sensors configured to generate a time series of sensor data, and the generated report further comprises one or more from among: the spectral analysis for the time period, and additional sensor data readings from the same time period, and/or an outcome or processing the additional sensor data readings from the same time period such as a metric or identification of a motility marker, and/or information derived from additional sensor data readings from the same time period.
Optionally, detecting peristalsis at a location of the ingestible capsule within the GI tract at the time period comprises, in the result of the spectral analysis, detecting presence or absence of a signal at one or more of a predefined set of peristalsis indicator frequency ranges.
Optionally, the process includes determining the location of the capsule within the GI tract based on the detected peristalsis; and determining the location of the ingestible capsule within the GI tract comprises, in the result of the spectral analysis, detecting presence or absence of a signal/component at one or more of a predefined set of peristalsis indicator frequency ranges.
Optionally, a predefined set of peristalsis indicator frequency ranges comprises one or more from among: a first peristalsis indicator frequency range, being a frequency range indicating stomach peristalsis; a second peristalsis indicator frequency range, being a frequency range indicating small intestine peristalsis; a third peristalsis indicator frequency range, being a frequency range indicating large intestine peristalsis.
Optionally, the ingestible capsule is determined to be in the stomach by presence of a signal in the first peristalsis indicator frequency range; the ingestible capsule is determined to be in the small intestine by presence of a signal in the second peristalsis indicator frequency range; the ingestible capsule is determined to be in the large intestine by absence of a signal in the first peristalsis indicator frequency range and absence of a signal in the second peristalsis indicator frequency range; and/or the ingestible capsule is determined to be in the large intestine by presence of a signal in the third peristalsis indicator frequency range.
Optionally, using the spectral analysis to detect peristalsis includes applying a minimum signal magnitude threshold to a magnitude of the detected signal at one of the predefined set of peristalsis indicator frequency ranges over the time period, and if the minimum signal magnitude threshold is satisfied, determining that peristalsis at the location of the ingestible capsule within the GI tract at the period of time is detected.
Optionally, using the spectral analysis to detect peristalsis includes determining a characteristic frequency in the result of the spectral analysis, and if the characteristic frequency is within one of the predefined set of peristalsis indicator frequency ranges, determining that the a signal is detected in the one of the predefined set of peristalsis indicator frequency ranges, and optionally determining a location of the ingestible capsule within the GI tract at the period of time is a location corresponding to the one of the predefined set of peristalsis indicator frequency ranges.
Optionally, the process includes determining the location of the capsule within the GI tract based on the detected peristalsis; the ingestible capsule further comprises one or more additional sensors, each additional sensor being configured to generate a time series of additional sensor data representing an environment at or surrounding the ingestible capsule; using the spectral analysis to determine a location of the ingestible capsule within the GI tract at a time period includes: detecting a motility marker in the time series of additional sensor data indicating a transition between locations within the GI tract, or presence in a location within the GI tract, to obtain an additional sensor data indication of a location of the ingestible capsule within the GI tract at a time period based on the detected transition or presence; generating the spectral analysis on the time series of motion sensor data for the same time period; and if a signal/component at a threshold magnitude at one of a predefined set of peristalsis indicator frequency ranges is detected in the spectral analysis, and a location indicated by the detection in the spectral analysis is consistent with the additional sensor data indication of location, determining the location of the capsule at the said indicated location at the time period.
Optionally, the process includes determining the location of the capsule within the GI tract based on the detected peristalsis; the ingestible capsule further comprises one or more additional sensors, each additional sensor being configured to generate a time series of additional sensor data representing an environment at or surrounding the ingestible capsule; using the spectral analysis to determine a location of the ingestible capsule within the GI tract at a time period includes: detecting a motility marker in the time series of additional sensor data indicating a transition between locations within the GI tract, or presence in a location within the GI tract, to obtain an additional sensor data indication of a location of the ingestible capsule within the GI tract at a time period based on the detected transition or presence; generating the spectral analysis on the time series of motion sensor data for the same time period; and if a location indicated in the spectral analysis by presence or absence of a signal within one of a predefined set of peristalsis indicator frequency ranges is consistent with the additional sensor data indication of location, determining the location of the capsule at the said indicated location at the time period.
Optionally, the one or more additional sensors includes one or more gas sensors from among: a spectrophotometer; a Surface Acoustic Wave sensor; a Bulk Acoustic Resonator Array; a VOC gas sensors; and a TCD gas sensors; the time series of additional sensor data comprising a time series of gas sensor data.
Optionally, the motility marker is a spike, step change, or inflection in the time series of gas sensor data, indicating that the ingestible capsule has crossed the gastric-duodenal junction, orthe ileocecal junction.
Optionally, the one or more additional sensors includes a reflectometer formed by an antenna in series with a directional coupler, the antenna being controlled by the processor to transmit an intermittent or continuous signal from which a reflectometer signal is obtainable; the motility marker is a measurement of amplitude and/or phase of the reflectometer signal indicating presence of the ingestible capsule in a location within the GI tract.
Optionally, the ingestible capsule includes a wireless data transmitter to transmit the time series of additional sensor data and the time series of motion sensor data to a remote apparatus for processing, and the antenna is an antenna of the data transmitter.
Optionally, the ingestible capsule includes a wireless data transmitter to transmit the frequency domain representation of the sensor data to a remote apparatus for processing, and the antenna is an antenna of the data transmitter.
Optionally, the ingestible capsule further comprises a wireless data transceiver to transmit the time series of motion sensor data to a remote apparatus for processing, the data processing hardware being a component of the remote apparatus, the ingestible capsule further comprises a therapeutic payload carrying compartment, a release mechanism, the process further comprising: at the remote apparatus: performing the process including determining the location of the capsule within the GI tract based on detected peristalsis, and in response to determining that the determined location of the ingestible capsule is a target release location for therapeutic matter within the therapeutic payload carrying compartment, transmitting a trigger signal to the wireless data transceiver; and at the ingestible capsule: receiving the trigger signal at the wireless data transceiver, and responding to the trigger signal by, immediately or at a predetermined delay, the release mechanism causing the therapeutic matter within the therapeutic payload carrying compartment to be released into the GI tract.
Optionally, the process includes determining the location of the capsule within the GI tract based on the detected peristalsis; using the spectral analysis to determine a location of the ingestible capsule within the GI tract at a time period includes: detecting a motility marker in the time series of motion sensor data indicating a transition between locations within the GI tract to obtain a motion sensor time series data indication of a location of the ingestible capsule within the GI tract at a time period based on the detected transition; generating the spectral analysis on the time series of motion sensor data for the same time period; and if a location is indicated by presence or absence of a signal or signals at a predefined set of peristalsis indicator frequency ranges in the result of the spectral analysis, and the indicated location is consistent with the motion sensor time series data indication of location, determining the location of the ingestible capsule at the said indicated location at the time period.
Optionally, the process includes determining the location of the capsule within the GI tract based on the detected peristalsis; the ingestible capsule further comprises a therapeutic payload carrying compartment and a release mechanism, and the process further comprises, in response to the determined location of the ingestible capsule being a target release location for therapeutic matter within the therapeutic payload carrying compartment, causing the therapeutic matter to be released into the GI tract.
Optionally, the process includes determining the location of the capsule within the GI tract based on the detected peristalsis; the ingestible capsule further comprises a GI tract sampling chamber and a sealing mechanism to open and close the GI tract sampling chamber, and the process further comprises, in response to the determined location of the ingestible capsule being a predefined target sampling location, causing the sealing mechanism to open and close the sampling chamber to obtain a GI tract sample.
Optionally, the sealing mechanism comprises a fluid-filled sack occupying the sampling chamber, a membrane maintained in a stretched state by the fluid-filled sack and being exposed to the external environment via an aperture or drain valve, a sack rupturing actuator, and a one-way sampling valve at an interface between the housing of the ingestible capsule and the external environment; the membrane being arranged to permit fluid from the fluid-filled sack to exit the sampling chamber via the aperture or drain valve, and to block a fluid path between the one-way sampling valve and the aperture or drain valve, wherein, in response to the determined location of the ingestible capsule being a predefined target sampling location, the sack rupturing actuator is actuated to rupture the sack and thereby to cause the fluid to flow from the sack out of the sampling chamber via the aperture or drain valve, and the membrane to become less stretched than in the stressed state and thereby to suck fluid into the sampling chamber via the one-way sampling valve.
Optionally, the using the spectral analysis to determine a location of the ingestible capsule within the GI tract at the time period is performed by a pre-trained machine learning algorithm.
Optionally, the process includes extracting from the spectral analysis respiration information comprising an indication of respiration rate.
Optionally, the extracted respiratory information comprises a measurement of a signal in one or more from a predefined set of respiration information frequency ranges, or detection of a signal or signal characteristics in the spectral analysis indicating one or more from among:
-sleep apnea (absence of respiration during sleep);
-normal respiration;
-Blots respiration;
-Kussmaul breathing;
-Cheyne Stokes respiration;
- Bradypnea;
-Tachypnea;
-Hyperpnea;
-Ataxic respiration;
-Air trapping;
-Obstructive respiration;
-Sighing;
-Apneustic respiration;
-Agonal respiration.
Optionally, the motion sensor comprises an accelerometer and the time series of motion sensor data comprises a time series of accelerometer data; and/or the motion sensor comprises a gyroscope and the time series of motion sensor data comprises a time series of gyroscope data.
Optionally, the method comprises repeating the process for a series of time periods during passage of the ingestible capsule through the GI tract. Optionally, the series of time periods are contiguous, or wherein the series of time windows are sliding so that adjacent time windows in the series partially overlap one another.
Optionally, wherein the motion sensor comprises a three-axis accelerometer and the motion sensor data comprises three time series each representing acceleration in a respective one of the three axes, and the process includes a pre-spectral analysis step comprising: combining the three time series into a single resultant time series; wherein the spectral analysis is generated from the single resultant time series.
Optionally, the sensor hardware comprises a gyroscope and the sensor data comprises a time series of gyroscope data representing changes to a frame of reference of the ingestible capsule relative to a fixed frame of reference; extracting from the gyroscope data a long axis rotation time series representing rotation of the ingestible capsule about the long axis defined by the capsule housing; wherein the spectral analysis is generated from the long axis rotation time series.
Optionally, the motion sensor is a three-axis accelerometer and the motion sensor data comprises three time series each representing acceleration in a respective one of the three axes, and generating the spectral analysis comprises: transforming each of the three time series into respective single axis frequency domain representations; combining the three single axis frequency domain representations to obtain a combined frequency domain representation.
Optionally, combining the three single axis frequency domain representations comprises comparing magnitude of a signal in a taiget frequency range from each of the single axis frequency domain representations, and selecting the single axis frequency domain representation with the greatest magnitude signal in the target frequency range as the combined frequency domain representation.
Optionally, combining the three single axis frequency domain representations comprises, for each component frequency in the frequency domain, combining a component magnitude from each of the single axis frequency domain representations, the resulting combination per component frequency being the combined frequency domain representation.,
Optionally, the combining is a summation, or a root sum squared.
Optionally, the spectral analysis is a value representing magnitude of a component at each of a series of component frequencies.
Optionally, the ingestible capsule further comprises the data processing hardware. Optionally, the ingestible capsule further comprises a wireless data transmitter to transmit the time series of motion sensor data to a remote apparatus for processing, the data processing hardware being a component of the remote apparatus.
Optionally, the process further comprises: generating a report including information extracted from the spectral analysis representing fluctuations, variations, or anomalies within spectral components.
Optionally, the ingestible capsule further comprises one or more additional sensors configured to generate a time series of sensor data, and the process includes generating and outputting a report including one or more from among: the spectral analysis for the time period, and a result of processing the spectral analysis for the time period comprising information indicating a respiration rate, information indicating a detection of peristalsis, or information indicating a physical activity type being undertaken by the subject; additional sensor data readings from the same time period, and/or an outcome or processing the additional sensor data readings from the same time period such as a metric or identification of a motility marker, and/or information derived from additional sensor data readings from the same time period.
Optionally, the one or more additional sensors comprise one or more from among:
- a gas sensor;
- a motion sensor;
- a temperature sensor;
= a relative humidity sensor;
- a reflectometer;
- a pulse oximetry sensor;
- an electromyographic sensor.
Optionally, one or more additional sensors external to the ingestible capsule are positioned externally on the skin of the subject, the one or more additional sensors being communicatively coupled to the ingestible capsule or to a receiver computing apparatus to which the ingestible capsule is communicatively coupled, one or more additional sensors configured to generate a time series of sensor data, and the process includes generating and outputting a report including one or more from among: the spectral analysis for the time period, and a result of processing the spectral analysis for the time period comprising information indicating a respiration rate, information indicating a detection of peristalsis, or information indicating a physical activity type being undertaken by the subject; additional sensor data readings from the same time period, and/or an outcome or processing the additional sensor data readings from the same time period such as a metric or identification of a motility marker, and/or information derived from additional sensor data readings from the same time period; wherein the one or more additional sensors comprises one or more from among:
- a pulse oximetry sensor; and
- an electromyographic sensor.
A method comprises: following ingestion of an ingestible capsule by a subject, the ingestible capsule housing a motion sensor configured to generate a time series of motion sensor data representing motion of the ingestible capsule during passage through the GI tract of a subject, at data processing hardware communicably coupled to the motion sensor, performing a process comprising: generating a spectral analysis of the time series of motion sensor data generated by the motion sensor over a time period during passage of the ingestible capsule through the GI tract, extracting from the spectral analysis respiration information comprising an indication of respiration rate.
Apparatus comprises: an ingestible capsule housing a motion sensor configured to generate a time series of motion sensor data representing motion of the ingestible capsule during passage through the GI tract of a subject; data processing hardware communicably coupled to the motion sensor, the data processing hardware being configured, following ingestion of the ingestible capsule by the subject, at data processing hardware communicably coupled to the motion sensor, to perform a process comprising: generating a spectral analysis of the time series of motion sensor data generated by the motion sensor over a time period during passage of the ingestible capsule through the GI tract, extracting from the spectral analysis respiration information comprising an indication of respiration rate.
A computer program comprises processing instructions which, when executed by processor hardware communicably coupled to a motion sensor housed in an ingestible capsule and configured to to generate a time series of motion sensor data representing motion of the ingestible capsule during passage through the GI tract of a subject, causes the processor hardware to perform a process comprising, following ingestion of the ingestible capsule by the subject: generating a spectral analysis of the time series of motion sensor data generated by the motion sensor over a time period during passage of the ingestible capsule through the GI tract, extracting from the spectral analysis respiration information comprising an indication of respiration rate. Optionally, the extracted respiratory information comprises a measurement of a signal in one or more from a predefined set of respiration information frequency ranges or detection of a signal or signal characteristics in the spectral analysis indicating one or more from among:
-sleep apnea (absence of respiration during sleep);
-normal respiration;
-Blots respiration;
-Kussmaul breathing;
-Cheyne Stokes respiration;
- Bradypnea;
-Tachypnea;
-Hyperpnea;
-Ataxic respiration;
-Air trapping;
-Obstructive respiration;
-Sighing;
-Apneustic respiration;
-Agonal respiration.
Optionally, the predefined set of respiration information frequency ranges includes a first respiration information frequency range indicating snoring, and a second respiration information frequency range indicating respiration.
Optionally, the first respiration information frequency range is between 12 and 18 cpm.
Optionally, the second respiration information frequency range is between 3600 and 18000cpm.
Optionally, the ingestible capsule further comprises, or is operably coupled to a separate, one or more additional sensors, each additional sensor being configured to generate a time series of additional sensor data; the additional sensor comprises a pulse oximetry sensor configured to generate a time series of pulse oximetry measurements representing concentration of oxygen in blood of the subject; the method further comprises generating and outputting a report comprising the extracted respiration information for the time window and a contemporaneous extract from the time series of pulse oximetry measurements.
Optionally, the report is generated and output by processor hardware and a wireless data transceiver on board the ingestible capsule. Optionally, the report is generated and output by a remote processing apparatus configured to receive data transmitted away from the ingestible capsule by a wireless data transceiver.
A method comprises: providing to a subject an ingestible capsule housing amotion sensor configured to generate a time series of motion sensor data representing motion of the ingestible capsule during passage through the GI tract; following ingestion of the ingestible capsule by the subject, at data processing hardware communicably coupled to the motion sensor, performing a process comprising: conducting a spectral analysis of the time series of motion sensor data generated by the motion sensor over a time period during passage of the ingestible capsule through the GI tract, using the spectral analysis to determine a physical activity being undertaken by the subject or to characterise a physical activity being undertaken by the subject.
An apparatus comprises: an ingestible capsule housing a motion sensor configured to generate a time series of motion sensor data representing motion of the ingestible capsule during passage through the GI tract of a subject; data processing hardware communicably coupled to the motion sensor, the data processing hardware being configured, following ingestion of the ingestible capsule by the subject, at data processing hardware communicably coupled to the motion sensor, to perform a process comprising: generating a spectral analysis of the time series of motion sensor data generated by the motion sensor over a time period during passage of the ingestible capsule through the GI tract, using the spectral analysis to determine a physical activity being undertaken by the subject or to characterise a physical activity being undertaken by the subject.
A computer program comprises processing instructions which, when executed by processor hardware communicably coupled to a motion sensor housed in an ingestible capsule and configured to to generate a time series of motion sensor data representing motion of the ingestible capsule during passage through the GI tract of a subject, causes the processor hardware to perform a process comprising, following ingestion of the ingestible capsule by the subject: generating a spectral analysis of the time series of motion sensor data generated by the motion sensor over a time period during passage of the ingestible capsule through the GI tract, using the spectral analysis to determine a physical activity being undertaken by the subject or to characterise a physical activity being undertaken by the subject.
An ingestible capsule, comprises: a housing, being a biocompatible indigestible housing including a sampling chamber; a power supply; a sampling mechanism; and a sensing mechanism, the sensing mechanism being sensitive to the environment external to the housing; the ingestible capsule being configured for passage through a gastrointestinal, GI, tract of a subject mammal, during which passage: the sensing mechanism is configured to output an output signal varying according to the GI tract environment external to the housing, wherein the sensing mechanism comprises one or more sensors from among:a VOC gas sensor;a TCD gas sensor ;a reflectometer formed by a transmission antenna of the ingestible capsule connected in series with a directional coupler configured to measure a reflected signal from the transmission antenna; and a motion sensor; the sampling mechanism is configured to cause a sample of fluid or matter from the GI tract to be sealed in the sampling chamber at a sampling timing determined according to the output signal.
Optionally, the ingestible capsule comprises processor hardware configured to identify in real time one or more ileocecal junction transition indicators in the output signal of the sensing mechanism, and to determine the sampling timing according to the identification of the ileocecal junction indicator.
Optionally, the sensing mechanism is a direct gas sensing mechanism comprising a VOC gas sensor, the direct gas sensing mechanism being housed within the capsule in a direct gas sensing portion sealed from other components of the ingestible capsule by a gas impermeable membrane and being exposed to a gas mixture in the environment external to the ingestible capsule via a gas permeable membrane in the housing at the location of the direct gas sensing portion, the output signal output by the sensing mechanism comprising VOC concentration readings of the VOC gas sensor.
Optionally, the direct gas sensing mechanism further comprises a TCD gas sensor, or wherein the ingestible capsule is configured to make TCD readings via a heater side of the VOC gas sensor, the output signal output by the sensing mechanism further comprising TCD readings of the VOC gas sensor and/or the TCD gas sensor.
Optionally, identifying the ileocecal junction transition indicator comprises identifying an increase in sensor side VOC gas sensor readings with a contemporaneous increase in H2 concentration, the H2 concentration being derived from TCD readings of the TCD gas sensor and/or heater side readings of the VOC gas sensor.
Optionally, identifying the ileocecal junction transition indicator comprises identifying an increase in sensor side VOC gas sensor readings with a contemporaneous increase in CH4 concentration, the CH4 concentration being derived from TCD readings of the TCD gas sensor and/or heater side readings of the VOC gas sensor.
Optionally, the sensing mechanism is a non-contact sensing mechanism housed in a portion of the ingestible capsule sealed from the environment external to the ingestible capsule by the housing, the non-contact sensing mechanism comprising at least one of a motion sensor and a reflectometer, the reflectometer comprising a transmission antenna connected in series with a directional coupler configured to measure a reflected signal from the transmission antenna, the output signal output by the sensing mechanism comprising a time series of motion sensor readings and/or reflectometer readings.
Optionally, the non-contact sensing mechanism comprises the reflectometer, and the ingestible capsule further comprises a diode detector and the diode detector forms a part of the reflectometer, the diode detector being configured to receive the reflected signal from the antenna and to measure an amplitude of the reflected signal, the reflectometer readings in the output signal comprising amplitude measurements of the reflected signal.
Optionally, the ingestible capsule further comprises a quadrature demodulator and the quadrature demodulator forms a part of the reflectometer, the quadrature demodulator being configured to receive the reflected signal from the antenna via the directional coupler and to extract phase information of the reflected signal relative to a carrier signal, the reflectometer readings in the output signal comprising the extracted phase information of the reflected signal.
Optionally, the ingestible capsule further comprises an antenna impedance control mechanism comprising a variable capacitor configured to vary impedance of the transmission antenna, and a controller, wherein the reflectometer and the antenna impedance control mechanism form a closed loop or feedback loop, and wherein the controller is configured to receive the measurements of the amplitude of the reflected signal from a diode detector and to execute a control algorithm to use the amplitude measurements to generate an antenna impedance control signal setting a capacitance of the variable capacitor to vary impedance of the antenna to reduce amplitude of the reflected signal, wherein the reflectometer readings in the output signal comprise readings of the antenna impedance control signal.
Optionally, the closed loop or feedback loop further comprises a quadrature demodulator, and wherein phase information is extracted by the quadrature demodulator and output to the controller, and wherein the controller is configured to use the amplitude information and the phase information to generate the antenna impedance control signal.
Optionally, the output signal output by the sensing mechanism comprises accelerometer readings and reflectometer readings, and determining the sampling timing comprises identifying that an ileocecal junction transition indicator is present in readings from the reflectometer and the accelerometer, including: processing the reflectometer readings and the accelerometer readings to identify the presence of a first ileocecal junction transition indicator in either one of the reflectometer readings and the accelerometer readings, processing the other one of the reflectometer readings and the accelerometer readings to identify a second ileocecal junction transition indicator within a predefined time window of a timing of the first ileocecal junction transition indicator, and in response to identifying the first ileocecal junction transition indicator and the second ileocecal junction transition indicator within the predefined time window, determining the sampling timing, being either immediate or after a predefined delay.
Optionally, the or each ileocecal junction transition indicator and/or gastric -duodenal transition indicator is a characteristic or combination of characteristics of: a reading, a series of readings, a pattern, a geometric feature, a statistical feature, and/or a mathematical feature, in a record of the output signal as a function of time; the characteristic or combination of characteristics being predefined as being caused by transition of the ingestible capsule across the ileocecal junction or from the stomach into the duodenum.
Optionally, the ingestible capsule comprises a microcontroller, and the sampling mechanism includes the microcontroller; the microcontroller being configured to: during an identification phase, on a rolling basis, record a representation of the output signal for a most recent time period of duration t, and to process the recorded representation of the output signal for the most recent time period of duration t to identify presence of the one or more ileocecal junction transition indicators; the microcontroller being configured, upon identification of the presence of the one or more ileocecal junction transition indicators, to determine the sampling timing and based on the determined sampling timing to cause the sampling mechanism to open and close the sampling chamber to obtain a GI tract sample.
Optionally, the ingestible capsule comprises a microcontroller, and the sampling mechanism includes the microcontroller; the microcontroller being configured to: during an identification phase, on a rolling basis, record a representation of the output signal for a most recent time period of duration t, and to process the recorded representation of the output signal for the most recent time period of duration t to identify presence of the one or more gastric -duodenal transition indicators; the microcontroller being configured, upon identification of the presence of the one or more gastric-duodenal transition indicators, to determine the sampling timing and based on the determined sampling timing to cause the sampling mechanism to open and close the sampling chamber to obtain a GI tract sample.
Optionally, the ingestible capsule comprises a microcontroller, and the sampling mechanism includes the microcontroller; the microcontroller being configured to: during an identification phase, on a rolling basis, record a representation of the output signal for a most recent time period of duration t, and to process the recorded representation of the output signal for the most recent time period of duration t to identify: presence of the one or more gastric -duodenal transition indicators; and following the identification of the presence of the one or more gastric-duodenal transition indicators, to identify presence of the one or more ileocecal junction transition indicators; the microcontroller being configured, upon identification of the presence of the one or more ileocecal junction transition indicators, to determine the sampling timing and based on the determined sampling timing to cause the sampling mechanism to open and close the sampling chamber to obtain a GI tract sample.
Optionally, the ingestible capsule comprises a wireless transceiver, and the antenna is configured, during an identification phase, to transmit a transmission signal representing the output signal from the sensing mechanism to remote processing apparatus; the transceiver being configured, upon receipt of a trigger signal from the remote processing apparatus, to cause, immediately or at a predetermined delay, the sampling mechanism to open and close the sampling chamber to obtain a GI tract sample.
Optionally, the sampling mechanism comprises a fluid-filled sack occupying the sampling chamber, a membrane maintained in a stretched state by the fluid-filled sack and being exposed to the external environment via an aperture or drain valve, a sack rupturing actuator, and a one-way sampling valve at an interface between the housing of the ingestible capsule and the external environment; the membrane being arranged to permit fluid from the fluid-filled sack to exit the sampling chamber via the aperture or drain valve, and to block a fluid path between the one-way sampling valve and the aperture or drain valve, wherein, in response to the determined location of the ingestible capsule being a predefined target sampling location, the sack rupturing actuator is actuated to rupture the sack and thereby to cause the fluid to flow from the sack out of the sampling chamber via the aperture or drain valve, and the membrane to become less stretched than in the stressed state and thereby to suck fluid into the sampling chamber from the GI tract via the one-way sampling valve.
Optionally, the sack rupturing actuator comprises a heating element arranged in contact with the fluid- filled sack and a supercapacitor configured to be trickle charged by the ingestible capsule power supply over a period of time beginning with ingestion of the ingestible capsule, and to be caused to release the charge to the heating element at the determined sampling timing under the control of the microcontroller to cause rupturing of the fluid-filled sack.
Optionally, the supercapacitor and the heating element are impedance matched, or are impedance matched to within a defined tolerance.
Optionally, the heating element is a resistive heater element comprising one or more from among:
SMT resistor; metallic resistive wire; nichrome;
MEMS heater element. Optionally, the sack rupturing actuator rupturing actuator comprises a power source and a LASER diode focussed on the elastic material membrane, wherein a microcontroller of the ingestible capsule is configured at the determined sampling timing to activate the LASER diode to rupture the fluid-filled sack.
Optionally, the sack rupturing actuator comprises a pre-sprung mechanical needle, wherein a microcontroller of the ingestible capsule is configured, at the determined sampling timing, to release the pre-sprung mechanical needle causing the pre-sprung mechanical needle to spring into the fluid- filled sack causing rupturing.
Optionally, the sack rupturing actuator comprises a power source, a shape memory alloy wire, and a rupturing member, the power source being configured, at the determined sampling timing and under control of the microcontroller, to transfer energy to the shape memory alloy wire, to initiate a phase change at material level of the shape memory alloy wire and thereby to exert a force on the rupturing member to cause the rupturing member to come into contact with, and to rupture, the fluid-filled sack.
Optionally, the sack rupturing actuator comprises a motor and a rupturing member, the microcontroller being configured, at the determined sampling timing, to power on the motor and thereby to exert a force on the rupturing member to cause the rupturing member to come into contact with, and to rupture, the fluid-filled sack.
Optionally, the ingestible capsule includes an environmental sensor, and the readings include readings of the environmental sensor, the environmental sensor being an environmental temperature sensor, an environmental relative humidity sensor, or an environmental temperature sensor and an environmental humidity sensor; the processing the recorded readings including determining an excretion event timing by detecting an excretion indicator, the excretion indicator being a change in the environmental sensor readings between an internal environmental condition of the subject mammal and an external environmental condition at a location of the subject mammal, the excretion event timing being a timing of excretion of the ingestible capsule by the subject mammal.
Optionally, the ingestible capsule comprising a wireless transceiver configured to transmit data transmission payload away from the ingestible capsule via Bluetooth, Bluetooth Long Range, and/or 433MHz radio transmission technique, the data transmission payload comprising one or more from among: a record of sampling timing; a record of excretion timing; a record of the one or more identified ileocecal junction transition indicators; a record of the one or more identified gastric-duodenal transition indicators; a record of an electrode signal indicating rupturing of the fluid-filled sack; a record of an electrode signal indicating a filled state of the sampling chamber; output signal output by the sensing mechanism; and a metric or metrics representing the output signal output by the sensing mechanism.
Optionally, transmission of the data transmission payload by the wireless transceiver is triggered by one or more from among: determining that an excretion event has occurred; determining sampling timing; determining sampling timing and that a predefined delay after sampling timing has expired; receipt at a microcontroller of the ingestible capsule of an electrode signal indicating rupturing of the fluid-filled sack.
Optionally, the sensing mechanism comprises a direct gas sensing mechanism and a non-contact sensing mechanism.
A method comprises: providing an ingestible capsule defined above to a subject mammal for ingestion; processing the output signal of the sensing mechanism to determine the sampling timing; causing the sampling mechanism to obtain a GI tract sample at the determined sampling timing.
A system comprises an ingestible capsule and a remote processing apparatus: the ingestible capsule, comprising: a housing, being a biocompatible indigestible housing including a sampling chamber; a power supply; a sampling mechanism; a wireless transceiver; and a sensing mechanism, the sensing mechanism being sensitive to an environment external to the housing; the ingestible capsule being configured for passage through a gastrointestinal, GI, tract of a subject mammal, during which passage: the sensing mechanism is configured to output an output signal varying according to GI tract environment external to the housing, wherein the sensing mechanism comprises one or more sensors from among: a VOC gas sensor; a TCD gas sensor; a reflectometer formed by a transmission antenna of the ingestible capsule connected in series with a directional coupler configured to measure a reflected signal from the transmission antenna; and a motion sensor; the sampling mechanism is configured to cause a sample of fluid or matter from the GI tract to be sealed in the sampling chamber at a sampling timing determined according to the output signal; wherein the capsule is configured, during an identification phase, to transmit a transmission signal representing the output signal to the remote processing apparatus via the wireless transceiver; the wireless transceiver being configured, upon receipt of a trigger signal from the remote processing apparatus, to cause, immediately or at a predetermined delay, the sampling mechanism to cause a sample of fluid or matter from the GI tract to be sealed in the sampling chamber; and the remote processing apparatus comprising a remote processing apparatus transceiver configured to communicate with the wireless data transceiver of the ingestible capsule including to receive the transmission signal representing the output signal, and a processor configured to process the output signal to identify in real time one or more ileocecal junction transition indicators and/or one or more gastric duodenal transition indicators in the output signal, and to cause the remote processing apparatus transceiver to transmit the trigger signal to the wireless data transceiver of the ingestible capsule according to the timing of the identified one or more ileocecal junction transition indicators and/or one or more gastric duodenal transition indicators.
List of Figures
Adetailed description of embodiments including apparatus, methods, programs, processes, and systems, is set out below, with particular reference to accompanying drawings, in which:
Figures la to Id illustrate methods;
Figure 2 illustrates apparatus;
Figures 3a and 3b illustrate schematically electronic components of ingestible capsules;
Figure 4 illustrates schematically electronic components of an ingestible capsule;
Figures 5a to 5c illustrate schematically electronic components of an ingestible capsule or a system including an ingestible capsule;
Figure 6a illustrates a time series of accelerometer data;
Figure 6b illustrates accelerometer data in the frequency domain;
Figure 6c illustrates accelerometer data in the frequency domain;
Figure 6d illustrates time series of sensor data from additional sensors and from an accelerometer;
Figure 7 illustrates a reflectometer;
Figure 8 illustrates time series sensor data from additional sensors and from an accelerometer;
Figure 9 illustrates time series sensor data from additional sensors and from an accelerometer;
Figure 10 illustrates schematically electronic components of an ingestible capsule;
Figure 11 illustrates schematically electronic components of an ingestible capsule;
Figure 12 illustrates a capsule with a sampling mechanism;
Figure 13 illustrates a method.
General
Figures la to Id illustrate methods. Figure 2 illustrates an apparatus suitable for performing the methods. Figures 3a and 3b are schematic illustrations of ingestible capsules 10. The method of Figure la is a method for determining a location of an ingestible capsule 10 within the GI tract of a subject 40, illustrated in Figure 2. As illustrated in Figures 3a and 3b, the ingestible capsule 10 houses a motion sensor 19. The motion sensor 19 is configured to generate a time series of motion sensor data representing acceleration, rotation, or positional changes experienced by the ingestible capsule 10 (otherwise referred to as raw accelerometer data). The motion sensor 19 is fixed in position within the ingestible capsule 10 so that the ingestible capsule 10 and the motion sensor 19 experience the same acceleration, rotation, and positional changes.
Location within the GI tract may be an indication of presence in either the stomach, the small intestine, or the large intestine. Optionally, the location may be provided to a greater level of specificity, such as proximal or distal small intestine.
The method of Figure lb is a method for detecting respiratory events and/or for extracting information relating to respiratory activity. Steps S101 to S103 are common to the methods of Figures la to Id. In the method of Figure lb, step S104B is optional, as indicated by the dashed lines. Information derived from the location determinations at S104B may be included in a report also including the respiratory information extraction at S105, for example, for diagnostic purposes. Or it may be that the respiratory analysis such as at SI 05 is conducted in the absence of motility analysis such as at S104B.
The method of Figure 1c is a method for detecting an activity type of a patient, such as running, walking, resting. In the method of Figure 1c, steps S104B and S105 are optional, as indicated by the dashed lines. Information derived from the location determinations at S104B may be included in a report also including the respiratory information extraction at S105 and the activity type determination at S106. Or it may be that the activity type determination at SI 06 is conducted in the absence of one or both of respiratory analysis such as at S105 and motility analysis such as at S104B.
Steps S104A to SI 06 may be referred to collectively as spectral analysis processing steps. Each of S104Ato SI 06 utilises the result of the spectral analysis from SI 03 to extract information, detect events, or determine information. The spectral analysis processing steps S104Ato SI 06 may be performed onboard the capsule or remotely (see Figure 2). The results of the spectral analysis processing steps may be included in a report generated on-board the capsule 10 and transmitted away to a receiver computing apparatus 30, or may be included in a report generated by remote processing apparatus and transmitted to a recipient such as the subject or a clinician.
Steps S 104B to S 106 may be performed in combination with one another, or separately. A single capsule 10 may be configured to perform any one of S104A to SI 06, all four of S104A to SI 06, or some combination thereof. Likewise, a system comprising an ingestible capsule 10 and remote processing apparatus may be configured to perform any one of S 104A to S 106, all four of S 104A to S 106, or some combination thereof.
Apparatus Arrangements Overview
As shown in Figure 2, apparatus arrangements for performing methods for determining location of the capsule 10 within the GI tract based on a spectral analysis of a time series of data generated by the motion sensor 19, such as illustrated by Figures la to Id, may comprise:
• only the ingestible capsule 10: in this case processing of the time series of motion sensor data to obtain a determination of location via spectral analysis is performed on-board the capsule by data processing hardware 15;
• the ingestible capsule 10 and remote processing apparatus, wherein the remote processing apparatus may comprise only a receiver computing apparatus 30 in direct data communication with the ingestible capsule 10, or may comprise a receiver computing apparatus 30 in direct data communication with the ingestible capsule 10 and one or more further computing apparatus 20 to receive data from the receiver computing apparatus 30 over a network.
Thus, the receiver computing apparatus 30 and the further computing apparatus 20 are optional. The receiver computing apparatus 30 may be a smart phone, a tablet, or some other personal computing device, or server computer, configured to pair, couple, or otherwise establish a direct data communication with a wireless data transceiver 18 of the ingestible capsule 10. The further computing apparatus 20 may be a smart phone, a tablet, or some other personal computing device, server computer, or cloud computing device/service/infrastructure in network communication with the receiver computing apparatus 30. The receiver computing apparatus 30 may be a personal device of the subject 30. The further computing apparatus 20 may be a device of a clinical service provider, an ingestible capsule provider, or some other entity.
Data communications between the capsule 10 and the receiver computing apparatus 30 may be oneway, wherein raw motion sensor data is transmitted from the capsule 10 to the receiver computing apparatus 30 for processing (by the receiver computing apparatus 30 and/or the further computing apparatus 20), and no data flows in the reverse direction. Alternatively, a result of processing may be transmitted back to the capsule 10.
In a particular implementation example based on Figure la, transmission from remote processing apparatus to the ingestible capsule 10 may be in response to determining at S 104B that a location of the capsule 10 within the GI tract is a target location for therapeutic matter being carried by the capsule 10 and thus the transmission is a trigger signal to trigger release of the therapeutic matter by the capsule 10.
Aprocess comprising the spectral analysis at S103, and the spectral analysis processing steps S104B to SI 06 may be performed on-board the ingestible capsule 10, may be performed by a receiver computing apparatus 30 in direct data communication with the ingestible capsule 10, or may be performed by further computing apparatus 20 in data communication with the receiver computing apparatus 30 over a network (such as the internet). The process may be performed by two or three of those elements in combination.
The apparatus arrangements of Figure 2 may also be referred to as systems. The subject 40 is illustrated for context but is not intended to form part of an apparatus or system.
Capsule Arrangements Overview
Figures 3a and 3b schematically illustrate basic capsule arrangements. The ingestible capsule 10 comprises at least a motion sensor 19 and a power source 16. Other components such as control circuitry may be present in the capsule 10 but are not illustrated. The ingestible capsule 10 of Figure 3a includes data processing hardware 15 comprising processor hardware 151 such as a CPU for processing data, and a memory hardware 152 for storing data, in preparation for and during processing, and/or processing results.
As illustrated in Figure 3b, the data processing hardware 15 is optional since the ingestible capsule 10 may comprise a wireless transceiver 18 to transmit the motion sensor data (and other sensor data generated by the capsule 10) away to remote apparatus (see Figure 2) for processing. Optionally, the ingestible capsule 10 may comprise data processing hardware 15 for on-board processing, and a wireless transceiver 18 to transmit a result of the on-board data processing to a remote apparatus for one or more from among further processing, storage, reporting, etc. Optionally, the spectral analysis step S 103 may be performed on-board the capsule 10, and the resultant frequency domain representation of the motion sensor data transmitted to the remote processing apparatus for the spectral analysis processing step or steps S104B-S106.
The ingestible capsule 10 illustrated in Figure 3a and in Figure 3b may further comprise additional sensor hardware such as an EMG 31, a pulse -oximetry sensor 32, or a gas sensor, which would be housed within a gas sensing headspace within a gas permeable membrane and sealed from the remainder of the components by an impermeable membrane. As discussed below, the ingestible capsule 10 may be of an arrangement configured to release therapeutic matter into the GI tract at a timing based on a location determined at S104B by spectral analysis of a time series of data generated by the motion sensor 19.
Motion sensor hardware
The motion sensor 19 may be a gyroscope. The motion sensor 19 may be an accelerometer. The motion sensor 19 may comprise a gyroscope and an accelerometer. For example, the motion sensor 19 may be a tri -axis accelerometer. The motion sensor 19 may be a 12 -bit tri-axis accelerometer. The motion sensor 19 may be a single-axis accelerometer or a two-axis accelerometer. The motion sensor 19 may comprise a piezo-film sensor, a surface MM capacitive sensor, a bulk capacitive sensor, and/or a piezo-electric electromechanical servo vibrational sensor. The motion sensor 19 may comprise a fibre optic accelerometer, a Hall effect accelerometer, a magnetoresistive accelerometer, and/or a strain gauge accelerometer.
On-the-fly versus retrospective processing & on-hoard versus remote processing
Methods for determining location of the capsule 10 within the GI tract based on a spectral analysis of a time series of data generated by the motion sensor 19, such as illustrated by Figure la, may be performed on-the-fly (during GI tract passage), or may be performed retrospectively (following GI tract passage).
Methods for extracting respiratory information from a spectral analysis of a time series of data generated by the motion sensor 19, such as illustrated by Figure lb, may be performed on-the-fly (during GI tract passage), or may be performed retrospectively (following GI tract passage).
Methods for determining an activity type of a subject 40 from a spectral analysis of a time series of data generated by the motion sensor 19, such as illustrated by Figure 1c, may be performed on-the-fly (during GI tract passage), or may be performed retrospectively (following GI tract passage).
In the on-the-fly processing case, the processing is retrospective insofar as the data being processed was generated by the motion sensor 19 in the past, but the processing is being performed more or less instantaneously after the end of a time period during which the time series represents to obtain a processing result representing the said time period, for example, a location of the capsule within the said time period.
On-the-fly processing may be useful in examples such as determining location in order to release therapeutic matter into a particular location within the GI tract. Such processing may be useful in order to reduce a data transmission overhead, so that rather than transmitting raw motion sensor data away from the capsule 10, it is only necessary to transmit results of a location determination for a time period or location determinations for a series of time periods. Or, for example, to transmit the spectral information resulting from the spectral analysis, that is, the frequency domain representation of the time series of motion sensor data, or a compressed or otherwise processed version thereof. Wherein processed or compressed may indicate that signals or components in one or more relevant frequency ranges are extracted and other signals or components discards. Relevant may be a predefined set of peristalsis indicator frequency ranges.
On-the-fly processing of the time series of motion sensor data to obtain a spectral analysis result at S 103 and a result of a spectral analysis processing step S 104B to S 106 may be performed on-board the capsule 10 by an arrangement such as illustrated in Figure 3a, or may be transmitted away from the capsule during passage through the GI tract for processing at a remote apparatus in an arrangement such as illustrated in Figure 3b.
Transmission of the raw motion sensor data (i.e. the time series of motion sensor data) from the capsule 10 to the remote apparatus may be during passage through the GI tract. For example, the wireless data transceiver 18 may pair or otherwise connect with the remote apparatus for transmission according to a protocol such as Bluetooth or Bluetooth Low Energy transmission protocol. Likewise, results of processing on-board the capsule may be transmitted to a remote apparatus via the same mechanism. Results of processing on-board the capsule may be stored on the capsule for reporting by transmission to a remote apparatus after detection of excretion from the GI tract (by detecting a freefall event via the motion sensor 19 or by changes detected by temperature or relative humidity sensors, if included) triggering a burst of data transmission in an inquiry mode.
Retrospective processing, which is taken to mean processing after passage through the GI tract, may be performed at a remote apparatus in an arrangement such as illustrated in Figures 2 and 3b.
In the case of processing on-board the capsule 10, there may still be a wireless data transceiver 18 for transmitting away a result of the processing to a remote apparatus, and in the case of there being additional sensor hardware, it may be that data from the additional sensor hardware is transmitted away via the wireless data transceiver 18. Likewise, the additional sensor data may be processed on board the capsule 10 and a processing result transmitted away. It may be that no data is transmitted away from the ingestible capsule 10, for example if the processing result is a location determination at S104B used to determine a release timing of therapeutic matter, then the processing result does not necessarily need to be transmitted away from the capsule 10 (however it may be transmitted away for reporting purposes). Retrospective processing may be useful in examples such as health reporting and diagnostics, when a clinician wishes to obtain a report on GI tract motility of a patient (comprising one or more from among whole gut transit time, small bowel residence time, large intestine residence time, gastric residence time, etc) based on the method of Figure la, on the respiratory activity or habits/pattems of a subject based on the method of Figure lb, or on the activity types of a subject based on the method of Figure 1c.
A report may include additional sensor data generated at each location within the GI tract. Wherein such additional sensor data may be generated by on-board gas sensors indicating gases present in the gas mixture surrounding the capsule 10 during its passage through the GI tract, noting that combining such sensor data with determinations of location from S104B in particular time windows enables a clinician to determine whether and to what extent gases indicative of disorders such as gastroparesis or SIBO are present. Of course, in such examples on-the-fly processing could also be implemented.
In retrospective processing implementations, the raw motion sensor data (that is, the time series of motion sensor data) is processed by a remote apparatus after the passage through the GI tract. Transmission of the motion sensor data from the capsule 10 to the remote apparatus may be during passage through the GI tract. For example, the wireless data transceiver 18 may pair or otherwise connect with the remote apparatus for transmission according to a protocol such as Bluetooth or Bluetooth Low Energy transmission protocol. In another example, the capsule 10 may detect excretion from the GI tract (by detecting a freefall event via the motion sensor 19 or by changes detected by temperature or relative humidity sensors, if included) and then trigger a burst of data transmission in an inquiry mode. Transmission protocols are discussed specifically in PCT/AU2023/050801.
Methods of Figures la to Id in more detail
SI 01 Capsule Ingestion
Step S101 is common to the methods ofFigures la to Id.
At step S101 the ingestible capsule 10 ingested by a subject 40. The subject may be a human subject. The ingestible capsule 10 may be obtained by the subject from a clinician (that is, a medical professional) for obtaining information about the condition of the GI tract, respiratory patterns, or other health information about a subject. Further, the ingestible capsule 10 may be provided as a means to deliver therapeutic matter directly to a particular location in the GI tract of the subject.
The ingestible capsule 10 may be configured to power on upon removal from a package in which it is supplied, or upon receipt of a custom wireless signal from a dedicated application on a remote apparatus such as receiver computing apparatus 30. Optionally, the ingestible capsule 10 may include a secondary wireless transceiver, which may use an NFC communication protocol. The secondary transceiver is for specific activation control signalling only, such as for initiating an active mode of the capsule 10 at an unpackaging stage or otherwise prior to ingestion of the capsule 10. The secondary transceiver is not active during the live phase of the capsule 10, i.e. during passage through the GI tract of the subject mammal. The secondary transceiver does not contribute to transmission of the data transmission payload from the capsule 10 to the receiver apparatus 30. The secondary transceiver may not be required to perform any transmission whatsoever, that is, the secondary transceiver may only be required to receive an activation control signal from a smartphone or tablet running an application. However, the NFC protocol may require two-way exchange of signals such as a handshake or coupling process to enable said activation control signal to be transmitted from the smartphone or tablet and received by the capsule 10. Nonetheless, since the secondary transceiver is inactive while the capsule 10 passes through the GI tract of the subject mammal, unlike in the case of the primary transceiver, there is no requirement that the secondary transceiver be configured to transmit signals from inside the GI tract of the subject mammal 40 to a receiver apparatus 30 external to the subject mammal.
Optionally, the secondary transceiver may be configured to receive an encoded activation control signal from a smartphone or tablet (e.g. the receiver computing apparatus 30) running an application configured for managing interactions between the smartphone or tablet (tablet in this context meaning tablet computer) and the capsule 10, which encoded activation control signal initiates a live phase of the capsule 10 during which capsule sensors take readings and the readings themselves or metrics and/or reports based on the readings are transmitted from the capsule 10 to the smartphone or table via the primary wireless data transceiver. Thus, the secondary wireless data transceiver is active in a listening phase which precedes a live phase of the capsule. The primary wireless data transceiver (and the other components such as the sensor hardware, processor hardware, etc) is inactive (i.e. consuming no power whatsoever) during the listening phase. Once the encoded activation control signal is received (and the capsule 10 powered on in response) the listening phase ends and the secondary wireless data transceiver becomes inactive. The primary wireless data transceiver is active during the live phase.
In order to conserve battery power, capsule 10 may operate in a standby or listening mode during the time between release from manufacturing and initiation of the live phase during which readings are recorded by the on-board sensors and transmitted away from the capsule. The standby or listening mode is an extremely low power mode (for example, the sensors and the data processing hardware is inactive during the standby or listening mode). A live phase of the capsule is initiated prior to ingestion by the subject 40. A mechanism for ending the standby or listening mode and entering a live phase may include a reed switch coupled to a magnet on the packaging which is triggered by release of the capsule from the packaging and when triggered powers on the processor, sensors, and primary transceiver (i.e. initiates the live phase). An alternative mechanism is based on Near Field Communication, NFC. In the alternative mechanism, the capsule 10 is maintained in the standby or listening mode (which in the particular example of the NFC is a SENSE mode) prior to being issued to the subject. In the listening mode, when an electromagnetic field is detected with an appropriately encoded activation control message, the on-board control circuitry (such as a microcontroller) enters a live phase. A receiver computing apparatus 30 running an application configured for the purpose of managing interactions with the capsule 10 and the processing of data received therefrom, and having NFC capability, can generate the appropriately encoded activation control message. In particular, a back-end server may link a user account to a particular capsule instance, so that when that user is logged in to the application and selects to activate a capsule, the application performs a lookup to the back-end server to determine how to encode the activation control message. In other words, optionally the encoding is unique per capsule. Alternatively, the encoding may be uniform across a batch of capsules or all capsules.
SI 02 Generate time series of motion sensor data
Step S102 is common to the methods ofFigures la to Id.
At S102 the capsule 10 is in a live phase and so the motion sensor 19 is configured to take readings. For example, under control of control circuitry 15 on board the capsule 10 controlling power supply to the accelerometer and readings therefrom.
An exemplary motion sensor 19 is an accelerometer measuring roll about three mutually orthogonal axes. The readings from the accelerometer 19 may be vectors with a component per axis, with each component indicating an instantaneous angular acceleration about the corresponding axis, or an average acceleration about the corresponding axis over the time period since the preceding live reading. Alternatively, the readings may give a three dimensional orientation of the capsule. The motion sensor 19 may be a gyroscope or angular rate sensor. The motion sensor 19 may be a magnetometer coupled to a magnet external to the subject. The magnet may be fixed to the subject or to a building or to an object. Some pre-processing of the raw motion sensor data may be performed between SI 02 and S103 to prepare the motion sensor data for transform from the time domain to the frequency domain at SI 03. Processing of the readings from the motion sensor 19 may be performed to generate a representation (such as a plot vs time) of aggregated (i.e. all three axes) motion sensor readings. In addition to being a basis for spectral analysis at S103, such a plot or representation may also be used to identify motility markers for events including an excretion event, gastric-duodenal transition, and ileocecal junction transition. The capsule orientation may be measured using a triaxial accelerometer and tracking the gravity vector or another fixed vector (such as provided by an external magnet) with respect to the capsule frame of reference.
Readings from the motion sensor are a time series, so that there is a time value implicitly or explicitly associated with each reading. In the explicit case, readings may be time-stamped, and in the implicit case the readings are chronological and separated by a predefined time resolution step so that a timing can be inferred from a time of initiation of the live phase and a position of the reading within the chronological order.
The motion sensor 19 may be a tri-axis accelerometer generating a single time series of accelerometer data or one time series of accelerometer data per axis.
In case the motion sensor data comprises three time series each representing acceleration in a respective one of the three axes, the process may include a pre-spectral analysis step between SI 02 and SI 03 comprising: combining the three time series into a single resultant time series representing pitch angle (or tilt angle) between a capsule reference axis in fixed relation to the capsule, and an earth reference axis in fixed relation to the earth. The pre-spectral analysis step may comprise combining the three time series into a single resultant time series, for example by a vector addition, a summation of magnitudes, or an RSS combination. Spectral analysis at S 103 would then be performed on the single resultant time series.
In an alternative case, the motion sensor data is accelerometer data comprising three contemporary time series each representing acceleration in a respective one of the three axes, and combining is performed in the frequency domain (as part of SI 03).
A preprocessing step may comprise discarding a time series representing an axis from which a predetermined number or proportion of readings are missing.
Time Series Duration and Other Parameters
The time series of motion sensor data is a truncated time series insofar as it represents motion of the capsule 10 during a subset of the overall time during which it is resident in the GI tract of the subject. The length of the time window determines the frequency resolution of the result of the spectral analysis. The sampling frequency of the motion sensor readings (i.e. the time separation between adjacent readings in the time series of motion sensor data) determines the maximum frequency that is detectable in the frequency domain representation of the accelerometer data. Motion sensor takes readings at a sampling rate fa. Each motion sensor reading represents a motion sensor reading duration l/fa. This is the fundamental sampling rate of the data. The size of the FFT (or other spectral analysis result) is N and the frequency resolution is fa/N.
The time series of motion sensor data may be divided into a series of time windows (either consecutive or sliding) each comprising M/fa, wherein M is a positive integer and is fixed or adaptive. M/fa is a duration of time covered by a time window, wherein M is the number of readings in the time series data.
The time window may be a period of time having a length, for example, between 4 minutes 20 minutes, between 5 minutes and nineteen minutes, between six minutes and eighteen minutes, between seven minutes and seventeen minutes, between eight minutes and sixteen minutes. The time window may have a length of ten minutes, that is, be between nine minutes and eleven minutes in length, or between eight minutes and twelve minutes in length, or between seven minutes and thirteen minutes in length, or between six minutes and fourteen minutes in length, or between five minutes and fifteen minutes in length. The time window may be between fifteen minutes and twenty five minutes in length, between twenty five minutes and thirty five minutes in length, between thirty five minutes and forty five minutes in length, or between forty five minutes and fifty five minutes in length, or between fifty minutes and sixty five minutes in length.
The time window may be as short as one sample l/fa, or as long as all samples in the time series M, or any length in between. Time window length may be fixed or adaptive. Applying an adaptive or variable time window duration function may provide greater spectral resolution at one time window and greater data loss immunity at another.
Figure 6a illustrates a time series of motion sensor data generated by an accelerometer and representing acceleration on the x axis relative to fixed gravitational vector g for a ten minute window 5 hours after ingestion of a sample ingestible capsule.
Step S103: Generate spectral analysis
Step S103 is common to the methods ofFigures la to Id.
Step SI 03 comprises conducting a spectral analysis of the time series of motion sensor data generated by the motion sensor over a time period during passage of the ingestible capsule through the GI tract.
The motion sensor data is time-sampled. In other words, data from the time series of motion sensor data belonging to a time window of duration T is extracted and processed at SI 03. Figure 6a illustrates an exemplary data sample wherein T is ten minutes and the timing is five hours after ingestion of the capsule 10 by the subject 40.
It is noted that spectral analysis may be performed on one or a series of such time windows. The series of time windows may be contiguous, or they may be partially overlapping.
In the method of Figure la, spectral analysis of a single time window may be sufficient to determine a capsule location at S104B, or spectral analysis of a series of time windows may be combined to determine a location of the capsule during the series of time windows, noting the relative loss in precision in the latter case. Time windows may be of a fixed length or may be adaptive.
In the method of Figure lb, spectral analysis of a single time window may be sufficient to enable component signals caused by respiratory function to be identified and extracted. Alternatively, spectral analysis of a series of time windows may be necessary to identify one or more patterns or events that can be attributed to respiratory function.
In the method of Figure 1c, spectral analysis of a single time window may be sufficient to enable an activity type of a subject to be determined. Alternatively, spectral analysis of a series of time windows may be necessary to identify one or more patterns or events that can be attributed to a particular activity type.
Spectral analysis at SI 03 comprises transforming the time series of motion sensor data from the time domain to the frequency domain. An example of a process for performing the transform is a Fast Fourier Transform, FFT
S104B
A result of spectral analysis at SI 03 is a frequency domain representation of the motion sensor data from the time window. The frequency domain representation may be a list, array, or another representation of signal magnitude in each of a series of component frequencies.
Figure 6b illustrates the result of a spectral analysis performed on the time series of motion sensor (accelerometer) data from Figure 6a. In this example it may be that the y-axis and z-axis data was also transformed to the frequency domain, but that the x-axis data had the greatest signal magnitude in the set of peristalsis indicator frequency ranges (which may, for example, be determined by a summation per axis of signal magnitudes in component frequencies falling within one or more frequency ranges in a predefined set of relevant frequency ranges (such as peristalsis indicator frequency ranges in the context of the method of Figure la), and a comparison of the summations to establish the greatest). In particular, as illustrated in Figure 6b, a peak in the frequency domain is observed at around 3 cycles per minute, which is within the frequency range indicating stomach peristalsis, as discussed below in relation to S104B. In the example of Figure 6b, the result of the spectral analysis is a measure of acceleration energy at each of a series of component frequencies. Figure 6b is an illustration of underlying data, and in implementation the underlying data may remain as a data list or array without being rendered in illustrative form such as in Figure 6b.
In implementations leveraging machine learning for the spectral analysis processing at S104B-S106, it may be that the underlying data is rendered into illustrative form and the resulting rendered version (such as a graph, for example) is provided as an input to the machine learning algorithm. Or, it may be that the numerical list or array is provided as input to the machine learning algorithm.
Figure 6c illustrates the result of a spectral analysis performed on a further time series of data generated by the same capsule 10. Figure 6c represents motion sensor data from an accelerometer at a ten minute time window 12 hours after ingestion.
The result of the spectral analysis is stored for use in the S104Bspectral analysis processing step S104B to S106. In the case of remote processing, the result of the spectral analysis is stored for reporting and other further processing. In the case of on-board processing, the result of the spectral analysis may be transmitted away from the capsule 10 to the receiver computing apparatus 30 for reporting and other further processing, or may be discarded after completion of S104Bspectral analysis processing S104B to S106.
The result of the spectral analysis stored for use in the spectral analysis processing step S104B-S106 may comprise a representation of signal magnitude at every component frequency in the frequency domain to which the accelerometer data is transformed at SI 03. Alternatively, data representing frequencies outside of a predefined set of relevant peristalsis indicator frequency ranges may be discarded. For example, power consumption on-board the capsule may be reduced by discarding some of the data at this stage.
The predefined set of relevant frequency ranges may be dependent upon which of the spectral analysis processing steps is to be performed. In the case of location determination S104B, there may be a predefined set of peristalsis indicator frequency ranges.
In the case of respiration analysis S105, it may be that there is a single frequency range associated with respiration, but that also a frequency range associated with snoring is defined. These may be referred to as respiration information frequency ranges. In the case of activity type determination S106, it may be that a predefined set of activity indicator frequency ranges are defined, including, for example, a frequency range indicating walking cadence at around 60cpm to 120cpm, and a frequency range indicating a running cadence at around 160cpm to 220cpm.
Regardless of whether S104Bthe spectral analysis processing step S104B-S106 is performed on-board the capsule or at a remote processing apparatus, the result of the spectral analysis from SI 03 may be transmitted to the remote processing apparatus for storage and reporting (and optionally for S104Bspectral analysis processing to be performed by the remote processing apparatus).
That is, even if the spectral analysis processing, such as determination of location S104B, is to be performed on-board the capsule 10, the result of the spectral analysis may be stored by the capsule 10 on the memory hardware 152 for use in S104Bspectral analysis processing and for transmitting away from the capsule by the wireless transceiver 18.
Step SI 04a: Detect Peristalsis
Using the spectral analysis to detect peristalsis SI 04a is an example of a spectral analysis processing step. Using the spectral analysis to detect peristalsis S104a may include interrogating or otherwise processing the spectral analysis to identify signals indicative of peristalsis in one of the regions of the GI tract. Identifying a signal at a predefined minimum energy or magnitude in a frequency range indicating peristalsis (i.e. one of a predefined set of peristalsis indicator frequency ranges) may be a detection of peristalsis. Rather than a predefined minimum energy, it may be that a characteristic frequency is identified among the spectral analysis (i.e. a frequency component showing a strongest signal among the frequency components) and if the characteristic frequency is within one of a predefined set of peristalsis indicator frequency ranges, then peristalsis is detected.
For example, there may be a predefined set of frequency ranges that indicate location of the capsule 10, these being the set of peristalsis indicator frequency ranges. The detecting at S104a may comprise, in the result of the spectral analysis, detecting presence or absence of a signal/component at one or more of a predefined set of peristalsis indicator frequency ranges. For example, total magnitude of signal at the one or more component frequencies within the frequency range meets a predefined minimum threshold, or an adaptive threshold. Thresholds are not required, since it may be that a characteristic frequency is extracted from the result of the spectral analysis at SI 03 and a determination made of whether the characteristic frequency belongs to one of the predefined set of peristalsis indicator frequency ranges. The predefined set of peristalsis indicator frequency ranges may comprise one or more from among:
- a first peristalsis indicator frequency range, being a frequency range indicating stomach peristalsis;
- a second peristalsis indicator frequency range, being a frequency range indicating small intestine peristalsis;
- a third peristalsis indicator frequency range, being a frequency range indicating large intestine peristalsis.
The first peristalsis indicator frequency range indicating stomach peristalsis may be around 3 cycles per minute. An exemplary range is from 2.5 to 3.5 cycles per minute.
The second peristalsis indicator frequency range indicating small intestine peristalsis may be around 10 cycles per minute (as illustrated in Figure 6c). An exemplary range is from 9.5 to 10.5 cycles per minute, or from 9 to 11 cycles per minute, or from 8.5 to 11.5 cycles per minute.
The third peristalsis indicator frequency range indicating large intestine peristalsis may be around 0.5 cycles per minute, around 1 cycle per minute, around 1.5 cycles per minute, or around 2 cycles per minute. An exemplary frequency range is from 0.5 to 2 cycles per minute, or from 1 to 2 cycles per minute, or from 0.5 to 2.5 cycles per minute, or from 1 to 2 cycles per minute.
Further information may be derived from the spectral analysis, in particular where the process is repeated for a series of time periods. For example, fluctuations, variations, or anomalies within particular spectral components (frequency ranges of interest such as peristalsis indicator frequency ranges or respiration information frequency ranges or patterns, or physical activity type indicator frequency ranges) or of the characteristic frequency may be recorded and reported, either on-board the capsule 10, or in case the process is performed at a remote processing apparatus, then at the remote processing apparatus. Such further information may be valuable for health monitoring and diagnostic purposes. An example of such further information is power distribution across the entire frequency range (or across the frequency ranges of interest) in one or a series of time periods. An example of such further information is rhythm or distribution of a centre frequency across a series of time periods (optionally across the entire passage through the GI tract). An example of such further information is the identification of gaps in the peristaltic wave, that is, is there a time period or time periods where signals in one of the peristalsis indicator frequency ranges is lower than chronologically adjacent time periods, or is not detectable whereas it is detectable in time periods before and after. An example of such further information is a metric or metrics calculated from the spectral analysis from among: centre frequency, frequency spread, power distribution, frequency gaps. Any of these further information elements may be identified or measured on-board the capsule 10 or at a remote processing apparatus by processing the spectral analysis, and included in a report generated and output at SI 07.
Generating the further information from the spectral analysis is an example of a spectral analysis processing step.
Step S104B: Determine location of the capsule within the GI tract
The method of Figure la includes S104B determining the location of the capsule within the GI tract at the time period represented by the time series of motion sensor data. Step S104B is optional in the methods of Figures lb and 1c.
Step S 104B comprises using the spectral analysis to determine a location of the ingestible capsule within the GI tract at the time period, based on the peristalsis detection at SI 04a. Wherein the time period in question is the time period during which the motion sensor readings were taken that form the time series of motion sensor data on which spectral analysis is conducted at SI 03.
Absence of a signal may also contribute to a location determination. Therefore, it is feasible to determine location at SI 04b in the absence of a positive detections at SI 04a.
The ingestible capsule may be determined to be in the stomach by presence of a signal in the first peristalsis indicator frequency range. The ingestible capsule may be determined to be in the small intestine by presence of a signal in the second peristalsis indicator frequency range. The ingestible capsule may be determined to be in the large intestine by absence of a signal in the first peristalsis indicator frequency range and absence of a signal in the second peristalsis indicator frequency range. The ingestible capsule may be determined to be in the large intestine by presence of a signal in the third peristalsis indicator frequency range.
In any of the spectral analysis steps S104A to S106, in addition to identifying primary or average frequencies, further information may be extracted from the spectral analysis result, such as instability at or around a specific frequency range. Instabilities may be the result of a health condition and hence may contribute to a diagnosis. Such further information may be included in a report to be transmitted away from the capsule 10, or in the case of remote processing may be included in a report to be output to a clinician, subject, or another recipient.
In Figure 6b (at 5 hours after ingestion), the spectral analysis shows a detectable spike at frequency components around 3cpm. This is an indication that magnitude(s) of the signal amplitudes (or a summation thereof) at the one or more frequency components within the first peristalsis indicator frequency range satisfies a threshold and that therefore at S104B a determination is made that, in the spectral analysis illustrated by Figure 6b, at the pertinent time window, the capsule 10 is located in the stomach. The 2nd harmonic at 6cpm is also detectable. Optionally in the determination at S104B detection of a signal at the 2nd harmonic may be used to confirm a detection at the first harmonic (the first harmonics being in the stated peristalsis indicator frequency ranges).
In Figure 6c (at 12 hours after ingestion), the spectral analysis shows a detectable spike at frequency components around lOcpm. This is an indication that magnitude(s) of the signal amplitudes (or a summation thereof) at the one or more frequency components within the first peristalsis indicator frequency range satisfies a threshold and that therefore at S104B a determination is made that, in the spectral analysis illustrated by Figure 6c, at the pertinent time window (12 hours after ingestion), the capsule 10 is located in the small intestine.
Figure 6d illustrates time series of additional sensor data. Figure 6d illustrates that the two sample determinations based on the spectral analysis results in Figures 6b and 6c are correct. Figure 6d further demonstrates the additional sensor data that may be generated by the capsule 10. Figure 6d shows sensor data from a plurality of additional sensors: capsules 10 may have no additional sensors, one additional sensor, or some subset of the additional sensors generating the data shown in Figure 6d (which corresponds to a capsule 10 hardware arrangement such as is illustrated in Figure 4). Other examples of additional sensors include pulse-oximetry sensors and EMG sensors, each of which may be housed within the ingestible capsule 10, or provided externally and affixed to a skin of the subject during GI tract passage of the ingestible capsule 10.
The determination at SI 04b may be based upon a spectral analysis result from a single spectral analysis representing a single time window. Alternatively, the determination S104b may be based upon plural spectral analysis results each representing a different (and optionally distinct i.e. non-overlapping) time window. In the case of a single time window, a determination may be based upon meeting a minimum threshold amount of energy (or other measure of signal magnitude) at frequencies within the respective peristalsis indicator frequency range. In the case of plural time windows, it may be that a minimum threshold amount of eneigy (or other measure of signal magnitude) needs to be met for a predefined proportion (such as three-quarters, two-thirds, etc) of a predefined number of time windows, in order to make a positive determination of location of the capsule 10 at the associated location. Or, it may be that the characteristic frequency from the spectral analysis results of n consecutive time windows is within a particular peristalsis indicator frequency range. The minimum signal threshold to apply to a series of time periods may be, for example, a minimum summation of signal energy in the frequency range over the series of time periods, or a minimum proportion of individual time windows for which the signal in the frequency range exceeds a minimum for the individual time window. For example if an individual time window minimum is satisfied for 3 out of 4 time windows then that may result in the minimum signal threshold being satisfied, but if the individual time window minimum is only satisfied for 2 out of the 4 time windows then that may not be sufficient.
The determination may be a two-step process including first detecting S 104a a signal within the or each of the predefined set of frequency ranges, and second determining location SI 04b by comparing the detected signal with a predefined threshold minimum to determine whether the detected signal is strong enough for a positive determination of presence of the capsule 10 within the location associated with the respective frequency range.
Alternatively it may be that a signal must exceed a threshold in order to be considered a detection, for example a threshold based on signal-to-noise ratio or signal-to-interference-plus-noise ratio. In such cases, the first and second steps are effectively combined.
In an alternative case, a pre-trained machine learning algorithm may process the result of the spectral analysis to determine the location of the ingestible capsule at the one or more time windows.
S105: Extracting Respiration Information and Other Frequency Ranges of Interest
Figure lb illustrates a method in which the spectral analysis result is analysed to extract information relating to respiration and associated health parameters. In addition or as an alternative to detecting signals in the set of peristalsis indicator frequency ranges, the process may include detecting signals in other relevant frequency ranges, for example, for health monitoring and diagnostics. Measurements representing signal amplitude or energy at one or a series of time windows in one or more from among a further set of frequency ranges may be calculated (either on-board or at a remote processing apparatus) and stored for reporting. The further set of frequency ranges may be the respiration information frequency ranges referred to above, which is not to be interpreted as solely indicating respiration, but also allied rhythmic processes such as heart beat and snoring.
In the case of on-board processing, the measurements at each of the further set of frequency ranges may be included in a data transmission payload transmitted by the wireless data transceiver 18 to remote processing apparatus. This is more efficient in terms of transmission overheads than transmitting the raw accelerometer data or even the spectral analysis across the entire frequency domain. The respiration information frequency ranges may include:
- a heart rate frequency range at around 50 to 120 cycles per minute;
- a respiration frequency range at around 12 to 18 cycles per minute;
- a snoring frequency range at around 3600 to 18000 cycles per minute.
Where information is referred as being stored for reporting in this and other contexts is taken to mean the data is output to, or otherwise made available to, an application or messaging interface. For example, such an application or messaging interface may be to provide the information to a clinician or to the subject.
In particular, the information extracted at SI 05 may be combined with contemporaneous readings from a pulse oximeter sensor 32, wherein combined is taken to mean reported in combination with (and aligned in terms of timings). For example, a report comprising an indication of time windows at which signals were or were not present in the respiration frequency ranges of interest, and the contemporaneous influence on pulse oximetry data, may be of particular interest to a clinician.
Combining SI 04a and SI 04b with SI 05 enable a clinician to perform health monitoring or diagnostics in which, for example, influence of sleep or snoring on GI tract motility is analysed.
The method of Figure lb, in which respiration information is extracted, may be used in a sleep study. In particular, one or more of the following may be detected in the spectral analysis and such detections included in the extracted respiration information for reporting and output at SI 07:
-sleep apnea (absence of respiration during sleep);
-normal respiration;
-Blots respiration;
-Kussmaul breathing;
-Cheyne Stokes respiration;
- Bradypnea;
-Tachypnea;
-Hyperpnea;
-Ataxic respiration;
-Air trapping;
-Obstructive respiration;
-Sighing;
-Apneustic respiration;
-Agonal respiration. Extracted respiration information may further include respiration rate and changes in rate. In particular, the extracted respiration information may be combined (in a report) with contemporaneous readings from an onboard or external pulse oximetry sensor 32. Furthermore, the extracted respiration information may be combined in a report with contemporaneous sensor data or information derived therefrom indicating movement and GI tract motility of the subject.
Extracted respiration information may be performed by pattern-matching based on a predefined set of frequency domain patterns each associated with a respiration pattern or respiration disorder. A pattern matching algorithm may be executed on-board the capsule or at the remote processing apparatus. The pattern may be in the spectral analysis for one time window or a series of time windows. The pattern may comprise a marker, signature, or some other identifiable characteristic that facilitates matching by the pattern matching algorithm. A classifier machine learning algorithm may be trained with training data comprising spectral analysis (from SI 03) for one or a series of time windows from patients known to have a particular respiratory condition, or to be exhibiting a particular respiratory pattern (normal breathing, disordered breathing), labelled with the condition or respiratory pattern as ground truth, training the machine learning algorithm to classify input representations of spectral analysis from SI 03 for one or a series of time windows to one of the respiratory conditions or respiratory pattern. In addition or alternative to the spectral analysis, one or more metrics derived from the spectral analysis may be included as input to the machine learning algorithm or pattern matching algorithm, such as centre frequency variability. Equivalent functionality may be provided by a pattern matching algorithm. In either case the algorithm may be applied on the capsule or at the remote processing apparatus. Examples of respiratory conditions or patterns include:
-sleep apnea (absence of respiration during sleep);
-normal respiration;
-Blots respiration;
-Kussmaul breathing;
-Cheyne Stokes respiration;
- Bradypnea;
-Tachypnea;
-Hyperpnea;
-Ataxic respiration;
-Air trapping;
-Obstructive respiration;
-Sighing;
-Apneustic respiration;
-Agonal respiration. In a simplified alternative, the respiratory condition or pattern may be identified in the spectral analysis by a signal at a particular component frequency, or by a derived metric such as centre frequency variability satisfying a condition.
The outcome of the pattern matching, the classifier machine learning algorithm, or the simplified alternative, may be included in a report to be output to a receive computing apparatus, to a message recipient, or to a particular storage location for later access by the subject or a clinician.
Further information may be derived from the spectral analysis, in particular where the process is repeated for a series of time periods. For example, fluctuations, variations, or anomalies within particular spectral components (frequency ranges of interest such as respiration information frequency ranges or fitting certain respiration patterns) or of frequencies in a heart rate range, may be recorded and reported, either on-board the capsule 10, or in case the process is performed at a remote processing apparatus, then at the remote processing apparatus. Such further information may be valuable for health monitoring and diagnostic purposes. An example of such further information is power distribution across the entire frequency range (or within the frequency ranges of interest) in one or a series of time periods. An example of such further information is rhythm or distribution of a centre frequency across a series of time periods (optionally across the entire passage through the GI tract). An example of such further information is the identification of gaps in the respiration information frequency ranges, that is, is there a time period or time periods where signals in one of the respiration indicator frequency ranges is lower than chronologically adjacent time periods, or is not detectable whereas it is detectable in time periods before and after. An example of such further information is a metric or metrics calculated from the spectral analysis from among: centre frequency, frequency spread, power distribution, frequency gaps. Any of these further information elements may be identified or measured on-board the capsule 10 or at a remote processing apparatus by processing the spectral analysis, and included in a report generated and output at SI 07.
Step SI 06: Physical activity analysis
Figure 1c illustrates a method in which the spectral analysis result is analysed to extract information relating to subject physical activity. Examples include strength training and gait analysis.
Cadence of subject gait may be an indicator of activity type in itself, for example a signal at a component frequency predefined as an indicator of walking (and optionally also associated with a contemporaneous net movement in the motion sensor data indicating movement) may lead to a determination of subject undertaking a walking activity. Likewise for running, albeit at a higher cadence. The spectral analysis may provide information from which a characterisation of a physical activity can be made, such as distance travelled, steps taken, reps performed, cadence, active time vs resting time, intensity (based on power distribution or total power across the full frequency range).
Activity type may be determined on-board at S 106 and a signal comprising the result output to a receiver computing apparatus, which may be a smart watch. The signal may be a trigger to the smart watch to start or finish activity tracking.
Beyond simply determining activity type, gait analysis may be used to detect sudden changes in gait, which may be a precursor to a fall. For example, the analysis at SI 06 may include comparing the gait of the subject at the time window to a preceding one or more time windows, and in the case of a sudden change, outputting a signal indicating the said change to a coupled smart watch or smart phone to warn of likelihood of a fall. The said coupled smart watch or smart phone may be configured to relay the warning to a registered contact of the subject.
Alternatively, the capsule 10 may be signalled from the coupled smart watch or smart phone to begin gait analysis, initiate an execution of the method of figure 1c, and report either the spectral analysis result or a detection of any unusual gait information to the smart watch or smart phone.
Alternatively, the capsule 10 may be signalled from the coupled smart watch or smart phone that the subject has initiated a physical activity of a specified type (examples include running, walking, aerobics, weightlifting), which signal triggers the capsule 10 to initiate the process of SI 02, SI 03, and SI 06 (see Figure 1c). Alternatively, the capsule 10 may be performing steps S102 and S103 regardless (for example in order to perform respiratory information extractions at SI 05 or peristalsis detection at S104a) and so the trigger is to being physical activity analysis S106. Noting that the process may be repeated for a series of time periods (being the sample length for the motion sensor data that is converted to the frequency domain at SI 03), therefore enabling physical activity monitoring over a duration composed of two or more such time periods. The analysis at S106 may comprise, based on the spectral analysis, characterising the physical activity according to a characterisation model predefined for the specified type of physical activity. For example, in the context of weightlifting movements corresponding to repetitions may be identified in the spectral analysis data and counted as the characterisation. In the context of running or walking, signals within cadence ranges may be identified so that the characterisation includes cadence information. Furthermore, analysis of distribution of signals in the cadence range and variability may enable unusual gait to be detected and included in the characterisation. Likewise, periods of rest may be identified and included in the characterisation.
Step SI 06 may be performed in the absence of steps SI 04a, SI 04b, and SI 05, or in combination with one or more of those steps. Step SI 07 Reporting
Any of the methods of Figures la to Id may include generating a report at S107. In Figures la to Id, dashed lines indicate optional steps.
In processes including generating a report, the process may further comprise outputting the generated report. In implementations in which the process is conducted on-board the ingestible capsule 10 and so the report is generated on-board, the outputting may comprise transmitting the report via a wireless transceiver (for example, via Bluetooth) to a paired receiver computing apparatus 30. For example, the report may be stored at the receiver computing apparatus 30, may be combined with further reports from the same ingestible capsule 10 (i.e. from the same GI tract passage), and may be relayed to a messaging recipient or uploaded to a remote computing apparatus for storage and optionally for further analysis. A report is a message or other data artefact comprising payload data (the specified information) and optionally also metadata for the purposes of enabling the transmission of the report itself from one device to another.
Where processes generate plural reports, those reports may be combined and treated as a single report for the purposes of data transmission. For example, a single set of messaging metadata may be combined with two or more such reports as payload data, to comprise a single combined report message. Such a single combined report message may be generated at the capsule 10 and transmitted from the capsule 10 to the receiver computing apparatus 30 via Bluetooth. Such a single combined report message may be generated at the receiver computing apparatus 30 and uploaded or otherwise sent to a remote computing apparatus or message recipient, either by combining individual reports generated by and received from the capsule 10 or by generating the individual reports at the receiver computing apparatus 30.
In any of the reports, in addition to a result or outcome of the spectral analysis processing step, the report may also include one or more from among:
- the spectral analysis for the time period, and
- additional sensor data readings from the same time period, and/or an outcome or processing the additional sensor data readings from the same time period such as a metric or identification of a motility marker, and/or information derived from additional sensor data readings from the same time period. A report, plural reports, or a single combined report, if generated on-board the capsule 10 by the memory hardware 152 and processor hardware 151, may be included as data transmission payload for transmission from the capsule 10 by the wireless transceiver 18 to a receiver.
Location tracking and motility reporting
The methods of Figures la to Id may be performed on a repeated basis to monitor the relevant information (capsule location within GI tract, respiration, activity type) across a plurality of time windows. The time windows need not run continuously. The time windows may be contiguous. The time windows may be partially overlapping. To save processing and/or data transmission resources on board the capsule 10, the time windows may be separated by gaps of five, ten, fifteen, thirty, sixty minutes, for example. The time windows themselves may be of the order of one minute, two minutes, five minutes, ten minutes, depending on the implementation.
The purpose of tracking the location may be to generate a motility report indicating a length of time the capsule 10 spent at each of plural locations within the GI tract such as stomach, small intestine, large intestine, or some combination thereof. Such information can be helpful in itself in gut health monitoring and diagnosis of conditions.
Said report may be augmented with additional sensor data for the same time window and/or with results of other spectral analysis processing steps S105 and/or S106.
Combination with additional sensor data
The capsule 10 may comprise one or more additional sensors, such as illustrated in Figure 4 and Figures 5a to 5c. Wherein additional in this context is taken to mean a sensor beyond the motion sensor 19. Noting that there may be plural motion sensors 19 (an accelerometer and a gyroscope or magnetometer) so the additional sensor may also be a motion sensor.
The additional sensors may provide time series data that is also used in location determinations. Alternatively or additionally, the additional sensors may provide data for which the peristalsis detected at SI 04a or the locations determined at SI 04b provide context. For example, the capsule 10 may include one or more gas sensors, and there may be gases or gas concentrations that, if present in a particular location in the GI tract, are indicators of good gut health, poor gut health, or are diagnostic markers for conditions. Such conditions may include, for example, gastroparesis and SIBO. Figure 4 illustrates an ingestible capsule 10 with a plurality of additional sensors. A single one from among the illustrated additional sensors may be included in a capsule 10, or some subset of those illustrated in Figure 4.
Figure 5a shows a particular selection, which includes the power source 16, motion sensor 19, wireless transceiver 18 comprising antenna 17 and directional coupler 171 to provide reflectometer readings, control circuitry 15 to control power supply to the other components and optionally also transfer of readings from the reflectometer and motion sensor 19 to the memory hardware 152, and processor hardware 151. Advantageously in the arrangement of Figure 5a the sensors are a motion sensor 19 and reflectometer, so no direct exposure to the environment is required. The arrangement of Figure 5a includes processor hardware 151. This is optional, noting that the arrangement of Figure 5a may be configured to transmit raw motion sensor data away from the capsule 10 to remote processing apparatus for generating the spectral analysis result at SI 03 and S104Banalysing or otherwise processing the spectral analysis result at S104B, S105, or S106. Alternatively the processor hardware 151 may be included and one or both of performing the spectral analysis SI 03 and the spectral analysis processing S104B-S106 performed on-board the capsule 10.
The optional additional sensors in the capsule 10 may be one or some combination from among:
- a gas sensor, which in particular may be a TCD gas sensor 131 and/or a VOC gas sensor;
- a temperature sensor 14a;
- a relative humidity sensor 14b;
- a pulse -oximetry sensor 32;
- an EMG sensor 31;
- a reflectometer formed by an antenna 17 of the wireless data transceiver 18 and a directional coupler 171 (noting that one or more of these components may be present on the capsule for data communication purposes irrespective of reflectometer functionality.
The capsule 10 may include one or both of a TCD gas sensor 131 and a VOC gas sensor 132. The gas sensors 13 are less than several mm in dimension each and are sensitive to particular gas constituents including oxygen, hydrogen, carbon dioxide and methane. In fact, the VOC sensor 132 may be configured to give sensor side readings and driver or heater side readings. The heater side readings may be used to determine thermal conductivity of a surrounding gas and thereby the heater side readings of the VOC are TCD readings. The sensor side readings are used to determine concentrations of volatile organic compounds in the surrounding gases and are VOC readings. The TCD sensor 131 may be, for example, a heating element coupled to a thermopile output, with the thermopile temperature varying due to energy conducted into the gas at the location of the capsule 10. The TCD sensor 131 measures rate of heat diffusion away from the heating element. The heater side of the VOC sensor (operating as a TCD sensor) and the sensor side of the TCD sensor have different operating ranges, so TCD readings from the two sensors collectively span a wider range of operating temperatures than either of the sensors individually. Both sensors have heating elements. The TCD sensor has a low operating temperature but with a high precision. The heater side of the VOC increases the operating range but has a lower precision for TCD readings than the TCD sensor. The larger collective thermal range achieved by the two gas sensors 13 in concert enables better resolution of analytes in the second processing branch. The thermal conductivity of constituent gases in the gas mixture of the GI tract varies with temperature and so by obtaining TCD readings at different operating temperatures the different gases can be resolved from each other. This may be leveraged in measuring concentrations of constituent gases in the gas mixture surrounding the capsule 10.
For ease of description the gas sensors are discussed here in the plural, though it is noted that the capsule 10 may not include any gas sensors or may include only a single gas sensor. The gas sensors are contained in a portion of the capsule 10 sealed from the power source 16 and other electronic components by a membrane 111. The outer surface of this portion of the capsule may be composed of a selectively permeable membrane 11, or there may be an aperture allowing the gas mixture surrounding the capsule 10 to enter into the portion of the capsule 10 housing the gas sensors (and the temperature sensor 14a and relative humidity sensor 14b, where included). For example, the gas sensors include respective heaters which are driven to heat sensing portions of the respective gas sensors to temperatures at which sensor readings are obtained (i.e. a measurement temperature). The heaters may be driven in pulses so that there is temporal variation in the sensing portion temperature and so that measurement temperatures are obtained for periods sufficient to take readings but without consuming the power that would be required to sustain the measurement temperature continuously.
The gas sensors may be calibrated, so that a gas sensor reading can be used to identify the composition and concentration of a particular gas. Calibration coefficients are gathered in manufacturing and applied to the recorded readings at the processing stage (i.e. by a server such as on the cloud or on-board the capsule 10). Otherwise, this calibration could be performed on the capsule 10, at the receiver computing apparatus 30, or on any device having access to the calibration coefficients and the recorded readings from the gas sensors. Such calibration relates to processing concerned with measuring the concentration of constituent gases in the gas mixture at the capsule 10. Context for the outputs of that processing may be provided by the determinations made at SI 04b providing a location of the capsule 10 within the GI tract at which said gas mixture is found. Instead of calibration, the gas sensors may be used on a relative measure basis, where there is no formal pre -calibration and it is simply the variability in readings that is used. Alternatively the gas sensors could be calibrated on-the-fly using stomach data as a baseline. Additional sensor data may be processed to identify one or more motility markers to use as part of the determination at SI 04b. More detail on the detection and precise form of said motility markers is set out in PCT/AU2022/051270, to which reference may be made. A summary is presented below for ease of reference.
Figure 5b illustrates a capsule arrangement in which the additional sensor hardware comprises an EMG 31. The EMG 31 may be on-board the capsule 10 or may be separate from the capsule 10 but provided as part of a system comprising the capsule 10 and the EMG 31. The capsule 10 may include an EMG (electromyographic) sensor comprising a pair of electrodes on an external surface of the ingestible capsule 10 at either end. The EMG sensor measures electrical activity in a medium or on a surface by measuring a potential difference across the pair of electrodes. Alternatively, the EMG sensor 31 may be separate from the capsule 10, and may comprise two or more electrodes affixed to the skin of the subject at locations corresponding to the GI tract. In the case of the EMG sensor 31 being on-capsule, the sensor data from the EMG sensor 31 may be processed on-board the capsule 10, or may be transmitted to the remote computing apparatus for processing. In the case of the skin-mounted EMG sensor 31, the sensor data, or one or more results from the processing of the sensor data by a computing apparatus in receipt of the said sensor data, may be transmitted to the wireless transceiver 18 of the capsule and then used by the on-board processor hardware 151.
By comparing contemporaneous EMG sensor data and spectral analysis results, electrical signals triggering muscular contractions can be compared with mechanical movements resulting from muscular contractions, and results of the comparison used in health assessments and diagnostics.
As with the additional sensor data discussed above, the EMG sensor data may be used to add confidence to location determinations made from the results of the spectral analysis of the motion sensor data, or may be used in reporting to add context to results, or in diagnostics that utilise the location determination.
One or more from among: the motion sensor data; the spectral analysis result; location determinations; peristalsis detections; respiratory information; gait analysis information; activity type determination; the additional sensor data; and detected motility event timings; may be included in a report. The reported data are contemporaneous, meaning that additional sensor data readings in a time series representing a time window are included in a report also comprising a spectral analysis result of the motion sensor data for the same time window, and/or an outcome or result of processing the said spectral analysis result. The report may be compiled on-board the capsule 10 (by the memory hardware 152 and processor hardware 151) and transmitted away during passage through the GI tract or in a burst or inquiry mode following detection of excretion (for example by detecting a freefall event), or the report may be compiled by the remote computing apparatus. Or the report may be compiled on-board the capsule 10 and by the remote computing apparatus in combination.
Figure 5c illustrates a pulse-oximetry sensor 32 as additional sensor hardware. As with the EMG sensor 31, the pulse-oximetry sensor 32 may be provided on-board the capsule 10 or as a separate part of a system also including the capsule 10. For example, the pulse -oximetry sensor may be finger-worn. In the case of the on-board pulse -oximetry sensor, the capsule housing 11 may comprise a window or aperture via which LED light is transmitted and reflected light sensed. Alternatively, the pulse-ox sensor 32 may comprise a light transmitter and sensor affixed to the exterior surface of the capsule housing 11.
Sensor data from the pulse-oximetry sensor may be included in a report generated by the capsule 10, or the capsule 10 in cooperation with the remote processing apparatus. The report may be used by a clinician for diagnostic purposes. For example, in respiration monitoring implementations, influence of disordered respiration or other respiration events detected in the result of the spectral analysis may be combined with the pulse-oximetry data. In particular, pulse-oximetry data from the small intestine may be particularly accurate due to the highly vascularized surfaces of the small intestine. Optionally, a first on-the-fly determination of location in the small intestine at SI 04b may be a trigger for the microcontroller 15 to turn on the pulse oximetry sensor 32 and start taking readings.
Figure 6d illustrates additional sensor data from a live phase of an ingestible capsule, that is, a powered- on phase of a capsule 10 within the GI tract of a subject. An ingestion event (marked T) may be determined from the additional sensor data, for example the rise in relative humidity, or may be determined from a user interaction with a user interface on the receiver computing apparatus 30.
Hydrogen concentration measurements are a metric derivable from TCD gas sensor readings, appropriately calibrated. H2 levels or TCD gas sensor readings themselves may be used as a basis for a gastric-duodenal transition indicator (marked ‘GDJ’). H2 levels may be sensed directly or may be derived, such as derived from TCD gas sensor readings. C02 concentration measurements are derivable by appropriate calibration of the TCD gas sensor readings. The ICJ indicator (marked ‘ICJ’) being a steep rise (i.e. positive gradient above a predefined threshold) in CO2 concentration. PCT/AU2022/051270, at [0300] to [0303], explains in more detail how by operating the TCD gas sensor at different sensing temperatures, different gases may be resolved. Extra information may be added by driving the VOC gas sensor heater side to take TCD measurements therefrom.
The gastric-duodenal transition event may be detected in the TCD gas sensor readings as a spike, 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.
An ilCJ indicator may be detected by identifying an increase in (sensor side) VOC gas sensor output exceeding a predefined threshold. Alternatively ileocecal junction transition indicator may be detected by identifying an increase in a metric derived from VOC gas sensor output such as CO4 concentration (marked ‘fermentation’ in Figure 6d). Optionally, a further criterion may be applied such as presence of a contemporaneous, or temporally adjacent to within a predefined temporal distance either side, increase in measured H2 levels exceeding a predefined threshold. Noting that H2 levels are determined from the TCD gas sensor output and/or heater-side VOC sensor output.
In the location determination processing, the determination at SI 04b may be based on the spectral analysis from SI 03 and peristalsis detections at SI 04a alone, or in combination with data from the one or more additional sensors. The data from the additional sensors may provide a motility marker being either an indication either of a location at which the capsule 10 is located (for example reflectometry measurements of the medium surrounding the capsule 10) or that a motility event has occurred (for example an inflection point, spike, or step change in concentration of a particular gas at a transition between two parts of the GI tract). Figure 6d illustrates timings of three motility markers T (ingestion), ‘ICJ’ (ileocecal junction transition indicator), and ‘GDJ’ (gastric duodenal junction transition indicator).
Such motility markers from the additional sensor data may be used in a deterministic way at S 104B, for example it may be that a determination that the capsule 10 is in the small intestine at a time window based on the spectral analysis from S 103 can only be made if a gastric emptying event has been detected in the additional sensor data preceding that time window. Likewise, it may be that a determination that the capsule 10 is in the large intestine at a time window based on the spectral analysis from SI 03 can only be made if an ileocecal junction transition event has been detected in the additional sensor data preceding that time window. Alternatively, the spectral analysis from SI 03 and the additional sensor data may be provided to a pretrained machine learning algorithm to classify capsule location at a particular time window.
Some calibration may be required in seeking to find motility markers in the additional sensor data such as gastric-duodenal transition indicators, since ingested foodstuffs at different temperatures change the environmental temperature in the stomach, which influences rate of heat diffusion. In the case of gas sensor readings taken after ingestion and before the gastric-duodenal transition (i.e. whilst the capsule 10 is in the stomach), processing of readings may include applying a moderation to TCD readings, from either gas sensor, in order to correct for variations in environmental temperature, based on environmental temperature readings by the environmental temperature sensor 14a. TCD readings are effectively measuring rate of heat loss to surroundings, and so accuracy is improved by measuring the temperature of the surroundings rather than by relying on assumption (i.e. prior knowledge of internal temperature of the subject mammal). However, the processing may rely on assumption, for example, if the capsule 10 does not include an environmental temperature sensor 14a or if there is some issue with the environmental temperature sensor readings, or, for example, if the level of accuracy provided by assumption is acceptable in a particular implementation. Gastric temperature may vary based on, for example, ingestion of liquids or foodstuffs by the subject mammal, or physical activity undertaken by the subject mammal 40. Environmental temperature is a term used in this document to refer to the temperature of the environment in which the capsule 10 is located, as distinct from operational temperatures of the gas sensors. The sensitivity of the gas sensors to different constituent gases vary according to the operating temperature of the sensors and the processing of the readings includes calibrating (also referred to as moderating or correcting) readings from the gas sensors according to contemporaneous operating temperature and optionally also according to contemporaneous environmental temperature.
In addition to the gas sensors 13 and the environmental sensor 14 (being a temperature sensor 14a and/or a humidity sensor 14b), the capsule electronics further include a microcontroller 15 or some other form of control circuitry, a power source 16, an antenna 17 or plural antennae, a wireless transceiver 18 or plural wireless transceivers, and optionally a reed switch (though in the case of there being two wireless transceivers the reed switch may be omitted) or some other mechanism to initiate data recording. The wireless transmitter 18 may operate in concert with the antenna 17 of the primary transceiver to transmit a data transmission payload including readings from the sensors (collectively referring to the gas sensors 13 and the environmental sensor 14) to a receiver apparatus 30 and/or a remote computer 20 for processing. Alternatively, sensor data may be processed on-board and results transmitted away via the wireless transmitter 18. Figure 4 illustrates the primary transceiver antenna 17 and directional coupler 171 as elements of the wireless transmitter 18, since the antenna is the physical means by which the wireless transmitter 18 transmits data to the receiver apparatus 30. The wireless transmitter 18 is also configured to buffer data for transmission. The wireless transmitter 18 may also be configured to encode the data with a code unique to the capsule 10 among a population of like capsules 10.
Figure 7 illustrates an exemplary reflectometer arrangement.
Optionally, the capsule 10 includes a reflectometer comprising a transmission antenna 17 connected in series with a directional coupler 171 configured to measure a reflected signal from the transmission antenna 17, the output signal output by the sensing mechanism comprising accelerometer readings and/or reflectometer readings.
Optionally, the capsule 10 includes the reflectometer, and the ingestible capsule further comprises a diode detector and the diode detector forms a part of the reflectometer, the diode detector being configured to receive the reflected signal from the antenna and to measure an amplitude of the reflected signal, the reflectometer readings in the output signal comprising amplitude measurements of the reflected signal.
Optionally, the ingestible capsule 10 further comprises a quadrature demodulator and the quadrature demodulator forms a part of the reflectometer, the quadrature demodulator being configured to receive the reflected signal from the antenna via the directional coupler and to extract phase information of the reflected signal relative to a carrier signal, the reflectometer readings in the output signal comprising the extracted phase information of the reflected signal.
Optionally, the ingestible capsule 10 further comprises an antenna impedance control mechanism comprising a variable capacitor configured to vary impedance of the transmission antenna, and a controller, wherein the reflectometer and the antenna impedance control mechanism form a closed loop or feedback loop, and wherein the controller is configured to receive the measurements of the amplitude of the reflected signal from a diode detector and to execute a control algorithm to use the amplitude measurements to generate an antenna impedance control signal setting a capacitance of the variable capacitor 172 to vary impedance of the antenna to reduce amplitude of the reflected signal, wherein the reflectometer readings in the output signal comprise readings of the antenna impedance control signal.
Optionally, the closed loop or feedback loop further comprises a quadrature demodulator, and wherein phase information is extracted by the quadrature demodulator and output to the controller, and wherein the controller is configured to use the amplitude information and the phase information to generate the antenna impedance control signal.
Optionally, the additional sensor data comprises reflectometer readings, and a motility marker may be detected therein. Specifically, an ileocecal junction transition indicator may be detected in readings from the reflectometer. Processing includes: processing the reflectometer readings to identify the presence of an ileocecal junction transition indicator in the reflectometer readings.
Figure 8 illustrates readings from a directional coupler 171 of a reflectometer and in particular illustrates step changes coinciding with the detected gastric duodenal transition indicator and the ileocecal junction transition indicator. With appropriate calibration the presence of the step change may be detected to directly detect one or both transition events. Furthermore, the antenna reflectance values themselves pre- or post- the transition events may be used as an indicator of capsule location.
Interconnections between electronic components may be via a central bus. This is one example of how power and data may be distributed between components. Other circuitry architecture may be implemented, for example, all connections may be via the microcontroller 15 which coordinates distribution of data and power between components. The sensors (the TCD sensor 131, the VOC sensor 132, the environmental sensor 14, the motion sensor 19, the EMG 31, the pulse-ox sensor 32, and/or the directional coupler 171) take readings under the instruction of the microcontroller 15, powered by the power source 16, and transfer the readings to the wireless transmitter 18 for transmission to the receiver apparatus via the antenna 17.
The dimension of the capsule may be less than 11.2 mm in diameter and 27.8 mm in length. The housing of the capsule 10 may be made of indigestible polymer, which is biocompatible. The housing may be smooth and non-sticky to allow its passage in the shortest possible time and to minimise risk of any capsule retention.
Detecting motility Markers in the Time Series of Motion Sensor Data
Detected motility markers described here may be utilised in determining release timing of therapeutic matter, or determining sampling timing.
Figure 9 shows time series of accelerometer readings as ‘roll’ in each of three mutually orthogonal dimensions and is marked with gastric emptying event, from which it can be seen that the change in accelerometer readings correlates temporally with a gastric emptying event. Therefore, accelerometer time series data may be utilised to provide an indicator of timing of a gastric-duodenal transition event which may be used to add confidence to a location determination at SI 04b. The capsule orientation is measured using a triaxial accelerometer and tracking the gravity vector with respect the capsule frame of reference. The capsule orientation is measured using a triaxial accelerometer and tracking the gravity vector with respect to the capsule frame of reference. When the capsule leaves the stomach it tends to experience rapid changes in its orientation as it transits through the duodenum and small intestine.
Different techniques may be used for processing the time series of accelerometer data. Metrics may be calculated from the raw readings, from which metrics one or more motility markers are detectable. A first technique is “angle travelled”, which accumulates the orientation change in excess of a 90 degree hysteresis angle. This technique tends to be robust to small changes in orientation experienced in the stomach and avoids some of the complexities of other approaches.
Angle travelled uses vector mathematics to calculate the angle between the gravity vector and a temporary vector. The temporary vector is pulled in the direction of the change in angle, only when this angle exceeds a given threshold (currently 90 Deg). It is then the accumulation of the change in the temporary vector that is visualized in the representation from which markers are identifiable. What is generally seen is that this measure does not change much in the stomach since the angle between the gravity and temporary vectors rarely exceed the threshold in any one direction, (small back and forth orientation changes in the stomach are effectively ignored by the inherent hysteresis of this algorithm) and that once in the tortuous lumen of the small intestine, this measure accumulates significantly due to the larger, more continuous orientation changes of the capsule. Thus, a step change in the cumulative angle travelled measure is a gastric-duodenal transition indicator.
In an exemplary implementation of angle travelled: the accelerometer readings may provide a reading of an orientation of the ingestible capsule relative to a frame of reference in fixed relation to a gravitational vector. Processing of the readings from the accelerometer may comprise recording an orientation of the ingestible capsule given by a first accelerometer reading as a reference orientation, and repetitively in respect of each successive accelerometer reading chronologically: determining whether the orientation of the ingestible capsule given by the respective accelerometer reading is more than a threshold angular displacement from the reference orientation, and if the threshold angular displacement is not met, progressing to the next accelerometer reading without changing the reference orientation, and if the threshold angular displacement is met, changing the reference orientation to align with the orientation of the ingestible capsule given by the respective accelerometer reading. An indicator, such as the gastric -duodenal transition indicator, may be a step change in the rate of change of the reference orientation. A second technique for processing accelerometer data may be referred to as total roll. Total roll calculates the angle between the gravity vector and each of the capsule X, Y and Z axes and expresses this as a continuous measure that can accumulate beyond 360 Deg. For example, if the capsule x axis is at an angle of 350 Deg and rotates by a further 20 Deg, the resulting angle is expressed as 370 Deg rather than 10 Deg. This helps when representing the readings as a plot from which markers are identified since it avoids the sudden angle changes associated with crossing the zero line. In the example a real change of 20 Deg would be visualized instead of an artificial change of 340 Deg. In addition to this basic approach, low pass filtering may be applied to filter the raw data to remove sensor noise. Additionally, angles are only calculated when the raw accelerometer data provide sufficient data to calculate a meaningful angle . An example of where this is not the case is when the two accelerometer axis values used to calculate the orientation angle around the third axis both approach zero. In this case the calculation will be dominated by sensor noise and so a meaningful angle cannot be determined.
The accelerometer readings provide a reading of an orientation of the ingestible capsule relative to a frame of reference in fixed relation to a gravitational vector. Exemplary processing of the readings from the accelerometer may comprise for each of three orthogonal axes in fixed spatial relation to the ingestible capsule derivable from the reading of the orientation, repetitively in respect of each successive accelerometer reading chronologically: calculating, as a scalar value, a change in the orthogonal axis relative to the gravitational vector from the preceding accelerometer reading; applying a low pass filter to the calculated changes; recording the cumulative filtered calculated changes. A marker serving as a gastric-duodenal transition indicator may be, for example, an increase (such as a spike or step change) in the rate of increase in the cumulative filtered calculated changes.
Therapeutic Matter Release Timing
Figures 10 & 11 illustrate schematically ingestible capsules configured to carry therapeutic matter into the GI tract of the subject and to release the therapeutic matter at a timing determined at least partially, or entirely, according the determination of location at SI 04b based on the spectral analysis at step SI 03 of the motion sensor data generated at S 102.
In Figure 10, the motion sensor 19 functions as a sensing mechanism. In the arrangement of Figure 10, a release mechanism 20 includes a microcontroller 15, and a determination of release timing is made by the microcontroller according to determination of capsule location within the GI tract by on-board processing of the time series of motion sensor data generated at S102. The processing hardware 152 may be a part of the microcontroller or distinct. In the arrangement of Figure 10, the microcontroller 15 comprises a memory 151 and a processor 152. The microcontroller 15 is configured with midware or software to perform its functionality with respect to determining release timing of the therapeutic payload (based on the processor hardware 152 determining a location of the ingestible capsule within the GI tract as coincident with a target release location of therapeutic matter carried in carrying compartment 22). The line around the release mechanism 20 is dashed to indicate that components therein do not necessarily perform functionality solely relating to the release mechanism 20 and may perform other functions. For example, the microcontroller 15 may perform functions including power and data distribution, data sampling, data processing, motility event indicator identification, release timing determination etc. In the arrangement of Figure 10, the processes of SI 03 onward from Figures la to Id is performed by the on-board processor hardware 152.
Figure 11 illustrates an arrangement which uses remote processing to determine release mechanism timing, the release mechanism 20 includes a wireless transceiver 18, and a determination of release timing is made by transmitting a representation of the time series of accelerometer data in an output signal to a remote processing apparatus, and receiving a notification signal in response, the notification signal being an instruction from the remote processing apparatus to trigger the actuator 21 to cause the therapeutic payload to be released (based on the remote processing apparatus performing S 103 to S 104b of Figure la and determining a location of the ingestible capsule within the GI tract as coincident with a target release location of therapeutic matter carried in carrying compartment 22).
In the arrangement of Figure 11, apparatus for determining location of the capsule within the GI tract includes remote processing apparatus, which comprises a receiver computing apparatus 30 and may also include a further computing apparatus 20.
Optionally, the wireless transceiver may be configured to function as a reflectometer to provide additional sensor data as discussed above. The wireless transceiver may be arranged as shown in Figure 7.
In the arrangement of Figure 10 or 11, the capsule 10 may be configured to release therapeutic matter carried by the capsule 10 directly into the GI tract of the subject at a timing based on the determination of location at SI 04b. The release timing may be immediately upon determination that the capsule 10 is located at a target release location of the therapeutic matter, or may be a predefined delay thereafter.
W02023087074 describes the configuration of an ingestible 10 with a therapeutic matter carrying compartment and release mechanism. Reference to that document could be made for a full description of those elements. A summary is provided herein for ease of reference, noting that further specific examples are provided in W02023087074.
An ingestible capsule 10 may comprise a housing 11, being a biocompatible indigestible housing including a therapeutic payload carrying compartment; a power supply; a release mechanism; and a sensing mechanism (comprising the accelerometer only or the accelerometer and the one or more additional sensors), the sensing mechanism being sensitive to the environment external to the housing. The ingestible capsule being configured for passage through a gastrointestinal, GI, tract of a subject mammal (at S 101), during which passage: the sensing mechanism is configured to output an output signal varying according to the GI tract environment external to the housing, wherein the sensing mechanism comprises only an accelerometer or an accelerometer and one or more sensors from among: a VOC gas sensor; a TCD gas sensor; a reflectometer formed by a transmission antenna of the ingestible capsule connected in series with a directional coupler configured to measure a reflected signal from the transmission antenna. The release mechanism is configured to cause a therapeutic payload to be released into the GI tract from the therapeutic payload carrying compartment at a release timing determined according to the output signal. In particular, the output signal from the motion sensor (at SI 02) is processed by steps SI 03 to SI 04b of Figure la to determine a location of the capsule 10 within the GI tract (noting that there will be some latency between data generation and determination), and when the determined location coincides with a target location for the therapeutic matter (being a parameter stored by the memory of the capsule 10 or the remote processing apparatus) the therapeutic payload is caused to be released immediately or at a predetermined delay.
The therapeutic payload (the therapeutic matter) may be one or more from among: a drug, a pharmaceutical formulation, a pre-biotic substance, a faecal transplant, and/or a pro-biotic substance.
Release Mechanism
The components illustrated in Figures 10 and 11 also include a release mechanism 20. Regardless of functional form, the release mechanism 20 includes a release actuator 21 in physical communication with the therapeutic payload carrying compartment 22. Different release mechanism 20 configurations are illustrated in W02023087074 at Figures 3A to 3E. Therapeutic payload may be drugs, prebiotics, probiotics, pharmaceuticals, faecal transplant matter, or other therapeutic matter configured for release into the GI tract for therapeutic effect.
The release actuator 21 is physically coupled to the releasable therapeutic payload carrying compartment, and in particular is physically coupled to a portion of the capsule housing at the therapeutic payload carrying compartment so that actuation of the actuator create an opening, aperture, or ruction, in the housing so that the therapeutic payload carrying compartment, and by extension the therapeutic payload itself, is exposed to the environment external to the capsule 10 and thus is released to the GI tract. The electronic components of the capsule 10 are sealed from the therapeutic payload carrying compartment. Alternatively, the capsule housing may contain the therapeutic payload carrying compartment within an open frame structure or via a portion having one or more apertures open to the environment external to the housing, with the therapeutic payload carrying compartment being closed via a valve or some other sealing member that is configured to be opened by the release actuator. For example, a kinked hose that is pulled by the release actuator to release the kink and to deploy the therapeutic payload to the environment external to the capsule 10. The configuration of the release actuator and hose may be such that deployment of the therapeutic payload takes place over a period of time as the capsule 10 transits the colon. For example, the period of time may be between 30 minutes and an hour, between an hour and two hours, or more than two hours.
Particular release actuators are illustrated in W02023087074 at Figures 7A and 7B. The therapeutic payload carrying compartment 22 may contain a balloon filled with the therapeutic matter, and optionally also further fluid such as liquid or gas or a combination thereof. The release actuator 21 causes the balloon to burst, releasing the therapeutic payload from the balloon and into the subject GI tract via one or more apertures in the capsule housing. It is noted that the portion of the ingestible capsule 10 containing the balloon, and having one or more apertures, is sealed from the portion of the ingestible capsule 10 containing the electronic components (unless a component is specifically described as being in the therapeutic payload carrying compartment 22, for example if required as part of the release actuator 21).
Since it is desirable to minimise power consumption (and thus to minimise size of power source required), the release actuator 21 may store potential energy, such as in a spring, which energy is released by the release actuator 21 in order to create the opening, aperture, perforation or ruction in the housing.
The housing is formed of a biocompatible indigestible polymer. Optionally, the polymer may be scored or otherwise formed to be thinner at the location of the portion physically coupled to the release actuator 21, so that the portion in question may be opened with a high degree of predictability. Furthermore, a surrounding region may be formed thicker, in order to be stronger and thus to reduce likelihood of the opening, aperture, perforation or ruction in the housing extending beyond the coupled portion.
A headspace may be defined in the capsule 10 which is in fluid isolation from the remainder of the capsule interior but is in communication with the GI tract via an aperture in the capsule housing. Within said headspace a perforable sealed (biocompatible, indigestible) film or foil contains a therapeutic payload, wherein the release actuator 21 is configured to perforate (i .e . rupture) the film or foil to release the payload to the GI tract via the aperture in the capsule housing. Noting that the film or foil may be across or partially across the aperture, or may be otherwise in spatial communication with the aperture so that perforation of the foil causes release of the payload into the GI tract via the aperture. The perforation of the foil or film may be by release of a spring pushing the foil or film against a perforating or puncturing member, or may be, for example, by rotation of a rotating member such as a motor that causes a peeling back, a puncturing, or a perforating of the foil or film. The release actuator 21 may be any actuation mechanism arranged to cause the release of packaged therapeutic payload from the package and into the GI tract.
Specific examples are illustrated in W02023087074 at Figures 7A to 7F.
Therapeutic Payload Carrying Compartment
The therapeutic payload carrying compartment 22 may comprise a single compartment carrying all (i.e. the required dosage) of the therapeutic payload. Optionally, the therapeutic payload carrying compartment 22 may comprise a plurality of sub-compartments, wherein each sub-compartment carries a portion (i.e. a fraction) of the required dosage of the therapeutic payload. In the case of the plurality of sub-compartments, the capsule 10 may be preset at time of manufacture, or configurable postmanufacture by a clinician (for example by sending a control signal from an external controller to the wireless transceiver 18 which, via the microcontroller 15 or otherwise, switches between two release modes), according to either of two release modes. One being an all-at-once release mode in which the plurality of sub-compartments are released by the release mechanism 21 at a single release timing (i.e. simultaneously or more-or-less simultaneously, such as one after another with no delay between releasing subsequent sub-compartments), and the other being an interval release mode in which the subcompartments are released by the release mechanism 21 in a series with predefined intervals between consecutive releases. The intervals may be all of a predefined equal length (i.e. regular intervals) or may be of predefined unequal lengths (i.e. irregular intervals). Thus, the release mechanism 21 may be controllable via the microcontroller 15 or otherwise to release the therapeutic matter at a single release timing or at plural distributed release timings.
Heating Element Release Mechanism
In a particular example of arrangements featuring a release mechanism, a release actuator may be an elastic material membrane rupturing mechanism comprising a power source and a heating element, the heating element arranged at least partially within, or against an interior surface of, the therapeutic payload carrying compartment, the at least a portion of the wall of the sealed chamber defined by the elastic material membrane being arranged to contact the heating element. The power source being configured, at the determined release timing and under control of the microcontroller, to transfer energy to the heating element, to increase a temperature of the heating element and by which temperature increase to rupture the elastic material membrane, thereby unsealing the sealed chamber. The power source 16 of the elastic material membrane rupturing mechanism may be a supercapacitor configured to be trickle charged by the ingestible capsule power supply over a period of time beginning with an initiation event of the ingestible capsule, and to be caused to release the charge to the heating element at the determined release timing under the control of the microcontroller. The supercapacitor and the heating element may be impedance matched, or impedance matched to within a defined tolerance. The heating element may be a resistive heater element comprising one or more from among:
SMT resistor; metallic resistive wire; nichrome;
MEMS heater element.
Other Release Mechanisms
In a further example of arrangements featuring a release mechanism, a release actuator may be an elastic material membrane rupturing mechanism including a power source 16 and a LASER diode focussed on the elastic material membrane, wherein a microcontroller of the ingestible capsule is configured at the determined release timing to activate the LASER diode to rupture the elastic material membrane, thereby unsealing the sealed chamber.
In a further example of arrangements featuring a release mechanism, a release actuator may be an elastic material membrane rupturing mechanism including a pre-sprung mechanical needle, wherein a microcontroller of the ingestible capsule is configured, at the determined release timing, to release the pre-sprung mechanical needle causing the pre-sprung mechanical needle to spring into the elastic material membrane causing the elastic material membrane to rupture, thereby unsealing the sealed chamber.
In a further example of arrangements featuring a release mechanism, a release actuator may be an elastic material membrane rupturing mechanism including the release mechanism comprises a microcontroller and a release actuator, and the therapeutic payload carrying compartment comprises a section of the ingestible capsule housing and a sealed chamber, an elastic material membrane defining at least a portion of a wall of the sealed chamber, within which sealed chamber a liquid diluent is sealed, the therapeutic payload being a lyophilized drug or other therapeutic matter in powdered, dehydrated, or other solid form, and being contained within the therapeutic matter carrying compartment in a space external to the sealed chamber and at least partially defined by the elastic material membrane, the section of the ingestible capsule housing comprising one or more apertures enabling fluid communication between the therapeutic payload carrying compartment and the exterior of the capsule, the one or more apertures being blocked by the elastic material membrane and unblocked following rupture of the elastic material membrane by an elastic material membrane rupturing mechanism at the determined release timing, the rupturing of the elastic material membrane allowing the liquid diluent to mix with the therapeutic payload within the therapeutic payload carrying compartment and to mix with fluids from the environment external to the capsule via the one or more apertures. GI Tract Sampling
As an alternative to the release mechanism, the ingestible capsule 10 may comprise a sampling mechanism to obtain a GI tract sample. The determination of timing is equivalent, so that references above to determining release timing may be applied here to the concept of determining sampling timing. The concept is the same: to identify a motility event and to determine sampling or release timing (as appropriate) accordingly.
The ingestible capsule 10 may comprise a chamber that is open to the surrounding environment in a first configuration, and closed to the surrounding environment in a second configuration. At a timing determined based on a trigger signal (either immediately upon receipt of the trigger signal or at a predefined delay), the chamber is changed either from the first configuration (open) to the second configuration (closed), or from the second configuration (closed) to the first configuration (open) and returned to the second configuration (closed). For example, a miniaturised motor may drive a sealable door member. The sampling may be passive, for example relying on gas flowing into the chamber. In the first configuration, there may an aperture allowing fluid to flow freely in and out of the chamber. Alternatively a semi-permeable membrane may remain in place, wherein the difference between the two configurations is that in the second, closed, configuration an impermeable membrane is coupled to the semi-permeable membrane to prevent fluids flowing across the membrane(s). The sampling may be active, in which in the first configuration a protruding member is extended beyond the housing of the ingestible capsule 10 and, after a period of time, retracted into the housing and the chamber returned to the closed configuration.
Recovery of the capsule 10 post-excretion may be achieved by detecting excretion (for example, based on temperature change sensed by a temperature sensor, or freefall detected by an accelerometer) causing a signal to be transmitted away from the capsule 10 by the wireless transceiver 18 to a receiver apparatus 30 to initiate the subject or a clinician to obtain the capsule before being flushed away.
An exemplary sampling mechanism is illustrated in Figure 12. The capsule housing 11 has two apertures or valved interfaces between the interior and exterior of the capsule 10: a one-way sampling valve 121 at a first end of the sampling chamber 126; and a drain aperture or drain valve 127 at a second opposing end of the sampling chamber 126. At ingestion (i.e. at all times between manufacture of the capsule 10 and sampling) a fluid-filled ballon or sack 123 at least partially occupies the sampling chamber 126. An elastic membrane 122 is in a stretched configuration (i.e. is storing elastic potential energy) between the fluid filled sack 123 and the interior surface of the capsule housing 11 which defines the sampling chamber 126. The elastic membrane 122 is arranged (that is, positioned and composed of an appropriate material) to permit fluid from the fluid-filled sack 123 to exit the sampling chamber 126 via the aperture or drain valve 127, and to block a fluid path between the one-way sampling valve 121 and the aperture or drain valve 127. In other words, fluid entering the sampling chamber 126 via the one-way sampling valve 121 is prevented from leaving the sampling chamber by a combination of the one-way sampling valve 121 and the elastic membrane 122.
The trigger signal that initiates the sampling mechanism may be a determination by a microcontroller 15 or other processor hardware 151 on-board the capsule that a determined location of the capsule 10 within the GI tract matches a target sampling location (being a parameter pre-stored or signalled to the capsule 10). Alternatively, capsule location within the GI tract may be determined by remote processing apparatus, which remote processing apparatus also stores an indication of target sampling location, so that a trigger signal sent to the capsule 10 is simply an instruction to initiate sampling, in the absence of any location information. Which is received by the data transceiver 18, and via a microcontroller or otherwise, triggers the sampling mechanism.
Determining capsule location to trigger sampling may be performed by the methods of Figure la to Id including capsule location determination SI 04b. As outlined above, the location determination step SI 04b causing triggering of the sampling mechanism, may be performed on-board the capsule 10 or may be performed remotely.
A microcontroller 15 may be in a listening mode for a trigger signal to trigger sampling (for example if location determination S104b is being performed at a remote processing apparatus), or the microcontroller 15 may store an indicator of a target sampling location, and may monitor location determinations may by one or more executions of SI 04b performed on-board the capsule to determine when the determined location at SI 04b matches the target sampling location. In either case, when the capsule 10 is determined to be at the target sampling location, the microcontroller 15 (which may be or include the on-board processor hardware 151 or other control circuitry) triggers a sack rupturing actuator 124.
In Figure 12 the sack-rupturing actuator 124 is a heater in contact with the fluid-filled sack 123 configured to actuate by heating quickly and causing the sack 123 to rupture. Other options include a miniaturised motor configured to actuate by driving a pin into the fluid-filled sack 123, or a laser light from a laser diode configured to actuate by focusing laser light onto a surface of the fluid-filled sack 123 to cause rupturing. The heater, or heating element, may be an SMT resistor; metallic resistive wire; nichrome; MEMS heater element. In another example, a pre-sprung mechanical needle may be released at the determined sampling timing to cause a point of the needle to contact the fluid-filled sack and cause rupturing. In another example, the sack rupturing actuator comprises a power source, a shape memory alloy wire, and a rupturing member, the power source being configured, at the determined sampling timing and under control of the microcontroller, to transfer energy to the shape memory alloy wire, to initiate a phase change at material level of the shape memory alloy wire and thereby to exert a force on the rupturing member to cause the rupturing member to come into contact with, and to rupture, the fluid- filled sack.
Electrodes on opposing sides of the sampling chamber may be included and used as a mechanism to measure how full the sampling chamber is.
Once triggered or actuated, the sack-rupturing mechanism 124 actuates to cause the sack 123 to rupture and thereby to cause the fluid from the sack 123 to flow from the sack 123 out of the sampling chamber 126 via the aperture or drain valve 127, and the elastic membrane 122 to become less stretched than in the stretched state and thereby to reduce pressure in the sampling chamber 126. By becoming less stretched, it is to be understood to mean that at least a portion of the elastic potential energy stored in the elastic membrane 122 is released. A pressure differential established between the sampling chamber
126 and the GI tract causes the one-way sampling valve 121 to open, to effectively suck GI track fluid into the sampling chamber 126 via the one-way sampling valve 121. The GI tract fluid (i.e. the sample) obtained reduces the pressure differential which causes the one-way sampling valve 127 to close and so the GI tract fluid is then retained in the sampling chamber 126 by the closed one-way sampling valve
127 and the elastic membrane 122 which blocks the aperture or drain valve 127.
The fluid-filled sack is filled with water or a saline solution not harmful to the GI tracked.
Target sampling location may be stomach, small intestine, large intestine, cecum, proximal small intestine, distal small intestine.
The power source 16 of the capsule 10 may be a lithium cell or a supercapacitor.
The elastic membrane 122 is to encapsulate the GI tract fluid and so is selected to be biocompatible, elastic, and stable.
The fluid-filled sack 123 is to be burstable with heat and to be stable and biocompatible.
The capsule 10 also includes a motion sensor 19 for generating the motion sensor data at SI 02 leading to the location determination at SI 04b. The capsule may also include a temperature sensor to take readings for the microcontroller 15 to determine when to switch the capsule from a sleep state to a live state (for example, wake every minute, take a reading, and if <35 degrees Celsius, return to sleep). In another option the capsule may wake every minute and take a reading from the motion sensor 19, and return to sleep if no movement is detected by the motion sensor 19, and so the temperature sensor may be omitted.
Timing of the actuation of the sack rupturing member 123, or some other representation of sampling time, may be included in a report such as at SI 07 to be transmitted away from the capsule 10 via Bluetooth. The capsule 10 may also be configured to monitor and feedback a filled state of the sampling chamber 126. The fluid occupying the fluid filled sack 126 prior to rupturing may be liquid or gas.
The timing of the GI tract sampling by the sampling mechanism is based on a determination of capsule location, and sampling is triggered when the determined capsule location matches a target sampling location.
The location determination may be based upon spectral analysis SI 03 of motion sensor data generated at SI 02 and processed according to the process described above including detecting peristalsis SI 04a in the spectral analysis and determining location S 104b based on the peristalsis detection. Alternatively, the location determination may be based upon a motility marker identified in a time series of data from a sensor. The sensor may be a motion sensor 19. Alternatively, the sensor may be a gas sensor, or a reflectometer.
The motility marker may be either an indication either of a location at which the capsule 10 is located (for example reflectometry measurements of the medium surrounding the capsule 10) or that a motility event has occurred (for example an inflection point, spike, or step change in concentration of a particular gas at a transition between two parts of the GI tract). Figure 6d illustrates timings of three motility markers T (ingestion), ‘ICJ’ (ileocecal junction transition indicator), and ‘GDJ’ (gastric duodenal junction transition indicator). Processes for identifying motility markers in time series of data from sensors are described elsewhere in this document and may be applied in the context of the present discussion of determining location of the capsule to determine GI tract sampling timing.
In the case of on-board processing, a microcontroller 15 on the capsule 10 may be monitoring output signals from a sensor (sensing mechanism) such as a VOC gas sensor, a TCD gas sensor, a motion sensor, a reflectometer, to identify either or both of a gastric-duodenal transition indicator or an ileocecal junction transition indicator to trigger the sampling mechanism. Reporting of information away from the capsule by Bluetooth or 433 MHz transmission may include an indication of timing of the sampling, and/or one or more elements such as a record of sampling timing; a record of excretion timing; a record of the one or more identified ileocecal junction transition indicators; a record of the one or more identified gastric -duodenal transition indicators; a record of an electrode signal indicating rupturing of the fluid-filled sack; a record of an electrode signal indicating a filled state of the sampling chamber; output signal output by the sensing mechanism; and a metric or metrics representing the output signal output by the sensing mechanism
It is noted that references to the sampling chamber being sealed are to imply releasably sealed, so that retrieval of the sample is possible by a technician or clinician. For example by perforating the membrane and syringing the content.
Power Source
The ingestible capsule 10 includes a power source. In the arrangements illustrated at Figures 2, 3a, 3b, 4, 5a to 5c, and 12 the power source may be a battery or may be a supercapacitor.
Vibration Therapy
Figure 13 illustrates a method or process, in which steps in common with methods of Figures la to Id are assigned like reference signs. The process of Figure 13 is performed by or in association with a capsule such as illustrated, for example, in Figures 3a, 3b, 4, 5a, 5b, 5c, but which also includes an onboard vibrating motor. The on-board vibrating motor may be, for example, an eccentric mass rotating motor, or a linear vibratory motor, or any motor configured to cause the capsule to vibrate.
The frequency and amplitude of oscillation are configurable at design time by selection of an appropriate motor, and may be further configurable at runtime by a controller on-board the capsule. For example, frequency of oscillation (in at least one of three spatial directions) may be between 10Hz and 100Hz, with an amplitude of between 0.1mm and 2.5mm. The vibrating motor is secured in fixed relation to the capsule housing, so that the vibrations are transmitted to the housing. The vibrating motor is under control of the on-board controller, and may be activated in response to a location determination such as at SI 04b. By detecting peristalsis at SI 04a and determining location of the capsule within the GI tract at SI 04b, or by other means, location of the capsule within the GI tract is determined and at S 113a a determination is made of whether a vibration therapy initiation condition is satisfied. A vibration therapy initiation condition may be the large bowel residence condition. A vibration therapy initiation condition may be partially based on the large bowel residence condition being satisfied, and partially based on another condition, such as energy remaining in the power source, absence of an override flag/switch. The large bowel residence condition may be simply that the capsule is resident in the large bowel. Alternatively, the large bowel residence condition may be that the capsule has been resident in the large bowel for more than a threshold time period. The threshold time period may be, for example, not less than one hour, not less than two hours, not less than three hours, not less than four hours, not less than five hours, not less than six hours, not less than eight hours, not less than ten hours, not less than twelve hours, not less than fourteen hours, not less than sixteen hours, not less than eighteen hours, not less than twenty hours, or not less than twenty four hours. In a subject wishing to initiate a bowel movement, the threshold time period may be selected to be a value associated with the capsule progressing to the distal portion of the bowel.
If the large bowel residence condition is not met at S 113a, the process of steps S 102 so S 113a is repeated (and may eventually be stopped by a termination event such as excretion or powering off of the capsule) . If the large bowel residence condition is met at SI 13a, the process continues to SI 13b and vibration is initiated. Optionally, the process of SI 02 to SI 04b may be performed repetitively until a termination event such as excretion or powering off of the capsule occurs.
Upon initiation of vibration at SI 13b, the vibrating motor is powered on and the capsule is caused to vibrate. The intention is to stimulate a bowel movement. The initiated vibration may be for a fixed time period or may continue indefinitely. The initiated vibration may be pulsed, wherein the vibrating motor is powered on for a pulse period and then powered off for a rest period, on a repeated basis, for the vibration duration. The vibration duration may be, for example, ten minutes, twenty minutes, thirty minutes, or one hour. The pulse periods may be, for example, five seconds, ten seconds, twenty seconds, thirty seconds. The rest periods may be, for example, five seconds, ten seconds, twenty seconds, thirty seconds. Completion of the vibration duration may be followed by an enforced period of inactivity so that the vibration motor cannot be powered on again for, for example, one hour, two hours, three hours, or four hours. The capsule may be configured to initiate only a finite number or vibration durations during GI tract passage, for example, one, two, three, four, or five.
Detection of an excretion event may cause the controller to power off the vibrating motor. The initiation of the vibrating motor, or the switching from the powered off state to the powered on state during a vibration duration, may be conditional upon the power source having a predefined amount of energy remaining. For example, the controller may be configured to guarantee the power source has sufficient energy at excretion to transmit a report away from the capsule to a receiver apparatus.
The vibrating motor may be configured to cause vibration in one spatial dimension, or in two or three mutually orthogonal spatial dimensions.
The controller may have a vibrating motor override flag or switch which, upon receipt of a predefined signal from a paired apparatus external to the body such as a smartphone or receiver apparatus paired with the capsule, prevents the vibrating motor being switched into a powered on state even if other conditions such as at S 113a are met. The purpose of such an override flag or switch would be to prevent the capsule from initiating or conducting vibration therapy if the patient/subject records a bowel movement at the paired apparatus (but which bowel movement does not result in excretion of the capsule itself). For example, a subject may ingest a capsule at time T=0 believing vibration therapy is required, but at time T=1 hour, experience a bowel movement. However, since the capsule was only ingested one hour ago, it is still resident in the stomach and so is not passed in the bowel movement. Experience of the bowel movement may remove the motivation to initiate or conduct vibration therapy via the capsule, and so by allowing the subject to log the bowel movement on the paired apparatus (i.e. via an app or another user interface), a signal is transmitted to the capsule which switches the override flag or switch to a state preventing the vibrating motor from being powered on. The default state of the override flag or switch may be a state which permits the powering on of the vibrating motor.
Optionally, measurement of time series of motion sensor data such as at S 102 may be suspended during the vibration duration, or more specifically whenever the vibrating motor is in a powered on state. Alternatively, the vibration caused by the vibrating motor may be extracted from the spectrograph generated at SI 03 prior to determination of location within the GI tract at SI 04b.
Methods, programs, and apparatus, are described in the following numbered statements:
Statement 1. A method comprising: following ingestion of an ingestible capsule by a subject, the ingestible capsule housing a motion sensor configured to generate a time series of motion sensor data representing motion of the ingestible capsule during passage through the GI tract of a subject, at data processing hardware communicably coupled to the motion sensor, performing a process comprising: generating a spectral analysis of the time series of motion sensor data generated by the motion sensor over a time period during passage of the ingestible capsule through the GI tract, extracting from the spectral analysis respiration information comprising an indication of respiration rate.
Statement 2. The method of Statement 1, wherein the extracted respiratory information comprises a measurement of a signal in one or more from a predefined set of respiration information frequency ranges.
Statement 3. The method of Statement 2, wherein the predefined set of respiration information frequency ranges includes a first respiration information frequency range indicating snoring, and a second respiration information frequency range indicating respiration.
Statement 4. The method of Statement 3, wherein the first respiration information frequency range is between 12 and 18 cpm.
Statement 5. The method of Statement 4, wherein the second respiration information frequency range is between 3600 and 18000cpm.
Statement 6. The method of any of Statements 1 to 5, wherein the ingestible capsule further comprises, or is operably coupled to a separate, one or more additional sensors, each additional sensor being configured to generate a time series of additional sensor data; the additional sensor comprises a pulse oximetry sensor configured to generate a time series of pulse oximetry measurements representing concentration of oxygen in blood of the subject; the method further comprises generating and outputting a report comprising the extracted respiration information for the time window and a contemporaneous extract from the time series of pulse oximetry measurements.
Statement 7. The method of Statement 6, wherein the report is generated and output by processor hardware and a wireless data transceiver on board the ingestible capsule.
Statement 8. The method of Statement 6, wherein the report is generated and output by a remote processing apparatus configured to receive data transmitted away from the ingestible capsule by a wireless data transceiver.
Statement 9. The method according to any of the preceding Statements, wherein the motion sensor comprises an accelerometer and the time series of motion sensor data comprises a time series of accelerometer data; and/or the motion sensor comprises a gyroscope and the time series of motion sensor data comprises a time series of gyroscope data.
Statement 10. The method according to any of the preceding Statements, wherein the method comprises repeating the process for a series of time periods during passage of the ingestible capsule through the GI tract.
Statement 11. The method according to Statement 10, wherein the series of time periods are contiguous, or wherein the series of time windows are sliding so that adjacent time windows in the series partially overlap one another.
Statement 12. The method according to any of the preceding Statements, wherein the motion sensor comprises a three-axis accelerometer and the motion sensor data comprises three time series each representing acceleration in a respective one of the three axes, and the process includes a pre-spectral analysis step comprising: combining the three time series into a single resultant time series; wherein the spectral analysis is generated from the single resultant time series.
Statement 13. The method according to any of the preceding Statements, wherein the sensor hardware comprises a gyroscope and the sensor data comprises a time series of gyroscope data representing changes to a frame of reference of the ingestible capsule relative to a fixed frame of reference; extracting from the gyroscope data a long axis rotation time series representing rotation of the ingestible capsule about the long axis defined by the capsule housing; wherein the spectral analysis is generated from the long axis rotation time series. Statement 14. The method according to any of the preceding Statements, wherein the motion sensor is a three-axis accelerometer and the motion sensor data comprises three time series each representing acceleration in a respective one of the three axes, and generating the spectral analysis comprises: transforming each of the three time series into respective single axis frequency domain representations; combining the three single axis frequency domain representations to obtain a combined frequency domain representation.
Statement 15. The method according to any of Statements 12 to 14, wherein combining the three single axis frequency domain representations comprises comparing magnitude of a signal in a taiget frequency range from each of the single axis frequency domain representations, and selecting the single axis frequency domain representation with the greatest magnitude signal in the target frequency range as the combined frequency domain representation. Statement 16. The method according to any of Statements 12 to 14, wherein combining the three single axis frequency domain representations comprises, for each component frequency in the frequency domain, combining a component magnitude from each of the single axis frequency domain representations, the resulting combination per component frequency being the combined frequency domain representation.,
Statement 17. The method according to Statement 16, wherein wherein the combining is a summation, or a root sum squared.
Statement 18. The method according to any of the preceding Statements, wherein the spectral analysis is a value representing magnitude of a component at each of a series of component frequencies.
Statement 19. The method according to any of the preceding Statements, wherein the ingestible capsule further comprises the data processing hardware.
Statement 20. The method according to any of the preceding Statements, wherein the ingestible capsule further comprises a wireless data transmitter to transmit the to transmit the time series of motion sensor data to a remote apparatus for processing, the data processing hardware being a component of the remote apparatus.
Statement 21. The method according to any of the preceding Statements, wherein the process further comprises: generating a report including information extracted from the spectral analysis representing fluctuations, variations, or anomalies within spectral components.
Statement 22. The method according to any of the preceding Statements, wherein the ingestible capsule further comprises one or more additional sensors configured to generate a time series of sensor data, and the process includes generating and outputting a report including one or more from among: the spectral analysis for the time period, and a result of processing the spectral analysis for the time period comprising information indicating a respiration rate, information indicating a detection of peristalsis, or information indicating a physical activity type being undertaken by the subject; additional sensor data readings from the same time period, and/or an outcome or processing the additional sensor data readings from the same time period such as a metric or identification of a motility marker, and/or information derived from additional sensor data readings from the same time period.
Statement 23. The method according to Statement 22, wherein the one or more additional sensors comprise one or more from among:
- a gas sensor;
- a motion sensor;
- a temperature sensor;
- a relative humidity sensor;
- a reflectometer;
- a pulse oximetry sensor;
- an electromyographic sensor.
Statement 24a. The method according to any of the preceding Statements, wherein one or more additional sensors external to the ingestible capsule are positioned externally on the skin of the subject, the one or more additional sensors being communicatively coupled to the ingestible capsule or to a receiver computing apparatus to which the ingestible capsule is communicatively coupled, one or more additional sensors configured to generate a time series of sensor data, and the process includes generating and outputting a report including one or more from among: the spectral analysis for the time period, and a result of processing the spectral analysis for the time period comprising information indicating a respiration rate, information indicating a detection of peristalsis, or information indicating a physical activity type being undertaken by the subject; additional sensor data readings from the same time period, and/or an outcome or processing the additional sensor data readings from the same time period such as a metric or identification of a motility marker, and/or information derived from additional sensor data readings from the same time period; wherein the one or more additional sensors comprises one or more from among:
- a pulse oximetry sensor; and
- an electromyographic sensor.
Statement 24b. The method according to any of the preceding Statements, wherein the process includes determining the location of the capsule within the GI tract based on the detected peristalsis; the ingestible capsule further comprises a vibrating motor arranged, when in a powered on state, to vibrate within the capsule to cause vibration of the capsule housing, and the process further comprises, in response to the determined location of the ingestible capsule satisfying a vibration therapy initiation condition, causing the vibrating motor to switch from a powered off state to the powered on state.
Statement 25. Apparatus comprising : an ingestible capsule housing a motion sensor configured to generate a time series of motion sensor data representing motion of the ingestible capsule during passage through the GI tract of a subject; data processing hardware communicably coupled to the motion sensor, the data processing hardware being configured, following ingestion of the ingestible capsule by the subject, at data processing hardware communicably coupled to the motion sensor, to perform a process comprising: generating a spectral analysis of the time series of motion sensor data generated by the motion sensor over a time period during passage of the ingestible capsule through the GI tract, extracting from the spectral analysis respiration information comprising an indication of respiration rate.
Statement 26. The apparatus of Statement 25, wherein the extracted respiratory information comprises a measurement of a signal in one or more from a predefined set of respiration information frequency ranges.
Statement 27. The apparatus of Statement 26, wherein the predefined set of respiration information frequency ranges includes a first respiration information frequency range indicating snoring, and a second respiration information frequency range indicating respiration. Statement 28. The apparatus of Statement 27, wherein the first respiration information frequency range is between 12 and 18 cpm.
Statement 29. The apparatus of Statement 28, wherein the second respiration information frequency range is between 3600 and 18000cpm.
Statement 30. The apparatus of any of Statements 25 to 29, wherein the ingestible capsule further comprises, or is operably coupled to a separate, one or more additional sensors, each additional sensor being configured to generate a time series of additional sensor data; the additional sensor comprises a pulse oximetry sensor configured to generate a time series of pulse oximetry measurements representing concentration of oxygen in blood of the subject; the method further comprises generating and outputting a report comprising the extracted respiration information for the time window and a contemporaneous extract from the time series of pulse oximetry measurements.
Statement 31. The apparatus of Statement 30 wherein the report is generated and output by processor hardware and a wireless data transceiver on board the ingestible capsule.
Statement 32. The apparatus of Statement 30, wherein the report is generated and output by a remote processing apparatus configured to receive data transmitted away from the ingestible capsule by a wireless data transceiver.
Statement 33. The apparatus according to any of Statements 25 to 32, wherein the motion sensor comprises an accelerometer and the time series of motion sensor data comprises a time series of accelerometer data; and/or the motion sensor comprises a gyroscope and the time series of motion sensor data comprises a time series of gyroscope data.
Statement 34. The apparatus according to any of Statements 25 to 33, wherein the process comprises repeating the process for a series of time periods during passage of the ingestible capsule through the GI tract.
Statement 35. The apparatus according to Statement 34, wherein the series of time periods are contiguous, or wherein the series of time windows are sliding so that adjacent time windows in the series partially overlap one another.
Statement 36. The apparatus according to any of Statements 25 to 35, wherein the motion sensor comprises a three-axis accelerometer and the motion sensor data comprises three time series each representing acceleration in a respective one of the three axes, and the process includes a pre-spectral analysis step comprising: combining the three time series into a single resultant time series ; wherein the spectral analysis is generated from the single resultant time series.
Statement 37. The apparatus according to any of Statements 25 to 36, wherein the sensor hardware comprises a gyroscope and the sensor data comprises a time series of gyroscope data representing changes to a frame of reference of the ingestible capsule relative to a fixed frame of reference; extracting from the gyroscope data a long axis rotation time series representing rotation of the ingestible capsule about the long axis defined by the capsule housing; wherein the spectral analysis is generated from the long axis rotation time series.
Statement 38. The apparatus according to any of Statements 25 to 37, wherein the motion sensor is a three-axis accelerometer and the motion sensor data comprises three time series each representing acceleration in a respective one of the three axes, and generating the spectral analysis comprises: transforming each of the three time series into respective single axis frequency domain representations; combining the three single axis frequency domain representations to obtain a combined frequency domain representation.
Statement 39. The apparatus according to any of Statements 36 to 38, wherein combining the three single axis frequency domain representations comprises comparing magnitude of a signal in a taiget frequency range from each of the single axis frequency domain representations, and selecting the single axis frequency domain representation with the greatest magnitude signal in the target frequency range as the combined frequency domain representation. Statement 40. The apparatus according to any of Statements 36 to 38, wherein combining the three single axis frequency domain representations comprises, for each component frequency in the frequency domain, combining a component magnitude from each of the single axis frequency domain representations, the resulting combination per component frequency being the combined frequency domain representation.,
Statement 41. The apparatus according to Statement 40, wherein wherein the combining is a summation, or a root sum squared.
Statement 42. The apparatus according to any of Statements 25 to 41, wherein the spectral analysis is a value representing magnitude of a component at each of a series of component frequencies.
Statement 43. The apparatus according to any of Statements 25 to 42, wherein the ingestible capsule further comprises the data processing hardware.
Statement 44. The apparatus according to any of Statements 25 to 43, wherein the apparatus further comprises a remote computing apparatus; the ingestible capsule further comprises a wireless data transmitter to transmit the time series of motion sensor data to the remote computing apparatus for processing, the data processing hardware being a component of the remote computing apparatus. Statement 45. The apparatus according to any of Statements 25 to 44, wherein the process further comprises: generating a report including information extracted from the spectral analysis representing fluctuations, variations, or anomalies within spectral components.
Statement 46. The apparatus according to any of Statements 25 to 45, wherein the ingestible capsule further comprises one or more additional sensors configured to generate a time series of sensor data, and the process includes generating and outputting a report including one or more from among: the spectral analysis for the time period, and a result of processing the spectral analysis for the time period comprising information indicating a respiration rate, information indicating a detection of peristalsis, or information indicating a physical activity type being undertaken by the subject; additional sensor data readings from the same time period, and/or an outcome or processing the additional sensor data readings from the same time period such as a metric or identification of a motility marker, and/or information derived from additional sensor data readings from the same time period.
Statement 47. The apparatus according to Statement 46, wherein the one or more additional sensors comprise one or more from among:
- a gas sensor;
- a motion sensor;
- a temperature sensor;
- a relative humidity sensor;
- a reflectometer;
- a pulse oximetry sensor;
- an electromyographic sensor.
Statement 48. The apparatus according to any of Statements 25 to 47, wherein the apparatus further comprises one or more additional sensors external to the ingestible capsule positioned externally on the skin of the subject, the one or more additional sensors being communicatively coupled to the ingestible capsule or to a remote computing apparatus to which the ingestible capsule is communicatively coupled, the one or more additional sensors being configured to generate a time series of sensor data, and the process includes generating and outputting a report including one or more from among: the spectral analysis for the time period, and a result of processing the spectral analysis for the time period comprising information indicating a respiration rate, information indicating a detection of peristalsis, or information indicating a physical activity type being undertaken by the subject; additional sensor data readings from the same time period, and/or an outcome or processing the additional sensor data readings from the same time period such as a metric or identification of a motility marker, and/or information derived from additional sensor data readings from the same time period; wherein the one or more additional sensors comprises one or more from among:
- a pulse oximetry sensor; and
- an electromyographic sensor.
Statement 49. The apparatus according to any of Statements 25 to 48, wherein the process includes determining the location of the capsule within the GI tract based on the detected peristalsis; the ingestible capsule further comprises a vibrating motor arranged, when in a powered on state, to vibrate within the capsule to cause vibration of the capsule housing, and the process further comprises, in response to the determined location of the ingestible capsule satisfying a vibration therapy initiation condition, causing the vibrating motor to switch from a powered off state to the powered on state.
DESCRIPTION ENDS.

Claims

1. A method comprising: following ingestion of an ingestible capsule by a subject, the ingestible capsule housing a motion sensor configured to generate a time series of motion sensor data representing motion of the ingestible capsule during passage through the GI tract of a subject, at data processing hardware communicably coupled to the motion sensor, performing a process comprising: generating a spectral analysis of the time series of motion sensor data generated by the motion sensor over a time period during passage of the ingestible capsule through the GI tract, using the spectral analysis to detect peristalsis at a location of the ingestible capsule within the GI tract at the time period.
2. The method according to claim 1, wherein the process further comprises: determining the location of the capsule within the GI tract based on the detected peristalsis.
3. The method according to any of the preceding claims, wherein the process further comprises: generating a report including information extracted from the spectral analysis at one or a set of predefined peristalsis indicator frequency ranges.
4. The method according to any of the preceding claims, wherein the process further comprises: generating and outputting to a receiver computing apparatus or message recipient a report including one or more from among: information extracted from the spectral analysis representing fluctuations, variations, or anomalies within spectral components; a metric or metrics calculated from the spectral analysis from among: centre frequency, frequency spread, power distribution, frequency gaps.
5. The method according to claim 3 or 4, wherein the ingestible capsule further comprises one or more additional sensors configured to generate a time series of sensor data, and the generated report further comprises one or more from among: the spectral analysis for the time period, and additional sensor data readings from the same time period, and/or an outcome or processing the additional sensor data readings from the same time period such as a metric or identification of a motility marker, and/or information derived from additional sensor data readings from the same time period.
6. The method according to any of the preceding claims, wherein detecting peristalsis at a location of the ingestible capsule within the GI tract at the time period comprises, in the result of the spectral analysis, detecting presence or absence of a signal at one or more of a predefined set of peristalsis indicator frequency ranges.
7. The method according to any of the preceding claims, wherein the process includes determining the location of the capsule within the GI tract based on the detected peristalsis; and determining the location of the ingestible capsule within the GI tract comprises, in the result of the spectral analysis, detecting presence or absence of a signal/component at one or more of a predefined set of peristalsis indicator frequency ranges.
8. The method according to any of the preceding claims, wherein a predefined set of peristalsis indicator frequency ranges comprises one or more from among: a first peristalsis indicator frequency range, being a frequency range indicating stomach peristalsis; a second peristalsis indicator frequency range, being a frequency range indicating small intestine peristalsis; a third peristalsis indicator frequency range, being a frequency range indicating large intestine peristalsis.
9. The method according to claim 8, wherein the ingestible capsule is determined to be in the stomach by presence of a signal in the first peristalsis indicator frequency range; the ingestible capsule is determined to be in the small intestine by presence of a signal in the second peristalsis indicator frequency range; the ingestible capsule is determined to be in the large intestine by absence of a signal in the first peristalsis indicator frequency range and absence of a signal in the second peristalsis indicator frequency range; and/or the ingestible capsule is determined to be in the large intestine by presence of a signal in the third peristalsis indicator frequency range.
10. The method according to any of the preceding claims, wherein using the spectral analysis to detect peristalsis includes applying a minimum signal magnitude threshold to a magnitude of the detected signal at one of the predefined set of peristalsis indicator frequency ranges over the time period, and if the minimum signal magnitude threshold is satisfied, determining that peristalsis at the location of the ingestible capsule within the GI tract at the period of time is detected.
11. The method according to any of the preceding claims, wherein using the spectral analysis to detect peristalsis includes determining a characteristic frequency in the result of the spectral analysis, and if the characteristic frequency is within one of the predefined set of peristalsis indicator frequency ranges, determining that the a signal is detected in the one of the predefined set of peristalsis indicator frequency ranges, and optionally determining a location of the ingestible capsule within the GI tract at the period of time is a location corresponding to the one of the predefined set of peristalsis indicator frequency ranges.
12. The method according to any of the preceding claims, wherein the process includes determining the location of the capsule within the GI tract based on the detected peristalsis; the ingestible capsule further comprises one or more additional sensors, each additional sensor being configured to generate a time series of additional sensor data representing an environment at or surrounding the ingestible capsule; using the spectral analysis to determine a location of the ingestible capsule within the GI tract at a time period includes: detecting a motility marker in the time series of additional sensor data indicating a transition between locations within the GI tract, or presence in a location within the GI tract, to obtain an additional sensor data indication of a location of the ingestible capsule within the GI tract at a time period based on the detected transition or presence; generating the spectral analysis on the time series of motion sensor data for the same time period; and if a signal/component at a threshold magnitude at one of a predefined set of peristalsis indicator frequency ranges is detected in the spectral analysis, and a location indicated by the detection in the spectral analysis is consistent with the additional sensor data indication of location, determining the location of the capsule at the said indicated location at the time period.
13. The method according to any of the preceding claims, wherein the process includes determining the location of the capsule within the GI tract based on the detected peristalsis; the ingestible capsule further comprises one or more additional sensors, each additional sensor being configured to generate a time series of additional sensor data representing an environment at or surrounding the ingestible capsule; using the spectral analysis to determine a location of the ingestible capsule within the GI tract at a time period includes: detecting a motility marker in the time series of additional sensor data indicating a transition between locations within the GI tract, or presence in a location within the GI tract, to obtain an additional sensor data indication of a location of the ingestible capsule within the GI tract at a time period based on the detected transition or presence; generating the spectral analysis on the time series of motion sensor data for the same time period; and if a location indicated in the spectral analysis by presence or absence of a signal within one of a predefined set of peristalsis indicator frequency ranges is consistent with the additional sensor data indication of location, determining the location of the capsule at the said indicated location at the time period.
14. The method according to claim 12 or 13, wherein the one or more additional sensors includes one or more gas sensors from among: a spectrophotometer; a Surface Acoustic Wave sensor; a Bulk Acoustic Resonator Array; a VOC gas sensors; and a TCD gas sensors; the time series of additional sensor data comprising a time series of gas sensor data.
15. The method according to claim 14, wherein the motility marker is a spike, step change, or inflection in the time series of gas sensor data, indicating that the ingestible capsule has crossed the gastric-duodenal junction, orthe ileocecal junction.
16. The method according to any of claims 12 to 15, wherein the one or more additional sensors includes a reflectometer formed by an antenna in series with a directional coupler, the antenna being controlled by the processor to transmit an intermittent or continuous signal from which a reflectometer signal is obtainable; the motility marker is a measurement of amplitude and/or phase of the reflectometer signal indicating presence of the ingestible capsule in a location within the GI tract.
17. The method according to any of claims 12 to 16, wherein the ingestible capsule includes a wireless data transmitter to transmit the time series of additional sensor data and the time series of motion sensor data to a remote apparatus for processing, and the antenna is an antenna of the data transmitter.
18. The method according to any of claims 12 to 17, wherein the ingestible capsule includes a wireless data transmitter to transmit the frequency domain representation of the sensor data to a remote apparatus for processing, and the antenna is an antenna of the data transmitter.
19. The method according to claim 18, wherein the ingestible capsule further comprises a wireless data transceiver to transmit the time series of motion sensor data to a remote apparatus for processing, the data processing hardware being a component of the remote apparatus, the ingestible capsule further comprises a therapeutic payload carrying compartment, a release mechanism, the process further comprising: at the remote apparatus: performing the process including determining the location of the capsule within the GI tract based on detected peristalsis, and in response to determining that the determined location of the ingestible capsule is a taiget release location for therapeutic matter within the therapeutic payload carrying compartment, transmitting a trigger signal to the wireless data transceiver; and at the ingestible capsule: receiving the trigger signal at the wireless data transceiver, and responding to the trigger signal by, immediately or at a predetermined delay, the release mechanism causing the therapeutic matter within the therapeutic payload carrying compartment to be released into the GI tract.
20. The method according to any of the preceding claims, wherein the process includes determining the location of the capsule within the GI tract based on the detected peristalsis; using the spectral analysis to determine a location of the ingestible capsule within the GI tract at a time period includes: detecting a motility marker in the time series of motion sensor data indicating a transition between locations within the GI tract to obtain a motion sensor time series data indication of a location of the ingestible capsule within the GI tract at a time period based on the detected transition; generating the spectral analysis on the time series of motion sensor data for the same time period; and if a location is indicated by presence or absence of a signal or signals at a predefined set of peristalsis indicator frequency ranges in the result of the spectral analysis, and the indicated location is consistent with the motion sensor time series data indication of location, determining the location of the ingestible capsule at the said indicated location at the time period.
21. The method according to any of the preceding claims, wherein the process includes determining the location of the capsule within the GI tract based on the detected peristalsis; the ingestible capsule further comprises a therapeutic payload carrying compartment and a release mechanism, and the process further comprises, in response to the determined location of the ingestible capsule being a target release location for therapeutic matter within the therapeutic payload carrying compartment, causing the therapeutic matter to be released into the GI tract.
22. The method according to any of the preceding claims, wherein the process includes determining the location of the capsule within the GI tract based on the detected peristalsis; the ingestible capsule further comprises a GI tract sampling chamber and a sealing mechanism to open and close the GI tract sampling chamber, and the process further comprises, in response to the determined location of the ingestible capsule being a predefined target sampling location, causing the sealing mechanism to open and close the sampling chamber to obtain a GI tract sample.
23. The method according to claim 22, wherein the sealing mechanism comprises a fluid-filled sack occupying the sampling chamber, a membrane maintained in a stretched state by the fluid-filled sack and being exposed to the external environment via an aperture or drain valve, a sack rupturing actuator, and a one-way sampling valve at an interface between the housing of the ingestible capsule and the external environment; the membrane being arranged to permit fluid from the fluid-filled sack to exit the sampling chamber via the aperture or drain valve, and to block a fluid path between the one-way sampling valve and the aperture or drain valve, wherein, in response to the determined location of the ingestible capsule being a predefined target sampling location, the sack rupturing actuator is actuated to rupture the sack and thereby to cause the fluid to flow from the sack out of the sampling chamber via the aperture or drain valve, and the membrane to become less stretched than in the stressed state and thereby to suck fluid into the sampling chamber via the one-way sampling valve.
24. The method according to any of the preceding claims, wherein the using the spectral analysis to determine a location of the ingestible capsule within the GI tract at the time period is performed by a pre-trained machine learning algorithm.
25. The method according to any of the preceding claims, further comprising extracting from the spectral analysis respiration information comprising an indication of respiration rate.
26. The method according to claim 25, wherein the extracted respiratory information comprises a measurement of a signal in one or more from a predefined set of respiration information frequency ranges, or detection of a signal or signal characteristics in the spectral analysis indicating one or more from among:
-sleep apnea (absence of respiration during sleep);
-normal respiration;
-Blots respiration;
-Kussmaul breathing;
-Cheyne Stokes respiration;
- Bradypnea;
-Tachypnea;
-Hyperpnea;
-Ataxic respiration;
-Air trapping;
-Obstructive respiration;
-Sighing;
-Apneustic respiration;
-Agonal respiration.
27. The method according to any of the preceding claims, wherein the motion sensor comprises an accelerometer and the time series of motion sensor data comprises a time series of accelerometer data; and/or the motion sensor comprises a gyroscope and the time series of motion sensor data comprises a time series of gyroscope data.
28. The method according to any of the preceding claims, wherein the method comprises repeating the process for a series of time periods during passage of the ingestible capsule through the GI tract.
29. The method according to claim 28, wherein the series of time periods are contiguous, or wherein the series of time windows are sliding so that adjacent time windows in the series partially overlap one another.
30. The method according to any of the preceding claims, wherein the motion sensor comprises a three-axis accelerometer and the motion sensor data comprises three time series each representing acceleration in a respective one of the three axes, and the process includes a pre-spectral analysis step comprising: combining the three time series into a single resultant time series ; wherein the spectral analysis is generated from the single resultant time series.
31. The method according to any of the preceding claims, wherein the sensor hardware comprises a gyroscope and the sensor data comprises a time series of gyroscope data representing changes to a frame of reference of the ingestible capsule relative to a fixed frame of reference; extracting from the gyroscope data a long axis rotation time series representing rotation of the ingestible capsule about the long axis defined by the capsule housing; wherein the spectral analysis is generated from the long axis rotation time series.
32. The method according to any of the preceding claims, wherein the motion sensor is a three-axis accelerometer and the motion sensor data comprises three time series each representing acceleration in a respective one of the three axes, and generating the spectral analysis comprises: transforming each of the three time series into respective single axis frequency domain representations; combining the three single axis frequency domain representations to obtain a combined frequency domain representation.
33. The method according to any of claims 30 to 32, wherein combining the three single axis frequency domain representations comprises comparing magnitude of a signal in a taiget frequency range from each of the single axis frequency domain representations, and selecting the single axis frequency domain representation with the greatest magnitude signal in the target frequency range as the combined frequency domain representation.
34. The method according to any of claims 30 to 32, wherein combining the three single axis frequency domain representations comprises, for each component frequency in the frequency domain, combining a component magnitude from each of the single axis frequency domain representations, the resulting combination per component frequency being the combined frequency domain representation.
35. The method according to claim 34, wherein wherein the combining is a summation, or a root sum squared.
36. The method according to any of the preceding claims, wherein the spectral analysis is a value representing magnitude of a component at each of a series of component frequencies.
37. The method according to any of the preceding claims, wherein the ingestible capsule further comprises the data processing hardware.
38. The method according to any of the preceding claims, wherein the ingestible capsule further comprises a wireless data transmitter to transmit the time series of motion sensor data to a remote apparatus for processing, the data processing hardware being a component of the remote apparatus.
39. The method according to any of the preceding claims, wherein the process further comprises: generating a report including information extracted from the spectral analysis representing fluctuations, variations, or anomalies within spectral components.
40. The method according to any of the preceding claims, wherein the ingestible capsule further comprises one or more additional sensors configured to generate a time series of sensor data, and the process includes generating and outputting a report including one or more from among: the spectral analysis for the time period, and a result of processing the spectral analysis for the time period comprising information indicating a respiration rate, information indicating a detection of peristalsis, or information indicating a physical activity type being undertaken by the subject; additional sensor data readings from the same time period, and/or an outcome or processing the additional sensor data readings from the same time period such as a metric or identification of a motility marker, and/or information derived from additional sensor data readings from the same time period.
41. The method according to claim 40, wherein the one or more additional sensors comprise one or more from among:
- a gas sensor;
- a motion sensor;
- a temperature sensor;
- a relative humidity sensor;
- a reflectometer;
- a pulse oximetry sensor;
- an electromyographic sensor.
42. The method according to any of the preceding claims, wherein one or more additional sensors external to the ingestible capsule are positioned externally on the skin of the subject, the one or more additional sensors being communicatively coupled to the ingestible capsule or to a receiver computing apparatus to which the ingestible capsule is communicatively coupled, one or more additional sensors configured to generate a time series of sensor data, and the process includes generating and outputting a report including one or more from among: the spectral analysis for the time period, and a result of processing the spectral analysis for the time period comprising information indicating a respiration rate, information indicating a detection of peristalsis, or information indicating a physical activity type being undertaken by the subject; additional sensor data readings from the same time period, and/or an outcome or processing the additional sensor data readings from the same time period such as a metric or identification of a motility marker, and/or information derived from additional sensor data readings from the same time period; wherein the one or more additional sensors comprises one or more from among:
- a pulse oximetry sensor; and
- an electromyographic sensor.
43. The method according to any of the preceding claims, wherein the process includes determining the location of the capsule within the GI tract based on the detected peristalsis; the ingestible capsule further comprises a vibrating motor arranged, when in a powered on state, to vibrate within the capsule to cause vibration of the capsule housing, and the process further comprises, in response to the determined location of the ingestible capsule satisfying a vibration therapy initiation condition, causing the vibrating motor to switch from a powered off state to the powered on state.
44. Apparatus comprising: an ingestible capsule housing a motion sensor configured to generate a time series of motion sensor data representing motion of the ingestible capsule during passage through the GI tract of a subject; data processing hardware communicably coupled to the motion sensor, the data processing hardware being configured, following ingestion of the ingestible capsule by the subject, at data processing hardware communicably coupled to the motion sensor, to perform a process comprising: generating a spectral analysis of the time series of motion sensor data generated by the motion sensor over a time period during passage of the ingestible capsule through the GI tract, using the spectral analysis to detect peristalsis at a location of the ingestible capsule within the GI tract at the time period.
45. The apparatus according to claim 44, the process further comprising: determining the location of the capsule within the GI tract based on the detected peristalsis.
46. The apparatus according to any of the preceding apparatus claims, wherein the process further comprises: generating a report including information extracted from the spectral analysis at one or a set of predefined peristalsis indicator frequency ranges.
47. The apparatus according to any of the preceding apparatus claims, wherein the process further comprises: generating and outputting to a receiver computing apparatus or message recipient a report including one or more from among: information extracted from the spectral analysis representing fluctuations, variations, or anomalies within spectral components; a metric or metrics calculated from the spectral analysis from among: centre frequency, frequency spread, power distribution, frequency gaps.
48. The apparatus according to claim 46 or 47, wherein the ingestible capsule further comprises one or more additional sensors configured to generate a time series of additional sensor data readings, and the generated report further comprises one or more from among: the spectral analysis for the time period, and additional sensor data readings from the same time period, and/or an outcome or processing the additional sensor data readings from the same time period such as a metric or identification of a motility marker, and/or information derived from additional sensor data readings from the same time period.
49. The apparatus according to any of the preceding apparatus claims, wherein detecting peristalsis at a location of the ingestible capsule within the GI tract at the time period comprises, in the result of the spectral analysis, detecting presence or absence of a signal at one or more of a predefined set of peristalsis indicator frequency ranges.
50. The apparatus according to any of the preceding apparatus claims, wherein the process includes determining the location of the capsule within the GI tract based on the detected peristalsis; and determining the location of the ingestible capsule within the GI tract comprises, in the result of the spectral analysis, detecting presence or absence of a signal/component at one or more of a predefined set of peristalsis indicator frequency ranges.
51. The apparatus according to any of the preceding apparatus claims, wherein a predefined set of peristalsis indicator frequency ranges comprises one or more from among: a first peristalsis indicator frequency range, being a frequency range indicating stomach peristalsis; a second peristalsis indicator frequency range, being a frequency range indicating small intestine peristalsis; a third peristalsis indicator frequency range, being a frequency range indicating large intestine peristalsis.
52. The apparatus according to claim 51, wherein the ingestible capsule is determined to be in the stomach by presence of a signal in the first peristalsis indicator frequency range; the ingestible capsule is determined to be in the small intestine by presence of a signal in the second peristalsis indicator frequency range; the ingestible capsule is determined to be in the large intestine by absence of a signal in the first peristalsis indicator frequency range and absence of a signal in the second peristalsis indicator frequency range; and/or the ingestible capsule is determined to be in the large intestine by presence of a signal in the third peristalsis indicator frequency range.
53. The apparatus according to any of the preceding apparatus claims, wherein using the spectral analysis to detect peristalsis includes applying a minimum signal magnitude threshold to a magnitude of the detected signal at one of the predefined set of peristalsis indicator frequency ranges over the time period, and if the minimum signal magnitude threshold is satisfied, determining that peristalsis at the location of the ingestible capsule within the GI tract at the period of time is detected.
54. The apparatus according to any of the preceding apparatus claims, wherein using the spectral analysis to detect peristalsis includes determining a characteristic frequency in the result of the spectral analysis, and if the characteristic frequency is within one of the predefined set of peristalsis indicator frequency ranges, determining that the a signal is detected in the one of the predefined set of peristalsis indicator frequency ranges, and optionally determining that a location of the ingestible capsule within the GI tract at the period of time is a location corresponding to the one of the predefined set of peristalsis indicator frequency ranges.
55. The apparatus according to any of the preceding apparatus claims, wherein the process includes determining the location of the capsule within the GI tract based on the detected peristalsis; the ingestible capsule further comprises one or more additional sensors, each additional sensor being configured to generate a time series of additional sensor data representing an environment at or surrounding the ingestible capsule; using the spectral analysis to determine a location of the ingestible capsule within the GI tract at a time period includes: detecting a motility marker in the time series of additional sensor data indicating a transition between locations within the GI tract, or presence in a location within the GI tract, to obtain an additional sensor data indication of a location of the ingestible capsule within the GI tract at a time period based on the detected transition or presence; generating the spectral analysis from the time series of motion sensor data for the same time period; and if a signal/component at a threshold magnitude at one of a predefined set of peristalsis indicator frequency ranges is detected in the spectral analysis, and a location indicated by the detection in the spectral analysis is consistent with the additional sensor data indication of location, determining the location of the capsule at the said indicated location at the time period.
56. The apparatus according to any of the preceding apparatus claims, wherein the process includes determining the location of the capsule within the GI tract based on the detected peristalsis; the ingestible capsule further comprises one or more additional sensors, each additional sensor being configured to generate a time series of additional sensor data representing an environment at or surrounding the ingestible capsule; using the spectral analysis to determine a location of the ingestible capsule within the GI tract at a time period includes: detecting a motility marker in the time series of additional sensor data indicating a transition between locations within the GI tract, or presence in a location within the GI tract, to obtain an additional sensor data indication of a location of the ingestible capsule within the GI tract at a time period based on the detected transition or presence; generating the spectral analysis from the time series of motion sensor data for the same time period; and if a location indicated in the spectral analysis by presence or absence of a signal within one of a predefined set of peristalsis indicator frequency ranges is consistent with the additional sensor data indication of location, determining the location of the capsule at the said indicated location at the time period.
57. The apparatus according to claim 55 or 56, wherein the one or more additional sensors includes one or more gas sensors from among: a spectrophotometer; a Surface Acoustic Wave sensor; a Bulk Acoustic Resonator Array; a VOC gas sensors; and a TCD gas sensors; the time series of additional sensor data comprising a time series of gas sensor data.
58. The apparatus according to claim 57, wherein the motility marker is a spike, step change, or inflection in the time series of gas sensor data, indicating that the ingestible capsule has crossed the gastric-duodenal junction, orthe ileocecal junction.
59. The apparatus according to any of claims 55 to 58, wherein the one or more additional sensors includes a reflectometer formed by an antenna in series with a directional coupler, the antenna being controlled by the processor to transmit an intermittent or continuous signal from which a reflectometer signal is obtainable; the motility marker is a measurement of amplitude and/or phase of the reflectometer signal indicating presence of the ingestible capsule in a location within the GI tract.
60. The apparatus according to any of claims 55 to 59, wherein the ingestible capsule includes a wireless data transmitter to transmit the time series of additional sensor data and the time series of motion sensor data to a remote apparatus for processing, and the antenna is an antenna of the data transmitter.
61. The apparatus according to any of claims 55 to 60, wherein the ingestible capsule includes a wireless data transmitter to transmit the frequency domain representation of the sensor data to a remote apparatus for processing, and the antenna is an antenna of the data transmitter.
62. The apparatus according to claim 61, wherein the apparatus further comprises a remote computing apparatus; the ingestible capsule further comprises a wireless data transceiver to transmit the time series of motion sensor data to a remote apparatus for processing, the data processing hardware being a component of the remote apparatus, the ingestible capsule further comprises a therapeutic payload carrying compartment, a release mechanism, the process further comprising: at the remote computing apparatus: performing the process including determining the location of the capsule within the GI tract based on detected peristalsis, and in response to determining that the determined location of the ingestible capsule is a target release location for therapeutic matter within the therapeutic payload carrying compartment, transmitting a trigger signal to the wireless data transceiver; and at the ingestible capsule: receiving the trigger signal at the wireless data transceiver, and responding to the trigger signal by, immediately or at a predetermined delay, the release mechanism causing the therapeutic matter within the therapeutic payload carrying compartment to be released into the GI tract.
63. The apparatus according to any of the preceding apparatus claims, wherein the process includes determining the location of the capsule within the GI tract based on the detected peristalsis; using the spectral analysis to determine a location of the ingestible capsule within the GI tract at a time period includes: detecting a motility marker in the time series of motion sensor data indicating a transition between locations within the GI tract to obtain a motion sensor time series data indication of a location of the ingestible capsule within the GI tract at a time period based on the detected transition; generating the spectral analysis from the time series of motion sensor data for the same time period; and if a location is indicated by presence or absence of a signal or signals at a predefined set of peristalsis indicator frequency ranges in the result of the spectral analysis, and the indicated location is consistent with the motion sensor time series data indication of location, determining the location of the ingestible capsule at the said indicated location at the time period.
64. The apparatus according to any of the preceding apparatus claims, wherein the process includes determining the location of the capsule within the GI tract based on the detected peristalsis; the ingestible capsule further comprises a therapeutic payload carrying compartment and a release mechanism, and the process further comprises, in response to the determined location of the ingestible capsule being a target release location for therapeutic matter within the therapeutic payload carrying compartment, causing the therapeutic matter to be released into the GI tract.
65. The apparatus according to any of the preceding apparatus claims, wherein the process includes determining the location of the capsule within the GI tract based on the detected peristalsis; the ingestible capsule further comprises a GI tract sampling chamber and a sealing mechanism to open and close the GI tract sampling chamber, and the process further comprises, in response to the determined location of the ingestible capsule being a predefined target sampling location, causing the sealing mechanism to open and close the sampling chamber.
66. The apparatus according to claim 65, wherein the sealing mechanism comprises a fluid-filled sack occupying the sampling chamber, a membrane maintained in a stretched state by the fluid-filled sack and being exposed to the external environment via an aperture or drain valve, a sack rupturing actuator, and a one-way sampling valve at an interface between the housing of the ingestible capsule and the external environment; the membrane being arranged to permit fluid from the fluid-filled sack to exit the sampling chamber via the aperture or drain valve, and to block a fluid path between the one-way sampling valve and the aperture or drain valve, wherein, in response to the determined location of the ingestible capsule being a predefined target sampling location, the sack rupturing actuator is actuated to rupture the sack and thereby to cause the fluid to flow from the sack out of the sampling chamber via the aperture or drain valve, and the membrane to become less stretched than in the stressed state and thereby to suck fluid into the sampling chamber via the one-way sampling valve.
67. The apparatus according to any of the preceding apparatus claims, wherein the using the spectral analysis to determine a location of the ingestible capsule within the GI tract at the time period is performed by a pre-trained machine learning algorithm.
68. The apparatus according to any of the preceding apparatus claims, further comprising extracting from the spectral analysis respiration information comprising an indication of respiration rate.
69. The apparatus according to claim 68, wherein the extracted respiratory information comprises a measurement of a signal in one or more from a predefined set of respiration information frequency ranges, respiration information frequency patterns, or detection of a signal or signal characteristics in the spectral analysis indicating one or more from among:
-sleep apnea (absence of respiration during sleep);
-normal respiration;
-Blots respiration;
-Kussmaul breathing;
-Cheyne Stokes respiration;
- Bradypnea;
-Tachypnea;
-Hyperpnea; -Ataxic respiration;
-Air trapping;
-Obstructive respiration;
-Sighing;
-Apneustic respiration;
-Agonal respiration.
70. The apparatus according to any of the preceding apparatus claims, wherein the motion sensor comprises an accelerometer and the time series of motion sensor data comprises a time series of accelerometer data; and/or the motion sensor comprises a gyroscope and the time series of motion sensor data comprises a time series of gyroscope data.
71. The apparatus according to any of the preceding apparatus claims, wherein the apparatus is configured to repeat the process for a series of time periods during passage of the ingestible capsule through the GI tract.
72. The apparatus according to claim 71, wherein the series of time periods are contiguous, or wherein the series of time windows are sliding so that adjacent time windows in the series partially overlap one another.
73. The apparatus according to any of the preceding apparatus claims, wherein the motion sensor comprises a three-axis accelerometer and the motion sensor data comprises three time series each representing acceleration in a respective one of the three axes, and the process includes a pre-spectral analysis step comprising: combining the three time series into a single resultant time series; wherein the spectral analysis is generated from the single resultant time series.
74. The apparatus according to any of the preceding apparatus claims, wherein the sensor hardware comprises a gyroscope and the sensor data comprises a time series of gyroscope data representing changes to a frame of reference of the ingestible capsule relative to a fixed frame of reference; extracting from the gyroscope data a long axis rotation time series representing rotation of the ingestible capsule about the long axis defined by the capsule housing; wherein the spectral analysis is generated from the long axis rotation time series.
75. The apparatus according to any of the preceding apparatus claims, wherein the motion sensor is a three-axis accelerometer and the motion sensor data comprises three time series each representing acceleration in a respective one of the three axes, and generating the spectral analysis comprises: transforming each of the three time series into respective single axis frequency domain representations; combining the three single axis frequency domain representations to obtain a combined frequency domain representation.
76. The apparatus according to any of claims 73 to 75, wherein combining the three single axis frequency domain representations comprises comparing magnitude of a signal in a taiget frequency range from each of the single axis frequency domain representations, and selecting the single axis frequency domain representation with the greatest magnitude signal in the target frequency range as the combined frequency domain representation.
77. The apparatus according to any of claims 73 to 75, wherein combining the three single axis frequency domain representations comprises, for each component frequency in the frequency domain, combining a component magnitude from each of the single axis frequency domain representations, the resulting combination per component frequency being the combined frequency domain representation.
78. The apparatus according to claim 77, wherein wherein the combining is a summation, or a root sum squared.
79. The apparatus according to any of the preceding apparatus claims, wherein the spectral analysis is a value representing magnitude of a component at each of a series of component frequencies.
80. The apparatus according to any of the preceding apparatus claims, wherein the ingestible capsule further comprises the data processing hardware.
81. The apparatus according to any of the preceding apparatus claims, wherein the apparatus further comprises a remote computing apparatus; the ingestible capsule further comprises a wireless data transmitter to transmit the time series of motion sensor data to the remote computing apparatus for processing, the data processing hardware being a component of the remote computing apparatus.
82. The apparatus according to any of the preceding apparatus claims, wherein the process further comprises: generating a report including information extracted from the spectral analysis representing fluctuations, variations, or anomalies within spectral components.
83. The apparatus according to any of the preceding apparatus claims, wherein the ingestible capsule further comprises one or more additional sensors configured to generate a time series of sensor data, and the process includes generating and outputting a report including one or more from among: the spectral analysis for the time period, and a result of processing the spectral analysis for the time period comprising information indicating a respiration rate, information indicating a detection of peristalsis, or information indicating a physical activity type being undertaken by the subject; additional sensor data readings from the same time period, and/or an outcome or processing the additional sensor data readings from the same time period such as a metric or identification of a motility marker, and/or information derived from additional sensor data readings from the same time period.
84. The apparatus according to claim 83, wherein the one or more additional sensors comprise one or more from among:
- a gas sensor;
- a motion sensor;
- a temperature sensor;
= a relative humidity sensor;
- a reflectometer;
- a pulse oximetry sensor;
- an electromyographic sensor.
85. The apparatus according to any of the preceding apparatus claims, wherein the apparatus further comprises one or more additional sensors external to the ingestible capsule positioned externally on the skin of the subject, the one or more additional sensors being communicatively coupled to the ingestible capsule or to a remote computing apparatus to which the ingestible capsule is communicatively coupled, the one or more additional sensors being configured to generate a time series of sensor data, and the process includes generating and outputting a report including one or more from among: the spectral analysis for the time period, and a result of processing the spectral analysis for the time period comprising information indicating a respiration rate, information indicating a detection of peristalsis, or information indicating a physical activity type being undertaken by the subject; additional sensor data readings from the same time period, and/or an outcome or processing the additional sensor data readings from the same time period such as a metric or identification of a motility marker, and/or information derived from additional sensor data readings from the same time period; wherein the one or more additional sensors comprises one or more from among:
- a pulse oximetry sensor; and
- an electromyographic sensor.
86. The apparatus according to any of the preceding apparatus claims, wherein the process includes determining the location of the capsule within the GI tract based on the detected peristalsis; the ingestible capsule further comprises a vibrating motor arranged, when in a powered on state, to vibrate within the capsule to cause vibration of the capsule housing, and the process further comprises, in response to the determined location of the ingestible capsule satisfying a vibration therapy initiation condition, causing the vibrating motor to switch from a powered off state to the powered on state.
87. A computer program comprising processing instructions which, when executed by processor hardware communicably coupled to a motion sensor housed in an ingestible capsule and configured to to generate a time series of motion sensor data representing motion of the ingestible capsule during passage through the GI tract of a subject, causes the processor hardware to perform a process comprising, following ingestion of the ingestible capsule by the subject: generating a spectral analysis of the time series of motion sensor data generated by the motion sensor over a time period during passage of the ingestible capsule through the GI tract, using the spectral analysis to detect peristalsis at a location of the ingestible capsule within the GI tract at the time period.
88. A method comprising: following ingestion of an ingestible capsule by a subject, the ingestible capsule housing a motion sensor configured to generate a time series of motion sensor data representing motion of the ingestible capsule during passage through the GI tract of a subject, at data processing hardware communicably coupled to the motion sensor, performing a process comprising: generating a spectral analysis of the time series of motion sensor data generated by the motion sensor over a time period during passage of the ingestible capsule through the GI tract, extracting from the spectral analysis respiration information comprising an indication of respiration rate.
89. The method of claim 88, wherein the extracted respiratory information comprises a measurement of a signal in one or more from a predefined set of respiration information frequency ranges or detection of a signal or signal characteristics in the spectral analysis indicating one or more from among:
-sleep apnea (absence of respiration during sleep);
-normal respiration;
-Blots respiration;
-Kussmaul breathing;
-Cheyne Stokes respiration;
- Bradypnea;
-Tachypnea;
-Hyperpnea;
-Ataxic respiration;
-Air trapping;
-Obstructive respiration;
-Sighing;
-Apneustic respiration;
-Agonal respiration.
90. The method of claim 89, wherein the predefined set of respiration information frequency ranges includes a first respiration information frequency range indicating snoring, and a second respiration information frequency range indicating respiration.
91. The method of claim 90, wherein the first respiration information frequency range is between 12 and 18 cpm (cycles per minute).
92. The method of claim 90, wherein the second respiration information frequency range is between 3600 and 18000cpm.
93. The method of any of claims 88 to 91, wherein the ingestible capsule further comprises, or is operably coupled to a separate, one or more additional sensors, each additional sensor being configured to generate a time series of additional sensor data; the additional sensor comprises a pulse oximetry sensor configured to generate a time series of pulse oximetry measurements representing concentration of oxygen in blood of the subject; the method further comprises generating and outputting a report comprising the extracted respiration information for the time window and a contemporaneous extract from the time series of pulse oximetry measurements.
94. The method of claim 93, wherein the report is generated and output by processor hardware and a wireless data transceiver on board the ingestible capsule.
95. The method of claim 93, wherein the report is generated and output by a remote processing apparatus configured to receive data transmitted away from the ingestible capsule by a wireless data transceiver.
96. Apparatus comprising: an ingestible capsule housing a motion sensor configured to generate a time series of motion sensor data representing motion of the ingestible capsule during passage through the GI tract of a subject; data processing hardware communicably coupled to the motion sensor, the data processing hardware being configured, following ingestion of the ingestible capsule by the subject, at data processing hardware communicably coupled to the motion sensor, to perform a process comprising: generating a spectral analysis of the time series of motion sensor data generated by the motion sensor over a time period during passage of the ingestible capsule through the GI tract, extracting from the spectral analysis respiration information comprising an indication of respiration rate.
97. The apparatus of claim 96, wherein the extracted respiratory information comprises a measurement of a signal in one or more from a predefined set of respiration information frequency ranges, or detection of a signal or signal characteristics in the spectral analysis indicating one or more from among:
-sleep apnea (absence of respiration during sleep);
-normal respiration;
-Blots respiration;
-Kussmaul breathing;
-Cheyne Stokes respiration;
- Bradypnea;
-Tachypnea;
-Hyperpnea;
-Ataxic respiration; -Air trapping;
-Obstructive respiration;
-Sighing;
-Apneustic respiration;
-Agonal respiration.
98. The apparatus of claim 96, wherein the predefined set of respiration information frequency ranges includes a first respiration information frequency range indicating snoring, and a second respiration information frequency range indicating respiration.
99. The apparatus of claim 98, wherein the first respiration information frequency range is between 12 and 18 cpm.
100. The apparatus of claim 99, wherein the second respiration information frequency range is between 3600 and 18000cpm.
101. The apparatus of any of claims 96 to 100, wherein the ingestible capsule further comprises, or is operably coupled to a separate, one or more additional sensors, each additional sensor being configured to generate a time series of additional sensor data; the additional sensor comprises a pulse oximetry sensor configured to generate a time series of pulse oximetry measurements representing concentration of oxygen in blood of the subject; the method further comprises generating and outputting a report comprising the extracted respiration information for the time window and a contemporaneous extract from the time series of pulse oximetry measurements.
102. The apparatus of claim 101 wherein the report is generated and output by processor hardware and a wireless data transceiver on board the ingestible capsule.
103. The apparatus of claim 101, wherein the report is generated and output by a remote processing apparatus configured to receive data transmitted away from the ingestible capsule by a wireless data transceiver.
104. A computer program comprising processing instructions which, when executed by processor hardware communicably coupled to a motion sensor housed in an ingestible capsule and configured to to generate a time series of motion sensor data representing motion of the ingestible capsule during passage through the GI tract of a subject, causes the processor hardware to perform a process comprising, following ingestion of the ingestible capsule by the subject: generating a spectral analysis of the time series of motion sensor data generated by the motion sensor over a time period during passage of the ingestible capsule through the GI tract, extracting from the spectral analysis respiration information comprising an indication of respiration rate.
105. A method comprising: following ingestion by a subject an ingestible capsule housing amotion sensor configured to generate a time series of motion sensor data representing motion of the ingestible capsule during passage through the GI tract; at data processing hardware communicably coupled to the motion sensor, performing a process comprising: conducting a spectral analysis of the time series of motion sensor data generated by the motion sensor over a time period during passage of the ingestible capsule through the GI tract, using the spectral analysis to determine a physical activity being undertaken by the subject or to characterise a physical activity being undertaken by the subject.
106. Apparatus comprising: an ingestible capsule housing a motion sensor configured to generate a time series of motion sensor data representing motion of the ingestible capsule during passage through the GI tract of a subject; data processing hardware communicably coupled to the motion sensor, the data processing hardware being configured, following ingestion of the ingestible capsule by the subject, at data processing hardware communicably coupled to the motion sensor, to perform a process comprising: generating a spectral analysis of the time series of motion sensor data generated by the motion sensor over a time period during passage of the ingestible capsule through the GI tract, using the spectral analysis to determine a physical activity being undertaken by the subject or to characterise a physical activity being undertaken by the subject.
107. A computer program comprising processing instructions which, when executed by processor hardware communicably coupled to a motion sensor housed in an ingestible capsule and configured to to generate a time series of motion sensor data representing motion of the ingestible capsule during passage through the GI tract of a subject, causes the processor hardware to perform a process comprising, following ingestion of the ingestible capsule by the subject: generating a spectral analysis of the time series of motion sensor data generated by the motion sensor over a time period during passage of the ingestible capsule through the GI tract, using the spectral analysis to determine a physical activity being undertaken by the subject or to characterise a physical activity being undertaken by the subject.
108. An ingestible capsule, comprising: a housing, being a biocompatible indigestible housing including a sampling chamber; a power supply; a sampling mechanism; and a sensing mechanism, the sensing mechanism being sensitive to the environment external to the housing; the ingestible capsule being configured for passage through a gastrointestinal, GI, tract of a subject mammal, during which passage: the sensing mechanism is configured to output an output signal varying according to the GI tract environment external to the housing, wherein the sensing mechanism comprises one or more sensors from among: a VOC gas sensor; a TCD gas sensor; a reflectometer formed by a transmission antenna of the ingestible capsule connected in series with a directional coupler configured to measure a reflected signal from the transmission antenna; and a motion sensor; the sampling mechanism is configured to cause a sample of fluid or matter from the GI tract to be sealed in the sampling chamber at a sampling timing determined according to the output signal.
109. The ingestible capsule according to claim 108, wherein the ingestible capsule comprises processor hardware configured to identify in real time one or more ileocecal junction transition indicators in the output signal of the sensing mechanism, and to determine the sampling timing according to the identification of the ileocecal junction indicator.
110. The ingestible capsule according to any of claims 108 to 109, wherein the sensing mechanism is a direct gas sensing mechanism comprising a VOC gas sensor, the direct gas sensing mechanism being housed within the capsule in a direct gas sensing portion sealed from other components of the ingestible capsule by a gas impermeable membrane and being exposed to a gas mixture in the environment external to the ingestible capsule via a gas permeable membrane in the housing at the location of the direct gas sensing portion, the output signal output by the sensing mechanism comprising VOC concentration readings of the VOC gas sensor.
111. The ingestible capsule according to claim 110, wherein the direct gas sensing mechanism further comprises a TCD gas sensor, or wherein the ingestible capsule is configured to make TCD readings via a heater side of the VOC gas sensor, the output signal output by the sensing mechanism further comprising TCD readings of the VOC gas sensor and/or the TCD gas sensor.
112. The ingestible capsule of claim 110 or 111, wherein identifying the ileocecal junction transition indicator comprises identifying an increase in sensor side VOC gas sensor readings with a contemporaneous increase in H2 concentration, the H2 concentration being derived from TCD readings of the TCD gas sensor and/or heater side readings of the VOC gas sensor.
113. The ingestible capsule of claim 110 or 111, wherein identifying the ileocecal junction transition indicator comprises identifying an increase in sensor side VOC gas sensor readings with a contemporaneous increase in CH4 concentration, the CH4 concentration being derived from TCD readings of the TCD gas sensor and/or heater side readings of the VOC gas sensor.
114. The ingestible capsule according to claim 108 or 109, wherein the sensing mechanism is a non-contact sensing mechanism housed in a portion of the ingestible capsule sealed from the environment external to the ingestible capsule by the housing, the non-contact sensing mechanism comprising at least one of a motion sensor and a reflectometer, the reflectometer comprising a transmission antenna connected in series with a directional coupler configured to measure a reflected signal from the transmission antenna, the output signal output by the sensing mechanism comprising a time series of motion sensor readings and/or reflectometer readings.
115. The ingestible capsule according to claim 114, wherein the non-contact sensing mechanism comprises the reflectometer, and the ingestible capsule further comprises a diode detector and the diode detector forms a part of the reflectometer, the diode detector being configured to receive the reflected signal from the antenna and to measure an amplitude of the reflected signal, the reflectometer readings in the output signal comprising amplitude measurements of the reflected signal.
116. The ingestible capsule of any of claims 108 to 115, wherein the ingestible capsule further comprises a quadrature demodulator and the quadrature demodulator forms a part of the reflectometer, the quadrature demodulator being configured to receive the reflected signal from the antenna via the directional coupler and to extract phase information of the reflected signal relative to a carrier signal, the reflectometer readings in the output signal comprising the extracted phase information of the reflected signal.
117. The ingestible capsule of any of claims 114 to 116, wherein the ingestible capsule further comprises an antenna impedance control mechanism comprising a variable capacitor configured to vary impedance of the transmission antenna, and a controller, wherein the reflectometer and the antenna impedance control mechanism form a closed loop or feedback loop, and wherein the controller is configured to receive the measurements of the amplitude of the reflected signal from a diode detector and to execute a control algorithm to use the amplitude measurements to generate an antenna impedance control signal setting a capacitance of the variable capacitor to vary impedance of the antenna to reduce amplitude of the reflected signal, wherein the reflectometer readings in the output signal comprise readings of the antenna impedance control signal.
118. The ingestible capsule of claim 117, wherein the closed loop or feedback loop further comprises a quadrature demodulator, and wherein phase information is extracted by the quadrature demodulator and output to the controller, and wherein the controller is configured to use the amplitude information and the phase information to generate the antenna impedance control signal.
119. The ingestible capsule according to any of claims 108 to 118, wherein the output signal output by the sensing mechanism comprises accelerometer readings and reflectometer readings, and determining the sampling timing comprises identifying that an ileocecal junction transition indicator is present in readings from the reflectometer and the accelerometer, including: processing the reflectometer readings and the accelerometer readings to identify the presence of a first ileocecal junction transition indicator in either one of the reflectometer readings and the accelerometer readings, processing the other one of the reflectometer readings and the accelerometer readings to identify a second ileocecal junction transition indicator within a predefined time window of a timing of the first ileocecal junction transition indicator, and in response to identifying the first ileocecal junction transition indicator and the second ileocecal junction transition indicator within the predefined time window, determining the sampling timing, being either immediate or after a predefined delay.
120. The ingestible capsule according to any of claims 108 to 119, wherein the or each ileocecal junction transition indicator and/or gastric-duodenal transition indicator is a characteristic or combination of characteristics of: a reading, a series of readings, a pattern, a geometric feature, a statistical feature, and/or a mathematical feature, in a record of the output signal as a function of time; the characteristic or combination of characteristics being predefined as being caused by transition of the ingestible capsule across the ileocecal junction or from the stomach into the duodenum.
121. The ingestible capsule according to any of claims 108 to 120, wherein the ingestible capsule comprises a microcontroller, and the sampling mechanism includes the microcontroller; the microcontroller being configured to: during an identification phase, on a rolling basis, record a representation of the output signal for a most recent time period of duration t, and to process the recorded representation of the output signal for the most recent time period of duration t to identify presence of the one or more ileocecal junction transition indicators; the microcontroller being configured, upon identification of the presence of the one or more ileocecal junction transition indicators, to determine the sampling timing and based on the determined sampling timing to cause the sampling mechanism to open and close the sampling chamber to obtain a GI tract sample.
122. The ingestible capsule according to any of any of claims 108 to 121, wherein the ingestible capsule comprises a microcontroller, and the sampling mechanism includes the microcontroller; the microcontroller being configured to: during an identification phase, on a rolling basis, record a representation of the output signal for a most recent time period of duration t, and to process the recorded representation of the output signal for the most recent time period of duration t to identify presence of the one or more gastric-duodenal transition indicators; the microcontroller being configured, upon identification of the presence of the one or more gastric-duodenal transition indicators, to determine the sampling timing and based on the determined sampling timing to cause the sampling mechanism to open and close the sampling chamber to obtain a GI tract sample.
123. The ingestible capsule according to any of the claims 108 to 122, wherein the ingestible capsule comprises a microcontroller, and the sampling mechanism includes the microcontroller; the microcontroller being configured to: during an identification phase, on a rolling basis, record a representation of the output signal for a most recent time period of duration t, and to process the recorded representation of the output signal for the most recent time period of duration t to identify: presence of the one or more gastric -duodenal transition indicators; and following the identification of the presence of the one or more gastric -duodenal transition indicators, to identify presence of the one or more ileocecal junction transition indicators; the microcontroller being configured, upon identification of the presence of the one or more ileocecal junction transition indicators, to determine the sampling timing and based on the determined sampling timing to cause the sampling mechanism to open and close the sampling chamber to obtain a GI tract sample.
124. The ingestible capsule according to any of claims 108 to 123, wherein the ingestible capsule comprises a wireless transceiver, and the antenna is configured, during an identification phase, to transmit a transmission signal representing the output signal from the sensing mechanism to remote processing apparatus; the transceiver being configured, upon receipt of a trigger signal from the remote processing apparatus, to cause, immediately or at a predetermined delay, the sampling mechanism to open and close the sampling chamber to obtain a GI tract sample.
125. The method according to any of claims 108 to 124, wherein the sampling mechanism comprises a fluid-filled sack occupying the sampling chamber, a membrane maintained in a stretched state by the fluid-filled sack and being exposed to the external environment via an aperture or drain valve, a sack rupturing actuator, and a one-way sampling valve at an interface between the housing of the ingestible capsule and the external environment; the membrane being arranged to permit fluid from the fluid-filled sack to exit the sampling chamber via the aperture or drain valve, and to block a fluid path between the one-way sampling valve and the aperture or drain valve, wherein, in response to the determined location of the ingestible capsule being a predefined target sampling location, the sack rupturing actuator is actuated to rupture the sack and thereby to cause the fluid to flow from the sack out of the sampling chamber via the aperture or drain valve, and the membrane to become less stretched than in the stressed state and thereby to suck fluid into the sampling chamber from the GI tract via the one-way sampling valve.
126. The ingestible capsule according to claim 125, wherein the sack rupturing actuator comprises a heating element arranged in contact with the fluid-filled sack and a supercapacitor configured to be trickle charged by the ingestible capsule power supply over a period of time beginning with ingestion of the ingestible capsule, and to be caused to release the charge to the heating element at the determined sampling timing under the control of the microcontroller to cause rupturing of the fluid-filled sack.
127. The ingestible capsule according to claim 126, wherein the supercapacitor and the heating element are impedance matched, or are impedance matched to within a defined tolerance.
128. The ingestible capsule according to any of claims 125 to 127, wherein the heating element is a resistive heater element comprising one or more from among:
SMT resistor; metallic resistive wire; nichrome;
MEMS heater element.
129. The ingestible capsule according to claim 125, wherein the sack rupturing actuator rupturing actuator comprises a power source and a LASER diode focussed on the elastic material membrane, wherein a microcontroller of the ingestible capsule is configured at the determined sampling timing to activate the LASER diode to rupture the fluid-filled sack.
130. The ingestible capsule according to claim 125, wherein the sack rupturing actuator comprises a pre-sprung mechanical needle, wherein a microcontroller of the ingestible capsule is configured, at the determined sampling timing, to release the pre-sprung mechanical needle causing the pre-sprung mechanical needle to spring into the fluid- filled sack causing rupturing.
131. The ingestible capsule according to claim 125, wherein the sack rupturing actuator comprises a power source, a shape memory alloy wire, and a rupturing member, the power source being configured, at the determined sampling timing and under control of the microcontroller, to transfer energy to the shape memory alloy wire, to initiate a phase change at material level of the shape memory alloy wire and thereby to exert a force on the rupturing member to cause the rupturing member to come into contact with, and to rupture, the fluid-filled sack.
132. The ingestible capsule according to claim 125, wherein the sack rupturing actuator comprises a motor and a rupturing member, the microcontroller being configured, at the determined sampling timing, to power on the motor and thereby to exert a force on the rupturing member to cause the rupturing member to come into contact with, and to rupture, the fluid-filled sack.
133. The ingestible capsule according to any of claims 108 to 132, wherein the ingestible capsule includes an environmental sensor, and the readings include readings of the environmental sensor, the environmental sensor being an environmental temperature sensor, an environmental relative humidity sensor, or an environmental temperature sensor and an environmental humidity sensor; the processing the recorded readings including determining an excretion event timing by detecting an excretion indicator, the excretion indicator being a change in the environmental sensor readings between an internal environmental condition of the subject mammal and an external environmental condition at a location of the subject mammal, the excretion event timing being a timing of excretion of the ingestible capsule by the subject mammal.
134. The ingestible capsule according to any of claims 108 to 133, the ingestible capsule comprising a wireless transceiver configured to transmit data transmission payload away from the ingestible capsule via Bluetooth, Bluetooth Long Range, and/or 433MHz radio transmission technique, the data transmission payload comprising one or more from among: a record of sampling timing; a record of excretion timing; a record of the one or more identified ileocecal junction transition indicators; a record of the one or more identified gastric-duodenal transition indicators; a record of an electrode signal indicating rupturing of the fluid-filled sack; a record of an electrode signal indicating a filled state of the sampling chamber; output signal output by the sensing mechanism; and a metric or metrics representing the output signal output by the sensing mechanism.
135. The ingestible capsule according to claim 134, wherein transmission of the data transmission payload by the wireless transceiver is triggered by one or more from among: determining that an excretion event has occurred; determining sampling timing; determining sampling timing and that a predefined delay after sampling timing has expired; receipt at a microcontroller of the ingestible capsule of an electrode signal indicating rupturing of the fluid-filled sack.
136. The ingestible capsule according to any of claims 108 to 135, wherein the sensing mechanism comprises a direct gas sensing mechanism and a non-contact sensing mechanism.
137. A method comprising: providing an ingestible capsule according to any of claims 108 to 136 to a subject mammal for ingestion; processing the output signal of the sensing mechanism to determine the sampling timing; causing the sampling mechanism to obtain a GI tract sample at the determined sampling timing.
138. A system comprising an ingestible capsule and a remote processing apparatus: the ingestible capsule, comprising: a housing, being a biocompatible indigestible housing including a sampling chamber; a power supply; a sampling mechanism; a wireless transceiver; and a sensing mechanism, the sensing mechanism being sensitive to an environment external to the housing; the ingestible capsule being configured for passage through a gastrointestinal, GI, tract of a subject mammal, during which passage: the sensing mechanism is configured to output an output signal varying according to GI tract environment external to the housing, wherein the sensing mechanism comprises one or more sensors from among: a VOC gas sensor; a TCD gas sensor; a reflectometer formed by a transmission antenna of the ingestible capsule connected in series with a directional coupler configured to measure a reflected signal from the transmission antenna; and a motion sensor; the sampling mechanism is configured to cause a sample of fluid or matter from the GI tract to be sealed in the sampling chamber at a sampling timing determined according to the output signal; wherein the capsule is configured, during an identification phase, to transmit a transmission signal representing the output signal to the remote processing apparatus via the wireless transceiver; the wireless transceiver being configured, upon receipt of a trigger signal from the remote processing apparatus, to cause, immediately or at a predetermined delay, the sampling mechanism to cause a sample of fluid or matter from the GI tract to be sealed in the sampling chamber; and the remote processing apparatus comprising a remote processing apparatus transceiver configured to communicate with the wireless data transceiver of the ingestible capsule including to receive the transmission signal representing the output signal, and a processor configured to process the output signal to identify in real time one or more ileocecal junction transition indicators and/or one or more gastric duodenal transition indicators in the output signal, and to cause the remote processing apparatus transceiver to transmit the trigger signal to the wireless data transceiver of the ingestible capsule according to the timing of the identified one or more ileocecal junction transition indicators and/or one or more gastric duodenal transition indicators.
139. The method, computer program, or apparatus according to any of the preceding claims, wherein the process includes determining the location of the capsule within the GI tract based on the detected peristalsis; the ingestible capsule further comprises a vibrating motor arranged, when in a powered on state, to vibrate within the capsule to cause vibration of the capsule housing, and the process further comprises, in response to the determined location of the ingestible capsule satisfying a vibration therapy initiation condition, causing the vibrating motor to switch from a powered off state to the powered on state.
PCT/AU2025/050151 2024-02-23 2025-02-21 Methods, programs, apparatus for obtaining health information from sensors in an ingestible capsule Pending WO2025175357A1 (en)

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