Method of determining body exit of an ingested capsule

A method of determining body exit of an ingestible capsule comprising the steps of providing (40) an ingestible capsule (20) having a pressure sensor (23), having (41) a subject ingest the capsule, recording (42a) measurements from the pressure sensor as the capsule passes through at least an end portion of a gastrointestinal tract of the subject, transmitting (44) the measurements to a processor (31) outside of the gastrointestinal tract of the subject, identifying (47) an increasing pressure sequence (65) in the measurements between a selected start time (62) and a transmission end time (63), comparing (48) the sequence to a reference (66), and using the comparison to make a determination (52) regarding the capsule exiting the gastrointestinal tract of the subject. The increasing pressure sequence may be the longest increasing pressure sequence in the measurements. The reference may be a logarithmic regression of the measurements. The ingestible capsule may further comprise a temperature sensor (22) and the method may further comprising the steps of recording (42b) measurements from the temperature sensor as the capsule passes through the end portion of the gastrointestinal tract of the subject, transmitting (43) the measurements to the processor, analyzing (46) the temperature measurements for a substantial drop (68) in the temperature measurements, and using the analysis of the temperature measurements to make the determination regarding the capsule exiting the gastrointestinal tract of the subject.

TECHNICAL FIELD

The present invention relates generally to ingestible capsules and, more particularly, to a process for determining the body exit of an ingested capsule.

BACKGROUND ART

Ingestible capsules are well-known in the prior art. Such capsules are generally small pill-like devices that can be ingested or swallowed by a patient. It is known that such capsules may include one or more sensors for determining physiological parameters of the gastrointestinal tract, such as sensors for detecting temperature, pH and pressure.

A number of methods of determining location of an ingestible capsule are known in the prior art. For example, it is known that signal strength or signal triangulation may be used to attempt to determine the location of an ingested capsule. However, the use of an RF signal has a number of disadvantages, including that it generally requires multiple antennas, various tissues may impact the signal differently, and patient movement may skew the results. It is also known that accelerometers may be used to attempt to determine location, but such methods also have disadvantages, such as drift, non-linear progression and rotational inaccuracy.

It is also known that certain physiological parameters may be associated with regions of the gastrointestinal tract. For example, a 1988 article entitled “Measurement of Gastrointestinal pH Profiles in Normal Ambulant Human Subjects” discloses pH measurements recorded by a capsule passing through the gastrointestinal tract. It is known that pH has been correlated with transitions from the stomach to the small bowel (gastric emptying) and from the distal small bowel to the colon (ileo-caecal) junction.

DISCLOSURE OF THE INVENTION

With parenthetical reference to corresponding parts, portions or surfaces of the disclosed embodiment, merely for the purposes of illustration and not by way of limitation, the present invention provides an improved method of determining body exit of an ingestible capsule comprising the steps of providing (40) an ingestible capsule (20) having a pressure sensor (23), having (41) a subject ingest the capsule, recording (42a) measurements from the pressure sensor as the capsule passes through at least an end portion of a gastrointestinal tract of the subject, transmitting (44) the measurements to a processor (31) outside of the gastrointestinal tract of the subject, identifying (47) an increasing pressure sequence (65) in the measurements between a selected start time (62) and a transmission end time (63), comparing (48) the sequence to a reference (66), and using the comparison to make a determination (52) regarding the capsule exiting the gastrointestinal tract of the subject.

The increasing pressure sequence may be the longest increasing pressure sequence in the measurements. The reference may be a logarithmic regression of the measurements. The ingestible capsule may further comprise a temperature sensor (22) and the method may further comprising the steps of recording (42b) measurements from the temperature sensor as the capsule passes through the end portion of the gastrointestinal tract of the subject, transmitting (43) the measurements to the processor, analyzing (46) the temperature measurements for a substantial drop (68) in the temperature measurements, and using the analysis of the temperature measurements to make the determination regarding the capsule exiting the gastrointestinal tract of the subject. The method may further comprise the step of conditioning (53) the measurements between the selected start time and the transmission end time to provide terminating pressure data as a function of time (64), and wherein the increasing pressure sequence is identified in the terminating pressure data. The step of conditioning the pressure measurements may comprise the steps of screening the measurements to verify that they are valid, converting the measurements to units of pressure, and scaling the units of pressure such that ambient atmospheric pressure is set at a zero baseline. The step of transmitting the measurements to a processor may comprise the steps of transmitting the measurements from the capsule to a receiver (17) outside of the gastrointestinal tract of the subject, and downloading the measurements from the receiver to the processor. The selected start time may be about one hour prior to the transmission end time. The method may further comprise the step of providing a positive determination (54) regarding the capsule exiting the gastrointestinal tract of the subject when the comparison indicates a match. A standard correlation coefficient of about 0.8 or greater may indicate that the comparison is a match and a standard correlation coefficient of less than about 0.8 may indicate that the comparison is not a match. The method may further comprise the step of providing a positive determination regarding the capsule exiting the gastrointestinal tract of the subject when the comparison indicates a match or there is the substantial drop in the temperature measurements. The method may further comprise the step of providing a negative determination (55) regarding the capsule exiting the gastrointestinal tract when the comparison indicates not a match and there is not the substantial drop in the temperature measurements. The ingestible capsule may further comprise a power source (21) adapted to provide current to an electrical circuit housed in the capsule and the method may further comprise the steps of measuring (43) voltage for the circuit as the capsule passes through the gastrointestinal tract of the subject, transmitting (44c) the voltage measurements to the processor, analyzing (45) the voltage measurements for a low voltage condition and using the analysis of the voltage measurements to make the determination regarding the capsule exiting the gastrointestinal tract of the subject. The method may further comprise the step of providing a negative determination regarding the capsule exiting the gastrointestinal tract when the low voltage condition is indicated, and the low voltage condition may comprise a voltage measurement of less than about 2.5 volts or the low voltage condition may comprise a series of decreasing voltage measurements over a time period. The method may further comprise the step of displaying (56) the determination regarding the capsule exiting the gastrointestinal tract of the subject on a display (32).

In another aspect the invention provides a method of determining body exit of an ingestible capsule comprising the steps of providing an ingestible capsule having a pressure sensor, a temperature sensor and a power source adapted to provide current to an electrical circuit housed in the capsule, having a subject ingest the capsule, recording measurements from the pressure sensor and the temperature sensor as the capsule passes through at least an end portion of a gastrointestinal tract of the subject, measuring voltage for the circuit as the capsule passes through the gastrointestinal tract of the subject, transmitting the measurements to a processor outside of the gastrointestinal tract of the subject, analyzing the voltage measurements for a low voltage condition, analyzing the temperature measurements for a substantial drop in the temperature measurements, identifying a longest consecutive increasing pressure sequence in the pressure measurements from a selected start time to a transmission end time to provide terminating pressure data as a function of time, comparing the pressure sequence to a reference, and making a determination regarding the capsule exiting the gastrointestinal tract of the subject as a function of the comparison, the analysis of the temperature measurements, and the analysis of the voltage measurements.

The step of making a determination regarding the capsule exiting the gastrointestinal tract of the subject may comprise the steps of determining if the comparison is a match, determining if there is a corresponding substantial drop in the temperature measurements and determining if there is a low voltage condition. The method may further comprise the step of providing a positive determination regarding the capsule exiting the gastrointestinal tract when the comparison is a match, there is the corresponding substantial drop in the temperature measurements, and there is not the low voltage condition. The method may further comprise the step of providing a negative determination regarding the capsule exiting the gastrointestinal tract when the comparison is not a match, there is not the corresponding substantial drop in the temperature measurements, or there is the low voltage condition.

In another aspect, the invention provides a method of determining body exit of an ingestible capsule comprising the steps of providing an ingestible capsule having a pressure sensor and a temperature sensor, having a subject ingest the capsule, recording measurements from the pressure sensor and the temperature sensor as the capsule passes through at least an end portion of a gastrointestinal tract of the subject, transmitting the measurements to a processor outside of the gastrointestinal tract of the subject, analyzing the temperature measurements for a decrease in temperature, providing (49) a terminating data (69) set for the pressure and temperature measurements between the first decrease in temperature (73) and the transmission end time (63), analyzing (51) the terminating data set to determine a relationship between the pressure and the temperature measurements, comparing (57) the relationship to a reference (71), and using the comparison to make a determination regarding the capsule exiting the gastrointestinal tract of the subject.

The reference may comprise a thermal coefficient of sensitivity for the pressure sensor in pressure units per units of temperature, and the relationship may comprise the slope of a linear regression of the terminating data set. The step of analyzing the terminating data set may comprise the steps of organizing the pressure and temperature measurements into data pairs (69), performing a linear regression with respect to the data pairs to provide a best fit line (70), and determining the slope of the best fit line. The step of comparing the relationship to a reference may comprise comparing the slope to the thermal coefficient of sensitivity for the pressure sensor. The method may further comprise the step of providing a positive determination (54) regarding the capsule exiting the gastrointestinal tract of the subject when the comparison is positive. The method may further comprise the step of conditioning the pressure measurements prior to the step of providing a terminating data set for the pressure and temperature measurements between the decrease in temperature and the transmission end time, and the step of conditioning the pressure measurements may comprise the steps of screening the pressure measurements to verify that they are valid, converting the pressure measurements to units of pressure, and scaling the units of pressure such that ambient atmospheric pressure is set at a zero baseline. The step of transmitting the measurements to a processor may comprise the steps of transmitting the measurements from the capsule to a receiver outside of the gastrointestinal tract of the subject, and downloading the measurements from the receiver to the processor. The selected start time may be about one hour prior to the transmission end time. The ingestible capsule may further comprise a power source adapted to provide current to an electrical circuit housed in the capsule and the method may further comprise the steps of measuring voltage for the circuit as the capsule passes through the gastrointestinal tract of the subject, transmitting the voltage measurements to the processor, analyzing the voltage measurements for a low voltage condition and using the analysis of the voltage measurements to make the determination regarding the capsule exiting the gastrointestinal tract of the subject. The low voltage condition may comprise a series of decreasing voltage measurements over a time period. The method may further comprise the steps of determining (50) a correlation value between temperature and pressure data in the terminating data set, and using the correlation value to make a determination regarding the capsule exiting the gastrointestinal tract of the subject, and the step of determining a correlation value between temperature and pressure data in the terminating data set may comprise the step of performing a linear regression with respect to the data set. The correlation value may be an R-squared correlation coefficient for the linear regression. A correlation coefficient of about 0.9 or greater may indicate that the determination is positive and a correlation coefficient of less than about 0.9 may indicate that the determination is not positive.

In another aspect, the invention provides a method of determining body exit of an ingestible capsule comprising the steps of providing an ingestible capsule having a pressure sensor and a temperature sensor, having a subject ingest the capsule, recording measurements from the pressure sensor and the temperature sensor as the capsule passes through at least an end portion of a gastrointestinal tract of the subject, transmitting the measurements to a processor outside of the gastrointestinal tract of the subject, analyzing the temperature measurements for a decrease in temperature, providing a terminating data set for the pressure and temperature measurements between the decrease in temperature and the transmission end time, determining (50) a correlation value between temperature and pressure data in the terminating data set, and using the correlation value to make a determination regarding the capsule exiting the gastrointestinal tract of the subject.

The step of determining a correlation value between temperature and pressure data in the terminating data set may comprise the step of performing a linear regression (70) with respect to the data set. The correlation value may be an R-squared correlation coefficient for the linear regression. A correlation coefficient of about 0.9 or greater may indicate that the determination is positive and a correlation coefficient of less than about 0.9 may indicate that the determination is not positive.

In another aspect, the invention provides a computer-readable medium having computer-executable instructions for performing a method comprising receiving pressure measurements recorded by a pressure sensor on an ingestible capsule ingested by a subject, identifying an increasing pressure sequence in the measurements between a selected start time and a transmission end time, comparing the sequence to a reference, and using the comparison to make a determination regarding the capsule exiting the gastrointestinal tract of the subject.

The increasing pressure sequence may be the longest increasing pressure sequence in the measurements. The reference may be a logarithmic regression of the measurements. The medium may further comprise receiving temperature measurements recorded by a temperature sensor on the ingestible capsule, analyzing the temperature measurements for a substantial drop in the temperature measurements, and using the analysis of the temperature measurements to make the determination regarding the capsule exiting the gastrointestinal tract of the subject. The medium may further comprise conditioning the measurements between the selected start time and the transmission end time to provide terminating pressure data as a function of time, and wherein the increasing pressure sequence is identified in the terminating pressure data, and conditioning the measurements may comprise screening the measurements to verify that they are valid, converting the measurements to units of pressure, and scaling the units of pressure such that ambient atmospheric pressure is set at a zero baseline. The selected start time may be about one hour prior to the transmission end time. The medium my further comprise the steps of receiving voltage measurements recorded by the ingestible capsule, analyzing the voltage measurements for a low voltage condition, and using the analysis of the voltage measurements to make the determination regarding the capsule exiting the gastrointestinal tract of the subject.

In another aspect, the invention provides a system for identifying the body exit of an ingestible capsule from a gastrointestinal tract comprising an ingestible capsule having a pressure sensor adapted to record pressure data as a function of time as the capsule passes through at least a portion of a subject's gastrointestinal tract, a receiver adapted to received the data when transmitted from the capsule, a processor adapted to communicate with the receiver, a display in communication with the processor, the processor programmed to receive pressure measurements recorded by the pressure sensor, identify an increasing pressure sequence in the measurements between a selected start time and a transmission end time, compare the sequence to a reference, and use the comparison to make a determination regarding the capsule exiting the gastrointestinal tract of the subject.

The increasing pressure sequence may be the longest increasing pressure sequence in the measurements, and the reference may be a logarithmic regression of the measurements. The ingestible capsule may further comprise a temperature sensor adapted to record temperature data as a function of time as the capsule passes through at least a portion of a subject's gastrointestinal tract, and the processor may be further programmed to receive temperature measurements recorded by the temperature sensor, analyze the temperature measurements for a substantial drop in the temperature measurements, and use the analysis of the temperature measurements to make the determination regarding the capsule exiting the gastrointestinal tract of the subject. The processor may be further programmed to condition the measurements between the selected start time and the transmission end time to provide terminating pressure data as a function of time, and wherein the increasing pressure sequence is identified in the terminating pressure data. Conditioning the measurements may comprise screening the measurements to verify that they are valid, converting the measurements to units of pressure, scaling the units of pressure such that ambient atmospheric pressure is set at a zero baseline. The selected start time may be about one hour prior to the transmission end time. The processor may be further programmed to receive voltage measurements recorded by the ingestible capsule, analyze the voltage measurements for a low voltage condition, and use the analysis of the voltage measurements to make the determination regarding the capsule exiting the gastrointestinal tract of the subject.

In another aspect, the invention provides a computer-readable medium having computer-executable instructions for performing a method comprising receiving pressure measurements recorded by a pressure sensor and temperature measurements recorded by a temperature sensor on an ingestible capsule ingested by a subject, analyzing the temperature measurements for a decrease in temperature, providing a terminating data set for the pressure and temperature measurements between the decrease in temperature and a transmission end time, analyzing the terminating data set to determine a relationship between the pressure and the temperature measurements, comparing the relationship to a reference, and using the comparison to make a determination regarding the capsule exiting the gastrointestinal tract of the subject. The reference may comprise a thermal coefficient of sensitivity for the pressure sensor in pressure units per units of temperature. The relationship may comprise the slope of a linear regression of the terminating data set. Analyzing the terminating data set may comprise organizing the pressure and temperature measurements into data pairs, performing a linear regression with respect to the data pairs to provide a best fit line, and determining the slope of the best fit line. Comparing the relationship to a reference may comprise comparing the slope to the thermal coefficient of sensitivity for the pressure sensor. The medium may further comprise determining a correlation value between temperature and pressure data in the terminating data set, and using the correlation value to make a determination regarding the capsule exiting the gastrointestinal tract of the subject. Determining a correlation value between temperature and pressure data in the terminating data set may comprise performing a linear regression with respect to the data set. The correlation value may be an R-squared correlation coefficient for the linear regression. A correlation coefficient of about 0.9 or greater may indicate that the determination is positive and a correlation coefficient of less than about 0.9 may indicate that the determination is not positive.

In another aspect, the invention provides a computer-readable medium having computer-executable instructions for performing a method comprising receiving pressure measurements recorded by a pressure sensor and temperature measurements recorded by a temperature sensor on an ingestible capsule ingested by a subject, analyzing the temperature measurements for a decrease in temperature, providing a terminating data set for the pressure and temperature measurements between the decrease in temperature and a transmission end time, determining a correlation value between temperature and pressure data in the terminating data set, and using the correlation value to make a determination regarding the capsule exiting the gastrointestinal tract of the subject.

Determining a correlation value between temperature and pressure data in the terminating data set may comprise performing a linear regression with respect to the data set, and the correlation value may be an R-squared correlation coefficient for the linear regression. A correlation coefficient of about 0.9 or greater may indicate that the determination is positive and a correlation coefficient of less than about 0.9 may indicate that the determination is not positive.

Accordingly, the general object is to provide a method for determining the body exit time of an ingestible capsule.

Another object is to provide a method for confirming the expulsion time of a capsule from the gastrointestinal tract of a subject based on pressure and temperature patterns.

These and other objects and advantages will become apparent from the foregoing and ongoing written specification, the drawings, and the claims.

DESCRIPTION OF PREFERRED EMBODIMENTS

Referring now to the drawings and, more particularly, toFIG. 1thereof, this invention provides a new method for determining the body exit time of an ingested capsule from the gastrointestinal tract of a subject, of which a first embodiment is generally indicated at14. As shown inFIG. 10, process14is performed using capsule system15, which generally includes ingestible capsule20, receiver17, and computer workstation19. Capsule20includes pressure sensor assembly23and temperature sensor22for taking measurements of pressure and temperature, respectively, of a subject's gastrointestinal tract, capacitor24, power source21, and transmitter16for transmitting the measurement data. Receiver17is configured to receive signals sent from transmitter16. Computer workstation19includes processor31and is programmed to process measurements from pressure sensor23, temperature sensor22, and capacitor24to determine capsule20's body exit time (BET).

As shown inFIG. 11, capsule20is generally a cylindrical member elongated about axis y-y and having generally rounded closed ends, somewhat resembling a medicament capsule. The capsule generally has a hard shell or casing which houses the transmitting electronics, a battery compartment, power supply21, transmitter16, an antenna, an activation switch, pressure sensor assembly23, temperature sensor22and capacitor24. Capsule20is adapted to be ingested or otherwise positioned within a tract to sense both pressure and temperature within the tract and to transmit such readings to receiver17. The capsule is generally provided with an outer surface to facilitate easy swallowing of the capsule. In this embodiment, capsule20is an autonomous swallowable capsule and is self-contained. Thus, capsule20does not require any wires or cables to, for example, receive power or transmit information. The pressure and/or temperature data is transmitted from capsule20within the gastrointestinal tract to a remote data receiver17.

Pressure sensor assembly23comprises a flexible sleeve26affixed to the shell of the capsule and defining a chamber28between the shell and the sleeve. Chamber28is filled with a fluid, which is a non-compressible medium that transfers a force acting upon sleeve26to sensing mechanism29of sensor23. In this embodiment, the fluid used is a dielectric gel. Alternatively, it is contemplated that other fluids, such as mineral oil, or an inert gas may be used. Sensor29is operatively arranged to communicate with chamber28through fluid port30at one end of the shell of the capsule. As shown inFIG. 11, pressure sleeve26of capsule20extends from a point below the middle of the capsule up over the top end of the capsule. Thus, pressure sensor29is operatively arranged to sense pressure within chamber28. An analog to digital converter is provided to convert the analog signal from sensor29to a digital signal.

In this embodiment, power supply21is a silver-oxide battery, although it is contemplated that other batteries may be used, such as a lithium battery. Power supply21is adapted to power the electrical components of capsule20when in the gastrointestinal tract of a subject.

Capsule20is ingested by a subject. Readings are then taken from sensors22,23, and24on capsule30as the capsule passes through at least the end of portion of the gastrointestinal tract of the subject. Data from temperature sensor22, pressure sensor23, and capacitor24is transmitted from transmitter16to data receiver17. Receiver17is generally worn on the belt of the subject and contains rechargeable batteries as its power source. Data receiver17records the transmitted data while the capsule passes through the subject's body. After data recording is complete, the data receiver is placed into a docking station. The docking station is connected to computer19through a USB connection. The docking station will recharge data receiver17's batteries and will transfer the recorded data from data receiver17to computer19. In this embodiment, computer19is a conventional laptop or desktop computer.

Once the data is downloaded to computer19, it is analyzed and used in determining the body exit time (BET) of capsule20from the subject. The computer workstation also uses the data to calculate several measures of confidence in the body exit time determination, which are used to make a determination if the BET calculation should be used or not52.

In this embodiment, computer19includes a processor31, data processing storage34, a monitor or display32and a user input device33. In this embodiment, monitor32is a computer screen. However, monitor32may be any other device capable of displaying an image or other data. In the preferred embodiment, user input device33includes a keyboard and a mouse. However, user input device33could be any other suitable input-output device for interfacing with data processor31.

The processing and analysis of the pressure, temperature, and voltage measurements from capsule20is generally provided using computer-executable instructions executed by a general-purpose computer, such as a server or personal computer19. However, it should be noted that this processing and analysis may be practiced with other computer system configurations, including internet appliances, hand-held devices, wearable computers, multi-processor systems, programmable consumer electronics, network PCs, mainframe computers and the like. The term computer or processor as used herein refers to any of the above devices as well as any other data processor. Some examples of processors are microprocessors, microcontrollers, CPUs, PICs, PLCs, PCs or microcomputers. A computer-readable medium comprises a medium configured to store or transport computer readable code, or in which computer readable code may be embedded. Some examples of computer-readable media are CD-ROM disks, ROM cards, floppy disks, flash ROMS, RAM, nonvolatile ROM, magnetic tapes, computer hard drives, conventional hard disks, and servers on a network. The computer systems described above are for purposes of example only. An embodiment of the invention may be implemented in any type of computer system or programming or processing environment. In addition, it is meant to encompass processing that is performed in a distributed computing environment, were tasks or modules are performed by more than one processing device or by remote processing devices that are run through a communications network, such as a local area network, a wide area network or the internet. Thus, the term processor is to be interpreted expansively.

Computer19is programmed to extract information from the pressure measurements taken by pressure sensor23, the temperature measurements taken by temperature sensor22, and the capacitor discharge times for capacitor24, and to use that data to make a determination regarding the BET of capsule20from the subject. The analysis and determination of BET is displayed in graphical form on monitor32for the user.

Referring now to the flow diagram inFIGS. 1A and 1B, capsule20is provided40to a subject and is ingested41by the subject. Temperature, pressure, and capacitor measurements are recorded42by sensors22and23and capacitor24. The raw data measurements are then transmitted43in data packets to receiver17, which is outside the gastrointestinal tract of the subject. After the recording period is complete, the receiver is then seated in a docking station connected to computer19through a USB connection which then transfers44the raw data from receiver17to computer19.

Next, the data is analyzed200by computer19and used to make a determination of whether the BET of capsule20can be established and, if so, the BET. This determination is a function of a number of different variables.

First, the raw data measurements are conditioned53by computer19through the removal of invalid packets, conversion of the data into proper units and the scaling of pressure to ambient. The invalid packets are screened using a conventional packet validation process. Next, the temperature and pressure measurements are respectively converted into units of degrees Celsius and millimeters of mercury. With respect to the capacitance measurements, capacitor24charges and discharges and the discharge times of capacitor24are recorded and transmitted within each data packet. The timing is then converted into a voltage reading. In this embodiment, power source voltage is calculated as 0.0195 multiplied by the discharge time less 2.0513. The constant 0.0195 is the voltage count portion and the constant 2.0513 is the voltage offset for this embodiment.

Next, computer19is programmed to identify256the last hour of data received from capsule20by receiver17. As shown inFIG. 2, the last recorded transmission is labeled as analysis end time63, and the time one hour prior to analysis end time63is labeled as analysis start time62.FIG. 3shows the cropped pressure data between the determined analysis start time62and analysis end time63. While in this embodiment, analysis end time63is defined as the transmission end time, it is contemplated that analysis end time63may be based on other parameters, such as an event that is recorded by the subject, elapsed time after ingestion, a particular recorded parameter, or a time otherwise identified by the user.

Signal filtering257of the pressure data with a moving average is then applied to smooth the cropped pressure data. In particular, in this embodiment a window of the five values on each side of each element in the data array is averaged together and this average value placed into a new array of smoothed values. This process is continued until all elements in the original array have been the center of a window. This smoothing is repeated three times to try to eliminate variations which might adversely impact the finding of the longest consecutive increasing sequence (LCIS) in pressure. While this smoothed data is used to determine the LCIS in pressure, it should be understood that the regressions discussed below may be applied to the unsmoothed data set after the LCIS in pressure has been determined.FIG. 4shows the pressure data fromFIG. 3after smoothing.

The program then searches246the conditioned temperature measurements between analysis begin time62and analysis end time63for a substantial and sustained temperature drop68, as shown inFIG. 7. If a substantial temperature drop68is identified249by this analysis46, the beginning73of that temperature drop is initially marked247as the BET. The beginning73of the drop in temperature68is identified by determining the average temperature for all of the temperature data and then searching backwards through the temperature data for the first temperature sample that is at least 1° C. less than the average. A substantial temperature drop is positively identified if such a drop in temperature of 1° C. or greater from the average is identified in the subject temperature measurements. However, if no substantial temperature drop is identified249, the program then analyzes263the pressure measurements in an attempt to determine the BET.

Unexpectedly, a certain pattern or sequence of increasing pressure65in the test data can be used to indicate the BET of capsule20. In particular, computer19is programmed to identify47the LCIS sequence65in the smoothed pressure data between selected analysis start time62and selected analysis end time63. The identified longest consecutive increasing pressure sequence65is characterized in this embodiment by a gradual and sustained increase in calibrated pressure of at least 1.6 mmHg/per minute continuing until the analysis end time (63). This LCIS is then compared to a reference48.

In this embodiment, computer19performs265a conventional linear regression analysis on the pressure vs. natural logarithm of time data for the increasing pressure sequence65. The following conventional linear regression equations are used for the slope and intercept of the best fit line66, and R2 is the coefficient of determination:

For the longest increasing pressure sequence of N data points (yi,ti); i=1 . . . N

The best fit line is given by

A high R2value indicates a strong linear correlation between pressure and ln (time). The calculated R2is unexpectedly a good indicator of whether the BET occurs at the beginning of the longest continuous increase in pressure. If R2is about 0.8 or greater, the pressure data is a good indicator of BET, and the start74of pressure tail65is marked as the BET as shown onFIG. 4. Alternatively, if the coefficient of determination is less than about 0.8, as shown inFIG. 6, then the pressure data is not used to determine BET.

In addition, the voltage data is used to evaluate45whether the BET determination is valid or not. Computer19is programmed to analyze the voltage measurements for a low voltage condition269. In the preferred embodiment, a low voltage condition is indicated when a series of decreasing voltage measurements over a time period are identified. Alternatively, the low voltage condition may be indicated when one or more voltage measurements are less than about 2.5 volts. However, the low voltage condition will depend on the particular circuitry of capsule20. A low voltage condition indicates a negative determination273regarding BET, as the pressure and temperature measurements are suspect. On the other hand, if a low voltage condition is not indicated and pressure tail65is identified that matches logarithmic curve66with a coefficient of determination (R2) of about 0.8 or greater, then a positive determination254for BET is marked, whether or not a drop in temperature68has been identified in temperature data249.

Computer19is programmed to provide other confirming or non-confirming variables for determining BET. As described above, computer19is programmed to search for a substantial drop in the temperature data246in the last hour of data62to63. If a substantial temperature drop has been identified249the computer19will then mark247the BET at the beginning of the temperature drop73.

Computer19analyzes the relationship51between the conditioned temperature and pressure data51and compares57such relationship to a reference and determines a correlation value50for the data. In this embodiment, the program provides a terminating data set49of pressure and temperature measurements69, which is essentially a plot of temperature verses pressure between the beginning73of the drop in temperature68and the end63of pressure tail65, as shown inFIG. 8.

The program then performs a conventional linear regression analysis249of the pressure and temperature measurements in the terminating data set49. The following conventional linear regression equations are used for the slope and intercept of the best fit line66, and R2 is the coefficient of determination:

For the sequence of N data points (yi,xi); i=1 . . . N

The best fit line is given by

FIG. 9is a plot of the pressure vs. temperature curve69from temperature drop point73to analysis end point63. The calculated slope of the best fit line is then checked250to see if it is within a target range. In this embodiment, the target range is set to the expected thermal coefficient of sensitivity for pressure sensor23. The thermal coefficient of sensitivity is a predetermined measure of how the pressure sensor measurement is expected to vary with temperature. In the preferred embodiment, the thermal coefficient of sensitivity of pressure sensor23is about −0.7 to about −3 mmHg/C. If the slope of line70does not fall within the target range, it will indicate a negative determination254for BET with respect to this variable. If the slope of best fit line70falls within the range of about −0.7 to about −3, it indicates a positive determination for BET with respect to the slope of the best fit line and the program will next analyze the R2of the best fit line252.

In this embodiment, the program determines R2of best fit line70. A high R2value indicates a strong linear correlation between pressure and temperature. The calculated R2is unexpectedly a good indicator of whether the BET occurs at the beginning of the LCIS in pressure. An R2of 0.9 or greater indicates that the data is likely to yield a positive estimate of BET, and prompts the computer19to check for a low voltage condition269in the data as discussed earlier. However, if the R2correlation coefficient of the linear regression is less than about 0.9, then the analysis indicates a negative determination254regarding BET.

After the computer19has determined whether the BET calculation is positive273or negative254, the result is displayed56on computer monitor32.

While the above embodiments have been described in relation to the gastrointestinal tract of a human, it is contemplated that the system may be used in connection with the gastrointestinal tract of other animals.

The present invention contemplates that many changes and modifications may be made. Therefore, while the presently-preferred form of the improved method has been shown and described, and a number of alternatives discussed, persons skilled in this art will readily appreciate that various additional changes and modifications may be made without departing from the spirit of the invention, as defined and differentiated by the claims.