Analysis compensation including segmented signals

• US 9,775,806 B2
• Filed: 09/20/2012
• Issued: 10/03/2017
• Est. Priority Date: 09/21/2011
• Status: Active Grant

• Current Assignee: Ascensia Diabetes Care Holdings AG (PHC Holdings Corporation)
• Original Assignee: Ascensia Diabetes Care Holdings AG (PHC Holdings Corporation)
• Inventors: Wu, Huan-Ping
• Primary Examiner(s): Vanni, G. Steven
• Application Number:
  US13/623,654
• Publication Number:
  US 20130071869A1
• Time in Patent Office: 1,839 Days
• Field of Search: None
• CPC Class Codes: A61K 31/198 Alpha-amino acids, e.g. alanine or edetic acid [EDTA] betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/19 lyophilised , i.e. freeze-dried, solutions or dispersions lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00
• CPC Class Codes: G01N 27/3274 Corrective measures, e.g. error detection, compensation for temperature or hematocrit, calibration coding of calibration information G01N33/48771

Abstract

A biosensor system determines analyte concentration from an output signal generated from a light-identifiable species or a redox reaction of the analyte. The biosensor system compensates at least 50% of the total error in the output signal with a primary function and may compensate a portion of the residual error with at least one residual function. A segmented signal processing (SSP) function may serve as the primary function, first residual function, or second residual function. Preferably, when the SSP function serves as the first residual function, the SSP function compensates at least 50% of the residual error remaining after primary compensation. Preferably, when the SSP function serves as the second residual function, the SSP function compensates at least 50% of the residual error remaining after primary and first residual compensation. The error compensation provided by the primary, first residual, and second residual functions may be adjusted with function weighing coefficients.

Claims

1. A method of operating a biosensor system, the method using the processor in performing steps comprising:

providing a biosensor system in the form of an analytical instrument including

a measurement device having electrical circuitry communicatively coupled to a processor, a storage medium, a signal generator, and a sensor interface, the processor having instructions and data stored in the storage medium, and

a test sensor having a base and a sample interface, the base forming a reservoir and a channel with an opening, the reservoir being in electrical or optical communication with the measurement device;

receiving the biological fluid sample in the opening of the reservoir, the biological fluid sample flowing through the channel to fill at least in part the reservoir of the test sensor, the biological fluid sample including the analyte;

in response to receiving the biological fluid sample in the reservoir, generating an input signal, by the processor, from the signal generator the input signal including at least two time-separated excitations, each excitation having a respective time period with an end-point;

transmitting the input signal by the sensor interface to the sample interface for applying the input signal to the biological fluid sample;

in response to the input signal and the concentration of the analyte in the biological fluid sample, generating, by the processor, an output signal from the test sensor, the output signal being one or more of a light-generated output signal in response to a light-identifiable species and an electrical output signal generated by a redox reaction;

segmenting, by the processor, within each period of excitation, the output signal during that excitation period into at least two segments with a regular or irregular segmenting interval, each segment including point readings obtained before the end-point of the input signal during that excitation period;

converting, by the processor, the at least two segments into at least two signal processing parameters, wherein the signal processing parameters describe a portion of a total error in the output signal;

determining, by the processor, a segmented signal processing function from the signal processing parameters;

using, by the processor, a predetermined reference correlation to relate the output signal to a plurality of known sample analyte concentrations;

in response to the predetermined reference correlation, using, by the processor, a conversion function to convert the output signal into one known sample analyte concentration of the plurality of known sample analyte concentrations;

determining, by the processor, a compensated value from the output signal in response to the conversion function and the segmented signal processing function;

determining, by the processor, the analyte concentration in the biological fluid sample from the compensated value of the output signal; and

outputting, by the processor, the analyte concentration to one or more of a display, a remote receiver, or a storage medium.

2. The method of claim 1, where the output signal is responsive to a concentration of a measurable species in the biological fluid sample and the concentration of the measurable species in the biological fluid sample is responsive to the concentration of the analyte in the biological fluid sample.

3. The method of claim 2, where the concentration of the measurable species in the biological fluid sample is responsive to a chemical reaction between the analyte, an enzyme, and a mediator, where the chemical reaction is the redox reaction.

4. The method of claim 2, where the measurable species is light-identifiable.

5. The method of claim 1, further comprising continuously applying the input signal to the sample until an analysis end-point is reached.

6. The method of claim 5, further comprising measuring at least three output signal values from the output signal.

7. The method of claim 1, where the input signal is gated and where each excitation is applied until an intermediate analysis end-point is reached.

8. The method of claim 7, further comprising measuring at least two output signal values from the output signal of each of the at least two excitations.

9. The method of claim 1, where the segmented signal processing function is predetermined.

10. The method of claim 9, where the at least two signal processing parameters are determined from the output signal with a parameter determining method selected from the group consisting of averaging of signals within a segment, determining ratios of the signal values from within a segment, determining differentials of the signal values from within a segment, determining time-based differentials, determining normalized differentials, determining time-based normalized differentials, determining one or more decay constants, and determining one or more decay rates.

11. The method of claim 9, where the at least two signal processing parameters are determined using a parameter determining method selected from the group consisting of determining differentials of the signal values from within a segment, determining time-based differentials, determining normalized differentials, and determining time-based normalized differentials.

12. The method of claim 9, where the at least two signal processing parameters are determined using a parameter determining method selected from the group consisting of determining time-based differentials and determining time-based normalized differentials.

13. The method of claim 1, further comprising:

converting the output signal with the conversion function before applying the segmented signal processing function.

14. The method of claim 13, where the determining the compensated value from the output signal in response to the conversion function and the segmented signal processing function, further comprises determining the compensated value from the output signal in response to a primary function, where the segmented signal processing function is not the primary function, and where the primary function describes a major error in the output signal and relates uncompensated output values and error contributors, the major error being attributable to one or more major error contributors selected from a group consisting of temperature, hematocrit, and hemoglobin.

15. The method of claim 14, where error described by the segmented signal processing function is substantially different than error described by the primary function.

16. The method of claim 14, further comprising modifying the segmented signal processing function and the primary function with function weighing coefficients.

17. The method of claim 14, where the primary function includes an index function, where the index function relates at least three error parameters to a previously determined expression of total error.

18. The method of claim 17, where the index function is complex, the complex index function comprising:

at least one term having a hematocrit error parameter, and

at least one term having a temperature error parameter.

19. The method of claim 18, where the complex index function includes a first term and a second term, where the first and the second terms are each modified by a different complex index function term weighing coefficient, the first and the second terms include respective error parameters of the at least three error parameters, the respective error parameters being independently selected from intermediate output signal values, values external to the output signal, or both.

20. The method of claim 14, where the segmented signal processing function describes at least 50% of residual error in the compensated value after the primary function compensates the output signal.

21. The method of claim 14, where the method further comprises determining the compensated value from the output signal in response to a residual function, the residual function compensating a compensation deficiency provided by the segmented signal processing function and the primary function, where the residual function is not the segmented signal processing function, and where the residual function is not the primary function.

22. The method of claim 21, further comprising modifying the segmented signal processing function, the primary function, and the residual function with function weighing coefficients.

23. The method of claim 21, where error described by the segmented signal processing function is substantially different error than error described by the residual function, and where error described by the segmented signal processing function is substantially different than error described by the primary function.

24. The method of claim 1, where the analyte concentration in the biological fluid sample determined from the compensated value includes 30% less relative error than if the analyte concentration in the biological fluid sample were determined from the output signal and the conversion function without the segmented signal processing function.

25. The method of claim 24, where the analyte concentration in the biological fluid sample determined from the compensated value includes 50% less relative error than if the analyte concentration in the biological fluid sample were determined from the output signal and the conversion function without the segmented signal processing function.

26. The method of claim 1, where the segmented signal processing function includes an index function relating at least a first and a second term to a previously determined expression of total error.

27. The method of claim 26, where the index function is complex, the at least two terms are segmented signal processing parameters independently selected from segmented output signal values, and where each of the at least two terms are modified by a different complex index function term weighing coefficient.

28. The method of claim 26, where the index function is complex, the complex index function including

at least one term having a hematocrit error parameter or a hemoglobin error parameter, and

at least one term having a temperature error parameter.

29. The method of claim 28, where the first and the second terms are each modified by a different complex index function term weighing coefficient, the first and the second terms each include respective segmented signal processing parameters of the one or more segmented signal processing parameters.

30. The method of claim 1, where the sample is blood and the analyte is glucose.

31. The method of claim 1, where the determining the compensated value includes altering a reference correlation of the conversion function with a change in slope value determined from the signal processing function, where the reference correlation relates the output signal to the other known sample analyte concentrations.

32. The method of claim 1, wherein the output signal is further selected from one or more of a current output signal generated by amperometry or voltammetry, a potential output signal generated by potentiometry or galvanometry, and an accumulated charge output signal generated by coulometry.

33. A biosensor system for determining an analyte concentration in a biological fluid sample, the biosensor system being an optical system or an electrochemical system, the biosensor system comprising:

a test sensor having a base and a sample interface, the base forming a reservoir and a channel with an opening, the opening being configured to receive the biological fluid sample and to allow the biological fluid sample to flow through the channel to fill at least in part the reservoir, the reservoir being in electrical or optical communication with the measurement device;

a measurement device in electrical or optical communication with the reservoir, the measurement device having electrical circuitry communicatively coupled to a processor, a storage medium, a signal generator, and a sensor interface, the processor having instructions and data stored in the storage medium, the instructions configured such that when executed by the processor the system is enabled so that;

in response to receiving the biological fluid sample in the reservoir, the signal generator applies an electrical or optical input signal to the sensor interface, the input signal including at least two time-separated excitations, each excitation having a respective time period with an end-point,

the input signal is transmitted by the sensor interface to the sample interface for applying the input signal to the biological fluid sample,

in response to the input signal and to the concentration of the analyte in the biological fluid sample, the processor generates an output signal from test sensor, the output signal being one or more of a light-generated output signal in response to a light-identifiable species and an electrical output signal generated by a redox reaction,

the processor compensates at least 50% of the total error in the output signal with a primary function, where the primary function describes a major error in the output signal and relates uncompensated output values and error contributors, the major error being attributable to one or more major error contributors selected from a group consisting of temperature, hematocrit, and hemoglobin,

if the primary function is not a segmented signal processing function, the processor compensates at least 5% of the remaining error in the output signal with a segmented signal processing function,

the processor segments, within each period of excitation, the output signal during that excitation period into at least two segments, each segment including point readings obtained before the end-point of the input signal that excitation period,

the processor converts the at least two segments into at least two signal processing parameters wherein the signal processing parameters describe a portion of the total error in the output signal,

the processor determines the segmented signal processing function from the signal processing parameter,

the processor determines a compensated value from the output signal in response to the primary function and the segmented signal processing function,

the processor determines the analyte concentration in the sample from the compensated value, and

wherein the processor outputs the analyte concentration to one or more of a display, a remote receiver, or a storage medium.

34. A method of operating a biosensor system for determining an analyte concentration in a biological fluid sample, the biosensor system being an optical sensor system or an electrochemical sensor system, the biosensor system including a measurement device and a test sensor, the measurement device having a processor, the test sensor being in electrical or optical communication with a reservoir, the method using the processor in performing steps comprising:

receiving the biological fluid sample in the reservoir of the test sensor, the biological fluid sample including the analyte;

applying an input signal to the biological fluid sample, the input signal including at least two time-separated excitations, each excitation having a respective time period with an end-point;

generating, via the biosensor system, an output signal responsive to the input signal and further responsive to the concentration of the analyte, the output signal being one or more of a light-generated output signal in response to a light-identifiable species and an electrical output signal generated by a redox reaction;

segmenting, within each period of excitation, the output signal during that excitation period into at least two segments, each segment including point readings obtained before the end-point of that excitation period;

converting the at least two segments into at least two signal processing parameters, wherein the signal processing parameters describe a portion of a total error in the output signal;

determining a segmented signal processing function from the signal processing parameter;

determining a compensated value from the output signal in response to the segmented signal processing function;

determining the analyte concentration from the compensated value of the output signal; and

outputting the analyte concentration to one or more of a display, a remote receiver, or a storage medium.

35. A method of operating a biosensor system for determining a desired segmented signal processing function that compensates an analyte concentration of a biological fluid sample, the biosensor system being an optical sensor system or an electrochemical sensor system, the biosensor system including a measurement device and a test sensor, the measurement device having a processor, the test sensor being in electrical or optical communication with a reservoir, the method using the processor in performing steps comprising:

receiving the biological fluid sample in the reservoir of the test sensor, the biological fluid sample including the analyte;

applying an input signal to the biological fluid sample, the input signal including at least two time-separated excitations, each excitation having a respective time period with an end-point;

generating, via the biosensor system, an output signal responsive to the input signal and further responsive to the concentration of the analyte, the output signal being one or more of a light-generated output signal in response to a light-identifiable species, an electrical output signal generated by an oxidation, an electrical output signal generated by a reduction and an electrical output signal generated by a redox reaction;

segmenting, within each period of excitation, the output signal during that excitation period into at least three segments, each segment including point readings obtained before the end-point of that excitation period;

converting the at least three segments into at least three segmented signal processing parameters;

selecting multiple ones of the at least three segmented signal processing parameters as potential terms in a segmented signal processing function, the selected multiple ones of the at least three segmented signal processing parameters describing at least a portion of a total error in the output signal;

determining a first exclusion value for the potential terms;

applying an exclusion test responsive to the first exclusion value for the potential terms;

identifying one or more of the potential terms for exclusion from the segmented signal processing function;

excluding one or more identified potential terms from the segmented signal processing function;

determining a desired segmented signal processing function based on at least two remaining identified potential terms of the segmented signal processing function;

determining a compensated value from the output signal in response to the desired segmented signal processing function;

determining the analyte concentration from the compensated value of the output signal; and

outputting the analyte concentration to one or more of a display, a remote receiver, or a storage medium.