Slope-based compensation including secondary output signals

• US 9,164,076 B2
• Filed: 05/27/2011
• Issued: 10/20/2015
• Est. Priority Date: 06/07/2010
• Status: Active Grant

• Current Assignee: Ascensia Diabetes Care Holdings AG (PHC Holdings Corporation)
• Original Assignee: Bayer Healthcare LLC (Bayer AG)
• Inventors: Huang, Dijia, Wu, Huan-Ping
• Primary Examiner(s): Lau, Tung S
• Assistant Examiner(s): SUN, XIUQIN
• Application Number:
  US13/117,872
• Publication Number:
  US 20110301857A1
• Time in Patent Office: 1,607 Days
• Field of Search: 702/19
• US Class Current: 1/1
• CPC Class Codes: G01N 27/3274 Corrective measures, e.g. error detection, compensation for temperature or hematocrit, calibration coding of calibration information G01N33/48771
• CPC Class Codes: G01N 33/48714 for determining substances foreign to the organism, e.g. drugs or heavy metals drugs by chemical analysis G01N33/94

Abstract

A biosensor system determines analyte concentration from analytic and/or secondary output signals. The biosensor system adjusts a correlation for determining analyte concentrations from output signals with one or more index functions extracted from the output signals. The index functions determine at least one slope deviation or normalized slope deviation from one or more error parameters. The slope-adjusted correlation between analyte concentrations and output signals may be used to determine analyte concentrations having improved accuracy and/or precision from output signals including components attributable to bias.

Claims

1. A method for determining an analyte concentration in a biological sample using a biosensor system comprising a sample interface having a working electrode and a counter electrode, a processor, and a signal generator connected to the processor, comprising:

generating by the processor, a command to direct the signal generator to provide an electrical input signal;

applying the electrical input signal provided by the signal generator to the biological sample through the working electrode and the counter electrode of the sample interface,

generating from the electrical input signal at least one output signal in response to a redox reaction of an analyte from the biological sample;

generating using the processor a second command to direct the signal generator to provide a second electrical input signal;

applying the second electrical input signal to the biological sample through an electrochemical or optical sensor system;

in response to the second command, generating multiple secondary output signals using the electrochemical or optical sensor system from the biological sample independently from the at least one output signal and redox reaction of the analyte from the biological sample;

determining by the processor at least one index function responsive to at least one error parameter from the at least one output signal and at least two error parameters from the multiple secondary output signals; and

determining by the processor, the analyte concentration in the biological sample from the at least one output signal and a slope compensation equation responsive to the at least one index function, where the slope compensation equation includes at least one reference correlation and at least one slope deviation,

where the at least one index function represents the influence of the error parameters on the slope deviation, and

where the at least one index function is responsive to at least one of a slope deviation of the error parameters and an intercept deviation of error parameters.

2. The method of claim 1 further comprising extracting the at least one index function from at least one of an intermediate signal and the secondary output signal.

3. The method of claim 1, where the determining the analyte concentration in the biological sample includes adjusting a correlation relating the output signal to the analyte concentration in the biological sample with the slope compensation equation.

4. The method of claim 3, where a %-bias of the determined analyte concentration is ±

10.4%.

5. The method of claim 3, where the %-bias of the determined analyte concentration is ±

5.4%.

6. The method of claim 1, where the determining the analyte concentration in the biological sample includes determining an analyte concentration without the slope compensation, then correcting the analyte concentration determined without the slope compensation equation with the slope compensation equation.

7. The method of claim 6, where a %-bias of the determined analyte concentration is ±

10.4%.

8. The method of claim 6, where the %-bias of the determined analyte concentration is ±

5.4%.

9. The method of claim 1, where the determining the analyte concentration in the biological sample includes adjusting the at least one output signal with the slope compensation equation.

10. The method of claim 9, where a %-bias of the determined analyte concentration is ±

10.4%.

11. The method of claim 9, where the %-bias of the determined analyte concentration is ±

5.4%.

12. The method of claim 1, where the slope compensation equation is responsive to an intercept deviation of the at least one error parameter.

13. The method of claim 1, where the index function is at least one of a complex index function and a part of a predictor function, where the slope compensation equation is responsive to the complex index function or to the predictor function.

14. The method of claim 13, where the predictor function is responsive to the total slope deviation.

15. The method of claim 13, further comprising selecting terms for inclusion in a complex index function responsive to an exclusion test.

16. The method of claim 1, where the at least one slope deviation is responsive to a %-bias of the analyte concentration otherwise determined from the at least one output signal.

17. A method for determining an analyte concentration in a biological sample using a biosensor system comprising a sample interface having a working electrode and a counter electrode, a processor, and a signal generator connected to the processor, the method comprising:

generating by the processor, a command to direct the signal generator to provide an electrical input signal;

applying the electrical input signal provided by the signal generator to the biological sample through the counter electrode and the working electrode of the sample interface,

generating from the electrical input signal, at least one analytic output signal in response to a redox reaction of an analyte from the biological sample;

generating using the processor a second command to direct the signal generator to provide a second electrical input signal;

generating a first secondary output signal from the biological sample in response to the second command;

generating a second secondary output signal in response to the second command;

determining by the processor at least one index function responsive to at least one error parameter from the first secondary output signal and one error parameter responsive to at least one error parameter from the second secondary output signal;

adjusting a correlation for determining the analyte concentration in the biological sample from the at least one analytic output signal with a slope compensation equation responsive to the at least one index function, where the slope compensation equation includes at least one reference correlation and at least one slope deviation; and

determining the analyte concentration in the biological sample from the at least one analytic output signal and the correlation,

where the at least one index function represents the influence of the error parameters on the slope deviation, and

where the at least one index function is responsive to at least one of a slope deviation of the error parameters or an intercept deviation of the error parameters.

18. The method of claim 17, further comprising determining the at least one index function responsive to at least one error parameter from the at least one analytic output signal.

19. The method of claim 17, further comprising determining the at least one index function responsive to at least one error parameter from an intermediate signal of the analytic output signal.

20. The method of claim 17, where the %-bias of the determined analyte concentration is ±

10.4%.

21. The method of claim 17, where the %-bias of the determined analyte concentration is ±

5.4%.

22. The method of claim 17, where the slope compensation equation is responsive to an intercept deviation of the at least one error parameter.

23. The method of claim 17, further comprising adjusting the slope and intercept deviations in response to the secondary output signal.

24. The method of claim 17, where the index function is at least one of a predictor function and a complex index function.

25. The method of claim 24, where the predictor function is responsive to the total slope deviation.

26. The method of claim 24, further comprising selecting terms for inclusion in a complex index function responsive to an exclusion test.

27. The method of claim 17, where the at least one slope deviation is responsive to a %-bias of the analyte concentration otherwise determined from the at least one output signal.

28. The method of claim 17, where the slope compensation equation includes error parameters from the analytic and secondary output signals.

29. The method of claim 17, where

the biological sample is whole blood,

a %-bias of the analyte concentration is from the hematocrit content of the whole blood,

one of the at least two error parameters is from the analytic output signal,

another of the at least two error parameters is from the secondary output signal, and where

the index function is responsive to the at least two error parameters.