Accurate analyte measurements for electrochemical test strip based on multiple discrete measurements defined by sensed physical characteristic(s) of the sample containing the analyte

• US 9,638,656 B2
• Filed: 12/28/2012
• Issued: 05/02/2017
• Est. Priority Date: 12/29/2011
• Status: Active Grant

• Current Assignee: Cilag Gmbh International (Johnson & Johnson)
• Original Assignee: LifeScan Scotland Limited (Johnson & Johnson)
• Inventors: Malecha, Michael
• Primary Examiner(s): White, Dennis M
• Application Number:
  US14/354,377
• Publication Number:
  US 20140291167A1
• Time in Patent Office: 1,586 Days
• CPC Class Codes: G01N 27/26 by investigating electrochemical variables; by using electrolysis or electrophoresis
• CPC Class Codes: G01N 27/3272 Test elements therefor, i.e. disposable laminated substrates with electrodes, reagent and channels optical biosensors G01N33/52
• 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: G16B 40/00 ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
• CPC Class Codes: G16B 40/10 Signal processing, e.g. from mass spectrometry [MS] or from PCR

Abstract

Various embodiments that allow for a more accurate analyte concentration by determining at least one physical characteristic, particularly hematocrit, of the blood sample containing the analyte, particularly glucose, and deriving a specific sampling time based on a relationship between the physical characteristic and sampling time so that the analyte concentration can be determined with greater accuracy with the specific sampling time point.

Claims

1. A method of determining an analyte concentration from a physiological sample with a biosensor having at least two electrodes and a reagent disposed on at least one electrode of the electrodes, the method comprising:

depositing a physiological sample on any one of the at least two electrodes to start an analyte test sequence;

applying a first signal to the sample to derive a physical characteristic of the sample;

driving a second signal to the sample for a first sampling time duration that overlaps with the test sequence to obtain a first transient signal output from the sample, the first transient signal correlated to both time and magnitude during the first sampling time duration;

extracting a specific sampling time during the test sequence in the first sampling time duration based on the physical characteristic of the sample, extracting the specific sampling time comprising calculating a defined specific sampling time in the first sampling time duration based on the physical characteristic of the sample;

obtaining from the transient signal a second transient signal over a second sampling time duration, the second sampling time duration defined based on the specific sampling time;

deriving respective magnitudes of the second transient signal at selected time intervals in the second sampling time duration; and

determining an analyte concentration based on respective magnitudes of the second transient signal at the selected time intervals.

2. The method of claim 1, further comprising:

defining the second sampling time duration based on the specific sampling time such that the second sampling time duration overlaps the first sampling time duration; and

dividing the second transient signal into discrete time intervals with respect to the second sampling time duration,

in which the second transient signal is referenced with respect to the second sampling time duration.

6. The method of claim 1, in which the second sampling time duration includes magnitudes of second transient signal measured before the specific sampling time, and

the specific range of time includes magnitudes of first transient signal measured before the specific sampling time.

7. The method of claim 1, in which the calculating step for the defined specific sampling time comprises utilizing an equation of the form:

x₁=a×

H²+bH+c

where

“

SpecificSamplingTime”

is designated as a time point from the start of the test sequence at which to sample the output signal of the biosensor,

H represents physical characteristic of the sample;

x₁ is about 4.3e5;

x₂ is about (−

)3.9; and

x₃ is about 4.8.

8. The method of claim 2, in which the step of defining the second sampling time duration comprises obtaining an absolute value of a difference between the defined specific sampling time and a predetermined time point to define a start time (T1) and an end time (T2) approximately equal to the specific sampling time point, and the first sampling time duration comprises about 10 seconds or less from the step of depositing the sample.

9. The method of claim 1, in which the step of obtaining further comprises defining a second sampling time duration that overlaps the first sampling time duration and includes a portion of the first transient signal and its magnitudes with respect to the time of the second sampling time duration, wherein the portion is designated as a second transient signal.

10. The method of claim 8, in which the step of obtaining the second transient signal comprises extracting from the first transient signal a portion of the first transient signal that is designated as a second transient signal that is within the second sampling time duration.

11. The method of claim 10, in which the deriving of respective magnitudes of the second transient signal at discrete selected time intervals comprises calculating a magnitude of the second transient signal during each selected time interval.

12. The method of claim 10, in which the dividing comprises dividing the second transient signal into at least 22 intervals in sequence starting from interval one at about the start time to interval twenty-two at about the end time.

13. The method of claim 11, in which the determination of analyte concentration is obtained by utilizing an equation of the form:

14. The method of claim 11, in which the determination of analyte concentration is obtained by utilizing an equation of the form:

15. The method of claim 11, in which the determination of analyte concentration is obtained by utilizing an equation of the form:

16. The method of claim 11, in which the determination of analyte concentration is obtained by utilizing an eauation of the form:

17. The method of claim 11, in which the determination of analyte concentration is obtained by utilizing an equation of the form:

18. The method of claim 11, in which the determination of analyte concentration is obtained by utilizing an equation of the form:

19. The method of claim 11, in which the magnitude of the second transient signal at each of the plurality of discrete intervals comprises an average magnitude of measured magnitudes at each discrete interval.

21. The method of claim 1, further comprising dividing the first transient signal into discrete intervals with respect to the specific range of time.

39. The method of claim 1, in which the obtaining comprises extracting from the first transient signal a second transient signal referenced with respect to the second sampling time duration.

40. The method of claim 1, in which the obtaining comprises removing signals from the first transient signals that are outside of the second sampling time duration to leave the second transient signal within the second sampling time duration.

41. The method of claim 39, in which the deriving comprises storing magnitudes of the second transient signal for each discrete interval in the second sampling time duration.

3. A method of determining an analyte concentration from a physiological sample with a biosensor having at least two electrodes and a reagent disposed on at least one electrode of the electrodes, the method comprising:

depositing a physiological sample on any one of the at least two electrodes to start an analyte test sequence;

applying a first signal to the sample to derive a physical characteristic of the sample;

extracting a specific sampling time in a first sampling time duration, extracting the specific sampling time comprising calculating a defined specific sampling time in the first sampling time duration based on the physical characteristic of the sample;

driving a second signal into the sample for the first sampling time duration;

measuring or sampling a first transient signal output from the sample for the duration of the first sampling time duration;

defining a specific range of time that includes the specific sampling time in the first sampling time duration,

obtaining plural magnitudes of the first transient signal (i) at respective discrete intervals within the specific range of time or (ii) at about the specific sampling time; and

determining the analyte concentration based on the magnitudes of the first transient signal from the obtaining step.

4. The method of claim 3, further comprising:

defining a specific range of time that includes the specific sampling time in the first sampling time duration, and obtaining plural magnitudes of the first transient signal at respective discrete intervals within the specific range of time.

5. The method of claim 3, further comprising:

obtaining plural magnitudes of the first transient signal output at time intervals other than at about the specific sampling time.

20. The method of claim 4, further comprising the step of dividing the first transient signal into discrete intervals with respect to the specific range of time.

22. The method of claim 20, in which the dividing comprises dividing the first transient signal into at least 22 intervals in sequence starting from interval one at about the start time to interval twenty-two at about the end time.

23. The method of claim 22, in which the determination of analyte concentration is obtained by utilizing an equation of the form:

24. The method of claim 22, in which the determination of analyte concentration is obtained by utilizing an equation of the form:

25. The method of claim 22, in which the determination of analyte concentration is obtained by utilizing an equation of the form:

26. The method of claim 22, in which the determination of analyte concentration is obtained by utilizing an equation of the form:

27. The method of claim 22, in which the determination of analyte concentration is obtained by utilizing an equation of the form:

28. The method of claim 22, in which the determination of analyte concentration is obtained by utilizing an equation of the form:

29. The method of claim 28, in which the magnitude of the first transient signal at each of the plurality of discrete intervals comprises an average magnitude of measured magnitudes at each discrete interval.

30. The method of claim 28, in which the applying of the first signal and the driving of the second signal is in sequential order.

31. The method of claim 28, in which the applying of the first signal overlaps with the driving of the second signal.

32. The method of claim 28, in which the applying of the first signal comprises directing an alternating signal to the sample so that a physical characteristic of the sample is determined from an output of the alternating signal.

33. The method of claim 28, in which the applying of the first signal comprises directing an optical signal to the sample so that a physical characteristic of the sample is determined from an output of the optical signal.

34. The method of claim 28, in which the physical characteristic comprises at least one of viscosity, hematocrit, temperature or density of the sample.

35. The method of claim 28, in which the physical characteristic comprises hematocrit and the analyte comprises glucose.

36. The method of claim 32, in which the directing comprises driving first and second alternating signals at different respective frequencies in which a first frequency comprises a lower frequency than the second frequency.

37. The method of claim 36, in which the first frequency is at least one order of magnitude lower than the second frequency.

38. The method of claim 37, in which the first frequency comprises any frequency in the range of about 10 kHz to about 250 kHz.