Rapid-read gated amperometry

• US 8,147,674 B2
• Filed: 11/14/2008
• Issued: 04/03/2012
• Est. Priority Date: 12/10/2007
• Status: Active Grant

• Current Assignee: Ascensia Diabetes Care Holdings AG (PHC Holdings Corporation)
• Original Assignee: Bayer Healthcare LLC (Bayer AG)
• Inventors: Wu, Huan-Ping
• Primary Examiner(s): Bell, Bruce
• Application Number:
  US12/271,032
• Publication Number:
  US 20090145779A1
• Time in Patent Office: 1,236 Days
• Field of Search: 205/775, 205/777.5, 205/792, 436/150, 436/149, 324/76.11
• US Class Current: 205/792
• CPC Class Codes: G01N 27/327 Biochemical electrodes , e.g. electrical or mechanical details for in vitro measurements
• CPC Class Codes: G01N 27/3273 Devices therefor, e.g. test element readers, circuitry details not specific to biochemical electrodes G01N33/4875

Abstract

A sensor system, device, and methods for determining the concentration of an analyte in a sample is described. Input signals including multiple duty cycles of sequential excitation pulses and relaxations are input to the sample. One or more signals output from the sample within 300 ms of the input of an excitation pulse may be correlated with the analyte concentration of the sample to improve the accuracy and/or precision of the analysis. Determining the analyte concentration of the sample from these rapidly measured output values may reduce analysis errors arising from the hematocrit effect, mediator background, and other error sources.

Claims

1. A method, comprising:

applying an input signal to a sample, where the input signal has at least 3 duty cycles within 10 seconds, and where each of the at least 3 duty cycles includes an excitation pulse and a relaxation;

measuring an output signal responsive to a measurable species within 300 milliseconds of an excitation pulse of at least one duty cycle; and

determining a concentration of an analyte in the sample in response to the measured output signal.

2. The method of claim 1, further comprising measuring the output signal within 300 milliseconds from the start of the excitation pulse of the at least one duty cycle.

3. The method of claim 1, where the input signal comprises at least 4 duty cycles within 7 seconds.

4. The method of claim 1, where a pulse width of the excitation pulse is from 0.1 to 2 seconds.

5. The method of claim 1, where a pulse width of the excitation pulse is from 0.3 to 0.8 seconds.

6. The method of claim 1, where a pulse interval of at least one of the at least 3 duty cycles is less than 3 seconds.

7. The method of claim 1, where a pulse width of the excitation pulse is from 0.3 to 0.5 seconds, and where a pulse interval of at least one of the at least 3 duty cycles is from 0.7 to 2 seconds.

8. The method of claim 1, further comprising measuring the output signal within less than 175 milliseconds of the excitation pulse of the at least one duty cycle.

9. The method of claim 8, further comprising measuring the output signal within less than 175 milliseconds from the start of the excitation pulse of the at least one duty cycle.

10. The method of claim 1, further comprising measuring the output signal within 60 to 150 milliseconds from the start of the excitation pulse of the at least one duty cycle.

11. The method of claim 1, comprising:

measuring an output signal responsive to the measurable species within 300 milliseconds of the start of the excitation pulse of at least one duty cycle applied within 7 seconds of starting an initial excitation pulse.

12. The method of claim 1, further comprising:

transferring at least one electron from the analyte in the sample to a mediator in a sensor strip; and

electrochemically exciting the measurable species in response to the input signal, where the measurable species is from at least one of the analyte and the mediator.

13. The method of claim 1, where the excitation pulse has a substantially constant voltage.

14. The method of claim 1, where the input signal includes square-wave excitations.

15. The method of claim 1, further comprising determining the concentration of the analyte in the sample with less bias than a concentration of the analyte determined in response to an output signal measured at more than 300 milliseconds from the start of the excitation pulse of one of the duty cycles.

16. The method of claim 15, further comprising determining the concentration of the analyte in the sample with less bias than a concentration of the analyte determined in response to an input signal having less than 3 duty cycles within 10 seconds.

17. The method of claim 1, further comprising recording at least one current as a function of time during the application of the input signal.

18. The method of claim 1, further comprising applying at least one data treatment to at least one current of the output signal.

19. The method of claim 1, further comprising:

exciting the measurable species internal to a diffusion barrier layer; and

substantially excluding from excitation the measurable species external to the diffusion barrier layer.

20. The method of claim 1, where the relaxation includes a current reduction to at least one-half the current flow at an excitation maxima of the excitation pulse.

21. The method of claim 1, where the relaxation includes a current flow reduction to at least an order of magnitude less than the current flow at an excitation maxima of the excitation pulse.

22. The method of claim 1, where the relaxation includes a substantially zero current flow.

23. The method of claim 1, where the relaxation is at least 0.5 seconds.

24. The method of claim 1, further comprising determining the analyte concentration from a transient decay, where the output signal includes the transient decay.

25. The method of claim 1, where the sample is at least one of a biological fluid and a derivative of a biological fluid.

26. The method of claim 1, where the measuring is performed by a portable measurement device.

27. The method of claim 1, where the input signal comprises a terminal read pulse not followed by a relaxation.

28. A method of reducing bias in a determined concentration of an analyte in a sample, comprising:

applying an input signal to the sample, where the input signal has at least 3 duty cycles within 10 seconds, and where each of the at least 3 duty cycles comprises an excitation pulse and a relaxation;

measuring an output signal responsive to a measurable species within 300 milliseconds of an excitation pulse of at least one of the at least 3 duty cycles; and

determining a concentration of the analyte in the sample in response to the measured output signal.

29. The method of claim 28, where the input signal comprises a terminal read pulse not followed by a relaxation.

30. The method of claim 28, further comprising measuring the output signal within 300 milliseconds from the start of the excitation pulse of the at least one duty cycle.

31. The method of claim 28, where a pulse width of the excitation pulse is from 0.3 to 0.8 seconds.

32. The method of claim 28, where a pulse interval of at least one of the at least 3 duty cycles is less than 3 seconds.

33. The method of claim 28, where a pulse width of the excitation pulse is from 0.3 to 0.5 seconds, and where a pulse interval of at least one of the at least 3 duty cycles is from 0.7 to 2 seconds.

34. The method of claim 28, further comprising measuring the output signal within 60 to 150 milliseconds from the start of the excitation pulse of the at least one duty cycle.

35. The method of claim 28, further comprising measuring the output signal from the input signal within 7 seconds of an initial excitation pulse.

36. The method of claim 28, where the excitation pulse has a substantially constant voltage.

37. The method of claim 28, further comprising determining the concentration of the analyte in the sample with less bias than a concentration of the analyte determined in response to an output signal measured at more than 300 milliseconds from the start of the excitation pulse of one of the duty cycles.

38. The method of claim 37, further comprising determining the concentration of the analyte in the sample with less bias than a concentration of the analyte determined in response to an input signal having less than 3 duty cycles within 10 seconds.

39. The method of claim 28, where the relaxation includes a current flow reduction to at least one-half the current flow at an excitation maxima of the excitation pulse.

40. The method of claim 28, where the relaxation includes a current flow reduction to at least an order of magnitude less than the current flow at an excitation maxima of the excitation pulse.

41. The method of claim 28, where the relaxation includes a substantially zero current flow.

42. The method of claim 28, where the relaxation is at least 0.5 seconds and is responsive to an open circuit.

43. The method of claim 28, where at least a portion of the bias is attributable to a hematocrit effect.

44. The method of claim 28, where the sample is at least one of a biological fluid and a derivative of a biological fluid.

45. The method of claim 28, further comprising determining the analyte concentration from a transient decay, where the output signal includes the transient decay.