Biosensor Methods Having Enhanced Stability and Hematocrit Performance

• US 20110115504A1
• Filed: 11/22/2010
• Published: 05/19/2011
• Est. Priority Date: 09/22/2006
• Status: Active Grant

• Current Assignee: Ascensia Diabetes Care Holdings AG (PHC Holdings Corporation)
• Original Assignee: Bayer Healthcare LLC (Bayer AG)
• Inventors: Maurer, Eric, Wu, Huan-Ping, Nelson, Christine D., Spradlin, Hope
• Granted Patent: US 8,702,965 B2
• Time in Patent Office: Days
• US Class Current: 324/692
• CPC Class Codes: C12Q 1/004 mediator-assisted
• CPC Class Codes: C12Q 1/006 for glucose
• CPC Class Codes: G01N 27/327 Biochemical electrodes , e.g. electrical or mechanical details for in vitro measurements
• 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 27/3273 Devices therefor, e.g. test element readers, circuitry details not specific to biochemical electrodes G01N33/4875
• 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 33/49 Blood chemical methods for determining blood cell populations G01N33/5094; chemical analysis of blood groups or blood types G01N33/80
• CPC Class Codes: G01N 33/5438 Electrodes
• CPC Class Codes: Y10S 435/817 Enzyme or microbe electrode

Abstract

The present invention relates to electrochemical sensor strips and methods of determining the concentration of an analyte in a sample or improving the performance of a concentration determination. The electrochemical sensor strips may include at most 8 μg/mm² of a mediator. The strips, the strip reagent layer, or the methods may provide for the determination of a concentration value having at least one of a stability bias of less than ±10% after storage at 50° C. for 4 weeks when compared to a comparison strip stored at −20° C. for 4 weeks, a hematocrit bias of less than ±10% for whole blood samples including from 20 to 60% hematocrit, and an intercept to slope ratio of at most 20 mg/dL. A method of increasing the performance of a quantitative analyte determination also is provided.

Claims

1-25. -25. (canceled)

26. A method of determining the concentration of an analyte in a sample, comprising:

applying a pulse sequence to the sample, the pulse sequence comprising at least 3 duty cycles within 30 seconds, where each duty cycle comprises an excitation and a relaxation;

determining current measurements from the sample responsive to the pulse sequence; and

determining the concentration of the analyte in the sample from the current measurements, the determined concentration having at least one of a stability bias of less than ±

10%, a hematocrit bias of less than ±

10% for whole blood samples over a 20 to 60% hematocrit range, and an intercept to slope ratio of at most 20 mg/dL.

27. The method of claim 26, the pulse sequence comprising at least 3 duty cycles within 9 seconds.

28. The method of claim 26, where the pulse sequence is complete in at most 5 seconds.

29. The method of claim 26, where the determining the concentration of the analyte in the sample includes determining the concentration of the analyte in the sample from the currents measurement taken within 2 seconds from the application of the pulse sequence.

31. The method of claim 26, where the excitations each have a duration from 0.01 to 3 seconds.

32. The method of claim 26, where the excitations have a summed duration of at most 10 seconds.

33. The method of claim 26, where the excitations are of amplitudes having a difference within 500 mV.

34. The method of claim 26, where the excitations comprise at most 45% of the time of the pulse sequence.

35. The method of claim 26, where the relaxations each have a duration of from 0.2 to 3 seconds.

36. The method of claim 26, where the pulse sequence includes an initial excitation from 0.75 to 3 seconds in duration, where the initial excitation is longer in duration than the excitations of the duty cycles.

37. The method of claim 26, where the stability bias is less than ±

5%.

38. The method of claim 26, where the stability bias is less than ±

5% after storage at 50°

C. for 4 weeks when compared to a comparison strip stored at −

20°

C. for 4 weeks.

39. The method of claim 26, where the hematocrit bias is less than ±

5% for whole blood samples including from 20 to 60% hematocrit.

40. The method of claim 26, where the intercept to slope ratio is at most 10 mg/dL.

51. The method of claim 26, where 45% or less of the total assay time is spent oxidizing the sample.

30. (canceled)

41. A method of increasing the performance of quantitative analyte determination comprising:

introducing an analyte containing sample having a liquid component to an electrochemical sensor strip, the strip having a base, a first conductor on the base, a second conductor on the base, and at least one first layer on at least the first conductor, where the at least one first layer includes a reagent layer including a polymeric binder and the sample provides electrical communication between the first and the second conductor;

applying an electric potential between the first and the second conductor in the form of at least 4 read pulses within 30 seconds;

measuring a current from at least one of the read pulses to provide a quantitative value of the analyte concentration in the sample with increased performance attributable to at least one performance parameter selected from the group consisting of a stability bias of less than ±

10% after the strip is stored at 50°

C. for 2 weeks, a hematocrit bias of less than ±

10% over a 20 to 60% hematocrit range for whole blood samples, an intercept to slope ratio of at most 10 mg/dL, and combinations thereof.

42. The method of claim 41, where the at least 4 read pulses are applied within 9 seconds.

43. The method of claim 41, where the read pulses are complete in at most 5 seconds of applying the electric potential.

44. The method of claim 41, where the current measured from at least one of the read pulses is measured within 2 seconds of applying the electric potential to provide the quantitative value of the analyte concentration in the sample.

45. The method of claim 41, where the read pulses have a duration of at most 2 seconds.

46. The method of claim 41, where the read pulses are of amplitudes having a difference within 500 mV.

47. The method of claim 41, where the stability bias is less than ±

5%.

48. The method of claim 41, where the stability bias is less than ±

5% after storage at 50°

C. for 4 weeks.

49. The method of claim 41, where the hematocrit bias is less than ±

5% over a 20 to 60% hematocrit range for whole blood samples.

50. The method of claim 41, where the intercept to slope ratio is at most 1 mg/dL.

52. The method of claim 41, where 45% or less of the total assay time is spent oxidizing the sample with the electric potential.

53. The method of claim 41, where the stability bias of less than ±

10% performance parameter is after the strip is stored at 25°

C. for 18 months.