Biosensor methods having enhanced stability and hematocrit performance

• US 8,702,965 B2
• Filed: 11/22/2010
• Issued: 04/22/2014
• 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: Wu, Huan-Ping, Nelson, Christine D., Maurer, Eric, Spradlin, Hope
• Primary Examiner(s): DIETERLE, JENNIFER M
• Application Number:
  US12/951,382
• Publication Number:
  US 20110115504A1
• Time in Patent Office: 1,247 Days
• Field of Search: 20440301-40315, 205/775, 205/777.5, 205/778, 205/792, 422/82.01, 422/68.1, 600345-348, 435/287.1, 435/817, 435/14
• US Class Current: 205/792
• 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. A method of determining the concentration of an analyte in a sample, comprising:

applying a sample to an electrochemical sensor strip, the senor strip including a first electrode, the first electrode including at least one first layer on a first conductor, the at least one first layer including an enzyme system and at most 8 μ

/mm² of a mediator,

where the mediator assists in transferring electrons between the analyte in the sample and the first conductor;

applying a pulse sequence to the sample, the pulse sequence comprising at least 2 duty cycles within 3 to 14 seconds, where each duty cycle comprises an excitation and a relaxation,

where the relaxation of each duty cycle provides an output current reduction to one-half or less of a current flow at an excitation maxima;

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.

2. The method of claim 1, the pulse sequence comprising at least 3 duty cycles within 9 seconds.

3. The method of claim 1, where the pulse sequence is complete in at most 5 seconds.

4. The method of claim 1, 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.

5. The method of claim 1, where the excitations each have a duration from 0.01 to 3 seconds.

6. The method of claim 1, where the excitations have a summed duration of at most 10 seconds.

7. The method of claim 1, where the excitations are of amplitudes having a difference within 500 mV.

8. The method of claim 1, where the excitations comprise at most 45% of the time of the pulse sequence.

9. The method of claim 1, where the relaxations each have a duration of from 0.2 to 3 seconds.

10. The method of claim 9, where the relaxation is responsive to an open circuit.

11. The method of claim 1, 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.

12. The method of claim 1, where the stability bias is less than ±

5%.

13. The method of claim 1, 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.

14. The method of claim 1, where the hematocrit bias is less than ±

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

15. The method of claim 1, where the intercept to slope ratio is at most 10 mg/dL.

16. The method of claim 1, where 45% or less of the total time of the method is spent oxidizing the sample.

17. The method of claim 1, where the relaxation is responsive to an open circuit.

18. The method of claim 1, where the pulse sequence comprises at least 3 duty cycles within 30 seconds.