Electrochemical methods and devices for use in the determination of hematocrit corrected analyte concentrations

• US 6,475,372 B1
• Filed: 02/02/2000
• Issued: 11/05/2002
• Est. Priority Date: 02/02/2000
• Status: Expired due to Term

• Current Assignee: Cilag Gmbh International (Johnson & Johnson), LifeScan IP Holdings, LLC
• Original Assignee: Lifescan Incorporated (Duv Holding Corporation)
• Inventors: Kermani, Mahyar Z., Ohara, Timothy J.
• Primary Examiner(s): Tung, T.
• Assistant Examiner(s): NOGUEROLA, ALEXANDER STEPHAN
• Application Number:
  US09/497,304
• Time in Patent Office: 1,007 Days
• Field of Search: 422/73, 436/66, 436/70, 436/67, 204/403, 204/406, 204/400, 205/775, 205/777.5, 205/779
• US Class Current: 205/777.5
• CPC Class Codes: G01N 27/3274 Corrective measures, e.g. error detection, compensation for temperature or hematocrit, calibration coding of calibration information G01N33/48771

Abstract

Methods and devices for determining the concentration of an analyte in a physiological sample are provided. In the subject methods, the physiological sample is introduced into an electrochemical cell having a working and reference electrode. A first electric potential is applied to the cell and the resultant cell current over a period of time is measured to determine a first time-current transient. A second electric potential of opposite polarity is then applied and a second a time-current transient is determined. The preliminary concentration of the analyte is then calculated from the first and/or second time-current transient. This preliminary analyte concentration less a background value is then multiplied by a hematocrit correction factor to obtain the analyte concentration in the sample, where the hematocrit correction factor is a function of the preliminary analyte concentration and the variable γ of the electrochemical cell. The subject methods and devices are suited for use in the determination of a wide variety of analytes in a wide variety of samples, and are particularly suited for the determination of analytes in whole blood or derivatives thereof, where an analyte of particular interest is glucose.

Claims

1. A method for determining the hematocrit corrected concentration of an analyte in a physiological sample, said method comprising:

(a) introducing said physiological sample into an electrochemical cell comprising;

(i) spaced apart working and reference electrodes; and

(ii) a redox reagent system comprising an enzyme and a mediator;

(b) applying a first electric potential having a first polarity to said reaction cell and measuring cell current as a function of time to obtain a first time-current transient;

(c) applying a second electric potential having a second polarity to said cell, wherein said second polarity is opposite said first polarity, and measuring cell current as a function of time to obtain a second time-current transient; and

(d) deriving a preliminary analyte concentration from said first and second time-current transients; and

(e) multiplying said preliminary analyte concentration less a background value by a hematocrit correction factor to derive said hematocrit corrected analyte concentration in said sample;

whereby the hematocrit corrected concentration of said analyte in said sample is determined.

2. The method according to claim 1, wherein said hematocrit correction factor modulates the preliminary analyte concentration value to remove the hematocrit derived component of said preliminary analyte concentration value.

3. The method according to claim 1, wherein said hematocrit correction factor is a function of said preliminary analyte concentration and γ

of said electrochemical cell.

4. The method according to claim 1, wherein said physiological sample is whole blood or a derivative thereof.

5. The method according to claim 1, wherein said analyte is glucose.

6. The method according to claim 1, wherein said method comprises employing a meter.

7. The method according to claim 1 wherein said first polarity is negative and said second polarity is positive.

8. The method according to claim 1 wherein the first polarity ranges form about 0.0 to −

0.6 V and said second polarity ranges from about 0.0 to 0.6 V.

9. The method according to claim 1, wherein said hematocrit correction factor substantially minimizes any error to said preliminary analyte concentration value caused by the hematocrit derived component of said preliminary analyte concentration value.

10. The method according to claim 1 wherein said second electric potential is applied immediately following the application of said first electric potential.

11. A method for determining the hematocrit corrected concentration of an analyte in a whole blood sample, said method comprising:

(a) introducing said whole blood sample into an electrochemical cell comprising;

(i) spaced apart working and reference electrodes; and

(ii) a redox reagent system comprising an enzyme and a mediator;

(b) applying a first electric potential having a first polarity to said reaction cell and measuring cell current as a function of time to obtain a first time-current transient;

(c) applying a second electric potential having a second polarity to said cell, wherein said second polarity is opposite said first polarity, and measuring cell current as a function of time to obtain a second time-current transient; and

(d) deriving a preliminary analyte concentration value from said first and second time-current transients; and

(e) multiplying said preliminary analyte concentration less a background value by a hematocrit correction factor that removes the hematocrit component from said preliminary concentration value to derive said hematocrit corrected analyte concentration in said sample;

whereby the hematocrit corrected concentration of said analyte in said sample is determined.

12. The method according to claim 11, wherein said hematocrit correcting factor is a function of said preliminary analyte concentration and a variable γ

of said electrochemical cell.

13. The method according to claim 11, wherein said analyte is glucose.

14. The method according to claim 11, wherein said enzyme is an oxidizing enzyme.

15. The method according to claim 14, wherein said oxidizing enzyme is a glucose oxidizing enzyme.

16. The method according to claim 11 wherein said first polarity is negative and said second polarity is positive.

17. The method according to claim 11 wherein the first polarity ranges form about 0.0 to −

0.6 V and said second polarity ranges from about 0.0 to 0.6 V.

18. A method for determining the hematocrit corrected concentration of glucose in a whole blood sample, said method comprising:

(a) introducing said whole blood sample into an electrochemical cell comprising;

(i) spaced apart working and reference electrodes; and

(ii) a redox reagent system comprising a glucose oxidizing enzyme and a mediator;

(b) applying a first electric potential having a first polarity to said reaction cell and measuring cell current as a function of time to obtain a first time-current transient;

(c) applying a second electric potential having a second polarity to said cell, wherein said second polarity is opposite said first polarity, and measuring cell current as a function of time to obtain a second time-current transient; and

(d) deriving a preliminary glucose concentration value from said first and second time-current transients; and

(e) multiplying said preliminary glucose concentration value less a background value by a hematocrit correction factor that removes the hematocrit component from said preliminary concentration value to derive said hematocrit corrected glucose concentration in said sample;

whereby the hematocrit corrected concentration of glucose in said sample is determined.

19. The method according to claim 18, wherein said hematocrit correction factor is a function of said preliminary analyte concentration and a variable γ

of said electrochemical cell.

20. The method according to claim 19, wherein said hematocrit correction factor equals:

21. The method according to claim 20, wherein said preliminary glucose concentration of said sample is greater than 40 mg/dL.

22. The method according to claim 20, wherein said variable γ

of said electrochemical cell is greater than 0.7.

23. The method according to claim 18 wherein said first polarity is negative and said second polarity is positive.

24. The method according to claim 18 wherein the first polarity ranges form about 0.0 to −

0.6 V and said second polarity ranges from about 0.0 to 0.6 V.

25. A meter for amperometrically measuring the concentration of an analyte in a physiological sample, said meter comprising:

(a) means for applying a first electric potential having a first polarity to an electrochemical cell comprising said sample and measuring cell current as a function of time to obtain a first time-current transient;

(b) means for applying a second electric potential having a second polarity to said electrochemical cell, wherein said second polarity is opposite said first polarity, and measuring cell current as a function of time to obtain a second time-current transient;

(c) means for determining a preliminary analyte concentration value and variable γ

from said first and second time-currents; and

(d) means for removing the hematocrit component from said preliminary concentration value to derive said analyte concentration in said sample.

26. The meter according to claim 25, wherein said means for removing the hematocrit component is a means for multiplying said preliminary analyte concentration value less a background value by a hematocrit correction factor.

27. The meter according to claim 25, wherein said hematocrit correction factor is a function of said preliminary analyte concentration and said variable γ

of said electrochemical cell.

28. The meter according to claim 27, wherein said hematocrit correction factor equals:

29. The meter according to claim 25, wherein said analyte is glucose.

30. The meter according to claim 25, wherein an electrochemical test strip is present in said meter.

31. A system for use in determining the concentration of an analyte in a physiological sample, said system comprising:

(a) an electrochemical test strip; and

(b) a meter comprising;

(1) means for applying a first electric potential having a first polarity to an electrochemical cell comprising said sample and measuring cell current as a function of time to obtain a first time-current transient;

(2) means for applying a second electric potential having a second polarity to said electrochemical cell, wherein said second polarity is opposite said first polarity, and measuring cell current as a function of time to obtain a second time-current transient;

(3) means for determining a preliminary analyte concentration value and variable γ

from said first and second time-currents; and

(4) means for removing the hematocrit component from said preliminary concentration value to derive said analyte concentration in said sample.