Method and apparatus for rapid electrochemical analysis

• US 20070074977A1
• Filed: 09/30/2005
• Published: 04/05/2007
• Est. Priority Date: 09/30/2005
• Status: Active Grant

• Current Assignee: Cilag Gmbh International (Johnson & Johnson)
• Original Assignee: Lifescan Incorporated (Duv Holding Corporation)
• Inventors: Zhang, Bin, Guo, Sherry, Hodges, Alastair, Chatelier, Ronald
• Granted Patent: US 7,749,371 B2
• Time in Patent Office: Days
• US Class Current: 205/792
• CPC Class Codes: A61B 2562/0295 Strip shaped analyte sensors for apparatus classified in A61B5/145 or A61B5/157 disposable multilayered or laminated electrodes G01N27/307; details of handling chemical test elements G01N33/4875
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/1486 using enzyme electrodes, e.g. with immobilised oxidase
• CPC Class Codes: G01N 27/3273 Devices therefor, e.g. test element readers, circuitry details not specific to biochemical electrodes G01N33/4875

Abstract

Methods and apparatus for electrochemically determining an analyte concentration value in a physiological sample are disclosed. The methods include using a test strip in which two time-current transients are measured by a meter electrically connected to an electrochemical test strip. Integrative current values are derived from the time-current transients and used in the calculation of analyte concentration.

Claims

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

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

(i) first and second electrodes in a spaced apart relationship; and

(ii) a reagent layer comprising an enzyme and a mediator;

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

(d) calculating a first current value from the second time-current transient;

(e) calculating a second current value from the second time-current transient and a third current value from the first time-current transient;

(f) calculating a ratio which comprises the second current value divided by the third current value; and

(g) multiplying the first current value less a background value by the ratio to derive analyte concentration.

2. The method according to claim 1, wherein steps (b) through (g) occur in less than about 10 seconds.

3. The method according to claim 1, wherein steps (b) through (g) occur in less than about 6 seconds.

4. The method according to claim 1, wherein the ratio is to a power p.

5. The method according to claim 1, wherein the analyte concentration is calculated based upon an equation [C]=(I₂/I₃)^P*((a*I₁)−

Z) where [C] is analyte concentration, I₁ is the first current value, I₂ is the second current value, I₃ is the third current value, and Z, p and a are calibration factors.

6. The method according to claim 5, wherein p is in the range of about 0.2 and 4 and a is in the range of about 0.2 and 4.

7. The method according to claim 6, wherein p is equal to one and a is equal to one.

8. The method according to claim 5, further comprising the step of empirically determining p and a.

9. The method according to claim 1, wherein the first current value is proportional to analyte concentration.

10. The method according to claim 1, wherein the first, second, and third current values comprise an integral of cell current as a function of time.

11. The method according to claim 1, wherein the first, second, and third current values comprise a summation of cell current.

12. The method according to claim 1, wherein the analyte is glucose.

13. The method according to claim 1, wherein the physiological sample is a material selected from the group consisting of whole blood, plasma, serum, interstitial fluid, and urine.

14. The method according to claim 1, wherein the first electrode and the second electrode comprise a conductive material chosen from the group consisting of gold, palladium, platinum, silver, iridium, doped tin oxide, and carbon.

15. The method according to claim 14, wherein the first electrode is palladium and the second electrode is gold.

16. The method according to claim 14, wherein the conductive material is sputtered onto an insulating sheet.

17. The method according to claim 1, wherein the conductive material is screen-printed onto an insulating sheet.

18. The method according to claim 1, wherein the reagent layer is disposed on the first electrode.

19. The method according to claim 18, wherein the first polarity is negative with respect to the second electrode and the second polarity is positive with respect to the second electrode.

20. The method according to claim 18, wherein the first electric potential ranges from about 0.0 to −

0.6 V with respect to the second electrode and the second electric potential ranges from about 0.0 to 0.6 V with respect to the second electrode.

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

22. The method according to claim 1, wherein the electrochemical cell has a volume which is less than about 1 microliter.

23. The method according to claim 1, wherein the enzyme is a material chosen from the group consisting of glucose oxidase, glucose dehydrogenase based on a methoxatin co-factor, and glucose dehydrogenase based on a nicotinamide adenine dinucleotide co-factor.

24. The method according to claim 1, wherein the mediator is a material chosen from the group consisting of ferricyanide, ferrocene, ferrocene derivatives, osmium bipyridyl complexes, and quinone derivatives.

25. The method according to claim 1, wherein the first electric potential is applied for a duration time ranging from about 1 second to about 5 seconds.

26. The method according to claim 1, wherein the second electric potential is applied for a duration time ranging from about 1 second to about 5 seconds.

27. The method according to claim 1, wherein the wherein the second and third current values are calculated at different time intervals.

28. A method for determining an analyte concentration in a physiological sample, the method comprising:

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

(i) first and second electrodes in a spaced apart relationship; and

(ii) a reagent layer comprising an enzyme and a mediator;

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

(e) calculating a first integrative current value from the first time-current transient and a second integrative current value from the second time-current transient;

(f) calculating a ratio which comprises the second current value divided by the first current value;

(g) calculating a correction factor that comprises the ratio;

(h) calculating an initial concentration value from the first and/or second time-current transients;

(h) multiplying the initial concentration value less a background value by the correction factor to derive the analyte concentration.

29. The method according to claim 28, wherein the first and second integrative current values comprise an integral of cell current as a function of time.

30. The method according to claim 28, wherein the first and second integrative current values comprise a summation of cell current as a function of time.

31. The method according to claim 28, wherein the analyte is glucose.

32. The method according to claim 28, wherein the physiological sample is a material selected from the group consisting of whole blood, plasma, serum, interstitial fluid, and urine.

33. A method for determining an analyte concentration in a physiological sample, the method comprising:

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

(i) first and second electrodes in a spaced apart relationship; and

(ii) a reagent layer comprising an enzyme and a mediator;

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

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

(d) calculating a first charge value from the second time-charge transient;

(e) calculating a second charge value from the second time-charge transient and a third charge value from the first time-charge transient;

(f) calculating a ratio based on the second charge value and the third charge value; and

(h) multiplying the first charge value less a background value by the ratio to derive analyte concentration.