SYSTEMS AND METHODS FOR DETERMINING A SUBSTANTIALLY HEMATOCRIT INDEPENDENT ANALYTE CONCENTRATION

• US 20110162978A1
• Filed: 01/22/2010
• Published: 07/07/2011
• Est. Priority Date: 10/05/2006
• Status: Active Grant

• Current Assignee: Cilag Gmbh International (Johnson & Johnson)
• Original Assignee: LifeScan Scotland Limited (Johnson & Johnson)
• Inventors: CARDOSI, Marco F., Day, Richard Michael, Comstock, Lorraine, Finch, Matthew, Mcevoy, Mary, Sutton, Thomas, Thompson, Arlene, Dolan, Michael Patrick, Blythe, Stephen Patrick, Bailey, Eric Jason, Anderson, Gretchen, Naylor, Nina Antonia, Leach, Christopher Philip, Day, Emma Vanessa Jayne, Mills, Leanne
• Granted Patent: US 8,293,096 B2
• Time in Patent Office: Days
• 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

A method and system is provided to allow for determination of substantially Hematocrit independent analyte concentration. In one example, an analyte measurement system is provided that includes a test strip and a test meter. The test strip includes a reference electrode and a working electrode, in which the working electrode is coated with a reagent layer. The test meter includes an electronic circuit and a signal processor. The electronic circuit applies a plurality of voltages to the reference electrode and the working electrode over respective durations. The signal processor is configured to determine a substantially hematocrit-independent concentration of the analyte from a plurality of current values as measured by the processor upon application of a plurality of test voltages to the reference and working electrodes over a plurality of durations interspersed with rest voltages lower than the test voltages being applied to the electrodes.

Claims

1. A method of determining a substantially hematocrit-independent concentration of an analyte in a fluid sample deposited on a test strip having a reference electrode and a working electrode, in which the working electrode is coated with a reagent layer, the method comprising:

applying a fluid sample to the test strip for a reaction period;

applying a first test voltage to the reference electrode and the working electrode and measuring a first current value therebetween, the first test voltage being an absolute value from about 100 millivolts to about 600 millivolts;

applying a first rest voltage between the reference electrode and the working electrode, the first rest voltage is an absolute value from about zero to about 50 millivolts;

applying a second test voltage between the reference electrode and the working electrode and measuring a second current value, in which the second test voltage is an absolute value from about 100 millivolts to about 600 millivolts;

applying a second rest voltage between the reference electrode and the working electrode, in which the second rest voltage is an absolute value from about zero to about 50 millivolts;

applying a third test voltage between the reference electrode and the working electrode and measuring a third current value, in which the third test voltage is an absolute value from about 100 millivolts to about 600 millivolts; and

calculating substantially hematocrit-independent concentration of the analyte from the first, second and third current values.

2. The method of claim 1, in which the calculating comprises calculating the substantially hematocrit-independent concentration of the analyte from the y-intercept of a graph representing log₁₀(I_i) versus log₁₀(time);

where;

I_i is the current value measured near the end of each test voltage and i ranges from about 1 to about 3; and

time is the time at which I_i is measured.

3. The method of claim 1, in which the duration of the first, second and third test voltages is equal and ranges from about 0.1 to about 1.0 seconds;

the duration of the first and second rest voltages is equal and ranges from about 0.05 to about 1.0 seconds;

the first, second and third current values are measured at about 0.1 to about 1.0 seconds after a test voltage is applied to the test strip;

the magnitude of the first, second and third test voltages is equal and is one of about 200 millivolts or about 400 millivolts; and

the reaction period is from about zero seconds to about five seconds.

4. The method of claim 1, in which the working electrode comprises a plurality of microelectrodes formed from gold.

5. The method of claim 1, in which the reagent layer comprises an enzyme, a mediator and a buffering solution in which the mediator is ruthenium hexamine chloride ranging in amount from about 15 percent to about 20 percent based on a ratio of a weight of the mediator to a volume of the buffering solution.

6. The method of claim 1, further comprising:

calculating a hematocrit fraction using the follow equation;

7. The method of claim 6, in which the calculating comprises calculating the substantially hematocrit-independent concentration of the analyte from the y-intercept of a graph representing log₁₀(I_i) versus log₁₀(time);

where;

I_i is the current value measured near the end of each test voltage and i ranges from about 1 to about 3; and

time is the time at which I_i is measured.

8. The method of claim 7, in which the duration of the first, second and third test voltages is equal and ranges from about 0.1 to about 1.0 seconds;

the duration of the first and second rest voltages is equal and ranges from about 0.05 to about 1.0 seconds;

the first, second and third current values are measured at about 0.1 to about 1.0 seconds after a test voltage is applied to the test strip;

the magnitude of the first, second and third test voltages is equal and is one of about 200 millivolts or about 400 millivolts; and

the reaction period is from about zero seconds to about five seconds.

9. A method of detecting the presence of sufficient quantity of a fluid sample deposited on a test strip having a reference electrode and a working electrode, in which the working electrode is coated with a reagent layer, the method comprising:

applying a forward test voltage between the reference electrode and the working electrode and measuring a forward current value near the end of the forward test voltage, in which the forward test voltage is from about 100 millivolts to about 600 millivolts;

applying a reverse test voltage of opposite polarity and substantially equal magnitude to the forward test voltage and measuring a reverse current value near the end of the reverse test voltage, the reverse test voltage being from about negative 100 millivolts to about negative 600 millivolts;

calculating a ratio of the reverse current value to the forward current value; and

determining if the ratio of the reverse current value to the forward current value is within an acceptance range, the acceptance range being substantially equal to two when the reference electrode is about twice the surface area of the working electrode.

10. The method of claim 9, in which the duration of the forward test voltage ranges from about 0.1 to about 1.0 seconds;

the magnitude of the forward test voltage is about 400 millivolts;

the forward current value is measured at about 0.1 to about 1.0 seconds after the forward test voltage is applied to the test strip;

the duration of the reverse test voltage ranges from about 0.1 to about 1.0 seconds;

the magnitude of the reverse test voltage is about 400 millivolts; and

the reverse current value is measured at about 0.1 to about 1.0 seconds after the reverse test voltage is applied to the test strip.

11. The method of claim 10, in which the working electrode comprises a plurality of microelectrodes formed from gold;

and

12. The method of claim 10, in which the reagent layer comprises an enzyme, a mediator and a buffering solution in which the mediator is ruthenium hexamine chloride ranging in amount from about 15 percent to about 20 percent based on a ratio of a weight of the mediator to a volume of the buffering solution.

13. The method of claim 9, further comprising:

plotting the first, second and third reverse current values as a function of an analyte concentration as measured on a reference instrument and calculating a slope m_reverse of the linear regressed line obtained therefrom;

plotting the first, second and third forward current values as a function of the analyte concentration as measured on a reference instrument and calculating a slope m_forward of the linear regressed line obtained therefrom;

calculating a ratio of m_reverse to m_forward; and

determining if the ratio of m_reverse to m_forward is m within an acceptance range, the acceptance range being substantially equal to two when the reference electrode is about twice the surface area of the working electrode, the first, second and third forward test voltages and first, second and third reverse test voltages are of equal magnitude and duration and the first, second, third and fourth rest voltages are of equal magnitude and duration.

14. The method of claim 13, in which the duration of the forward test voltage ranges from about 0.1 to about 1.0 seconds;

the magnitude of the forward test voltage is about 400 millivolts;

the forward current value is measured at about 0.1 to about 1.0 seconds after the forward test voltage is applied to the test strip;

the duration of the reverse test voltage ranges from about 0.1 to about 1.0 seconds;

the magnitude of the reverse test voltage is about 400 millivolts; and

the reverse current value is measured at about 0.1 to about 1.0 seconds after the reverse test voltage is applied to the test strip.

15. The method of claim 14, in which the reagent layer comprises an enzyme, a mediator and a buffering solution in which the mediator is ruthenium hexamine chloride ranging in amount from about 15 percent to about 20 percent based on a ratio of a weight of the mediator to a volume of the buffering solution.

16. A method of checking a functionality of a test strip having a reference electrode and a working electrode with the working electrode being coated with a reagent layer, the method comprising:

applying a fluid sample to the test strip for a reaction period;

applying a first test voltage between the reference electrode and the working electrode and measuring a first current value, in which the first test voltage is an absolute value from about 100 millivolts to about 600 millivolts;

applying a first rest voltage between the reference electrode and the working electrode, the first rest voltage is an absolute value from about zero to about 50 millivolts;

applying a second test voltage between the reference electrode and the working electrode and measuring a second current value, in which the second test voltage is an absolute value from about 100 millivolts to about 600 millivolts;

applying a second rest voltage between the reference electrode and the working electrode, in which the second rest voltage is an absolute value from about zero to about 50 millivolts;

applying a third test voltage between the reference electrode and the working electrode and measuring a third current value, in which the third test voltage is an absolute value from about 100 millivolts to about 600 millivolts;

applying a third rest voltage between the reference electrode and the working electrode, in which the third rest voltage is an absolute value from about zero to about 50 millivolts;

applying a fourth test voltage between the reference electrode and the working electrode and measuring a fourth current value, in which the fourth test voltage is an absolute value from about 100 millivolts to about 600 millivolts;

applying a fourth rest voltage between the reference electrode and the working electrode, in which the fourth rest voltage is an absolute value from about zero to about 50 millivolts;

applying a fifth test voltage between the reference electrode and the working electrode and measuring a fifth current value, in which the fifth test voltage is an absolute value from about 100 millivolts to about 600 millivolts;

generating a curve representing the first, second, third, fourth and fifth current values as a function of pulse time, in which the pulse time is measured relative to initiation of the first test voltage;

using least squares regression to fit the curve to the following equation;

17. The method of claim 16, in which the duration of the first, second, third, fourth and fifth test voltages is equal and ranges from about 0.1 to about 1.0 seconds;

the magnitude of the first, second, third, fourth and fifth test voltages is equal and is about 400 millivolts;

the first, second, third, fourth and fifth current values are measured at about 0.1 to about 1.0 seconds after a test voltage is applied to the test strip the duration of the first, second, third and fourth rest voltages is equal and ranges from about 0.05 to about 1.0 seconds.

18. An analyte measurement system comprising:

a test strip comprising a reference electrode and a working electrode, in which the working electrode is coated with a reagent layer; and

a test meter comprising;

an electronic circuit that applies a plurality of voltages to the reference electrode and the working electrode over respective durations; and

a signal processor configured to determine a substantially hematocrit-independent concentration of the analyte from a plurality of current values as measured by the processor upon application of a plurality of test voltages to the reference and working electrodes over a plurality of durations interspersed with rest voltages lower than the test voltages being applied to the electrodes.

19. The system of claim 18, in which the substantially hematocrit-independent concentration of the analyte is calculated from the y-intercept of a graph representing log₁₀(I_i) versus log₁₀(time);

where;

I_i is the current value measured near the end of each of the first, second and third test voltages and i ranges from about 1 to about 3; and

time is the time at which I_i is measured.

20. The system of claim 18, in which the duration of the first, second and third test voltages is equal and ranges from about 0.1 to about 1.0 seconds;

the duration of the first and second rest voltages is equal and ranges from about 0.05 to about 1.0 seconds;

the first, second and third current values are measured at about 0.1 to about 1.0 seconds after a test voltage is applied to the test strip;

the magnitude of the first, second and third test voltages is equal and is one of about 200 millivolts or about 400 millivolts; and

the reaction period is from about zero seconds to about five seconds.

21. The system of claim 20, in which the reference electrode and the working electrode are comprised of gold.

22. The system of claim 21, in which the reference electrode and the working electrode are comprised of carbon.

23. The system of claim 22, in which the working electrode comprises a plurality of microelectrodes formed from gold.

24. The system of claim 107, in which the reagent layer comprises an enzyme, a mediator and a buffering solution in which the mediator is ruthenium hexamine chloride ranging in amount from about 15 percent to about 20 percent based on a ratio of a weight of the mediator to a volume of the buffering solution.

25. The system of claim 24, in which the meter further comprises a display comprising:

a section for displaying an analyte concentration;

a range indicator for indicating whether the analyte concentration is within a normal range; and

a graphical element for pointing from the general direction of the analyte concentration to a region on the range indicator in which the analyte concentration falls, and the range indicator comprises a plurality of ranges represented as a continuum.