Multi-region and potential test sensors, methods and systems

• US 9,846,136 B2
• Filed: 03/22/2010
• Issued: 12/19/2017
• Est. Priority Date: 09/24/2007
• Status: Active Grant

• Current Assignee: Ascensia Diabetes Care Holdings AG (PHC Holdings Corporation)
• Original Assignee: Ascensia Diabetes Care Holdings AG (PHC Holdings Corporation)
• Inventors: Wu, Huan-Ping, Zhong, Weiping, Perry, Joseph E., Maurer, Eric, Jung, Sung-Kwon
• Primary Examiner(s): Fritchman, Rebecca M
• Application Number:
  US12/728,457
• Publication Number:
  US 20100267161A1
• Time in Patent Office: 2,829 Days
• Field of Search: 436149, 422 8201
• CPC Class Codes: C12Q 1/001 Enzyme electrodes
• 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 27/3274 Corrective measures, e.g. error detection, compensation for temperature or hematocrit, calibration coding of calibration information G01N33/48771

Abstract

Biosensor systems including a measurement device and test sensors including at least three independently addressable electrodes, with at least two of the electrodes being substantially chemically isolated are disclosed. One or more working electrodes may be combined with two or more counter electrodes. The two or more counter electrodes may operate at different potentials to provide for multi-analyte electrochemical analysis. Analysis methods are provided to perform multi-analyte electrochemical analysis and test sensors are provided having resistance to chemical mixing between secondary analysis regions.

Claims

1. An analyte test sensor, comprising:

at least two substrates in the form of a base and a lid combined to form a reservoir, the reservoir having a primary area between eight secondary analysis regions, the eight secondary analysis regions including a first region, a second region, a third region, a fourth region, a fifth region, a sixth region, a seventh region, and an eight region, the eight secondary analysis regions being distinct, separate, and structurally isolated to resist or eliminate diffusive or convective mixing of reagents between the secondary analysis regions during one or more analyses of a sample, the primary area having a sample port where sample introduction occurs into the test sensor;

four working electrodes including a first working electrode, a second working electrode, a third working electrode, and a fourth working electrode, the four working electrodes being distinct and separate, each of the working electrodes including a first conductor and a reagent composition, each of the reagent compositions having a different redox potential; and

four counter electrodes including a first counter electrode, a second counter electrode, a third counter electrode, and a fourth counter electrode, the four counter electrodes being distinct and separate, each of the counter electrodes including a second conductor and at least one redox species,

wherein each of the four working electrodes and the four counter electrodes is disposed in a respective separate one of the eight secondary analysis regions such that the first region has the first working electrode and its respective first conductor and reagent composition, the second region has the second working electrode and its respective first conductor and reagent composition, the third region has the third working electrode and its respective first conductor and reagent composition, the fourth region has the fourth working electrode and its respective first conductor and reagent composition, the fifth region has the first counter electrode and its respective second conductor and at least one redox species, the sixth region has the second counter electrode and its respective second conductor and at least one redox species, the seventh region has the third counter electrode and its respective second conductor and at least one redox species, and the eighth region has the fourth counter electrode and its respective second conductor and at least one redox species;

wherein the first conductors of the working electrodes are electrically connected; and

wherein the second conductors of the counter electrodes are not electrically connected.

2. The test sensor of claim 1, wherein at least one of the secondary analysis regions opposes another one of the second secondary analysis regions across the primary area.

3. The test sensor of claim 1, wherein at least two of the secondary analysis regions are staggered on opposing sides of the primary area.

4. The test sensor of claim 2, wherein at least two of the secondary analysis regions are staggered on opposing sides of the primary area.

5. The test sensor of claim 2, wherein at least one of the secondary analysis regions branch from the primary area at an angle other than 90°

.

7. The test sensor of claim 4, wherein at least one of the secondary analysis regions branch from the primary area at an angle other than 90°

.

8. The test sensor of claim 2, wherein at least one of the secondary analysis regions branch from the primary area at an angle of less than 90°

.

9. The test sensor of claim 3, wherein at least one of the secondary analysis regions branch from the primary area at an angle of less than 90°

.

10. The test sensor of claim 4, wherein at least one of the secondary analysis regions branch from the primary area at an angle of less than 90°

.

11. The test sensor of claim 1, wherein the four working electrodes are disposed in four of the secondary analysis regions on one side of the primary area, and the four counter electrodes are disposed in four other secondary analysis regions on another side of the primary area.

12. The test sensor of claim 1, further comprising another conductor connected to one of the counter electrodes and extending into the primary area.

13. The test sensor of claim 1, wherein the reservoir is a multi-T-channel design.

14. The test sensor of claim 1, wherein the reservoir is a multi-Y-channel design.

15. The test sensor of claim 1, wherein the counter electrodes are configured to operate at different potentials.

16. The test sensor of claim 1, wherein the counter electrodes are configured to operate at different potentials separated by at least 50 mV.

17. The test sensor of claim 1, wherein the sample is a biological fluid, and wherein the secondary analysis regions are arranged so that when the biological fluid enters the reservoir and flows to the secondary analysis regions, the biological fluid does not flow across more than one electrode to reach another electrode.

18. The test sensor of claim 10, wherein the sample is a biological fluid, and wherein the secondary analysis regions are arranged so that when the biological fluid enters the reservoir and flows to the secondary analysis regions, the biological fluid does not flow across more than one electrode to reach another electrode.

19. The test sensor of claim 1, wherein a single straight line drawn passing through the primary area and the secondary analysis regions cannot be drawn between any two electrodes.

20. The test sensor of claim 10, wherein a single straight line drawn passing through the primary area and the secondary analysis regions cannot be drawn between any two electrodes.

21. The test sensor of claim 1, wherein at least two of the counter electrodes are configured to operate at different potentials.

22. The test sensor of claim 10, wherein at least two of the counter electrodes are configured to operate at different potentials.

23. The test sensor of claim 21, wherein the different potentials are separated by at least 50 mV.

24. The test sensor of claim 22, wherein the different potentials are separated by at least 50 mV.

25. The test sensor of claim 21, wherein different redox species of the at least two counter electrodes are selected from the group consisting of a metal verses an electroactive organic molecule and the elemental identity of a metal.

26. The test sensor of claim 22, wherein different redox species of the at least two counter electrodes are selected from the group consisting of a metal verses an electroactive organic molecule and the elemental identity of a metal.

27. The test sensor of claim 21, wherein the different redox potential is provided by first and second redox species having different ratios of the conjugates of a redox pair.

28. The test sensor of claim 22, wherein the different potential configuration is provided by first and second redox species having different ratios of the conjugates of a redox pair.

29. The test sensor of claim 1, further comprising at least one reference electrode.

30. The test sensor of claim 10, further comprising at least one reference electrode.

6. The test sensor of 3, wherein at least one of the secondary analysis regions branch from the primary area at an angle other than 90°

.

31. An analyte test sensor, the test sensor comprising:

at least two substrates in the form of a base and a lid combined to form a reservoir, the reservoir including at least one primary area located between at least eight secondary analysis regions, the eight secondary analysis regions including a first region, a second region, a third region, a fourth region, a fifth region, a sixth region, a seventh region, and an eighth region, the eight secondary analysis regions being distinct, separate, and structurally isolated to resist or eliminate diffusive or convective mixing of reagents between the secondary analysis regions during one or more analyses of a sample;

four working electrodes and four counter electrodes including a first working electrode, a second working electrode, a third working electrode, a fourth working electrode, a first counter electrode, a second counter electrode, a third counter electrode, and a fourth counter electrode, each of the four working electrodes and the four counter electrodes being distinct and separate, each of the four working electrodes including a first conductor and a reagent composition, each of the reagent compositions having a different redox potential, each of the four counter electrodes including a second conductor and at least one redox species, the first conductors of the four working electrodes being electrically connected and the second conductors of the four counter electrodes not being electrically connected, each of the four working electrodes and the four counter electrodes being disposed in a respective separate one of the eight secondary analysis regions such that the first region has the first working electrode and its respective first conductor and reagent composition, the second region has the second working electrode and its respective first conductor and reagent composition, the third region has the third working electrode and its respective first conductor and reagent composition, the fourth region has the fourth working electrode and its respective first conductor and reagent composition, the fifth region has the first counter electrode and its respective second conductor and at least one redox species, the sixth region has the second counter electrode and its respective second conductor and at least one redox species, the seventh region has the third counter electrode and its respective second conductor and at least one redox species, and the eighth region has the fourth counter electrode and its respective second conductor and at least one redox species;

at least one sample port in fluid communication with the primary area, wherein the at least one sample port is where sample introduction occurs into the test sensor;

a first vent in fluid communication with the first region; and

a second vent in fluid communication with the second region.

32. An analyte test sensor, comprising:

at least two substrates in the form of a base and a lid combined to form a reservoir, the reservoir having a primary area between at least eight secondary analysis regions, the eight secondary analysis regions including a first region, a second region, a third region, a fourth region, a fifth region, a sixth region, a seventh region, and an eight region, the eight secondary analysis regions being distinct, separate, and structurally isolated to resist or eliminate diffusive or convective mixing of reagents between the secondary analysis regions during one or more analyses of a sample, the primary area having a sample port where sample introduction occurs into the test sensor;

four working electrodes and four counter electrodes including a first working electrode, a second working electrode, a third working electrode, a fourth working electrode, a first counter electrode, a second counter electrode, a third counter electrode, and a fourth counter electrode, each of the four working electrodes and the four counter electrodes being distinct and separate, each of the four working electrodes including a first conductor and a reagent composition, each of the reagent compositions having a different redox potential, each of the four counter electrodes including a second conductor and at least one redox species, the redox species of at least one counter electrode being different than the redox species of another counter electrode, the first conductors being electrically connected and the second conductors not being electrically connected;

wherein each of the four working electrodes and the four counter electrodes is disposed in a respective separate one of the eight secondary analysis regions such that the first region has the first working electrode and its respective first conductor and reagent composition, the second region has the second working electrode and its respective first conductor and reagent composition, the third region has the third working electrode and its respective first conductor and reagent composition, the fourth region has the fourth working electrode and its respective first conductor and reagent composition, the fifth region has the first counter electrode and its respective second conductor and at least one redox species, the sixth region has the second counter electrode and its respective second conductor and at least one redox species, the seventh region has the third counter electrode and its respective second conductor and at least one redox species, and the eighth region has the fourth counter electrode and its respective second conductor and at least one redox species;

where at least one of the conductors is disposed between the two substrates; and

wherein the sample port is defined at least by the two substrates and an edge of the conductor disposed between the two substrates, the edge of the conductor defining at least one of the working electrode and the counter electrode.

33. An analyte test sensor, comprising:

at least two substrates in the form of a base and a lid combined to form a reservoir, the reservoir including at least one primary area, at least one sample port, at least one vent, and at least eight secondary analysis regions, the eight secondary analysis regions including a first region, a second region, a third region, a fourth region, a fifth region, a sixth region, a seventh region, and an eight region, the eight secondary analysis regions being distinct, separate, and structurally isolated to resist or eliminate diffusive or convective mixing of reagents between the secondary analysis regions during one or more analyses of a sample;

four working electrodes and four counter electrodes including a first working electrode, a second working electrode, a third working electrode, a fourth working electrode, a first counter electrode, a second counter electrode, a third counter electrode, and a fourth counter electrode, each of the four working electrodes and the four counter electrodes being distinct and separate, each of the four working electrodes including a first conductor and a reagent composition, each of the reagent compositions having a different redox potential, each of the four counter electrodes including a second conductor and at least one redox species, the redox species of at least one counter electrode being different than the redox species of another counter electrode, the first conductors of the working electrodes being electrically connected, the second conductors of the counter electrodes not being electrically connected;

wherein each of the four working electrodes and the four counter electrodes is disposed in a respective separate one of the eight secondary analysis regions such that the first region has the first working electrode and its respective first conductor and reagent composition, the second region has the second working electrode and its respective first conductor and reagent composition, the third region has the third working electrode and its respective first conductor and reagent composition, the fourth region has the fourth working electrode and its respective first conductor and reagent composition, the fifth region has the first counter electrode and its respective second conductor and at least one redox species, the sixth region has the second counter electrode and its respective second conductor and at least one redox species, the seventh region has the third counter electrode and its respective second conductor and at least one redox species, and the eighth region has the fourth counter electrode and its respective second conductor and at least one redox species;

wherein the structural isolation of the secondary analysis regions is achieved by at least one of;

(a) a cross-sectional area of an entrance to each of the eight secondary analysis regions, (b) a distance between any two electrodes within each of the eight secondary analysis regions, or (c) a physical arrangement of each of the eight secondary analysis regions in relation to each other and in relation to the primary area, wherein the at least one sample port is where sample introduction occurs into the test sensor; and

wherein a fluid sample entering the at least one sample port does not flow across more than one electrode of the four working electrodes and the four counter electrodes to reach another electrode of the four working electrodes and the four counter electrodes.

34. An analyte test sensor, comprising;

at least two substrates in the form of a base and a lid combined to form a reservoir, the reservoir including at least one primary area and at least eight secondary analysis regions, the eight secondary analysis regions including a first region, a second region, a third region, a fourth region, a fifth region, a sixth region, a seventh region, and an eight region, the eight secondary analysis regions being distinct, separate, and structurally isolated such that chemical analysis of reagents is different in each of the secondary analysis regions during one or more analyses of a sample, the primary area having a sample port where sample introduction occurs into the test sensor;

four working electrodes and four counter electrodes including a first working electrode, a second working electrode, a third working electrode, a fourth working electrode, a first counter electrode, a second counter electrode, a third counter electrode, and a fourth counter electrode, each of the four working electrodes and the four counter electrodes being distinct and separate, each of the four working electrodes including a first conductor and a reagent composition, each of the reagent compositions having a different redox potential, each of the four counter electrodes including a second conductor and at least one redox species, the first conductors being electrically connected, the second conductors not being electrically connected;

wherein each of the four working electrodes and the four counter electrodes is disposed in a respective separate one of the eight secondary analysis regions such that the first region has the first working electrode and its respective first conductor and reagent composition, the second region has the second working electrode and its respective first conductor and reagent composition, the third region has the third working electrode and its respective first conductor and reagent composition, the fourth region has the fourth working electrode and its respective first conductor and reagent composition, the fifth region has the first counter electrode and its respective second conductor and at least one redox species, the sixth region has the second counter electrode and its respective second conductor and at least one redox species, the seventh region has the third counter electrode and its respective second conductor and at least one redox species, and the eighth region has the fourth counter electrode and its respective second conductor and at least one redox species;

wherein a first redox species in electrical communication with the second conductor of the first counter electrode is different than a second redox species in electrical communication with the second conductor of the second counter electrode;

wherein when a sample consists essentially of a pH 7 phosphate buffer, 0.1 M sodium phosphate, and 16% (w/w) polyvinyl pyrrolidone polymer having a weight average molecular weight of 2000 that is introduced to the first and the second secondary analysis regions at an atmospheric relative humidity of 45°

I and at a temperature of 22°

C., mixing of the first and the second redox species is not observed by an analysis technique selected from the group consisting of cyclic voltammetry and chemoamperometry within 12 minutes if the test sensor is not mechanically disturbed.

35. An analyte biosensor system, comprising:

at least two substrates in the form of a base and a lid combined to form a reservoir, the reservoir including at least one primary area, at least one sample port, at least two vents, and at least eight secondary analysis regions, the eight secondary analysis regions including a first region, a second region, a third region, a fourth region, a fifth region, a sixth region, a seventh region, and an eight region, the eight secondary analysis regions being distinct, separate, and structurally isolated such that chemical analysis of reagents is different in each of the secondary analysis regions during one or more analyses of a sample, the at least one sample port being where sample introduction occurs into the test sensor;

four working electrodes and four counter electrodes including a first working electrode, a second working electrode, a third working electrode, a fourth working electrode, a first counter electrode, a second counter electrode, a third counter electrode, and a fourth counter electrode, each of the four working electrodes and the four counter electrodes being distinct and separate, each of the four working electrodes including a first conductor and a reagent composition, each of the reagent compositions having a different redox potential, each of the four counter electrodes including a second conductor and at least one redox species, the redox species of at least one counter electrode being different than the redox species of another counter electrode, the first conductors being electrically connected, the second conductors not being electrically connected, each of the four working electrodes and the four counter electrodes being disposed in a respective separate one of the eight secondary analysis regions such that the first region has the first working electrode and its respective first conductor and reagent composition, the second region has the second working electrode and its respective first conductor and reagent composition, the third region has the third working electrode and its respective first conductor and reagent composition, the fourth region has the fourth working electrode and its respective first conductor and reagent composition, the fifth region has the first counter electrode and its respective second conductor and at least one redox species, the sixth region has the second counter electrode and its respective second conductor and at least one redox species, the seventh region has the third counter electrode and its respective second conductor and at least one redox species, and the eighth region has the fourth counter electrode and its respective second conductor and at least one redox species;

a sample interface in electrical communication with the conductors in the reservoir;

a sensor interface in electrical communication with the sample interface; and

a processor in electrical communication with the sensor interface, the processor being operable to determine the time when a fluid sample enters the reservoir and contacts the first working electrode, the processor being further operable to determine the time when a fluid sample enters the sample reservoir and contacts the first counter electrode;

wherein the structural isolation of the eight secondary analysis regions is achieved by at least one of (a) a cross-sectional area of an entrance to each of the eight secondary analysis regions, (b) a distance between any two electrodes within each of the eight secondary analysis regions, or (c) a physical arrangement of each of the eight secondary analysis regions in relation to each other and in relation to the primary area.

36. An analyte biosensor system, comprising:

a test sensor including a sample interface disposed on a first substrate in the form of a base, the sample interface being in electrical communication with a reservoir formed by combining the first substrate and a second substrate in the form of a lid, the reservoir having a primary area with at least one sample port and at least eight secondary analysis regions, the eight secondary analysis regions including a first region, a second region, a third region, a fourth region, a fifth region, a sixth region, a seventh region, and an eight region, the eight secondary analysis regions being distinct, separate, and structurally isolated such that chemical analysis of diffusive or convective mixing of reagents is different in each of the secondary analysis regions during one or more analyses of a sample, the at least one sample port being where sample introduction occurs into the test sensor;

four working electrodes and four counter electrodes including a first working electrode, a second working electrode, a third working electrode, a fourth working electrode, a first counter electrode, a second counter electrode, a third counter electrode, and a fourth counter electrode, each of the four working electrodes and the four counter electrodes being distinct and separate, each of the four working electrodes including a first conductor and a reagent composition, each of the reagent compositions having a different redox potential, each of the four counter electrodes including a second conductor and at least one redox species, the redox species of at least one counter electrode being different than the redox species of another counter electrode, the first conductors of the four working electrodes being electrically connected, the second conductors of the four counter electrodes not being electrically connected, each of the four working electrodes and the four counter electrodes being disposed in a respective separate one of the eight secondary analysis regions such that the first region has the first working electrode and its respective first conductor and reagent composition, the second region has the second working electrode and its respective first conductor and reagent composition, the third region has the third working electrode and its respective first conductor and reagent composition, the fourth region has the fourth working electrode and its respective first conductor and reagent composition, the fifth region has the first counter electrode and its respective second conductor and at least one redox species, the sixth region has the second counter electrode and its respective second conductor and at least one redox species, the seventh region has the third counter electrode and its respective second conductor and at least one redox species, and the eighth region has the fourth counter electrode and its respective second conductor and at least one redox species;

a sample interface in electrical communication with each of the first conductors and the second conductors in the reservoir; and

a measurement device including a computer readable storage medium, a processor, and a signal generator, where the signal generator is in electrical communication with the sensor interface, and where the sensor interface is in electrical communication with the sample interface;

wherein the processor is operable to

apply a first input signal at a first potential from the signal generator to at least one of the four working electrodes and at least a first counter electrode of the four counter electrodes,

apply a second input signal at a second potential from the signal generator to at least one of the four working electrodes and at least a second counter electrode of the four counter electrodes,

measure a first output signal from at least one of the four working electrodes and the first counter electrode, the first output signal being responsive to the first input signal,

measure a second output signal from at least one of the four working electrodes and the second counter electrode the second output signal being responsive to the second input signal,

analyze the first and the second output signals,

determine a first concentration of at least one first measurable species in a biological sample disposed in the reservoir at the potential of the first input signal,

determine a second concentration of at least one second measurable species in the biological sample disposed in the reservoir at the potential of the second input signal, and

convert at least one of the first and the second concentrations into a concentration of the analyte in the biological sample disposed in the reservoir.