Electrochemical biosensor test strip

Abstract

An electrochemical biosensor test strip with four new features. The test strip includes an indentation for tactile feel as to the location of the strips sample application port. The sample application port leads to a capillary test chamber, which includes a test reagent. The wet reagent includes from about 0.2% by weight to about 2% by weight polyethylene oxide from about 100 kilodaltons to about 900 kilodaltons mean molecular weight, which makes the dried reagent more hydrophilic and sturdier to strip processing steps, such as mechanical punching, and to mechanical manipulation by the test strip user. The roof of the capillary test chamber includes a transparent or translucent window which operates as a “fill to here” line, thereby identifying when enough test sample (a liquid sample, such as blood) has been added to the test chamber to accurately perform a test. The test strip may further include a notch located at the sample application port. The notch reduces a phenomenon called “dose hesitation”.

Description

wherein [Analyte] represents the concentration of the analyte in the sample (see FIG. 6), i_7.5 is the current (in microamps) measured at 7.5 seconds after application of the potential difference applied between the electrodes, C is the slope of line 30 (FIG. 6), and d is the axis intercept (FIG. 6).

By making measurements with known concentrations of analyte, calibration curve 30 (FIG. 6) may be constructed. This calibration will be stored in the Read Only Memory (ROM) key of the meter and will be applicable to a particular lot of test strips. Lines 31 and 32 in FIG. 6 represent other hypothetical calibration curves for two other different lots of test strips. Calibration for these biosensor lots would generate slightly different values for C and d in the above algorithm.

In a preferred method for analysis of glucose from a sample of human whole blood, current measurements are made at 0.5 second intervals from 3 seconds to 9 seconds after the potential difference is applied between the electrodes. These current measurements are correlated to the concentration of glucose in the blood sample.

In this example of measuring glucose from a blood sample, current measurements are made at different times (from 3 seconds to 9 seconds after application of the potential difference), rather than at a single fixed time (as described above), and the resulting algorithm is more complex and may be represented by the following equation:
[Glucose]=C₁i₁+C₂i₂+C₃i₃+ . . . C_ni_n+d,
wherein i₁ is the current measured at the first measurement time (3 seconds after application of the 300 millivolt potential difference), i₂ is the current measured at the second measurement time (3.5 seconds after application of the 300 millivolt potential difference), i₃ is the current measured at the third measurement time (4 seconds after application of the 300 millivolt potential difference), i_n is the current measured at the n^th measurement time (in this example, at the 13^th measurement time or 9 seconds after application of the 300 millivolt potential difference), C₁, C₂, C₃, and C_n are coefficients derived from a muiltivariate regression analysis technique, such as Principle Components Analysis or Partial Least Squares, and d is the regression intercept (in glucose concentration units).

Alternatively, the concentration of glucose in the sample being measured may be determined by integrating the curve generated by plotting current, i, versus measurement time over some time interval (for example, from 3 seconds to 9 seconds after application of the 300 millivolt potential difference), thereby obtaining the total charge transferred during the measurement period. The total charge transferred is directly proportional to the concentration of glucose in the sample being measured.

Further, the glucose concentration measurement may be corrected for differences between environmental temperature at the time of actual measurement and the environmental temperature at the time calibration was performed. For example, if the calibration curve for glucose measurement was constructed at an environmental temperature of 23° C., the glucose measurement is corrected by using the following equation:
[Glucose]_corrected=[Glucose]_measured×(1−K(T−23° C.)),
wherein T is the environmental temperature (in ° C.) at the time of the sample measurement and K is a constant derived from the following regression equation:
Y=K(T−23),
wherein $Y=\frac{{\left[\mathrm{Glucose}\right]}_{\mathrm{measured}\mathrm{at}23°C.}-{\left[\mathrm{Glucose}\right]}_{\mathrm{measured}\mathrm{at}7°C.}}{{\left[\mathrm{Glucose}\right]}_{\mathrm{measured}\mathrm{at}7°C.}}$
In order to calculate the value of K, each of a multiplicity of glucose concentrations is measured by the meter at various temperatures, T, and at 23° C. (the base case). Next, a linear regression of Y on T−23 is performed. The value of K is the slope of this regression.

Various features of the present invention may be incorporated into other electrochemical test strips, such as those disclosed in U.S. Pat. Nos. 5,120,420; 5,141,868; 5,437,999; 5,192,415; 5,264,103; and 5,575,895, the disclosures of which are hereby incorporated by reference.

Claims

1. A test strip, having an indentation along an edge for tactile identification of a sample application port, said test strip comprising:

a first insulating substrate having first and second surfaces, an indentation along an edge and a vent hole;

at least two electrically conductive tracks affixed to the first surface of the first insulating substrate;

a second insulating substrate having first and second surfaces, an indentation along an edge, and first and second openings, the second surface being affixed to the conductive tracks and the first surface of the first insulating substrate, the first opening exposing a portion of the conductive tracks for electrical connection to a meter capable of measuring an electrical property, the second opening being located along said edge and exposing a different portion of the conductive tracks and the vent hole;

a test reagent overlaying at least a portion of the conductive tracks exposed by the second opening; and

a roof having first and second surfaces and an indentation along an edge, the second surface of the roof being affixed to the first surface of the second insulating substrate and positioned so that the second surface of the roof and the surface of the first insulating substrate form opposing walls of a capillary fill chamber with a sample application port at said edge of the second insulating substrate, wherein the second opening in the second insulating substrate and the indentations in the first insulating substrate, the second insulating substrate, and the roof are aligned to thereby provide for tactile identification of the sample application port.

2. The test strip of claim 1, wherein the second surface of the roof includes a hydrophilic coating.

3. The test strip of claim 1, wherein the test reagent includes

reaction components appropriate for performing a test and from about 1.75% by weight to about 17.5% by weight polyethylene oxide having a mean molecular weight from about 100 kilodaltons to about 900 kilodaltons,

wherein the reagent will redissolve or resuspend upon addition of an aqueous test sample to the reagent.

4. The test strip of claim 1, wherein the test reagent includes reaction components appropriate for performing a test, and a dissolvable or suspendable film forming mixture including from about 0.2% by weight to about 2% by weight polyethylene oxide having a mean molecular weight from about 100 kilodaltons to about 900 kilodaltons,

wherein the test reagent may be applied to the test strip in a wet form, may be subsequently dried, and then redissolved or resuspended upon addition of an aqueous test sample to the dried reagent.

5. The test strip of claim 4, wherein the second surface of the roof includes a hydrophilic coating.

6. The test strip of claim 1, wherein the roof has a solid transparent or translucent window, which is dimensioned and positioned so that the window overlays the entire width of the electrically conductive track that is closest to the indentation of the first insulating substrate and at least about ten percent of the width of the other electrically conductive track.

7. The test strip of claim 6, wherein the second surface of the roof includes a hydrophilic coating.

8. The test strip of claim 6, wherein the test reagent includes

reaction components appropriate for performing a test and from about 1.75% by weight to about 17.5% by weight polyethylene oxide having a mean molecular weight from about 100 kilodaltons to about 900 kilodaltons,

wherein the reagent will redissolve or resuspend upon addition of an aqueous test sample to the reagent.

9. The test strip of claim 6, wherein the test reagent includes reaction components appropriate for performing a test, and a dissolvable or suspendable film forming mixture including from about 0.2% by weight to about 2% by weight polyethylene oxide having a mean molecular weight from about 100 kilodaltons to about 900 kilodaltons,

wherein the test reagent may be applied to the test strip in a wet form, may be subsequently dried, and then redissolved or resuspended upon addition of an aqueous test sample to the dried reagent.

10. The test strip of claim 9, wherein the second surface of the roof includes a hydrophilic coating.

11. The test strip of claim 1, further comprising:

a first notch along the indentation in the first insulating substrate, and a notch along the indentation in the roof, both first and second notches being positioned so that they overlay one another.

12. The test strip of claim 11, wherein the second surface of the roof includes a hydrophilic coating.

13. The test strip of claim 11, wherein the test reagent includes

reaction components appropriate for performing a test and from about 1.75% by weight to about 17.5% by weight polyethylene oxide having a mean molecular weight from about 100 kilodaltons to about 900 kilodaltons,

wherein the reagent will redissolve or resuspend upon addition of an aqueous test sample to the reagent.

14. The test strip of claim 11, wherein the test reagent includes reaction components appropriate for performing a test, and a dissolvable or suspendable film forming mixture including from about 0.2% by weight to about 2% by weight polyethylene oxide having a mean molecular weight from about 100 kilodaltons to about 900 kilodaltons,

wherein the test reagent may be applied to the test strip in a wet form, may be subsequently dried, and then redissolved or resuspended upon addition of an aqueous test sample to the dried reagent.

15. The test strip of claim 14, wherein the second surface of the roof includes a hydrophilic coating.

16. The test strip of claim 11 wherein the roof has a solid transparent or translucent window, which is dimensioned and positioned so that the window overlays the entire width of the electrically conductive track that is closest to the indentation of the first insulating substrate and at least about ten percent of the width of the other electrically conductive track.

17. The test strip of claim 16, wherein the second surface of the roof includes a hydrophilic coating.

18. The test strip of claim 16, wherein the test reagent includes reaction components appropriate for performing a test, and a dissolvable or suspendable film forming mixture including from about 0.2% by weight to about 2% by weight polyethylene oxide having a mean molecular weight from about 100 kilodaltons to about 900 kilodaltons,

wherein the test reagent may be applied to the test strip in a wet form, may be subsequently dried, and then redissolved or resuspended upon addition of an aqueous test sample to the dried reagent.

19. The test strip of claim 18, wherein the second surface of the roof includes a hydrophilic coating.

20. The test strip of claim 16, wherein the test reagent includes reaction components appropriate for the test, and a dissolvable or suspendable film forming mixture including from about 0.2% weight to about 2% by weight polyethylene oxide having a mean molecular weight of 300 kilodaltons.

21. The test strip of claim 20, wherein the polyethylene oxide is about 0.71% by weight.

22. The test strip of claim 16, wherein the test reagent includes

reaction components appropriate for performing a test and from about 1.75% by weight to about 17.5% by weight polyethylene oxide having a mean molecular weight from about 100 kilodaltons to about 900 kilodaltons,

wherein the reagent will redissolve or resuspend upon addition of an aqueous test sample to the reagent.

23. The test strip of claim 22, wherein the mean molecular weight of the polyethylene oxide is 300 kilodaltons.

24. The test strip of claim 23, wherein the amount of polyethylene oxide, in the reagent is about 6.2% by weight.

25. A test strip comprising:

a first insulating substrate having first and second surfaces, a notch along an edge, and a vent hole;

at least two electrically conductive tracks affixed to the first surface of the first insulating substrate;

a second insulating substrate having first and second surfaces and first and second openings, the second surface being affixed to the conductive tracks and the first surface of the first insulating substrate, the first opening exposing a portion of the conductive tracks for electrical connection to a meter capable of measuring an electrical property, the second opening being located along an edge of the second insulating substrate and exposing a different portion of the conductive tracks, the notch in the first insulating substrate, and the vent hole;

a test reagent overlaying at least a portion of the conductive tracks exposed by the second opening; and

a roof having first and second surfaces and a notch along an edge, the second surface of the roof being affixed to the first surface of the second insulating substrate and positioned so that 1) the second surface of the roof and the first surface of the first insulating substrate form opposing walls of a capillary fill chamber with a sample application port at said edge of the second insulating substrate, and 2) the notch in the roof overlays the notch in the first insulating substrate;

whereby the notch in the roof and the notch in the first insulating substrate will cause a liquid aqueous sample, when touched to the sample application port, to flow into the capillary chamber without significant hesitation.

26. A test strip, comprising:

a first insulating substrate having first and second surfaces and a vent hole;

at least two electrically conductive tracks affixed to the first surface of the first insulating substrate;

a second insulating substrate having first and second surfaces and first and second openings, the second surface being affixed to the conductive tracks and the first surface of the first insulating substrate, the first opening exposing a portion of the conductive tracks for electrical connection to a meter capable of measuring an electrical property, the second opening being located along an edge of the second insulating substrate and exposing a different portion of the conductive tracks and the vent hole;

a test reagent overlaying at least a portion of the conductive tracks exposed by the second opening; and

a roof having first and second surfaces and a solid transparent or translucent window, the second surface of the roof being affixed to the first surface of the second insulating substrate and positioned so that it overlays the second opening of the second insulating substrate and so that the second surface of the roof and the first surface of the first insulating substrate form opposing walls of a capillary fill chamber with a sample application port at said edge of the second insulating substrate, and the transparent or translucent window being dimensioned and positioned so that the window extends from the sample application port, and overlays the entire width of one of the electrically conductive tracks and at least about ten percent of the width of the other electrically conductive track.

27. A test strip, having an indentation along an edge for tactile identification of a sample application port, said test strip comprising:

a first insulating substrate having first and second surfaces and an indentation along an edge;

at least two electrically conductive tracks affixed to the first surface of the first insulating substrate;

a second insulating substrate having first and second surfaces, an indentation along an edge and an opening, the second surface being affixed to the conductive tracks and the first surface of the first insulating substrate, the second insulating substrate configured to expose a portion of the conductive tracks for electrical connection to a meter capable of measuring an electrical property, the opening being located along said edge and exposing a different portion of the conductive tracks;

a test reagent overlaying at least a portion of the conductive tracks exposed by the opening;

a roof having first and second surfaces and an indentation along an edge, the second surface of the roof being affixed to the first surface of the second insulating substrate and positioned so as to overlay the opening and so that the second surface of the roof and the first surface of the first insulating substrate form opposing walls of a capillary fill chamber with a sample application port at said edge of the second insulating substrate; and

a vent hole communicating with the capillary fill chamber;

wherein the opening in the second insulating substrate and the indentations in the first insulating substrate, the second insulating substrate, and the roof are aligned to thereby provide for tactile identification of the sample application port.

28. The test strip of claim 27, wherein the roof has a solid transparent or translucent window, which is dimensioned and positioned so that the window overlays the entire width of the electrically conductive track that is closest to the indentation of the first insulating substrate and at least about ten percent of the width of the other electrically conductive track.

29. The test strip of claim 27 further comprising a first notch along the indentation of the first insulating substrate, and a notch along the indentation in the roof, both first and second notches being positioned so that they overlay one another.

30. The test strip of claim 29 wherein the roof has a solid transparent or translucent window, which is dimensioned and positioned so that the window overlays the entire width of the electrically conductive track that is closest to the indentation of the first insulating substrate and at least about ten percent of the width of the other electrically conductive track.

31. A test strip comprising:

a first insulating substrate having first and second surfaces and a notch along an edge;

at least two electrically conductive tracks affixed to the first surface of the first insulating substrate;

a second insulating substrate having first and second surfaces and an opening, the second surface being affixed to the conductive tracks and the first surface of the first insulating substrate, the second insulating substrate configured to expose a portion of the conductive tracks for electrical connection to a meter capable of measuring an electrical property, the opening being located along an edge of the second insulating substrate and exposing a different portion of the conductive tracks, aid overlaying the notch in the first insulating substrate;

a test reagent overlaying at least a portion of the conductive tracks exposed by the opening;

a roof having first and second surfaces and a notch along an edge, the second surface of the roof being affixed to the first surface of the second insulating substrate and positioned so that 1) the second surface of the roof and the first surface of the first insulating substrate form opposing walls of a capillary fill chamber with a sample application port at said edge of the second insulating substrate, and 2) the notch in the roof overlays the notch in the first insulating substrate; and

a vent hole communicating with the capillary fill chamber;

whereby the notch in the roof and the notch in the first insulating substrate will cause a liquid aqueous sample, when touched to the sample application port, to flow into the capillary chamber without significant hesitation.

32. A test strip comprising:

a first insulating substrate having first and second surfaces;

at least two electrically conductive tracks affixed to the first surface of the first insulating substrate;

a second insulating substrate having first and second surfaces and an opening, the second surface being affixed to the conductive tracks and the first surface of the first insulating substrate, the second insulating substrate configured to expose a portion of the conductive tracks for electrical connection to a meter capable of measuring an electrical property, the opening being located along an edge of the second insulating substrate and exposing a different portion of the conductive tracks;

a test reagent overlaying at least a portion of the conductive tracks exposed by the opening;

a roof having first and second surfaces and a solid transparent or translucent window, the second surface of the roof being affixed to the first surface of the second insulating substrate and positioned so that it overlays the opening of the second insulating substrate and so that the second surface of the roof and the first surface of the first insulating substrate form opposing walls of a capillary fill chamber with a sample application port at said edge of the second insulating substrate, and the transparent or translucent window being dimensioned and positioned so that the window extends from the sample application port, and overlays the entire width of one of the electrically conductive tracks and at least about ten percent of the width of the other electrically conductive track; and

a vent hole communicating with the capillary fill chamber.

33. An electrochemical test strip for conducting testing for the concentration of glucose in a blood sample, comprising:

a strip body including an edge extending about the perimeter of said strip body, said strip body defining a capillary channel and a vent in fluid communication with the capillary channel, said strip body comprising a sample application port open at a location along the edge, the capillary channel extending from the sample application port to at least the vent;

at least working and counter electrodes spaced from each other and positioned within the capillary channel at a location spaced from the perimetric edge; and

a test reagent adjacent at least the working electrode,

the strip body defining an indentation in the edge extending through the entire strip body, the sample application port being located at the indentation, the indentation being wider than the sample application port.

34. The test strip of claim 33 in which said strip body comprises a bottom substrate, a spacer layer, and a top substrate, the spacer layer including an opening defining the capillary chamber and sample application port, the bottom and top substrates including recessed edge portions defining the indentation.

35. The test strip of claim 34 in which the recessed edge portions are aligned in an overlying relationship.

36. The test strip of claim 33 in which the edge includes first and second substantially collinear edge portions, the indentation including an edge portion located adjacent and between, and spaced inwardly of, the first and second edge portions.

37. The test strip of claim 36 in which the first and second edge portions are straight edge portions.

38. The test strip of claim 36 in which said strip body comprises a bottom substrate, a spacer layer, and a top substrate, the spacer layer including an opening defining the capillary chamber and sample application port, the bottom and top substrates including recessed edge portions defining the indentation.

39. The test strip of claim 38 in which the recessed edge portions are aligned in an overlying relationship.

40. The test strip of claim 33 in which the strip body defines a second indentation within the first indentation, the second indentation being narrower than, and extending inwardly of, the first indentation.

41. The test strip of claim 40 in which the sample application port is wider than the second indentation.

42. The test strip of claim 41 in which said strip body comprises a bottom substrate, a spacer layer, and a top substrate, the spacer layer including an opening defining the capillary chamber and sample application port, the bottom and top substrates including recessed edge portions defining the first and second indentations.

43. The test strip of claim 41 in which the second indentation is v-shaped.

44. The test strip of claim 41 in which the edge includes first and second substantially collinear edge portions, the first indentation including an edge portion located adjacent and between, and spaced inwardly of, the first and second edge portions.

45. The test strip of claim 44 in which the first and second edge portions are straight edge portions.

46. The test strip of claim 44 in which the second indentation is v-shaped.

47. An electrochemical test strip for conducting testing for the concentration of glucose in a blood sample, comprising:

a strip body including an edge extending about the perimeter of said strip body, said strip body defining a capillary channel and a vent in fluid communication with the capillary channel, said strip body comprising a sample application port open at a location along the edge, the capillary channel extending from the sample application port to at least the vent;

at least working and counter electrodes spaced from each other and positioned within the capillary channel at a location spaced from the perimetric edge; and

a test reagent adjacent at least the working electrode,

the strip body defining an indentation in the edge extending through the entire strip body, the sample application port being located at the indentation, the sample application port being wider than the indentation.

48. The test strip of claim 47 in which said strip body comprises a bottom substrate, a spacer layer, and a top substrate, the spacer layer including an opening defining the capillary chamber and sample application port, the bottom and top substrates including recessed edge portions defining the indentation.

49. The test strip of claim 48 in which the recessed edge portions are aligned in an overlying relationship.

50. The test strip of claim 47 in which the edge and the indentation are configured to form points at their junctures.

51. The test strip of claim 47 in which the indentation is v-shaped.

52. The test strip of claim 51 in which said strip body comprises a bottom substrate, a spacer layer, and a top substrate, the spacer layer including an opening defining the capillary chamber and sample application port, the bottom and top substrates including recessed edge portions defining the indentation.

53. The test strip of claim 47 in which the edge includes first and second substantially collinear edge portions, the indentation being located adjacent and between, and extending inwardly of, the first and second edge portions.

54. The test strip of claim 53 in which the first and second edge portions are straight edge portions.

55. The test strip of claim 54 in which said strip body comprises a bottom substrate, a spacer layer, and a top substrate, the spacer layer including an opening defining the capillary chamber and sample application port, the bottom and top substrates including recessed edge portions defining the indentation.

56. The test strip of claim 53 in which the first and second edge portions and the indentation are configured to form points at the junctures of each of the first and second edge portions and the indentation.

57. The test strip of claim 56 in which the first and second edge portions are straight edge portions.

58. The test strip of claim 57 in which said strip body comprises a bottom substrate, a spacer layer, and a top substrate, the spacer layer including an opening defining the capillary chamber and sample application port, the bottom and top substrates including recessed edge portions defining the indentation.

59. The test strip of claim 56 in which the indentation is v-shaped.

60. An electrochemical test strip for conducting testing for the concentration of glucose in a blood sample, comprising:

a strip body including an edge extending about the perimeter of said strip body, said strip body defining a capillary channel and a vent in fluid communication with the capillary channel, said strip body comprising a sample application port open at a location along the edge, the capillary channel extending from the sample application port to at least the vent;

at least working and counter electrodes spaced from each other and positioned within the capillary channel at a location spaced from the perimetric edge; and

a test reagent adjacent at least the working electrode,

the strip body defining a v-shaped indentation in the edge extending through the entire strip body, and the sample application port being located at the indentation.