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. A system for determining the concentration of glucose in a blood sample, the system comprising:

a test meter;

a test strip comprising:

a strip body including an edge surface 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 surface, the capillary channel having opposed sides 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 edge surface;

a test reagent adjacent at least the working electrode; and

visualization means associated with the capillary channel and including a solid, transparent or translucent viewing material extending from at least adjacent the sample application port and overlying at least a portion of the capillary channel including said working electrode and at least a portion of said counter electrode,

said strip body having opaque portions which, in combination with said viewing material, define a window effective for providing visual confirmation that a sufficient area of the working and counter electrodes is covered with sample to have a minimum sample amount for said test strip; and

wherein said test meter is adapted to:

receive said test strip,

connect to said working and counter electrodes,

apply a potential difference between said working and counter electrodes, and

determine the concentration of glucose in the blood sample.

34. A system for determining the concentration of glucose in a blood sample, the system comprising:

a test meter;

a test strip comprising:

a strip body including an edge surface 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 perimetric edge surface, the capillary channel extending from the sample application port to at least the vent, said strip body further defining a test area along the capillary channel between the sample application port and the vent;

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

a test reagent received within the test area of the capillary channel and adjacent at least the working electrode;

said strip body including a solid, transparent or translucent viewing material overlying at least a portion of the capillary channel, including from a portion thereof at or generally adjacent the sample application port continuously up to and including said working electrode and at least a portion of said counter electrode, the viewing material permitting visualization of the blood sample as it moves through the capillary channel to the test area;

said strip body further including opaque portions defining a fill area viewable through the viewing material, the fill area extending from adjacent the sample application port continuously up to the working electrode and at least a part of the counter electrode and limited to an area of the capillary channel needed to be filled to conduct an accurate test;

wherein observation through the viewing material of the blood sample within the capillary channel up to said electrodes comprises confirmation of sufficient blood sample being introduced into the capillary channel to conduct a test; and

wherein said test meter is adapted to:

receive said test strip,

connect to said working and counter electrodes,

apply a potential difference between said working and counter electrodes, and

determine the concentration of glucose in the blood sample.

35. A system for determining the concentration of glucose in a blood sample, the system comprising:

a test meter;

a test strip comprising:

a strip body including an edge surface 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 surface, the capillary channel having opposed sides 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 surface;

a test reagent adjacent at least the working electrode; and

visualization means associated with the capillary channel for enabling a user to visually identify when a sufficient amount of blood sample has been added to the capillary channel to accurately perform a test, said visualization means including a solid, transparent or translucent viewing material extending from at least adjacent the sample application port and overlying at least a portion of the capillary channel including said working electrode and at least a portion of said counter electrode, said visualization means further including said strip body having colored portions generally aligned with the opposed sides of the capillary channel from adjacent the sample application port to at least one of the electrodes, the viewing material and the colored portions defining a viewing area required to be filled to have a minimum sample amount for said test strip, the colored portions having a color which sufficiently contrasts with the color of the sample as viewed through the viewing material as to enable a user of reasonable visual acuity to determine if the viewing area is entirely full of the sample; and

wherein said test meter is adapted to:

receive said test strip,

connect to said working and counter electrodes,

apply a potential difference between said working and counter electrodes, and

determine the concentration of glucose in the blood sample.