Disposable sensor and method of making

• US 6,287,451 B1
• Filed: 06/02/1999
• Issued: 09/11/2001
• Est. Priority Date: 06/02/1999
• Status: Expired due to Term

• Current Assignee: Nova Biomedical Corporation (Nova Chemicals)
• Original Assignee: Nova Biomedical Corporation (Nova Chemicals)
• Inventors: Young, Chung Chang, Cai, Xiaohua, Winarta, Handani, Seto, Fung
• Primary Examiner(s): Tung, T.
• Assistant Examiner(s): NOGUEROLA, ALEXANDER STEPHAN
• Application Number:
  US09/324,443
• Time in Patent Office: 832 Days
• Field of Search: 204/403, 204/412, 205/777.5, 205/775, 205/792, 216/52, 438/460, 438/462, 438/463
• US Class Current: 205/777.5
• CPC Class Codes: C12Q 1/002 Electrode membranes
• CPC Class Codes: G01N 27/3272 Test elements therefor, i.e. disposable laminated substrates with electrodes, reagent and channels optical biosensors G01N33/52

Abstract

A disposable electrode strip for testing a fluid sample including a laminated strip with a first and second end, a reference electrode embedded in the laminated strip proximate to the first end, at least two working electrodes embedded in the laminated strip proximate to the first end and the reference electrode, an open path for receiving a fluid sample beginning from the first end and being sufficiently long to expose the reference electrode and the working electrodes to the fluid sample, and conductive contacts located at the second end of the laminated strip. The laminated strip has a base layer with a conductive coating, a reagent holding layer, a channel forming layer and a cover. One of the working electrodes contains a reagent substantially similar to the reagent of the reference electrode and a second working electrode contains a reagent having an enzyme.

Claims

1. A disposable electrode strip for testing a fluid sample comprising:

a laminated strip having a first strip end, a second strip end and a vent opening spaced from said first strip end, said laminated strip comprising a base layer with at least three electrodes delineated thereon, a reagent holding layer carried on said base layer, said reagent holding layer having at least three cutouts, a channel forming layer carried on said reagent holding layer, and a cover;

an enclosed channel between said first strip end and said vent opening, said enclosed channel containing said at least three cutouts;

a first reagent disposed in a first cutout of said at least three cutouts forming a reference electrode;

a second reagent disposed in a second cutout of said at least three cutouts forming a first working electrode, said second reagent being substantially similar to said first reagent;

a third reagent disposed in a third cutout of said at least three cutouts forming a second working electrode, said third reagent containing an enzyme; and

conductive contacts at said second strip end and insulated from said enclosed channel.

2. The electrode strip of claim 1 wherein said enzyme is glucose oxidase.

3. The electrode strip of claim 1 wherein said first reagent, said second reagent and said third reagent contain a redox mediator.

4. The electrode strip of claim 3 wherein said first reagent, said second reagent and said third reagent further contain at least one of a stabilizer, a binder, a surfactant, and a buffer.

5. The electrode strip of claim 4 wherein said stabilizer is a polyalkylene glycol, said binder is a cellulose material, and said surfactant is a polyoxyethylene ether.

6. The electrode strip of claim 5 wherein said stabilizer is polyethylene glycol, said binder is methyl cellulose, said surfactant is t-octylphenoxypolyethoxyethanol, and said buffer is a citrate buffer.

7. The electrode strip of claim 6 wherein said first reagent and said second reagent are made of a mixture having starting components comprising about 1 wt % of said potassium ferricyanide, about 2.5 wt % of said polyethylene glycol, about 1 wt % of said methyl cellulose, about 0.03 wt % of said t-octylphenoxypolyethoxyethanol, and said citrate buffer is about 0.05M.

8. The electrode strip of claim 6 wherein said third reagent is made of a mixture having starting components comprising about 6.5 wt % of said potassium ferricyanide, about 2.5 wt % of said polyethylene glycol, about 1 wt % of said methyl cellulose, about 0.03 wt % of said t-octylphenoxypolyethoxyethanol, and said pH buffer is about a 0.05M citrate buffer, and about 1 wt % of said enzyme.

9. The electrode strip of claim 8 wherein said enzyme is glucose oxidase.

10. The electrode strip of claim 4 wherein said first reagent, said second reagent and said third reagent are made from a mixture having starting components comprising about 1 wt % to about 6.5 wt % of said redox mediator, about 2.5 wt % of said stabilizer, about 1 wt % of said binder, and about 0.03 wt % of said surfactant in said buffer.

11. The electrode strip of claim 10 wherein said citrate buffer is about 0.05M.

12. The electrode strip of claim 3 wherein said redox mediator is at least one metal complex.

13. The electrode strip of claim 3 wherein said at least one redox mediator is selected from the group consisting of potassium ferricyanide and other inorganic and organic redox mediators.

14. The electrode strip of claim 1 wherein said base layer has a conductive coating disposed thereon for forming said at least three electrodes.

15. The electrode strip of claim 14 wherein said conductive coating is gold.

16. The electrode strip of claim 14 wherein said conductive coating comprising gold and tin oxide.

17. The electrode strip of claim 14 wherein said base layer, said reagent holding layer, said channel forming layer, and said cover are made of a plastic dielectric material.

18. The electrode strip of claim 17 wherein said plastic material is selected from the group consisting of polyvinyl chloride, polycarbonate, polysulfone, nylon, polyurethane, cellulose nitrate, cellulose propionate, cellulose acetate, cellulose acetate butyrate, polyester, acrylic, and polystyrene.

19. The electrode strip of claim 1 wherein said enclosed channel is hydrophilic.

20. The electrode strip of claim 1 wherein said enclosed channel has a volume of about 1.44 microliters.

21. The electrode strip of claim 1 wherein said cover has a hydrophilic coating on at least one side.

22. The electrode strip of claim 1 wherein said channel forming layer has a thickness sufficient to optimize the flow of said fluid sample along said open path.

23. The electrode strip of claim 22 wherein said thickness is about 0.007 inches (0.1778 mm).

24. The electrode strip of claim 1 wherein the surface area of said first working electrode is substantially same as the surface area of said second working electrode.

25. A method of using an electrode strip for determining the concentration of an analyte, said electrode strip having a first working electrode, a second working electrode and a reference electrode wherein said first working electrode contains an enzyme capable of catalyzing a reaction involving a substrate for the enzyme, said first working electrode, said second working electrode and said reference electrode being disposed in a fluid sample channel for measuring a fluid sample, said method comprising:

disposing said fluid sample into said channel of said electrode strip;

applying a potential between said reference electrode and said first working electrode which contains said enzyme;

measuring a first current generated between said first working electrode and said reference electrode and correlating said first current to a concentration of said analyte in said fluid sample;

measuring a resistance value of said fluid sample between said second working electrode and said reference electrode;

applying said resistance value to a first equation and determining the hematocrit level of said fluid sample; and

calculating a corrected concentration of said analyte using a second equation to correct for the presence of hematocrit in said sample.

26. The method of claim 25 wherein said method further comprising:

applying a potential between said reference electrode and said second working electrode;

measuring a second current generated between said second working electrode and said reference electrode;

subtracting said second current from said first current and obtaining a current difference, correlating said current difference to a concentration of said analyte in said fluid sample.

27. The method of claim 26 wherein said method further includes triggering said current measuring step when said fluid sample contacts said first working electrode, said second working electrode and said reference electrode creating said first current and said second current.

28. The method of claim 27 wherein said method further includes reading a current value for each of said first current and said second current at about a time where said current values for each of said first current and said second current reach a steady-state.

29. The method of claim 28 wherein said reading is taken at about 20 seconds after said current measuring step is triggered.

30. A disposable electrode strip for detecting or measuring the concentration of at least one analyte in a fluid sample, said electrode strip comprising:

an insulating base strip having a first base end and a second base end;

a conductive layer disposed on one side of said base strip delineating at least three electrically-distinct conductive paths insulated from each other;

a first electrical insulator sized smaller than said insulating base strip and overlaying a substantial portion of said conductive layer, said first insulator having at least a first cutout portion and a second cutout portion spaced from said first base end, said first cutout portion exposing a limited area of a first of

said at least three conductive paths and said second cutout portion exposing a limited area of a second and a third of said at least three conductive paths;

at least two electrode materials wherein a first material of said at least two electrode materials is a reagent for measuring the concentration of said at least one analyte and wherein a second material of said at least two electrode materials is a material suitable for use as a reference material and for measuring the resistance of said fluid sample, said first material being disposed in said first cutout potion and said second material being disposed in said second cutout portion, said second material being scored to isolate said second material disposed on said second of said at least three conductive paths from said second material disposed on said third of said at least three conductive paths; and

a second electrical insulator sized to fit over and coextensive with said first electrical insulator, said second insulator having an opening configured to expose an area of said first insulator a limited distance from said first base end of said insulating base strip, said area including said at least two cutout portions of said first insulator; and

a third electrical insulator sized to fit over and coextensive with said second insulator creating a sample fluid channel, said third insulator having a third insulator vent aperture spaced from said first base end and configured to expose at least a small portion of said opening of said second insulator.

31. The strip of claim 30 wherein said sample fluid channel has a volume of 1.44 microliters.

32. The strip of claim 30 wherein said sample fluid channel is hydrophilic.

33. The device of claim 30 wherein said first material and said second material are mixtures having starting components comprising a redox mediator, a stabilizer, a binder, a surfactant, and a buffer.

34. The strip of claim 33 wherein said redox mediator is at least one metal complex selected from the group consisting of ferrocene, ferrocene derivatives and potassium ferricyanide, said stabilizer is a polyalkylene glycol, said binder is a cellulose material, said surfactant is a polyoxyethylene ether, and said buffer has a pH of about 5 to about 6.

35. The strip of claim 34 wherein said mediator is potassium ferricyanide, said stabilizer is polyethylene glycol, said binder is methyl cellulose, said surfactant is t-octylphenoxypolyethoxyethanol, and said buffer is a citrate buffer.

36. The strip of claim 35 wherein said first material is made of a mixture having starting components comprising about 1 wt % of said potassium ferricyanide, about 2.5 wt % of said polyethylene glycol, about 1 wt % of said methyl cellulose, and about 0.03 wt % of said t-octylphenoxypolyethoxyethanol in said citrate buffer.

37. The strip of claim 35 wherein said second material is made of a mixture having starting components comprising about 6.5 wt % of said potassium ferricyanide, about 2.5 wt % of said polyethylene glycol, about 1 wt % of said methyl cellulose, about 0.03 wt % of said t-octylphenoxypolyethoxyethanol, and about 1 wt % of an enzyme in said citrate buffer.

38. The strip of claim 37 wherein said enzyme is glucose oxidase.

39. The strip of claim 30 wherein said insulating base strip, said first electrical insulator, said second electrical insulator, and said third electrical insulator are made from a plastic material selected from the group consisting of polyvinyl chloride, polycarbonate, polysulfone, nylon, polyurethane, cellulose nitrate, cellulose propionate, cellulose acetate, cellulose acetate butyrate, polyester, acrylic, and polystyrene.

40. A method of making multiple, disposable sensors wherein each sensor has a first working electrode, a second working electrode and a reference electrode, wherein said first working electrode contains an enzyme capable of catalyzing a reaction involving a substrate for the enzyme, said first working electrode, said second working electrode and said reference electrode being disposed in a fluid sample channel for measuring a fluid sample, said method comprising:

obtaining a base strip of an insulating material having a layer of conductive material disposed thereon, said base strip having a first edge and a second edge;

scribing in said conductive material a plurality of lines in a repetitive pattern wherein said plurality of lines contain a repetitive pattern forming three conductive paths in each of said repetitive pattern;

disposing a first middle layer of insulating material over said base strip, said first middle layer having a repetitive pattern of three cutouts wherein each cutout of each of said repetitive pattern exposes an electrode portion of each of said three conductive paths of each repetitive pattern wherein said repetitive pattern of said three cutouts are spaced from said first edge of said base strip, and wherein said first middle layer is sized to expose a contact portion of each of said three conductive paths of each repetitive pattern for a distance from said second edge of said base strip;

disposing a first reagent material on two of said three cutouts of each repetitive pattern and a second reagent material on the other of said three cutouts of each repetitive pattern;

drying said first reagent material and said second reagent material;

overlaying a second middle layer of insulating material over and coextensive with said first middle layer;

said second middle layer having a plurality of elongated cutout portions in a repetitive pattern wherein each of said elongated cutout portions exposes a corresponding repetitive pattern of said three cutouts said first middle layer;

disposing a top layer of insulating material over and coextensive with said second middle layer, said top layer having a plurality of vent openings in a repetitive pattern wherein each of said vent openings exposes a portion of a corresponding repetitive pattern of said elongated cutout portion furthest from said first edge of said base strip; and

separating each of said repetitive pattern forming one of each of said disposable sensors.

41. The method of claim 40 further comprising drying said first reagent material and said second reagent material at a temperature and for a length of time sufficient to allow said first reagent material and said second reagent material to solidify and adhere to each of said electrode portion of each of said repetitive pattern of said three conductive paths.

42. The method of claim 40 further comprising cutting along said first edge of each of said sensors and transverse to said sensors a predetermined distance creating a sample inlet port.