Biosensors comprising heat sealable spacer materials

• US 20070240984A1
• Filed: 04/18/2006
• Published: 10/18/2007
• Est. Priority Date: 04/18/2006
• Status: Abandoned Application

• Current Assignee: Nipro Diagnostics, Inc.
• Original Assignee: Nipro Diagnostics, Inc.
• Inventors: Popovich, Natasha, Slomski, Dennis
• Application Number:
  US11/405,537
• Publication Number:
  US 20070240984A1
• Time in Patent Office: Days
• US Class Current: 204/403.10
• CPC Class Codes: G01N 27/3272 Test elements therefor, i.e. disposable laminated substrates with electrodes, reagent and channels optical biosensors G01N33/52

Abstract

Disclosed herein is a biosensor for measuring analyte in a fluid that comprises a substrate layer having disposed thereon at least one each of an electrode, cathode, anode, and a novel spacer material. The spacer material according to the present disclosure comprises a heat sealable organic layer that covers at least a portion of the anode and defines at least one edge of the anode, wherein the spacer material has at least one hole punched through it and defines a cavity or well for accepting chemistry. Also disclosed is a method of making such biosensors.

Claims

1. A biosensor for measuring analyte in a fluid, said biosensor comprising:

a substrate layer, said substrate layer comprising;

at least one electrode;

at least one cathode;

at least one anode;

at least one spacer material, wherein said spacer material comprises a heat sealable organic layer that covers at least a portion of the anode and defines at least one edge of said anode, wherein said spacer material has at least one hole punched through it, said hole defining at least one sample cavity or well;

a reaction reagent system located in said at least cavity or well, said reaction reagent system comprising an electron mediator and an oxidation-reduction enzyme specific for said analyte; and

a cover disposed over the sample cavity or well to form at least one capillary gap into which blood could be drawn.

2. The biosensor of claim 1, wherein said heat sealable organic layer comprises a polyester containing film with a polyolefin layer disposed thereon.

3. The biosensor of claim 2, wherein said polyester containing film comprises polyethylene terephthalate (PET).

4. The biosensor of claim 1, wherein said heat sealable layer activates at or above 85°

C.

5. The biosensor of claim 1, wherein said heat sealable layer defines two of four edges of said anode.

6. The biosensor of claim 5, wherein the two remaining edges of the anode are defined by lines ablated into said substrate layer by a laser.

7. The biosensor of claim 1, comprising two or more fill detect electrodes.

8. The biosensor of claim 1, wherein the at least one electrode is conducting and comprises a metal chosen from or derived from gold, platinum, rhodium, palladium, silver, iridium, carbon, steel, metallorganics, and mixtures thereof.

9. The biosensor of claim 8, wherein the at least one carbon electrode further comprising Cr.

10. The biosensor of claim 1, wherein the at least one electrode is semiconducting.

11. The biosensor of claim 10, wherein the semiconducting electrode comprises a material chosen from tin oxide, indium oxide, titanium dioxide, manganese oxide, iron oxide, and zinc oxide.

12. The biosensor of claim 10, wherein the at least one semiconducting electrode comprises zinc oxide doped with indium, tin oxide doped with indium, indium oxide doped with zinc, or indium oxide doped with tin.

13. The biosensor of claim 10, wherein the at least one semiconducting electrode comprises an allotrope of carbon doped with boron, nitrogen, or phosphorous.

14. The biosensor of claim 1, wherein the analyte is chosen from glucose, cholesterol, lactate, acetoacetic acid (ketone bodies), theophylline, and hemoglobin A1c.

15. The biosensor of claim 14, wherein the analyte comprises glucose and the at least one oxidation-reduction enzyme specific for the analyte is chosen from glucose oxidase, PQQ-dependent glucose dehydrogenase and NAD-dependent glucose dehydrogenase.

16. The biosensor of claim 1, wherein the electron mediator comprises a ferricyamide material, ferrocene carboxylic acid or a ruthenium containing material.

17. The biosensor of claim 16, wherein the ferricyamide material comprises potassium ferricyamide and the ruthenium containing material comprises ruthenium hexaamine (III) trichloride.

18. The biosensor of claim 1, wherein the reaction reagent system further comprises at least one buffer material comprising potassium phosphate.

19. The biosensor of claim 1, wherein the reaction reagent system further comprises at least one surfactant chosen from non-ionic, anionic, and zwitterionic surfactants.

20. The biosensor of claim 1, wherein the reaction reagent system further comprises at least one polymeric binder chosen from hydroxypropyl-methyl cellulose, sodium alginate, microcrystalline cellulose, polyethylene oxide, hydroxyethylcellulose, polypyrrolidone, PEG, and polyvinyl alcohol.

21. The biosensor of claim 1, wherein the reaction reagent system comprises 0.01 to 0.3% of a non-ionic surfactant and 0.1 to 3%, of a polymeric binder material.

22. The biosensor of claim 1, wherein the reaction reagent system comprises 0.05 to 0.25% of an alkyl phenoxy polyethoxy ethanol and 0.5 to 2.0% of polyvinyl alcohol.

23. The biosensor of claim 1, wherein the reaction reagent system comprises one or more secondary redox probes chosen from transition metal complexes, simple ions, organometallics, organic dyes, simple organics, and organic redox-active molecules.

24. The biosensor of claim 23, wherein the transition metal complexes comprise ferrocene derivatives, the simple ions comprise Fe(III) or Mn(II), the organic dyes comprise cresyl blue, the simple organics comprise gentisic acid (2,4-benzoic acid), and trihydrohybenzoic acid, and the organic redox-active molecules comprise peptides containing redox-active amino acids, and particles on the order of nm in size that contain redox-active components.

25. The biosensor of claim 1, wherein the heat sealable organic layer covers at least a portion of the electrode, or cathode, or a portion of both the electrode and cathode.

26. A method of making a biosensor for measuring an analyte, said method comprising:

applying an electroactive material onto a substrate to form a coated substrate;

forming patterns into said coated substrate layer by ablating the electroactive material with a laser, wherein said patterns form an electrode array comprising at least one electrode, cathode, and anode;

applying an organic film on said substrate such that it covers at least a portion of said patterns, wherein at least one hole has been punched into said organic film prior to depositing it onto said substrate, said hole forming at least one well when deposited onto said substrate, wherein said organic film comprises a heat sealable layer that covers at least a portion of the anode and defines at least one edge of said anode;

laminating said organic film onto said substrate by applying heat and pressure to said organic film; and

depositing within said at least one well a reaction reagent system comprising an electron mediator and an oxidation-reduction enzyme specific for said analyte; and

optionally applying a cover to form a capillary for sample application.

27. The method of claim 26, wherein said electroactive material is deposited by sputtering.

28. The method of claim 27, wherein said electroactive material comprises a conducting or semiconducting material.

29. The method of claim 28, wherein said conducting material comprises a metal chosen from or derived from gold, platinum, rhodium, palladium, silver, iridium, carbon, steel, metallorganics, and mixtures thereof.

30. The method of claim 29, wherein the at least one carbon electrode further comprising Cr.

31. The method of claim 28, wherein the semiconducting material is chosen from tin oxide, indium oxide, titanium dioxide, manganese oxide, iron oxide, and zinc oxide.

32. The method of claim 31, wherein the semiconducting material comprises zinc oxide doped with indium, tin oxide doped with indium, indium oxide doped with zinc, or indium oxide doped with tin.

33. The method of claim 28, wherein the semiconducting material comprises an allotrope of carbon doped with boron, nitrogen, or phosphorous.

34. The method of claim 26, wherein the electron mediator comprises a ferricyamide material, ferrocene carboxylic acid or a ruthenium containing material.

35. The method of claim 34, wherein the ferricyamide material comprises potassium ferricyamide and the ruthenium containing material comprises ruthenium hexaamine (III) trichloride.

36. The method of claim 26, wherein the reaction reagent system further comprises at least one buffer material comprising potassium phosphate.

37. The method of claim 26, wherein the reaction reagent system further comprises at least one surfactant chosen from non-ionic, anionic, and zwitterionic surfactants.

38. The method of claim 26, wherein the reaction reagent system further comprises at least one polymeric binder chosen from hydroxypropyl-methyl cellulose, sodium alginate, microcrystalline cellulose, polyethylene oxide, hydroxyethylcellulose, polypyrrolidone, PEG, and polyvinyl alcohol.

39. The method of claim 26, wherein the reaction reagent system comprises 0.01 to 0.3% of a non-ionic surfactant and 0.1 to 3%, of a polymeric binder material.

40. The method of claim 26, wherein the reaction reagent system comprises 0.05 to 0.25% of an alkyl phenoxy polyethoxy ethanol and 0.5 to 2.0% of polyvinyl alcohol.

41. The method of claim 26, wherein the reaction reagent system comprises one or more secondary redox probes chosen from transition metal complexes, simple ions, organometallics, organic dyes, simple organics, and organic redox-active molecules, and combinations thereof.

42. The method of claim 41, wherein the transition metal complexes comprise ferrocene derivatives, the simple ions comprise Fe(III) or Mn(II), the organic dyes comprise cresyl blue, the simple organics comprise gentisic acid (2,4-benzoic acid), and trihydrohybenzoic acid, and the organic redox-active molecules comprise peptides containing redox-active amino acids, and particles on the order of nm in size that contain redox-active components.

43. The method of claim 26, wherein said laminating of the organic film onto said substrate is performed at a temperature ranging from 300 to 400°

F. and pressure ranging from 20 to 60 psi.

44. A biosensor for measuring glucose levels in blood, said biosensor comprising:

a substrate layer, said substrate layer comprising;

at least one electrode;

at least one cathode;

at least one anode;

at least one spacer material that comprises a polyethylene terephthalate (PET) with a polyolefin layer disposed thereon, wherein said spacer material activates at or above 85°

C., and defines two of four edges of said anode, the two remaining edges of the anode being defined by lines ablated into said substrate layer by a laser,

wherein said spacer material has at least one hole punched through it, said hole defining a sample cavity or well;

a reaction reagent system located in said cavity or well, said reaction reagent system comprising an electron mediator chosen from a ferricyamide material, ferrocene carboxylic acid or a ruthenium containing material, and an oxidation-reduction enzyme chosen from glucose oxidase, PQQ-dependent glucose dehydrogenase and NAD-dependent glucose dehydrogenase; and

a cover disposed over the sample cavity or well to form at least one capillary gap into which blood could be drawn.

45. The biosensor of claim 44, wherein the reaction reagent system comprises one or more secondary redox probes chosen from transition metal complexes, simple ions, organometallics, organic dyes, simple organics, and organic redox-active molecules.

46. The biosensor of claim 45, wherein the transition metal complexes comprise ferrocene derivatives, the simple ions comprise Fe(III) or Mn(II), the organic dyes comprise cresyl blue, the simple organics comprise gentisic acid (2,4-benzoic acid), and trihydrohybenzoic acid, and the organic redox-active molecules comprise peptides containing redox-active amino acids, and particles on the order of nm in size that contain redox-active components.