Heterogeneous membrane electrodes

• US 20040231984A1
• Filed: 06/01/2004
• Published: 11/25/2004
• Est. Priority Date: 12/02/2002
• Status: Active Grant

• Current Assignee: Siemens Healthcare Diagnostics Incorporated (Siemens AG)
• Original Assignee: Epocal Incorporated (Siemens AG)
• Inventors: Bales, Michael, Oussova, Alexandra, Varlan, Anca, Lauks, Imants
• Granted Patent: US 7,767,068 B2
• Time in Patent Office: Days
• US Class Current: 204/416
• CPC Class Codes: B01L 2200/025 Align devices or objects to ensure defined positions relative to each other
• CPC Class Codes: B01L 2200/148 Specific details about calibrations
• CPC Class Codes: B01L 2300/0645 Electrodes
• CPC Class Codes: B01L 2300/0825 Test strips
• CPC Class Codes: B01L 2300/0883 Serpentine channels
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/0683 mechanically breaking a wall or membrane within a channel or chamber
• CPC Class Codes: B01L 3/5027 by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: G01N 27/301 Reference electrodes
• CPC Class Codes: G01N 27/307 Disposable laminated or multilayered electrodes G01N27/3272 takes precedence
• CPC Class Codes: G01N 27/31 Half-cells with permeable membranes, e.g. semi-porous or perm-selective membranes

Abstract

The present invention relates to planar electrochemical sensors with membrane coatings used to perform chemical analyses. The object of this invention is to provide unit-use disposable sensors of very simple and inexpensive construction, preferably with only a single membrane coating on an electrode. The invented devices are potentiometric salt-bridge reference electrodes and dissolved gas sensors constructed with a heterogeneous membrane coating of a conductor. The heterogeneous membrane, which is an intimate admixture of a hydrophobic and a hydrophilic compartment, concurrently supports constrained transport of non-volatile species through its hydrophilic compartment and rapid gas and water vapor transport through its hydrophobic compartment.

Claims

1. An electrode for use in an electrochemical sensing device for the analysis of an aqueous sample, comprising

an electric conductor;

an insulator covering the conductor except in an electrode region; and

a heterogeneous membrane for direct contact with the sample, the heterogeneous membrane being in physical contact with the insulator at the electrode region and in electrical contact with the conductor in the electrode region, wherein the heterogeneous membrane is an intimate admixture of a hydrophobic, gas permeable compartment and a hydrophilic compartment which is electrolyte salt permeable.

2. The electrode of claim 1, wherein the hydrophilic compartment constitutes an internal reagent reservoir

3. The electrode of claim 1, further comprising

a hydrophilic layer in electrical contact with the conductor in the electrode region, wherein the heterogeneous membrane is in physical contact with the insulating layer at the electrode region and in electrical contact with the hydrophilic layer in the electrode region, at least one of the hydrophilic layer and the hydrophilic compartment of the heterogeneous membrane constituting an internal reservoir.

4. The electrode as defined in claim 1, wherein the membrane layer is in a substantially dry, inactive condition and convertible into a wet-up, active condition by exposure to an aqueous fluid.

5. The electrode as defined in claim 2, wherein the membrane layer is in a substantially dry, inactive condition and convertible into a wet-up, active condition by exposure to an aqueous fluid and the internal reservoir includes reagents and in the active condition, upon exposure to the aqueous sample fluid, permits diffusion of the reagents from the membrane layer into the sample fluid.

6. The electrode as defined in claim 5, wherein the membrane in the active condition further permits diffusion of contaminants into the membrane layer.

7. The electrode as defined in claim 1 for use in a unit-use disposable salt-bridge reference electrode.

8. The electrode as defined in claim 1 for use in a unit-use disposable potentiometric gas sensor.

9. The electrode as defined in claim 1 for use as a unit-use disposable polarographic gas electrode.

10. The electrode as defined in claim 1, wherein the conductor is a gold layer.

11. The electrode as defined in claim 1, wherein the heterogeneous membrane is a layer cast from a liquid.

12. The electrode as defined in one of claim 1, wherein the heterogeneous membrane is cast from an oil in water emulsion

13. The electrode as defined in claim 12, wherein the oil portion of the emulsion comprises a polymer or polymer precursor or, a mixtures of polymers or polymer precursors, or derivatized polymers or polymer precursors selected from the following polymer families:

polysiloxanes, polyurethanes, polyphosphazenes, polybutadienes, polyisoprenes, epoxies, polyvinylacetates

14. The electrode as defined in claim 12, wherein the water portion of the emulsion comprises a dissolved polymer or a polymer precursor, or mixtures of polymers or derivatized polymers selected from the following group of polymer families:

polyvinylalcohols, polyhydroxymethacrylates, polyacrylamides, polysaccharides, cellulosic polymers and gelatins

15. The electrode as defined in claim 11, wherein the heterogeneous membrane is cast by a method selected from the group of printing by dispensing through a nozzle, pin-transfer printing, spin-coating, dip-coating, and screen-printing.

16. The electrode as defined in claim 1, wherein the hydrophobic compartment comprises a polymer or a derivatized polymer, or mixtures of polymers or derivatized polymers selected from the following group of polymer families:

polysiloxanes, polyurethanes, polyphosphazenes, polybutadienes, polyisoprenes, epoxies, polyvinylacetates and combinations thereof.

17. The electrode as defined in claim 1, wherein the hydrophilic compartment includes a hydrophilic polymer or a mixture of polymers including derivatized polymers selected from the following group of polymer families:

polyvinylalcohols, polyhydroxyacrylates, polyacrylamides, polysaccharides, cellulosic polymers and gelatins and combinations thereof.

18. The electrode of claim 1, for use in a sensing device constructed for sequential exposure of the electrode to an aqueous calibrator fluid and the sample fluid.

19. The electrode of claim 1, wherein the hydrophobic compartment includes a gas permeable polymer and the hydrophilic compartment includes a hydrophilic polymer, at least one of the hydrophobic polymer and the hydrophilic polymer being cross-linkable.

20. The electrode of claim 19, wherein the at least one polymer is at least partially cross-linked.

21. The heterogeneous membrane of claim 20, wherein the at least one polymer was cross-linked by a photo-initiated cross-linking process.

22. The electrode of claim 19, wherein the membrane is cast from a liquid and the cross-linking is performed after casting

23. The electrode of claim 1, wherein the heterogeneous membrane has a gas diffusion coefficient and a salt diffusion coefficient and wherein the gas diffusion coefficient is at least 10 times larger than the salt diffusion coefficient.

24. The electrode of claim 23, wherein the gas diffusion coefficient is at least 50 times larger than the salt diffusion coefficient.

25. The electrode of claim 1, wherein the heterogeneous membrane has a gas diffusion coefficient and a salt diffusion coefficient and wherein the gas diffusion coefficient is greater than 1×

10<sup>−

6</sup> cm² s<sup>−

1</sup> and the salt diffusion coefficient is less than 1×

10<sup>−

7</sup> cm² s<sup>−

1</sup>.

26. The electrode of claim 1, wherein the hydrophilic compartment is less than 5% by volume of the total volume of the heterogeneous membrane.

27. The electrode of claim 1, wherein the electric conductor is a metal foil and the insulator is a foil laminated thereto.

28. The electrode as defined in claim 2 for use as a potentiometric reference electrode, wherein the internal reservoir also includes a redox salt for electrochemical reaction at the electric conductor.

29. The electrode as defined in claim 28 for use as a potentiometric reference electrode, wherein the hydrophilic compartment comprises a salt composition which is approximately equi-transferrent.

30. The electrode as defined in claim 28, wherein the redox salt is selected from the group of ferrocyanide, ferricyanide, Prussian blue and combinations thereof.

31. The electrode as defined in claim 1 for use as a potentiometric reference electrode, wherein the heterogeneous membrane comprises a hydrophobic compartment containing acrylated siloxane and a hydrophilic compartment containing polyvinylalcohol.

32. The electrode of claim 1 for use as a polarographic oxygen electrode, wherein the heterogeneous membrane has an oxygen permeability of less than 6×

10<sup>−

13</sup> mole cm<sup>−

1</sup> s<sup>−

1</sup> atm<sup>−

1</sup>.

33. The electrode of claim 1 for use as a polarographic oxygen electrode wherein the hydrophobic compartment contains a compound selected from the group of acrylated epoxy, acrylated urethane, blends thereof and copolymers of at least one of acrylated epoxy and acrylated urethane with a polyol, and the hydrophilic compartment contains polyvinylalcohol.

34. The electrode of claim 2 for use as a potentiometric carbon dioxide electrode, wherein the internal reservoir contains bicarbonate salt and a pH sensitive redox salt.

35. The electrode of claim 34, wherein the internal reservoir also contains carbonic anhydrase.

36. The electrode of claim 34, wherein the pH sensitive redox salt is selected from the group of hydroquinone, benzoquinone, and combinations thereof.

37. The electrode of claim 34, wherein the bicarbonate salt is loaded into the dry internal reservoir in an amount to give a concentration in the range of 50 mM to 800 mM after wet up.

38. The electrode of claim 1 for use as a potentiometric carbon dioxide electrode, wherein the hydrophobic compartment contains acrylated siloxane and the hydrophilic compartment contains polyvinylalcohol.

39. The electrode of claim 1 for use in an electrochemical sensing apparatus for the analysis of an enzyme substrate in an aqueous sample, wherein the internal reservoir contains an enzyme and a redox salt.

55. An electrochemical sensing device for the analysis of an aqueous sample, comprising a diagnostic card body, and

an electrode as defined in claim 1 mounted to the card body.

56. The electrochemical sensing device as defined in claim 55, for use as a potentiometric reference electrode, wherein one of the hydrophilic compartment and the hydrophilic layer contains bicarbonate salt and a pH sensitive redox salt.

57. The electrochemical sensing device as defined in claim 56, wherein the hydrophilic compartment comprises a salt composition which is approximately equi-transferrent.

58. The electrochemical sensing device as defined in claim 55, wherein the hydrophobic compartment contains acrylated siloxane and the hydrophilic compartment contains polyvinylalcohol.

59. The electrochemical sensing device of claim 55, for use as a polarographic oxygen sensor, wherein the heterogeneous membrane has an oxygen permeability of less than 6×

10<sup>−

13</sup> mole cm<sup>−

1</sup> s<sup>−

1</sup> atm<sup>−

1</sup>.

60. The electrochemical sensing device of claim 59, wherein the hydrophobic compartment contains epoxy-polyol and the hydrophilic compartment contains polyvinylalcohol.

61. The electrochemical device of claim 56, wherein the one of the hydrophilic compartment and hydrophilic layer further contains carbonic anhydrase.

40. An electrode for use in an electrochemical sensing device for the analysis of an aqueous sample, comprising

an electric conductor;

an insulating layer on the conductor, the insulating layer having a through-going aperture defining an electrode region; and

a heterogeneous membrane for direct contact with the sample, the membrane in physical contact with the insulating layer in the electrode region and in electrical contact with the conductor, wherein the heterogeneous membrane is an intimate admixture of hydrophobic, gas permeable compartments and hydrophilic electrolyte salt permeable compartments so that the membrane has interpenetrating networks of the hydrophobic and hydrophilic compartments.

41. A heterogeneous membrane for an electrochemical sensing electrode for direct exposure to a sample, the membrane comprising

a number of first hydrophobic, gas permeable compartments;

and

a number of second hydrophilic electrolyte salt permeable compartments, wherein the first and second compartments are intimately admixed to form an interpenetrating network.

42. The heterogeneous membrane of claim 41, wherein the hydrophobic compartments are in excess by volume over the hydrophilic compartments so that a gas diffusion coefficient of a gas species through the hydrophobic compartments is larger than a salt diffusion coefficient of species dissolved in water.

43. The heterogeneous membrane of claim 42, wherein the gas diffusion coefficient is at least 10 times larger than the salt diffusion coefficient.

44. The heterogeneous membrane of claim 42, wherein the gas diffusion coefficient is at least 50 times larger than the salt diffusion coefficient.

45. The heterogeneous membrane of claim 41, wherein the heterogeneous membrane has a gas diffusion coefficient and a salt diffusion coefficient and wherein the gas diffusion coefficient is greater than 1×

10<sup>−

8</sup> cm² s<sup>−

1</sup> and the salt diffusion coefficient is less than 1×

10<sup>−

7</sup> cm² s<sup>−

1</sup>.

46. The heterogeneous membrane of claim 41, wherein the hydrophilic compartments constitute less than 5% by volume of the total volume of the heterogeneous membrane.

47. The heterogeneous membrane of claim 41, wherein the hydrophilic compartments constitute an internal reagent reservoir containing at least a bicarbonate salt and a pH sensitive redox couple.

48. The heterogenous membrane of claim 41, wherein the hydrophobic compartments include a polydimethylsiloxane hydrophobic polymer and the hydrophilic compartment includes a cross-linked polyvinylalcohol containing bicarbonate salt and quinhydrone.

49. A method of manufacturing a heterogeneous membrane as defined in claim 41 in the form of an oil-in-water emulsion, comprising the steps of

dissolving components of the hydrophilic compartment in an aqueous solution;

premixing components of an oil phase of the emulsion;

admixing the aqueous solution and oil phase to a smooth blend avoiding foam formation;

emulsifying the resulting mixture; and

printing the emulsified membrane components onto an electrode carrier.

50. The method of claim 49, wherein the emulsified membrane components are applied to the electrode carrier by one of pin transfer printing and micro dispensing.

51. The method of claim 49, wherein the components of the hydrophilic compartment include a hydrophilic binder polymer, an emulsifier and a salt.

52. The method of claim 49, wherein the oil phase of the emulsion includes a hydrophobic polymer.

53. The method of claim 52, wherein the oil phase further includes a cross-linker.

54. The method of claim 49, wherein the step of emulsifying is carried out on ice and the shear rate during the emulsifying is gradually increased until a specific surface area of about 2.5 m²/mL is achieved, corresponding to a mean particle dimension of less than 1 micrometer.