Enzyme sensor with a cover membrane layer covered by a hydrophilic polymer

• US 20060275857A1
• Filed: 05/16/2006
• Published: 12/07/2006
• Est. Priority Date: 05/17/2005
• Status: Active Grant

• Current Assignee: Radiometer Medical ApS (Danaher Corporation)
• Original Assignee: Radiometer Medical ApS (Danaher Corporation)
• Inventors: Clausen, Lydia Dahl, Kjaer, Thomas
• Granted Patent: US 7,959,791 B2
• Time in Patent Office: Days
• US Class Current: 435/23
• CPC Class Codes: C12Q 1/002 Electrode membranes

Abstract

The present disclosure relates to an improved enzyme sensor comprising a cover membrane layer of a porous polymeric material, the outer surface and pore mouths of at least one face of the porous polymeric material being covered by a hydrophilic polymer. The sensor is useful determining the presence or amount of biologicial analytes, e.g., glucose, lactate, creatine, creatinine, etc.

Claims

1. An enzyme sensor for determining the concentration of an analyte in a fluid sample, comprising

an electrode,

at least one enzyme layer and

a cover membrane layer for the at least one enzyme layer,

wherein the cover membrane comprises at least one porous polymeric material, and wherein the outer surface and pore mouths of at least one face of the at least one porous polymeric material are covered by a hydrophilic polymer selected from hydrophilic polyurethanes and hydrophilic poly(meth)acrylates.

2. The enzyme sensor according to claim 1, wherein the at least one porous polymeric material of the cover membrane layer is at least partly impregnated with the hydrophilic polymer.

3. The enzyme sensor according to claim 1, wherein the at least one porous polymeric material has a porosity of in the range of about 0.002 to about 30% (vol/vol).

4. The enzyme sensor according to claim 1, wherein the at least one porous polymeric material is track-etched.

5. The enzyme sensor according to claim 4, wherein the pore density of the at least one porous polymeric material is in the range of about 40,000 to about 40,000,000 pores per cm².

6. The enzyme sensor according to claim 4 or claim 5, wherein average pore size of the at least one porous polymeric material is in the range of about 0.05 to about 250 nm.

7. The enzyme sensor according to claim 1, wherein the hydrophilic polymer is selected from hydrophilic polyurethanes.

8. The enzyme sensor according to claim 7, wherein the hydrophilic polyurethanes are selected from aliphatic polyether urethanes, aliphatic polyether urethaneureas, cycloaliphatic polyether urethanes, cycloaliphatic polyether urethaneureas, aromatic polyether urethanes, aromatic polyether urethaneureas, aliphatic polyester urethanes, aliphatic polyester urethaneureas, cycloaliphatic polyester urethanes, cycloaliphatic polyester urethaneureas, aromatic polyester urethanes, and aromatic polyester urethaneureas.

9. The enzyme sensor according to claim 1, wherein the hydrophilic polymer is selected from hydrophilic poly(meth)acrylates.

10. The enzyme sensor according to claim 1, wherein the hydrophilic polymer is wettable to a water content in the range of about 10 to about 95% (w/w).

11. The enzyme sensor according to claim 1, wherein the cover membrane layer is in a wet form and has a thickness in the range of about 5 to about 40 μ

m when the sensor is a conventional sensor.

12. The enzyme sensor according to claim 1, wherein the cover membrane layer is in a wet form and has a thickness in the range of about 1 to about 20 μ

m when the sensor is a planar sensor.

13. The enzyme sensor according to claim 1, wherein the hydrophilic polymer layer of the cover membrane is in a dry form and has a thickness of in the range of about 100 to about 2,000% of the average size of the pores of the at least one porous polymeric material.

14. The enzyme sensor according to claim 1, wherein the hydrophilic polymer layer of the cover membrane is in a dry form and has a thickness of in the range of about 0.1 to about 5 μ

m.

15. The enzyme sensor according to claim 1, wherein the cover membrane is in a dry form or a wet form and the ratio between the thickness of the cover membrane in the wet form and the thickness of the cover membrane in the dry form is in the range of about 2:

1 to about 1;

1.

16. The enzyme sensor according to claim 1, wherein the cover membrane is in a dry form or a wet form and the ratio between the thickness of the hydrophilic polymer layer of the cover membrane in the wet form and the thickness of the hydrophilic polymer layer of the cover membrane in the dry form is in the range of about 100:

1 to about 1;

1.

17. The enzyme sensor according to claim 1, wherein the weight ratio between the at least one porous polymeric material and the hydrophilic polymer when the hydrophilic polymer is in a non-wetted form is in the range of about 100:

1 to about 1;

1.

18. The enzyme sensor according to claim 1, wherein the cover membrane is the outermost layer of the sensor.

19. The enzyme sensor according to claim 1, wherein the at least one porous polymeric material is selected from polyethylene terephthalate, polyvinyl chloride, polycarbonate and mixtures thereof.

20. The enzyme sensor according to claim 1 further comprising 1 to 3 layers separating the electrode and the at least one enzyme layer.

21. The enzyme sensor according to claim 20, wherein at least one layer separating the electrode and the at least one enzyme layer is a water-containing porous spacer layer.

34. An apparatus for determining the concentration of an analyte in a fluid sample, comprising one or more enzyme sensors as defined in any one of the claims 1, 22, 23, 24 and 25.

35. A method of determining the concentration of an analyte in a fluid sample, comprising the steps of contacting the fluid sample with an enzyme sensor according to any one of the claims 1, 22, 23, 24 and 25, and conducting at least one measurement involving the electrode of the enzyme sensor.

22. An enzyme sensor for determining the concentration of creatine in a fluid sample, comprising

a metal electrode,

a water-containing porous spacer layer in contact with the metal electrode,

an interference limiting layer in contact with the porous spacer layer,

an enzyme layer comprising sarcosine oxidase and creatinase in contact with the interference limiting layer, and

a cover membrane layer for the enzyme layer,

wherein the cover membrane layer comprises a porous polyethylene terephthalate material, and

wherein the outer surface and pore mouths of at least one face of the porous polyethylene terephthalate material are covered by a hydrophilic polyurethane comprising backbone segments of polyethylene glycol in a weight ratio of polyethylene glycol segments of at least about 5% (w/w) and/or have a water content when wetted of at least about 25% (w/w).

23. An enzyme sensor for determining the concentration of creatinine in a fluid sample, comprising

a metal electrode,

a water-containing porous spacer layer in contact with the metal electrode,

an interference limiting layer in contact with the porous spacer layer,

an enzyme layer comprising sarcosine oxidase, creatininase and creatinase in contact with the interference limiting layer, and

a cover membrane layer for the enzyme layer,

wherein the cover membrane layer comprises a porous polyethylene terephthalate material, and

wherein the outer surface and pore mouths of at least one face of the porous polyethylene terephthalate material are covered by a hydrophilic polyurethane comprising backbone segments of polyethylene glycol in a weight ratio of polyethylene glycol segments of at least about 5% (w/w) and/or have a water content when wetted of at least about 25% (w/w).

24. An enzyme sensor for determining the concentration of lactate in a fluid sample, comprising

a metal electrode,

an interference limiting layer in contact with the metal electrode,

an enzyme layer comprising lactate oxidase in contact with the interference limiting layer, and

a cover membrane layer for the enzyme layer,

wherein the cover membrane layer comprises a porous polyethylene terephthalate material, and

wherein the outer surface and pore mouths of at least one face of the porous polyethylene terphthalate material are covered by a hydrophilic polyurethane comprising backbone segments of polyethylene glycol in a weight ratio of polyethylene glycol segments of at least about 5% (w/w) and/or have a water content when wetted of at least about 25% (w/w).

25. An enzyme sensor for determining the concentration of glucose in a fluid sample, comprising

a metal electrode,

an interference limiting layer in contact with the metal electrode,

an enzyme layer comprising glucose oxidase in contact with the interference limiting layer, and

a cover membrane layer for the enzyme layer,

wherein the cover membrane layer comprises a porous polyethylene terephthalate material, and

wherein the outer surface and pore mouths of at least one face of the porous polyethylene terephthalate material are covered by a hydrophilic polyurethane comprising backbone segments of polyethylene glycol in a weight ratio of polyethylene glycol segments of at least about 5% (w/w) and/or have a water content when wetted of at least about ²5% (w/w).

26. A membrane comprising a track-etched porous polymeric material, wherein the outer surface and pore mouths of at least one face of the porous polymeric material is at least partly impregnated with a hydrophilic polymer selected from hydrophilic polyurethanes and hydrophilic poly(meth)acrylates.

29. The membrane according to any one of the claims 26-28, wherein the hydrophilic polymer is a hydrophilic polyurethane.

27. A membrane comprising a porous polyethylene terephthalate material, wherein the outer surface and pore mouths of at least one face of the porous polyethylene terephthalate material are at least partly impregnated with a hydrophilic polymer selected from hydrophilic polyurethanes and hydrophilic poly(meth)acrylates.

28. A membrane comprising a porous polyvinyl chloride material, wherein the outer surface and pore mouths of at least one face of the porous polyvinyl chloride material are at least partly impregnated with a hydrophilic polymer selected from hydrophilic polyurethanes and hydrophilic poly(meth)acrylates.

30. A method of cleaning an enzyme sensor, said sensor comprising an electrode, at least one enzyme layer and a cover membrane layer for the at least one enzyme layer, the method comprising the step of contacting the surface of the cover membrane with a cleaning solution comprising a protease.

31. The method according to claim 30, wherein the protease is subtilisin.

32. The method according to claim 30, further comprising the steps of measuring the concentration of an analyte before and after the step of contacting the cover membrane with the cleaning solution.

33. The method according to claim 30, wherein the cover membrane comprises at least one porous polymeric material, wherein the outer surface and pore mouths of at least one face of the at least one porous polymeric material are covered by a hydrophilic polymer selected from hydrophilic polyurethanes and hydrophilic poly(meth)acrylates.