BIOSENSOR MEMBRANE COMPOSITION, BIOSENSOR, AND METHODS FOR MAKING SAME

• US 20130126349A1
• Filed: 08/05/2011
• Published: 05/23/2013
• Est. Priority Date: 08/06/2010
• Status: Active Grant

• Current Assignee: Microchips Biotech, Inc. (Keratin Biosciences, Inc.)
• Original Assignee: MicroCHIPS Inc.
• Inventors: Zhang, Yanan
• Granted Patent: US 9,322,103 B2
• Time in Patent Office: Days
• US Class Current: 204/403.12
• CPC Class Codes: A61B 5/14865 invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors
• CPC Class Codes: B01D 2323/12 Specific ratios of components used
• CPC Class Codes: B01D 2323/16 Swelling agents
• CPC Class Codes: B01D 2323/30 Cross-linking
• CPC Class Codes: B01D 2325/36 Hydrophilic membranes
• CPC Class Codes: B01D 67/0088 Physical treatment with compounds, e.g. swelling, coating or impregnation
• CPC Class Codes: B01D 69/144 containing embedded or bound biomolecules
• CPC Class Codes: B01D 71/54 Polyureas; Polyurethanes
• CPC Class Codes: B01D 71/70 Polymers having silicon in the main chain, with or without sulfur, nitrogen, oxygen or carbon only
• CPC Class Codes: B01D 71/701 Polydimethylsiloxane
• CPC Class Codes: C12Q 1/002 Electrode membranes
• CPC Class Codes: C25B 13/08 based on organic materials
• CPC Class Codes: G01N 27/3271 Amperometric enzyme electrodes for analytes in body fluids, e.g. glucose in blood amperometry per se G01N27/49; aspects concerning the enzyme reagent C12Q1/001
• CPC Class Codes: G01N 27/3335 the membrane containing at least one organic component G01N27/3271 takes precedence; aspects concerning the enzyme reagent in enzyme electrodes C12Q1/001

Abstract

Selectively permeable membranes for biosensors are provided. In one embodiment, the membrane includes a polymer mixture that includes a polyurethane component, a siloxane component, and a hydrogel component, the components in the mixture in amounts of about 60 to about 80 wt % polyurethane, about 10 to about 20 wt % siloxane, and about 10 to about 20 wt % hydrogel. The membrane has a surface restructured to be hydrophilic, with the restructured surface being crosslinked ed via reactive end groups on at least one of the polyurethane, the siloxane, and the hydrogel components. In another embodiment, the membrane includes a solvent cast film which includes a mixture of a first polyether-based thermoplastic polyurethane copolymer, a polyether-based polyurethane copolymer, and, optionally, a second polyether-based thermoplastic polyurethane copolymer.

Claims

1. A selectively permeable membrane for a biosensor, comprising:

a polymer mixture which comprises a polyurethane component, a siloxane component, and a hydrogel component, the components being present in the mixture in amounts of about 60 to about 80 wt % polyurethane, about 10 to about 20 wt % siloxane, and about 10 to about 20 wt % hydrogel,

wherein the membrane has a surface restructured to be hydrophilic, and the polymer mixture of the membrane with the restructured surface is crosslinked via reactive end groups on at least one of the polyurethane component, the siloxane component, and the hydrogel component.

2. The membrane of claim 1, wherein the polyurethane component comprises a BIOSPAN™

polyurethane polymer.

3. The membrane of claim 1, wherein the siloxane component comprises polydimethylsiloxane.

4. The membrane of claim 1, wherein the hydrogel component comprises polyethylene glycol which is bis(amine) terminated.

5. The membrane of claim 1, wherein the components are present in the mixture in amounts of about 75 wt % polyurethane, about 15 wt % siloxane, and about 10 wt % hydrogel.

6. A biosensor comprising:

a substrate;

at least one electrode disposed on the substrate;

at least one enzyme layer disposed on the at least one electrode; and

at least one selectively permeable membrane fixed on the at least one enzyme layer, wherein the at least one selectively permeable membrane comprises a polymer mixture which comprises a polyurethane component, a siloxane component, and a hydrogel component, the components being present in the mixture in amounts of about 60 to about 80 wt % polyurethane, about 10 to about 20 wt % siloxane, and about 10 to about 20 wt % hydrogel,

wherein the at least one selectively permeable membrane has a surface restructured to be hydrophilic, and the polymer mixture of the membrane with the restructured surface is crosslinked via reactive end groups on at least one of the polyurethane component, the siloxane component, and the hydrogel component.

7. The membrane of claim 6, wherein the polyurethane component comprises a BIOSPAN™

polyurethane polymer.

8. The membrane of claim 6, wherein the siloxane component comprises polydimethylsiloxane.

9. The membrane of claim 6, wherein the hydrogel component comprises polyethylene glycol which is bis(amine) terminated.

10. The membrane of claim 6, wherein the components are present in the mixture in amounts of about 75 wt % polyurethane, about 15 wt % siloxane, and about 10 wt % hydrogel.

11. The membrane of claim 6, wherein the at least one enzyme layer comprises glucose oxidase.

12. A method for making a selectively permeable membrane comprising:

mixing a polyurethane component, a siloxane component, and a hydrogel component together with a first solvent for the components to form a polymer solution mixture;

depositing the polymer solution mixture on a substrate;

evaporating the first solvent from the polymer solution mixture to form a film of a polymer mixture, the film having a surface opposing the substrate;

applying a solvent mixture onto the surface of the film to partially re-dissolve and swell the film, wherein the solvent mixture comprises a hydrophilic constituent and a hydrophobic constituent; and

evaporating the solvent mixture from the partially redissolved and swollen film to reform the surface with hydrophilic molecules of the polymer mixture redistributed toward the reformed surface.

13. The method of claim 12, wherein the polymer mixture comprises about 60 to about 80 wt % polyurethane, about 10 to about 20 wt % siloxane, and about 10 to about 20 wt % hydrogel.

14. The method of claim 12, wherein the first solvent comprises tetrahydrofuran or another volatile organic solvent.

15. The method of claim 12, wherein the solvent mixture comprises water and tetrahydrofuran in volume ratio of about 1:

2.

16. The method of claim 12, further comprising cross-linking the polymer mixture.

17. A selectively permeable membrane for a biosensor, comprising:

a solvent cast film which comprises a mixture of

a first polyether-based thermoplastic polyurethane copolymer, and

a polyether-based polyurethane copolymer,

wherein the polyether-based thermoplastic polyurethane copolymer, or the polyether-based polyurethane copolymer, or both comprise at least one siloxane repeat unit.

18. The membrane of claim 17, wherein when the polyether-based polyurethane copolymer comprises at least one siloxane repeat unit, the copolymers are present in the film in a proportion in the range of about 1:

3 to about 1;

4 polyether-based thermoplastic polyurethane copolymer to polyether-based polyurethane copolymer.

19. The membrane of claim 17, further comprising a second polyether-based thermoplastic polyurethane copolymer.

20. The membrane of claim 19, wherein the additional polyether-based thermoplastic polyurethane copolymer comprises at least one siloxane repeat unit.

21. The membrane of claim 19, wherein when the polyether-based thermoplastic polyurethane copolymer comprises at least one siloxane repeat unit, the copolymers are present in the film in a proportion in the range of about 2:

1;

1 polyether-based polyurethane copolymer to polyether-based thermoplastic polyurethane copolymer to additional polyether-based thermoplastic polyurethane copolymer.

22. The membrane of claim 17, wherein the polyether-based thermoplastic polyurethane copolymer is TECOPHILIC™

SP-85A-150.

23. The membrane of claim 17, wherein the polyether-based thermoplastic polyurethane copolymer is PURESIL™

.

24. The membrane of claim 17, wherein the at least one siloxane repeat unit comprises a silicone repeat unit.

25. The membrane of claim 17, wherein the polyether-based polyurethane copolymer comprises BIOSPAN™

or BIOSPAN™

-S.

26. A selectively permeable membrane for a biosensor, comprising:

a solvent cast film which consists essentially of a mixture of

a first polyether-based thermoplastic polyurethane copolymer, and

a polyether-based polyurethane copolymer,

wherein the thermoplastic polyurethane copolymer, or the polyether-based polyurethane copolymer, or both comprise at least one siloxane repeat unit.

27. The membrane of claim 26, wherein when the polyether-based polyurethane copolymer comprises at least one siloxane repeat unit, the copolymers are present in the film in a proportion in the range of about 1:

3 to about 1;

4 thermoplastic polyurethane copolymer to polyether-based polyurethane copolymer.

28. The membrane of claim 26, further comprising a second polyether-based thermoplastic polyurethane copolymer.

29. The membrane of claim 28, wherein the additional polyether-based thermoplastic polyurethane copolymer comprises at least one siloxane repeat unit.

30. The membrane of claim 28, wherein when the thermoplastic polyurethane copolymer comprises at least one siloxane repeat unit, the copolymers are present in the film in a proportion in the range of about 2:

1;

1 polyether-based polyurethane copolymer to polyether-based thermoplastic polyurethane copolymer to additional polyether-based thermoplastic polyurethane copolymer.

31. A biosensor comprising:

a substrate;

at least one electrode disposed on the substrate;

at least one enzyme layer disposed on the at least one electrode; and

at least one selectively permeable membrane fixed on the at least one enzyme layer, wherein the at least one selectively permeable membrane comprises a solvent cast film which comprises a mixture of a first polyether-based thermoplastic polyurethane copolymer, and a polyether-based polyurethane copolymer, wherein the polyether-based thermoplastic polyurethane copolymer, or the polyether-based polyurethane copolymer, or both comprise at least one siloxane repeat unit.

32. The biosensor of claim 31, wherein when the polyether-based polyurethane copolymer comprises at least one siloxane repeat unit, the copolymers are present in the film in a proportion in the range of about 1:

3 to about 1;

4 polyether-based thermoplastic polyurethane copolymer to polyether-based polyurethane copolymer.

33. The biosensor of claim 31, wherein the membrane further comprises a second polyether-based thermoplastic polyurethane copolymer.

34. The biosensor of claim 33, wherein the additional polyether-based thermoplastic polyurethane copolymer comprises at least one siloxame repeat unit.

35. The biosensor of claim 33, wherein when the thermoplastic polyurethane copolymer comprises at least one siloxane repeat unit, the copolymers are present in the film in a proportion in the range of about 2:

1;

1 polyether-based polyurethane copolymer to polyether-based thermoplastic polyurethane copolymer to additional polyether-based thermoplastic polyurethane copolymer.

36. A method for making a selectively permeable membrane comprising:

applying onto a substrate a polymer solution mixture which comprises a mixture of a first polyether-based thermoplastic polyurethane copolymer, and a polyether-based polyurethane copolymer, wherein the polyether-based thermoplastic polyurethane copolymer, or the polyether-based polyurethane copolymer, or both comprise at least one siloxane repeat unit, in solution with a volatile organic solvent; and

evaporating the volatile organic solvent from the polymer solution mixture to form a film of a polymer mixture on the substrate.

37. The method of claim 36, wherein when the polyether-based polyurethane copolymer comprises at least one siloxane repeat unit, the copolymers are present in the film in a proportion in the range of about 1:

3 to about 1;

4 polyether-based thermoplastic polyurethane copolymer to polyether-based polyurethane copolymer.

38. The method of claim 36, wherein the mixture further comprises a second polyether-based thermoplastic polyurethane copolymer.

39. The method of claim 38, wherein the additional polyether-based thermoplastic polyurethane copolymer comprises at least one siloxane repeat unit.

40. The method of claim 38, wherein when the polyether-based thermoplastic polyurethane copolymer comprises at least one siloxane repeat unit, the copolymers are present in the film in a proportion in the range of about 2:

1;

1 polyether-based polyurethane copolymer to polyether-based thermoplastic polyurethane copolymer to additional polyether-based thermoplastic polyurethane copolymer.