Selectively permeable coated membrane

• US 8,394,022 B2
• Filed: 10/29/2008
• Issued: 03/12/2013
• Est. Priority Date: 10/30/2007
• Status: Active Grant

• Current Assignee: Sensile Medical AG (Gerresheimer AG)
• Original Assignee: Sensile Pat Ag
• Inventors: Klok, Harm-Anton, Lavanant, Laurent
• Primary Examiner(s): WOOLWINE, SAMUEL C
• Application Number:
  US12/260,515
• Publication Number:
  US 20090112075A1
• Time in Patent Office: 1,595 Days
• Field of Search: None
• US Class Current: 600/309
• CPC Class Codes: A61B 5/0031 Implanted circuitry
• CPC Class Codes: A61B 5/14503 invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors A61B5/1459, A61B5/1464, A61B5/1473, A61B5/1482, A61B5/14865 take precedence
• CPC Class Codes: A61B 5/14525 using microdialysis
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• 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 2323/283 Reducing the pores
• CPC Class Codes: B01D 2323/38 Graft polymerization
• CPC Class Codes: B01D 67/0093 Chemical modification
• CPC Class Codes: B01D 67/00931 by introduction of specific groups after membrane formation, e.g. by grafting
• CPC Class Codes: Y10T 428/249978 Voids specified as micro

Abstract

There is provided a selectively permeable biointerface membrane, permitting selective diffusion of analyte therethrough, for use in an analyte sensor comprising a nanoporous substrate and a coating, on the nanoporous substrate, comprising a plurality of polymer chains whereby each polymer chain is attached at one chain end thereof to a surface of the nanoporous substrate. There are also provided methods for the preparation of the selectively permeable membrane and an analyte sensor comprising the membrane.

Claims

1. An implantable analyte sensor comprising a biointerface membrane permitting selective diffusion of an analyte therethrough, said membrane comprising a nanoporous substrate and a coating on said nanoporous substrate restricting a pore size of the nanoporous substrate, said coating comprising a plurality of bio-compatible polymer chains, whereby each polymer chain is covalently attached at one chain end thereof to a surface of the nanoporous substrate via a 5-(2-bromo-2-methylpropanamido)-2-hydroxybenzoic acid group and whereby the polymer chains are formed by a surface-initiated controlled polymerization process from the nanoporous substrate.

2. The sensor according to claim 1, wherein the sensor is a glucose sensor.

3. The sensor according to claim 1, wherein the polymer chains are formed by polymerisation of one or more monomer selected from the group consisting of 2-hydroxyethyl methacrylate, glycidyl methacrylate, (polyethylene glycol) methacrylate, (polyethylene glycol) methylether methacrylate, ethylene glycol dimethacrylate, and poly(ethylene glycol)dimethacrylate.

4. The sensor according to claim 3, wherein the polymer chains are composed of poly(poly(ethylene glycol) methacrylate) chains.

5. The sensor according to claim 1, wherein the substrate is a nanoporous alumina substrate.

6. The sensor according to claim 5, wherein the nanoporous substrate has a pore size of at least 20 nm and no more than 100 nm.

7. The sensor according to claim 1, wherein the nanoporous substrate has a pore size of at least 2 nm and no more than 200 nm.

8. The sensor according to claim 1, wherein the coating of the nanoporous substrate has a thickness of at least 10 nm and no more than 100 nm.

9. The sensor according to claim 1, wherein the membrane has a pore size in the range of from 0.1 nm to 10 nm.

10. The implantable analyte sensor according to claim 1, wherein said polymer chains comprise water soluble monomers.

11. A bio-interface membrane for an analyte sensor permitting selective diffusion of an analyte therethrough comprising:

a nanoporous substrate and a coating on said nanoporous substrate, said coating comprising a plurality of bio-compatible polymer chains, whereby each polymer chain is covalently attached at one chain end thereof to a surface of the nanoporous substrate via a 5-(2-bromo-2-methylpropanamido)-2-hydroxybenzoic acid group and whereby the polymer chains are formed by a surface-initiated controlled polymerization process from the nanoporous substrate, said coating restricting a pore size of the pores of the nanoporous substrate so as to provide selective diffusion of the analyte through the membrane.

12. The membrane according to claim 11, wherein the analyte is glucose.

13. The membrane according to claim 11, wherein the polymer chains are formed by polymerisation of one or more monomer selected from the group consisting of 2-hydroxyethyl methacrylate, glycidyl methacrylate, (polyethylene glycol) methacrylate, (polyethylene glycol) methylether methacrylate, ethylene glycol dimethacrylate, and poly(ethylene glycol)dimethacrylate.

14. The membrane according to claim 13, wherein the polymer chains are composed of poly(poly(ethylene glycol) methacrylate) chains.

15. The membrane according to claim 11, wherein the substrate is a nanoporous alumina substrate.

16. The membrane according to claim 15, wherein the nanoporous substrate has a pore size of at least 20 nm and no more than 100 nm.

17. The membrane according to claim 11, wherein the nanoporous substrate has a pore size of at least 2 nm and no more than 200 nm.

18. The membrane according to claim 11, wherein the coating of the nanoporous substrate has a thickness of at least 10 nm and no more than 100 nm.

19. The membrane according to claim 11, wherein the membrane has a pore size in the range of from 0.1 nm to 10 nm.

20. The membrane according to claim 11, wherein said polymer chains comprise water soluble monomers.

21. A method for the preparation of a selectively permeable biointerface membrane for use in an analyte sensor, comprising chemically binding a monolayer of an initiator group onto a surface of a nanoporous substrate, and subsequently carrying out a polymerisation by a surface-initiated controlled polymerization process from the monolayer of said initiator group to form a coating on the nanoporous substrate comprising a plurality of bio-compatible polymer chains, whereby each polymer chain is attached at one chain end thereof to a surface of the nanoporous substrate via a 5-(2-bromo-2-methylpropanamido)-2-hydroxybenzoic acid group, said coating restricting a pore size of the nanoporous substrate so as to provide selective diffusion of an analyte through the membrane, wherein said surface-initiated controlled polymerization process comprises surface initiated atom transfer radical polymerisation.

22. The method according to claim 21, wherein the nanoporous substrate is a nanoporous alumina substrate.

23. The method according to claim 22, wherein the nanoporous substrate has a pore size of at least 20 nm and no more than 100 nm.

24. The method according to claim 21, wherein the nanoporous substrate has a pore size of at least 2 nm and no more than 200 nm.

25. The method according to claim 21, wherein the coating of the nanoporous substrate has a thickness of at least 10 nm and no more than 100 nm.

26. The method according to claim 21, wherein the thickness of the nanoporous coating is controlled by controlling the length of time of the polymerisation.

27. The method according to claim 21, wherein the polymer chains are formed by polymerisation of one or more monomer selected from the group consisting of 2-hydroxyethyl methacrylate, glycidyl methacrylate, (polyethylene glycol) methacrylate, (polyethylene glycol) methylether methacrylate, ethylene glycol dimethacrylate, and poly(ethylene glycol)dimethacrylate.

28. The method according to claim 27, wherein the polymer chains are composed of poly(poly(ethylene glycol) methacrylate) chains.

29. The method according to claim 21, wherein said polymer chains comprise water soluble monomers.