Lyotropic liquid crystal coated analyte monitoring device and methods of use
The present invention is directed to membranes composed liquid crystals having continuous aqueous channels, such as a lyotropic liquid crystal, including a cubic phase lyotropic liquid crystal, and to electrochemical sensors equipped with such membranes. The membranes are useful in limiting the diffusion of an analyte to a working electrode in an electrochemical sensor so that the sensor does not saturate and/or remains linearly responsive over a large range of analyte concentrations. Electrochemical sensors equipped with membranes of the present invention demonstrate considerable sensitivity and stability, and a large signal-to-noise ratio, in a variety of conditions.
1. An electrochemical analyte sensor for determining the concentration of an analyte, comprising:
a working electrode comprising:
a sensing layer comprising an analyte-responsive enzyme and a redox mediator in contact with the electrode;
a non-crosslinked cubic phase lyotropic liquid crystal membrane disposed on top of the sensing layer, and
a counter or a reference or a counter/reference electrode in electrochemical communication with the working electrode.
2. The electrochemical sensor of claim 1 , wherein the analyte-responsive enzyme is a glucose-responsive enzyme.
3. The electrochemical sensor of claim 2 , wherein the glucose-responsive enzyme is a wired enzyme.
4. The electrochemical sensor of claim 2 , wherein the glucose-responsive enzyme is a glucose-dehydrogenase.
5. The electrochemical sensor of claim 4 , wherein the glucose-dehydrogenase is an FAD-dependent glucose dehydrogenase.
6. The electrochemical sensor of claim 4 , wherein the glucose-dehydrogenase is glucose oxidase.
7. The electrochemical sensor of claim 1 , wherein the redox mediator comprises a ruthenium-containing complex and/or an osmium-containing complex.
8. The electrochemical sensor of claim 1 , wherein the cubic phase lyotropic liquid crystal is substantially non-hydrolyzable in the presence of a lipase.
9. The electrochemical sensor of claim 1 , wherein the cubic phase lyotropic liquid crystal comprises a compound of the formula:
10. The electrochemical sensor of claim 9 , wherein the cubic phase lyotropic liquid crystal comprises Vitamin E acetate.
11. The electrochemical sensor of claim 1 , wherein the sensor is adapted so that at least a portion of the sensor is positionable beneath the skin of a user.
12. The electrochemical sensor of claim 1 , wherein the sensor comprises an anticlotting agent.
13. The electrochemical sensor of claim 12 , wherein the anticlotting agent is heparin.
14. The electrochemical sensor of claim 12 , wherein the cubic phase lyotropic liquid crystal comprises the anticlotting agent.
15. The electrochemical sensor of claim 1 , wherein the cubic phase lyotropic liquid crystal membrane is adapted to limit the flux of glucose or lactate thereacross.
16. The electrochemical sensor of claim 1 , wherein the analyte is glucose.
17. An electrode for use in a biosensor for determining the concentration of an analyte, comprising:
a sensing layer comprising an analyte-responsive enzyme and a redox mediator in contact with the electrode, and
a non-crosslinked cubic phase lyotropic liquid crystal membrane disposed on top of the sensing layer.
18. The electrode of claim 17 , wherein the analyte-responsive enzyme is a glucose-responsive enzyme.
19. The electrode of claim 17 , wherein the redox mediator comprises a complex selected from the group consisting of a ruthenium-containing complex and an osmium-containing complex.
20. The electrode of claim 18 , wherein the glucose-responsive enzyme is a wired enzyme.
21. The electrode of claim 18 , wherein the glucose-responsive enzyme is a glucose-dehydrogenase.
22. The electrode of claim 21 , wherein the glucose-dehydrogenase is an FAD-dependent glucose dehydrogenase.
23. The electrode of claim 21 , wherein the glucose-dehydrogenase is glucose oxidase.
24. The electrode of claim 17 , wherein the redox mediator comprises a ruthenium containing complex and/or an osmium-containing complex.
25. The electrode of claim 17 , wherein the cubic phase lyotropic liquid crystal is substantially non-hydrolyzable in the presence of a lipase.
26. The electrode of claim 17 , wherein the cubic phase lyotropic liquid crystal comprises a compound of the formula:
27. The electrode of claim 26 , wherein the cubic phase lyotropic liquid crystal comprises Vitamin E acetate.
28. The electrode of claim 17 , wherein the cubic phase lyotropic liquid crystal membrane is adapted to limit the flux of glucose or lactate thereacross.
29. The electrode of claim 17 , wherein the cubic phase lyotropic liquid crystal membrane is adapted to limit the flux of glucose or lactate thereacross in vivo.
30. The electrode of claim 17 , wherein the sensing layer comprises an anticlotting agent such as heparin.
31. The electrochemical sensor of claim 1 , wherein the cubic phase lyotropic liquid crystal is non-polymeric.
32. The electrode of claim 17 , wherein the cubic phase lyotropic liquid crystal is non-polymeric.
33. The electrochemical sensor of claim 1 , wherein the cubic phase lyotropic liquid crystal is isotropic.
34. The electrode of claim 17 , wherein the cubic phase lyotropic liquid crystal is isotropic.
35. The electrochemical sensor of claim 1 , wherein the cubic phase lyotropic liquid crystal comprises a link between a polar head and a hydrocarbon tail other than an ester.
36. The electrode of claim 17 , wherein the cubic phase lyotropic liquid crystal comprises a link between a polar head and a hydrocarbon tail other than an ester.
37. The electrochemical sensor of claim 35 , wherein the link between a polar head and hydrocarbon tail is an ether linkage.
38. The electrode of claim 36 , wherein the link between a polar head and hydrocarbon tail is an ether linkage.