Ocular analyte sensor

• US 6,681,127 B2
• Filed: 02/15/2001
• Issued: 01/20/2004
• Est. Priority Date: 08/26/1999
• Status: Expired due to Term

• Current Assignee: EyeSense AG
• Original Assignee: Novartis Ag
• Inventors: March, Wayne Front
• Primary Examiner(s): Winakur, Eric F.
• Assistant Examiner(s): Kremer, Matthew J
• Application Number:
  US09/784,471
• Publication Number:
  US 20010034500A1
• Time in Patent Office: 1,069 Days
• Field of Search: 600/316, 600/317, 600/318, 600/322, 600/329
• US Class Current: 600/319
• CPC Class Codes: A61B 5/0002 Remote monitoring of patients using telemetry, e.g. transmission of vital signals via a communication network A61B5/07 takes precedence; transmission systems for measured values G08C; transmission H04B; transmission of digital information H04L; wireless communication networks H04W
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/1455 using optical sensors, e.g. spectral photometrical oximeters
• CPC Class Codes: A61B 5/411 Detecting or monitoring allergy or intolerance reactions to an allergenic agent or substance
• CPC Class Codes: Y10S 977/905 Specially adapted for travel through blood circulatory system

Abstract

An ophthalmic lens comprising a receptor moiety can be used to determine the amount of an analyte in an ocular fluid. The receptor moiety can bind either a specific analyte or a detectably labeled competitor moiety. The amount of detectably labeled competitor moiety which is displaced from the receptor moiety by the analyte is measured and provides a means of determining analyte concentration in an ocular fluid, such as tears, aqueous humor, or interstitial fluid. The concentration of the analyte in the ocular fluid, in turn, indicates the concentration of the analyte in a fluid or tissue sample of the body, such as blood or intracellular fluid.

Claims

1. An apparatus for detecting an analyte in an ocular fluid, comprising:

an ophthalmic lens;

a receptor moiety in and/or on said ophthalmic lens, wherein said receptor moiety comprises an analyte/competitor moiety binding site, wherein the analyte can reversibly bind at said analyte/competitor moiety binding site; and

a detectable label in and/or on said ophthalmic lens.

2. The apparatus of claim 1 which further comprises a competitor moiety comprising the detectable label in and/or on the ophthalmic lens.

3. The apparatus of claim 1 which is selected from the group consisting of a contact lens, an intraocular lens, a subconjunctival lens, an intracorneal lens, and a shunt or implant that can rest in the cul de sac of an eye.

4. The apparatus of claim 1, wherein the analyte is selected from the group consisting of an electrolyte, a metallic element, a polypeptide hormone, a chronically administered medication, an acutely administered medication, a small molecule hormone, a marker of inflammation, a marker of allergy, a lipid, a protein, a marker of infection, and a metabolite.

5. The apparatus of claim 1, wherein the ocular fluid is selected from the group consisting of tears, aqueous humor, and interstitial fluid.

6. The apparatus of claim 1, wherein said ophthalmic lens comprises said receptor moiety therein, wherein the receptor moiety is covalently bound to lens material of the ophthalmic lens.

7. The apparatus of claim 2, wherein said ophthalmic lens comprises said receptor moiety therein, wherein said ophthalmic lens comprises a polymer meshwork, wherein pores of the polymer meshwork (a) permit the competitor moiety to bind reversibly to the analyte/competitor moiety binding site and (b) prevent the receptor moiety and the competitor moiety from diffusing out of the ophthalmic lens.

8. The apparatus of claim 2, wherein said ophthalmic lens comprises a coating on the surface of said ophthalmic lens, wherein the coating includes:

a receptor moiety layer;

a polyelectrolyte layer; and

a competitor moiety layer.

9. The apparatus of claim 2, wherein the detectable label is a fluorescent label.

10. An apparatus for detecting glucose in an ocular fluid, comprising an ophthalmic lens having a coating thereon, wherein the coating includes:

a receptor moiety layer, wherein receptor moieties in the receptor moiety layer comprise glucose/competitor moiety binding sites;

a first and a second polyelectrolyte layer; and

a competitor moiety layer, wherein competitor moieties in the competitor moiety layer comprise detectable labels.

11. The apparatus of claim 10, wherein the receptor moiety layer comprises concanavalin A molecules.

12. The apparatus of claim 10, wherein the competitor moiety layer comprises fluorescein dextran molecules.

13. An analyte sensor system, comprising:

(a) an ophthalmic lens for detecting an analyte in an ocular fluid, comprising;

(i) a receptor moiety which comprises an analyte/competitor moiety binding site; and

(ii) a competitor moiety comprising a detectable label; and

(b) a detector configured to detect the detectable label.

14. The analyte sensor system of claim 13, wherein the detector includes a fluorophotometer.

15. The analyte sensor system of claim 13, further comprising a transmitter coupled to the detector and configured to transmit to a pump a signal indicating whether the detectable label is detected by the detector, wherein the pump is configured to vary a concentration of the analyte in a body fluid or tissue.

16. The analyte sensor system of claim 15, wherein the transmitter is contained in a personal accessory.

17. The analyte sensor system of claim 15, further comprising the pump.

18. The analyte sensor system of claim 15, wherein the transmitter is further configured to transmit the signal to the pump wirelessly.

19. The analyte sensor system of claim 15, wherein the analyte is glucose and the body fluid is blood.

20. The analyte sensor system of claim 19, wherein the receptor moiety is concanavalin A.

21. The analyte sensor system of claim 19, wherein the competitor moiety is fluorescein dextran.

22. The analyte sensor system of claim 19, wherein the pump is an insulin pump.

23. The analyte sensor system of claim 13 wherein the ophthalmic lens is selected from the group consisting of a contact lens, an intraocular lens, a subconjunctival lens, an intracorneal lens, rand a shunt or implant that can rest in the cul de sac of an eye.

24. The analyte sensor system of claim 13, wherein the ophthalmic lens comprises a polymer meshwork, wherein pores of the polymer meshwork (a) permit a competitor moiety to bind reversibly to the analyte/competitor moiety binding site and (b) prevent the receptor moiety and the competitor moiety from diffusing out of the ophthalmic lens.

25. The analyte sensor system of claim 13, wherein the ophthalmic lens comprises a coating on its surface, wherein the coating includes:

a receptor moiety layer including the receptor moiety;

a polyelectrolyte layer; and

a competitor moiety layer including the competitor moiety.

26. The analyte sensor system of claim 13, wherein the ocular fluid is selected from the group consisting of tears, aqueous humor, and interstitial fluid.

27. A method for measuring the concentration of an analyte in an ocular fluid, comprising the steps of:

(a) contacting the ocular fluid with an ophthalmic lens, wherein the ophthalmic lens comprises;

(i) a receptor moiety which comprises an analyte/competitor moiety binding site; and

(ii) a competitor moiety which comprises a detectable label; and

(b) detecting the detectable label, wherein the amount of detectable label detected indicates the concentration of the analyte in the ocular fluid.

28. The method of claim 27, wherein the ophthalmic lens is selected from the group consisting of a contact lens, an intraocular lens, a subconjunctival lens, an intracorneal lens, and a shunt or implant that can rest in the cul de sac of an eye.

29. The method of claim 27, wherein the analyte is selected from the group consisting of electrolytes and small molecules, metallic elements, polypeptide hormones, chronically administered medications, acutely administered medications, small molecule hormones, markers of inflammation, markers of allergy, lipids, proteins, markers of infection, and metabolites.

30. The method of claim 27, wherein the ocular fluid is selected from the group consisting of tears, aqueous humor, and interstitial fluid.

31. The method of claim 27, wherein the receptor moiety is covalently bound to lens material of the ophthalmic lens.

32. The method of claim 27, wherein the ophthalmic lens comprises a polymer meshwork, wherein pores in the polymer meshwork (a) permit a competitor moiety to bind reversibly to the analyte/competitor moiety binding site and (b) prevent the receptor moiety and the competitor moiety from diffusing out of the ophthalmic lens.

33. The method of claim 32, wherein the ocular fluid is selected from the group consisting of tears, aqueous humor, and interstitial fluid.

34. The method of claim 27, wherein the ophthalmic lens comprises a coating on its surface, wherein the coating includes:

a receptor moiety layer including the receptor moiety;

a polyelectrolyte layer; and

a competitor moiety layer including the competitor moiety.

35. The method of claim 27, wherein the detectable label is a fluorescent label.

36. A method for varying the concentration of an analyte in an ocular fluid, comprising the steps of:

(a) contacting the ocular fluid with an ophthalmic lens, wherein the ophthalmic lens comprises;

(i) a competitor moiety which comprises a detectable label; and

(ii) a receptor moiety which comprises an analyte/competitor moiety binding site;

(b) detecting the detectable label, wherein the amount of detectable label detected indicates the concentration of the analyte in a body tissue or fluid;

(c) transmitting a signal indicating the concentration of the analyte in the ocular fluid to a pump configured to vary the concentration of the analyte in the body tissue or fluid; and

(d) providing a regulator moiety via the pump to the body tissue or fluid, whereby the concentration of the analyte in the body tissue or fluid is varied.

37. The method of claim 36 wherein the detectable label is a fluorescent label.

38. The method of claim 37 wherein the detectable label is detected by a fluorophotometer.

39. The method of claim 38 wherein the fluorophotometer is contained in a personal accessory.

40. The method of claim 36 wherein the ocular fluid is selected from the group consisting of tears, aqueous humor, and interstitial fluid.

41. The method of claim 36 wherein the analyte is glucose.

42. The method of claim 41 wherein the receptor moiety is concanavalin A.

43. The method of claim 41 wherein the competitor moiety is fluorescein dextran.

44. The method of claim 41 wherein the regulator moiety is insulin.

45. The method of claim 36 wherein the ophthalmic lens is selected from the group consisting of a contact lens, an intraocular lens, a subconjunctival lens, an intracorneal lens, and a shunt or implant that can rest in the cul de sac of an eye.

46. The method of claim 36, wherein the receptor moiety is covalently bound to lens material of the ophthalmic lens.

47. The method of claim 36, wherein the ophthalmic lens comprises a polymer meshwork, wherein pores of the polymer meshwork (a) permit a competitor moiety to bind reversibly to the analyte/competitor moiety binding site and (b) prevent the receptor moiety and the competitor moiety from diffusing out of the ophthalmic lens.

48. The method of claim 36, wherein the ophthalmic lens comprises on its surface a coating including:

a receptor moiety layer having the receptor moiety;

a polyelectrolyte layer; and

a competitor moiety layer having the competitor moiety.

49. A kit for detecting an analyte in an ocular fluid, comprising:

an ophthalmic lens comprising a receptor moiety which comprises an analyte/competitor moiety binding site; and

instructions for using the ophthalmic lens to detect the analyte.

50. The kit of claim 49, further comprising a competitor moiety comprising a detectable label.

51. The kit of claim 50, further comprising a detector configured to detect the detectable label.

52. A kit for detecting glucose in an ocular fluid, comprising:

a contact lens comprising concanavalin A and fluorescein dextran; and

instructions for using the contact lens to detect glucose in the ocular fluid.

53. The kit of claim 52, further comprising a detector for detecting fluorescence of fluorescein dextran which is not bound to the concanavalin A.