Method and apparatus for non-invasive monitoring of blood substances using self-sampled tears

• US 7,133,712 B2
• Filed: 04/01/2003
• Issued: 11/07/2006
• Est. Priority Date: 04/05/2002
• Status: Expired due to Fees

• Current Assignee: Eyelab Group, LLC
• Original Assignee: Eyelab Group, LLC
• Inventors: Kim, Jong Sik, Cui, Gang, Gillespie, Donald E., Meyerhoff, Mark E., Nam, Hakhyun, Cha, Geun Sig, Flanders, Zvi, Cohan, Bruce E.
• Primary Examiner(s): Nasser, Robert L.
• Application Number:
  US10/404,702
• Publication Number:
  US 20030211625A1
• Time in Patent Office: 1,316 Days
• Field of Search: None
• US Class Current: 600/345
• CPC Class Codes: A61B 2562/0295 Strip shaped analyte sensors for apparatus classified in A61B5/145 or A61B5/157 disposable multilayered or laminated electrodes G01N27/307; details of handling chemical test elements G01N33/4875
• CPC Class Codes: A61B 5/1486 using enzyme electrodes, e.g. with immobilised oxidase
• CPC Class Codes: C12Q 1/006 for glucose
• CPC Class Codes: C12Q 1/32 involving dehydrogenase
• CPC Class Codes: C12Q 1/54 involving glucose or galactose
• CPC Class Codes: G01N 2001/1056 Disposable (single-use) samplers
• CPC Class Codes: G01N 2001/149 Capillaries; Sponges
• CPC Class Codes: G01N 2035/0465 Loading or unloading the conveyor
• CPC Class Codes: G01N 27/3272 Test elements therefor, i.e. disposable laminated substrates with electrodes, reagent and channels optical biosensors G01N33/52
• CPC Class Codes: G01N 33/528 Atypical element structures, e.g. gloves, rods, tampons, toilet paper
• CPC Class Codes: Y10T 436/144444 Glucose

Abstract

A method and apparatus for non-invasively determining the concentration of a substance in blood, such as glucose, include a sample portion arranged for contacting an eye region of a user to obtain a tear fluid sample, a sensor in communication with the sample portion for generating a signal related to the tear substance concentration, and a processor in communication with the sensor for determining a blood substance concentration corresponding to the tear substance concentration.

Claims

1. A method for determining the concentration of a substance in blood, the method comprising:

providing a test apparatus having a housing and a test probe received therein;

receiving a tear fluid sample via engagement of the test probe with an eye region of a user while the test probe is received within the test apparatus;

processing the tear fluid sample using the test apparatus to determine a tear substance concentration; and

correlating the determined tear substance concentration with a blood substance concentration.

2. The method according to claim 1, wherein the substance includes glucose.

3. The method according to claim 1, wherein receiving the tear fluid sample includes a user self-sampling the tear fluid sample from his eye region.

4. The method according to claim 1, wherein receiving the tear fluid sample includes engaging a lower lid region and obtaining tear fluid from a tear meniscus.

5. The method according to claim 1, further comprising displaying the blood substance concentration.

6. The method according to claim 1, further comprising storing the blood substance concentration.

7. The method according to claim 1, wherein the test probe includes a capillary member.

8. The method according to claim 1, wherein the test probe includes a wicking membrane.

9. The method according to claim 1, wherein the test probe includes an enzyme for reacting with the substance in the tear fluid sample.

10. The method according to claim 9, wherein the enzyme includes glucose dehydrogenase.

11. The method according to claim 9, wherein the test probe includes an electrode system provided therein, and wherein processing the tear fluid sample includes applying a voltage to the electrode system to induce an electrochemical reaction of the enzyme and the substance in the tear fluid sample, and detecting a current produced by the electrochemical reaction from which the tear substance concentration is determined.

12. The method according to claim 1, wherein receiving the tear fluid sample includes obtaining a tear fluid sample of less than about 0.5 μ

L.

13. The method according to claim 1, wherein a test time is about 5 seconds.

14. The method according to claim 1, wherein the test apparatus is capable of detecting glucose concentrations less than about 20 mg/dL with a resolution of at least 5 mg/dL.

15. The method according to claim 1, wherein the test probe is removable from the housing.

16. The method according to claim 1, wherein the housing is generally pen-shaped.

17. The method according to claim 1, further comprising providing an audible indication to the user.

35. The method according to claim 14, wherein the sample portion includes an inlet extending outwardly therefrom.

36. The method according to claim 35, wherein the inlet includes a capillary member.

37. The method according to claim 35, wherein the inlet includes a wicking membrane.

38. The method according to claim 14, wherein the enzyme includes glucose dehydrogenase.

39. The method according to claim 38, wherein the sample portion includes pyrrolo-quinoline-quinone as a coenzyme.

40. The method according to claim 14, wherein the sample portion includes an electron transfer mediator.

41. The method according to claim 14, wherein the electron transfer mediator includes a ruthenium complex.

42. The method according to claim 40, wherein the sample portion includes a base plate, a cover plate, and a spacer disposed between and joining the base and cover plates, the base and cover plates including a converse-type electrode system, wherein processing the tear fluid sample includes applying a voltage to the electrode system to induce an electrochemical reaction of the enzyme and the electron transfer mediator with glucose in the tear fluid sample and generate a current related to tear glucose concentration.

43. The method according to claim 42, further comprising amplifying the generated current.

44. The method according to claim 42, wherein processing the signal includes determining a tear glucose concentration from the generated current and multiplying the tear glucose concentration by a calibration factor to determine the corresponding blood glucose concentration.

18. A method for determining glucose concentration in a tear fluid sample, the method comprising:

providing a test apparatus having a housing and a test probe received therein, the test probe arranged for contacting an eye region of a user;

receiving a tear fluid sample via engagement of the test probe with an eye region of a user while the test probe is received within the test apparatus; and

processing the tear fluid sample using the test apparatus to determine the glucose concentration in the tear fluid sample.

19. The method according to claim 18, wherein receiving the tear fluid sample includes a user self-sampling the tear fluid sample from his eye region.

20. The method according to claim 18, wherein the test apparatus includes an enzyme for reacting with glucose in the tear fluid sample.

21. The method according to claim 20, wherein the enzyme include glucose dehydrogenase.

22. The method according to claim 18, wherein receiving the tear fluid sample includes obtaining a tear fluid sample of less than about 0.5 μ

L.

23. The method according to claim 18, wherein a test time is about 5 seconds.

24. The method according to claim 18, wherein the test apparatus is capable of detecting glucose concentrations less than about 20 mg/dL with a resolution of at least 5 mg/dL.

25. The method according to claim 18, wherein the test probe is removable from the housing.

26. The method according to claim 18, wherein receiving the tear fluid sample includes a user self-sampling the tear fluid sample from his eye region.

27. The method according to claim 18, further comprising displaying the tear glucose concentration.

28. The method according to claim 18, further comprising storing the tear glucose concentration.

29. The method according to claim 18, wherein the test probe includes a capillary member.

30. The method according to claim 18, wherein the test probe includes a wicking membrane.

31. The method according to claim 18, wherein the housing is generally pen-shaped.

32. The method according to claim 18, further comprising providing an audible indication to the user.

33. A method for determining blood glucose concentration, the method comprising:

providing a test apparatus including a sample portion, the sample portion having an enzyme provided therein;

receiving a tear fluid sample via engagement of the sample portion with an eye region of a user, wherein a volume of the tear fluid sample is less than about 0.5 μ

L;

reacting the tear fluid sample with the enzyme to generate a signal related to the tear glucose concentration;

processing the signal using the test apparatus to obtain a blood glucose concentration corresponding to the tear glucose concentration; and

providing an output indicative of the blood glucose concentration.

34. The method according to claim 33, wherein receiving the tear fluid sample includes a user self-sampling the tear fluid sample from his eye region.

45. The method according to claim 33, wherein a test time is about 5 seconds.

46. The method according to claim 33, wherein the test apparatus is capable of detecting glucose concentrations less than about 20 mg/dL with a resolution of at least 5 mg/dL.

47. The method according to claim 33, wherein the sample portion is removable from the test apparatus.

48. The method according to claim 33, wherein receiving the tear fluid sample includes a user self sampling the tear fluid sample from his eye region.

49. The method according to claim 33, wherein providing an output includes displaying the blood glucose concentration.

50. The method according to claim 33, further comprising storing the blood glucose concentration.

51. The method according to claim 33, wherein the housing is generally pen-shaped.

52. The method according to claim 33, further comprising providing an audible indication to the user.