Sensor system

• US 20050221276A1
• Filed: 02/03/2005
• Published: 10/06/2005
• Est. Priority Date: 10/11/2002
• Status: Active Grant

• Current Assignee: Case Western Reserve University
• Original Assignee: Case Western Reserve University, George Rozakis
• Inventors: Yang, Jian, Rozakis, George, Gratzl, Miklos, Tohda, Koji
• Granted Patent: US 7,964,390 B2
• Time in Patent Office: Days
• US Class Current: 435/4
• CPC Class Codes: C12Q 1/001 Enzyme electrodes
• CPC Class Codes: Y10S 435/808 Optical sensing apparatus
• CPC Class Codes: Y10T 436/144444 Glucose

Abstract

A sensor probe suited for implanting into the skin of a person includes a sensor body which may be formed from a polymer which includes 2-hydroxyethyl methacrylate (HEMA). A sensing system is supported by the body. The sensing system exhibits a detectable change when the probe is exposed to the analyte in the fluid. The sensing system may include an enzyme capable of catalyzing a reaction of the analyte to form a reaction product and a dye system which absorbs in the infrared region of the spectrum in response to the reaction product.

Claims

1. A sensor probe for detecting an analyte in a fluid comprising:

a sensor support body formed from a polymer which includes 2-hydroxyethyl methacrylate (HEMA);

a sensing system supported by the body, the sensing system exhibiting a detectable change when the probe is exposed to the analyte in the fluid.

2. The probe of claim 1, wherein at least a portion of the sensing system is immobilized on beads.

3. The sensor probe of claim 2, wherein a first component of the sensing system is immobilized on a first set of the beads and a second component of the sensing system is immobilized on a second set of the beads.

4. The sensor probe of claim 3, wherein the beads comprises one or more materials selected from the group consisting of:

cellulose acetate (CA), cellulose acetate phthalate (CAP), poly(vinyl chloride), octadecyl silica gel (ODS silica gel), and bovine albumin/glutaraldehyde.

5. The sensor probe of claim 1, wherein the sensing system comprises an enzyme capable of catalyzing a reaction of the analyte to form a reaction product.

6. The sensor probe of claim 5, wherein the enzyme is associated with a first set of beads and the sensing system further comprises a dye which is associated with a second set of beads, the dye exhibiting a detectable change in response to a reaction product of a reaction between the enzyme and the analyte.

7. The sensor probe of claim 2, wherein the sensing system includes a dye which exhibits a detectable change in the IR region of the spectrum in response to at least one of the analyte and a reaction product thereof.

8. The sensor probe of claim 7, wherein the IR absorbing dye exhibits the detectable change in the IR region of the spectrum in response to a reaction product of the analyte.

9. The sensor probe of claim 7, wherein the IR absorbing dye exhibits the detectable change in the IR region of the spectrum in response to a change in pH.

10. The sensor probe of claim 9, wherein the IR absorbing dye provides a maximum color change at a pH of about 5.0 to 7.5.

11. The sensor probe of claim 7, wherein the IR absorbing dye comprises a ketocyanine dye.

12. The sensor probe of claim 7, wherein the IR absorbing dye includes a dye selected from the group consisting of:

2,5-bis{[3,3-dimethyl-1-propylindolenine]ethylidene}cyclopentanone;

2,5-bis{[1-ethylbenzooxazolenine]ethylidene}cyclopentanone;

2,5-bis{[1,3,3-trimethylbenz[e]indolenine]ethylidene}cyclopentanone;

2,5-bis{[1-ethylbenzothiazolenine]ethylidene}cyclopentanone;

2-{[3-ethylbenzothiazolidene]ethylidene}-5-{[1,3,3-trimethylbenz[e]indolenine]ethylidene}cyclopentanone; and

combinations thereof.

13. The sensor probe of claim 5, wherein the analyte includes glucose and the enzyme includes at least one (of glucose oxidase and glucose dehydrogenase.

14. The sensor probe of claim 1, wherein the sensing system comprises:

an ionophore which extracts an ion from the reaction product, and

a chromoionophore sensitive to the ion which exhibits a detectable color change in response to the ion.

15. The sensor probe of claim 14, wherein the chromoionophore is associated with a different set of the beads than the ionophore.

16. The sensor probe of claim 14, wherein the chromoionophore is a hydrogen ion selective chromoionophore.

17. The sensor probe of claim 14, wherein the chromoionophore absorbs predominantly in the infrared region of the spectrum.

18. The sensor probe of claim 14, wherein the sensing system further comprises a lipophilic anion.

19. The sensor probe of claim 1, further including at least one reference element which does not exhibit a color change in response to the analyte.

20. The sensor probe of claim 1, wherein the sensor body comprises an analyte-permeable membrane having a multilayer structure, the membrane spacing the sensing system from the fluid, at least one of the layers comprising HEMA.

21. The sensor probe of claim 20, wherein the membrane further comprises one or more of:

a layer which is negatively charged and which reduces efflux of gluconic acid from the sensor probe, thereby improving glucose sensitivity;

a layer of which comprises at least one of an anti-infection agent and an antihistamine;

a layer comprising one or more of heparin and chitosan; and

a layer comprising polyurethane.

22. The sensor probe of claim 2, wherein the beads have an average diameter of less than 10 micrometers.

23. The sensor probe of claim 1, wherein the body defines at least one cavity which encloses at least a portion of the sensing system.

24. The sensor probe of claim 23, further comprising a negatively charged hydrophilic gel disposed in the cavity.

25. The sensor probe of claim 24, wherein the negatively charged hydrophilic gel is selected from the group consisting of polyvinyl sulfate, polystyrenesulfonate, and combinations thereof.

26. The sensor probe of claim 2, wherein the sensing system comprises a plurality of sensing elements, each of the sensing elements providing a maximum color change at a pH which differs from other sensing elements, each of the sensing elements being associated with a different set of the beads.

27. The sensor probe of claim 1, wherein the analyte is selected from the group consisting of glucose, lactate, oxygen, galactose, urea, creatinin, pH, K⁺, Na⁺, and combinations thereof.

28. The sensor probe of claim 1, wherein the body defines first and second cavities, the sensing system comprising a first sensing element associated with a first set of beads disposed in a first of the cavities for detecting a first analyte and a second sensing element associated with a second set of beads disposed in a second of the cavities for detecting a second analyte different from the first analyte.

29. A sensor system comprising:

the probe of claim 1;

and

a detector capable of detecting the exhibited change.

30. The sensor system of claim 29, wherein the detector detects the change when the probe is implanted in the body of a person, the detector located external to the person.

31. A sensor probe comprising:

an enzyme capable of catalyzing a reaction of the analyte to form a reaction product; and

a dye system which absorbs in the infrared region of the spectrum in response to the reaction product.

32. The sensor probe of claim 31, further comprising:

a housing which encloses the dye system.

33. The sensor probe of claim 32, wherein the dye system is supported on beads within the housing.

34. The sensor probe of claim 31, wherein the dye system exhibits the detectable change in the IR region of the spectrum in response to a change in pH.

35. The sensor probe of claim 31, wherein the dye system provides a maximum color change at a pH of about 5.0 to 7.5.

36. The sensor probe of claim 31, wherein the dye system comprises a ketocyanine dye.

37. The sensor probe of claim 31, wherein the dye is selected from the group consisting of:

2,5-bis{[3,3-dimethyl-1-propylindolenine]ethylidene}cyclopentanone;

2,5-bis{[1-ethylbenzooxazolenine]ethylidene}cyclopentanone;

2,5-bis{[1,3,3-trimethylbenz[e]indolenine]ethylidene}cyclopentanone;

2,5-bis{[1-ethylbenzothiazolenine]ethylidene}cyclopentanone;

2-{[3-ethylbenzothiazolidene]ethylidene}-5-{[1,3,3-trimethylbenz[e]indolenine]ethylidene}cyclopentanone; and

combinations thereof.

38. The sensor probe of claim 31, wherein the analyte is selected from the group consisting of glucose, lactate, oxygen, galactose, urea, creatinin, pH, K⁺, and Na⁺.

39. The sensor probe of claim 31, wherein the analyte includes glucose and the enzyme includes at least one of glucose oxidase and glucose dehydrogenase.

40. The sensor probe of claim 31, wherein the dye system exhibits the detectable change in the IR region of the spectrum in response to a reaction product of the analyte.

41. A sensor system comprising the probe of claim 31 and a detector configured for detecting the absorption in the infrared region of the spectrum.

42. The sensor system of claim 41, wherein the detector detects the absorption when the probe is implanted in the body of a person, the detector located external to the person.

43. The sensing system of claim 41, wherein the detector includes at least one of a watch or pager-type color CCD camera and a spectrometer.

44. A method of detecting an analyte, in a fluid comprising:

positioning a sensor probe in the fluid, the sensor probe including;

a sensing element which in the infrared region of the spectrum in response to the analyte; and

detecting the change with a detection system.

45. The method of claim 44, further including:

implanting the sensor probe into a person'"'"'s eye.

46. The method of claim 44, further including:

mounting the sensor on one of a contact lens and the person'"'"'s glasses.

47. The method of claim 44, further including:

simultaneously detecting multiple analytes.