Method and apparatus for optically measuring concentration of an analyte

• US 5,212,099 A
• Filed: 01/18/1991
• Issued: 05/18/1993
• Est. Priority Date: 01/18/1991
• Status: Expired due to Term

• Current Assignee: Eastman Kodak Company
• Original Assignee: Eastman Kodak Company
• Inventors: Marcus, Michael A.
• Primary Examiner(s): Housel, James C.
• Assistant Examiner(s): Snay, Jeffrey R.
• Application Number:
  US07/643,403
• Time in Patent Office: 851 Days
• Field of Search: 436/39, 436/147, 436/149, 436/164, 436/172, 436/805, 422/82.05, 422/82.06, 422/82.07, 422/82.08, 422/82.09, 422/82.11, 356/36, 356/38, 356/301, 356/312, 356/316, 356/317, 356/440, 356/445, 250/458.1, 250/459.1
• US Class Current: 436/172
• CPC Class Codes: G01N 2021/1725 Modulation of properties by light, e.g. photoreflectance
• CPC Class Codes: G01N 2021/772 Tip coated light guide
• CPC Class Codes: G01N 2021/773 Porous polymer jacket; Polymer matrix with indicator
• CPC Class Codes: G01N 2021/7786 Fluorescence
• CPC Class Codes: G01N 21/1717 with a modulation of one or more physical properties of the sample during the optical investigation, e.g. electro-reflectance
• CPC Class Codes: G01N 21/648 using evanescent coupling or surface plasmon coupling for the excitation of fluorescence
• CPC Class Codes: G01N 21/7703 using reagent-clad optical fibres or optical waveguides using measurement of total internal reflection or attenuated total reflection G01N21/552; optical fibres or waveguides per se G02B
• CPC Class Codes: G01N 2201/122 Kinetic analysis; determining reaction rate

Abstract

Apparatus and method in which a beam of radiant energy (16) is passed into a medium at a wavelength selected to cause a response of an analyte in the medium or of a sensor (10,14) exposed to the medium, the sensor comprising a reagent whose optical properties change in response to the presence of the analyte in the medium. A perturbing pulse of energy (22) is passed into the medium to alter the response of the analyte or reagent to the beam of radiation; and the time rates of change in the intensity of the transmitted radiant energy are measured (18,24,26,28) while the intensity is changing due to the perturbing pulse, after each such perturbing pulse starts or ends or both, such rates of change being proportional to the concentration of the analyte in the medium. Both the beam of radiant energy and the perturbing pulse may be passed through optic fibers into the medium or sensor.

Claims

1. A method for measuring the concentration of an analyte in a medium, comprising the steps of:

directing a beam of radiant energy along an optical path into said medium at a wavelength selected to cause a response of said analyte;

periodically directing a perturbing pulse of energy into said medium to alter in a controlled manner the concentration of said analyte along said path and thereby the response of said analyte to said beam of radiant energy;

detecting the response of said analyte to said beam of radiant energy while the response is changing due to the influence of the perturbing pulse, after the perturbing pulse starts or ends or both;

determining the time rate of change of said response; and

correlating said time rate of change to the concentration of said analyte.

2. A method according to claim 1, wherein said medium is a fluid and said analyte responds to said beam of radiant energy by fluorescing.

3. A method according to claim 1, wherein said medium is a fluid and said analyte responds to said beam of radiant energy by absorbing at least a portion of said radiant energy.

4. A method according to claim 1, wherein said medium is a fluid and said analyte responds to said beam of radiant energy by scattering at least a portion of said radiant energy.

5. A method according to claim 1, wherein said medium is a fluid and said analyte responds to said beam of radiant energy by reflecting at least a portion of said radiant energy.

6. A method according to one of claims 1 to 5, wherein said response is a change in the intensity of radiation leaving said medium.

7. A method according to claim 1, wherein said perturbing pulse comprises acoustic energy.

8. A method according to claim 1, wherein said perturbing pulse comprises energy from an electrical field.

9. A method according to claim 1, wherein said perturbing pulse comprises energy from a magnetic field.

10. A method according to claim 1, wherein said perturbing pulse comprises ultraviolet, visible or infrared radiant energy.

11. A method according to claim 1, wherein said perturbing pulse comprises microwave energy.

12. A method according to claim 1, wherein said perturbing pulse comprises heat energy.

13. A method for measuring the concentration of an analyte in a medium, comprising the steps of:

providing a reagent whose optical properties change in response to the concentrations of said analyte;

exposing said reagent to said analyte in said medium;

directing a beam of radiant energy along an optical path into said reagent at a wavelength selected to affect said beam of radiant energy as a function of the concentration of said analyte;

periodically directing a perturbing pulse of energy into said reagent to alter in a controlled manner both the concentration of said analyte along said path and the optical spectral characteristics of said reagents as a function of the concentration of said analyte;

detecting the effect of said reagent on said beam of radiant energy while the response is changing due to the influence of the perturbing pulse, after the perturbing pulse starts or ends or both;

determining the time rate of change of said effect; and

correlating said time rate of change to the concentration of said analyte.

14. A method according to claim 13, wherein said optical property of said reagent is fluorescence.

15. A method according to claim 13, wherein said optical property of said reagent is absorbance.

16. A method according to claim 13, wherein said optical property of said reagent is its ability to scatter at least a portion of said radiant energy.

17. A method according to claim 13, wherein said optical property of said reagent is its ability to reflect at least a portion of said radiant energy.

18. A method according to one of claims 13 to 17, wherein said effect is a change in the intensity of radiation leaving said medium.

19. A method according to claim 13, wherein said perturbing pulse comprises acoustic energy.

20. A method according to claim 13, wherein said perturbing pulse comprises energy from an electrical field.

21. A method according to claim 13, wherein said perturbing pulse comprises energy from a magnetic field.

22. A method according to claim 13, wherein said perturbing pulse comprises ultraviolet , visible or infrared radiant energy.

23. A method according to claim 13, wherein said perturbing pulse comprises microwave energy.

24. A method according to claim 13, wherein said perturbing pulse comprises heat energy.

25. Apparatus for measuring the concentration of an analyte in a medium, comprising:

means for directing a beam of radiant energy along an optical path into said medium at a first wavelength selected to cause a response of said analyte;

means for periodically directing a perturbing pulse of energy into said medium and for altering in a controlled manner the concentration of said analyte along said path and thereby the response of said analyte to said beam of radiant energy;

means for detecting the time rate of change of the intensity of radiation leaving said medium as the response of said analyte to said beam of radiant energy while the response is changing due to the influence of the perturbing pulse, after the perturbing pulse starts or ends or both; and

means for correlating said time rate of change to the concentration of said analyte.

26. Apparatus according to claim 25, wherein said medium is a fluid and said analyte responds to said beam of radiant energy by fluorescing.

27. Apparatus according to claim 25, wherein said medium is a fluid and said analyte responds to said beam of radiant energy by absorbing at least a portion of said radiant energy.

28. Apparatus according to claim 25, wherein said medium is a fluid and said analyte responds to said beam of radiant energy by scattering at least a portion of said radiant energy.

29. Apparatus according to claim 25, wherein said medium is a fluid and said analyte responds to said beam of radiant energy by reflecting at least a portion of said radiant energy.

30. Apparatus according to claim 25, wherein said perturbing pulse comprises acoustic energy.

31. Apparatus according to claim 25, wherein said perturbing pulse comprises energy from an electrical field.

32. Apparatus according to claim 25, wherein said perturbing pulse comprises energy from a magnetic field.

33. Apparatus according to claim 25, wherein said perturbing pulse comprises ultraviolet, visible or infrared radiant energy.

34. Apparatus according to claim 25, wherein said perturbing pulse comprises microwave energy.

35. Apparatus according to claim 25, wherein said perturbing pulse comprises heat energy.

36. Apparatus according to claim 25, wherein said medium is a waveguide.

37. Apparatus according to claim 25, wherein said means for directing a beam comprises a continuous source of radiant energy and an optic fiber for receiving radiant energy from said continuous source at one end and emitting radiant energy from said continuous source into said medium at the other end.

38. Apparatus according to claim 37, wherein said means for directing a perturbing pulse comprises an intermittent source of radiant energy and means for coupling radiation from said intermittent source into said optic fiber.

39. Apparatus according to claim 37, wherein said means for directing a perturbing pulse comprises an intermittent source of radiant energy and an optic fiber for receiving said pulse at one end and emitting said pulse onto said medium at the other end.

40. Apparatus for measuring the concentration of an analyte in a medium, comprising:

a sensor element including a reagent whose optical properties change in response to the concentration of said analyte;

means for exposing said reagent to said analyte in said medium;

means for directing a beam of radiant energy along an optical path into said reagent at a wavelength selected to affect said beam of radiant energy as a function of the concentration of said analyte;

means for periodically directing a perturbing pulse of energy into said reagent and for altering in a controlled manner both concentration of said analyte along said path and the optical spectral characteristics of said reagent as a function of the concentration of said analyte;

means for detecting the time rate of change of the intensity of radiation leaving said reagent as the effect of said reagent on said beam of radiant energy while said effect is changing due to the influence of the perturbing pulse, after the perturbing pulse starts or ends or both; and

means for correlating said time rate of change to the concentration of said analyte.

41. Apparatus according to claim 40, wherein said optical property of said reagent is fluorescence.

42. Apparatus according to claim 40, wherein said optical property of said reagent is absorbance.

43. Apparatus according to claim 40, wherein said optical property of said reagent is its ability to scatter at least a portion of said radiant energy.

44. Apparatus according to claim 40, wherein said optical property of said reagent is its ability to reflect at least a portion of said radiant energy.

45. apparatus according to claim 40, wherein said means for directing a perturbing pulse comprises an intermittent source of radiant energy and an optic fiber for receiving said pulse at one end and emitting said pulse into said sensor.

46. Apparatus according to claim 40, wherein said perturbing pulse comprises acoustic energy.

47. Apparatus according to claim 40, wherein said perturbing pulse comprises energy from an electrical field.

48. Apparatus according to claim 40, wherein said perturbing pulse comprises energy from a magnetic field.

49. Apparatus according to claim 40, wherein said perturbing pulse comprises ultraviolet, visible or infrared radiant energy.

50. Apparatus according to claim 40, wherein said perturbing pulse comprises microwave energy.

51. Apparatus according to claim 40, wherein said perturbing pulse comprises heat energy.

52. Apparatus according to claim 40, wherein said sensor element comprises waveguide having a coating including said reagent.

53. Apparatus according to claim 40, wherein said means for directing a beam comprises a continuous source of radiant energy and an optic fiber for receiving radiant energy from said continuous source at one end and emitting radiant energy from said continuous source into said sensor.

54. Apparatus according to claim 53, wherein said means for directing a perturbing pulse comprises an intermittent source of radiant energy and means for coupling radiation from said intermittent source into said optic fiber.

55. Apparatus according to claim 53, wherein said sensor element comprises a portion of said optic fiber and said reagent is comprised in a reflective coating on the tip of said optic fiber.

56. Apparatus according to claim 53, wherein said sensor element comprises a portion of said optic fiber and said reagent is comprised in a coating surrounding at least a portion of said optic fiber.