Specificity of analyte detection in etalons

• US 9,161,714 B2
• Filed: 08/21/2008
• Issued: 10/20/2015
• Est. Priority Date: 08/21/2008
• Status: Active Grant

• Current Assignee: Xerox Corporation (Xerox Holdings Corp.)
• Original Assignee: Palo Alto Research Center, Inc. (Xerox Holdings Corp.)
• Inventors: Martini, Joerg, Bruce, Richard H., Torres, Francisco E., Kiesel, Peter, Recht, Michael I., Roe, Jeffrey N.
• Primary Examiner(s): HENSON, DEVIN B
• Application Number:
  US12/195,942
• Publication Number:
  US 20100049015A1
• Time in Patent Office: 2,616 Days
• Field of Search: 600/310, 600/316, 600/319, 600/347, 356/246, 356/451, 356/454, 356/519
• US Class Current: 1/1
• CPC Class Codes: A61B 5/0031 Implanted circuitry
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/1459 invasive, e.g. introduced into the body by a catheter A61B5/1464 takes precedence
• CPC Class Codes: G01N 21/33 using ultraviolet light G01N21/39 takes precedence
• CPC Class Codes: G01N 21/359 using near infrared light

Abstract

A system and method is provided for detecting concentration of an analyte in a fluid. A first container includes (i) an optical cavity detection region, (ii) a reservoir for one or more modifiers of one or more optical properties of the optical cavity detection region, and (iii) a set of one or more bounding regions through which objects in the fluid can transfer into the container. The optical cavity detection region and the reservoir define separate areas of the first container. The movement of the one or more modifiers between the reservoir and the optical cavity detection region is responsive to changes in concentration of the analyte. A second container includes an optical cavity detection region, and a set of one or more bounding regions through which objects in the fluid can transfer into the container. Also provided are optical components for guiding light into the optical cavity detection regions of the first and second containers.

Claims

1. A system for detecting concentration of an analyte in a fluid, the system comprising:

a first container including (i) an optical cavity detection region having a first side and a second side opposite the first side, the first side and the second side at least partially bounded by light reflective components, and further configured to permit passage of light therethrough, (ii) a reservoir for one or more modifiers of one or more optical properties of said optical cavity detection region, the reservoir configured to define boundaries of the optical cavity detection region, and the reservoir extending substantially from the first side to the second side of the optical cavity detection region and (iii) a set of one or more bounding regions through which objects in the fluid can transfer into the container;

the optical cavity detection region and the reservoir defining separate areas of the first container;

the movement of said one or more modifiers between said reservoir and said optical cavity detection region being responsive to changes in concentration of said analyte;

a second container including an optical cavity detection region having a first side and a second side opposite the first side, the first side and the second side at least partially bounded by light reflective components, and further configured to permit passage of light therethrough, and a set of one or more bounding regions through which objects in the fluid can transfer into the container;

an illumination source located a distance external from the first container and the second container and configured to generate the light passing through the optical cavity detection region; and

a detector component located a distance external from the first container and the second container on a side opposite the illumination source and configured to detect the light exiting from the optical cavity detection region.

2. A system according to claim 1, which is implantable or partially implantable in or underneath skin in contact with interstitial fluid.

3. A system according to claim 1, wherein the external illumination source and the external detector component are located in relationship to each other such that at least some of the light from the external illumination source input into the first container and the second container and then output from the first container and the second container is detected by the external detector component.

4. A system according to claim 1, wherein said illumination source is one of a UV illumination source providing light with wavelengths between 220 and 320 nanometers or a near IR illumination source providing light with wavelengths between 750 and 1500 nanometers.

5. A system according to claim 1, wherein said illumination source is one or more of a vertical cavity surface emitting laser (VCSEL), a solid state laser, a Distributed Feed Back (DFB) laser, a Distributed Bragg Reflector (DBR) laser or a resonant cavity light emitting diode (LED).

6. A system according to claim 1, wherein at least one of said modifiers are amplifying material which amplify the changes in one or more optical property of said optical cavity detection region in said first container.

7. A system according to claim 1, wherein said analyte binds reversibly to a receptor contained within the reservoir and at least one of said modifiers binds reversibly to the same receptor in competition with said analyte.

8. A system according to claim 7, wherein the second container is devoid of said modifiers.

9. A system according to claim 7, wherein the receptor is one of (i) immobilized, (ii) kept within the reservoir by chemical or physical crosslinking, or (iii) kept within the reservoir by one or more filters that allow passage of said modifiers into the optical cavity detection region and said analyte into the reservoir, while preventing or minimizing passage of a larger receptor species out of the reservoir.

10. A system according to claim 7, wherein the analyte is glucose, the modifier comprises dextran, and the receptor comprises a protein having at least one binding site for glucose and dextran.

11. A system according to claim 7, wherein the analyte is one of urea, insulin, lactate, ions, therapeutic drugs or immunosuppressant drugs, and the receptor is one of lectin, concanavalin A lectin, Fab fragments, hormone receptors, drug receptors, aptamers, catalytically inactive enzyme, or molecularly-imprinted polymers.

12. A system according to claim 1, wherein at least one of said modifiers binds reversibly to a receptor contained within the reservoir and also binds to said analyte in competition with the receptor.

13. A system according to claim 12, wherein the second container is devoid of said modifiers.

14. A system according to claim 12, wherein the receptor is one of (i) immobilized, (ii) kept within the reservoir by chemical or physical crosslinking, or (iii) kept within the reservoir by one or more filters that allow passage of said modifiers into the optical cavity detection region and said analyte into the reservoir, while preventing or minimizing passage of a larger receptor species out of the reservoir.

15. A system according to claim 12, wherein the analyte is glucose, the modifier is a protein having at least one binding site for glucose and dextran, and the receptor comprises dextran.

16. A system according to claim 12, wherein the analyte is one of urea, insulin, lactate, ions, therapeutic drugs or immunosuppressant drugs, and the modifier is one of lectin, concanavalin A lectin, Fab fragments, hormone receptors, drug receptors, aptamers, catalytically inactive enzyme, or molecularly-imprinted polymers.

17. A system according to claim 1, wherein said bounding regions through which objects in the fluid can transfer into said first and second containers are covered with one or more filters.

18. A system according to claim 17, wherein at least one of said filters are comprised of macromolecule, ultrafiltration, and/or molecular weight cut-off filter media.

19. A system according to claim 17, wherein at least one of said filters minimize or prevent the migration of said modifiers out of said first container.

20. A system according to claim 17, wherein the at least one of said filters is sized to restrict objects greater than a certain size from entering the interior of the said first and second containers.

21. A system according to claim 20, wherein said filter size is approximately 30 k Daltons.

22. A system according to claim 20, wherein said filter size is approximately 15 k Daltons.

23. A system according to claim 20, wherein said filter size is approximately 3 k Daltons.

24. A system according to claim 20, wherein said filter size is approximately 1-6 nanometers.

25. A system according to claim 1, further comprising

one or more additional containers each configured as an optical cavity at least partially bounded by light reflective components and each one or more additional containers including (i) an optical cavity detection region, (ii) a reservoir for one or more modifiers of one or more optical properties of said optical cavity detection region, and (iii) a set of one or more bounding regions through which objects in the fluid can transfer into the container;

the optical cavity detection region and the reservoir of each such container defining separate areas of the container;

the movement of one or more modifiers between said reservoir and said optical cavity detection region of each additional container being responsive to changes in concentration of one or more compounds in the fluid; and

optical components for guiding light into said optical cavity detection regions within said additional containers.

26. A system according to claim 25, with one or more of said compounds being distinct analytes different from the analyte specified in claim 1.

27. A system according to claim 26, wherein the illumination source and the detector component are configured to measure one or more optical properties of three or more optical cavity detection regions in the system.

28. A system according to claim 27, wherein the illumination source produces infrared illumination.

29. A system according to claim 27, wherein said containers are configured to be implanted, or partially implanted, in or underneath skin in contact with interstitial fluid, and wherein said detector component is not implanted.

30. A system according to claim 27, wherein the optical property of at least one of said optical cavity detection regions is an intensity or polarization of light transmitted through or reflected from the optical cavity detection region.

31. A system according to claim 27, wherein the optical property of at least one of said optical cavity detection regions is an intensity of light transmitted through or reflected from the optical cavity detection region over a range of wavelengths.

32. A system according to claim 27, wherein one or more of the optical cavity detection regions are is configured and operated as an inhomogeneous optical cavity, and a corresponding optical property being detected is an intensity of light transmitted through or reflected from the optical cavity detection region as a function of position wherein the transmitted or reflected light leaves the one or more optical cavity detection regions.

33. A system according to claim 27, wherein the light transmitted through or reflected from at least one of said optical cavity detection regions also passes through a variable filter, and a corresponding optical property being detected is an intensity of light transmitted through or reflected from the at least one optical cavity detection region and the variable filter, as a function of location along the variable filter.

34. A system according to claim 25, one or more of said compounds being an interfering compound that alters the responsiveness of one or more containers to one or more analytes.

35. A system according to claim 34, wherein one of said one or more analytes is glucose, the modifier in the first container comprises dextran, a receptor in the first container comprises a protein having at least one binding site for glucose and dextran, and said interfering compound is maltose.

36. A system according to claim 34, wherein one of said one or more analytes is glucose, the modifier in the first container is a protein having at least one binding site for glucose and dextran, a receptor in the first container comprises dextran, and said interfering compound is maltose.

37. A system according to claim 34 wherein the illumination source and the detector component are configured to measure one or more optical properties of three or more optical cavity detection regions in the system.

38. A system according to claim 37, wherein the illumination source produces infrared illumination.

39. A system according to claim 37, wherein said containers are configured to be implanted, or partially implanted, in or underneath skin in contact with interstitial fluid, and said detector component is not implanted.

40. A system according to claim 37, wherein the optical property of at least one of said optical cavity detection regions is an intensity or polarization of light transmitted through or reflected from the optical cavity detection region.

41. A system according to claim 37, wherein the optical property of at least one of said optical cavity detection regions is an intensity of light transmitted through or reflected from the optical cavity detection region over a range of wavelengths.

42. A system according to claim 37, wherein one or of the more optical cavity detection regions are configured and operated as an inhomogeneous optical cavity, and a corresponding optical property being detected is an intensity of light transmitted through or reflected from the optical cavity detection region as a function of position wherein the transmitted or reflected light leaves the one or more optical cavity detection regions.

43. A system according to claim 37, wherein the light transmitted through or reflected from at least one of said optical cavity detection regions also passes through a variable filter, and a corresponding optical property being detected is an intensity of light transmitted through or reflected from the at least one optical cavity detection region and the variable filter, as a function of location along the variable filter.

44. A system according to claim 25, wherein the illumination source and the detector component are configured to measure one or more optical properties of three or more optical cavity detection regions in the system.

45. A system according to claim 1, wherein the illumination source and the detector component are configured to measure one or more optical properties of the optical cavity detection regions in the first and second containers.

46. A system according to claim 45, wherein the illumination source produces infrared illumination.

47. A system according to claim 45, wherein said containers are configured to be implanted, or partially implanted, in or underneath skin in contact with interstitial fluid, and wherein said detector component is not implanted.

48. A system according to claim 45, wherein the optical property of at least one of said optical cavity detection regions is an intensity or polarization of light transmitted through or reflected from the optical cavity detection region.

49. A system according to claim 45, wherein the optical property of at least one of said optical cavity detection regions is an intensity of light transmitted through or reflected from the optical cavity detection region over a range of wavelengths.

50. A system according to claim 45, wherein one or more of the optical cavity detection regions are configured and operated as an inhomogeneous optical cavity, and a corresponding optical property being detected is an intensity of light transmitted through or reflected from the optical cavity detection region as a function of position wherein the transmitted or reflected light leaves the one or more optical cavity detection regions.

51. A system according to claim 45, wherein the light transmitted through or reflected from at least one of said optical cavity detection regions also passes through a variable filter, and a corresponding optical property being detected is an intensity of light transmitted through or reflected from the at least one optical cavity detection region and the variable filter, as a function of location along the variable filter.

52. A system according to claim 45, wherein said detector component comprises one or more photodetectors.

53. A system according to claim 45, wherein said illumination source and said detector component are in optical contact with said system through optical fibers.

54. A system according to claim 45, wherein the detector component is configured to monitor a RF signal from said first and second container using a RF receiver.

55. A system according to claim 1, wherein said analyte binds reversibly to a receptor contained within the optical cavity detection region in the first container and at least one of said modifiers binds reversibly to the same receptor in competition with said analyte.

56. A system according to claim 55, wherein the second container is devoid of said modifiers.

57. A system according to claim 55, wherein the receptor is one of (i) immobilized, (ii) kept within the optical cavity detection region in the first container by chemical or physical crosslinking, or (iii) kept within the optical cavity detection region in the first container by one or more filters that allow passage of said modifiers into the reservoir and said analyte into the said optical cavity detection region in the first container, while preventing or minimizing passage of a larger receptor species out of the optical cavity detection region.

58. A system according to claim 55, wherein the analyte is glucose, the modifier comprises dextran, and the receptor comprises a protein having at least one binding site for glucose and dextran.

59. A system according to claim 55, wherein the analyte is one of urea, insulin, lactate, ions, therapeutic drugs or immunosuppressant drugs, and the receptor is one of lectin, concanavalin A lectin, Fab fragments, hormone receptors, drug receptors, aptamers, catalytically inactive enzyme, or molecularly-imprinted polymers.

60. A system according to claim 1, wherein at least one of said modifiers binds reversibly to a receptor contained within the optical cavity detection region in the first container and also binds to said analyte in competition with the receptor.

61. A system according to claim 60, wherein the second container is devoid of said modifiers.

62. A system according to claim 60, wherein the receptor is one of (i) immobilized, (ii) kept within the optical cavity detection region in the first container by chemical or physical crosslinking, or (iii) kept within the optical cavity detection region in the first container by one or more filters that allow passage of said modifiers into the reservoir and said analyte into the said optical cavity detection region in the first container, while preventing or minimizing passage of a larger receptor species out of the optical cavity detection region.

63. A system according to claim 60, wherein the analyte is glucose, the modifier is a protein having at least one binding site for glucose and dextran, and the receptor comprises dextran.

64. A system according to claim 60, wherein the analyte is one of urea, insulin, lactate, ions, therapeutic drugs or immunosuppressant drugs, and the modifier is one of lectin, concanavalin A lectin, Fab fragments, hormone receptors, drug receptors, aptamers, catalytically inactive enzyme, or molecularly-imprinted polymers.

65. The system according to claim 1, wherein the reservoir includes a first reservoir area defined at least on one side by a filter and on a another side by another different filter, and a second reservoir area defined at least on one side by a wall and on another side by a filter.

66. The system of claim 1, wherein the reservoir includes lamella components.

67. The system of claim 66, wherein the lamella components are functionalized by dextran.

68. The system of claim 1, wherein the reservoir includes foam components.

69. The system of claim 68, wherein the foam components are functionalized by dextran.

70. The system of claim 1, wherein the reservoir includes hydrogel components.

71. The system of claim 70, wherein the hydrogel components, are functionalized by dextran.

72. The system of claim 1, wherein the reservoir includes interwoven fibers.

73. The system of claim 72, the wherein interwoven fibers, are functionalized by dextran.

74. The system of claim 1, wherein the reservoir includes an inner surface of a molecular weight cut-off filter.

75. The system of claim 74, wherein the inner surface of the molecular weight cut-off filter is functionalized by dextran.

76. The system according to claim 1, further including the light reflective components configured to phase-shift the light generated by the illumination source and the light generated by the illumination source is the same light, phase-shifted, that is detected by the detector component configured to detect the phase-shifted light.

77. The system according to claim 1, wherein the reservoir is configured to include at least one of a filter, a lamella, a foam and a fiber.

78. The system according to claim 1, wherein the illumination source is configured to transmit light substantially parallel to the boundaries of the optical detection region and the reservoir.

79. A system for detecting concentration of an analyte in a fluid, the system comprising:

a first container configured as an optical cavity at least partially bounded by light reflective components, the first container including (i) an optical cavity detection region, (ii) a reservoir for one or more modifiers of one or more optical properties of said optical cavity detection region, and (iii) a set of one or more bounding regions through which objects in the fluid can transfer into the container;

the optical cavity detection region and the reservoir defining separate areas of the first container;

the movement of said one or more modifiers between said reservoir and said optical cavity detection region being responsive to changes in concentration of said analyte;

a second container configured as an optical cavity at least partially bounded by light reflective components, the second container including an optical cavity detection region and a set of one or more bounding regions through which objects in the fluid can transfer into the container;

at least a third container including an optical cavity detection region, said third container being a reference container with the optical cavity detection region preloaded with a known reference fluid and sealed so fluid external to said third container cannot enter the interior of said third container;

an illumination source located a distance external from the first container, the second container, and the at least third container; and

a detector component located a distance external from the first container, the second container and the at least third container.

80. A system according to claim 79, wherein the illumination source and the detector component are configured to measure one or more optical properties of three or more optical cavity detection regions in the system.

81. A system according to claim 80, wherein the illumination source produces infrared illumination.

82. A system according to claim 80, wherein said containers are configured to be implanted, or partially implanted, in or underneath skin in contact with interstitial fluid, and wherein said detector component is not implanted.

83. A system according to claim 80, wherein the optical property of at least one of said optical cavity detection regions is an intensity or polarization of light transmitted through or reflected from the optical cavity detection region.

84. A system according to claim 80, wherein the optical property of at least one of said optical cavity detection regions is an intensity of light transmitted through or reflected from the optical cavity detection region over a range of wavelengths.

85. A system according to claim 80, wherein one or more of the optical cavity detection regions are configured and operated as an inhomogeneous optical cavity, and a corresponding optical property being detected is an intensity of light transmitted through or reflected from the optical cavity detection region as a function of position wherein the transmitted or reflected light leaves the one or more optical cavity detection regions.

86. A system according to claim 80, wherein the light transmitted through or reflected from at least one of said optical cavity detection regions also passes through a variable filter, and a corresponding optical property being detected is an intensity of light transmitted through or reflected from the at least one optical cavity detection region and the variable filter, as a function of location along the variable filter.

87. A system for detecting concentration of an analyte in a fluid, the system comprising:

a first container configured as an optical cavity at least partially bounded by light reflective components, the first container including (i) an optical cavity detection region, (ii) a reservoir for one or more modifiers of one or more optical properties of said optical cavity detection region, and (iii) a set of one or more bounding regions through which objects in the fluid can transfer into the container;

the optical cavity detection region and the reservoir defining separate areas of the first container;

the movement of said one or more modifiers between said reservoir and said optical cavity detection region being responsive to changes in concentration of said analyte;

a second container configured as an optical cavity at least partially bounded by light reflective components, the second container including an optical cavity detection region and a set of one or more bounding regions through which objects in the fluid can transfer into the container;

one or more additional containers each configured as an optical cavity at least partially bounded by light reflective components and each one or more additional containers including (i) an optical cavity detection region, (ii) a reservoir for one or more modifiers of one or more optical properties of said optical cavity detection region, and (iii) a set of one or more bounding regions through which objects in the fluid can transfer into the container;

the optical cavity detection region and the reservoir of each such container defining separate areas of the container;

the movement of one or more modifiers between said reservoir and said optical cavity detection region of each additional container being responsive to changes in concentration of one or more compounds in the fluid;

an illumination source located a distance external from the first container, the second container and the one or more additional containers;

optical components for guiding light into said optical cavity detection regions; and

a detector component located a distance external from the first container, the second container and the one or more additional containers, wherein a measurement from the first container alone provides a less precise analyte concentration than a measurement from the second container alone, and the first container provides an accuracy to deduce a more accurate measurement from the second container.