SPECIFICITY OF ANALYTE DETECTION IN ETALONS

• US 20100049015A1
• Filed: 08/21/2008
• Published: 02/25/2010
• 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: Roe, Jeffrey N., Kiesel, Peter, Bruce, Richard H., Torres, Francisco E., Martini, Joerg, Recht, Michael I.
• Granted Patent: US 9,161,714 B2
• Time in Patent Office: Days
• US Class Current: 600/310
• 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, (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 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; and

optical components for guiding light into said optical cavity detection regions within said first and second containers.

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

3. A system according to claim 1 additionally having an operatively associated illumination source.

4. A system according to claim 3 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 3 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 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.

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

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

11. 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 of 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 the larger receptor species out of the reservoir.

12. A system according to claim 8 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 of 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 the larger receptor species out of the reservoir.

13. 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.

14. A system according to claim 8 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.

15. 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.

16. A system according to claim 8 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 30k Daltons.

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

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

26. A system according to claim 1 further comprising

one or more additional containers that each 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 such 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.

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

28. A system according to claim 26, one or more of the said compounds being an interfering compound that alters the responsiveness of one or more containers to one or more analytes.

29. A system according to claim 28, wherein one of said one or more analytes is glucose, the modifier in the first container comprises dextran, the receptor in the first container comprises a protein having at least one binding site for glucose and dextran, and said interfering compound is maltose.

30. A system according to claim 28, 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, the receptor in the first container comprises dextran, and said interfering compound is maltose.

31. A system according to claim 1, further including one or more illumination sources, and a detecting means for measuring one or more optical properties of the optical cavity detection regions in the first and second containers.

32. A system according to claim 25, further including one or more illumination sources, and a detecting means for measuring one or more optical properties of three or more optical cavity detection regions in the system.

33. A system according to claim 26, further including one or more illumination sources, and a detecting means for measuring one or more optical properties of three or more optical cavity detection regions in the system.

34. A system according to claim 27, further including one or more illumination sources, and a detecting means for measuring one or more optical properties of three or more optical cavity detection regions in the system.

35. A system according to claim 28, further including one or more illumination sources, and a detecting means for measuring one or more optical properties of three or more optical cavity detection regions in the system.

36. A system according to claim 31, wherein one or more of said illumination sources produce infrared illumination.

37. A system according to claim 32, wherein one or more of said illumination sources produce infrared illumination.

38. A system according to claim 34, wherein one or more of said illumination sources produce infrared illumination.

39. A system according to claim 35, wherein one or more of said illumination sources produce infrared illumination.

40. A system according to claim 31, wherein said containers are implanted, or partially implanted, in or underneath the skin in contact with interstitial fluid, and wherein said detecting means is not implanted.

41. A system according to claim 32, wherein said containers are implanted, or partially implanted, in or underneath the skin in contact with interstitial fluid, and wherein said detecting means is not implanted.

42. A system according to claim 34, wherein said containers are implanted, or partially implanted, in or underneath the skin in contact with interstitial fluid, and wherein said detecting means is not implanted.

43. A system according to claim 35, wherein said containers are implanted, or partially implanted, in or underneath the skin in contact with interstitial fluid, and said detecting means is not implanted.

44. A system according to claim 31, wherein the optical property of at least one of said optical cavity detection regions is the intensity or polarization of light transmitted through or reflected from the optical cavity detection region.

45. A system according to claim 32, wherein the optical property of at least one of said optical cavity detection regions is the intensity or polarization of light transmitted through or reflected from the optical cavity detection region.

46. A system according to claim 34, wherein the optical property of at least one of said optical cavity detection regions is the intensity or polarization of light transmitted through or reflected from the optical cavity detection region.

47. A system according to claim 35, wherein the optical property of at least one of said optical cavity detection regions is the intensity or polarization of light transmitted through or reflected from the optical cavity detection region.

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

49. A system according to claim 32, wherein the optical property of at least one of said optical cavity detection regions is the intensity of light transmitted through or reflected from the optical cavity detection region over a range of wavelengths.

50. A system according to claim 34, wherein the optical property of at least one of said optical cavity detection regions is the intensity of light transmitted through or reflected from the optical cavity detection region over a range of wavelengths.

51. A system according to claim 35, wherein the optical property of at least one of said optical cavity detection regions is the intensity of light transmitted through or reflected from the optical cavity detection region over a range of wavelengths.

52. A system according to claim 31, wherein one or more optical cavity detection region is configured and operated as an inhomogeneous optical cavity, and the corresponding optical property being detected is the 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 optical cavity detection region.

53. A system according to claim 32, wherein one or more optical cavity detection region is configured and operated as an inhomogeneous optical cavity, and the corresponding optical property being detected is the 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 optical cavity detection region.

54. A system according to claim 34, wherein one or more optical cavity detection region is configured and operated as an inhomogeneous optical cavity, and the corresponding optical property being detected is the 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 optical cavity detection region.

55. A system according to claim 35, wherein one or more optical cavity detection region is configured and operated as an inhomogeneous optical cavity, and the corresponding optical property being detected is the 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 optical cavity detection region.

56. A system according to claim 31, wherein the light transmitted through or reflected from at least one of said optical cavity detection regions also passes through a variable filter, and the corresponding optical property being detected is the intensity of light transmitted through or reflected from the optical cavity detection region and the variable filter, as a function of location along the variable filter.

57. A system according to claim 32, wherein the light transmitted through or reflected from at least one of said optical cavity detection regions also passes through a variable filter, and the corresponding optical property being detected is the intensity of light transmitted through or reflected from the optical cavity detection region and the variable filter, as a function of location along the variable filter.

58. A system according to claim 34, wherein the light transmitted through or reflected from at least one of said optical cavity detection regions also passes through a variable filter, and the corresponding optical property being detected is the intensity of light transmitted through or reflected from the optical cavity detection region and the variable filter, as a function of location along the variable filter.

59. A system according to claim 35, wherein the light transmitted through or reflected from at least one of said optical cavity detection regions also passes through a variable filter, and the corresponding optical property being detected is the intensity of light transmitted through or reflected from the optical cavity detection region and the variable filter, as a function of location along the variable filter.

60. A system according to claim 31, wherein said detecting means comprises one or more photodetectors.

61. A system according to claim 32, wherein said detecting means comprises one or more photodetectors.

62. A system according to claim 34, wherein said detecting means comprises one or more photodetectors.

63. A system according to claim 35, wherein said detecting means comprises one or more photodetectors.

64. A system according to claim 31, wherein said illumination source and said detecting means are in optical contact with said system through optical fibers.

65. A system according to claim 32, wherein said illumination source and said detecting means are in optical contact with said system through optical fibers.

66. A system according to claim 34, wherein said illumination source and said detecting means are in optical contact with said system through optical fibers.

67. A system according to claim 35, wherein said illumination source and said detecting means are in optical contact with said system through optical fibers.

68. A system according to claim 31, wherein the detecting means comprises monitoring a RF signal from said device using a RF receiver.

69. A system according to claim 32, wherein the detecting means comprises monitoring a RF signal from said device using a RF receiver.

70. A system according to claim 34, wherein the detecting means comprises monitoring a RF signal from said device using a RF receiver.

71. A system according to claim 35, wherein the detecting means comprises monitoring a RF signal from said device using a RF receiver.

72. A system according to claim 26, wherein the measurement from a first container alone provides a less precise analyte concentration than the measurement from a second container alone, and the first container provides sufficient accuracy to deduce a more accurate measurement from the second container.

73. 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.

74. 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.

75. A system according to claim 73 wherein the second container is devoid of said modifiers.

76. A system according to claim 74, wherein the second container is devoid of said modifiers.

77. A system according to claim 73 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 of 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 the larger receptor species out of the optical cavity detection region.

78. A system according to claim 74 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 of 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 the larger receptor species out of the optical cavity detection region.

79. A system according to claim 73 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.

80. A system according to claim 74 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.

81. A system according to claim 73 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.

82. A system according to claim 74 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.