Method of detecting the concentration of an analyte

• US 7,961,326 B2
• Filed: 08/21/2008
• Issued: 06/14/2011
• 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, Recht, Michael I., Roe, Jeffrey N., Kiesel, Peter, Bruce, Richard H., Torres, Francisco E.
• Primary Examiner(s): Toatley; Gregory J
• Assistant Examiner(s): BRYANT, REBECCA CAROLE
• Application Number:
  US12/195,997
• Publication Number:
  US 20100045993A1
• Time in Patent Office: 1,027 Days
• Field of Search: 356 39- 42, 356/433, 356/436, 356440-442, 600160-182
• US Class Current: 356/433
• 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. The method comprises detecting an optical property of a first region of two or more regions in a system, the first region located in a container having a reservoir for one or more modifiers of one or more optical properties of the first region. The movement of the one or more modifiers is responsive to changes in concentration of the analyte. A next step detects an optical property of a second region of the two or more regions in the system, the second region located in a container having a reservoir for one or more modifiers of one or more optical properties of the second region. The movement of the one or more modifiers is responsive to changes in concentration of a compound, where the compound is something other than the analyte. The detected optical property of the first region and the detected optical property of the second region are used in embodiments to separate the effect of the analyte on the detected optical property of the first region from the effect of the compound, where the compound is an interfering compound.

Claims

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

providing a reflective optical cavity system having two or more light-transmissive regions at least partially bounded by components having light-transmissive and light-reflective properties, at least two of the components having substantially parallel surfaces;

detecting an optical property of a first region of the two or more regions in the system, the first region located in a container having a reservoir for one or more modifiers of one or more optical properties of the first region, the movement of said one or more modifiers being responsive to changes in concentration of said analyte;

detecting an optical property of a second region of the two or more regions in the system, the second region located in a container having a reservoir for one or more modifiers of one or more optical properties of the second region;

the movement of said one or more modifiers being responsive to changes in concentration of a compound other than said analyte in the fluid;

using said detected optical property of the first region and said detected optical property of the second region to separate the effect of said analyte on said detected optical property of the first region from the effect of said compound other than said analyte, said compound being an interfering compound; and

determining the concentration of the analyte based on the difference in the effect of the analyte and the effect of the compound other than the analyte.

2. A method according to claim 1 wherein one or more optical property detected is the intensity of light transmitted through or reflected from an optical cavity detection region and further including determining the shift in the spectral position of one or more intensity peak.

3. A method according to claim 2 further including determining the shift in the spectral position of one or more intensity peak divided by the free spectral range.

4. A method according to claim 1 further including determining changes in refractive index in the first and second containers of a system with a first container in which the first region is located and a second container in which the second region is located.

5. A method according to claim 1 further including determining changes in optical absorbance in the first and second containers of a system with a first container in which the first region is located and a second container in which the second region is located.

6. A method according to claim 4 further including determining a concentration of the first analyte by the determined refractive index.

7. A method according to claim 5 further including determining a concentration of the first analyte by the determined absorption.

8. A method according to claim 1 further including, detecting an optical property of an optical cavity detection region in at least a third container which is preloaded with a known reference fluid, the preloaded third container being sealed so the fluid external to the third container cannot enter the interior of the third container, the third container being a reference container.

9. A method according to claim 1 further including implanting the first and second containers which are physically connected in or underneath the skin in contact with interstitial fluid.

10. A method according to claim 1 further including illuminating the first and second containers with an operatively associated illumination source.

11. A method according to claim 1 further including providing one or more illumination sources, and a detecting means for measuring one or more properties of the first and second containers.

12. A method according to claim 11 further including implanting or partially implanting the first and second containers, in or underneath the skin in contact with interstitial fluid, and wherein the detecting means is not implanted.

33. A method according to claim 1 further comprising the step of generating a radiofrequency from the detected optical property of the first region and the second region of the system and monitoring said radiofrequency signals generated by the system, using a radiofrequency receiver.

13. A method for detecting concentration of an analyte in a fluid, the method comprising:

providing a reflective optical cavity system having two or more light-transmissive regions at least partially bounded by components having light-transmissive and light-reflective properties, at least two of the components having substantially parallel surfaces;

detecting an optical property of a first optical cavity detection region of the two or more optical cavity detection regions in the system, the first optical cavity detection region located in a container having a reservoir for one or more modifiers of one or more optical properties of said region, the movement of said one or more modifiers between said reservoir and said first optical cavity detection region being responsive to changes in concentration of said analyte;

detecting an optical property of a second optical cavity detection region of the two or more optical cavity detection regions in the system, the second optical cavity detection region located in a second container;

using the difference in the optical property detected from the first optical cavity detection region and the optical property detected from the second optical cavity detection region to determine the concentration of the analyte in said fluid.

14. A method according to claim 13 wherein one or more optical property detected is the intensity of light transmitted through or reflected from an optical cavity detection region, and further including determining the shift in the spectral position of one or more intensity peak divided by the free spectral range.

15. A method according to claim 13 further including implanting or partially implanting the first and second containers in or underneath the skin in contact with interstitial fluid.

16. A method according to claim 13 further including inputting light into the first and second containers with an operatively associated illumination source.

17. A method according to claim 13 wherein the reservoir contains a receptor.

18. A method according to claim 13 wherein the said first optical cavity detection region contains a receptor.

19. A method according to claim 17 wherein analyte is glucose, the modifier comprises dextran, and the receptor comprises a protein having at least one binding site for glucose and dextran.

20. A method according to claim 17 wherein analyte is glucose, the receptor comprises dextran, and the modifier comprises a protein having at least one binding site for glucose and dextran.

21. A method according to claim 17 wherein the analyte is one of urea, insulin, lactate, ions, therapeutic drugs or immunosuppressant drugs, and the receptor is one of lectin, concanavalin A, Fab fragments, hormone receptors, drug receptors, aptamers or molecularly-imprinted polymers.

22. A method according to claim 18 wherein analyte is glucose, the modifier comprises dextran, and the receptor comprises a protein having at least one binding site for glucose and dextran.

23. A method according to claim 18 wherein analyte is glucose, the receptor comprises dextran, and the modifier comprises a protein having at least one binding site for glucose and dextran.

24. A method according to claim 18 wherein the analyte is one of urea, insulin, lactate, ions, therapeutic drugs or immunosuppressant drugs, and the receptor is one of lectin, concanavalin A, Fab fragments, hormone receptors, drug receptors, aptamers or molecularly-imprinted polymers.

25. A method according to claim 13 further including,

detecting an optical property of an optical cavity detection region in a third container preloaded with a known reference fluid, the preloaded third container being sealed so the fluid external to the third container cannot enter the interior of the third container, the third container being a reference container.

26. A method according to claim 13 further comprising:

detecting one or more optical properties of one or more additional optical cavity detection regions in the system, the one or more additional optical cavity detection regions located in corresponding one or more additional containers, each container having a reservoir for one or more modifiers of one or more optical properties, the movement of said one or more modifiers being responsive to changes in concentration of a compound in the fluid; and

determining the concentration of a compound using detected optical properties.

27. A method according to claim 26 wherein the said compound is an interfering compound that alters the responsiveness of the one or more containers to one or more analytes.

28. A method according to claim 27 wherein one of the one or more analytes is glucose, a modifier in the first container comprises dextran, a receptor in the first container comprises a protein having at least one binding site for the glucose and dextran, and the interfering compound is maltose.

29. A method according to claim 27 wherein one of the one or more analytes is glucose, a modifier in the first container comprises a protein having at least one binding site for the glucose and dextran, a receptor in the first container comprises dextran, and the interfering compound is maltose.

30. A method according to claim 13 further including implanting or partially implanting the first and second containers, in or underneath the skin in contact with interstitial fluid, and wherein the detecting means is not implanted.

31. A method according to claim 13 wherein the optical property of at least one of the optical cavity detection regions is the intensity or polarization of light transmitted through or reflected from the optical cavity detection region.

32. A method according to claim 13 wherein the optical property of at least one of the optical cavity detection regions is the intensity of light transmitted through or reflected from the optical cavity detection region over a range of wavelengths.

34. A method according to claim 13 further comprising the step of generating a radiofrequency from the detected optical property of the first region and the second region of the system and monitoring said radiofrequency signals generated by the system, using a radiofrequency receiver.