OPTICAL DETERMINATION OF PH AND GLUCOSE

• US 20080188722A1
• Filed: 02/06/2007
• Published: 08/07/2008
• Est. Priority Date: 02/06/2007
• Status: Active Grant

• Current Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Original Assignee: GluMetrics, Inc.
• Inventors: Romey, Matthew A., Markle, David R., Wessling, Ritchie A., Suri, Jeff T.
• Granted Patent: US 7,751,863 B2
• Time in Patent Office: Days
• US Class Current: 600/316
• CPC Class Codes: A61B 5/1451 for interstitial fluid
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14539 for measuring pH
• CPC Class Codes: A61B 5/1459 invasive, e.g. introduced into the body by a catheter A61B5/1464 takes precedence
• CPC Class Codes: G01N 2400/00 Assays, e.g. immunoassays or enzyme assays, involving carbohydrates
• CPC Class Codes: G01N 33/66 involving blood sugars, e.g. galactose
• CPC Class Codes: G01N 33/84 involving inorganic compounds or pH

Abstract

Embodiments of the present invention are directed to an optical sensor capable of measuring two analytes simultaneously with a single indicator system. In preferred embodiments, the sensor comprises a fluorescent dye having acid and base forms that facilitate ratiometric pH sensing, wherein the dye is further associated with a glucose binding moiety and configured to generate a signal that varies in intensity with the concentration of glucose.

Claims

1. A device for determining two or more analyte concentrations, comprising:

an optical sensor, comprising an indicator system, comprising;

a fluorophore that exists in at least first and second different forms depending on a concentration of a first analyte, wherein the different forms can be distinguished based on their respective first and second emissions; and

a binding moiety that binds a second analyte, wherein the binding moiety is operably coupled to said fluorophore, and wherein binding of said second analyte by said binding moiety causes an optical change in the apparent concentration of said fluorophore related to a concentration of said second analyte;

wherein a ratio of said first and second emissions is independent of the concentration of said second analyte;

a light source; and

a detector.

2. The device of claim 1, wherein said fluorophore is a fluorescent dye.

3. The device of claim 2, wherein said fluorescent dye is a discrete compound.

4. The device of claim 3, wherein said fluorescent dye is selected from HPTS, SNARF-1, SNAFL-1, TSPP and derivatives thereof.

5. The device of claim 2, wherein said fluorescent dye is selected from the group consisting of:

HPTS-CysMA, HPTS-LysMA, and polymers comprised thereof.

6. The device of claim 1, wherein said binding moiety comprises a quencher and one or more binding sites for reversibly binding the second analyte.

7. The device of claim 6, wherein said quencher is a viologen.

8. The device of claim 6, wherein said one or more binding sites comprises a benzylboronic acid group.

9. The device of claim 1, wherein said binding moiety is a viologen-boronic acid adduct.

10. The device of claim 1, wherein said binding moiety is 3,3′

-oBBV or derivatives thereof.

11. The device of claim 1, wherein said optical sensor comprises physiologically compatible materials and is sized for intravascular deployment.

12. The device of claim 1, wherein said first analyte is H⁺ (pH).

13. The device of claim 1, wherein said second analyte is a polyhydroxyl compound.

14. The device of claim 13, wherein said polyhydroxyl compound is glucose.

15. The device of claim 1, further comprising a controller.

16. The device of claim 1, wherein said indicator system further comprises a means for immobilizing said fluorophore and said binding moiety.

17. The device of claim 16, wherein said means for immobilizing comprises a hydrogel.

18. The device of claim 1, wherein the fluorophore and binding moiety of said indicator system comprise a single molecule.

20. A method for determining blood pH and glucose concentration with one fluorescent dye, comprising:

providing the device of claim 1;

inserting said sensor into a blood vessel;

irradiating said sensor at the first excitation wavelength;

detecting a first fluorescence emission of said sensor at an emission wavelength;

irradiating said sensor at a second excitation wavelength;

measuring a second fluorescence emission of said sensor at the emission wavelength;

ratiometrically determining the blood pH; and

determining the blood glucose concentration corrected for pH.

21. The method of claim 20, further comprising

computing a ratio of the intensities of said first and second fluorescence emissions;

determining the pH of said sample by comparing said ratio with a pH standard curve;

selecting a standard glucose response curve, wherein the standard glucose response curve is corresponding to the determined pH; and

determining the glucose concentration by comparing said first or second fluorescent emission to said standard glucose response curve.

19. A device for determining blood pH and glucose concentration, comprising:

a sensor comprising an optical fiber sized for deployment intravascularly, said sensor further comprising;

a water-insoluble polymer matrix, wherein said polymer matrix is permeable to glucose;

a fluorescent dye associated with said polymer matrix, wherein the fluorescent dye exhibits at least first and second different forms depending on pH, wherein the different forms can be distinguished based on their respective first and second emissions;

a quencher comprising an aromatic boronic acid substituted viologen, adapted to reversibly bind an amount of glucose related to the blood glucose concentration, wherein said quencher is associated with said polymer matrix and operably coupled to the fluorescent dye, and wherein the quencher is configured to modulate the light emitted by said fluorescent dye related to the amount of bound polyhydroxyl compound;

at least one excitation light source; and

an emission light detector.