OPTICAL DETERMINATION OF PH AND GLUCOSE

• US 20100274110A1
• Filed: 07/02/2010
• Published: 10/28/2010
• 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 8,498,682 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 the determination of two analyte concentrations, comprising:

an optical sensor comprising an indicator system, said indicator system comprising;

a fluorophore that exists in at least a first and a second different form,

wherein the form of the fluorophore depends on a concentration of a first analyte, and

wherein the different forms are distinguishable based on their respective emissions;

a binding moiety that is operably coupled to said fluorophore and capable of binding a second analyte,

wherein a ratio of the respective emissions of the fluorophore is independent of the concentration of said second analyte;

wherein binding of said second analyte to said binding moiety induces

a change in the emission intensity of said fluorophore;

at least one light source configured to excite said fluorophore;

at least one detector configured to simultaneously detect both said respective emission wavelengths and the emission intensity of said fluorophore; and

a controller configured to monitor signals from said at least one detector,

wherein said controller comprises an algorithm for determining the concentration of said first analyte based on the ratio of the respective emissions and the concentration of said second analyte based on the emission intensity of said fluorophore.

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, wherein said indicator system further comprises a means for immobilizing said fluorophore and said binding moiety.

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

18. The device of claim 1, wherein said algorithm further corrects the concentration of said second analyte for the concentration of said first analyte.

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

19. A device configured to monitor real-time blood glucose concentration, corrected for pH, comprising:

a sensor sized and configured for intravascular deployment comprising;

an optical fiber;

a polymer matrix that is water-insoluble and permeable to glucose;

a fluorescent dye associated with said polymer matrix,

wherein said fluorescent dye is selected from the group consisting of;

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

wherein the fluorescent dye exhibits at least a first and a second pH-dependent and distinguishable emission wavelength;

a quencher comprising an aromatic boronic acid substituted viologen,

wherein said quencher is (i) adapted to reversibly bind glucose, (ii) associated with said polymer matrix and operably coupled to the fluorescent dye, and (iii) configured to quench the emission intensity of said fluorescent dye in relation to the amount of glucose bound;

at least one excitation light source;

at least one emission light detector configured to detect said distinguishable emissions said fluorescent dye; and

a controller configured to monitor signals from said at least one emission light detector, wherein said controller comprises an algorithm for;

comparing the ratio of the first and second distinguishable emissions with a pH calibration curve to determine the pH of the blood;

correlating the emission quenching with a standard curve at the determined pH to determine the blood glucose concentration corrected for pH.