Optical determination of ph and glucose

• US 7,751,863 B2
• Filed: 02/06/2007
• Issued: 07/06/2010
• Est. Priority Date: 02/06/2007
• Status: Expired due to Fees

• Current Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Original Assignee: GluMetrics, Inc.
• Inventors: Romey, Matthew A., Suri, Jeff T., Markle, David R., Wessling, Ritchie A.
• Primary Examiner(s): Winakur; Eric F
• Assistant Examiner(s): Berhanu; Etsub D
• Application Number:
  US11/671,880
• Publication Number:
  US 20080188722A1
• Time in Patent Office: 1,246 Days
• Field of Search: 600/310, 600/316, 600/317, 600/322, 436/164, 436/166, 422/82.08
• US Class Current: 600/317
• 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 method for determining blood pH and glucose concentration with one fluorescent dye, comprising:

providing a device comprising;

an optical sensor, comprising an indicator system, comprising;

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

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

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

at least one light source;

at least one detector configured to detect both said first and second emissions; and

a controller configured to monitor signals from said at least one detector and determine said ratio;

inserting said sensor into a blood vessel;

irradiating said sensor using said at least one light source;

detecting the first emission corresponding to the first form of the fluorophore;

detecting the second emission corresponding to the second form of the fluorophore;

ratiometrically determining the blood pH using said controller; and

determining the blood glucose concentration corrected for pH using said controller.

2. The method of claim 1, further comprising:

using said controller to;

compute a ratio of the intensities of the first and second emissions;

determine the blood pH by comparing said ratio with a pH standard curve;

select a standard glucose response curve corresponding to the determined pH; and

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

3. The method of claim 1, wherein said at least one light source comprises first and second light sources that generate respective first and second different excitation wavelengths.

4. The method of claim 1, wherein the first and second different forms of the fluorophore absorb light at a single excitation wavelength and generate the first and second emissions at different wavelengths.

5. The method of claim 3, wherein the first and second different forms of the fluorophore absorb light at respective first and second different excitation wavelengths and generate the first and second emissions at different wavelengths.

6. The method of claim 1, wherein said fluorophore is a fluorescent dye.

7. The method of claim 6, wherein said fluorescent dye is a discrete compound.

8. The method of claim 7, wherein said fluorescent dye is selected from the group consisting of:

HPTS, SNARF-1, TSPP and derivatives thereof.

9. The method of claim 6, wherein said fluorescent dye is selected from the group consisting of:

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

10. The method of claim 1, wherein said binding moiety comprises a quencher and one or more binding sites for reversibly binding glucose.

11. The method of claim 10, wherein said quencher is a viologen.

12. The method of claim 10, wherein said one or more binding sites comprises a benzylboronic acid group.

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

14. The method of claim 1, wherein said binding moiety is 3,3′

-oBBV or derivatives thereof.

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

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

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

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