Dry insertion and one-point in vivo calibration of an optical analyte sensor

• US 9,757,057 B2
• Filed: 11/06/2013
• Issued: 09/12/2017
• Est. Priority Date: 11/07/2012
• Status: Active Grant

• Current Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Inventors: Gallant, Stuart L., Markle, William H., Goharlaee, Manouchehr
• Primary Examiner(s): WINAKUR, ERIC FRANK
• Application Number:
  US14/073,661
• Publication Number:
  US 20140128694A1
• Time in Patent Office: 1,406 Days
• CPC Class Codes: A61B 2562/043 in a linear array
• CPC Class Codes: A61B 2562/223 Optical cables therefor
• 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 5/1455 using optical sensors, e.g. spectral photometrical oximeters
• CPC Class Codes: A61B 5/1459 invasive, e.g. introduced into the body by a catheter A61B5/1464 takes precedence
• CPC Class Codes: A61B 5/14735 comprising an immobilised reagent
• CPC Class Codes: A61B 5/1495 Calibrating or testing of in-vivo probes

Abstract

Disclosed are embodiments that relate to the deployment of a glucose sensor comprising an optical fiber into a physiological fluid, wherein the optical fiber has disposed along a distal region thereof a chemical indicator system comprising a fluorophore and a glucose binding moiety immobilized within a hydrogel, wherein the components of the chemical indicator system are in a dry state before deployment. Also disclosed is a one-point in vivo calibration of the chemical indicator system based on an independently measured glucose concentration.

Claims

1. A method for monitoring glucose concentration in a physiological fluid in a patient, comprising:

providing a sensor comprising an equilibrium fluorescence chemical indicator system immobilized in a hydrogel disposed along a distal region of an optical fiber, wherein the hydrogel comprising the immobilized chemical indicator system is in a dry state;

deploying the distal region of the optical fiber in the physiological fluid, wherein the hydrogel with immobilized chemical indicator system disposed along the distal region of the optical fiber is deployed in a dry state;

allowing the hydrogel with immobilized chemical indicator system to hydrate in vivo in the physiological fluid;

after in vivo hydration, performing an in vivo calibration of the fluorescent response of the immobilized chemical indicator system against an independently measured glucose concentration in the physiological fluid; and

monitoring the glucose concentration in the physiological fluid after calibration.

2. The method of claim 1, wherein the chemical indicator system comprises a fluorophore having acid and base forms.

3. The method of claim 2, wherein the in vivo calibration is corrected based on an estimated pH of the physiological fluid.

4. The method of claim 3, wherein the pH of the physiological fluid is estimated based on a ratio of fluorescent emissions from the acid and base forms of the fluorophore.

5. The method of claim 1, further comprising measuring the temperature of the physiological fluid.

6. The method of claim 5, wherein the in vivo calibration is corrected based on the measured temperature of the physiological fluid.

7. The method of claim 1, wherein the hydrogel is hydrated for at least about 10 minutes.

8. The method of claim 1, wherein the hydrogel is hydrated for approximately 1-2 hours.

9. The method of claim 1, further comprising performing a factory calibration of the chemical indicator system against a known glucose solution and storing the factory calibration data.

10. The method of claim 1, wherein the in vivo calibration comprises applying the equation:

G=M*Ln(Glu)+B

wherein G is a fluorescence intensity of the chemical indicator system, Glu is the glucose concentration in the physiological fluid, M is the slope of the straight line approximation at calibration, and B is the intercept of the straight line approximation at calibration;

wherein G is adjusted by a calibration factor to take into account pH using the equation

11. The method of claim 1, wherein the in vivo calibration comprises applying the equation:

G=M*Ln(Glu)+B

wherein G is a fluorescence intensity of the chemical indicator system, Glu is the glucose concentration in the physiological fluid, M is the slope of the straight line approximation at calibration, and B is the intercept of the straight line approximation at calibration.

12. The method of claim 1, wherein the in vivo calibration is a one-point calibration.

13. A method for monitoring glucose concentration in a physiological fluid in a patient, comprising:

providing a sensor comprising an equilibrium fluorescence chemical indicator system immobilized in a hydrogel disposed along a distal region of an optical fiber, wherein the hydrogel comprising the immobilized chemical indicator system is in a dry state;

deploying the distal region of the optical fiber in the physiological fluid without performing ex vivo calibration, wherein the hydrogel with immobilized chemical indicator system disposed along the distal region of the optical fiber is deployed in a dry state;

allowing the hydrogel with immobilized chemical indicator system to hydrate in vivo in the physiological fluid for at least 10 minutes;

after in vivo hydration, performing a one-point in vivo calibration of the fluorescent response of the immobilized chemical indicator system against an independently measured glucose concentration in the physiological fluid; and

monitoring the glucose concentration in the physiological fluid after calibration.

14. The method of claim 13, wherein the one-point in vivo calibration comprises applying the equation:

G=M*Ln(Glu)+B

wherein G is a fluorescence intensity of the chemical indicator system, Glu is the glucose concentration in the physiological fluid, M is the slope of the straight line approximation at calibration, and B is the intercept of the straight line approximation at calibration.

15. The method of claim 14, wherein G is adjusted by a calibration factor to take into account pH using the equation

16. The method of claim 13, wherein the hydrogel is hydrated for approximately 1-2 hours.