EQUILIBRIUM NON-CONSUMING FLUORESCENCE SENSOR FOR REAL TIME INTRAVASCULAR GLUCOSE MEASUREMENT

• US 20150080685A1
• Filed: 04/17/2014
• Published: 03/19/2015
• Est. Priority Date: 05/10/2007
• Status: Active Grant

• Current Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Inventors: Markle, David R., Markle, William
• Granted Patent: US 9,693,720 B2
• Time in Patent Office: Days
• US Class Current: 600/316
• 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: A61B 5/14735 comprising an immobilised reagent

Abstract

Embodiments of the present invention relates to analyte sensors. In particular, the preferred embodiments of the present invention relate to non-consuming intravascular glucose sensors based on fluorescence chemistry.

Claims

1-21. -21. (canceled)

22. A sensor for determining glucose concentration comprising:

an optical fiber comprising a fluorescence chemical indicator, the chemical indicator system comprising a fluorophore that generates a fluorescence emission signal when excited by light and a glucose binding moiety to modulate the fluorescence emission signal, wherein the fluorophore is selected from the group consisting of a pyranine derivative, HPTS, an HPTS derivative, SNARF-1, SNARFL-1, a 6-methylquinolinium moiety, and TSPP, and wherein the extent of modulation of the fluorescence emission signal by the glucose binding moiety is related to the amount of glucose bound to the glucose binding moiety;

a light source; and

a detector.

23. The sensor of claim 22, wherein the fluorescence emission signal comprises a fluorescence intensity.

24. The sensor of claim 22, wherein the fluorescence emission signal comprises a fluorescence lifetime.

25. The sensor of claim 22, wherein the light source is a laser.

26. The sensor of claim 22, wherein the light source is a light emitting diode.

27. The sensor of claim 22, wherein the sensor further comprises a hydrogel that substantially immobilizes the glucose binding moiety and the fluorophore and is permeable to glucose.

28. The sensor of claim 22, wherein the sensor further comprises a membrane wherein the glucose binding moiety and the fluorophore are substantially retained within a volume at least partially enclosed by the membrane.

29. A method for determining the glucose concentration comprising:

inserting the sensor of claim 22 into a patient;

exciting the fluorophore with light;

detecting a fluorescence emission signal from the fluorophore; and

determining the concentration of glucose.

30. The method of claim 29, wherein the light is a pulse of light.

31. The method of claim 30, further comprising measuring the decay of the fluorescence emission signal over time;

and calculating a fluorescence lifetime.

32. The method of claim 29, wherein the light is frequency modulated.

33. The method of claim 32, further comprising measuring the phase shift between the fluorescence emission signal and the light.

34. The method of claim 33, further comprising calculating a fluorescence lifetime.

35. The method of claim 32, further comprising measuring a modulation ratio;

and calculating a fluorescence lifetime.

36. The method of claim 29, further comprising measuring the fluorescence intensity of the fluorescence emission signal.

37. The sensor of claim 22, wherein the glucose binding moiety comprises an aromatic boronic acid.

38. The sensor of claim 37, wherein the aromatic boronic acid is coupled to a viologen.

39. The sensor of claim 22, wherein the fluorophore and the glucose binding moiety are not covalently bound to one another.

40. The sensor of claim 22, wherein the fluorophore comprises an acid form that absorbs light at a first excitation wavelength and a base form that absorbs light at a second excitation wavelength, such that a pH-dependent shift in absorption enables dual-excitation ratiometric determination of pH and glucose.

41. The sensor of claim 22, wherein the sensor further comprises a hydrogel that covalently bonds the glucose binding moiety and the fluorophore and is permeable to glucose.

42. The sensor of claim 22, wherein the HPTS derivative is selected from the group consisting of acetoxy-HPTS-MA, HPTS-CO₂, HPTS-PEG, HPTS-triCysMA, and HPTS-LysMA.

43. The sensor of claim 22, wherein the fluorophore is HPTS-triCysMA.