Method and apparatus for glucose monitoring

• US 20070105176A1
• Filed: 09/28/2006
• Published: 05/10/2007
• Est. Priority Date: 09/28/2005
• Status: Active Grant

• Current Assignee: Penn State Research Foundation (Pennsylvania State University), Texas A&M University System
• Original Assignee: Penn State Research Foundation (Pennsylvania State University)
• Inventors: Pishko, Michael, Rounds, Rebecca, Beier, Hope, Yadavalli, Vamsi, Ibey, Bennett, Cote, Gerard
• Granted Patent: US 7,704,704 B2
• Time in Patent Office: Days
• US Class Current: 435/14
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: C12Q 1/54 involving glucose or galactose
• CPC Class Codes: G01N 33/53 Immunoassay; Biospecific binding assay; Materials therefor
• CPC Class Codes: G01N 33/54366 Apparatus specially adapted for solid-phase testing

Abstract

This disclosure relates to systems, devices, and methods of sensing an analyte. An implantable sensor may be contacted with a test sample under conditions that permit a binding protein and a ligand of the sensor to interact in an analyte-dependent manner to produce an analyte-dependent signal, and (b) detecting the analyte-dependent signal with a detector. A binding protein may reversibly bind an analyte and/or a ligand. A binding protein may have a higher binding affinity for an analyte than for a ligand. A binding protein and a ligand may each include a fluorophore, the absorption and/or emission properties of which may change in an analyte-dependent manner. A binding protein and/or a ligand may be bound to an active or inactive substrate. Some embodiments of systems, devices, and methods may be practiced in vitro, in situ, and/or in vivo. Systems and/or devices of the disclosure may be configured to be wearable.

Claims

1. A device for sensing an analyte, said device comprising:

a ligand selected from the group consisting of dextran, a functionalized polymer, and a functionalized nano-particle;

a first fluorophore selected from the group consisting of a fluoresceine, a rhodamine, a cyanine, an alexafluore, and combinations thereof;

a sugar-binding lectin selected from the group consisting of Concanavalin A, glucose binding protein, glucose oxidase, glucose apo-oxidase, and combinations thereof; and

a second fluorophore selected from the group consisting of a fluoresceine, a rhodamine, a cyanine, an alexafluore, and combinations thereof,

wherein the first fluorophore is linked to the ligand and the second fluorophore is linked to the sugar-binding lectin and wherein the first fluorophore is a reference fluorophore and the second fluorophore is quenchable fluorophore and the second fluorophore is a reference fluorophore.

2. A device according to claim 1 further comprising a hydrogel.

3. A device according to claim 2, wherein the ligand is present uniformly throughout the hydrogel.

4. A device according to claim 2, wherein the sugar-binding lectin is present uniformly throughout the hydrogel.

5. A device according to claim 2, wherein the hydrogel is porous.

6. A device according to claim 2 further comprising a membrane enclosing at least a portion of the hydrogel.

7. A system for sensing glucose, said system comprising:

(a) an implantable glucose-sensing device comprising;

a hydrogel;

a ligand selected from the group consisting of dextran, a functionalized polymer, and a functionalized nano-particle;

a first fluorophore selected from the group consisting of a fluoresceine, a rhodamine, a cyanine, an alexafluore, and combinations thereof;

a sugar-binding lectin selected from the group consisting of Concanavalin A, glucose binding protein, glucose oxidase, glucose apo-oxidase, and combinations thereof; and

a second fluorophore selected from the group consisting of a fluoresceine, a rhodamine, a cyanine, an alexafluore, and combinations thereof,

wherein the ligand and the sugar-binding lectin are present throughout the matrix of the hydrogel,

wherein the first fluorophore is linked to the ligand and the second fluorophore is linked to the sugar-binding lectin,

wherein the first fluorophore is a fluorescence resonance energy transfer donor or fluorescence resonance energy transfer acceptor and the second fluorophore is a fluorescence resonance energy transfer donor or fluorescence resonance energy transfer acceptor provided that at least one of the fluorophores is a fluorescence resonance energy transfer donor and at least one of the fluorophores is a fluorescence resonance energy transfer acceptor; and

(b) a light source configured and arranged to illuminate the implantable glucose sensing device with light of a wavelength sufficient to excite the fluorescence resonance energy transfer donor;

(c) a detector (a) in optical communication with the implantable glucose sensing device and (b) configured and arranged to detect at least at least one wavelength of light from the implantable glucose sensing device and produce a detected light signal;

(d) a processor in communication with the detector and configured and arranged to receive and process at least one detected light signal to produce a glucose metric;

(e) a display operably linked to the processor and configured and arranged to receive and display the glucose metric; and

(f) a power source operably linked to at least the light source, the detector, the processor, and the display.

8. A system according to claim 7, wherein the glucose metric is selected from the group consisting of a glucose concentration, a change in glucose concentration, a rate of change of glucose concentration, an amount of glucose, a change in the amount of glucose, a rate of change of the amount of glucose, and combinations thereof.

9. A system according to claim 7 further comprising an alarm in communication with the processor.

10. A system according to claim 9, wherein the alarm is configured and arranged to alert when the glucose metric is below a preset threshold.

11. A system according to claim 9, wherein the alarm is configured and arranged to alert when the glucose metric is above a preset threshold.

12. A system according to claim 9, wherein the alarm is configured and arranged to alert when the glucose metric is within a preset range.

13. A system according to claim 7 further comprising a housing, wherein the light source, the detector, the processor, and the power source are at least partially enclosed within the housing.

14. A system according to claim 13, wherein the housing is configured and arranged to be worn by a subject.

15. A system according to claim 7, wherein the power source is a battery.

16. A system according to claim 7, wherein the light source is selected from the group consisting of a laser diode, a light-emitting diode, a light bulb, luciferase, and combinations thereof.

17. A system according to claim 7, wherein the detector is selected from the group consisting of a photodiode with an interference filter, a prism with a charge-coupled device array detection element, a grating with a charge-coupled device array detection element, a photomultiplier tube, and combinations thereof.

18. A system according to claim 7, wherein the ligand is immobilized on a substrate selected from the group consisting of an active substrate and an inactive substrate.

19. A system according to claim 7, wherein the sugar-binding lectin is immobilized on a substrate selected from the group consisting of an active substrate and an inactive substrate.

20. A method of sensing glucose, said method comprising:

contacting an implantable glucose sensor with a test sample under conditions that permit the binding protein and ligand of the sensor to interact in a glucose dependent manner to produce a glucose-dependent signal;

detecting the glucose-dependent signal with a detector; and

processing a glucose-dependent signal to produce a glucose metric, wherein

21. A device for sensing an analyte, said device comprising:

a ligand selected from the group consisting of dextran, a functionalized polymer, and a functionalized nano-particle;

a first fluorophore selected from the group consisting of a fluoresceine, a rhodamine, a cyanine, an alexafluore, and combinations thereof;

a sugar-binding lectin selected from the group consisting of Concanavalin A, glucose binding protein, glucose oxidase, glucose apo-oxidase, and combinations thereof; and

a second fluorophore selected from the group consisting of a fluoresceine, a rhodamine, a cyanine, an alexafluore, and combinations thereof,

wherein the first fluorophore is linked to the ligand and the second fluorophore is linked to the sugar-binding lectin and wherein the first fluorophore is a fluorescence resonance energy transfer donor or fluorescence resonance energy transfer acceptor and the second fluorophore is a fluorescence resonance energy transfer donor or fluorescence resonance energy transfer acceptor provided that at least one of the fluorophores is a fluorescence resonance energy transfer donor and at least one of the fluorophores is a fluorescence resonance energy transfer acceptor.