Optical detector of organic analyte

• US 20050096516A1
• Filed: 10/30/2003
• Published: 05/05/2005
• Est. Priority Date: 10/30/2003
• Status: Abandoned Application

• Current Assignee: Medtronic Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Incorporated (Medtronic Plc)
• Inventors: Lichlyter, Darcy J., Soykan, Orhan, Grant, Sheila A.
• Application Number:
  US10/698,050
• Publication Number:
  US 20050096516A1
• Time in Patent Office: Days
• US Class Current: 600/317
• CPC Class Codes: A61B 5/0002 Remote monitoring of patients using telemetry, e.g. transmission of vital signals via a communication network A61B5/07 takes precedence; transmission systems for measured values G08C; transmission H04B; transmission of digital information H04L; wireless communication networks H04W
• CPC Class Codes: A61B 5/0031 Implanted circuitry
• CPC Class Codes: A61B 5/0071 by measuring fluorescence emission
• CPC Class Codes: A61B 5/0084 for introduction into the body, e.g. by catheters A61B5/1459 takes precedence
• CPC Class Codes: A61B 5/14507 specially adapted for measuring characteristics of body fluids other than blood devices for taking samples of body liquids A61B10/0045
• CPC Class Codes: A61M 5/14276 specially adapted for implantation
• CPC Class Codes: G01N 2021/6441 with two or more labels
• CPC Class Codes: G01N 21/6428 Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 21/6452 Individual samples arranged in a regular 2D-array, e.g. multiwell plates
• CPC Class Codes: G01N 21/77 by observing the effect on a chemical indicator
• CPC Class Codes: G01N 33/542 with steric inhibition or signal modification, e.g. fluorescent quenching

Abstract

The invention is directed to techniques for optically detecting changes in concentration of analytes in the body of a patient via fluorescent resonant energy transfer (FRET). An analyte detector implantable in the body of the patient includes a plurality of fluorophore-tagged sensing elements that bind to a specific analyte. A light emitter emits energy at a wavelength that is within the absorption spectrum of a donor fluorescent dye, and a light detector detects the energy fluoresced by donor and acceptor fluorescent dyes in the analyte detector. The relative intensity of energy fluoresced by the dyes is a function of the concentration of the analyte. A processor monitors the change in concentration of the analyte over time and may take action, such as directing the therapy device to administer therapy, when the change in concentration surpasses a predetermined threshold.

Claims

1. A method comprising:

emitting energy at a first wavelength toward an analyte detector implanted in a body of a patient, the analyte detector including a binding site for an analyte, and the analyte detector including at least two fluorescent dyes;

detecting energy emitted by a first one of the dyes at a second wavelength based on fluorescent resonant energy transfer from a second one of the dyes in response to the emitted energy at the first wavelength; and

detecting a change in a concentration of the analyte as a function of the detected energy.

2. The method of claim 1, further comprising comparing the detected change to a threshold.

3. The method of claim 1, further comprising taking action when the detected change surpasses a threshold, wherein taking action comprises at least one of generating an alert and generating a communication to a therapy device.

4. The method of claim 1, further comprising detecting energy at a third wavelength emitted by the second one of the dyes in response to the emitted energy at the first wavelength.

5. The method of claim 4, further comprising determining a ratio between a detected intensity of the energy at the second wavelength and a detected intensity of energy at the third wavelength.

6. The method of claim 4, wherein detecting the change in concentration of the analyte comprises detecting a change in an intensity of the energy at the second wavelength relative to a detected intensity of energy at the third wavelength.

7. The method of claim 4, wherein the first one of the dyes absorbs energy received from the second one of the dyes at the third wavelength via fluorescent resonant energy transfer and emits energy at the second wavelength in response to receiving the energy at the third wavelength.

8. The method of claim 1, wherein the energy is visible light.

9. The method of claim 1, wherein the analyte comprises cardiac troponin-T antigen.

10. The method of claim 1, wherein the analyte comprises at least one of a D-dimer that accompanies an ischemic stroke, a virus, insulin, an administered medication, an illegal drug, a food pathogen, a biological toxin, and a biological warfare agent.

11. A system comprising:

a light emitter to emit energy at a first wavelength;

an analyte detector implanted in a body of a patient, the analyte detector including a binding site for an analyte and at least two fluorescent dyes;

a light detector to detect energy at a second wavelength emitted by a first one of the dyes based on fluorescent resonant energy transfer from a second one of the dyes in response to the emitted energy at the first wavelength; and

a processor to detect a change in a concentration of the analyte as a function of the energy detected by the light detector.

12. The system of claim 11, wherein at least one of the fluorescent dyes comprises fluorescein 5-isothiocyanate, tetramethylrhodamine 5-isothiocyanate, tetramethylrhodamine 6-isothiocyanate and aminomethylcoumarin acetate.

13. The system of claim 11, further comprising a therapy device to deliver therapy to the patient based on the detection of the change in a concentration.

14. The system of claim 13, wherein the therapy device comprises at least one of an implanted drug delivery device, a pacemaker and an electrical stimulator that stimulates at least one of an organ, a muscle and a nerve.

15. The system of claim 13, further comprising a communication module to generate a wireless communication from the processor to the therapy device.

16. The system of claim 13, wherein the processor is configured to compare the detected change to a threshold.

17. The system of claim 11, further comprising an alert module to notify the patient based on the detection of the change in a concentration.

18. The system of claim 11, wherein the a light emitter and the light detector are implanted in the body of the patient.

19. The system of claim 11, wherein the light detector is configured to detect energy at a third wavelength emitted by the second one of the dyes in response to the emitted energy at the first wavelength.

20. The system of claim 19, wherein the processor is configured to determine a ratio between a detected intensity of the energy at the second wavelength and a detected intensity of energy at the third wavelength.

21. The system of claim 19, wherein the processor is configured to detect the change in concentration of the analyte by detecting a change in an intensity of the energy at the second wavelength relative to a detected intensity of energy at the third wavelength.

22. A device comprising:

a substrate;

two fluorescent dyes; and

a plurality of sensing elements anchored to the substrate, each sensing element including a binding site for an analyte, and each sensing element configured to bring the dyes into proximity to allow fluorescent resonant energy transfer when the analyte binds to the binding site.

23. The device of claim 22, wherein at least one of the fluorescent dyes comprises fluorescein 5-isothiocyanate, tetramethylrhodamine 5-isothiocyanate, tetramethylrhodamine 6-isothiocyanate and aminomethylcoumarin acetate.

24. The device of claim 22, further comprising an anchoring agent to anchor at least one sensing element to the substrate.

25. The device of claim 24, wherein the anchoring agent comprises Protein A.

26. The device of claim 24, wherein the substrate comprises at least one of silicone and glass.

27. The device of claim 22, wherein at least one sensing element comprises an antibody molecule.

28. The device of claim 27, wherein the antibody molecule comprises a Troponin-T antibody molecule.

29. The device of claim 22, wherein the substrate comprises a permeable material to anchor the sensing element to the substrate.

30. The device of claim 29, wherein the permeable material comprises at least one of a hydrogel and a matrix of polytetrafluoroethylene.

31. The device of claim 22, wherein the substrate includes a surface having ridges and grooves.

32. The device of claim 22, wherein the device is implantable in a patient.

33. A computer-readable medium comprising instructions for causing a programmable processor to:

control a light emitter to emit energy at a first wavelength toward an analyte detector implanted in a body of a patient, the analyte detector including a binding site for an analyte, and the analyte detector including at least two fluorescent dyes;

receive a signal from a detector as a function of energy emitted by a first one of the dyes at a second wavelength based on fluorescent resonant energy transfer from a second one of the dyes in response to the emitted energy at the first wavelength; and

detecting a change in a concentration of the analyte as a function of the received signal.

34. The medium of claim 33, the instructions further causing the processor to compare the detected change to a threshold.

35. The medium of claim 33, the instructions further causing the processor to take action when the detected change surpasses a threshold, wherein taking action comprises at least one of notifying a patient and generating a communication to a therapy device.

36. The medium of claim 33, the instructions further causing the processor to receive a signal from the detector as a function of energy at a third wavelength emitted by the second one of the dyes in response to the emitted energy at the first wavelength.

37. The medium of claim 36, the instructions further causing the processor to determine a ratio between a detected intensity of the energy at the second wavelength and a detected intensity of energy at the third wavelength.