Optical detector for use in therapy

• US 8,940,522 B2
• Filed: 08/22/2011
• Issued: 01/27/2015
• Est. Priority Date: 04/25/2003
• Status: Active Grant

• Current Assignee: Medtronic Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Incorporated (Medtronic Plc)
• Inventors: Soykan, Orhan, Donovan, Maura G., Thompson, Amy E.
• Primary Examiner(s): LAM, ANN Y
• Application Number:
  US13/214,860
• Publication Number:
  US 20120046642A1
• Time in Patent Office: 1,254 Days
• Field of Search: None
• US Class Current: 435/287.1
• CPC Class Codes: A61B 5/0071 by measuring fluorescence emission
• CPC Class Codes: A61B 5/0075 by spectroscopy, i.e. measuring spectra, e.g. Raman spectroscopy, infrared absorption spectroscopy A61B5/0071 takes precedence
• CPC Class Codes: A61B 5/0084 for introduction into the body, e.g. by catheters A61B5/1459 takes precedence
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/4839 combined with drug delivery
• CPC Class Codes: A61B 5/7203 for noise prevention, reduction or removal
• CPC Class Codes: C12Q 1/37 involving peptidase or proteinase
• CPC Class Codes: C12Q 1/56 involving blood clotting factors, e.g. involving thrombin, thromboplastin, fibrinogen
• CPC Class Codes: G01N 2021/6415 with two excitations, e.g. strong pump/probe flash
• CPC Class Codes: G01N 2021/6441 with two or more labels
• CPC Class Codes: G01N 2021/6484 Optical fibres
• CPC Class Codes: G01N 2021/8528 Immerged light conductor
• 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 21/8507 Probe photometers, i.e. with optical measuring part dipped into fluid sample
• CPC Class Codes: G01N 33/86 involving blood coagulating time or factors, or their receptors

Abstract

Activation of an enzyme in a bodily fluid is detected based on the amount of cleavage of a substrate for the enzyme. The substrate is tagged with two fluorescent dyes—a donor and an acceptor. The tagged substrate is presented to the bodily fluid. A device emits energy at a first wavelength into the bodily fluid, and detects energy at second and third wavelengths emitted by the dyes in response to the energy at the first wavelength. Prior to enzymatic cleavage of the substrate, the acceptor emits energy at the third wavelength in response to energy at the second wavelength received through fluorescent resonant energy transfer (FRET) from the donor. After enzymatic cleavage of the substrate, the donor emits energy at the second wavelength. The device can determine the concentration of activated enzyme within the bodily fluid based on the relative intensities of energy at the second and third wavelengths.

Claims

1. A method of delivering a therapy using an implantable medical device, comprising:

presenting a tagged substrate into a bodily fluid, wherein the bodily fluid is blood, wherein the bodily fluid contains an enzyme and a protein substrate, and wherein presenting the tagged substrate to the bodily fluid comprises controlling a substrate pump to present the tagged substrate to the blood via a catheter with a distal end located in a blood vessel of a patient, and further wherein the tagged substrate is tagged with at least two fluorescent dyes;

emitting energy at a first wavelength into the bodily fluid that contains the enzyme and the protein substrate, and into which the substrate tagged with the at least two fluorescent dyes has been presented;

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

providing a therapy device comprising a therapy pump configured to deliver a therapy based on the detected energy.

2. The method of claim 1, wherein emitting and detecting energy comprises emitting and detecting energy via an optical fiber that includes a distal end located in a blood vessel of a patient.

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

4. The method of claim 1, wherein the enzyme is a protease enzyme.

5. The method of claim 1, further comprising:

storing information relating to the detected energy; and

delivering the information to a user.

6. The method of claim 1, further comprising activating an alarm in response to the detected energy.

7. The method of claim 1, wherein the method further comprises determining an amount of cleaved tagged substrate based on the detected energy, and wherein the therapy pump delivers the therapy based on the determined amount of cleaved tagged substrate.

8. The method of claim 7, further comprising detecting energy emitted by the second one of the dyes at a third wavelength in response to the emitted energy at the first wavelength, wherein determining an amount of cleaved tagged substrate comprises:

determining a ratio between a first detected intensity of energy at the second wavelength and a second detected intensity of energy at the third wavelength, and

determining the amount of cleaved tagged substrate within the bodily fluid based on the ratio.

9. The method of claim 8, wherein the tagged substrate includes a first product and a second product, wherein the first product is tagged with the first one of the dyes and the second product is tagged with the second one of the dyes,

wherein the tagged substrate is cleavable by the enzyme in the bodily fluid, and

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 prior to cleavage of the tagged substrate by the enzyme.

10. The method of claim 1, wherein the tagged substrate comprises a substrate similar to the protein substrate.