Diagnostic device and method

• US 6,222,619 B1
• Filed: 09/18/1997
• Issued: 04/24/2001
• Est. Priority Date: 09/18/1997
• Status: Expired due to Term

• Current Assignee: University of Utah Research Foundation (State of Utah)
• Original Assignee: University of Utah Research Foundation (State of Utah)
• Inventors: Durtschi, Jacob D., Christensen, Douglas A., Herron, James N.
• Primary Examiner(s): Font, Frank G.
• Assistant Examiner(s): MERLINO, AMANDA H
• Application Number:
  US08/933,203
• Time in Patent Office: 1,314 Days
• Field of Search: 356/39, 356/317, 356/318, 356/417, 422/82.06, 422/82.07, 422/81, 422/82.09, 436/66
• US Class Current: 356/39
• CPC Class Codes: G01N 2333/4712 Muscle proteins, e.g. myosin, actin, protein
• CPC Class Codes: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
• CPC Class Codes: G01N 33/68 involving proteins, peptides or amino acids involving lipoproteins G01N33/92

Abstract

A method and apparatus of diagnosing a cardiac disease state in as little as two minutes involving the utilization of an evanescent wave assay system in conjunction with a data acquisition and analysis procedure that monitors the precision of assay results in real time (i.e., while data is being acquired). The method includes diagnosing a disease state using a diagnostic procedure (e.g., an immunoassay) wherein the testing device informs the person conducting the test of the results of the test as soon as reliable test data is obtained (generally, <5% variation in the reaction rate of the assay). After which point, the diagnostic procedure may be terminated.

Claims

1. A method of performing an assay comprising:

providing an assay system which receives a biological liquid sample potentially containing at least one analyte of interest and outputs a light signal indicative of the rate of reaction between said analyte of interest and a reactive element within the assay system;

continuously measuring light emitted from said assay system over time;

continuously correlating said rate of reaction to a concentration of said analyte of interest; and

determining the concentration of at least one analyte of interest in said biological liquid sample based on said correlation of said light in a time period less than about five minutes.

2. The method of claim 1, wherein said at least one analyte of interest is an ischemic marker.

3. The method of claim 2, wherein said ischemic marker is selected from the group comprising troponin I, CK-MB, and myoglobin.

4. The method of claim 1, wherein said assay system comprises:

a light source;

a biosensor comprising a waveguide having at least one planar surface, said waveguide associated in liquid tight attachment with a first member, said first member, in conjunction with the waveguide, defining at least one reservoir for containing said biological liquid sample, the planar surface of said waveguide being associated in part with capture molecules, and an inlet and outlet in fluid communication with said reservoir for infusing and draining said biological liquid sample into and out of said reservoir so as to allow the biological liquid sample to contact said capture molecules; and

a light detector for detecting light passed through said planar surface.

5. The method of claim 4, further comprising:

simultaneously introducing tracers molecules and a biological liquid sample potentially containing at least one analyte of interest into said at least one reservoir of said biosensor, wherein said tracer molecules are complementary with said respective capture molecules and emit fluorescent light in response to stimulation by light of an appropriate wavelength; and

introducing a light beam from said light source into said waveguide to propagate light of said appropriate wavelength to stimulation a fluorescent light response in said tracer molecules which have attached to a portion of at least one said analyte of interest which has been captured by said capture molecules on said waveguide planar surface.

7. The method according to claim 1, wherein said at least one analyte of interest is a marker released from cardiac tissue only after a myocardial infarction.

8. The method according to claim 7, wherein said marker is selected from the group consisting of myoglobin and serum glutamic oxalacetic transaminase.

9. The method according to claim 1, wherein said at least one analyte of interest is a cardiac specific marker.

10. The method according to claim 9, wherein said cardiac specific marker comprises at least one of troponin I, troponin T, and CK-MB.

11. The method according to claim 1, wherein said determining the concentration comprises simultaneously determining the concentrations of a plurality of analytes of interest in said biological liquid sample.

12. The method according to claim 1, further comprising continuing with said determining until a reliable determination is made of whether said at least one analyte is present in an amount indicative of a metabolic or disease state.

13. The method according to claim 12, further comprising reporting said reliable determination.

14. The method according to claim 13, wherein said reporting is effected by an audio or visual alarm.

6. An assay system for analyzing a biological liquid sample, comprising:

a light source;

a waveguide having at least one planar surface and being optically associated with a rear lens oriented for reading light from said light source passing through said waveguide, to monitor coupling efficiency and beam quality;

a first member associated in liquid tight attachment with said waveguide, wherein said first member, in conjunction with the waveguide, defining at least one reservoir for containing the biological liquid sample while a planar surface of the waveguide defines a floor or ceiling of said reservoir, the planar surface being associated in part with capture molecules;

an inlet and outlet in fluid communication with said reservoir for infusing and draining said biological liquid into said reservoir so as to allow the biological liquid to contact said capture molecules;

a light detector for detecting light passed through said planar surface, which generates a signal indicating the intensity of said detected light; and

a controller for monitoring the intensity signal and correlates said signal to the concentration of said analyte of interest in said biological sample.

15. A method of diagnosing a cardiac disease state in a patient, the method comprising:

providing an assay system which;

receives a biological liquid sample from the patient, the sample potentially containing at least one analyte selected from the group consisting of troponin-I, CK-MB, myoglobin, and mixtures thereof; and

outputs a light signal indicative of a reaction between said at least one analyte and a reactive element within the assay system;

continuously measuring light emitted from said assay system over time;

continuously correlating the reaction to a concentration of said at least one analyte; and

determining the concentration of said at least one analyte in said biological liquid sample based on said correlation of said emitted light in a time period less than about five minutes.

16. The method according to claim 15, wherein the determination of the concentration comprises simultaneously determining the concentrations of a plurality of analytes of interest potentially in the sample.

17. The method according to claim 15, further comprising:

continuing with said determination until a reliable determination is made of whether said at least one analyte is present in an amount indicative of a metabolic or disease state.

18. The method according to claim 17, further comprising reporting said reliable determination.

19. The method according to claim 18, wherein the report of the reliability determination is effected by an audio or visual alarm.