Multiple output referencing system for evanescent wave sensor

• US 5,525,466 A
• Filed: 05/20/1994
• Issued: 06/11/1996
• Est. Priority Date: 06/07/1991
• Status: Expired due to Term

• Current Assignee: Siemens Healthcare Diagnostics Incorporated (Siemens AG)
• Original Assignee: CIBA Vision Corporation (Bayer AG)
• Inventors: Cook, Thomas A., Love, Walter F., Schulkind, Richard L., Slovacek, Rudolf E., Walczak, Irene M.
• Primary Examiner(s): Housel, James C.
• Assistant Examiner(s): Chin, Christopher L.
• Application Number:
  US08/246,391
• Time in Patent Office: 753 Days
• Field of Search: 385/12, 385/129, 385/130, 356/243, 356/306, 356/448, 422/82.05, 422/82.08, 422/82.11, 435/6, 435/287, 435/291, 435/808, 436/518, 436/527, 436/164, 436/172, 436/805
• US Class Current: 435/6.11
• CPC Class Codes: G01N 2021/6439 with indicators, stains, dyes, tags, labels, marks
• CPC Class Codes: G01N 2021/7709 Distributed reagent, e.g. over length of guide
• CPC Class Codes: G01N 2021/7793 Sensor comprising plural indicators
• 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 21/648 using evanescent coupling or surface plasmon coupling for the excitation of fluorescence
• CPC Class Codes: G01N 21/7703 using reagent-clad optical fibres or optical waveguides using measurement of total internal reflection or attenuated total reflection G01N21/552; optical fibres or waveguides per se G02B
• CPC Class Codes: Y10S 435/808 Optical sensing apparatus
• CPC Class Codes: Y10S 436/805 Optical property

Abstract

An evanescent wave system and method including an optical sensor for use in assaying a reference material and at least one molecular species or analyte in a test medium or test sample for diagnostic and other applicable purposes. The sensor includes a waveguide for propagating a radiation input along its length. The radiation input causes evanescent electromagnetic waves that are capable of stimulating output emissions that are indicative of a reference material and of one or more molecular species or analytes. By comparing the emission(s) indicative of the reference material to the emission indicative of the presence of the molecular species or analyte, the presence and concentration of the molecule in the sample can be determined. The reference material provides for normalization and/or calibration of the system.

Claims

1. An evanescent wave sensor for receiving one or more electromagnetic radiation input signals and emitting at least two output signals, said sensor comprising:

a waveguide sensor having at least one wave propagating surface including a reactant coating immobilized thereon comprising molecular species that specifically bind to an analyte that may be present in a test medium; and

a fluorescent reference material which is attached to said waveguide, wherein the sensor surface receives one or more electromagnetic radiation input signals and emits an output electromagnetic radiation signal dependent on the presence of at least one analyte and another output electromagnetic radiation signal from the fluorescent reference material;

such that the reference material provides for normalization and/or calibration of the sensor.

2. The sensor of claim 1 wherein the molecular species is selected from the group consisting of:

antigens,

antibodies,

amino acid sequences, and

nucleic acid sequences.

3. The sensor of claim 1, wherein the waveguide comprises two separate surfaces or a cone.

4. The sensor of claim 1 wherein the waveguide comprises a hollow waveguide.

5. The sensor of claim 1 wherein the waveguide comprises an optical fiber.

6. The sensor of claim 1 wherein the waveguide comprises a planar structure having opposed parallel surfaces.

7. The sensor of claim 1 wherein the electromagnetic radiation signal from the reference material is used to test the sensor for effects of storage or aging.

8. The sensor of claim 1, wherein the signal from the reference material is used to correlate the variability between sensors in a given manufacturing batch/lot or assay.

9. The sensor of claim 1, wherein the signal from the reference material is used to examine variations in excitation and collection efficiency between waveguides due to waveguide manufacture or handling during coating.

10. The sensor of claim 1, wherein the signals from the reference material is used to detect defective waveguides.

11. The sensor of claim 1 further including means for isolating the fluorescent reference material from the analyte or molecular species, wherein said means for isolating includes encapsulation of said fluorescent reference material within the reactant coating on the waveguide.

12. The sensor of claim 11 in which said means for isolating comprises an encapsulation material having an index of refraction substantially equal to the index of refraction of the test medium.

13. The sensor of claim 1 wherein the molecular species is selected from the group consisting of:

receptors and ligands.

14. The sensor of claim 1, when said sensor further comprises:

an optical processor having a lens arranged to launch light into the waveguide to generate evanescent wave electromagnetic fields; and

a detector for measuring light emitted from the wave guide to form a sensor system.

15. An evanescent wave sensor system for receiving one or more light input signals and emitting at least two output signals, comprising:

a sensor having at least one wave propagating surface for propagating light input along the surface;

said surface including a reactant coating immobilized thereon having a molecular species that specifically binds to a molecule that may be present in a medium or test sample and a fluorescent reference material;

wherein the surface is capable of receiving light input signals and causing a reference output signal dependent on the reference material and an output signal dependent on the presence of at least one molecule in said medium or test sample; and

wherein the reference material provides normalization and/or calibration of the system.

16. A method for analyzing a test medium comprising:

propagating a light input along at least one wave propagating surface of a sensor;

contacting the wave propagating surface with said test medium;

propagating light along the wave propagating surface to generate evanescent wave electromagnetic fields at the surface to irradiate the test medium; and

detecting light reentering the wave propagating surface and emitted from the wave propagating surface,

wherein the surface has a reactant coating including a fluorescent reference material and a binding partner of at least one analyte, said surface being capable of receiving the light input and causing a reference output signal dependent on the reference material, at least one light output signal from a labelled species dependent on the presence of at least on analyte and wherein the reference material provides for normalization and/or calibration of the system.

17. The method of claim 16 in which detecting includes monitoring at least a first output signal indicative of the presence of at least a first analyte and a reference output signal indicative of the presence of the reference material.