Multiple output referencing system for evanescent wave sensor

• US 5,738,992 A
• Filed: 04/09/1996
• Issued: 04/14/1998
• Est. Priority Date: 06/07/1991
• Status: Expired due to Term

• Current Assignee: Siemens Healthcare Diagnostics Incorporated (Siemens AG)
• Original Assignee: Chiron Corporation (Bayer AG)
• Inventors: Love, Walter F., Walczak, Irene M., Cook, Thomas A., Schulkind, Richard L., Slovacek, Rudolf E.
• Primary Examiner(s): Chin, Christopher L.
• Application Number:
  US08/629,595
• Time in Patent Office: 735 Days
• Field of Search: 385/12, 385/141, 385/142, 385/143, 385/129, 385/130, 356/243, 356/306, 356/448, 422/82.05, 422/82.08, 422/82.11, 435/6, 435/287.1, 435/287.2, 435/288.7, 435/808, 436/164, 436/172, 436/518, 436/527, 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. A system for measuring at least one signal from a waveguide sensor, the system comprising:

a waveguide sensor having at least one wave propagating surface including a reactant coating immobilized thereon, the reactant coating including a first molecular species and a labeled molecular species, the first molecular species being bound to the waveguide sensor, the first molecular species being bound to the labeled molecular species, and the labeled molecular species having an excitation wavelength and an emission wavelength;

a fluorescent reference material attached to the wave guide, the fluorescent reference material having an excitation wavelength and an emission wavelength;

a source capable of emitting electromagnetic radiation at the excitation wavelength of the fluorescent reference material;

a first detector capable of detecting the emission wavelength of the fluorescent reference material; and

a coupler for transmitting electromagnetic radiation along a first path from the source to the waveguide sensor to the first detector.

2. A system in accordance with claim 1, further comprising a first dichroic element and a first filter, the first dichroic element being disposed between the source and the waveguide sensor along the first path, the first filter being disposed between the source and the first dichroic element along the first path, the first filter being capable of transmitting electromagnetic radiation at the excitation wavelength of the labeled molecular species and the excitation wavelength of the fluorescent reference material.

3. A system in accordance with claim 2, further comprising a second dichroic element and a second filter, the second dichroic element being disposed between the waveguide sensor and the first detector along the first path, the second filter being disposed between the second dichroic element and the first detector along the first path, the second filter being capable of filtering electromagnetic radiation at the emission wavelength of the labeled molecular species.

4. A system in accordance with claim 3, further comprising a second detector capable of detecting the emission wavelength of the labeled molecular species, wherein the coupler is capable of transmitting electromagnetic radiation along a second path from the source to the waveguide sensor to the second detector, and wherein the source is capable of emitting electromagnetic radiation at the excitation wavelength of the labeled molecular species.

5. A system in accordance with claim 4, further comprising a third filter disposed between the second dichroic element and the second detector along the second path, the third filter being capable of filtering electromagnetic radiation at the emission wavelength of the fluorescent reference material.

6. A system in accordance with claim 1, further comprising a second detector capable of detecting the emission wavelength of the labeled molecular species, wherein the coupler is capable of transmitting electromagnetic radiation along a second path from the source to the waveguide sensor to the second detector, and wherein the source is capable of emitting electromagnetic radiation at the excitation wavelength of the labeled molecular species.

7. A system in accordance with claim 6, further comprising a third filter disposed between the second dichroic element and the second detector along the second path, the third filter being capable of filtering electromagnetic radiation at the emission wavelength of the fluorescent reference material.

8. A system in accordance with claim 1, wherein the labeled molecular species is selected from the group consisting of antigens, antibodies, amino acid sequences, nucleic acid sequences and mixtures thereof.

9. A system in accordance with claim 1, wherein the first molecular species is selected from the group consisting of antigens, antibodies, amino acid sequences, nucleic acid sequences and mixtures thereof.

10. A system for measuring at least one signal from an evanescent waveguide sensor, the system comprising:

a waveguide sensor capable of emitting first and second wavelengths;

a fluorescent reference material attached to the waveguide sensor, the fluorescent reference material having an emission wavelength approximately equal to the first wavelength;

a source capable of emitting electromagnetic radiation at the first and second wavelengths;

a first detector capable of detecting electromagnetic radiation at the first wavelength;

a second detector capable of detecting electromagnetic radiation at the second wavelength; and

a coupler for transmitting electromagnetic radiation along a first path from the source to the waveguide sensor to the first detector and along a second path from the source to the waveguide sensor to the second detector.

11. A system in accordance with claim 10, further comprising a first dichroic element and a first filter, the first dichroic element being disposed between the source and the waveguide sensor along the first and second paths, the first filter being disposed between the source and the first dichroic .element along the first path, the first filter being capable of transmitting electromagnetic radiation at the first and second wavelengths.

12. A system in accordance with claim 11, further comprising a second dichroic element and a second filter, the second dichroic element being disposed between the waveguide sensor and the first detector along the first path, the second filter being disposed between the second dichroic element and the first detector along the first path, the second filter being capable of filtering electromagnetic radiation at the second wavelength.

13. A system in accordance with claim 12, further comprising a third filter disposed between the second dichroic element and the second detector along the second path, the third filter being capable of filtering electromagnetic radiation at the first wavelength.

14. A system in accordance with claim 13, further comprising a first molecular species and a labeled molecular species capable of binding to the analyte, the labeled molecular species having an emission wavelength approximately equal to the second wavelength.

15. A system in accordance with claim 14, wherein the labeled molecular species is selected from the group consisting of labeled antigens, labeled antibodies, labeled amino acid sequences, labeled nucleic acid sequences and mixtures thereof.

16. A system in accordance with claim 10, further comprising a first molecular species and a labeled molecular species, the labeled molecular species having an emission wavelength approximately equal to the second wavelength.

17. A system in accordance with claim 16, wherein the labeled molecular species is selected from the group consisting of labeled antigens, labeled antibodies, labeled amino acid sequences, labeled nucleic acid sequences and mixtures thereof.

18. A system for measuring at least one signal from a waveguide sensor, the system comprising:

a waveguide sensor having at least one wave propagating surface including a reactant coating mobilized thereon, the reactant coating including a first molecular species and a labeling molecular species, the first molecular species being bound to the waveguide sensor and the labeling molecular species having an excitation wavelength and an emission wavelength, the labeling molecular species being bound to the first molecular species;

a fluorescent reference material attached to the wave guide, the fluorescent reference material having an excitation wavelength and an emission wavelength;

a source capable of emitting electromagnetic radiation at the excitation wavelength of the fluorescent reference material;

a first detector capable of detecting the emission wavelength of the fluorescent reference material; and

a coupler for transmitting electromagnetic radiation along a first path from the source to the waveguide sensor to the first detector.

19. A system in accordance with claim 18, further comprising a first dichroic element and a first filter, the first dichroic element being disposed between the source and the waveguide sensor along the first path, the first filter being disposed between the source and the first dichroic element along the first path, the first filter being capable of transmitting electromagnetic radiation at the excitation wavelength of the labeling molecular species and the excitation wavelength of the fluorescent reference material.

20. A system in accordance with claim 19, further comprising a second dichroic element and a second filter, the second dichroic element being disposed between the waveguide sensor and the first detector along the first path, the second filter being disposed between the second dichroic element and the first detector along the first path, the second filter being capable of filtering electromagnetic radiation at the emission wavelength of the labeling molecular species.

21. A system in accordance with claim 20, further comprising a second detector capable of detecting the emission wavelength of the labeling molecular species, wherein the coupler is capable of transmitting electromagnetic radiation along a second path from the source to the waveguide sensor to the second detector, and wherein the source is capable of emitting electromagnetic radiation at the excitation wavelength of the labeling molecular species.

22. A system in accordance with claim 21, further comprising a third filter disposed between the second dichroic element and the second detector along the second path, the third filter being capable of filtering electromagnetic radiation at the emission wavelength of the fluorescent reference material.

23. A system in accordance with claim 18, further comprising a second detector capable of detecting the emission wavelength of the labeling molecular species, wherein the coupler is capable of transmitting electromagnetic radiation along a second path from the source to the waveguide sensor to the second detector, and wherein the source is capable of emitting electromagnetic radiation at the excitation wavelength of the labeling molecular species.

24. A system in accordance with claim 23, further comprising a third filter disposed between the second dichroic element and the second detector along the second path, the third filter being capable of filtering electromagnetic radiation at the emission wavelength of the fluorescent reference material.

25. A system in accordance with claim 18, wherein the labeling molecular species is selected from the group consisting of labeled antigens, labeled antibodies, labeled amino acid sequences, labeled nucleic acid sequences and mixtures thereof.

26. A system in accordance with claim 18, wherein the first molecular species is selected from the group consisting of antigens, antibodies, amino acid sequences, nucleic acid sequences and mixtures thereof.