Dielectric waveguide sensors and their use in immunoassays

• US 4,880,752 A
• Filed: 02/24/1989
• Issued: 11/14/1989
• Est. Priority Date: 09/21/1984
• Status: Expired due to Fees

• Current Assignee: CIBA Vision Corporation (Novartis Ag)
• Original Assignee: CIBA Vision Corporation (Novartis Ag)
• Inventors: Love, Walter F., Keck, Donald B.
• Primary Examiner(s): Evans, F. L.
• Application Number:
  US07/298,524
• Time in Patent Office: 263 Days
• Field of Search: 356/300, 356/319, 356/445, 356/317, 356/318, 356/417, 250/458.1, 250/459.1, 250/461.1, 250/461.2, 250/227, 350/96.29, 350/96.33, 350/96.32, 436/527, 436/535, 436/805, 436/807, 436/172, 422/57-59, 422/68, 435/7, 435/288, 435/291, 435/808
• US Class Current: 435/7.72
• CPC Class Codes: B01D 53/1493 Selection of liquid materials for use as absorbents
• CPC Class Codes: B01D 53/507 by treating the gases with other liquids
• CPC Class Codes: C01B 17/60 Isolation of sulfur dioxide from gases
• CPC Class Codes: C07D 241/08 with oxygen atoms directly attached to ring carbon atoms
• CPC Class Codes: G01N 2021/7786 Fluorescence
• 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: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
• CPC Class Codes: G01N 33/552 Glass or silica
• CPC Class Codes: Y10S 435/808 Optical sensing apparatus
• CPC Class Codes: Y10S 435/968 High energy substrates, e.g. fluorescent, chemiluminescent, radioactive
• CPC Class Codes: Y10S 436/805 Optical property
• CPC Class Codes: Y10S 436/807 Apparatus included in process claim, e.g. physical support structures

Abstract

The present invention relates to novel dielectric waveguide (i.e., fiber optic) sensors for use in spectrophotometric assays of analytes in fluids. More particularly, the use of these sensors in immunoassays is disclosed.

Claims

1. A dielectric waveguide for use in fluorescence assays of an analyte in a fluid, comprising:

(a) a core having an index of refraction (N₁) and an opening in the core;

(b) a cladding about the core having an index of refraction (N₂) which is less than N₁ ; and

(c) a reactant coating about the opening of the core which comprises an analyte-binder, wherein the core is transmissive to radiation which can excite fluorescence of a fluorescent tag and transmissive to fluorescent radiation from the fluorescent tag.

2. The dielectric waveguide of claim 1 wherein the core has hollow opening throughout its length.

3. The dielectric waveguide of claim 1 wherein the waveguide has a fiber shape with two ends, one of which has a mirror coating.

4. The dielectric waveguide of claim 1 wherein the waveguide has a fiber shape and a mirror coating on cladding.

5. The dielectric waveguide of claim 1 wherein the reactant coating is an immobilized antibody.

6. The dielectric waveguide of claim 1 wherein the reactant coating is an immobilized antigen.

7. The dielectric waveguide of claim 1 wherein the reactant coating is an enzyme.

8. A method of spectrophotometrically assaying an analyte in a fluid comprising:

(a)

contacting the dielectric waveguide of claim 1 with the fluid for a time sufficient for the analyte and the analyte-binder to be able to interact;

(b) propagating radiation down the waveguide core so as to irradiate the interacting analyte and analyte-binder in the presence of a fluorescent tag;

(c) detecting the fluorescence radiation resulting from the irradiation of the analyte interaction by monitoring the waveguide.

9. An improved apparatus for spectrophotometrically assaying an analyte in a fluid having a radiation source and a means for detecting fluorescence radiation, the improvement comprising:

(a) the dielectric waveguide of claim 1;

(b) a means for guiding radiation from the source, to the waveguide such that it is propagated down the waveguide; and

(c) a means for guiding the fluorescence signal radiation from the waveguide to the detection means.

10. A multi-element dielectric waveguide for use in fluorescence assays of an analyte in a fluid comprising:

(a) a support fiber having an index of refraction (N_A) and an opening therethrough;

(b) a second core fiber axially positioned within the support fiber opening and having an index of refraction (N_B);

(c) a means for maintaining the axial position of the core fiber within the support fiber; and

(d) a reactant coating on the support fiber or on the core fiber which comprises an analyte-binder, wherein the support fiber and the core fiber are transmissive to radiation which can excite fluorescence of a fluorescent tag and transmissive to fluorescent radiation from the fluorescent tag.

11. The dielectric waveguide of claim 10 wherein N_B is greater than N_A.

12. The dielectric waveguide of claim 10 wherein N_B is equal to N_A.

13. The dielectric waveguide of claim 10 wherein N_B is less than N_A.

14. The dielectric waveguide of claim 10 wherein a mirror coating is placed about the outside of support fiber.

15. The dielectric wavegude of claim 10 wherein the core fiber has a cladding on the outside with an index of refraction N_C which is greater than N_B.

16. The dielectric waveguide of claim 10 wherein the core fiber has a reactant coating which, in the presence of electromagnetic radiation, interacts with the analyte to form a signal radiation.

17. The dielectric waveguide of claim 10 wherein the support fiber has a reactant coating which, in the presence of electromagnetic radiation, interacts with the analyte to form a signal radiation.

18. A method of spectrophotometrically assaying an analyte in a fluid comprising:

(a) contacting the dielectric waveguide of claim 10 with the fluid for a time sufficient for the analyte and the analyte-binder to be able to interact;

(b) propagating radiation down the core fiber so as to irradiate the combination of analyte and analyte-binder in the presence of a fluorescent tag;

(c) detecting the fluorescence radiation from the irradiated analyte and analyte-binder interaction by monitoring the waveguide.

19. A method of spectrophotometrically assaying an analyte in a fluid comprising:

(a) contacting the dielectric waveguide of claim 10 with the fluid for a time sufficient for the analyte and the analyte-binder to be able to interact;

(b) propagating radiation down the support fiber so as to irradiate the combination of analyte and analyte-binder in the presence of a fluorescent tag;

(c) detecting the fluorescence radiation from the irradiated analyte and analyte-binder interaction by monitoring the waveguide.

20. A method of spectrophotometrically assaying an analyte in a fluid comprising:

(a) contacting the dielectric waveguide of claim 10 with the fluid for a time sufficient for the analyte and the analyte-binder to be able to interact;

(b) propagating radiation within the fluid so as to irradiate the combination of analyte and analyte-binder in the presence of a fluorescent tag;

(c) detecting the fluorescence radiation from the irradiated analyte and reactant interaction by monitoring the waveguide.

21. A dielectric waveguide for use in fluorescence assays of an analyte in a fluid comprising:

(a) a core having an index of refraction (N_X) and an opening therethrough;

(b) a series of claddings about the core having alternating indices of refraction (N₂) and (N₁) where N₂ is less than N₁ and only one of either can equal N_X, and of such a number and configuration so as to enable radiation which can excite the fluorescence of a fluorescent tag to propagate within the core opening and to enable the fluorescent radiation from the fluorescent tag to propagate within the core opening and;

(c) a reactant coating on the core surface which comprises an analyte-binder.

22. A method of spectrophotometrically assaying an analyte comprising:

(a) contacting the dielectric waveguide of claim 21 with the fluid for a time sufficient for the analyte and the analyte-binnder to interact;

(b) propagating radiation down the waveguide so as to irradiate the combination of analyte and analyte-binder in the presence of a fluorescent tag; and

(c) detecting the fluorescence radiation resulting from the irradiation of the analyte and analyte-binder interaction by monitoring the fluid.