Optical fiber evanescent field excited fluorosensor and method of manufacture

• US 6,103,535 A
• Filed: 05/30/1997
• Issued: 08/15/2000
• Est. Priority Date: 05/31/1996
• Status: Expired due to Fees

• Current Assignee: University of Maryland
• Original Assignee: University of Maryland
• Inventors: Davis, Christopher C., Fielding, Alexander J., Pilevar, Saeed, Portugal, Frank
• Primary Examiner(s): Chin, Christopher L.
• Application Number:
  US08/866,080
• Time in Patent Office: 1,173 Days
• Field of Search: 385/12, 385/123, 422/58, 422/83, 422/82.05, 422/82.08, 422/82.11, 435/5, 435/6, 435/7.4, 435/7.32, 435/287.1, 435/287.2, 435/288.7, 435/808, 436/164, 436/172, 436/518, 436/527, 436/805
• US Class Current: 436/518
• CPC Class Codes: G01N 2021/772 Tip coated light guide
• CPC Class Codes: G01N 2021/7786 Fluorescence
• 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: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
• CPC Class Codes: Y10S 435/808 Optical sensing apparatus
• CPC Class Codes: Y10S 436/805 Optical property

Abstract

An optical fiber is tapered, preferably adiabatically, and has a material coated on it for chemical bonding with fluorophores. When the fluorophores couple with the material, evanescent radiation generated fibers causes the fluorophores to fluoresce, and the fluorescence is coupled back into the fiber.

Claims

1. A probe for detecting a chemical, the probe comprising:

a single mode optical fiber having a tapered portion having a single taper in which a diameter of the optical fiber is reduced from a larger diameter to a smaller diameter; and

a coating disposed on a surface of the tapered portion of the optical fiber, the coating having a property of binding with the chemical when brought in contact with the chemical.

2. A probe as in claim 1, wherein:

the optical fiber comprises a core and a cladding which are tapered simultaneously such that the boundry between core and cladding disappears in the tapered portion to become a structure of glass surrounded by air.

3. A probe as in claim 2, wherein the surface is on the core, and wherein the coating is in contact with the core.

4. A probe as in claim 1, further comprising:

light emitting means for emitting a light beam to be coupled into the tapered portion of the optical fiber;

light detecting means for detecting fluorescence generated by the chemical when the chemical is bound to the coating and exposed to evanescent radiation generated in the tapered portion under influence of the light beam, the fluorescence entering the optical fiber through the tapered portion; and

coupling means for (i) coupling the light beam from the light emitting means into the tapered portion and (ii) coupling the fluorescence from the tapered portion to the light detecting means.

5. A probe as in claim 4, wherein the light emitting means comprises a near infrared semi-conductor laser diode.

6. A probe as in claim 5, wherein the light emitting means further comprises chopping means, disposed in a path of the light beam, for modulating the light beam.

7. A probe as in claim 5, wherein the light emitting means further comprises pulse generator means for modulating the laser diode to emit the light beam as pulses and prevent over exposing the fluorophores and avoid photo bleaching.

8. A probe as in claim 7, wherein the light detecting means comprises:

means for producing a voltage in accordance with the fluorescence; and

means for pulse averaging the voltage under control of the pulse generator means.

9. A probe as in claim 7, wherein the laser diode is a fiber pigtailed tunable semiconductor laser diode.

10. A probe as in claim 9, wherein in the light detecting means comprises:

a Super Notch Holographic Filter (SNHF) for filtering an undesired wavelength from the fluoroescence; and

a detector for detecting the fluorescence after the filter means has filtered the undesired wavelength from the fluoroescence.

11. A probe as in claim 10, wherein the filter means comprises a further optical fiber having a fiber Bragg grating filter formed therein, the fiber Bragg grating filter being tuned to filter the undesired wavelength.

12. A probe as in claim 11, wherein the detector comprises a fiber pigtailed detector.

13. A probe as in claim 1, wherein the coating is sensitive to pH.

14. A probe as in claim 1, wherein the coating is sensitive to temperature.

15. A probe as in claim 1, which detects a biological agent.

16. A probe as in claim 15, wherein the biological agent is airborne and is sampled from the air and presented to the probe.

17. A probe as in claim 15, wherein the biological agent is a product of biological activity of a microorganism.

18. A probe as in claim 15, wherein the biological agent is a virus, a part of a virus, or a product of a virus.

19. A probe as in claim 15, wherein the biological agent is a fungus, a part of a fungus, or a product of a fungus.

20. A probe as in claim 1, with a coating for detecting a chemical occurring in a cavity in a solid mass.

21. A probe as in claim 1, which detects a chemical occurring in an on-stream effluent.

22. A probe as in claim 1, wherein the chemical is intact DNA or a portion of DNA (oligonucleotide).

23. A probe as in claim 1, wherein the chemical is intact RNA or a portion of RNA (oligonucleotide).

24. A probe as in claim 1, wherein the coating is covalently attached to the surface.

25. A probe as in claim 1, wherein the coating is non-covalently attached to the surface.

26. A probe as in claim 1, wherein the chemical is a chemical that is displaced from the coating in a presence of a second chemical.

27. A probe as in claim 1, wherein the chemical is a chemical that is detectable in a nonaqueous environment or a semiaqueous environment, so photobleaching is minimized.

28. A probe as in claim 1 wherein the optical fiber is mounted in a holder to provide structural stability and the holder is chemically cleaned, surface-treated, and heat-cured to prevent binding of the chemical to be detected to the holder.

29. A probe as in claim 1, wherein the optical fiber is mounted in a holder to provide structural stability and the holder is made of a material that has an intrinsic property of not binding to the chemical.

30. A probe as in claim 1, wherein the chemical is a protein.

31. A probe as in claim 30, wherein the protein is an enzyme.

32. A probe as in claim 30, wherein the protein is a receptor.

33. A probe as in claim 1, further comprising a flow cell having separate ports for fluid entry and exit, the optical fiber being inserted into the flow cell.