Fiber optic direct-sensing bioprobe using a phase-tracking approach

• US 5,804,453 A
• Filed: 02/09/1996
• Issued: 09/08/1998
• Est. Priority Date: 02/09/1996
• Status: Expired due to Term

• Current Assignee: Pall ForteBio Corp.
• Original Assignee: Duan-Jun Chen
• Inventors: Chen, Duan-Jun
• Primary Examiner(s): Hutzell, Paula K.
• Assistant Examiner(s): BAKALYAR, HEATHER
• Application Number:
  US08/599,298
• Time in Patent Office: 942 Days
• Field of Search: 435/176, 422/82.07, 350/96.29, 436/501, 436/518, 424/130.1-137.1, 356/345, 385/12
• US Class Current: 436/518
• CPC Class Codes: G01N 2021/772 Tip coated light guide
• CPC Class Codes: G01N 2021/7759 Dipstick; Test strip
• CPC Class Codes: G01N 2021/7779 interferometric
• 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

Abstract

A fiber optic bioprobe in which an immobilized biolayer, such as an antigen or antibody, acts as a sensing etalon of a Fabry-Perot interferometer. The bioprobe is used in a system in which a shift in the spectral dispersion pattern, caused by reflected out-of-phase beams, is used to determine a concentration of a substance in a sample solution.

Claims

1. A method of determining the concentration of a substance in a sample solution, using a fiber optic probe having a reagent at its distal end to which the substance bonds, the method comprising steps of:

a) immersing the distal end of the fiber optic probe into the sample solution;

b) optically coupling a light source with a proximal end of the fiber optic probe;

c) detecting a first light beam, and a second light beam, reflected at the distal end of the fiber optic probe;

d) detecting an interference pattern formed by the first and second light beams at a first time;

e) detecting an interference pattern formed by the first and second light beams at a second time; and

f) determining whether the substance is present in the sample solution based on whether a shift occurs in the interference patterns.

2. The method of claim 1 further comprising a step of determining a concentration of the substance based on a shift in the interference patterns and based on a differential between the first and second times.

3. The method of claim 1 wherein each step of detecting includes sub-steps of:

i) dispersing an interference beam, formed by the first and second light beams, onto a spectrometer to form a spectral dispersion pattern;

ii) determining a periodic function based on the spectral dispersion pattern; and

iii) determining a phase of the periodic function.

4. The method of claim 1 further comprising a step of:

modulating the frequency of the light source optically coupled with the proximal end of the fiber optic probe,

wherein the step of determining whether the substance is present in the sample solution based on whether a shift occurs in the spectral patterns is synchronized with the frequency of the light source.

5. The method of claim 1 wherein the first time is before a reaction of the substance and the reagent layer and the second time is after the reaction of the substance and the reagent layer.

6. The method of claim 1 wherein the first and second times occur during a reaction of the substance and the reagent layer.

7. The method of claim 1 wherein the second time approaches the first time thereby allowing continuous monitoring.

8. A system for detecting the concentration of a substance in a sample solution, the system comprising:

a) a light source for providing a light beam;

b) a fiber optic probe including a fiber optic section having a proximal end for receiving an incident light beam and a distal end tip, and a reagent layer immobilized on the distal end tip, the fiber optic probe for producing at least a first reflected beam and a second reflected beam from the incident light beam;

c) a detector for detecting an interference pattern formed by the first and second reflected beams;

d) a coupler for optically coupling the light source with the fiber optic probe and for optically coupling the fiber optic probe with the detector; and

e) a processor for determining a phase associated with an interference pattern detected by the detector at a first time and for determining a phase associated with an interference pattern detected by the detector at a second time and for determining the concentration of the substance based on a shift in the phases associated with the interference patterns detected by the detector at the first and second times.

9. The system of claim 8 wherein the detector is a spectrometer.

10. The system of claim 8 wherein the detector is a one-dimensional charge coupled device.

11. The system of claim 8 wherein the detector is a 1×

1024 charge coupled device.

12. The system of claim 8 wherein the processor includes:

i) a periodic signal interpreter/generator for generating a first periodic signal based on the interference pattern detected by the detector at the first time and a second periodic signal based on the interference pattern detected by the detector at the second time;

ii) a phase tracker for determining a phase of the first periodic signal and a phase of the second periodic signal; and

iii) a computer for computing a phase difference between the phases of the first and second periodic signals and for determining the concentration of the substance in the sample solution based on the phase difference.

13. The system of claim 8 wherein the coupler is a "Y" coupler.

14. The system of claim 8 wherein the light source is a broadband light source.

15. The system of claim 8 wherein the light source is a tunable laser diode.

16. The system of claim 8 further comprising a frequency modulator, coupled with the light source, for modulating the frequency of the light beam provided by the light source.

17. The system of claim 16 wherein the processor is synchronized with the frequency modulator.

18. The system of claim 8 further comprising:

a second fiber optic probe for determining the concentration of a second substance in the sample solution;

an optical multiplexer, coupled between the light source and each of the fiber optic probe and the second fiber optic probe, for optically coupling the light source with one of the fiber optic probes in a time division manner; and

an optical demultiplexer, coupled between each of the fiber optic probes and the detector,

wherein the optical multiplexer and the optical demultiplexer are synchronized with respect to each other such that only one of the fiber optic probes may be actively coupled with both the light source and the detector at any time.

19. The system of claim 8 wherein the first time is before a reaction of the substance and the reagent layer and the second time is after the reaction of the substance and the reagent layer such that the processor is provided with end point data.

20. The system of claim 8 wherein the first and second times occur during a reaction of the substance and the reagent layer.

21. The system of claim 20 wherein the second time approaches the first time thereby allowing continuous monitoring.