Fiber optic array sensors, apparatus, and methods for concurrently visualizing and chemically detecting multiple analytes of interest in a fluid sample

• US 5,320,814 A
• Filed: 11/25/1992
• Issued: 06/14/1994
• Est. Priority Date: 01/25/1991
• Status: Expired due to Term

• Current Assignee: Trustees of Tufts College
• Original Assignee: Trustees of Tufts College
• Inventors: Barnard, Steven M., Walt, David R.
• Primary Examiner(s): Warden, Robert J.
• Assistant Examiner(s): NOT, DEFINED
• Application Number:
  US07/981,884
• Time in Patent Office: 566 Days
• Field of Search: 422/82.07, 422/82.06, 422/82.08, 422/82.09, 422/86, 422/88, 128/634, 385/12, 436/167, 436/172, 436/127, 436/128, 436/129, 436/130, 436/139, 436/140, 436/141, 436/142, 436/800, 250/227.23
• US Class Current: 422/82.07
• CPC Class Codes: G01N 2021/6434 Optrodes
• CPC Class Codes: G01N 2021/6439 with indicators, stains, dyes, tags, labels, marks
• CPC Class Codes: G01N 2021/6484 Optical fibres
• CPC Class Codes: G01N 2021/772 Tip coated light guide
• CPC Class Codes: G01N 2021/773 Porous polymer jacket; Polymer matrix with indicator
• 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 21/7703 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 21/80 Indicating pH value
• CPC Class Codes: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
• CPC Class Codes: G02B 6/02042 Multicore optical fibres
• CPC Class Codes: G02B 6/06 the relative position of the fibres being the same at both ends, e.g. for transporting images

Abstract

The present invention provides a unique fiber optic sensor which is able to provide a viewing zone for visual examination of a sample and its surrounding environment; and is able to conduct multiple assays concurrently using a plurality of different dyes immobilized at individual spatial positions within a dye sensing zone on the surface of the sensor. The present invention also provides apparatus for making precise optical determinations and measurements for multiple analytes of interest concurrently and provides methods of detection for multiple analytes of interest which can be correlated with specific parameters or other ligands for specific applications and purposes.

Claims

1. A fiber optic sensor useful in an apparatus for detecting at least one analyte of interest in a fluid sample, the detection of each analyte being correlatable with an individual optical determination, said fiber optic sensor comprising:

a preformed, unitary fiber optic array comprising a plurality of individually clad, fiber optic strands disposed co-axially along their lengths and having two discrete optic array ends each of which is formed of multiple strand end faces, said preformed, unitary fiber optic array being of determinable configuration and dimensions, said two discrete optic array ends of said preformed, unitary fiber optic array presenting two discrete optic array surfaces for introduction and conveyance of light energy;

at least one sensing zone comprising not less than one light energy absorbing dye disposed as an uninterrupted deposit in aligned organization upon multiple strand end faces on one of said discrete optic fiber array surfaces of said preformed, unitary fiber optic array, the different spatial positioning of each uninterrupted dye deposit in aligned organization within said at least one sensing zone on said one of said discrete surfaces serving to identify and distinguish each light energy absorbing dye from all other light energy absorbing dyes disposed within said at least one sensing zone, each spatially positioned uninterrupted dye deposit reacting with one analyte of interest; and

at least one sample viewing zone adjacent to said at least one sensing zone on said one of said discrete optic array surfaces of said preformed, unitary fiber optic array, said at least one sample viewing zone being formed of said multiple strand end faces in aligned organization and in fixed spatial position on said discrete optic array surface.

2. The fiber optic sensor as recited in claim 1 wherein said sensing zone comprises at least two different light energy absorbing dyes disposed individually at different spatial positions on said one of said discrete optic array surfaces.

3. The fiber optic sensor as recited in claim 1 wherein the wavelength of light energy absorbed by said not less than one light energy absorbing dye is selected from the group consisting of infrared, visible and ultraviolet wavelengths.

4. The fiber optic sensor as recited in claim 1 wherein said not less than one light energy absorbing dye is selected from the group consisting of fluorophores, fluorescent enzyme substrates, and fluorescent antibody conjugates.

5. An apparatus for detecting at least one analyte of interest in a fluid sample, the detection of each analyte being correlatable with an individual optical determination, said apparatus comprising:

a fiber optic sensor comprised of

(a) a preformed, unitary fiber optic array comprising a plurality of individually clad, fiber optic strands disposed co-axially along their lengths and having two discrete optic array ends each of which is formed of multiple strand end faces, said preformed, unitary fiber optic array being of determinable configuration and dimensions, said two discrete optic array ends of said preformed, unitary fiber optic array presenting two discrete optic array surfaces for introduction and conveyance of light energy;

(b) at least one sensing zone comprising not less than one light energy absorbing dye disposed as an uninterrupted deposit in aligned organization upon said multiple strand end faces at different spatial positions on one of said discrete optic fiber array surfaces of said preformed, unitary fiber optic array, the different spatial positioning of each uninterrupted dye deposit in aligned organization within said at least one sensing zone on said one of said discrete surfaces serving to identify and distinguish each light energy absorbing dye from all other light energy absorbing dyes disposed within said at least one sensing zone, each spatially positioned uninterrupted dye deposit reacting with one analyte of interest; and

(c) at least one sample viewing zone adjacent to said at least one sensing zone on said one of said discrete optic array surfaces of said preformed, unitary fiber optic array, said at least one sample viewing zone being formed of said multiple strand end faces in aligned organization and in fixed spatial position on said one of said discrete optic array surface ends;

means for placing said spatially positioned uninterrupted dye deposit within said at least one sensing zone on one of said discrete optic array surfaces of said fiber optic sensor into reactive contact with a fluid sample;

means for introducing light energy to one of said discrete optic array surfaces of said fiber optic sensor such that said plurality of individually clad fiber optical strands convey said introduced light energy concurrently and illuminate said spatially positioned uninterrupted dye deposit within said at least one sensing zone on said optic array surface;

means for detecting emerging light energy from said illuminated spatially positioned uninterrupted dye deposit within said at least one sensing zone on one of said discrete optic array surfaces, said detected emerging light energy serving as an optical determination for one analyte of interest in the fluid sample; and

means for concurrently observing the fluid sample via said at least one sample viewing zone on one of said discrete optic array surfaces.

6. The detection apparatus as recited in claim 5 further comprising automated means for concurrently introducing light energy and detecting emerging light.

7. The detection apparatus as recited in claim 5 wherein said means for detecting emerging light energy provides a visualized discrete optical image.

8. The detection apparatus as recited in claim 5 further comprising a computer controlled imaging and data processing system.

9. A method for detecting at least one analyte of interest in a fluid sample, the detection of each analyte being correlatable with an individual optical determination, said method comprising the steps of:

obtaining a fiber optic sensor comprised of

(a) a preformed, unitary fiber optic array comprising a plurality of individually clad, fiber optic strands disposed co-axially along their lengths and having two discrete optic array ends each of which is formed of multiple strand end faces, said preformed, unitary fiber optic array being of determinable configuration and dimensions, said two discrete optic array ends of said preformed, unitary fiber optic array presenting two discrete optic array surfaces for introduction and conveyance of light energy;

(b) at least one sensing zone comprising not less than one light energy absorbing dye disposed as an uninterrupted deposit in aligned organization upon said multiple strand end faces at different spatial positions on one of said discrete optic fiber array surfaces of said preformed, unitary fiber optic array, the different spatial positioning of each uninterrupted dye deposit in aligned organization upon said one of said discrete optic array surfaces serving to identify and distinguish each light energy absorbing dye from all other light energy absorbing dyes disposed within said at least one sensing zone, each spatially positioned uninterrupted dye deposit reacting with one analyte of interest; and

(c) at least one sample viewing zone adjacent to said at least one sensing zone on said one of said discrete optic array surfaces of said preformed, unitary fiber optic array, said at least one sample viewing zone being formed of said multiple strand end faces in aligned organization and in fixed spatial position on said one of said discrete optic array surfaces;

placing said spatially positioned uninterrupted dye deposit within said at least one sensing zone on one of said discrete optic array surfaces of said fiber optic sensor into reactive contact with a fluid sample;

introducing light energy to one of said discrete optic array surfaces of said fiber optic sensor such that said plurality of individually clad fiber optical strands convey said introduced light energy concurrently and illuminate said spatially positioned uninterrupted dye deposit within said at least one sensing zone on said optic array surface;

detecting emerging light energy from said illuminated spatially positioned uninterrupted dye deposit within said at least one sensing zone on one of said discrete optic array surfaces, said detected emerging light energy serving as an optical determination for one analyte of interest in the fluid sample; and

concurrently observing the fluid sample via said at least one sample viewing zone on one of said discrete optic array surfaces.

10. The detection method as recited in claim 9 wherein said detection is made in-vivo.

11. The detection method as recited in claim 9 wherein said detection is made in-vitro.

12. The detection method as recited in claim 9 wherein said detection is made using an automatic imaging and data processing system.