Imaging fiber optic array sensors, apparatus, and methods for concurrently detecting multiple analytes of interest in a fluid sample

• US 5,244,636 A
• Filed: 01/25/1991
• Issued: 09/14/1993
• Est. Priority Date: 01/25/1991
• Status: Expired due to Term

• Current Assignee: Trustees of Tufts College
• Original Assignee: Trustees of Tufts College
• Inventors: Walt, David R., Barnard, Steven M.
• Primary Examiner(s): Warden, Robert J.
• Assistant Examiner(s): NOT, DEFINED
• Application Number:
  US07/645,787
• Time in Patent Office: 963 Days
• Field of Search: 422/68.1, 422/82.05, 422/82.06, 422/82.07, 422/82.08, 422/82.09, 435/808, 435/291, 436/164, 436/172, 436/800, 436/805, 128/634, 356/39, 250/227.23, 385/12
• US Class Current: 422/82.07
• CPC Class Codes: G01N 2021/6434 Optrodes
• CPC Class Codes: G01N 2021/773 Porous polymer jacket; Polymer matrix with indicator
• CPC Class Codes: G01N 2021/7786 Fluorescence
• CPC Class Codes: G01N 2021/7793 Sensor comprising plural indicators
• CPC Class Codes: G01N 21/6456 Spatial resolved fluorescence measurements; Imaging
• 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: 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
• CPC Class Codes: G02B 6/3624 Fibre head, e.g. fibre probe termination optical details of light guide terminations G02B6/241; reshaping of light guides G02B6/2552; optical details of coupling light into or out of fibre end G02B6/262
• CPC Class Codes: G02B 6/3644 the coupling means being through-holes or wall apertures
• CPC Class Codes: G02B 6/3652 the additional structures being prepositioning mounting areas, allowing only movement in one dimension, e.g. grooves, trenches or vias in the microbench surface, i.e. self aligning supporting carriers
• CPC Class Codes: G02B 6/3672 with fibres arranged in a regular matrix array

Abstract

The present invention provides a unique fiber optic sensor which is able to conduct multiple assays and analysis concurrently using a plurality of different dyes immobilized at individual spatial positions 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 of interest 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 optical 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; and

at least 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 array surfaces of said preformed, unitary fiber optic array, the different spatial positioning of each uninterrupted deposit in aligned organization upon said one discrete optic array surface serving to identify and distinguish each light energy absorbing dye from all other light energy absorbing dyes which may be disposed on said one discrete optic array surface, each spatially positioned dye reacting specifically with one analyte of interest.

3. The fiber optic sensor as recited in claim 1 or 2 wherein said light energy is one selected from the group consisting of infrared, visible, and ultraviolet wavelengths.

4. The fiber optic sensor as recited in claim 1 or 2 wherein said at least one light energy absorbing dye is selected from the group consisting of fluorophores, fluorescent enzyme substrates, and fluorescent antibody conjugates.

5. The fiber optic sensor as recited in claim 1 or 2 wherein said at least one light energy absorbing dye is a chromophore.

2. A fiber optic sensor for concurrently detecting multiple analytes of interest in a fluid sample, the detection of each analyte of interest 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 optical 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; and

at least two different light energy absorbing dyes disposed individually as an uninterrupted deposit in aligned organization upon said multiple strand end faces at different spatial positions on one of said discrete optic array surfaces of said preformed, unitary fiber optic array, the different spatial positioning of each uninterrupted deposit in aligned organization upon said one discrete optic array surface serving to identify and distinguish each light energy absorbing dye from all other light energy absorbing dyes disposed on said one discrete optic array surface, each of said spatially positioned dyes reacting specifically with one analyte of interest.

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

a fiber optic sensor comprised of

a preformed, unitary fiber optic array comprising a plurality of individually clad, fiber optical 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, and

at least 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 array surfaces of said preformed, unitary fiber optic array, the different spatial positioning of each uninterrupted deposit in aligned organization upon said one discrete optic array surface serving to identify and distinguish each light energy absorbing dye from all other light energy absorbing dyes which may be disposed on said one discrete optic array surface, each spatially positioned dye reacting specifically with one analyte of interest;

means for placing said spatially positioned dye on said one discrete optic array surface of said fiber optic sensor into reactive contact with a fluid sample;

means for introducing light energy to an optic array surface of said fiber optic sensor such that said fiber optical strands convey said introduced light energy concurrently and illuminate said spatially positioned dye on said one discrete optic array surface; and

means for detecting emerging light energy from said illuminated spatially positioned dye disposed on said one discrete optic array surface, said detected emerging light energy serving as an optical determination for one analyte of interest in the fluid sample.

8. The detection apparatus as recited in claim 6 or 7 further comprising automated means for concurrently introducing light energy and concurrently detecting emerging light energy.

9. The detection apparatus as recited in claim 6 or 7 wherein said detected emerging light energy is visualized as a discrete image of varying light intensity.

10. The detection apparatus as recited in claim 6 or 7 further comprising a computer controlled imaging and data processing system.

7. An apparatus for concurrently detecting multiple analytes of interest in a fluid sample, the detection of each analyte of interest being correlatable with an individual optical determination, said apparatus comprising:

a fiber optic sensor comprised of

a preformed, unitary fiber optic array comprising a plurality of individually clad, fiber optical 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 or light energy, and

at least two different light energy absorbing dyes disposed individually as an uninterrupted deposit in aligned organization upon said multiple strand end faces at different spatial positions on one of said discrete optic array surfaces of said preformed, unitary fiber optic array, the different spatial positioning of each uninterrupted deposit in a aligned organization upon said one discrete optic array surface serving to identify and distinguish each light energy absorbing dye from all other light energy absorbing dyes disposed on said one discrete optic array surface, each of said spatially positioned dyes reacting specifically with one analyte of interest;

means for placing said spatially positioned dyes on said one discrete optic array surface of said fiber optic sensor into reactive contact with a fluid sample;

means for concurrently introducing light energy to the optic array surface of said fiber optic sensor such that said fiber optical strands convey said introduced light energy concurrently and illuminate said spatially positioned dyes on said one discrete optic array surface concurrently; and

means for concurrently detecting emerging light energy from each of said illuminated spatially positioned dyes disposed on said one discrete optic array surface, said detected emerging light energy from each of said spatially positioned dyes serving as an optical determination for one analyte of interest in the fluid sample.

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

obtaining a fiber optic sensor comprised of

a preformed, unitary fiber optic array comprising a plurality of individually clad, fiber optical 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, and

at least one 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 array surfaces of said preformed, unitary fiber optic array, the different spatial positioning as each uninterrupted deposit in aligned organization upon said one discrete optic array surface serving to identify and distinguish each light energy absorbing dye from all other light energy absorbing dyes which may be disposed on said one discrete optic array surface, each spatially positioned dye reacting specifically with one analyte of interest;

placing said spatially positioned dye on said one discrete optic array surface of said fiber optic sensor into reactive contact with a fluid sample;

introducing light energy to an optic array surface of said fiber optic sensor such that said fiber optical strands convey said introduced light energy concurrently and illuminate said spatially positioned dye on said one discrete optic array surface; and

detecting emerging light energy from said illuminated spatially positioned dye disposed on said one discrete optic array surface, said detected emerging light energy serving as an optical determination for one analyte of interest in the fluid sample.

13. The detection method as recited in claim 11 or 12 wherein said detection is made in-vitro.

14. The detection method as recited in claim 11 or 12 wherein said detection is made in-vivo.

15. The detection method as recited in claim 11 or 12 wherein said detection is performed using an automated imaging and data processing system.

12. A method for concurrently detecting multiple analytes of interest in a fluid sample, the detection of each analyte of interest being correlatable with an individual optical determination, said method comprising the steps of:

obtaining a fiber optic sensor comprised of

a preformed, unitary fiber optic array comprising a plurality of individually clad, fiber optical 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, and

at least two different light energy absorbing dyes disposed individually as an uninterrupted deposit in aligned organization upon said multiple strand end faces at different spatial positions on one of said discrete optic array surfaces of said preformed, unitary fiber optic array, the different spatial positioning of each uninterrupted deposit in aligned organization upon said one discrete optic array surface serving to identify and distinguish each light energy absorbing dye from all other light energy absorbing dyes disposed on said one discrete optic array surface, each of said spatially positioned dyes reacting specifically with one analyte of interest;

placing said spatially positioned dyes on said one discrete optic array surface of said fiber optic sensor into reactive contact with a fluid sample;

concurrently introducing light energy to an optic array surface of said fiber optic sensor such that said fiber optical strands convey said introduced light energy concurrently and illuminate said spatially positioned dyes on said one discrete optic array surface concurrently; and

concurrently detecting emerging light energy from each of said illuminated spatially positioned dyes disposed on said one discrete optic array surface, said detected emerging light energy from each of said spatially positioned dyes serving as an optical determination for one analyte of interest in the fluid sample.