Optical sensor apparatus for far-field viewing and making optical analytical measurements at remote locations

• US 5,814,524 A
• Filed: 12/14/1995
• Issued: 09/29/1998
• Est. Priority Date: 12/14/1995
• Status: Expired due to Term

• Current Assignee: Trustees of Tufts College
• Original Assignee: Trustees of Tufts College
• Inventors: Chadha, Suneet, Michael, Karri L, Walt, David R.
• Primary Examiner(s): Chin, Christopher L.
• Application Number:
  US08/572,005
• Time in Patent Office: 1,020 Days
• Field of Search: 385/12, 385/115, 385/123, 422/55, 422/57, 422/58, 422/82.05-82.09, 422/82.11, 435/287.1, 435/287.2, 435/288.7, 435/808, 436/164, 436/165, 436/172, 436/518, 436/527, 436/800, 436/805
• US Class Current: 436/518
• 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 21/6452 Individual samples arranged in a regular 2D-array, e.g. multiwell plates
• CPC Class Codes: G01N 21/6456 Spatial resolved fluorescence measurements; Imaging
• CPC Class Codes: Y10S 435/808 Optical sensing apparatus
• CPC Class Codes: Y10S 436/80 Fluorescent dyes, e.g. rhodamine
• CPC Class Codes: Y10S 436/805 Optical property

Abstract

The present invention is an optical sensor apparatus for far-field viewing and imaging as well as for the optical detection and analytical measurement of at least one species of analyte in a remotely-positioned fluid sample. The apparatus employs an imaging fiber comprising a fiber optic array and a Gradient Index lens; and utilizes a remotely-positioned solid substrate having light energy absorbing indicator ligands on an external surface for reactive contact with individual species of analytes when present in a fluid sample. The optical sensor apparatus is able to view an object and provide an image of the object located at a pre-set optical distance remote from the imaging fiber. The apparatus is also able to detect and identify, qualitatively and quantitatively, one or more analytes of interest in a flowing solid, gaseous, or liquid sample at remote locations distanced from the imaging fiber itself.

Claims

1. An optical sensor apparatus for far-field viewing and detection of at least one species of analyte in a remotely-position fluid sample, the detection of a species of analyte being correlatable with far-field optical determination, said optical sensor apparatus comprising:

a far-field imaging fiber comprised of

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

(b) a gradient index lens joined to and optically aligned with an optic array end surface of said unitary fiber optic array for far-field viewing of an object located within a predetermined range of optical distances from said lens;

a remotely-positioned solid substrate spaced apart from but lying within said predetermined range of optical distances from said imaging fiber, said solid substrate providing, at least one discrete reaction surface in alignment with and suitable for far-field viewing via said imaging fiber,

at least one light energy absorbing indicator ligand disposed on said discrete reaction surface of said remotely-positioned solid substrate, said indicator ligand providing a characteristic detectable optical response of time-varying light intensity at at least one wavelength, said response being indicative of an individual species of analyte when present in a fluid sample;

means for placing a fluid sample into reactive contact with said light energy absorbing indicator ligand on said reaction surface of said remotely-positioned solid substrate;

means for introducing excitation light energy to said light energy absorbing indicator ligand on said reaction surface of said remotely-positioned solid substrate; and

means for detecting light energy emerging from said indicator ligand on said reaction surface of said remotely-positioned solid substrate which has been introduced and collected by said imaging fiber, said detected emerging light energy serving as a measure for determining a species of analyte in the fluid sample.

3. The optical sensor apparatus as recited in claim 1 or 2 wherein said gradient index lens further comprises an anti-reflective coating.

4. The optical sensor apparatus as recited in claim 1 or 2 wherein said indicator ligand comprises a fluorophoric dye.

5. The optical sensor apparatus as recited in claim 1 or 2 wherein said indicator ligand comprises a chromophoric dye.

6. The optical sensor apparatus as recited in claim 1 or 2 wherein said indicator ligand comprises a moiety selected from the group consisting enzymes, antibodies, oligonucleotides, fluorescent precursor compositions, and chromophore precursor compositions.

7. The optical sensor apparatus as recited in claim 1 or 2 wherein said solid substrate further comprises a plurality of different reaction surfaces.

8. The optical sensor apparatus as recited in claim 1 or 2 wherein said solid substrate further comprises a housing.

9. The optical sensor apparatus as recited in claim 1 or 2 further comprises ingress means for delivering a fluid sample to said reaction surface of said solid substrate.

10. The optical sensor apparatus as recited in claim 1 or 2 further comprises egress means for removing a fluid sample from said reaction surface of said solid substrate.

11. The optical sensor apparatus as recited in claim 1 or 2 wherein said solid substrate takes form as an entity selected from the group consisting of a multiwell plate, a bead, a sieve, a screen, a netting, a multiwell tray, a multiwell rack, a dish, and a cover slip.

12. The optical sensor apparatus as recited in claim 1 or 2 wherein said reaction surface of said solid substrate comprises a coating material for inhibiting undesirable chemical or biological reactions.

2. An optical sensor apparatus for far-field viewing and detection of multiple species of analyte in a remotely-positioned fluid sample, the detection of a species of analyte being correlatable with an individual far-field optical determination, said optical sensor apparatus comprising:

a far-field imaging fiber comprised of

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

(b) a gradient index lens joined to and optically aligned with an optic array end of said unitary fiber optic array for far-field viewing of an object located within a predetermined range of optical distances from said lens;

a remotely-positioned solid substrate spaced apart from but lying with said predetermined range of optical distances from said imaging fiber, said solid substrate providing at least one discrete reaction surface in alignment with and suitable for far-field viewing via said imaging fiber;

at plurality of light energy absorbing indicator ligands disposed individually at different spatial locations on said discrete reaction surface of said remotely-positioned solid substrate, at least one of said indicator ligands providing a characteristic detectable optical response of time-varying light intensity at at least one wavelength, said response being indicative of an individual species of analyte when present in a fluid sample;

means for placing a fluid sample into reactive contact with said plurality of light energy absorbing indicator ligands on said reaction surface of said remotely-positioned solid substrate;

means for introducing excitation light energy of predetermined wavelength to at least one of said light energy absorbing indicator ligands on said reaction surface of said remotely-positioned solid substrate; and

means for detecting light energy emerging individually from at least one of said indicator ligands on said reaction surface of said remotely-positioned solid substrate which has been introduced to and collected by said imaging fiber, each detected emerging light energy serving as a measure for determining the presence of one species of analyte in the fluid sample.