Optical sensor, optical sensing apparatus, and methods for detecting an analyte of interest using spectral recognition patterns

• US 5,512,490 A
• Filed: 08/11/1994
• Issued: 04/30/1996
• Est. Priority Date: 08/11/1994
• Status: Expired due to Term

• Current Assignee: Trustees of Tufts College
• Original Assignee: Trustees of Tufts College
• Inventors: Walt, David R., Kauer, John S.
• Primary Examiner(s): Snay, Jeffrey R.
• Application Number:
  US08/289,001
• Time in Patent Office: 628 Days
• Field of Search: 422/82.06, 422/82.07, 422/82.05, 422/82.08, 422/86, 422/91, 436/171, 436/172, 436/164, 250/458.1, 250/271, 250/461.1, 250/461.2, 250/459.1, 356/317, 356/318, 356/417
• US Class Current: 436/171
• CPC Class Codes: G01N 2021/6484 Optical fibres
• 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 21/6452 Individual samples arranged in a regular 2D-array, e.g. multiwell plates
• CPC Class Codes: G01N 21/77 by observing the effect on a chemical indicator

Abstract

The present invention is an optical detection and identification system and provides an optic sensor, an optic sensing apparatus and methodology for detecting and evaluating one or more analytes or ligands of interest, either alone or in admixture. The optic sensor of the system is comprised of a supporting member and an array formed of heterogeneous, semi-selective thin films which function as sensing receptor units and are able to detect a variety of different analytes and ligands using spectral recognition patterns.

Claims

1. An optical sensor for detecting an analyte of interest in a fluid sample, said optical sensor comprising:

a supporting member; and

an optic array formed of multiple semi-selective sensing receptor units which differ in their constituent chemical formulations, which differ in their spectral characteristics, which are immobilized at different spatial positions on said supporting member for reactive contact with the fluid sample, and which react concurrently and semi-selectively but spectrally differently with an individual analyte of interest, each of said multiple semi-selective sensing receptor units of said optic array being comprised of

a polymeric substance of predetermined chemical composition, and

a semi-selective dye compound of predetermined chemical composition which has characteristic spectral properties, is disposed in admixture with said polymeric substance, and can react semi-selectively and spectrally differently over time with more than one analyte,

(a) wherein said admixed dye compound absorbs light energy of a predetermined wavelength and, in the presence of said polymeric substance without an analyte able to react semi-selectively, yields a baseline spectral response over time which is optically detectable and recognizable as showing an absence of analyte, and

(b) wherein said admixed dye compound absorbs light energy of a predetermined wavelength and, in the presence of said polymeric substance and at least one analyte of interest able to react semi-selectively, generates a modified spectral response over time which is optically detectable and recognizable as showing the spectral consequence of semi-selective reaction with the analyte of interest,

said multiple semi-selective sensing receptor units of said optic array presenting a plurality of differing and alternative modified spectral responses after concurrent semi-selective reaction with the analyte of interest in the fluid sample, the spectral pattern formed collectively by said plurality of differing and alternative modified spectral responses resulting in spectral recognition progression pattern means by which to detect and identify that analyte of interest.

2. An optical sensor for detecting a first analyte of interest which is intermixed with at least one other analyte of interest in a fluid sample, said optical sensor comprising:

a supporting member; and

an optic array formed of multiple semi-selective sensing receptor units which differ in their constituent chemical formulations, which differ in their spectral characteristics, which are immobilized at different spatial positions on said supporting member for reactive contact with the fluid sample, and which react concurrently and semi-selectively but spectrally differently with an individual analyte of interest, each of said multiple semi-selective sensing receptor units of said optic, array being comprised of

a polymeric substance of predetermined chemical composition, and

a semi-selective dye compound of predetermined chemical composition which has characteristic spectral properties, is disposed in admixture with said polymeric substance, and can react semi-selectively and spectrally differently over time with more than one analyte,

(a) wherein said admixed dye compound absorbs light energy of a predetermined wavelength and, in the presence of said polymeric substance without an analyte able to react semi-selectively, yields a baseline spectral response which is optically detectable and recognizable as showing an absence of analyte, and

(b) wherein said admixed dye compound absorbs light energy of a predetermined wavelength and, in the presence of said polymeric substance and a first analyte of interest able to react semi-selectively, generates a first modified spectral response over time which is optically detectable and recognizable as showing the spectral consequence of semi-selective reaction with the first analyte of interest, and

(c) wherein said admixed dye compound absorbs light energy of a predetermined wavelength and, in the presence of said polymeric substance and at least a second analyte of interest able to react semi-selectively, generates a second modified spectral response which is optically detectable and recognizable as showing the spectral consequence of semi-selective reaction with the second analyte of interest,

said multiple semi-selective sensing receptor units of said optic array presenting a plurality of differing and alternative modified spectral responses after semi-selective reaction with each of said first and second analytes of interest, the spectral pattern formed collectively by said plurality of differing and alternative modified spectral responses for each of said first and second analytes of interest resulting in individual spectral recognition progression pattern means by which to detect and identify each of the analytes of interest in the fluid sample.

3. An optical sensing apparatus for detecting an analyte of interest in a fluid sample, said optical sensing apparatus comprising:

a supporting member; and

an optic array formed of multiple semi-selective sensing receptor units which differ in their constituent chemical formulations, which differ in their spectral characteristics, which are immobilized at different spatial positions on said supporting member for reactive contact with the fluid sample, and which react concurrently and semi-selectively but spectrally differently with an individual analyte of interest, each of said multiple semi-selective sensing receptor units of said optic array being comprised of

a polymeric substance of predetermined chemical composition, and

a semi-selective dye compound of predetermined chemical composition which has characteristic spectral properties, is disposed in admixture with said polymeric substance, and can react semi-selectively and spectrally differently with more than one analyte,

(a) wherein said admixed dye compound absorbs light energy of a predetermined wavelength and, in the presence of said polymeric substance without an analyte able to react semi-selectively, yields a baseline spectral response over time which is optically detectable and recognizable as showing an absence of analyte, and

(b) wherein said admixed dye compound absorbs light energy of a predetermined wavelength and, in the presence of said polymeric substance and at least one analyte of interest able to react semi-selectively, generates a modified spectral response over time which is optically detectable and recognizable as showing the spectral consequence of semi-selective reaction with the analyte of interest,

said multiple semi-selective sensing receptor units of said optic array presenting a plurality of differing and alternative modified spectral responses after concurrent semi-selective reaction with the analyte of interest in the fluid sample, the spectral pattern formed collectively by said plurality of differing and alternative modified spectral responses for an analyte of interest resulting in spectral recognition progression pattern means by which to detect and identify that analyte of interest;

means for introducing a fluid sample to said optic array for semi-selective reactive contact;

means for introducing light energy of a predetermined wavelength to said multiple semi-selective sensing receptor units of said optic array; and

computerized optical detection and evaluation means for optically detecting said plurality of differing and alternative modified spectral responses generated by said semi-selective sensing receptor units and for evaluating said resulting spectral recognition progression pattern means to determine the presence of that analyte of interest in the fluid sample.

4. An optical sensing apparatus for detecting a first analyte of interest which is intermixed with at least one other analyte of interest in a fluid sample, said optical sensing apparatus comprising:

a supporting member; and

an optic array formed of multiple semi-selective sensing receptor units which differ in their constituent chemical formulations, which differ in their spectral characteristics, which are immobilized at different spatial positions on said supporting member for reactive contact with the fluid sample, and which react concurrently and semi-selectively but spectrally differently with an individual analyte of interest, each of said multiple semi-selective sensing receptor units of said optic array being comprised of

a polymeric substance of predetermined chemical composition, and

a semi-selective dye compound of predetermined chemical composition which has characteristic spectral properties, is disposed in admixture with said polymeric substance, and can react semi-selectively and spectrally differently over time with more than one analyte,

(a) wherein said admixed dye compound absorbs light energy of a predetermined wavelength and, in the presence of said polymeric substance without an analyte able to react semi-selectively, yields a baseline spectral response over time which is optically detectable and recognizable as showing an absence of analyte, and

(b) wherein said admixed dye compound absorbs light energy of a predetermined wavelength and, in the presence of said polymeric substance and a first analyte of interest able to react semi-selectively, generates a modified spectral response over time which is optically detectable and recognizable as showing the spectral consequence of semi-selective reaction with the analyte of interest, and

(c) wherein said admixed dye compound absorbs light energy of a predetermined wavelength and, in the presence of said polymeric substance and at least a second analyte of interest able to react semi-selectively, generates a second modified spectral response over time which is optically detectable and recognizable as showing the spectral consequence of semi-selective reaction with the second analyte of interest,

said multiple semi-selective sensing receptor units of said optic array presenting a plurality of differing and alternative modified spectral responses after concurrent semi-selective reaction with each of the first and second analytes of interest, the spectral pattern formed collectively by said plurality of differing and alternative modified spectral responses for each of the first and second analytes of interest resulting in individual spectral recognition progression pattern means by which to detect and identify each of the analytes of interest in the fluid sample;

means for introducing a fluid sample to said optic array for semi-selective reactive contact;

means for introducing light energy of a predetermined wavelength to said multiple semi-selective sensing receptor units of said optic array; and

computerized optical detection and evaluation means for optically detecting said plurality of differing and alternative modified spectral responses generated by said semi-selective sensing receptor units and for evaluating said resulting spectral recognition progression pattern means individually to determine the presence of each of the analytes of interest in the fluid sample.

5. An optical method for detecting an analyte of interest in a fluid sample, said optical method comprising the steps of:

providing an optical sensor comprised of

a supporting member; and

an optic array formed of multiple semi-selective sensing receptor units which differ in their constituent chemical formulations, which differ in their spectral characteristics, which are immobilized at different spatial positions on said supporting member for reactive contact with the fluid sample, and which react concurrently and semi-selectively but spectrally differently with an individual analyte of interest, each of said multiple semi-selective sensing receptor units of said optic array being comprised of

(a) a polymeric substance of predetermined chemical composition, and

(b) a semi-selective dye compound of predetermined chemical composition which has characteristic spectral properties, is disposed in admixture with said polymeric substance, and can react semi-selectively and spectrally differently over time with more than one analyte,

(i) wherein said admixed dye compound absorbs light energy of a predetermined wavelength and, in the presence of said polymeric substance without an analyte able to react semi-selectively, yields a baseline spectral response progression over time which is optically detectable and recognizable as showing an absence of analyte, and

(ii) wherein said admixed dye compound absorbs light energy of predetermined wavelength and, in the presence of said polymeric substance and an analyte of interest able to react semi-selectively, generates a modified spectral response over time which is optically detectable and recognizable as showing the spectral consequence of semi-selective reaction with the analyte of interest,

said multiple semi-selective sensing receptor units of said optic array presenting a plurality of differing and alternative modified spectral responses after concurrent semi-selective reaction with the analyte of interest, the spectral pattern formed collectively by said plurality of differing and alternative modified spectral responses resulting in spectral recognition progression pattern means by which to detect and identify that analyte of interest;

introducing the fluid sample to said optical sensor for semi-selective reactive contact;

introducing light energy of a predetermined wavelength to said multiple semi-selective sensing receptor units of said optical sensor;

optically detecting said plurality of differing and alternative modified spectral responses generated over time by said semi-selective sensing receptor units of said optical sensor collectively to form said resulting spectral recognition progression pattern means; and

evaluating said resulting spectral recognition progression pattern means using computerized means to determine the presence of that analyte of interest in the fluid sample.

6. An optical method for detecting a first analyte of interest which is intermixed with at least one other analyte of interest in a fluid sample, said method comprising the steps of:

providing an optical sensor comprising;

a supporting member; and

an optic array formed of multiple semi-selective sensing receptor units which differ in their constituent chemical formulations, which differ in their spectral characteristics, which are immobilized at different spatial positions on said supporting member for reactive contact with the fluid sample, and which react concurrently and semi-selectively but spectrally differently with an individual analyte of interest, each of said multiple semi-selective sensing receptor units of said optic array being comprised of

(a) a polymeric substance of predetermined chemical composition, and

(b) a semi-selective dye compound of predetermined chemical composition which has characteristic spectral properties, is disposed in admixture with said polymeric substance, and can react semi-selectively and spectrally differently over time with more than one analyte,

(i) wherein said admixed dye compound absorbs light energy of a predetermined wavelength and, in the presence of said polymeric substance without an analyte able to react semi-selectively, yields a baseline spectral response over time which is optically detectable and recognizable as showing an absence of analyte, and

(ii) wherein said admixed dye compound absorbs light energy of a predetermined wavelength and, in the presence of said polymeric substance and a first analyte of interest able to react semi-selectively, generates a first modified spectral response over time which is optically detectable and recognizable as showing the spectral consequence of semi-selective reaction with the first analyte of interest, and

(iii) wherein said admixed dye compound absorbs light energy of a predetermined wavelength and, in the presence of said polymeric substance and at least a second analyte of interest able to react semi-selectively, generates a second modified spectral response over time which is optically detectable and recognizable as showing the spectral consequence of semi-selective reaction with a second analyte of interest,

said multiple semi-selective sensing receptor units of said optic array presenting a plurality of differing and alternative modified spectral responses after concurrent semi-selective reaction with each of the first and second analytes of interest, the spectral pattern formed collectively by said plurality of differing and alternative modified spectral responses for each of the first and second analytes of interest resulting in individual spectral recognition progression pattern means by which to detect and identify each of the analytes of interest;

introducing the fluid sample to said optical sensor for semi-selective reactive contact;

introducing light energy of a predetermined wavelength to said multiple semi-selective sensing receptor units of said optical sensor;

optically detecting said plurality of differing and alternative modified spectral responses generated by said semi-selective sensing receptor units of said optical sensor collectively to form individual resulting spectral recognition progression pattern means; and

evaluating said resulting spectral recognition progression pattern means individually using computerized means to determine the presence of each of the analytes of interest in the fluid sample.