CA2283742A1 - Fiber optic sensor with encoded microspheres - Google Patents

Fiber optic sensor with encoded microspheres Download PDF

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Publication number
CA2283742A1
CA2283742A1 CA002283742A CA2283742A CA2283742A1 CA 2283742 A1 CA2283742 A1 CA 2283742A1 CA 002283742 A CA002283742 A CA 002283742A CA 2283742 A CA2283742 A CA 2283742A CA 2283742 A1 CA2283742 A1 CA 2283742A1
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Prior art keywords
beads
chemical
optical
subpopulation
wells
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CA002283742A
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French (fr)
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CA2283742C (en
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David R. Walt
Karri L. Michael
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Tufts University
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Trustees Of Tufts College
David R. Walt
Karri L. Michael
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    • G01N21/7703—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator using reagent-clad optical fibres or optical waveguides
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    • Y10S435/808—Optical sensing apparatus

Abstract

A microsphere-based analytic chemistry system is disclosed in which microspheres carrying different chemical functionalities may be mixed together while the ability is retained to identify the functionality on each bead using an optically interrogatable encoding scheme. An optical fiber bundle sensor is also disclosed in which the separate microsphere may be optically coupled to discrete fibers or groups of fibers within the bundle. The functionalities are encoded on the separate microspheres using fluorescent dyes and then affixed to wells etched in the end of the bundle. Thus, a single sensor may carry thousands of chemistries. Only those microspheres exhibiting reactions then need to be decoded to identify the corresponding functionality.

Claims (38)

1. An analytic chemistry system, comprising a population of beads including separate subpopulations, each subpopulation carrying chemical functionality which changes an optical signature of the beads in the presence of targeted analytes, beads in each subpopulation having an optical signature which is encoded with a description of the chemical functionality carried by that subpopulation.
2. The system described in Claim 1, wherein the beads are encoded using dyes.
3. The system described in Claim 2, wherein the dyes are entrapped within the beads and the chemical functionality is on surfaces of the beads.
4. The system described in Claim 1, wherein the beads are encoded using fluorescent dyes.
5. The system described in Claim 1, wherein the beads are encoded by controlling a ratio of at least two dyes.
6. The system described in Claim 1, wherein the chemical functionality changes the optical signature by producing an optically active chemical in the presence of targeted analytes.
7. The system described in Claim 1, wherein the optical signature is changed by the chemical functionalities of the beads by the presence or absence of a fluorescent signal.
8. The system described in Claim 1, wherein the chemical functionalities of the beads support sites for hybridization.
9. The system described in Claim 1, wherein the beads are affixed to a distal end of an optical fiber bundle.
10. The system described in Claim 1, wherein the beads are located within etched wells at terminal ends of optical fibers of the bundle.
11. A chemical analysis method, comprising preparing separate subpopulations of beads, each subpopulation carrying chemical functionalities that change optical signatures of the beads in the presence of targeted analytes;
encoding optical signature of the beads in each subpopulation with a description of the chemical functionalities carried by that subpopulation;
combining the subpopulations to produce a system;
applying the system;
detecting changes in the optical signatures indicative of a presence of the targeted analytes;
and decoding optical signature of the beads to identify the chemical functionalities.
12. The.method described in Claim 11, wherein encoding the optical signatures with the chemical functionalities comprises doping the beads with fluorescent dyes.
13. The method described in Claim 11, wherein encoding the optical signatures with chemical functionalities comprises attaching encoding dyes to the beads.
14. The method described in Claim 11, wherein encoding the optical signatures with the chemical functionalities comprises controlling a ratio of at least two dyes carried by each bead.
15. The method described in Claim 11, further comprising:
encoding the beads with the chemical functionalities by entrapping dyes within or attaching dyes to the beads; and applying the chemical functionalities to the beads.
16. The method described in Claim 11, further comprising enabling the chemical functionalities to produce an optically active species in the presence of targeted-analytes to change the optical signature.
17. The method described in Claim 11, further comprising changing the optical signature by the presence or absence of a fluorescent signal from the beads.
18. The method described in Claim 11, further comprising enabling the chemical functionalities to hybridize.
19. An analytic chemistry sensor, comprising:

a bundle of optical fibers;
a population of beads carrying chemical functionalities at a distal end of the fiber optic bundle, light from individual bead being coupled into separate or groups of separate fibers of the bundle for transmission to the proximal end of the bundle.
20. The sensor described in Claim 19, wherein each one of the beads is located within separate wells formed at terminal ends of optical fibers of the bundle.
21. The sensor described in Claim 20, wherein the wells are formed by anisotropic etching of the cores of the optical fibers with respect to the cladding.
22. The sensor described in Claim 19, further comprising a light source for exciting optically active chemicals bound to the chemical functionalities.
23. The sensor described in Claim 19, wherein the population of beads includes separate subpopulations, each subpopulation carrying a different chemical functionality and an optically interrogatable code descriptive of the chemical functionality.
24. The sensor described in Claim 23, further comprising a light source for exciting optically active chemicals bound to the chemical functionalities.
25. The sensor described in Claim 23, wherein code of each subpopulation comprises fluorescent dyes.
26. The sensor described in Claim 23, further comprising a filter and a frame capturing camera for detecting optical signatures indicative of a status of the chemical functionalities and optical signatures indicative of the encoding of the beads.
27. A method for constructing and using an analytic chemistry sensor, comprising:
forming wells at terminal ends of optical fibers within a bundle;
distributing beads carrying chemical functionalities within the wells; and monitoring a status of the chemical functionalities from a proximal end of the bundle.
28. The method described in Claim 27, wherein forming the wells comprises anisotropically etching of cores of the optical fibers with respect to cladding.
29. The method described in Claim 27, further comprising forming a population of beads in the wells from separate subpopulations, each subpopulation carrying a different chemical functionality and an optically interrogatable code descriptive of the chemical functionality.
30. The method described in Claim 29, further comprising randomly distributing the subpopulations within the wells.
31. The method described in Claim 29, further comprising serially adding the subpopulations to the wells.

24 What is claimed is:
32. A composition comprising a plurality of optical fibers in an optical fiber array and a population of microspheres, wells at a first terminal end of said array, a plurality of said wells containing at least one of said microspheres.
33. A composition comprising:
a) a population of microspheres comprising separate subpopulations, each subpopulation comprising:
1) a chemical functionality for interacting with a target analyte; and ii) an encoding optical signature that can be used to identify said chemical functionality; and b) an optical fiber array, wherein said microspheres are located within wells at a first terminal end of said array.
34. A composition according to claim 33 wherein said encoding optical signature comprises at least one fluorescent dye.
35. A composition according to claim 33 or 34 wherein said encoding optical signature comprises a ration of at least two or more fluorescent dyes.
36. A composition according to claim 33, 34, or 35 wherein said chemical functionality is selected from the group consisting of nucleic acids, antibodies and enzymes.
37. A composition according to claim 33, 34, or 35 wherein said chemical functionality is selected from the group consisting of fluorophores, chromophores, phosphors, pH
indicators, cation indicators, anion indicators, metal ion indicators, ion salt indicators, oxygen indicators, and carbon dioxide indicators.
33. A. composition according to claim 33, 34, 35, 36 and 37 further comprising a detecting optical signature for each subpopulation that can be used to identity the presence or absence of a target analyte.
39. A composition according to claim 38 wherein said detecting optical signature comprises at least one dye selected from the group consisting of fluorophores, chromophores, and phosphors.
40. A composition according to claim 32, 33, 34, 35, 36, 37,
38, or 39 further comprising a light source.
41. A composition according to claim 40 further comprising a light detector.
42. A method of determining the presence of a target analyte in a sample comprising:
a) contacting said sample with a composition comprising:
i) a population of microspheres comprising separate subpopulations, each subpopulation comprising:
1) a chemical functionality for interacting with a target analyte; and 2) an encoding optical signature that can be used to identify said chemical functionality;
ii) an optical fiber array, wherein. said microspheres are located within wells at a first terminal end of said array; and b) determining the presence or absence of the target analyte.
43 . A method according to claim 42 further comprising identifying the location of each microsphere subpopulation on said terminal end.
44. A method according to claim 42 or 43 wherein said encoding optical signature comprises at least one fluorescent dye.
45. A method according to claim 42 , 43 or 44 wherein said encoding optical signature comprises a ratio of at least two or more fluorescent dyes.
45. A method according to claim 42, 43, 44, or 45 wherein said target analyte is a nucleic acid.
47. A method according to claim 42, 43, 44, 45, or 46 wherein said chemical functionality is selected from the group consisting of nucleic acids, enzymes, and antibodies.
48. A method according to claim 42, 43, 44 or 45 wherein said chemical functionality is selected from the group consisting of fluorophores, chromophores, phosphors, pH
indicators, cation indicators, anion indicators, metal ion indicators, ion salt, indicators, oxygen indicators, and carbon dioxide indicators.
49. A method according to claim 42, 43, 44, 45, 46, 47 or 48 further comprising providing a detecting optical signature for each subpopulation, said detecting optical signature used to identify the presence or absence of a target analyte.

50. A composition according to claim 49 wherein said detecting optical signature comprise; at least one dye selected from the group consisting of fluorophores, chromophores, and phosphors.
51. A method of making a composition comprising:
a) forming wells at a terminal end of an optical fiber array;
and b) distributing microspheres within said wells, wherein said microspheres comprise separate subpopulations, each subpopulation comprising:
i) a chemical functionality for interacting with a target analyte; and ii) an encoding optical signature that can be used to identity said chemical functionality.
52. A method according to claim 51, wherein said forming comprises anisotropically etching the cores of the individual fibers of said array.
53. A method according to claim 51 ar 52 wherein said distributing comprises serially adding said subpopulations to said wells.
54. A method according to claim 51, 52 or 53 further comprising providing a detecting optical signature for each subpopulation, said detecting optical signature used to identify the presence or absence of a target analyte.
55. A method according to claim 54 wherein said providing comprises incorporating in each subpopulation at least one dye selected from the group consisting of fluorophores, chromophores, and phosphors.
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PCT/US1998/005025 WO1998040726A1 (en) 1997-03-14 1998-03-13 Fiber optic sensor with encoded microspheres

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