Fiber optic sensor with encoded microspheres

• US 20020122612A1
• Filed: 04/20/2001
• Published: 09/05/2002
• Est. Priority Date: 03/14/1997
• Status: Abandoned Application

• Current Assignee: Trustees of Tufts College
• Original Assignee: Trustees of Tufts College
• Inventors: Walt, David R., Michael, Karri Lynn
• Application Number:
  US09/840,012
• Publication Number:
  US 20020122612A1
• Time in Patent Office: Days
• US Class Current: 385/12
• CPC Class Codes: B01J 2219/00317 Microwell devices, i.e. having large numbers of wells
• CPC Class Codes: B01J 2219/00466 in a slurry
• CPC Class Codes: B01J 2219/005 Beads
• CPC Class Codes: B01J 2219/00524 in the shape of fiber bundles
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/0061 The surface being organic
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00621 by physical means, e.g. trenches, raised areas
• CPC Class Codes: B01J 2219/00626 Covalent
• CPC Class Codes: B01J 2219/0063 Other, e.g. van der Waals forces, hydrogen bonding
• CPC Class Codes: B01J 2219/00637 by coating it with another layer
• CPC Class Codes: B01J 2219/00648 by the use of solid beads
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00677 Ex-situ synthesis followed by deposition on the substrate
• CPC Class Codes: B01J 2219/00704 integrated with the reactor apparatus
• CPC Class Codes: B01J 2219/00725 Peptides
• CPC Class Codes: B01J 2219/0074 Biological products
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C12Q 1/6837 : using probe arrays or probe chips C12Q1/6874 takes precedence
• CPC Class Codes: C40B 40/10 : Libraries containing peptides or polypeptides, or derivatives thereof
• CPC Class Codes: G01N 15/1433 : using image recognition
• CPC Class Codes: G01N 15/1456 : without spatial resolution of the texture or inner structure of the particle, e.g. processing of pulse signals
• CPC Class Codes: G01N 15/1459 : the analysis being performed on a sample stream
• CPC Class Codes: G01N 15/1468 : with spatial resolution of the texture or inner structure of the particle
• CPC Class Codes: G01N 2015/1438 : Using two lasers in succession
• CPC Class Codes: G01N 2015/1465 : image analysis on colour image
• CPC Class Codes: G01N 2021/6484 : Optical fibres
• CPC Class Codes: G01N 2021/7786 : Fluorescence
• CPC Class Codes: G01N 2035/0097 : monitoring reactions as a function of time
• 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 21/7703 : 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 33/54346 : Nanoparticles
• CPC Class Codes: Y10S 359/90 : Methods
• CPC Class Codes: Y10S 435/808 : Optical sensing apparatus

Abstract

A microsphere-based analytic chemistry system and method for making the same is disclosed in which microspheres or particles carrying bioactive agents may be combined randomly or in ordered fashion and dispersed on a substrate to form an array while maintaining the ability to identify the location of bioactive agents and particles within the array using an optically interrogatable, optical signature encoding scheme. In a preferred embodiment, a modified fiber optic bundle or array is employed as a substrate to produce a high density array. The disclosed system and method have utility for detecting target analytes and screening large libraries of bioactive agents. In a preferred embodiment the methods include detecting a change in an optical property around a microsphere on an array.

Claims

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 functicnalities 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.

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.

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.

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.

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.