Fiber optic sensor with encoded microspheres

• US 6,266,459 B1
• Filed: 11/29/1999
• Issued: 07/24/2001
• Est. Priority Date: 03/14/1997
• Status: Expired due to Term

• Current Assignee: Trustees of Tufts College
• Original Assignee: Trustees of Tufts College
• Inventors: Michael, Karri Lynn, Walt, David R.
• Primary Examiner(s): NGO, HUNG NHAT
• Application Number:
  US09/450,829
• Time in Patent Office: 603 Days
• Field of Search: 385/12, 385/13, 385/31, 385/33, 385/38, 385/147, 385/901, 385/35, 359/368, 356/236, 435/808, 430/164, 430/172, 430/800, 430/805, 250/556
• 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 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. A method for the detection of target analyte in a sample comprising:

a) providing a population of beads distributed on a surface, said population comprising subpopulations, each subpopulation comprising a chemical functionality;

b) contacting said beads with said sample; and

c) detecting a change in an optical property around at least one of said beads in a subpopulation as an indication of the presence of said target analyte.

2. A method according to claim 1 wherein said surface is a fiber optic bundle.

3. A method according to claim 1 wherein said fiber optic bundle comprises wells comprising said beads.

4. A method according to claim 1 further providing a diffusion retardant to prevent diffusion away from said beads.

5. A method according to claim 1 wherein each subpopulation further comprises a different optically interrogatable code.

6. A method according to claim 5 wherein said interrogatable code comprises an optical dye.

7. A method according to claim 5 wherein said interrogatable code comprises a mixture of optical dyes.

8. A method according to claim 6 wherein said optical dye is entrapped within said bead.

9. A method according to claim 1 wherein said chemical functionality is an enzyme.

10. A method according to claim 1 wherein said chemical functionality is an oligonucleotide.

11. A method according to claim 1 wherein said target analyte comprises a label.

12. A method according to claim 9 wherein said target analyte is a substrate for said enzyme.

13. A method according to claim 1 or 9 wherein said target analyte directly or indirectly produces a substrate for said chemical functionality.

14. A method according to claim 1 wherein at least one of said subpopulations comprises a first and a second chemical functionality.

15. A method according to claim 14 wherein said first chemical functionality is an oligonucleotide.

16. A method according to claim 14 or 15 wherein one of said chemical functionalities is an enzyme.

17. A method according to claim 14 wherein said first chemical functionality comprises an enzyme and said second chemical functionality comprises a dye.

18. A method according to claim 14 wherein said first chemical functionality produces a substrate for said second chemical functionality.

19. A method according to claim 14 or 15 wherein said target analyte interacts with said first chemical functionality.

20. A method of detecting nucleic acid sequences comprising:

a) providing a population of beads distributed on a surface, said population comprising subpopulations, each subpopulation comprising;

i) a different oligonucleotide probe;

ii) an enzyme;

b) contacting said beads with a sample comprising at least one target sequence, whereby said target nucleic acid sequence binds to at least one of said oligonucleotide probes; and

c) detecting a change in an optical property around at least one of said beads in a subpopulation as an indication of the target nucleic acid sequence.

21. A method for the detection of target analyte in a sample comprising:

a) providing a population of beads distributed on a surface, said population comprising subpopulations, each subpopulation comprising;

i) a first chemical functionality; and

ii) a second chemical functionality;

b) contacting said beads with said sample; and

c) detecting a change in an optical property around at least one of said beads in a subpopulation as an indication of the presence of said target analyte.