Optical fiber bundle for detecting binding of chemical species

• US 20050026209A1
• Filed: 09/01/2004
• Published: 02/03/2005
• Est. Priority Date: 01/08/1999
• Status: Abandoned Application

• Current Assignee: Applied Biosystems LLC (Thermo Fisher Scientific Incorporated)
• Original Assignee: Applied Biosystems LLC (Thermo Fisher Scientific Incorporated)
• Inventors: Vann, Charles S.
• Application Number:
  US10/932,608
• Publication Number:
  US 20050026209A1
• Time in Patent Office: Days
• US Class Current: 506/16
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 2219/00326 Movement by rotation
• CPC Class Codes: B01J 2219/0043 for direct application of reagents, e.g. through openings in a shutter
• CPC Class Codes: B01J 2219/00495 Means for heating or cooling the reaction vessels
• CPC Class Codes: B01J 2219/00515 in the shape of strings
• CPC Class Codes: B01J 2219/00524 in the shape of fiber bundles
• CPC Class Codes: B01J 2219/00572 Chemical means
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/0059 Sequential 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 2219/00612 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 2219/00635 by reactive plasma treatment
• CPC Class Codes: B01J 2219/00637 by coating it with another layer
• CPC Class Codes: B01J 2219/00657 One-dimensional arrays
• CPC Class Codes: B01J 2219/00675 In-situ synthesis on the substrate
• CPC Class Codes: B01J 2219/00702 Processes involving means for analysing and characterising the products
• CPC Class Codes: B01J 2219/00711 Light-directed synthesis
• CPC Class Codes: B01J 2219/00722 : Nucleotides
• CPC Class Codes: B01L 3/5023 : with a sample being transported to, and subsequently stored in an absorbent for analysis
• CPC Class Codes: B01L 3/5085 : for multiple samples, e.g. microtitration plates
• CPC Class Codes: B82Y 30/00 : Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C40B 40/06 : Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 50/14 : Solid phase synthesis, i.e. wherein one or more library building blocks are bound to a solid support during library creation; Particular methods of cleavage from the solid support
• CPC Class Codes: C40B 60/14 : for creating libraries
• CPC Class Codes: G01N 21/6452 : Individual samples arranged in a regular 2D-array, e.g. multiwell plates
• CPC Class Codes: G01N 21/648 : using evanescent coupling or surface plasmon coupling for the excitation of fluorescence
• 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 2201/0833 : Fibre array at detector, resolving

Abstract

The system includes a bundle of elongate optical fibers, multiple probes, a well, a light source and a detector. The optical fibers each have a first end remote from a second end. Each of the multiple probes is attached to one of the optical fibers within a predetermined section between each of the optical fiber'"'"'s first and second ends. The well is configured to hold a solution comprising a target and to receive at least the predetermined section of each of the optical fibers. The light source is configured to direct light into the first end of each of the optical fibers. Finally, the detector is configured to detect light emitted by the binding of the target to at least one of the multiple probes. In some embodiments, there are multiple bundles and multiple wells.

Claims

1. A system for detecting binding of two chemical species, comprising:

a bundle of elongate optical fibers, each having a first end remote from a second end;

multiple probes, each attached to one of said optical fibers within a predetermined section between each of said optical fiber'"'"'s first end and second end;

a well configured to hold a solution comprising a target and to receive at least said predetermined section of each of said optical fibers;

a light source configured to direct light into said first end of each of said optical fibers; and

a detector configured to detect light emitted by the binding of said target to at least one of said multiple probes.

2. The system of claim 1, further comprising multiple bundles and multiple wells.

3. The system of claim 1, wherein said detector is disposed in proximity to said second end of at least one of said optical fibers.

4. The system of claim 1, wherein said light source is disposed in proximity to said first end of at least one of said optical fibers.

5. The system of claim 1, wherein each of said wells is configured and dimensioned to receive a length of said bundle therein, and where a cross-section of said well is larger than a cross-section of said bundle.

6. The system of claim 1, wherein said optical fibers in said bundle are substantially parallel to one another.

7. The system of claim 1, wherein said optical fibers in said bundle are parallel to one another.

8. The system of claim 1, wherein said second ends of each of said optical fibers are coated with a reflective coating.

9. The system of claim 1, wherein said bundle comprises multiple adjacent layers of parallel optical fibers.

10. The system of claim 1, wherein said bundle comprises a layer of parallel optical fibers rolled into a cylinder.

11. The system of claim 1, wherein said bundle comprises multiple concentric layers of parallel optical fibers forming a cylinder.

12. The system of claim 1, wherein said bundle comprises a spiral layer of parallel optical fibers.

13. The system of claim 1, wherein said bundle comprises substantially parallel fibers forming a ring near said first ends and a bundle near said second ends.

14. The system of claim 1, wherein said bundle comprises parallel fibers forming a ring at said first ends and a bundle as said second ends.

15. The system of claim 1, wherein said light source is configured to generate an evanescent wave about a circumference of each of said optical fibers.

16. The system of claim 1, wherein predetermined lengths of said optical fibers near said first ends and said second ends are substantially parallel to one another.

17. The system of claim 1, wherein predetermined lengths of said optical fibers near said first ends and said second ends are parallel to one another.

18. The system of claim 1, wherein predetermined lengths near said first ends are substantially parallel to one another.

19. The system of claim 1, wherein predetermined lengths near said first ends are parallel to one another.

20. The system of claim 1, wherein predetermined lengths near said second ends are substantially parallel to one another.

21. The system of claim 1, wherein predetermined lengths near said second ends are parallel to one another.

22. The system of claim 1, wherein said first ends of said optical fibers are spaced further apart from one another than said second ends of said optical fibers.

23. The system of claim 1, wherein said predetermined section is near said optical fibers'"'"' second ends, and wherein a diameter of said bundle at said predetermined section is smaller than a diameter of said well.

24. The system of claim 1, further comprising a motion device for sequentially directing light from said light source into each of said optical fibers.

25. The system of claim 24, further comprising a control system for controlling said motion device.

26. The system of claim 1, further comprising a motion device for sequentially positioning said detector adjacent an illuminated optical fiber.

27. The system of claim 26, further comprising a control system for controlling said motion device.

28. The system of claim 1, wherein said light source is an excitation laser or an arc lamp.

29. The system of claim 1, wherein said detector is photon multiplier tube.

30. The system of claim 8, wherein said reflective coating is made from a metal.

31. A system for detecting binding of two chemical species, comprising:

multiple bundles of elongated optical fibers, where each optical fiber has a first end remote from a second end;

multiple probes, each attached to one of said optical fibers within a predetermined section between said optical fiber'"'"'s first and second ends;

multiple wells, each configured to hold a solution comprising a target and to receive at least said predetermined section of each of said optical fibers of at least one of said multiple bundles;

a light source configured to direct light into said first end of each of said optical fibers; and

a detector configured to detect light emitted by the binding of said target to at least one of said multiple probes.

32. A system for detecting binding of two chemical species, comprising:

a bundle of elongated optical fibers comprising first ends remote from second ends, wherein said first ends are spaced further apart from one another than said second ends, and wherein predetermined lengths of said optical fibers near said first ends are substantially parallel to one another and predetermined lengths of said optical fibers near said second ends are substantially parallel to one another;

multiple probes, each attached to one of said optical fibers within a predetermined section between said first and second ends.

33. A method for detecting binding of two chemical species, comprising:

contacting a target with multiple probes each attached to a different elongated optical fiber of a bundle of elongated optical fibers between a first end and a second end of each of said optical fibers;

directing light at said first end of each of said optical fibers;

detecting at said second end of each of said optical fibers light emitted by the binding of said target to at least one of said multiple probes.

34. The method of claim 33, further comprising, before said contacting, attaching said probes to said optical fibers.

35. The method of claim 33, wherein said contacting comprises dipping said bundle into a solution congaing said target therein.

36. The method of claim 35, further comprising, before said contacting, placing target solution into a well.

37. The method of claim 33, wherein said detecting further comprises identifying those optical fibers that emit the most light.

38. The method of claim 37, wherein said identifying further comprises detecting those optical fibers that emit fluoresce the most.

39. The method of claim 33, wherein said directing further comprises forming an evanescent wave near a surface of each fiber.

40. The method of claim 33, further comprising separately directing and detecting for each optical fiber in said bundle.

41. The method of claim 33, further comprising directing and detecting for all optical fiber in said bundle simultaneously.

42. The method of claim 33, further comprising, prior to said contacting, forming a bundle of said optical fibers by stacking parallel layers of optical fibers adjacent to one another, rolling a layer of parallel optical fibers into a spiral, forming concentric rings of parallel sheets of optical fibers, or a bundle of randomly oriented fibers.

43. A method for making an optical fiber having known probes attached thereto, comprising:

providing a known sequence in a solution;

inserting a first probe having a zip code sequence (TSO-Zip) attached thereto into said solution;

inserting a second probe that is labeled into said solution;

allowing said first and second probes to hybridize with said known sequence;

adding first and second ligation enzymes into said solution;

allowing said first and second probes to covalently bond to each other using said first ligation enzyme to form a ligated probe sequence;

removing said ligated probe sequence from said known sequence;

inserting a fiber into said solution, wherein said fiber has a third probe attached thereto;

inserting a Zip template into said solution, wherein said Zip template is configured to hybridize to both said TSO-Zip and said third probe;

allowing said TSO-Zip and said third probe to covalently bond to each another using said second ligation enzyme; and

removing said TSO-Zip and said third probe from said Zip template sequence.

44. A method for making an optical fiber having known probes attached thereto, comprising:

providing a known sequence in a solution;

inserting a first probe into said solution, wherein said first probe has a zip code sequence (TSO-Zip) attached thereto and a sequence for hybridization with a universal forward primer attached to said TSO-Zip;

adding a second probe into said solution, wherein said second probe is attached to a sequence for hybridization with a universal reverse primer;

adding a forward primer to said solution;

adding a reverse primer to said solution, wherein said reverse primer is labeled;

adding polymerase to said solution;

allowing said first and second probes to hybridize with said known sequence;

inserting a ligation enzyme into said solution;

allowing said first and second probes to covalently bond to each other using said ligation enzyme to form a ligated probe sequence;

removing said ligated probe sequence from said known sequence;

amplifying said ligated probe sequence using said forward primer, said reverse primer, said polymerase and said ligated probe sequence through a polymerase chain reaction (PCR) technique;

inserting a fiber into said solution, wherein said fiber has a third probe attached thereto; and

allowing said TSO-Zip and said third probe to hybridize to one another.

45. A method for making an optical fiber having known probes attached thereto, comprising:

providing a known sequence in a solution;

inserting a first probe into said solution, wherein at least part of said first probe has a sequence that will hybridize with a portion of said known sequence, and wherein said probe has a biotin attached thereto;

inserting a ligation enzyme into said solution;

inserting a fiber into said solution, wherein said fiber has a second probe attached thereto, wherein at least part of said second probe has a sequence that will hybridize with a portion of said known sequence;

allowing said first probe and said second probe to hybridize to said known target;

allowing said first and second probes to covalently bond to each other using said ligation enzyme to form a ligated probe sequence;

removing said ligated probe sequence from said known sequence; and

attaching a label to said biotin.