Analysis of target molecules using an encoding system

• US 6,440,667 B1
• Filed: 07/28/1999
• Issued: 08/27/2002
• Est. Priority Date: 06/07/1989
• Status: Expired due to Fees

• Current Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Original Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Inventors: Solas, Dennis W., Dower, William J., Fodor, Stephen P. A.
• Primary Examiner(s): ZITOMER, STEPHANIE W
• Application Number:
  US09/362,089
• Time in Patent Office: 1,126 Days
• Field of Search: 435/6, 435/7.1, 435/287.2, 435/288.3, 536/23.1, 536/24.3, 530/350, 530/300, 530/387.1
• US Class Current: 506/3
• 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 2219/00315 Microtiter plates
• CPC Class Codes: B01J 2219/00432 Photolithographic masks
• CPC Class Codes: B01J 2219/00434 Liquid crystal masks
• CPC Class Codes: B01J 2219/00436 Maskless processes
• CPC Class Codes: B01J 2219/00459 Beads
• CPC Class Codes: B01J 2219/00468 by manipulation of individual beads
• CPC Class Codes: B01J 2219/00475 Sheets
• CPC Class Codes: B01J 2219/005 Beads
• CPC Class Codes: B01J 2219/00527 Sheets
• CPC Class Codes: B01J 2219/00529 DNA chips
• CPC Class Codes: B01J 2219/00531 essentially square
• 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 2219/00608 DNA chips
• CPC Class Codes: B01J 2219/0061 The surface being organic
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00617 by chemical means
• 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 2219/00644 : the porous medium being present in discrete locations, e.g. gel pads
• 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 2219/00689 : using computers
• CPC Class Codes: B01J 2219/00695 : Synthesis control routines, e.g. using computer programs
• CPC Class Codes: B01J 2219/00711 : Light-directed synthesis
• CPC Class Codes: B01J 2219/00722 : Nucleotides
• CPC Class Codes: B01J 2219/00725 : Peptides
• CPC Class Codes: B82Y 10/00 : Nanotechnology for information processing, storage or transmission, e.g. quantum computing or single electron logic
• CPC Class Codes: B82Y 30/00 : Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C07B 2200/11 : Compounds covalently bound to a solid support
• CPC Class Codes: C07C 229/14 : to carbon atoms of carbon skeletons containing rings
• CPC Class Codes: C07C 229/16 : to carbon atoms of hydrocarbon radicals substituted by amino or carboxyl groups, e.g. ethylenediamine-tetra-acetic acid, iminodiacetic acids
• CPC Class Codes: C07D 263/44 : Two oxygen atoms
• CPC Class Codes: C07D 317/62 : with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to atoms of the carbocyclic ring
• CPC Class Codes: C07H 19/04 : Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
• CPC Class Codes: C07H 19/10 : with the saccharide radical esterified by phosphoric or polyphosphoric acids
• CPC Class Codes: C07H 21/00 : Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
• CPC Class Codes: C07K 1/042 : characterised by the nature of the carrier
• CPC Class Codes: C07K 1/045 : using devices to improve synthesis, e.g. reactors, special vessels
• CPC Class Codes: C07K 1/047 : Simultaneous synthesis of different peptide species; Peptide libraries
• CPC Class Codes: C07K 17/06 : attached to the carrier via a bridging agent
• CPC Class Codes: C07K 17/14 : Peptides being immobilised on, or in, an inorganic carrier
• CPC Class Codes: C07K 7/06 : having 5 to 11 amino acids
• CPC Class Codes: C12Q 1/6809 : Methods for determination or identification of nucleic acids involving differential detection
• CPC Class Codes: C12Q 1/6816 : characterised by the detection means C12Q1/6804 takes precedence
• CPC Class Codes: C12Q 1/6827 : for detection of mutation or polymorphism
• CPC Class Codes: C12Q 1/6834 : Enzymatic or biochemical coupling of nucleic acids to a solid phase
• CPC Class Codes: C12Q 1/6837 : using probe arrays or probe chips C12Q1/6874 takes precedence
• CPC Class Codes: C12Q 1/6874 : involving nucleic acid arrays, e.g. sequencing by hybridisation
• CPC Class Codes: C12Q 2535/131 : Allele specific probes
• CPC Class Codes: C12Q 2563/149 : Particles, e.g. beads
• CPC Class Codes: C12Q 2565/626 : being a flow cytometer
• CPC Class Codes: C40B 40/06 : Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 40/10 : Libraries containing peptides or polypeptides, or derivatives thereof
• CPC Class Codes: C40B 60/14 : for creating libraries
• CPC Class Codes: G01N 15/1433 : using image recognition
• 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 21/6458 : Fluorescence microscopy fluorescence microscopes per se G02B21/0076 and G02B21/16
• CPC Class Codes: G03F 7/00 : Photomechanical, e.g. photolithographic, production of textured or patterned surfaces, e.g. printing surfaces; Materials therefor, e.g. comprising photoresists; Apparatus specially adapted therefor using photoresist structures for special production processes, see the relevant places, e.g. B44C, H01L, e.g. H01L21/00, H05K
• CPC Class Codes: G03F 7/265 : Selective reaction with inorganic or organometallic reagents after image-wise exposure, e.g. silylation
• CPC Class Codes: G03F 7/38 : Treatment before imagewise removal, e.g. prebaking G03F7/265 takes precedence
• CPC Class Codes: G11C 13/0014 : comprising cells based on organic memory material
• CPC Class Codes: G11C 13/0019 : comprising bio-molecules

Abstract

The present invention provides methods and apparatus for sequencing, fingerprinting and mapping biological macromolecules, typically biological polymers. The methods make use of a plurality of sequence specific recognition reagents which can also be used for classification of biological samples, and to characterize their sources.

Claims

1. A method of identifying a target molecule in a sample, comprising:

(a) contacting the target molecule with a collection of substrates, wherein different substrates bear different binding reagents and a binding reagent encoding system, whereby the target molecule binds to one or more of;

the substrates via the reagent;

(b) separating the substrates that bind the target molecule from the substrates that do not bind the target molecule; and

(c) identifying the reagent on a separated substrate by reading the binding reagent encoding system on the separated substrate and thereby identifying said bound target molecule.

2. The method of claim 1, wherein the reagent is a probe.

3. The method of claim 2, wherein the probe is an oligonucleotide.

4. The method of claim 1, wherein the target molecule is a polymer.

5. The method of claim 4, wherein the target molecule is a polynucleotide.

6. The method of claim 4, wherein the target molecule is a polypeptide.

7. The method of claim 1, wherein the target molecule is a nucleic acid.

8. The method of claim 1, wherein the substrates are impregnated with a fluorescent molecule.

9. The method of claim 1, wherein the encoding system is a magnetic system, shape encoding system, color endocing system, or a combination thereof.

10. The method of claim 1, wherein the substrates are beads.

11. The method of claim 1, wherein the substrates are fibers.

12. The method of claim 1, wherein the substrates comprise glass.

13. The method of claim 12, wherein the glass is a microscope slide.

14. The method of claim 1, wherein the substrates have a three dimensional contour.

15. The method of claim 1, wherein the reagent is an oligomer.

16. The method of claim 15, wherein the oligomer is a nucleic acid.

17. The method of claim 15, wherein the oligomer comprises nucleotides.

18. The method of claim 15, wherein the oligomer is a peptide.

19. The method of claim 1, wherein the reagent is an oligonucleotide.

20. A method of identifying a target molecule in a sample, comprising:

(a) contacting the target molecule with a collection of substrates, wherein different substrates bear different binding reagents and a reagent encoding system, whereby one or more of the substrate bind to the target molecule via the binding reagent; and

(b) identify the binding reagent on the substrate bound to the target by reading the reagent encoding system on the individual bound substrate and thereby identifying said target molecule.

21. The method of claim 20, wherein the reagent is a probe.

22. The method of claim 21, wherein the probe is an oligonucleotide.

23. The method of claim 20, wherein the target molecule is a polymer.

24. The method of claim 23, wherein the target molecule is a polynucleotide.

25. The method of claim 23, wherein the target molecule is a polypeptide.

26. The method of claim 20, wherein the target molecule is a nucleic acid.

27. The method of claim 20, wherein the substrates are impregnated with a fluorescent molecule.

28. The method of claim 20, wherein the encoding system is a magnetic encoding system, shape encoding system, color encoding system, or a combination thereof.

29. The method of claim 20, wherein the substrates are beads.

30. The method of claim 20, wherein the substrates are fibers.

31. The method of claim 20, wherein the substrates comprise glass.

32. The method of claim 31, wherein the glass is a microscope slide.

33. The method of claim 20, wherein the substrates have a three dimensional contour.

34. The method of claim 20, wherein the reagent is an oligomer.

35. The method of claim 34, wherein the oligomer is a nucleic acid.

36. The method of claim 34, wherein the oligomer comprises nucleotides.

37. The method of claim 34, wherein the oligomer is a peptide.

38. The method of claim 20, wherein the reagent is an oligonucleotide.

39. A method of identifying a target nucleic acid in a sample, comprising:

(a) contacting the target nucleic acid with a collection of beads, wherein different beads bear different probe nucleic acids and a probe encoding system, whereby one or more of the beads bind to the target nucleic acid via hybridization between the probe nucleic acid and the target nucleic acid; and

(b) identifying the different probes on the one or more beads which are bound to the target nucleic acid by reading the encoding system on the individual target bound bead and thereby identifying said target nucleic acid.

40. A method of identifying a target nucleic acid in a sample according to the method of claim 39 and further comprising sorting the one or more beads that bind to the target nucleic acid from beads that do not bind to the target nucleic acid.

41. The method of claim 40, wherein the beads are sorted with a cell sorting device.

42. The method of claim 39, wherein at least one of the different probes is an oligonucleotide.

43. The method of claim 39, wherein at least one of the different probes is a polynucleotide.

44. The method of claim 39, wherein the bead is tagged with a fluorescent tag of a color encoding system.

45. The method of claim 39, wherein the target nucleic acid has a label and hybridization results in the individual bound bead to be tagged with the label.

46. The method of claim 45, wherein the label is a green or red fluorescent label.

47. The method of claim 45, wherein the label is selected from the group consisting of radioisotopes, chemiluminescent or bioluminescent compounds, chromogens, heavy metal atoms, electron spin labels, magnetic labels, enzyme-linked labels, and labeled binding proteins.

48. The method of claim 39, wherein the encoding system is a magnetic encoding system, shape encoding system, color encoding system, or a combination thereof.

49. The method of claim 39, wherein the collection of beads has at least 10² different probes.

50. The method of claim 39, wherein the collection of beads has at least 10³ different probes.

51. The method of claim 39, wherein the collection of beads has at least 10⁴ different probes.

52. The method of claim 39, wherein the collection of beads has at least 10⁵ different probes.

53. The method of claim 39, wherein the collection of beads has at least 10⁶ different probes.