Products for detecting nucleic acids

• US 6,451,536 B1
• Filed: 09/27/2000
• Issued: 09/17/2002
• Est. Priority Date: 12/06/1990
• 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:
  US09/670,563
• Time in Patent Office: 720 Days
• Field of Search: 435/288.3, 435/6, 536/23.1, 536/24.3
• 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 2219/00315 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 2219/00626 : 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 2219/00641 : the porous medium being continuous, e.g. porous oxide substrates
• 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: 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 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: C12Q 1/6804 : Nucleic acid analysis using immunogens immunoassay G01N33/53
• 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 2525/151 : repeat or repeated sequences, e.g. VNTR, microsatellite, concatemer
• CPC Class Codes: C12Q 2525/179 : incorporating arbitrary or random nucleotide sequences
• CPC Class Codes: C12Q 2525/185 : incorporating bases where the precise position of the bases in the nucleic acid string is important
• CPC Class Codes: C12Q 2525/204 : specific length of the oligonucleotides
• CPC Class Codes: C12Q 2545/101 : with an internal standard/control
• CPC Class Codes: C12Q 2563/119 : the label being proteinic
• CPC Class Codes: C12Q 2563/149 : Particles, e.g. beads
• CPC Class Codes: C12Q 2563/173 : staining/intercalating agent, e.g. ethidium bromide
• CPC Class Codes: C12Q 2565/507 : characterised by the density of the capture oligonucleotide
• CPC Class Codes: C12Q 2565/513 : characterised by the pattern of the arrayed oligonucleotides
• CPC Class Codes: C12Q 2565/514 : characterised by the use of the arrayed oligonucleotides as identifier tags, e.g. universal addressable array, anti-tag or tag complement array
• 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: 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. An array comprising a solid substrate and a plurality of positionally distinguishable polynucleotides attached to the solid substrate at a density of at least 100 different polynucleotides per cm²;

wherein each of the attached polynucleotides comprises at least about 25 nucleotides and has a predetermined nucleotide sequence, a target complementary to at least one of the predetermined nucleotide sequences specifically binds to at least one known position on the solid substrate, and at least one of the attached polynucleotides is comprised of an unnatural nucleotide or unnatural nucleotide analogue.

2. The array of claim 1, wherein each of the positionally distinguishable polynucleotides is attached to the solid substrate within a square of less than about 10 microns by 10 microns.

3. The array of claim 1, wherein the density of positionally distinguishable polynucleotides attached to the solid substrate is at least 300 polynucleotides per cm².

4. The array of claim 1, wherein each of the attached polynucleotides comprises at least about 50 nucleotides.

5. The array of claim 1, wherein the plurality of attached polynucleotides comprises at least 3000 different polynucleotides.

6. The array of claim 1, wherein the solid substrate is glass or plastic.

7. The array of claim 1, wherein the solid substrate is a bead or fiber.

8. An array comprising a solid substrate and a plurality of positionally distinguishable polynucleotides attached to the solid substrate at a density of at least 100 different polynucleotides per cm²;

wherein each of the attached polynucleotides has a predetermined nucleotide sequence and at least one of the attached polynucleotides is comprised of an unnatural nucleotide or unnatural nucleotide analogue.

9. The array of claim 8, wherein each of the positionally distinguishable polynucleotides is attached to the solid substrate within a square of less than about 500 microns by 500 microns.

10. The array of claim 8, wherein each of the positionally distinguishable polynucleotides is attached to the solid substrate within a square of less than about 100 microns by 100 microns.

11. The array of claim 8, wherein each of the positionally distinguishable polynucleotides is attached to the solid substrate within a square of less than about 50 microns by 50 microns.

12. The array of claim 8, wherein each of the positionally distinguishable polynucleotides is attached to the solid substrate within a square of less than about 10 microns by 10 microns.

13. The array of claim 8, wherein the density of positionally distinguishable polynucleotides attached to the solid substrate is at least 300 polynucleotides per cm².

14. The array of claim 8, wherein the density of positionally distinguishable polynucleotides attached to the solid substrate is at least 1000 polynucleotides per cm².

15. The array of claim 8, wherein the density of positionally distinguishable polynucleotides attached to the solid substrate is at least 3000 polynucleotides per cm².

16. The array of claim 8, wherein the density of positionally distinguishable polynucleotides attached to the solid substrate is at least 10,000 polynucleotides per cm₂.

17. The array of claim 8, wherein the density of positionally distinguishable polynucleotides attached to the solid substrate is at least 30,000 polynucleotides per cm².

18. The array of claim 8, wherein the density of positionally distinguishable polynucleotides attached to the solid substrate is at least 100,000 polynucleotides per cm².

19. The array of claim 8, wherein each of the attached polynucleotides comprises at least about 25 nucleotides.

20. The array of claim 8, wherein each of the attached polynucleotides comprises at least about 50 nucleotides.

21. The array of claim 8, wherein the plurality of attached polynucleotides comprises at least 3000 different polynucleotides.

22. The array of claim 8, wherein the solid substrate has a surface area of less than about 4 square centimeters.

23. The array of claim 8, wherein the solid substrate has a surface area of less than about 11 cm².

24. The array of claim 8, wherein the solid substrate is glass.

25. The array of claim 8, wherein the solid substrate is plastic.

26. The array of claim 8, wherein the solid substrate is a bead.

27. The array of claim 8, wherein the solid substrate is a fiber.