Method for comparing copy number of nucleic acid sequences

• US 6,309,822 B1
• Filed: 12/23/1996
• Issued: 10/30/2001
• 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:
  US08/772,376
• Time in Patent Office: 1,772 Days
• Field of Search: 435/6, 435/287.2, 435/288.3, 435/288.7, 536/24.3, 536/24.31, 536/23.1
• US Class Current: 506/9
• 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 2219/00612 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 2219/00637 : 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 1/6809 : 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 1/6837 : 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 2539/101 : Subtraction analysis
• CPC Class Codes: C12Q 2565/501 : being an array of oligonucleotides
• 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 for comparing and identifying differences in nucleic acid sequences using a plurality of sequence specific recognition reagents (i.e., probes comprising a nucleic acid complementary to a nucleic acid sequence in collections to be compared) bound to a solid surface.

Claims

1. A method for comparing and identifying differences if any in nucleic acid sequences in two or more collections of labeled nucleic acids, the method comprising:

providing a plurality of probes bound to a solid surface, at least some of said plurality comprising a nucleic acid complementary to a nucleic acid sequence in said collections to be compared;

contacting the probes with

a first collection of labeled nucleic acids having a first label, and

at least a second collection of labeled nucleic acids having a

second label;

wherein said first and second labels are distinguishable from each other and wherein said labeled nucleic acids in said first and second collections bind to said probes; and

detecting the binding for each of the first and at least second labeled nucleic acids to the probes;

thereby comparing and identifying differences if any in said nucleic acid sequences in said two or more collections.

2. The method as recited in claim 1 wherein the labeled nucleic acids are from two cell types and are labeled with labels of first and second fluorescent reporters.

3. The method as recited in claim 2 wherein said first and second fluorescent reporters are different colors of flurescent reporters.

4. The method as recited in claim 3 wherein said colors are red and green.

5. The method as recited in claim 1 wherein said probes are provided by synthesis of RNA or DNA on the solid surface.

6. The method of claim 1 wherein the nucleic acids are DNA.

7. The method of claim 1 wherein the nucleic acids are cDNA.

8. The method of claim 1 wherein the first and second labeled nucleic acids comprise human DNA.

9. The method of claim 1 wherein the nucleic acids are greater than about 25 nucleotides in complexity.

10. The method of claim 1 wherein the solid surface is glass.

11. The method of claim 1 wherein the first and second labels are fluorescent labels.

12. The method of claim 1 wherein the first labeled nucleic acids comprise mRNA or cDNA from a test cell and the second labeled nucleic acids comprise mRNA or cDNA from a reference cell.

13. The method of claim 1 wherein the first labeled nucleic acids are from a test genome and the second labeled nucleic acids are from a normal reference genome.

14. The method of claim 1 wherein the first labeled nucleic acids are from a tumor.

15. The method according to claim 1 wherein the plurality of probes includes more than 100 probes per square centimeter bound to said solid surface.

16. The method according to claim 1 wherein the plurality of probes includes more than 1000 probes per square centimeter bound to said solid surface.

17. The method according to claim 1 wherein the plurality of probes includes more than 10,000 probes per square centimeter bound to said solid surface.