Arrays of materials attached to a substrate

• US 5,744,305 A
• Filed: 06/06/1995
• Issued: 04/28/1998
• Est. Priority Date: 06/07/1989
• Status: Expired due to Term

• Current Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Original Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Inventors: Fodor, Stephen P.A., Pirrung, Michael C., Stryer, Lubert, Read, J. Leighton
• Primary Examiner(s): Zitomer, Stephanie W.
• Assistant Examiner(s): Tran, Paul B.
• Application Number:
  US08/466,632
• Time in Patent Office: 1,057 Days
• Field of Search: 435/6, 435/7.92, 435/7.95, 435/7.94, 435/9.73, 435/969, 436/518, 436/527, 436/807, 436/809, 530/334, 536/24.3, 536/25.3, 536/25.32
• 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 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00617 by chemical means
• CPC Class Codes: B01J 2219/00626 Covalent
• CPC Class Codes: B01J 2219/00637 : 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 2219/00689 : 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 19/073 : with 2-deoxyribosyl as the saccharide radical
• CPC Class Codes: C07H 19/173 : with 2-deoxyribosyl as the saccharide radical
• CPC Class Codes: C07H 21/04 : with deoxyribosyl as saccharide radical
• 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 1/062 : for alpha- or omega-carboxy functions
• 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 1/6837 : 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: 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: C40B 80/00 : Linkers or spacers specially adapted for combinatorial chemistry or libraries, e.g. traceless linkers or safety-catch linkers
• CPC Class Codes: G01N 15/1433 : using image recognition
• CPC Class Codes: G01N 21/253 : for batch operation, i.e. multisample apparatus analytical automats G01N35/00
• 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 7/0045 : with organic non-macromolecular light-sensitive compounds not otherwise provided for, e.g. dissolution inhibitors
• 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
• CPC Class Codes: Y02P 20/55 : Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
• CPC Class Codes: Y10S 435/969 : Multiple layering of reactants
• CPC Class Codes: Y10S 435/973 : Simultaneous determination of more than one analyte
• CPC Class Codes: Y10S 436/807 : Apparatus included in process claim, e.g. physical support structures
• CPC Class Codes: Y10S 436/809 : Multifield plates or multicontainer arrays

Abstract

A synthetic strategy for the creation of large scale chemical diversity. Solid-phase chemistry, photolabile protecting groups, and photolithography are used to achieve light-directed spatially-addressable parallel chemical synthesis. Binary masking techniques are utilized in one embodiment. A reactor system, photoremovable protective groups, and improved data collection and handling techniques are also disclosed. A technique for screening linker molecules is also provided.

Claims

1. An array of oligonucleotides, the array comprising:

a planar, non-porous solid support having at least a first surface; and

a plurality of different oligonucleotides attached to the first surface of the solid support at a density exceeding 400 different oligonucleotides/cm², wherein each of the different oligonucleotides is attached to the surface of the solid support in a different predefined region, has a different determinable sequence, and is at least 4 nucleotides in length.

2. The array of claim 1, wherein each different oligonucleotides is from about 4 to about 20 nucleotides in length.

3. The array of claim 1, wherein each different oligonucleotide is at least 10 nucleotides in length.

4. The array of claim 1, wherein each different oligonucleotide is at least 20 nucleotides in length.

5. The array of claim 1, wherein the array comprises at least 1,000 different oligonucleotides attached to the first surface of the solid support.

6. The array of claim 1, wherein the array comprises at least 10,000 different oligonucleotides attached to the first surface of the solid support.

7. The array of claim 1, wherein each of the different predefined regions is physically separated from each other of the different regions.

8. The array of claim 1, wherein said planar non-porous solid support is glass.

9. The array of claim 1, wherein said oligonucleotides are attached to the first surface of the solid support through a linker group.

10. The array of claim 1, wherein the oligonucleotide in the different predefined regions are at least 20% pure.

11. The array of claim 1, wherein the oligonucleotides in the different predefined regions are at least 50% pure.

12. The array of claim 1, wherein the oligonucleotide in the different predefined regions are at least 80% pure.

13. The array of claim 1, wherein the oligonucleotide in the different predefined regions are at least 90% pure.

14. The array of claim 1, wherein said array is produced by a binary synthesis process, said process comprising the steps of:

providing a planar, non-porous solid support, said solid support having a plurality of compounds immobilized on a surface thereof, said compounds having protecting groups coupled thereto;

deprotecting a first portion of said plurality of compounds on said surface and not a second portion of said plurality of compounds;

reacting said first portion of said plurality of compounds with a first component of said oligonucleotide;

deprotecting at least a third portion of said plurality of compounds on said surface, said third portion comprising a fraction of said first portion of said plurality of compounds;

reacting said at least third portion of said plurality of compounds with a second component of said oligonucleotide; and

optionally repeating said binary synthesis steps to produce said oligonucleotide array.

15. An array of polynucleotides, the array comprising:

a planar non-porous solid support having at least a first surface; and

a plurality of different polynucleotides attached to the first surface of the solid support at a density exceeding 400 different polynucleotides/cm², wherein each of the different polynucleotides is attached to the surface of the solid support in a different predefined region, has a different determinable sequence, and is at least 4 nucleotides in length.

16. The array of claim 15, wherein each different polynucleotide is at least 20 nucleotides in length.

17. The array of claim 15, wherein the array comprises at least 1,000 different polynucleotides attached to the first surface of the solid support.

18. The array of claim 15, wherein the array comprises at least 10,000 different polynucleotides attached to the first surface of the solid support.

19. The array of claim 15, wherein each of the different selected regions is physically separated from each of the other selected regions.

20. The array of claim 15, wherein said planar non-porous solid support is glass.

21. The array of claim 15, wherein said polynucleotides are attached to the first surface of the solid support through a linker group.

22. The array of claim 15, wherein the polynucleotides in the different predefined. regions comprise polynucleotides that are at least 20% pure.

23. The array of claim 15, wherein the polynucleotides in the different predefined regions comprise polynucleotides that are at least 50% pure.

24. The array of claim 15, wherein the polynucleotides in the different predefined regions are at least 80% pure.

25. The array of claim 15, the polynucleotides in the different predefined regions are at least 90% pure.

26. The array of claim 15, wherein said array is produced by a binary synthesis process, said process comprising the steps of:

providing a planar, non-porous solid support, said solid support having a plurality of compounds immobilized on a surface thereof, said compounds having protecting groups coupled thereto;

deprotecting a first portion of said plurality of compounds on said surface and not a second portion of said plurality of compounds;

reacting said first portion of said plurality of compounds with a first reactant;

deprotecting at least a third portion of said plurality of compounds on said surface, said third portion comprising a fraction of said first portion of said plurality of compounds;

reacting said at least third portion of said plurality of compounds with a second reactant; and

optionally repeating said binary synthesis steps to produce said polynucleotide array.