Combinatorial strategies for polymer synthesis

• US 7,736,906 B2
• Filed: 06/17/2002
• Issued: 06/15/2010
• Est. Priority Date: 11/22/1991
• Status: Expired due to Fees

• Current Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Original Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Inventors: Modlin, Douglas N., Winkler, James L., Ross, Debra A., Aldwin, Lois, Buchko, Christopher J., Fodor, Stephen P. A.
• Primary Examiner(s): Ludlow; Jan M
• Application Number:
  US10/172,939
• Publication Number:
  US 20040092032A1
• Time in Patent Office: 2,920 Days
• Field of Search: 436/174, 436/178, 436/180, 436/183
• US Class Current: 436/174
• 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 2219/00364 Pipettes
• CPC Class Codes: B01J 2219/00367 capillary
• CPC Class Codes: B01J 2219/00369 in multiple or parallel arrangements
• CPC Class Codes: B01J 2219/00378 Piezoelectric or ink jet dispensers
• CPC Class Codes: B01J 2219/00389 Feeding through valves
• CPC Class Codes: B01J 2219/00416 Vacuum
• CPC Class Codes: B01J 2219/0043 for direct application of reagents, e.g. through openings in a shutter
• CPC Class Codes: B01J 2219/00432 Photolithographic masks
• 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 2219/00536 in the shape of disks
• 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 2219/00619 : using hydrophilic or hydrophobic regions
• 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 2219/00659 : Two-dimensional arrays
• CPC Class Codes: B01J 2219/00686 : Automatic
• 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: B01J 2219/00725 : Peptides
• 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 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 1/045 : 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: 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 35/1072 : with provision for selective pipetting of individual channels
• CPC Class Codes: Y10S 436/809 : Multifield plates or multicontainer arrays
• CPC Class Codes: Y10T 436/143333 : Saccharide [e.g., DNA, etc.]
• CPC Class Codes: Y10T 436/25 : including sample preparation
• CPC Class Codes: Y10T 436/255 : including use of a solid sorbent, semipermeable membrane, or liquid extraction
• CPC Class Codes: Y10T 436/2575 : Volumetric liquid transfer

Abstract

A method and device for forming large arrays of polymers on a substrate (401). According to a preferred aspect of the invention, the substrate is contacted by a channel block (407) having channels (409) therein. Selected reagents are delivered through the channels, the substrate is rotated by a rotating stage (403), and the process is repeated to form arrays of polymers on the substrate. The method may be combined with light-directed methodologies.

Claims

1. A method of making an array of molecules comprising:

obtaining a substrate having a substantially flat first surface;

forming a plurality of hydrophilic reaction regions on the first surface of the substrate by;

coating the first surface of the substrate with a hydrophilic material having a plurality of reactive functional groups, wherein said plurality of reactive functional groups comprise coupled thereto a plurality of hydrophobic photo protecting groups;

activating regions where said plurality of hydrophilic reaction regions are to be located, wherein the hydrophobic photo protecting groups are removed to re-liberate the hydrophilic material with the plurality of the reactive functional groups, wherein the activated regions are surrounded by hydrophobic constraining regions comprised of intact photo protecting groups, which prevent flow of reactants from the reaction regions;

wherein the first surface includes greater than 100 reaction regions at a density of at least 1000 reaction regions/cm²; and

attaching molecules to the reaction regions to form an array.

2. The method of claim 1 wherein the substrate comprises glass, pyrex, quartz, silicon, or polymer.

3. The method of claim 2 wherein the molecules are attached to the substrate using said reactive functional group.

4. The method of claim 3 wherein the reactive functional group is selected from the group consisting of an amine, a hydroxyl, a carboxyl, and a thio group.

5. The method of claim 1 wherein the molecules are selected from the group consisting of peptides, oligonucleotides, nucleic acids, and amino acids.

6. The method of claim 1 including a cover on the substrate.

7. The method of claim 1 including greater than 1000 reaction regions and a density of reaction regions being at least 1000/cm².

8. The method of claim 1 wherein the hydrophilic material is amino propyltriethoxysilane.

9. The method of claim 1 wherein the hydrophobic photo protecting groups are in the class of nitrobenzyl protection groups.

10. The method of claim 1 wherein the attaching molecules to the reaction regions to form an array includes a coupling step using a volume of solution of less than 5 nl that is contained within the hydrophilic reaction region.