Combinatorial kit for polymer synthesis

• US 6,136,269 A
• Filed: 04/21/1995
• Issued: 10/24/2000
• Est. Priority Date: 11/22/1991
• Status: Expired due to Term

• 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, Fodor, Stephen P. A., Buchko, Christopher J.
• Primary Examiner(s): LUDLOW, JAN M
• Application Number:
  US08/426,202
• Time in Patent Office: 2,013 Days
• Field of Search: 422/61, 422/102, 422/100, 422/99, 435/101, 435/286.2, 435/286.4, 435/6, 435/7.1, 435/7.4, 435/7.92, 435/961, 435/968, 435/969, 435/970, 435/973, 435/975, 435/287.1, 435/287.2, 435/287.3 , 435/287.9, 435/289.1, 435/292.1, 435/297.1, 435/299.1, 435/305.1, 435/305.2, 436/518, 436/527, 436/528, 436/530-532, 436/807, 436/809, 436/89, 436/116, 530/333-337, 935/88
• US Class Current: 506/40
• 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 2219/00617 : 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 2219/00637 : by coating it with another layer
• CPC Class Codes: B01J 2219/00659 : Two-dimensional arrays
• CPC Class Codes: B01J 2219/00675 : In-situ synthesis on the substrate
• CPC Class Codes: B01J 2219/00686 : Automatic
• CPC Class Codes: B01J 2219/00689 : using computers
• 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: C07K 5/1008 : the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala
• CPC Class Codes: C07K 5/1016 : and aromatic or cycloaliphatic
• 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 50/14 : Solid phase synthesis, i.e. wherein one or more library building blocks are bound to a solid support during library creation; Particular methods of cleavage from the solid support
• 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: Y02P 20/55 : Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
• CPC Class Codes: Y10S 435/97 : Test strip or test slide
• CPC Class Codes: Y10S 435/973 : Simultaneous determination of more than one analyte
• CPC Class Codes: Y10T 436/143333 : Saccharide [e.g., DNA, etc.]
• CPC Class Codes: Y10T 436/2575 : Volumetric liquid transfer

Abstract

A 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 methodolgies.

Claims

1. A kit for use in forming diverse polymer sequences on a substrate, comprising:

a substrate having a surface comprising active sites thereon for the reaction of a selected reagent;

a channel block, said channel block having a first surface and a plurality of recessed regions disposed in said first surface;

one or more apertures in communication with the plurality of recessed regions;

a holder for engaging said first surface of said channel block with a surface of said substrate;

a translator, said translator moving said channel block and said substrate relative to each other; and

a reagent delivery system for injecting selected reagents into said one or more apertures.

2. The kit as recited in claim 1, wherein said one or more apertures extend through a back surface of said channel block.

3. The kit as recited in claim 1, said active sites being protected by a plurality of protecting groups.

4. The kit as recited in claim 3, further comprising a deprotecting agent for removing said protecting groups.

5. The kit as recited in claim 3, further comprising a light source for exposing selected portions of said substrate to light for removal of at least some of said plurality of protecting groups on said substrate at said selected portions, said plurality of protecting groups being removable upon exposure to light.

6. The kit as recited in claim 5, further comprising a light mask, said light mask comprising regions opaque to said light source and regions transmissive to said light source.

7. The kit as recited in claim 6, wherein said reagent delivery system comprises a dispenser.

8. The kit as recited in claim 7, wherein said dispenser comprises a plurality of pipets, each of said plurality of pipets being coupled to at least one of said one or more apertures.

9. The kit as recited in claim 7, wherein said dispenser is selected from the group consisting of a pipettor, a piezoelectric pump, an electrophoretic pump, an osmotic pump, and a cell sorter.

10. The kit as recited in claim 7, wherein said dispenser is a pellet dispenser.

11. The kit of claim 7, further comprising a translational mechanism for translating said dispenser to each of said plurality of recessed regions.

12. An apparatus for delivering fluids to a plurality of selected regions on surface of a substrate, comprising

a substrate having selected regions thereon, said selected regions having a surface comprising active sites thereon for the reaction of a selected reagent;

a body of a channel block having a first surface, said first surface having a plurality of recessed regions disposed therein, whereby when said first surface is mated with said surface of said substrate, said plurality of recessed regions are adjacent to said selected regions on said surface of said substrate;

a plurality of fluid inlets disposed in said body, each of said plurality of fluid inlets being fluidly connected to at least one of said plurality of recessed regions; and

a translator, said translator moving said channel block and said substrate relative to each other.

13. The apparatus of claim 12, wherein said plurality of fluid inlets comprises a plurality of apertures disposed through said body of said channel block, whereby each of said plurality of apertures is fluidly connected to at least one of said plurality of recess regions.

14. The apparatus of claim 12, further comprising a holder for engaging said first surface of said channel block to said surface of said substrate.

15. The apparatus of claim 12, wherein said channel block is an etched silicon wafer.

16. The apparatus of claim 12, wherein said plurality of recessed regions comprises greater than about 10 recessed grooves disposed in said first surface of said channel block.

17. The apparatus of claim 12, wherein said plurality of recessed regions comprises greater than about 400 grooves disposed in said first surface of said channel block.

18. The apparatus of claim 12, wherein said plurality of recessed regions comprises greater than about 8000 grooves disposed in said first surface of said channel block.

19. The apparatus of claim 12, further comprising a dispenser for delivering selected fluids to said plurality of fluid inlets.

20. The apparatus of claim 19, wherein said dispenser is selected from the group consisting of a pipettor, a piezoelectric pump, an electrophoretic pump, an osmotic pump, and a cell sorter.

21. The kit as recited in claim 19, wherein said dispenser is a pellet dispenser.

22. The apparatus of claim 19, further comprising a translational mechanism for translating said dispenser to each of said plurality of recessed regions.