APPARATUS FOR POLYMER SYNTHESIS

• US 20100298171A1
• Filed: 05/24/2010
• Published: 11/25/2010
• Est. Priority Date: 05/22/2009
• Status: Abandoned Application

• Current Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Original Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Inventors: Meijles, Peter, Pawloski, Adam, McGall, Glenn H., Shirazi, Mohsen
• Application Number:
  US12/786,287
• Publication Number:
  US 20100298171A1
• Time in Patent Office: Days
• US Class Current: 506/32
• 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 2219/00286 Reactor vessels with top and bottom openings
• CPC Class Codes: B01J 2219/00353 Pumps
• CPC Class Codes: B01J 2219/00389 Feeding through valves
• CPC Class Codes: B01J 2219/00432 Photolithographic masks
• CPC Class Codes: B01J 2219/00527 Sheets
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00608 DNA chips
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00626 Covalent
• CPC Class Codes: B01J 2219/00637 by coating it with another layer
• CPC Class Codes: B01J 2219/00725 Peptides
• CPC Class Codes: C12Q 1/6834 Enzymatic or biochemical coupling of nucleic acids to a solid phase
• CPC Class Codes: C40B 40/04 Libraries containing only organic compounds
• 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

Abstract

Novel processes are disclosed for the large scale preparation of arrays of polymer sequences wherein each array includes a plurality of different, positionally distinct polymer sequences having known monomer sequences. In one embodiment, two substrates are processed simultaneously in a reaction chamber, wherein the substrates are facing each other and in contact with a monomer solution. In a further embodiment, multiple rotating flow cells are used in combination with a photolysis equipment to synthesize wafers.

Claims

1. A method of preparing a plurality of polymer arrays on a surface of a plurality of substrates, the method comprising:

(a) providing a substrate A having a first surface and a substrate B having a second surface, wherein the first surface of substrate A is facing the second surface of substrate B in a reaction chamber;

(b) activating the first surface and the second surface;

(c) simultaneously coupling a monomer to the first surface of substrate A and to the second surface of substrate B in a reaction chamber with a monomer solution, wherein the monomer solution is in contact with the first surface of substrate A and the second surface of substrate B ;

(d) repeating steps (b) and (c) in different selected regions of the first and second surfaces to form a plurality of different polymer sequences in different known locations on the first and second surfaces of substrate A and B.

2. The method according to claim 1, wherein activating comprises directing an activation radiation at the first surface of substrate A and second surface of substrate B.

3. The method according to claim 2, wherein the activation radiation is selected from the group consisting of electron beam radiation, gamma radiation, x-ray radiation, ultra-violet radiation, visible light, and infrared radiation.

4. The method according to claim 1, wherein the first surface and the second surface have reactive functional groups thereon, the reactive functional groups being protected by a protective group.

5. The method according to claim 4, wherein the reactive functional groups are attached to the first and second surfaces via a linker.

6. The method according to claim 4, wherein the protective group is selected from the group consisting of orthonitrobenzyl derivatives, 6-nitroveratryloxycarbonyl, 2-nitrobenzyloxycarbonyl, alpha, alpha-dimethyl-dimethoxybenzyloxycarbonyl, o-hydroxy-alpha-methyl cinnamoyl derivatives and mixtures thereof.

7. The method according to claim 1, wherein the method further comprises rotating the reaction chamber to mix the monomer solution during the activating step.

8. The method according to claim 7, wherein the substrate is glass.

9. The method according to claim 1, wherein activation comprises using a mask having transparent locations and opaque locations to direct light at the selected locations.

10. The method according to claim 1, wherein the polymer sequences comprise nucleic acid sequences, and the monomers in the reaction fluids comprise nucleotides.

11. The method according to claim 1, wherein the polymer sequences comprise polypeptide sequences, and the monomers in the reaction fluids comprise amino acids.

12. A system for synthesizing a plurality of monomers on a plurality of substrates comprising:

a reaction chamber;

a system for delivering reaction fluids containing selected monomers to the reaction chamber; and

a substrate A having a first surface;

a substrate B having a second surface, wherein the first and second surfaces are exposed to the reaction fluids in the reaction chamber simultaneously; and

an activating system for activating the first surface of substrate A and the second surface of substrate B.

13. The system according to claim 12, wherein the activating system comprises directing an activation radiation at the first surface of substrate A and second surface of substrate B.

14. The system according to claim 13, wherein the activating system is selected from the group consisting of electron beam radiation, gamma radiation, x-ray radiation, ultra-violet radiation, visible light, and infrared radiation.

15. The system according to claim 12, wherein the first surface and the second surface have reactive functional groups thereon, the reactive functional groups being protected by a protective group.

16. The system according to claim 15, wherein the reactive functional group is attached to the substrate via a linker.

17. The system according to claim 15, wherein the protective group is selected from the group consisting of orthonitrobenzyl derivatives, 6-nitroveratryloxycarbonyl, 2-nitrobenzyloxycarbonyl, alpha, alpha-dimethyl-dimethoxybenzyloxycarbonyl, o-hydroxy-alpha-methyl cinnamoyl derivatives and mixtures thereof.

18. The system according to claim 12, further comprising a means for rotating to mix the reaction fluids during the exposure process to the reaction fluids.

19. The system according to claim 12, wherein the first surface of substrate A is facing towards the second surface of substrate B in the reaction chamber thereby enclosing a cavity within the reaction chamber, the cavity including an inlet for flowing reaction fluids containing monomers into said cavity and an outlet for flowing reaction fluids out of the cavity.

20. The system according to claim 12, wherein the substrate comprises glass.

21. The system according to claim 12, wherein the activation step comprises using a mask having transparent locations and opaque locations to direct light at the selected locations.

22. A method of preparing a plurality of polymer arrays on a surface of a substrate, the method comprising:

(a) providing at least one substrate having a surface;

(b) activating the surface of at least one substrate;

(c) coupling a monomer to the surface of the at least one substrate with a monomer solution in a reaction chamber;

(d) repeating steps (b) and (c) in different selected regions of the surface to form a plurality of different polymer sequences in different known locations on the surface of the substrate;

(e) using the monomer solution to activate a surface of a different substrate by repeating steps (a) through (d) on the different substrate using the monomer solution.