Device for chemical and biochemical reactions using photo-generated reagents

• US 7,544,638 B2
• Filed: 01/13/2003
• Issued: 06/09/2009
• Est. Priority Date: 02/11/1998
• Status: Expired due to Term

• Current Assignee: University of Houston Law Center (University of Houston System), Board of Regents of the University of Michigan (University of Michigan)
• Original Assignee: University of Houston (University of Houston System), Board of Regents of the University of Michigan (University of Michigan)
• Inventors: Gao, Xiaolian, Zhou, Xiaochuan, Gulari, Erdogan
• Primary Examiner(s): Schultz; J D
• Assistant Examiner(s): Lundgren; Jeffrey S.
• Application Number:
  US10/340,928
• Publication Number:
  US 20080318806A1
• Time in Patent Office: 2,339 Days
• Field of Search: 435/4, 435/6, 435/7.1, 435/283.1, 435/286.1, 435/286.2, 435/287.1, 435/287.2, 435/288.3, 436/94, 436/145, 436/518, 436/523, 436/524, 436/527, 436/528, 436/72, 436/805, 436/91, 422/129, 422/131, 530/334
• US Class Current: 506/27
• 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 2219/00434 Liquid crystal masks
• CPC Class Codes: B01J 2219/00439 using micromirror arrays
• CPC Class Codes: B01J 2219/00497 Features relating to the solid phase supports
• CPC Class Codes: B01J 2219/00527 Sheets
• CPC Class Codes: B01J 2219/00529 DNA chips
• 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 2219/00641 the porous medium being continuous, e.g. porous oxide substrates
• 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 2219/00689 : using computers
• 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: B01J 2219/00731 : Saccharides
• 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 40/12 : Libraries containing saccharides or polysaccharides, 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: 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

Abstract

This invention provides method and apparatus for performing chemical and biochemical reactions in solution using in situ generated photo-products as reagent or co-reagent. In particular, the present invention provides methods and devices for generating a photogenerated reaction in solution on a substrate comprising generating a light beam using an optical device system comprising a light source and a computer-controlled spatial optical modulator comprising a digital micromirror device and using the spatial optical modulator to direct light to fluidly isolated reaction sites under conditions such that a photogenerated reaction takes place. The method and apparatus of the present invention have applications in parallel synthesis of molecular sequence arrays on solid surfaces.

Claims

1. A method for parallel synthesis of an array of selected multimers on a substrate comprising fluidly isolated reaction sites containing one or more protected initiation moieties, the method comprising:

(a) selectively irradiating, using a spatial optical modulator comprising a digital micromirror device, fluidly isolated reaction sites to generate deprotected initiation moieties at the irradiated fluidly isolated reaction sites;

wherein the deprotected initiation moieties are generated by;

(i) contacting the substrate with a liquid solution comprising one or more photo-reagent precursors, such that the liquid solution is in contact with the initiation moieties; and

(ii) selectively irradiating fluidly isolated reaction sites to produce one or more photo-generated reagents, wherein the photo-generated reagents are effective to deprotect the initiation moieties at the irradiated fluidly isolated reaction sites;

(b) coupling one or more monomers to the deprotected initiation moieties to generate new protected initiation moieties; and

(c) repeating steps (a)-(b) until the array of selected multimers has been synthesized;

wherein the coupling reactions to synthesize the array of selected multimers occur with a yield of 98% or greater.

2. The method of claim 1, wherein the selected multimers are DNA.

3. The method of claim 2, wherein the DNA is selected from the group consisting of nucleotide phosphoramidites and analogs thereof.

4. The method of claim 1, wherein the selected multimers are oligonucleotides.

5. The method of claim 1, wherein the selected multimers are RNA.

6. The method of claim 1, wherein the selected multimers are DNA/RNA hybrids.

7. The method of claim 1, wherein the selected multimers are peptides.

8. The method of claim 1, wherein the selected multimers are carbohydrates.

9. The method of claim 1, wherein the photo-reagent precursors are selected from the group consisting of acid precursors and base precursors.

10. The method of claim 1, wherein the monomer comprises an unprotected reactive site and a protected reactive site.

11. The method of claim 1, wherein the protected initiation moieties are protected by an acid-labile group.

12. The method of claim 1, wherein the protected initiation moieties comprise linker molecules, wherein each of the linker molecules comprise a reactive functional group protected by an acid-labile group.

13. A method for generating a photogenerated reaction in solution on a substrate comprising:

a) generating a light beam using an optical device system comprising a light source and a computer-controlled spatial optical modulator comprising a digital micromirror device; and

b) redirecting the light beam using the spatial optical modulator comprising a digital micromirror device to a fluidly isolated reaction site on said substrate under conditions such that a photogenerated reaction takes place, wherein said photogenerated reaction comprises contacting said substrate with a liquid solution comprising one or more photo-reagent precursors, said precursors selected from the group consisting of acid precursors and base precursors, such that the liquid solution is in contact with initiation moieties on said substrate and selectively irradiating fluidly isolated reaction sites with said micromirror device to produce one or more photo-generated reagents, wherein said photo-generated reagents deprotect initiation moieties at the irradiated, fluidly isolated reaction sites.

14. The method of claim 13, wherein the digital micromirror device comprises a plurality of micromirrors.

15. The device of claim 14, wherein the micromirrors are individual rocking mirrors.

16. A method for parallel synthesis of an array of selected multimers on a substrate comprising isolated reaction sites containing one or more protected initiation moieties, the method comprising:

(a) selectively irradiating, using a spatial optical modulator comprising a digital micromirror device, fluidly isolated reaction sites to generate deprotected initiation moieties at the irradiated isolated reaction sites, wherein generating said deprotected initiation moieties comprises;

(i) contacting the substrate with a liquid solution comprising one or more photo-reagent precursors, said precursors selected from the group consisting of acid precursors and base precursors, such that the liquid solution is in contact with the initiation moieties; and

(ii) selectively irradiating fluidly isolated reaction sites to produce one or more photo-generated reagents, wherein the photo-generated reagents deprotect the initiation moieties at the irradiated, fluidly isolated reaction sites;

(b) coupling one or more monomers to the deprotected initiation moieties to generate new protected initiation moieties; and

(c) repeating steps (a)-(b) until the array of selected multimers has been synthesized;

wherein the coupling reactions to synthesize the array of selected multimers occur with a yield of 98% or greater.

17. The method of claim 16, wherein the selected multimers are DNA.

18. The method of claim 17, wherein the DNA is selected from the group consisting of nucleotide phosphoramidites and analogs thereof.

19. The method of claim 16, wherein the selected multimers are oligonucleotides.

20. The method of claim 16, wherein the monomer comprises an unprotected reactive site and a protected reactive site.

21. The method of claim 16, wherein the protected initiation moieties are protected by an acid-labile group.

22. The method of claim 16, wherein the protected initiation moieties comprise linker molecules, wherein each of the linker molecules comprise a reactive functional group protected by an acid-labile group.