Method and apparatus for chemical and biochemical reactions using photo-generated reagents

• US 20040035690A1
• Filed: 11/01/2002
• Published: 02/26/2004
• Est. Priority Date: 02/11/1998
• Status: Abandoned Application

• Current Assignee: Board of Regents of the University of Michigan (University of Michigan)
• Original Assignee: Board of Regents of the University of Michigan (University of Michigan)
• Inventors: Gulari, Erdogan
• Application Number:
  US10/285,824
• Publication Number:
  US 20040035690A1
• Time in Patent Office: Days
• US Class Current: 204/157.15
• 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. Specifically, the method and apparatus of the present invention have applications in parallel synthesis of molecular sequence arrays on solid surfaces.

Claims

1. A method, comprising:

a) providing;

i) a plurality of protected polypeptides attached to a substrate, each of said protected polypeptides comprising at least one protecting group, said substrate configured so as to comprise of a plurality of isolated reaction sites;

ii) a mixture comprising triarylsulfonium antimonyhexafluoride; and

iii) a laser;

b) contacting one or more of said isolated reaction sites with said mixture to create one or more contacted reaction sites; and

c) illuminating one or more said contacted reaction sites with said laser under conditions such that said protecting group of at least one protected polypeptide is removed so as to create a deprotected polypeptide.

2. The method of claim 1, wherein said mixture further comprises dichloromethane.

3. The method of claim 2, wherein said mixture further comprises perylene.

4. The method of claim 1, wherein said substrate prior to step (a) was derivatized.

5. The method of claim 4, wherein said substrate is derivatized with triethoxysilane.

6. The method of claim 1, wherein said protecting group is tert-butoxycarbonyl.

7. The method of claim 1, further comprising step d) contacting said deprotected polypeptide with a first protected monomer under conditions such that said first protected monomer is coupled to said polypeptide to create a first extended polypeptide, said first protected monomer comprising a protecting group.

8. The method of claim 7, further comprising step e) illuminating said first extended polypeptide with said laser under conditions such that said protecting group of said first protected monomer is removed so as to create a second extended polypeptide.

9. The method of claim 8, further comprising step (f) contacting said second extended polypeptide with a second protected monomer under conditions such that said second protected monomer is coupled to said second extended polypeptide to create a third extended polypeptide, said third extended polypeptide comprising a protecting group.

10. The method of claim 1, wherein said plurality of isolated reaction sites of step (a) is selected from the group consisting of reaction wells, reactor assembly cartidges and non-wetting surfaces.

11. A method, comprising:

a) providing;

i) a plurality of protected first monomers attached to a substrate, each of said protected first monomers comprising at least one protecting group, said substrate configured so as to comprise of a plurality of isolated reaction sites;

ii) a mixture comprising trisarylsulfonium antimonyhexafluoride; and

iii) a laser;

b) contacting one or more of said isolated reaction sites with said mixture to create one or more contacted reaction sites; and

c) illuminating one or more said contacted reaction sites with said laser under conditions such that said protecting group of at least one protected first monomer is removed so as to create a deprotected first monomer.

12. The method of claim 11, wherein said mixture further comprises dichloromethane.

13. The method of claim 12, wherein said mixture further comprises perylene.

14. The method of claim 11, wherein said substrate prior to step (a) is derivatized.

15. The method of claim 14, wherein said substrate is derivatized with tertbutoxycarbonyl.

16. The method of claim 11, further comprising step d) contacting said deprotected first monomer with a protected second monomer under conditions such that said protected second monomer is coupled to said first monomer to create a first protected biopolymer, said protected second monomer comprising a protecting group.

17. The method of claim 16, further comprising step e) illuminating said first protected biopolymer with said laser under conditions such that said protecting group of said protected second monomer is removed so as to create a first deprotected biopolymer.

18. The method of claim 17, further comprising step (f) contacting said first deprotected biopolymer with a third protected monomer under conditions such that said third protected monomer is coupled to said first deprotected biopolymer to create a second protected biopolymer, said second protected biopolymer comprising a protecting group.

19. The method of claim 11, wherein said monomer comprises an amino acid.

20. A method, comprising:

a) providing;

i) a plurality of protected linkers attached to a substrate, each of said protected linkers comprising at least one protecting group, said substrate configured so as to comprise of a plurality of isolated reaction sites;

ii) a mixture comprising triarylsulfonium antimonyhexafluoride; and

iii) a laser;

b) contacting one or more of said protected linkers with said mixture to create one or more contacted protected linkers; and

c) illuminating one or more said protected linkers with said laser under conditions such that said protecting group of at least one of said protected linkers is removed so as to create a deprotected linker.

21. The method of claim 20, wherein said mixture further comprises dichloromethane.

22. The method of claim 21, wherein said mixture further comprises perylene.

23. The method of claim 20, wherein said substrate prior to step (a) is derivatized.

24. The method of claim 23, wherein said substrate was derivatized with tertbutoxycarbonyl.

25. The method of claim 20, further comprising step d) contacting said deprotected linker with a first protected monomer under conditions such that said first protected monomer is coupled to said deprotected linker to create a first multimer, said first protected monomer comprising a protecting group.

26. The method of claim 25, further comprising step e) illuminating said first multimer with said laser under conditions such that said protecting group of said first protected monomer is removed so as to create a deprotected first multimer.

27. The method of claim 26, further comprising step (f) contacting said deprotected first multimer with a second protected monomer under conditions such that said second protected monomer couples with said deprotected first monomer to create a second multimer, said second protected monomer comprising a protecting group.