Device for chemical and biochemical reactions using photo-generated reagents

• US 20030138363A1
• Filed: 09/11/2002
• Published: 07/24/2003
• Est. Priority Date: 02/11/1998
• Status: Active Grant

• Current Assignee: University of Houston Law Center (University of Houston System), 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: Gao, Xiaolian, Zhou, Xiaochuan, Gulari, Erdogan
• Granted Patent: US 7,491,680 B2
• Time in Patent Office: Days
• US Class Current: 422/186
• 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) generating a light beam;

b) redirecting said light beam with a micromirror such that it is directed to a reaction site under conditions such that a photogenerated reaction takes place, said reaction site comprising a compound bound to a substrate.

2. The method of claim 1, wherein said light beam is redirected with a plurality of micromirrors.

3. The method of claim 2, wherein said micromirrors are individual rocking mirrors.

4. The method of claim 2, further comprising prior to step b) controlling said micromirrors with a computer.

5. A method of deprotecting initiating moieties attached to a solid surface comprising:

a) providing initiating moieties at a plurality of specific reaction sites on a solid surface;

b) contacting at least a portion of said initiating moieties with a liquid solution comprising one or more photo-reagent precursors, said precursors selected from the group consisting of acid precursors and base precursors; and

c) exposing said solid surface to a desired light pattern so as to cause formation of a photo-reagent from said photo-reagent precursor, said photo-reagent directly deprotecting said initiating moieties so as to create deprotected initiating moieties.

6. The method of claim 5, wherein said desired light pattern is generated using micromirrors.

7. The method of claim 6, wherein said micromirrors are individual rocking mirrors.

8. The method of claim 5, wherein after step c) a predetermined set of said specific reaction sites are unexposed to said desired light pattern.

9. A method of deprotecting initiating moieties attached to a solid surface comprising:

a) providing;

i) initiating moieties at a plurality of specific reaction sites on a solid surface; and

ii) a system, comprising a light source and a plurality of mirrors, configured to generate a desired light pattern;

b) contacting at least a portion of said initiating moieties with a liquid solution comprising one or more photo-reagent precursors, said precursors selected from the group consisting of acid precursors and base precursors; and

c) exposing said solid surface to said desired light pattern so as to cause formation of a photo-reagent from said photo-reagent precursor, said photo-reagent directly deprotecting said initiating moieties so as to create deprotected initiating moieties.

10. The method of claim 9, wherein said mirrors are micromirrors.

11. The method of claim 10, wherein said mirrors are individual rocking mirrors.

12. The method of claim 9, wherein said system further comprises a computer configured for controlling said mirrors.

13. The method of claim 9, wherein after step c) a predetermined set of said specific reaction sites are unexposed to said desired light pattern.

14. The method of claim 9, wherein said initiating moieties comprise linker molecules, each of said linker molecules comprising a reactive functional group protected by an acid-labile protecting group.

15. A method of deprotecting initiating moieties attached to a solid surface comprising:

a) providing;

i) initiating moieties at a plurality of specific reaction sites on a solid surface; and

ii) an optical arrangement, comprising;

a plurality of mirrors;

a light source configured to generate a light beam,

a filter in-line with said light source configured to generate a desired light wavelength,

a condenser lens in-line with said filter configured to focus said desired light wavelength,

a reflector in-line with said condenser lens configured to redirect said desired light wavelength onto said plurality of mirrors so as to generate a desired light pattern,

a projection lens in-line with said mirrors configured to expose said solid surface to said desired light pattern;

b) contacting at least a portion of said initiating moieties with a liquid solution comprising one or more photo-reagent precursors, said precursors selected from the group consisting of acid precursors and base precursors; and

c) exposing said solid surface to said desired light pattern so as to cause formation of a photo-reagent from said photo-reagent precursor, said photo-reagent directly deprotecting said initiating moieties so as to create deprotected initiating moieties.

16. The method of claim 15, wherein said mirrors are individual rocking mirrors.

17. The method of claim 16, further comprising prior to step c) controlling said mirrors with a computer.

18. The method of claim 15, wherein after step c) a predetermined set of said specific reaction sites are unexposed to said desired light pattern.

19. A method of deprotecting initiating moieties attached to a solid surface comprising:

a) contacting said initiating moieties with a liquid solution comprising one or more photo-reagent precursors, said precursors selected from the group consisting of acid precursors and base precursors; and

b) irradiating said liquid solution to cause formation of a photo-reagent from said photo-reagent precursor, said photo-reagent directly deprotecting said initiating moieties so as to create deprotected initiating moieties.

20. The method of claim 19 wherein said liquid solution further comprises photosensitizers for enhancing the conversion of said photo-reagent precursors.

21. The method of claim 19 wherein said liquid solution further comprises stabilizers for improving the yield of said deprotected initiating moieties.

23. The method of claim 19 or 22 wherein said irradiating of step (a) produces protons.

24. The method of claim 23 wherein said protons contact said initiating moieties by diffusion.

22. A method of deprotecting initiating moieties attached to a solid surface comprising:

a) irradiating a liquid solution comprising one or more photo-reagent precursors to cause conversion of said photo-reagent precursors; and

b) contacting the irradiated liquid solution with said solid surface under conditions such that said solution is contained within defined areas on said solid surface, thereby deprotecting the initiating moieties.

25. A method of simultaneously deprotecting initiating moieties at a plurality of specific reaction sites on a substrate, said initiating moieties being attached to said substrate, the method comprising:

a) contacting a liquid solution comprising one or more photo-reagent precursors with said substrate such that said liquid solution is in contact with said initiating moieties;

b) isolating said specific reaction sites; and

c) irradiating a selected number of the isolated reaction sites to produce photo-generated reagents thereby simultaneously deprotecting said initiating moieties at the irradiated reaction sites.

26. The method of claim 25 wherein said specific reaction sites are isolated using isolation mechanisms selected from the group consisting of reaction wells, reactor cartridges and non-wetting surfaces.

27. The method of claim 25 wherein said selected number of isolated reaction sites is irradiated under computer control.

28. The method of claim 27 wherein said computer control comprises a programmable light projection device comprising a programmable spatial optical modulator.

29. The method of claim 28 wherein said programmable spatial optical modulator is selected from the group consisting of digital micromirror device, reflective liquid crystal display device, and transmissive liquid crystal display device.

30. The method of claim 26 wherein said production of photo-generated reagent at a selected number of isolated reaction sites is controlled by the light dosage applied to each irradiated reaction site.