METHOD AND APPARATUS FOR CHEMICAL AND BIOCHEMICAL REACTIONS USING PHOTO-GENERATED REAGENTS

• US 20020081582A1
• Filed: 02/10/1999
• Published: 06/27/2002
• Est. Priority Date: 02/11/1998
• Status: Active Grant

• Current Assignee: University of Houston (University of Houston System), 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 Law Center (University of Houston System), Board of Regents of the University of Michigan (University of Michigan)
• Inventors: ZHOU, XIAOCHUAN, GULARI, ERDOGAN, GAO, XIAOLIAN
• Granted Patent: US 6,426,184 B1
• Time in Patent Office: Days
• US Class Current: 435/6
• 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 device for synthesizing a multimer or a plurality of multimers comprising:

a chemical reactor comprising one or more isolated reaction sites; and

an optical system operably linked to the chemical reactor, which optical system selectively irradiates one or more reaction sites.

2. The device of claim 1 further comprising a reagent manifold operably linked to the chemical reactor.

3. The device of claim 1 further comprising a controller for controlling the optical system.

4. The device of claim 3 wherein the controller is a computer.

5. A device for synthesizing a multimer or a plurality of multimers comprising:

a chemical reactor comprising one or more isolated reaction sites;

a reagent manifold operably linked to the chemical reactor;

an optical system operably linked to the chemical reactor, which optical system selectively irradiates one or more reaction sites; and

a controller operably linked to the optical system for controlling the selective irradiation of reaction sites.

6. The device of claim 5 wherein the optical system comprises a light source, filter system, lenses, spatial optical modulator, and reflectors.

7. The device of claim 5 wherein the light source is selected from the group consisting of mercury lamp, a xenon lamp, a halogen lamp, a laser, and a light emitting diode.

8. The device of claim 6 wherein the spatial optical modulator is selected from the group consisting of digital micromirror device, reflective liquid crystal display device, and transmissive liquid crystal display device.

9. A method for synthesizing one or more selected multimers on a substrate comprising one or more initiating moieties, the method comprising:

(a) adding one or more photogenerated acid precursors to the substrate;

(b) irradiating the substrate to generate a photogenerated acid from the precursors, which acid deblocks the initiating moieties;

(c) coupling one or more monomers to the deblocked initiating moiety;

(d) repeating steps (a)-(c) until the selected multimers have been synthesized.

10. The method of claim 9 wherein the selected multimers are DNA.

11. The method of claim 9 wherein the selected multimers are RNA.

12. The method of claim 9 wherein the selected multimers are DNA/RNA hybrids.

13. The method of claim 9 wherein the selected multimers are peptides.

14. The method of claim 9 wherein the selected multimers are carbohydrates.

15. The method of claim 9 wherein the photogenerated acids are selected from the group consisting of photogenerated acids of Table 1a.

16. A method for synthesizing an array of selected oligonucleotides on a substrate comprising isolated reaction sites containing initiating moieties, the method comprising:

(a) adding one or more photogenerated acid precursors to the substrate;

(b) differentially irradiating isolated reaction sites to generate a photogenerated acid from the precursors, which acid deblocks the initiating moieties in the irradiated isolated reaction sites;

(c) coupling one or more monomers to the deblocked initiating moieties;

(d) repeating steps (a)-(c) until the array of selected oligonucleotides has been synthesized.

17. A method for synthesizing an array of selected multimers on a substrate comprising isolated surface sites containing initiating moieties, the method comprising:

(a) adding one or more photogenerated reagent precursors to the substrate;

(b) differentially irradiating isolated reaction sites to generate a photogenerated reagent from the precursors, which reagent activates the initiating moieties in the irradiated isolated reaction sites;

(c) coupling one or more monomers to the activated initiating moieties;

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

18. A method for simultaneously modulating chemical conditions at an array of isolated reaction sites on a substrate, the method comprising:

(a) adding one or more photogenerated reagent precursors to the substrate;

(b) differentially irradiating isolated reaction sites to differentially generate predetermined amounts of photogenerated reagents from the precursors, which affect chemical conditions in the irradiated isolated reaction sites.