METHOD FOR FORMING MOLECULAR SEQUENCES ON SURFACES

• US 20070224616A1
• Filed: 03/23/2007
• Published: 09/27/2007
• Est. Priority Date: 03/24/2006
• Status: Abandoned Application

• Current Assignee: University of Houston (University of Houston System), Board of Regents of the University of Michigan (University of Michigan), University of Michigan
• Original Assignee: University of Houston (University of Houston System)
• Inventors: Gao, Xiaolian, Zhou, Xiaochuan, Gulari, Erdogan, Rouillard, Jean-Marie
• Application Number:
  US11/690,368
• Publication Number:
  US 20070224616A1
• 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 2219/00585 Parallel 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 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00675 In-situ synthesis on the substrate
• 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 2219/00729 Peptide nucleic acids [PNA]
• 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: C40B 50/18 using a particular method of attachment to the solid support
• CPC Class Codes: G01N 33/54353 with ligand attached to the carrier via a chemical coupling agent coatings G01N33/54393

Abstract

A method for forming molecular sequences includes derivatizing an unconfined substrate surface with at least one linker containing a protected reactive group. The substrate is contacted with a solution containing a photogenerated reagent precursor and a buffer and/or a neutralizer. A photogenerated reagent is generated in at least a portion of the solution. The photogenerated reagent is configured to initiate the formation of at least one active region on the substrate surface. A monomer is coupled to the active region.

Claims

1. A method for forming a molecular sequence, comprising:

derivatizing an unconfined substrate surface with at least one linker containing a protected reactive group;

contacting the substrate with a solution containing a photogenerated reagent precursor and at least one of a buffer or a neutralizer;

generating a photogenerated reagent in at least a portion of the solution, the photogenerated reagent configured to initiate the formation of at least one active region on the substrate surface; and

coupling a monomer to the at least one active region.

2. The method as defined in claim 1 wherein the photogenerated reagent precursor is selected from a photoacid generating molecule and a photobase generating molecule.

3. The method as defined in claim 2 wherein the photogenerated reagent is selected from an acid and a base.

4. The method as defined in claim 1 wherein generating the photogenerated reagent is accomplished via selectively exposing at least one region of the substrate to electromagnetic radiation.

5. The method as defined in claim 4 wherein the photogenerated reagent is substantially confined to the at least one exposed region via the at least one of the buffer or neutralizer.

6. The method as defined in claim 1 wherein the photogenerated reagent diffuses to a surface of the substrate where it catalyzes deprotection of the protected reactive group, thereby exposing a reactive group and forming the at least one active region.

7. The method as defined in claim 1 wherein prior to coupling the monomer to the at least one active region, the method further comprises removing the solution from the substrate.

8. The method as defined in claim 1 wherein the monomer has two ends, one of the two ends being unprotected and an other of the two ends having a protected reactive group attached thereto.

9. The method as defined in claim 8 wherein the contacting, the generating, and the coupling steps are repeated to form a predetermined sequence.

10. The method as defined in claim 1 wherein the solution further comprises at least one of a sensitizer, a stabilizer, a viscosity additive, or combinations thereof.

11. The method as defined in claim 1 wherein the photogenerated reagent is an acid, and wherein the buffer or neutralizer is selected from pyridine, lutidine, piperidine, primary amines, secondary amines, tertiary amines, derivatives thereof, and combinations thereof.

12. The method as defined in claim 1 wherein the photogenerated reagent is a base, and wherein the buffer or neutralizer is selected from benzillic acid, aluminum chloride, iron (III) chloride, boron trifluoride, ytterbium (III) triflate, butyric acid, propionic acid, phenol, and combinations thereof.

13. The method as defined in claim 1 wherein the monomer has two unprotected ends.

14. The method as defined in claim 1 wherein the monomer is in a solution containing at least one activator.

15. The method as defined in claim 14 wherein the at least one activator is selected from tetrazole;

4,5,dicyanoimidazole (DCI);

pyridiniumtrifluoroacetate;

5-ethlythiotetrazole;

(3,5-dintrophenyl)-1H-tetrazole;

trimethylchlorosilane;

activator 42 (5-(bis-3,5-trifluormethylphenyl)1-H-tetrazole;

derivatives thereof, and combinations thereof.

16. A molecular sequence formed by the method of claim 1.

17. An apparatus, comprising:

an unconfined substrate surface; and

a molecular sequence coupled to the unconfined substrate surface.

18. The apparatus as defined in claim 17 wherein the molecular sequence includes a first monomer coupled to the unconfined substrate surface via a reactive group of a linker.

19. The apparatus as defined in claim 18 wherein the reactive group initially contains a protection group that is removed via a photogenerated reagent.

20. The apparatus as defined in claim 17 wherein the molecular sequence is formed of a plurality of monomers coupled together.

21. The apparatus as defined in claim 20 wherein each of the plurality of monomers is selected from nucleotides, locked nucleic acid monomers, amino acids, monosaccharides, disaccharides, and combinations thereof.