Polymer synthesis

• US 20020136772A1
• Filed: 03/26/2002
• Published: 09/26/2002
• Est. Priority Date: 03/26/2001
• Status: Abandoned Application

• Current Assignee: Linden Technologies Incorporated
• Original Assignee: Linden Technologies Incorporated
• Inventors: Huang, Tai-Nang
• Application Number:
  US10/108,165
• Publication Number:
  US 20020136772A1
• Time in Patent Office: Days
• US Class Current: 424/493
• 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 2219/00387 Applications using probes
• CPC Class Codes: B01J 2219/00533 essentially rectangular
• CPC Class Codes: B01J 2219/00608 DNA chips
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00637 by coating it with another layer
• CPC Class Codes: C40B 50/18 using a particular method of attachment to the solid support

Abstract

A nucleotide compound is activated by an aerosol of a liquid composition that includes, dissolved therein, an activator compound that triggers the covalent coupling of the nucleotide compound to the support. The nucleotide compound can be deposited on the substrate, for example, as a thin film or a particulate composition.

Claims

1. A method comprising:

depositing a nucleotide compound as a particulate composition, the nucleotide compound having a first functional group on a solid support that includes a second functional group attached thereto, and

contacting the solid support with an aerosol of a liquid composition that includes, dissolved therein, an activator compound that triggers the coupling of the first functional group to the second functional group.

2. The method of claim 1 wherein the particulate composition is dry at the instance of the depositing.

3. The method of claim 1 wherein the particulate composition is suspended in a dielectric liquid at the instance of the depositing.

4. The method of claim 1 wherein the liquid composition includes a high boiling point organic solvent.

5. The method of claim 4 wherein the high boiling point organic solvent is a dinitrile, diethyl carbonate or propylene carbonate.

6. The method of claim 5 wherein the high boiling point organic solvent is propylene carbonate.

7. The method of claim 4 wherein the liquid composition is a mixture that includes high boiling point organic solvent and a low boiling point organic solvent.

8. The method of claim 7 wherein the low boiling point solvent is methylene chloride or acetonitrile.

9. The method of claim 7 wherein the mixture is between 20:

80 and 80;

20.

10. The method of claim 7 wherein the mixture includes propylene carbonate and acetonitrile.

11. The method of claim 1 wherein the nucleotide compound further comprises a protecting group.

12. The method of claim 11 wherein the nucleotide residue includes a protecting group attached to C-3′

of the nucleotide residue.

13. The method of claim 11 wherein the nucleotide residue includes a protecting group attached to C-5′

of the nucleotide residue.

14. The method of claim 1 wherein the first functional group is an activated phosphorous group.

15. The method of claim 14 wherein the second functional group is a hydroxyl group.

16. The method of claim 1 wherein the activator compound is tetrazole, 5-(pnitrophenyl)-1H-tetrazole, 5-ethylthio-1H-tetrazole, 4,5-dichloroimidazole, benzimidazolium triflate, or 4,5 dicyano-imidazole.

17. The method of claim 16 wherein the activator compound is tetrazole or 5-ethylthio-1H-tetrazole

18. The method of claim 16 wherein the concentration of the activator compound in the organic solvent is between 0.1 M and 1.0 M.

19. The method of claim 11 wherein the protecting group is acid-sensitive.

20. The method of claim 1 further comprising reacting uncoupled second functional groups with a capping reagent.

21. The method of claim 20 wherein the capping reagent is an acylating reagent.

22. The method of claim 21 wherein the acylating reagent is acetic anhydride.

24. The method of claim 31 wherein the nucleic acid subunits are dissolved in a low boiling point solvent.

25. The method of claim 24 further comprising evaporating the low boiling point solvent prior to contacting the solid support with an aerosol of organic solvent.

26. The method of claim 25 wherein a dry thin film is formed by the evaporating.

28. The method of claim 27 wherein the nucleotide compound includes a protecting group.

30. The method of claim 29 wherein the dry deposition is a thin film.

31. The method of claim 29 wherein the dry deposition comprises a particulate material.

32. The method of claim 29 further comprising reacting uncoupled second reactive groups with a capping reagent.

33. The method of claim 29 wherein the compound is a nucleotide residue.

34. The method of claim 29 wherein the forming comprising depositing the compound dissolved in a low boiling point solvent onto the substrate, and evaporating the low boiling point solvent.

35. The method of claim 33 wherein the first reactive group includes a phosphoramidite.

36. The method of claim 33 wherein the activator compound is a weak acid.

37. The method of claim 36 wherein the activator compound is tetrazole, 5-(p-nitrophenyl)-1H-tetrazole, 5-ethylthio-1H-tetrazole, 4,5-dichloroimidazole, benzimidazolium triflate, or 4,5 dicyano-imidazole.

23. A method comprising:

depositing, on a solid support, different nucleic acid subunits at different addresses, each nucleic acid building block having a first functional group on a solid support that includes a second functional group attached thereto, and

contacting a section of the solid support with an aerosol of an organic solvent that includes an activator reagent dissolved therein, wherein at least a plurality of addresses within the section are concurrently contacted by the aerosol, the activator reagent triggers the coupling of the functional group to the second functional group, and the long axis of the contacted section is at least 0.02 meters.

27. A method comprising:

depositing a nucleotide compound dissolved in a low boiling point solvent, the nucleotide compound having a first functional group, on a solid support that includes a second functional group attached thereto, and

contacting the solid support with an aerosol of a liquid composition that includes, dissolved therein, an activator compound that triggers the covalent coupling of the first functional group to the second functional group, wherein the liquid composition is a mixture of a low boiling point solvent and a high boiling point solvent.

29. A method comprising,

forming a dry deposition of a compound having a first reactive group on a substrate, wherein the substrate has an immobilized second reactive group, and

contacting an organic solvent to the substrate, the solvent having an activator compound dissolved therein, thereby immobilizing the compound to the substrate by coupling the first and second reactive groups.