Uses of cationic salts for polynucleotide synthesis

• US 7,524,950 B2
• Filed: 04/29/2005
• Issued: 04/28/2009
• Est. Priority Date: 10/31/2001
• Status: Expired due to Fees

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Agilent Technologies, Inc.
• Inventors: LeProust, Eric, Peck, Bill, Cogan, Peter, Caruthers, Marvin H., Dellinger, Douglas J.
• Primary Examiner(s): McIntosh, III; Traviss C
• Application Number:
  US11/117,884
• Publication Number:
  US 20050287555A1
• Time in Patent Office: 1,460 Days
• Field of Search: None
• US Class Current: 536/25.3
• CPC Class Codes: B01J 2219/00378 Piezoelectric or ink jet dispensers
• CPC Class Codes: B01J 2219/00608 DNA chips
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00626 Covalent
• CPC Class Codes: B01J 2219/00675 In-situ synthesis on the substrate
• CPC Class Codes: B01J 2219/00677 Ex-situ synthesis followed by deposition on the substrate
• 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: C07H 21/02 with ribosyl as saccharide radical
• CPC Class Codes: C07H 21/04 with deoxyribosyl as saccharide radical
• 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

Abstract

Inkjet printhead solvents and methods of forming an addressable nucleotide array are disclosed.

Claims

1. A method of forming an addressable nucleotide array, comprising providing a first nucleotide compound selected from a nucleotide, an oligonucleotide, and a polynucleotide, wherein the first nucleotide compound is dissolved in a first solution including a first co-solvent and a second co-solvent, wherein the first co-solvent comprises an organic salt, wherein the organic salt comprises a substituted heterocyclic organic cation and an anion, wherein the organic salt has a pKa of about 6 to 8, wherein the organic salt does not reduce the reaction characteristics of the first solution, wherein the first solution has a viscosity of about 5 to 20 cP and a surface tension of about 25 to 45 mN/m at a temperature of about 30 to 40°

C.;

disposing the first solution onto a first position on a substrate, wherein a structure is disposed in the first position, wherein the structure has a second nucleotide compound disposed thereon, wherein the second nucleotide compound is selected from a nucleotide, an oligonucleotide, and a polynucleotide; and

disposing a second solution on the first position of the substrate, wherein the second solution includes an activator, wherein the activator initiates the formation of a third nucleotide compound that includes the first nucleotide compound and the second nucleotide compound.

2. The method of claim 1, wherein the anion is selected from chloride methylsulfate (CH₃SO₄⁻

), trifluoroacetate (CF₃CO₂⁻

), heptafluorobutanoate (CF₃(CF₂)₂CO₂⁻

), triflate (CF₃SO₂⁻

), nonaflate (C₂F₅SO₂⁻

), tosylate anion, dicyanimide anion, bis(trifluoromethylsulfonyl)imide ((CF₃SO₂)₂N⁻

), bis(perfluoroethylsulfonyl)imide ((C₂F₅SO₂)₂N⁻

), tris(trifluoromethylsulfonyl)methide ((CF₃SO₂)₃C⁻

), and combinations thereof.

3. The method of claim 1, wherein the cation is an N-substituted pyridine having the formula

4. The method of claim 1, wherein the cation has the formula

5. The method of claim 1, wherein the cation is a 1,3 di-substituted imidazole organic cations selected from 1,3-dimethyl-imidazolium, 1-ethyl-3-methyl-imidazolium, 1-butyl-3-methyl-imidazolium, 1-hexyl-3-methyl-imidazolium, 1-decyl-3-methyl-imidazolium, 1-dodecyl-3-methyl-imidazolium, 1-methyl-3-octyl-imidazolium, 1-methyl-3-tetradecyl-imidazolium, 1,2-dimethyl-3-propyl-imidazolium, 1-ethyl-2,3-dimethyl-imidazolium, 1-butyl-2,3-dimethyl-imidazolium.

6. The method of claim 1, wherein the solution has a viscosity of about 15 to 20 cP and a surface tension of about 20 to 30 mN/m at a temperature of about 30 to 40°

C.

7. The method of claim 1, wherein disposing the first solution is conducted using an inkjet printhead.

8. The method of claim 1, wherein the second co-solvent is selected from acetonitrile, propylene carbonate, adiponitrile, ethylene carbonate, diethyl carbonate, and combinations thereof.

9. The method of claim 1, wherein the second co-solvent is selected from tetrahydrofuran, dimethylformamide, methylene chloride, adiponitrile, toluene, dioxane, dimethylsulfoxide, succinonitrile, N-methyl pyrrolidone, sulfolane, nitromethane, nitrobenzene, and combinations thereof.

10. The method of claim 1, further comprising:

a) disposing a fourth nucleotide compound onto the first position on the substrate, wherein the fourth nucleotide compound is selected from a nucleotide, an oligonucleotide, and a polynucleotide, wherein the fourth nucleotide compound is dissolved in a fourth solution including the first co-solvent and the second co-solvent, wherein the first co-solvent comprises the organic salt, wherein the fourth solution has a viscosity of about 5 to 20 cP and a surface tension of about 25 to 45 at a temperature of about 30 to 40°

C.;

b) disposing the second solution on the first position of the substrate, wherein the activator initiates the formation of a fifth nucleotide compound that includes the first nucleotide compound, the second nucleotide compound, and the fourth nucleotide compound; and

c) repeating steps a) and b) to form a target nucleotide compound.

11. The method of claim 10, wherein the activator is an organic salt, wherein the organic salt comprises a substituted heterocyclic organic cation and an anion.

12. The method of claim 11, wherein the organic salt is methylimidazolium (trifluoromethylsulfonyl)imide.

13. The method of claim 10, wherein the solution has a contact angle from 45 to 70.

14. A method of forming an addressable nucleotide array, comprising

providing a first nucleotide compound selected from a nucleotide, an oligonucleotide, and a polynucleotide, wherein the first nucleotide compound is dissolved in a first solution including a first solvent, wherein the first solvent comprises an organic salt, wherein the organic salt comprises a substituted heterocyclic organic cation and an anion, wherein the first solution has a viscosity of about 5 to 20 cP and a surface tension of about 25 to 45 mN/m at a temperature of about 30 to 40°

C.;

disposing the first solution onto a first position on a substrate, wherein a structure is disposed in the first position, wherein the structure has a second nucleotide compound disposed thereon, wherein the second nucleotide compound is selected from a nucleotide, an oligonucleotide, and a polynucleotide; and

disposing a second solution on the first position of the substrate, wherein the second solution includes an activator, wherein the activator initiates the formation of a third nucleotide compound that includes the first nucleotide compound and the second nucleotide compound.

15. The method of claim 14, wherein the anion selected from chloride methylsulfate (CH₃SO₄⁻

), trifluoroacetate (CF₃CO₂⁻

), heptafluorobutanoate (CF₃(CF₂)₂CO₂⁻

), triflate(CF₃SO₂⁻

), nonaflate (C₂F₅SO₂⁻

), tosylate anion, dicyanimide anion, bis(trifluoromethylsulfonyl)imide ((CF₃SO₂)₂N⁻

), bis(perfluoroethylsulfonyl)imide ((C₂F₅SO₂)₂N⁻

), tris(trifluoromethylsulfonyl)methide ((CF₃SO₂)₃C⁻

), and combinations thereof.

16. The method of claim 14, wherein the cation is an N-substituted pyridine having the formula

17. The method of claim 14, wherein the cation has the formula

18. The method of claim 14, wherein the cation is a 1,3di-substituted imidazole organic cations selected from 1,3-dimethyl-imidazolium, 1-ethyl-3-methyl-imidazolium, 1-butyl-3-methyl-imidazolium, 1-hexyl-3-methyl-imidazolium, 1-decyl-3-methyl-imidazolium, 1-dodecyl-3-methyl-imidazolium, 1-methyl-3-octyl-imidazolium, 1-methyl-3-tetradecyl-imidazolium, 1,2-dimethyl-3-propyl-imidazolium, 1-ethyl-2,3-dimethyl-imidazolium, 1-butyl-2,3-dimethyl-imidazolium, and combinations thereof.

19. The method of claim 14, wherein the solution has a viscosity of about 15 to 20 cP and a surface tension of about 20 to 30 mN/m at a temperature of about 30 to 40°

C.

20. The method of claim 14, wherein disposing the first solution is conducted using an inkjet printhead.

21. The method of claim 14, wherein the organic salt has a pKa of about 6 to 8.

22. An inkjet printhead solvent, comprising:

an organic salt including a substituted heterocyclic organic cation and an anion, wherein the organic salt has a pKa of about 6 to 8, wherein the first solution has a viscosity of about 5 to 20 cP and a surface tension of about 25 to 45 mN/m at a temperature of about 30 to 40°

C., wherein a first nucleotide compound is dissolved in a first solution including the organic salt.

23. The inkjet printhead solvent of claim 22, wherein the cation is an N-substituted pyridine having the formula

24. The inkjet printhead solvent of claim 22, wherein the cation has the formula

25. The inkjet printhead solvent of claim 22, wherein the cation is a 1,3 di-substituted imidazole organic cations selected from 1,3-dimethyl-imidazolium, 1-ethyl-3-methyl-imidazolium, 1-butyl-3-methyl-imidazolium, 1-hexyl-3-methyl-imidazolium, 1-decyl-3-methyl-imidazolium, 1-dodecyl-3-methyl-imidazolium, 1-methyl-3-octyl-imidazolium, 1-methyl-3-tetradecyl-imidazolium, 1,2-dimethyl-3-propyl-imidazolium, 1-ethyl-2,3-dimethyl-imidazolium, 1-butyl-2,3-dimethyl-imidazolium, and combinations thereof.

26. The inkjet printhead solvent of claim 22, wherein the anion is selected from chloride methylsulfate (CH₃SO₄⁻

), trifluoroacetate (CF₃CO₂⁻

), heptafluorobutanoate (CF₃(CF₂)₂CO₂⁻

), triflate (CF₃SO₂⁻

), nonaflate (C₂F₅SO₂⁻

), tosylate anion, dicyanimide anion, bis(trifluoromethylsulfonyl)imide ((CF₃SO₂)₂N⁻

), bis(perfluoroethylsulfonyl)imide ((C₂F₅SO₂)₂N⁻

), tris(trifluoromethylsulfonyl)methide ((CF₃SO₂)₃C⁻

), and combinations thereof.

27. The inkjet printhead solvent of claim 22, further comprising a co-solvent selected from acetonitrile, propylene carbonate, adiponitrile, ethylene carbonate, diethyl carbonate, and combinations thereof.

28. The inkjet printhead solvent of claim 22, further comprising a co-solvent selected from tetrahydrofuran, dimethylformamide, methylene chloride, adiponitrile, toluene, dioxane, dimethylsulfoxide, succinonitrile, N-methyl pyrrolidone, sulfolane, nitromethane, nitrobenzene, and combinations thereof.