Apparatus and methods for arraying solution onto a solid support

• US 6,365,349 B1
• Filed: 07/21/1998
• Issued: 04/02/2002
• Est. Priority Date: 07/22/1997
• Status: Expired due to Term

• Current Assignee: Operon Biotechnologies, Inc. (Eurofins Scientific SE)
• Original Assignee: Qiagen Genomics, Inc.
• Inventors: Moynihan, Kristen, Tabone, John C., Ness, Jeffrey Van
• Primary Examiner(s): Sisson, Bradley L.
• Application Number:
  US09/120,689
• Time in Patent Office: 1,351 Days
• Field of Search: 298/46, 298/25, 439/66, 435/6, 435/91.1, 435/91.2, 435/183, 435/287.2, 436/94, 536/23.1, 536/24.3, 536/24.31, 536/24.33
• US Class Current: 435/6.12
• 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 2219/00527 Sheets
• 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 2219/0061 The surface being organic
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00626 Covalent
• CPC Class Codes: B01J 2219/00637 by coating it with another layer
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01L 3/021 Pipettes, i.e. with only one conduit for withdrawing and redistributing liquids
• CPC Class Codes: B01L 3/0255 characterized by the form or material of the pin tip
• CPC Class Codes: B01L 3/5085 for multiple samples, e.g. microtitration plates
• CPC Class Codes: C07G 3/00 Glycosides polysaccharides C08B
• CPC Class Codes: C40B 40/06 Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 60/14 for creating libraries
• CPC Class Codes: G01N 1/10 in the liquid or fluent state burettes, pipettes B01L3/02; sampling of ground water E02D1/06; metering by volume of fluids or fluent solid material G01F11/00, G01F13/00
• CPC Class Codes: G01R 1/06716 : Elastic
• CPC Class Codes: G01R 1/06738 : related to tip portion

Abstract

A method for depositing biomolecule onto a solid support, the method including the steps of: immersing a tip of a spring probe into a solution of biomolecule; removing said tip from said solution to provide biomolecule solution adhered to said tip; and contacting said biomolecule solution with a solid support to thereby transfer biomolecule solution from said tip to said solid support. The spring probe has a planar tip but it otherwise identical to commercial spring probes. The solution of biomolecule contains a thickening agent in addition to biomolecule, where oligonucleotide is a preferred biomolecule.

Claims

1. A spring probe comprising a tubular housing encasing a compression spring, said spring in mechanical communication with a plunger, said plunger having a first region extending out of said housing, said first region comprising a cone-shaped fluted tip terminating as a flat surface, said surface perpendicular to a longitudinal axis of said housing, said cone-shaped tip having in cross-section two exterior sides adjacent said surface which, if said sides extended past said surface, would meet at a point positioned a distance of about 0.00001-0.010 inches beyond said surface.

2. The spring probe of claim 1 where the cone-shaped fluted tip comprises a gold surface.

3. The spring probe of claim 1 wherein said cone-shaped tip has in cross-section two exterior sides adjacent said surface which, if said sides extended past said surface, would meet at a point positioned a distance of about 0.001-0.005 inches beyond said surface.

4. The spring probe of claim 1 wherein said first region comprises a plurality of cone-shaped flutes, the flutes separated by vanes converging toward said flat surface at an angle between approximately 15°

and 120°

.

5. The spring probe of claim 1 wherein said first region comprises a plurality of cone-shaped flutes, the flutes separated by vanes converging toward said flat surface at an angle between approximately 60°

and 90°

.

6. A composition comprising a thickening agent at a concentration of about 35 vol % to about 80 vol % based on the total volume of the composition, an oligonucleotide at a concentration ranging from 0.001 μ

g/mL to 10 μ

g/mL, and water.

7. The composition of claim 6 wherein the thickening agent is a polyhydric alcohol having at least three hydroxyl groups.

8. The composition of claim 7 wherein the polyhydric alcohol is selected from the group consisting of glycerol, trimethylolpropane, trimethylolethane, pentaerythritol, and saccharides.

9. The composition of claim 8 wherein the saccharide is selected from the group consisting of mannitol, sucrose, fructose, lactose, cellulose and corn syrup.

10. The composition of claim 7 wherein the oligonucleotide is at a concentration of 0.05 μ

g/mL to 0.5 μ

g/mL.

11. The composition of claim 6 wherein the thickening agent is glycerol present at a concentration of 40 vol % to 60 vol %.

12. The composition of claim 6 wherein the oligonucleotide is at a concentration ranging from 0.01 μ

g/mL to 1 μ

g/mL.

13. The composition of claim 6 wherein the oligonucleotide comprises 15 to 50 nucleotides.

14. The composition of claim 6 wherein the oligonucleotide comprises 50 to 1,000 nucleotides.

15. The composition of claim 6 wherein the oligonucleotide is single stranded.

16. The composition of claim 6 wherein the oligonucleotide is duplex.

17. The composition of claim 6 wherein the oligonucleotide has an amino (—

NH₂) group at a 5′

end of the oligonucleotide.

18. The composition of claim 17 wherein the oligonucleotide has a hexylamine (—

(CH₂)₆—

NH₂) group at a 5′

end of the oligonucleotide.

19. The composition of claim 17 further comprising trichlorotriazine.

20. The composition of claim 6 having a pH of 7 to 9 and further comprising a buffering agent.

21. The composition of claim 20 wherein the buffering agent is selected from the group consisting of sodium phosphate, sodium borate, sodium carbonate and Tris HCl.

22. The composition of claim 6 having a temperature of 18-25°

C.

23. The composition of claim 6 having a viscosity at 20°

C. of about 6 to 80 centipoise at 25°

C.