Combinatorial strategies for polymer synthesis

• US 6,040,193 A
• Filed: 08/04/1998
• Issued: 03/21/2000
• Est. Priority Date: 11/22/1991
• Status: Expired due to Fees

• Current Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Original Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Inventors: Ross, Debra A., Aldwin, Lois, Buchko, Christopher J., Modlin, Douglas N., Winkler, James L., Fodor, Stephen P. A.
• Primary Examiner(s): LUDLOW, JAN M
• Application Number:
  US09/129,463
• Time in Patent Office: 595 Days
• Field of Search: 436/180, 436/94, 436/89, 422/100, 73/863, 73/864, 73/864.81, 141/31
• US Class Current: 506/16
• 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 2219/00364 Pipettes
• CPC Class Codes: B01J 2219/00367 capillary
• CPC Class Codes: B01J 2219/00369 in multiple or parallel arrangements
• CPC Class Codes: B01J 2219/00378 Piezoelectric or ink jet dispensers
• CPC Class Codes: B01J 2219/00389 Feeding through valves
• CPC Class Codes: B01J 2219/00416 Vacuum
• CPC Class Codes: B01J 2219/0043 for direct application of reagents, e.g. through openings in a shutter
• CPC Class Codes: B01J 2219/00432 Photolithographic masks
• CPC Class Codes: B01J 2219/00475 Sheets
• CPC Class Codes: B01J 2219/005 Beads
• CPC Class Codes: B01J 2219/00527 Sheets
• CPC Class Codes: B01J 2219/00529 DNA chips
• CPC Class Codes: B01J 2219/00531 essentially square
• CPC Class Codes: B01J 2219/00536 in the shape of disks
• 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 2219/00659 : Two-dimensional arrays
• CPC Class Codes: B01J 2219/00675 : In-situ synthesis on the substrate
• CPC Class Codes: B01J 2219/00686 : Automatic
• CPC Class Codes: B01J 2219/00689 : using computers
• CPC Class Codes: B01J 2219/00702 : Processes involving means for analysing and characterising the products
• 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: 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: C07K 5/1008 : the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala
• CPC Class Codes: C07K 5/1016 : and aromatic or cycloaliphatic
• 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 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: G01N 35/1072 : with provision for selective pipetting of individual channels
• CPC Class Codes: Y02P 20/55 : Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
• CPC Class Codes: Y10S 435/97 : Test strip or test slide
• CPC Class Codes: Y10S 435/973 : Simultaneous determination of more than one analyte
• CPC Class Codes: Y10T 436/143333 : Saccharide [e.g., DNA, etc.]
• CPC Class Codes: Y10T 436/2575 : Volumetric liquid transfer

Abstract

An array is created by moving a dispenser toward a solid support until a tip of the dispenser touches the support, withdrawing the tip from the surface and releasing a drop of 5 nanoliters or less in an area smaller than 1 mm² to create an array of at least 100 spots.

Claims

1. A method of forming an array of polymers on a solid support, comprising:

(a) moving a dispenser containing a solution of a polymer toward a surface of a solid support until a tip of the dispenser touches the surface, moving the dispenser away from the surface and releasing a droplet of 5 nl or less from the dispenser, the droplet contacting the surface at a localized area smaller than 1 mm², whereby the polymer attaches to the surface of the support at the localized area;

(b) repeating (a) to attach a different polymer at a different localized area until an array of at least 100 different polymers at different localized areas is formed.

2. The method of claim 1 wherein said dispenser comprises a capillary.

3. The method of claim 1 wherein said localized areas are spaced between 5 and 100 microns.

4. The method of claim 1 wherein said surface comprises a hydrophobic material surrounding hydrophilic localized areas to which the polymers are attached.

5. The method of claim 1 wherein said dispenser comprises a micropipette.

6. The method of claim 1, wherein the polymers comprise nucleic acids.

7. The method of claim 6 wherein said nucleic acids are obtained from cell extracts.

8. The method of claim 6, wherein (a) and (b) are repeated to produce an array of at least 1000 different nucleic acids occupying localized areas within 1 cm² of the surface of the support.

9. The method of claim 1, wherein the support is glass, quartz or silicon.

10. The method of claim 1, wherein the solution of the polymer is an aqueous solution.

11. The method of claim 1, wherein the support bears at least two reference points for positioning the dispenser over at least one of said localized areas for release of said droplet.

12. The method of claim 11, wherein the reference points comprise global reference points for positioning the dispenser over a local region of the surface of the support, and local reference points within the local region for positioning the dispenser over at least one of said localized areas within the local region.

13. The method of claim 12, wherein the dispenser further comprises a camera for identifying the reference points.

14. The method of claim 1, wherein the polymers are each at least 20% pure within their respective localized areas.