Combinatorial strategies for polymer synthesis
View Patent ↗A method for producing arrays by depositing a resist on a substrate, selectively removing a portion of the resist to expose localized areas, dispensing a monomer to occupy a localized area of less than 1 cm 2 of the surface of the support, allowing the monomer to bind directly or indirectly to the support and repeating the steps to produce an array of at least 10 different polymers is formed.
1. A method of forming an array of polymers on a support having one or more localized areas comprising
(a) depositing a resist onto a surface of the support;
(b) selectively removing a portion of the resist to expose one or more localized areas;
(c) dispensing a first monomer onto the surface of the support at the one or more localized areas wherein the one or more localized areas are smaller than 1 cm 2 ;
(d) allowing the first monomer to attach directly or indirectly to the surface of the support at the one or more localized areas;
(e) repeating steps (a) and (b) and then dispensing an additional group of added monomers onto the surface of the support at the one or more localized areas in a manner to couple with a compound at the one or more localized areas until an array of at least 10 different polymers at different localized areas is formed.
2. The method of claim 1 , wherein the monomers are dispensed in droplets of 5 nl or less.
3. The method of claim 1 wherein the monomer is dissolved in solution.
4. The method of claim 1 wherein the resist includes polymethylmethacrylate or polysulfone.
5. The method of claim 1 wherein the step of dispensing includes a dispenser positioned between about 5 microns and about 50 microns away from the support when dispensing the monomers.
6. The method of claim 1 wherein the step of dispensing includes a dispenser positioned about 10 microns away from the support when dispensing the monomers.
7. The method of claim 2 wherein the droplet fits within a region having a diameter of less than about 300 microns.
8. The method of claim 1 wherein the monomer comprises a nucleotide or an amino acid.
9. The method of claim 1 wherein the polymer comprises a nucleic acid or polypeptide.
10. The method of claim 1 wherein the polymer comprises at least 2 monomers.
11. The method of claim 1 wherein the polymer comprises greater than 100 monomers.
12. The method of claim 1 wherein the polymer comprises 2, 3, 4, 5, 6, 10, 15, 20, 30, 40, 50, 75, or 100 monomers.
13. The method of claim 1 wherein the support is selected from the group consisting of substantially flat substrates, substrates having raised or depressed regions, beads, gels, sheets, particles, strands, precipitates, spheres, containers, capillaries, pads, slices, films, plates, and slides.
14. The method of claim 1 wherein the support comprises a gel.
15. The method of claim 1 wherein the support comprises biological materials, nonbiological materials, organic materials or inorganic materials.
16. The method of claim 1 wherein the support is a disc, square, or circle.
17. The method of claim 1 wherein the one or more localized areas are smaller than 1 mm 2 .
18. The method of claim 1 wherein the one or more localized areas are smaller than 0.5 mm 2 .
19. The method of claim 1 wherein the one or more localized areas are smaller than 10,000 μm 2 .
20. The method of claim 1 wherein the one or more localized areas are smaller than 100 μm 2 .
21. The method of claim 1 wherein an array of at least 100 different polymers at different localized areas is formed.
22. The method of claim 1 wherein an array of at least 1000 different polymers at different localized areas is formed.
23. The method of claim 1 wherein an array of at least 10,000 different polymers at different localized areas is formed.
24. The method of claim 1 wherein an array of at least 100,000 different polymers at different localized areas is formed.
25. The method of claim 1 wherein an array of at least 1,000,000 different polymers at different localized areas is formed.
26. The method of claim 1 , wherein an array of at least 1000 different polymers occupying localized areas within 1 cm 2 of the surface of the support.
27. The method of claim 1 , wherein the support comprises glass, derivatized glass, pyrex, quartz, a polymeric material, polystyrene, polycarbonate, silicon or a gel.
28. The method of claim 3 , wherein the solution comprises an aqueous solution.
29. The method of claim 1 wherein the step of dispensing includes a dispenser comprising a plurality of dispensing units, wherein the plurality of dispensing units is in fluid communication with a solution comprising a monomer and wherein steps (c) and (e) comprise dispensing a droplet of 5 nl or less from one or more of the plurality of dispensing units.
30. The method of claim 29 wherein the plurality of dispensing units comprises a manifold of a plurality of delivery lines.
31. The method of claim 29 wherein the plurality of dispensing units comprises an array of pipettes.
32. The method of claim 29 wherein the plurality of dispensing units comprises a series of tubes.
33. The method of claim 29 wherein the plurality of dispensing units includes control valves.
34. The method of claim 1 wherein the monomer is bound indirectly to the surface of the support via a linker molecule.
35. The method of claim 1 wherein the step of dispensing includes a dispenser that is moved relative to the support.
36. The method of claim 1 wherein the support is moved relative to a dispenser.
37. The method of claim 1 wherein the one or more localized areas are spaced less than about 3 mm apart.
38. The method of claim 1 wherein the one or more localized areas are spaced less than between about 5 microns and 100 microns apart.
39. The method of claim 1 wherein the one or more localized areas has an angular relation between each localized area of about 1 degree.
40. The method of claim 1 wherein the one or more localized areas has an angular relation between each localized area of about 0.1 degree.
41. The method of claim 1 wherein the support comprises at least about 100 localized areas.
42. The method of claim 1 wherein the support comprises at least about 1000 localized areas.
43. The method of claim 1 wherein the support comprises at least about 10,000 localized areas.
44. The method of claim 1 wherein the support comprises at least about 1000 localized areas per cm 2 of surface of substrate.
45. The method of claim 1 wherein the support comprises at least about 10,000 localized areas per cm 2 of surface of substrate.
46. The method of claim 1 wherein the support comprises a strand including one or more of glass, derivatized glass, quartz, or a polymeric material.
47. The method of claim 1 wherein the surface of the support is cleaned prior to the step of dispensing a monomer.
48. The method of claim 1 wherein the step of dispensing includes a dispenser comprising a pipette.
49. The method of claim 1 wherein the step of dispensing includes a dispenser comprising a capillary tube.
50. A method of forming an array of compounds on a support having one or more localized areas comprising
(a) depositing a resist onto a surface of the support;
(b) selectively removing a portion of the resist to expose one or more localized areas;
(c) dispensing a compound onto the surface of the support at the one or more localized areas wherein the one or more localized areas are smaller than 1 cm 2 ;
(d) allowing the compound to attach directly or indirectly to the surface of the support at the one or more localized areas;
(e) repeating steps (a) through (d) until an array of at least 10 different polymers at different localized areas is formed.
51. The method of claim 50 wherein the compound is selected from the group consisting of a nucleotide, amino acid, nucleic acid or polypeptide.
52. The method of claim 50 wherein the compound is dispensed in droplets of 5 nl or less.