Methods for performing patterned chemistry
Provided are methods for performing patterned chemistry and arrays prepared thereby.
1. A method of making an array of molecules, comprising:
providing a substrate having a surface wherein the surface has a plurality of features, each of the features being defined and outlined by an electrically neutral perimeter wall to reduce lateral diffusion of reagents and at least some of the features comprising a first plurality of active sites, wherein the electrically neutral perimeter wall comprises a metal chosen from the group consisting of gold, chrome and tin, and wherein the surface of the feature comprises a different material than the electrically neutral perimeter wall,
applying a first chemical reaction mixture onto the surface such that the first chemical reaction mixture is evenly distributed across the first plurality of active sites, wherein the first chemical reaction mixture comprises a first molecule having a first functional group capable of attaching to the active site, a second functional group capable of forming a covalent bond and a protecting group capping the second functional group, whereby the first molecule is coupled to the first plurality of active sites.
2. The method of claim 1 further comprising
selectively forming a second plurality of active sites in at least some of the features,
applying a second chemical reaction mixture onto the surface such that the second chemical reaction mixture is evenly distributed across the second plurality of active sites, wherein the second chemical reaction mixture comprises a second molecule having a first functional group capable of attaching to the active site, a second functional group capable of forming a covalent bond and a protecting group capping the second functional group, whereby the second molecule is coupled to the second plurality of active sites.
3. The method of claim 1 , wherein after the first chemical reaction mixture is applied onto the surface, the method further comprises heating the substrate.
4. The method of claim 3 , wherein the heating the substrate comprises heating the substrate with a hot plate.
5. The method of claim 2 , wherein selectively forming a second plurality of active sites in at least some of the features comprises
depositing a photosensitive layer over the substrate wherein the photosensitive layer comprises a deprotecting reagent precursor that upon activation generates a deprotecting reagent capable of causing the removal of the protecting group,
activating at least a portion of the photosensitive layer; and
removing the photosensitive layer.
6. The method of claim 5 , wherein activating at least a portion of the photosensitive layer comprises exposing at least a portion of the photosensitive layer to radiation.
7. The method of claim 1 wherein the electrically neutral perimeter wall is formed by a process comprising,
depositing a metal film onto a surface of a substrate;
forming a patterned photosensitive layer on the metal film;
etching the metal film in areas not covered by the photosensitive layer to form the plurality of features that are defined by the electrically neutral perimeter wall; and
removing the patterned photosensitive layer.
8. The method of claim 7 , wherein prior to depositing the metal film onto the surface of the substrate, the substrate has a thermal oxide film on the surface.
9. The method of claim 7 , wherein prior to depositing the metal film on the surface of the substrate, the substrate has a thermal oxide film, wherein the substrate is a wafer and the thermal oxide film is on both sides of the wafer.
10. The method of claim 1 , wherein the electrically neutral perimeter wall comprises a series of pillars or a series of particles.
11. The method of claim 1 , wherein the electrically neutral perimeter wall comprises a molecule having an affinity for the first chemical reaction mixture.
12. The method of claim 1 , wherein the first chemical reaction mixture further comprises a polymer matrix.
13. The method of claim 12 , wherein the polymer matrix comprises at least one polymer selected from poly(methyl methacrylate), polystyrene, polycarbonate, polyethylene glycol, and poly(choloromethyl methacrylate).
14. The method of claim 1 , wherein the first molecule is an amino acid having an amino group that is optionally capped with a protecting group, wherein the protecting group is a fluorenylmethyloxycarbonyl group, a t-butoxycarbonyl group or an optionally substituted trityl group capping the amino group.
15. The method of claim 1 , wherein the first chemical reaction mixture further comprises a solvent.
16. The method of claim 15 , wherein the solvent is N-methyl-2-pyrrolidone.
17. The method of claim 1 , wherein the first chemical reaction mixture further comprises DIC, a base chosen from DIEA and 4,4′-trimethylenedipiperidine, isopropyl-9H-trioxanthen-9-one, bis(4-tert-butylphenyl)iodonium triflate or 2-nitrobenzyl p-nitrophenylcarbonate or 1-hydroxybenzotriazole hydrate.
18. The method of claim 1 , wherein the first molecule is a nucleotide.
19. The method of claim 18 , wherein the first molecule is a nucleotide having a dimethoxy trityl group capping the second functional group.
20. The method of claim 18 , wherein the first chemical reaction mixture further comprises a polymer matrix, wherein the polymer matrix comprises poly(methyl methacrylate), polystyrene, polycarbonate or polyethylene glycol.
21. The method of claim 1 , wherein the array of molecules is chosen from the consisting of peptides, oligonucleotides, polyamide polynucleotide (PNA), deoxyribopolynucleotide (DNA), ribopolynucleotide (RNA), DNA copies of deoxyribopolynucleotide (cDNA) and combinations thereof.