Printing oligonucleotide arrays
First Claim
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1. A method of forming selected polymers on a substrate, said method comprising:
- providing a substrate comprising a layer of linker molecules thereon, each of said linker molecules having a protective group at its distal end away from the substrate;
applying a barrier layer overlying said linker molecule layer, said applying step forming selected exposed regions of said linker molecule layer;
exposing said selected exposed regions of said linker molecule layer to a deprotecting agent in a vapor phase, wherein said vapor phase removes more than 80% of the protective groups in said selected exposed regions; and
coupling selected monomers to form said selected polymers on the substrate.
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Abstract
A method and apparatus for selectively applying a print material onto a substrate for the synthesis of an array of oligonucleotides at selected regions of a substrate. The print material includes a barrier material, a monomer sequence, a nucleoside, a deprotection agent, a carrier material, among other materials. The method and apparatus also relies upon standard DMT based chemistry, and a vapor phase deprotection agent such as solid TCA and the like.
44 Citations
39 Claims
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1. A method of forming selected polymers on a substrate, said method comprising:
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providing a substrate comprising a layer of linker molecules thereon, each of said linker molecules having a protective group at its distal end away from the substrate;
applying a barrier layer overlying said linker molecule layer, said applying step forming selected exposed regions of said linker molecule layer;
exposing said selected exposed regions of said linker molecule layer to a deprotecting agent in a vapor phase, wherein said vapor phase removes more than 80% of the protective groups in said selected exposed regions; and
coupling selected monomers to form said selected polymers on the substrate. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16)
nucleic acids, polynucleotides, oligonucleotides, polypeptides, polysaccharides, oligosaccharides, phospholipids, polyurethanes, polyesters, polycarbonates, polyureas, polyamides, polyethyleneimines, polyarylene sulfides, polysiloxanes, polyimides, polyacetates.
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16. The method of claim 1, wherein said polymer is selected from the group consisting of:
- nucleic acids, polynucleotides, oligonucleotides, polypeptides, and polysaccharides.
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17. A method of deprotecting selected regions of a substrate, said method comprising:
- providing a substrate comprising a layer of linker molecules thereon, each of said linker molecules having a protective group;
applying a deprotection agent in vapor phase wherein the vapor phase removes more than 80% of the protective groups on selected regions of said linker molecule layer, wherein said deprotection occurs at atmospheric pressure or at a pressure lower than atmospheric pressure, and wherein said linker molecule layer remains covalently bonded to said substrate after said deprotection. - View Dependent Claims (18, 19, 20, 21, 22, 23)
- providing a substrate comprising a layer of linker molecules thereon, each of said linker molecules having a protective group;
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24. A method of applying a print medium in a vapor phase in selected regions of a substrate to remove a protective group, said method comprising the steps of:
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providing a partially completed substrate comprising an array of monomers, said partially completed substrate having a top surface;
selectively applying a print medium comprising a barrier material, a receptor, a deprotection agent, a monomer group, a carrier material, an activator, or a combination thereof, to selected regions of said substrate top surface;
wherein said vapor phase removes more than 80% of protective groups in the selected regions; and
said selectively applying step comprises a printing method selected from the group consisting of;
relief press printing, letter press printing, gravure printing, intaglio printing, stencil printing, ion beam proximity printing, ink jet printing, bubble jet printing, lithography, and xerography, and wherein said array of monomers remains covalently bonded to said substrate after applying said print medium.- View Dependent Claims (25, 26, 27, 28, 29, 30, 31, 32)
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33. A method of synthesizing nucleic acids or polynucleotides comprising the steps of:
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a) providing oligonucleotides having proximal ends and distal ends, said proximal ends coupled to a substrate having a surface, and said distal ends having a removable protective group;
b) removing said protective groups with a deprotection agent in vapor phase to expose functional groups, wherein said vapor phase removes more than 80% of said protective groups, and wherein said oligonucleotides in step a) remain coupled to said substrate after removal of said protective groups; and
c) covalently bonding an oligonucleotide to said exposed functional groups. - View Dependent Claims (34, 35, 36, 37, 38, 39)
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Specification