Substrate preparation process
First Claim
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1. A method of forming an array of polymers on a surface of a substrate, comprising:
- providing a substrate having a first surface coated with functional groups protected with a photolabile protecting group, and a second surface having a layer disposed thereon, said layer including one or more of an index matching compound, a light absorbing compound and an antireflective compound; and
sequentially activating and coupling monomers in different selected regions of said substrate to form a plurality of different polymer sequences in different known locations on said surface of said substrate, wherein said activating step comprises directing an activation radiation at said first surface of said substrate.
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Abstract
The present invention provides novel processes for the large scale preparation of arrays of polymer sequences wherein each array includes a plurality of different, positionally distinct polymer sequences having known monomer sequences. The methods of the invention combine high throughput process steps with high resolution photolithographic techniques in the manufacture of polymer arrays.
51 Citations
49 Claims
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1. A method of forming an array of polymers on a surface of a substrate, comprising:
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providing a substrate having a first surface coated with functional groups protected with a photolabile protecting group, and a second surface having a layer disposed thereon, said layer including one or more of an index matching compound, a light absorbing compound and an antireflective compound; and
sequentially activating and coupling monomers in different selected regions of said substrate to form a plurality of different polymer sequences in different known locations on said surface of said substrate, wherein said activating step comprises directing an activation radiation at said first surface of said substrate. - View Dependent Claims (2, 3, 4, 5, 6)
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7. A method of forming a plurality of individual polymer arrays, comprising:
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providing a plurality of substrate wafers, each of said substrate wafers having a first surface, said first surface having functional groups disposed thereon, said functional groups being protected with a removable protecting group;
exposing a plurality of first selected regions on said first surface of each of said substrate wafers to an activator at an activation station to remove said removable protecting groups from said functional groups in said first selected regions;
first moving said substrate wafers batch-wise to a coupling station;
contacting said plurality of wafers with a monomer containing solution at said coupling station, to couple first selected monomers to said functional groups in said selected regions on said surface of said plurality of substrate wafers;
first returning said substrate wafers batch-wise to said activation station;
exposing a plurality of second selected regions on said first surface of each of said substrate wafers to an activator at said activation station to remove said removable protecting groups from said functional groups in said second selected regions;
second moving said substrate wafers batch-wise to said coupling station;
contacting said plurality of wafers with a monomer containing solution in said coupling station, to couple second selected monomers to said functional groups in said selected regions on said surface of said plurality of substrate wafers;
repeating said exposing and contacting steps to form a plurality of individual polymer arrays on said first surface of each of said substrate wafers. - View Dependent Claims (8, 9, 10, 11, 12, 13, 14, 15, 16)
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17. A method of forming an array of polymers on a surface of a substrate, comprising:
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derivatizing said surface of said substrate by contacting said surface of said substrate with a solution of aminoalkyltrialkoxysilane to provide amine functional groups on said first surface of said substrate;
protecting said functional groups with a protecting group;
activating first selected regions on said first surface of said substrate by removing said protecting groups from said functional groups in said first selected regions;
coupling a first monomer to said functional groups in said first selected regions;
activating second selected regions on said first surface of said substrate by removing said protecting groups from said functional groups in said second selected regions;
coupling a second monomer to said functional groups in said second selected regions;
repeating said activating and coupling steps to form a plurality of different polymer sequences, each of said different polymer sequences being coupled to said surface of said substrate in a different known location. - View Dependent Claims (18, 19, 20, 21, 22)
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23. A method of forming an array of polymers on a surface of a substrate, comprising:
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stripping said surface of said substrate with a stripping solution;
providing functional groups on said surface of said substrate;
protecting said functional groups with a photolabile protecting group;
exposing first selected regions on said first surface of said substrate to an activation radiation to remove said photolabile protecting groups from said functional groups in said first selected regions;
coupling a first monomer to said functional groups in said first selected regions;
exposing second selected regions on said first surface of said substrate wafers to an activation radiation to remove said photolabile protecting groups from said functional groups in said second selected regions;
coupling a second monomer to said functional groups in said second selected regions;
repeating said exposing and coupling steps to form a plurality of different polymer sequences, each of said different polymer sequences being coupled to said surface of said substrate in a different known location. - View Dependent Claims (24, 25)
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26. A method of coupling monomers to selected regions on a surface of a substrate, comprising:
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providing functional groups on said surface of said substrate, said functional groups being protected with a photoprotecting group;
exposing said selected regions to an activation radiation to remove said photolabile protecting group in said selected regions, said exposing step comprising directing an activation radiation at said selected regions on said surface of said substrate by shining said activation radiation through a photolithographic mask, said photolithographic mask including transparent regions and opaque regions, said transparent regions being smaller than said selected regions, whereby when said activation radiation is shone through said transparent regions in said mask, said activation radiation is diffracted to expose substantially all of said selected regions; and
coupling monomers to said functional groups in said selected regions. - View Dependent Claims (27, 28)
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29. A method of forming polymer sequences on a solid substrate, comprising:
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providing functional groups on said surface of said substrate;
coupling monomers to said functional groups on said surface of said substrate, said monomers having chemical groups reversibly coupled thereto, whereby said chemical groups enhance the lipophilicity of said monomers. - View Dependent Claims (30, 31, 32, 33, 34)
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- 35. A method of deprotecting an array of polymer sequences synthesized on a solid support, comprising contacting said array with a solution containing a substituted alkylamine.
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39. A method of forming an array of polymer sequences on a surface of a substrate by sequentially deprotecting and coupling monomers in selected regions of said surface of said substrate to produce a plurality of different polymer sequences in different known locations of said surface of said substrate, the method comprising aligning deprotection and coupling steps in adjacent selected regions to minimize a number of differential synthesis steps between said adjacent regions.
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40. A method of forming an array of polymer sequences wherein each polymer sequence has a subsequence of monomers common to a sequence that is complementary to a target sequence, but wherein at least one position within said subsequence is substituted with each member of a basis set of monomers, the method comprising coupling all monomers in a same layer of a first of said polymer sequences in a same synthesis cycle as corresponding monomers in a second of said polymer sequences.
- 41. A method of photoprotecting a functional group coupled to a solid support, the method comprising exposing said functional group to a photoprotecting group transfer agent having the formula:
Specification