Monoliths with attached recognition compounds, arrays thereof and uses thereof

Abstract

Provided herein are monoliths with attached recognition compounds which selectively bind ligands, methods of preparing such monoliths, arrays thereof and uses thereof. For example, monoliths provided herein can be used in columns and arrays thereof.

1 .- 20 . (canceled) 
     
     
         21 . A method of routing a mixture of k nucleic acids tags, each nucleic acid tag operatively linked to a chemical reaction site or ligand, to m spatial locations, where m and k are integers greater than 1, comprising:
 contacting the mixture of k nucleic acids with an array, which comprises m spatial locations where each spatial location comprises a support with a monolith attached to the support, wherein each monolith includes a covalently attached polymer which selectively hybridizes to one of the k nucleic acid tags; and   hybridizing each of the k nucleic acid tags with the complementary polymer in one of the m spatial locations of the array.   
     
     
         22 . The method of  claim 21 , further comprising eluting the k nucleic acid tags from the polymer to m spatially defined locations. 
     
     
         23 . The method of  claim 21 , wherein the array comprises a block including m discrete spatial locations. 
     
     
         24 . The method of  claim 23 , wherein the array comprises more than one operatively linked block. 
     
     
         25 . The method of  claim 21 , wherein the rate constant of hybridizing the nucleic acid tags with the polymer at the one or more spatial locations is between about 1×10 2  M −1 s −1  and about 1×10 6  M −1 s −1 . 
     
     
         26 . The method of  claim 21 , wherein the yield of hybridizing the nucleic acid tags with the polymer at the one or more spatial locations is greater than about 40%. 
     
     
         27 . The method of  claim 21 , wherein the yield of hybridizing the nucleic acid tags with the polymer at the one or more spatial locations is greater than about 90%. 
     
     
         28 . The method of  claim 21 , wherein the polymer is a capture oligonucleotide. 
     
     
         29 . The method of  claim 28 , wherein the capture oligonucleotide comprises between about 10 nucleotides and about 50 nucleotides in length, 15 nucleotides and about 45 nucleotides in length, 10 nucleotides and about 30 nucleotides in length, between about 15 nucleotides and about 24 nucleotides in length or between about 19 nucleotides and about 20 nucleotides in length. 
     
     
         30 . The method of  claim 28 , wherein the capture oligonucleotides are orthogonal. 
     
     
         31 . The method of  claim 28 , wherein the T m  of the capture oligonucleotides is between about 49° C. and about 53° C. 
     
     
         32 . The method of  claim 28 , wherein k is greater than or equal to 10 and about 40% of the nucleic acid tags are hybridized to complementary capture oligonucleotides and the number of complementary capture oligonucleotides is greater than or equal to 10. 
     
     
         33 . The method of  claim 28 , wherein k is greater than 10 and about 90% of the nucleic acid tags are hybridized to complementary capture oligonucleotides and the number of complementary capture oligonucleotides is greater than or equal to 10. 
     
     
         34 . The method of  claim 28 , wherein the nucleic acid tags are hybridized to the capture oligonucleotides at a temperature at or below about 10° C. of the T m  of the capture oligonucleotides. 
     
     
         35 . The method of  claim 21 , wherein the support is comprised of titanium, aluminum alloys, stainless steel, doped metals, glass, quartz, polycarbonate, fused silica, poly (methyl methacrylate), plastics, polyether ether ketone, doped polyether ether ketone, doped polystyrene, cyclic olefin copolymer, polyetheriimide, doped polypropylene or combinations thereof. 
     
     
         36 . The method of  claim 21 , wherein the array is a series of columns, which are operatively linked. 
     
     
         37 . The method of  claim 21 , wherein the monolith is an organic polymer monolith. 
     
     
         38 . The method of  claim 21 , wherein the support binds between about 0.5 fmol/μl and about 0.4 nmol/μl of the nucleic acid tag. 
     
     
         39 . The method of  claim 21 , wherein the nucleic acid tag comprises between about 20 nucleotides and about 1000 nucleotides in length, between about 50 nucleotides and about 800 nucleotides in length, between about 100 nucleotides and about 600 nucleotides in length, between about 150 nucleotides and about 300 nucleotides in length. 
     
     
         40 . The method of  claim 21 , wherein the ligand is a peptide, a peptoid or an organic compound of molecular weight of between about 50 and about 3000 daltons. 
     
     
         41 . The method of  claim 21 , wherein the monolith is covalently attached to the support. 
     
     
         42 . The method of  claim 21 , wherein the monolith is covalently attached to the support through an amide, ester, urea, urethane, carbon-silicon, carbon-nitrogen, carbon-carbon, ether, thioether, silicon-oxygen or disulfide bond. 
     
     
         43 . A method of routing a mixture of k nucleic acids tags to m spatial locations, where m and k are integers greater than 1 comprising:
 contacting the mixture of k nucleic acids with an array, which comprises m spatial locations where each spatial location comprises a support, with a monolith attached to the support, wherein each monolith includes a covalently attached polymer which selectively hybridizes to one of the k nucleic acid tags; and   hybridizing each of the k nucleic acid with the complementary polymer in one of the m spatial locations of the array.   
     
     
         44 . A method of preparing a nucleic acid programmed library of chemical compounds comprising:
 (a) routing k nucleic acid tags using the method of  claim 21 ;   (b) eluting each nucleic acid tag from the polymer to m spatially defined locations;   (c) reacting the m spatially localized nucleic acid tags with x different chemical subunits, wherein x is an integer greater than 1;   (d) pooling the k nucleic acid tags with x different attached chemical subunits; and   (e) repeating steps (a) through (d) y times where y is an integer greater than 1.   
     
     
         45 . The method of  claim 44 , wherein the nucleic acid tags eluted in step (b) are immobilized by an anionic exchange resin after step (b) and are eluted from the anionic exchange resin after step (c). 
     
     
         46 . The method of  claim 44 , wherein the members of the library are greater than about 1000 members.