Microarray having a base cleavable linker

Abstract

There is disclosed a microarray having base cleavable linkers and a process of making the microarray. The microarray has a solid surface with known locations, each having reactive hydroxyl groups. The density of the known locations is greater than approximately 100 locations per square centimeter. Optionally, oligomers are synthesized in situ onto the cleavable linkers and subsequently cleaved using a cleaving base. Optionally, the oligomers are cleaved and recovered as a pool of oligomers.

1 . A compound of formula: 
       
         
           
           
               
               
           
         
       
       where ‘MA’ is a microarray with a plurality of electronically addressable electrodes, where the microarray includes a surface with a plurality of hydroxyl reactive group associated with the plurality of electronically addressable electrodes, where the Compound is attached through one or more of the plurality of hydroxyl reactive groups in a plurality of known locations, where ‘Base’ of the compound denotes one of adenine (A), cytosine (C), guanine (G), thymine (T) and uracil (U) on the 5′ hydroxyl of the Compound, where ‘Remainder of Oligonucleotide Strand’ of the Compound denotes one or more oligonucleotides, where the Compound is susceptible to cleavage by introducing a base to generate a 3′ phosphate nucleoside species including the one or more oligonucleotides. 
     
     
         2 . The compound of  claim 1 , where the one or more oligonucleotides is selected from the group consisting of DNA, RNA and combinations thereof. 
     
     
         3 . The compound of  claim 1 , where the one or more oligonucleotides are synthesized in situ by a method selected from the group consisting of (a) printing reagents via ink jet or other printing technology and using regular phosphoramidite chemistry, (b) maskless photo-generated acid controlled synthesis and using regular phosphoramidite chemistry, (c) mask-directed parallel synthesis using photo-cleavage of photolabile protecting groups, and (d) maskless parallel synthesis using photo-cleavage of photolabile protecting groups and digital photolithography. 
     
     
         4 . The compound of  claim 1 , where the cleaving base is selected from the group consisting of ammonium hydroxide, electrochemically generated base, sodium hydroxide, potassium hydroxide, methylamine, and ethylamine and combinations thereof. 
     
     
         5 . The compound of  claim 1 , where the Compound is synthesized with a sulfonate amidite. 
     
     
         6 . The compound of  claim 5 , where the sulfonyl amidite moiety is 2-[2-(4,4′-dimethoxytrityloxy)ethylsulfonyl)ethyl-(2-cyanoethyl)-(N,N-dii-sopropyl)-phosphoramidite. 
     
     
         7 . The compound of  claim 1 , where a porous reaction layer is attached to the known locations to provides the one or more of the plurality of hydroxyl reactive groups in the plurality of known locations. 
     
     
         8 . The compound of  claim 1 , where a Spacer having a reactive hydroxyl groups is bound to the one or more of the plurality of hydroxyl reactive groups in the plurality of known locations. 
     
     
         9 . The compound of  claim 8 , where a sulfonyl amidite moiety is bound to the reactive hydroxyl groups of the Spacer. 
     
     
         10 . The compound of  claim 8 , where the spacer is approximately a one-mer to a thirty five-mer. 
     
     
         11 . The compound of  claim 10 , where a porous reaction layer provides the one or more of the plurality of hydroxyl reactive groups in the plurality of known locations. 
     
     
         12 . The compound of  claim 1 , where the porous reaction layer comprises a chemical species or mixture of chemical species selected from the group consisting of a monosaccharide, a disaccharide, and a trisaccharides. 
     
     
         13 . The compound of  claim 12 , where the monosaccharide is selected from the group consisting of allose, altrose, arabinose, deoxyribose, erythrose, fructose, galactose, glucose, gulose, idose, lyxose, mannose, psicose, L-rhamnose, ribose, ribulose, sedoheptulose, D-sorbitol, sorbose, sylulose, tagatose, talose, threose, xylulose, and xylose. 
     
     
         14 . The compound of  claim 12 , where the disaccharide is selected from the group consisting of amylose, cellobiose, lactose, maltose, melibiose, palatinose, sucrose, and trehalose. 
     
     
         15 . The compound of  claim 12 , where the triaccharide is selected from the group consisting of raffinose and melezitose.