Patent ID: 8034912

Claim:
A method for massively parallel oligonucleotide probe synthesis and release of the synthesized oligonucleotides from an array of probes on a solid substrate, the method comprising: providing a solid substrate; attaching a plurality of linkers to the substrate, each linker comprising a cleavable moiety, wherein the cleavable moiety is activatable only at a distinct set of conditions and wherein activation of the cleavable moiety disrupts the linker to allow release of the synthesized oligonucleotides and to provide a substrate with a plurality of attached linkers, wherein the linker has the structure shown below and wherein PG 1 is protecting group 1, PG 2 is protecting group 2, B is a naturally or non-naturally occurring base, and the linker is attached to the substrate through the 5′-hydroxyl group; attaching a first monomer to at least one of the plurality of attached linkers to provide an attached first monomer; attaching a second monomer to a least one of the attached first monomers or the plurality of attached linkers to provide an attached second monomer; attaching a third monomer to a least one of the attached first monomer, the attached second monomer or the plurality of attached linkers to provide an attached third monomer; repeating the steps of attaching monomers until the desired array of synthesized oligonucleotides is complete; and subjecting the array to the distinct set of conditions to activate the cleavable moieties, wherein activation comprises removal of PG 2 , wherein removal of PG 2 allows base-induced intramolecular transesterification, and wherein transesterification releases the synthesized oligonucleotides from the array.