Library compositions and methods for acyclic identification of aptamers

A method for identifying an aptamer that binds to a target comprising the steps of:

• (a) providing a plurality of starting libraries each comprising a starting pool of aptamer candidates, each of said aptamer candidates of substantially the same length while having a primary structure and at least one common pre-selected secondary structure, said primary structure comprising at least a variable nucleotide sequence where nucleotides at “m” number of positions are being varied, said common pre-selected secondary structure varying among said plurality of starting libraries;
• (b) reducing the sequence complexity in each of said plurality of starting starting libraries by a factor of at least about 100 to a plurality of intermediary libraries of surviving aptamer candidates;
• (c) amplifying each of said plurality of intermediary libraries to a plurality of over-represented libraries of said surviving aptamer candidates such that, for every 100 pmol of said surviving aptamer candidates, each surviving aptamer candidate has, on average, at least about three copies;
• (d) mixing said plurality of over-represented libraries into a comprehensive library with surviving aptamer candidates of varying secondary structures;
• (e) contacting said comprehensive library with a target under a buffer condition that allows binding between members of said comprehensive library and said target;
• (f) isolating at least one aptamer candidate that is bound to said target;
• and
• (g) determining the sequence of said bound aptamer candidate.