A method has been developed for selecting single or multiple aptamer pairs for a target molecule in a free solution. These methods utilize a novel collaborative evolutionary attempt to select an aptamer pair for one or more targets, and the pairing of one or more aptamers at target binding triggers the aptamer amplifiability. In this way, the enrichment of the aptamer ligand through one or more rounds of selection process is based primarily on the close proximity of the target-tailored form of the aptamer within the glass solution. Target binding and enrichment are coupled using positive or negative selection methods. These techniques are generally applicable to many different types of target molecules and provide alternatives to antibodies, drugs, or other binding molecules for analytical, manufacturing, and therapeutic purposes.
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