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Systematic evolution of ligands by exponential enrichment, abbreviated SELEX, is an in vitro selection strategy that repeatedly selects binding nucleic acid variants and amplifies their recoverable sequences. In an RNA implementation, a sequence pool is transcribed, exposed to a target, partitioned into retained and unretained material, and regenerated through reverse transcription, polymerase chain reaction and renewed transcription. A binding molecule recovered by this process can be an aptamer.

The 1990 experiment by C. Tuerk and L. Gold randomized eight positions in an RNA region associated with bacteriophage T4 DNA polymerase, defining $4^8=65,536$ possible sequences. Repeated binding selection and amplification recovered preferred variants.^[ref] Gold's firsthand retrospective connects the name and experimental design to this work.^[ref]

An original equilibrium model explains a practical tradeoff. With free target concentration $T$ maintained approximately constant and single-site dissociation constants $K_A,K_B$, ideal binding fractions areFor stipulated $K_A=1$ nM and $K_B=100$ nM, target at 10 nM gives binding fractions about 0.909 and 0.0909: tenfold relative retention. At 1 nM they become 0.5 and approximately 0.00990: 50.5-fold relative retention. Lowering target strengthens discrimination in this model but also loses more desired molecules. This is the target-concentration tradeoff in affinity selection.

If the desired class starts at fraction $p$, its ideal post-selection fraction is $p{s}_A/[p{s}_A+(1-p)s_B]$, assuming equal subsequent amplification. For $p=0.001$, the two target concentrations above give approximately 0.00991 and 0.04812. These constructed values are not yields from the historical experiment, and the model excludes target depletion, kinetic wash losses and sequence-dependent amplification.

Enrichment therefore measures success in the whole selection protocol. Binding to a support, survival through washing or preferential amplification can change sequence abundance without improving the intended binding affinity. Independent binding measurements and appropriate control selections distinguish those mechanisms from target recognition. Iteration is powerful because it makes rare sequences recoverable, while also repeatedly applying every bias in the experimental cycle.