Robotic‐assisted capture‐SELEX of RNA aptamers binding to small molecules

Due to their small size, stability, and cost‐effectiveness compared to antibodies, aptamers developed by Systematic Evolution of Ligands by Exponential Enrichment (SELEX) are promising candidates for the detection of small molecules. In SELEX, a small target molecule is usually covalently immobilised on a surface to separate bound from unbound nucleic acid sequences. However, this immobilisation alters the molecule, i.e. additional chemical entities are added and the electron distribution is altered, compromising the enrichment properties. To overcome this problem, a capture SELEX method has been successfully developed in which the RNA or DNA libraries are bound to a surface via a complementary oligodeoxynucleotides and the soluble ligand is used to capture nucleic acids that bind to it from that surface. Here, we describe the development of an automated version of the capture SELEX method for the identification of RNA aptamers that bind small molecules. This method is fully automated and performs up to 12 iterative selection cycles without manual interference in 72 hours. The approach is therefore suitable as rapid route to aptamers and enables resource‐efficient test selections to assess ‘aptamerogenicity’ of a target.