Formaldehyde Cross-Linking-Assisted Phase Separation for Protein Aptamer Selection

With the merits of easy synthesis, strong modifiability, and high affinity, aptamers have been broadly applied for protein targeting in bioanalysis, diagnosis, and therapeutics. The selection of protein-targeted aptamers is currently largely dependent on solid–liquid separation by using different types of nano- or micro-beads. However, the use of beads inescapably introduces unwanted nonspecific binding and thus affects selection efficiency. In order to sidestep this obstacle, we herein report an integrated technique to facilitate the discovery and development of protein-targeting aptamers by incorporating formaldehyde cross-linking with phase separation (FCPS). The feasibility and universality of FCPS were confirmed by the successful selection of two aptamers that could target various antibodies. Unlike traditional approaches, the proposed technique avoids the use of beads and enables the rapid generation of aptamers after only one to three rounds of selection. The as-selected aptamers were further used to regulate and control antibody activity, showing potential applications in biomedicine.