Over the last few decades, nucleic acids have proven to be an exceptionally versatile material capable of molecular recognition, catalysis, construction of complex patterns, and even nanomechanical motions. In particular, the molecular recognition capability of nucleic acid constructs called aptamers, stands out as a key element because they can serve as a switch to control a wide range of molecular functions that can give rise to novel materials capable of performing complex molecular functions. However, the discovery of such aptamers poses a significant challenge, in large part, due to the lack of an efficient experimental methodology.

This dissertation focuses on the development of novel methodologies for generating high-performance aptamers and further nucleic acid materials capable of performing complex functions in a highly controlled manner. I first demonstrate a novel technique that combines the advantages of a volume dilution challenge with microfluidics technology for the rapid isolation of high-performance aptamers. I describe the optimal workflow of aptamer discovery by combining a highly efficient microfluidic selection with high-throughput sequencing and aptamer arrays. Next, I demonstrate a novel in vitro selection method that allows the discovery of aptamers that undergo binding-induced structure-switching and show the generation of structure-switching aptamers capable of biosensing and/or molecular delivery. Finally, I describe an innovative strategy to synthesize hybrid materials capable of performing complex, multi-step molecular processes by integrating these aptamers with polymer materials and demonstrate their use for targeted drug delivery.