"On-site small-molecule detection is important for applications such as drug screening environmentalmonitoring, food safety, and medical diagnostics. Existing on-site assays such as chemical tests suffer from frequent false-positives and false-negatives, while immunoassays are greatly limited by their short shelf-life, batch-to-batch variation, and the costly and time-consuming process of developing new target-specific antibodies. These problems can be overcome by using aptamers, oligonucleotide-based bio-affinity elements isolated in vitro via Systematic Evolution of Ligands by EXponential enrichment (SELEX). Recently, my lab has achieved numerous successes related to aptamer isolation, engineering, and sensor development. Specifically, we have engineered a variety of new aptamers with different functionalities—such as broad target recognition, cooperative target binding, dye displacement, and structure-switching—and utilized these functionalized aptamers to develop a host of innovative aptamer-based sensing platforms that employ a variety of modalities to achieve rapid and sensitive detection of small-molecule targets including ATP, cocaine, dehydroisoadrosterone-3-sulfate, synthetic cathinones, and tetrahydrocannabinol in complex biological samples. Based on these successes, we have developed novel SELEX methods to isolate aptamers with inherent functionalities using rationally designed libraries, selection conditions, and strategies. Such aptamers are customized for solving real-world problems and represent the most optimal solution for specific sensing applications. All findings reported here have served as a solid foundation for developing novel, customized SELEX methods to generate functionalized aptamers, enabling downstream development of sensors for any small molecule of interest."