@article{alkhamis_canoura_willis_wang_perry_xiao_2023, title={Comparison of Aptamer Signaling Mechanisms Reveals Disparities in Sensor Response and Strategies to Eliminate False Signals}, volume={145}, ISSN={["1520-5126"]}, DOI={10.1021/jacs.3c03640}, abstractNote={Aptamers are nucleic acid-based affinity reagents that have been incorporated into a variety of molecular sensor formats. However, many aptamer sensors exhibit insufficient sensitivity and specificity for real-world applications, and although considerable effort has been dedicated to improving sensitivity, sensor specificity has remained largely neglected and understudied. In this work, we have developed a series of sensors using aptamers for the small-molecule drugs flunixin, fentanyl, and furanyl fentanyl and compare their performance─in particular, focusing on their specificity. Contrary to expectations, we observe that sensors using the same aptamer operating under the same physicochemical conditions produce divergent responses to interferents depending on their signal transduction mechanism. For instance, aptamer beacon sensors are susceptible to false-positives from interferents that weakly associate with DNA, while strand-displacement sensors suffer from false-negatives due to interferent-associated signal suppression when both the target and interferent are present. Biophysical analyses suggest that these effects arise from aptamer-interferent interactions that are either nonspecific or induce aptamer conformational changes that are distinct from those induced by true target-binding events. We also demonstrate strategies for improving the sensitivity and specificity of aptamer sensors with the development of a "hybrid beacon," wherein the incorporation of a complementary DNA competitor into an aptamer beacon selectively hinders interferent─but not target─binding and signaling, while simultaneously overcoming signal suppression by interferents. Our results highlight the need for systematic and thorough testing of aptamer sensor response and new aptamer selection methods that optimize specificity more effectively than traditional counter-SELEX.}, number={22}, journal={JOURNAL OF THE AMERICAN CHEMICAL SOCIETY}, author={Alkhamis, Obtin and Canoura, Juan and Willis, Connor and Wang, Linlin and Perry, Jacob and Xiao, Yi}, year={2023}, month={May}, pages={12407–12422} }
 @article{canoura_liu_perry_willis_xiao_2023, title={Suite of Aptamer-Based Sensors for the Detection of Fentanyl and Its Analogues}, volume={4}, ISSN={["2379-3694"]}, DOI={10.1021/acssensors.2c02463}, abstractNote={Fentanyl and its analogues are potent synthetic opioids that are commonly abused and are currently the number one cause of drug overdose death in the United States. The ability to detect fentanyl with simple, rapid, and low-cost tools is crucial for forensics, medical care, and public safety. Conventional on-site testing options for fentanyl detection─including chemical spot tests, lateral-flow immunoassays, and portable Raman spectrometers─each have their own unique flaws that limit their analytical utility. Here, we have developed a series of new aptamer-based assays and sensors that can detect fentanyl as well as several of its analogues in a reliable, accurate, rapid, and economic manner. These include colorimetric, fluorescent, and electrochemical sensors, which can detect and quantify minute quantities of fentanyl and many of its analogues with no response to other illicit drugs, cutting agents, or adulterants─even in interferent-ridden binary mixtures containing as little as 1% fentanyl. Given the high performance of these novel analytical tools, we foresee the potential for routine use by medical and law enforcement personnel as well as the general public to aid in rapid and accurate fentanyl identification.}, journal={ACS SENSORS}, author={Canoura, Juan and Liu, Yingzhu and Perry, Jacob and Willis, Connor and Xiao, Yi}, year={2023}, month={Apr} }