Aptamer-based biosensors: from SELEX to biomedical diagnostics

With excellent binding properties, stability, programmable structures, and ease of modification, DNA aptamers are promising for developing biosensors for both point-of-care and continuous monitoring applications. Over the last few years, significant progress has been made in the selection of high-quality aptamers for important target molecules, fundamental understanding of aptamer binding, and biosensor development, especially in the form of portable sensors, continuous in vivo monitoring and wearable devices. For small molecule targets, library-immobilization-based selection has yielded over 100 high-quality short aptamers with well-defined secondary structures. For protein targets, engineering polyvalent aptamers and slow off-rate aptamers can better mimic the binding properties of antibodies allowing extensive washing and binding in complex sample matrices. New methods in cell-SELEX have also provided insights into the isolation of aptamers against rare surface biomarkers. This review aims to capture these developments, which will build a solid foundation for future research and development in aptamer-based biosensors. • New aptamer selection methods reviewed for small molecules, proteins and cells. • Wearable biosensors, in vivo continuous monitoring devices and lateral flow devices based on aptamers described. • Critical comparison of different aptamer selection and sensing strategies.