Development of photoelectrochemical DNA biosensors based on plasmonic/photoelectrochemcial interactions

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Biosensors are devices used to detect and/or quantify biological analytes such as nucleic acids, proteins, and metabolites for managing diseases and monitoring health. Handheld biosensors that bring this analytical capability to the patients' bedsides, patients' homes, local clinics, and in general, the point-of-care, are envisioned to significantly improve the quality of healthcare while reducing its cost by enabling preventive, expedited, and patient-centered clinical decision making. Nucleic acids such as DNA and RNA are important predictive, early diagnosis, and treatment selection and monitoring biomarkers, and there is an ongoing effort towards creating handheld nucleic acid biosensors. In spite of these efforts, there are currently no commercially-available handheld nucleic acid biosensors, similar in functionality to electrochemical glucose monitors, for disease management. The difficulty in creating handheld nucleic acid biosensors is that on one hand, they are required to meet the sensitivity, specificity and multiplexing required for clinical decision making; and, on the other hand, they need to offer these through portable, rapid, easy-to-use, and inexpensive platforms that are suitable for use in non-laboratory settings. Developing new knowledge in the field of photoelectrochemical signal transduction for addressing the requirements of handheld nucleic acid biosensors is at the center of this research program.***Photoelectrochemical nucleic acid biosensors use photo-active materials to translate nucleic acid hybridization into changes in electrical currents. These devices offer a larger signal-to-noise ratio compared to their widely-explored electrochemical counterparts that use electrical signals for excitation and measurement. Furthermore, given that signal readout is done electrically, photoelectrochemical sensors still benefit from the ease of multiplexing and the inexpensive readout instrumentation available to electrochemical devices. We propose to develop a novel photoelectrochemical biosensor based on the newly discovered short range (<20 nm) interactions between photoelectrochemical and plasmonic materials. In this sensing strategy, nucleic acid hybridization causes a plasmonic nanoparticle to be removed from the vicinity of the photoelectrochemical material, which will generate an increase in the generated photoelectrochemical current. Furthermore, built-in signal amplification strategies, based on DNA self-assembly, will be incorporated – for the first time – within this class of biosensors to enhance the generated current and the analytical sensitivity of the device. The proposed research will allow us to generate new knowledge for developing the first multiplexed nucleic acid biosensor based on photoelectrochemical/plasmonic interactions, for meeting the requirements of point-of-care biosensors.