EAGER: Demonstrating the Physics of Novel Solution-Phase Electrochemical Aptamer Sensors

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Continuous glucose monitoring for diabetes is a historical achievement in modern diagnostics, but unfortunately is an isolated success despite numerous acute needs across the broader field of human medicine. Glucose monitoring remains an isolated success because glucose sensors are based on enzymes which can be challenging to develop for analytes other than metabolites (e.g. glucose, lactate, ethanol). An alternate class of sensors called electrochemical aptamer sensors are simpler to develop for analytes beyond glucose (hormones, drugs, proteins), but aptamer sensors have not yet demonstrated the longevity of use required for most medical applications and often have limits in their sensitivity. These longevity and sensitivity challenges, at least in part, exist because a perfect layer of aptamer must be assembled and retained on an electrode surface. This project will demonstrate and explore the physics of a new sensor approach based on solution-phase electrochemical aptamer sensors. Simply, the aptamers are allowed to float freely in solution, and when an analyte binds with an aptamer the aptamer changes in shape in a way that is measurable by an electrode. Solution-phase electrochemical aptamer sensors will provide significant advantages in terms of (1) breakthrough longevity and robustness due to their simplicity, and (2) improved sensitivity due to their highly tunable physics. This project aligns with the goal of enabling personalized medicine, by creating a new approach for biosensors that allow continuous biosensing of hormones, peptides, therapeutic drugs, and other markers across human health and medicine. Building upon preliminary work, this project pursues two specific aims. Aim 1 - demonstrate the underlying physics of solution-phase electrochemical aptamer sensors using existing aptamer designs developed for optically measured aptamers. The rationale for pursuing this aim is that leveraging fully characterized and modeled aptamers will allow a rapid theoretical understanding of new experimental data in this project. The product of this aim will be at least one aptamer that can then be redesigned in Aim 2. Aim 2 - create a rationale toolset for modifying aptamer design for achieving maximum changes in electrochemical signal. By demonstrating this fundamental design toolset before pursuing application-specific work, this second aim will enable all researchers to more rapidly advance a new field of solution-phase electrochemical aptamer sensors. The product of this aim will be both new knowledge of the physics of solution-phase electrochemical aptamer sensors, and a launch-pad for follow-on work in both fundamental and applied proposals to create continuous biosensors that can be worn on the body or implanted in the body.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.