Electrodetection of Small Molecules by Conformation-Mediated Signal Enhancement

Electrochemical biosensors allow the rapid, selective, and sensitive transduction of critical biological parameters into measurable signals. However, current electrochemical biosensors often fail to selectively and sensitively detect small molecules because of their small size and low molecular complexity. We have developed an electrochemical biosensing platform that harnesses the analyte-dependent conformational change of highly selective solute-binding proteins to amplify the redox signal generated by analyte binding. Using this platform, we constructed and characterized two biosensors that can sense leucine and glycine, respectively. We show that these biosensors can selectively and sensitively detect their targets over a wide range of concentrations-up to 7 orders of magnitude-and that the selectivity of these sensors can be readily altered by switching the bioreceptor's binding domain. Our work represents a new paradigm for the design of a family of modular electrochemical biosensors, where access to electrode surfaces can be controlled by protein conformational changes.