Reagentless biomolecular analysis using a molecular pendulum

The development of reagentless sensors that can detect molecular analytes in biological fluids could enable a broad range of applications in personalized health monitoring. However, only a limited set of molecular inputs can currently be detected using reagentless sensors. Here, we report a sensing mechanism that is compatible with the analysis of proteins that are important physiological markers of stress, allergy, cardiovascular health, inflammation and cancer. The sensing method is based on the motion of an inverted molecular pendulum that exhibits field-induced transport modulated by the presence of a bound analyte. We measure the sensor's electric field-mediated transport using the electron-transfer kinetics of an attached reporter molecule. Using time-resolved electrochemical measurements that enable unidirectional motion of our sensor, the presence of an analyte bound to our sensor complex can be tracked continuously in real time. We show that this sensing approach is compatible with making measurements in blood, saliva, urine, tears and sweat and that the sensors can collect data in situ in living animals.