Coupled Nanomechanical Resonator with Protein-Interaction Vibration for an Ultrasensitive Label-Free Biosensor

A mechanical-resonator biosensor detects target molecules attached to the resonator surface through a change in resonant frequency caused by the mass-loading effect. Since mass-detection sensitivity can be improved by thinning resonator thickness, much effort has been devoted to the development of a thinner resonator. Here, we propose a much more effective strategy for an ultrasensitive mechanical-resonator biosensor. When the resonator frequency is close to the local vibration at a specific interaction between target and receptor molecules (∼30 GHz), a significantly large frequency change can occur because of energy coupling between the resonator vibration and target-receptor vibration (similar to avoided crossing). For realizing this strategy, we developed an ultrahigh-frequency nanomechanical resonator of multilayer graphene. The resonator-frequency change near the avoided-crossing frequency is about 10 times higher than that caused by the mass-loading effect, which allowed label-free detection of C-reactive protein with a detection limit of 10 pg/mL or less even in serum.