Dynamic plasmonic imaging of electromechanically driven nano-oscillators for charge-resolved multiplex biosensing

Multiplexed profiling of diverse biomarkers is essential for precision diagnostics, but remains challenging for label-free sensors because signals typically scale with analyte mass. Here, we present a dynamic plasmonic imaging platform based on electromechanically driven nano-oscillators for multiplexed, label-free quantification of nucleic acids, proteins, and small molecules within a unified sensing architecture. Size-encoded nanoparticles tethered to a plasmonic surface are electrically actuated to oscillate vertically within the evanescent field and tracked by distance-resolved surface plasmon resonance imaging. Molecular binding alters the effective surface charge of each nano-oscillator, modulating the electrostatic-driven forces and changing oscillation amplitude. This charge-to-motion transduction mechanism reduces dependence on molecular mass and enhances sensitivity for low–molecular weight analytes. This platform simultaneously detects microRNAs, proteins, and small molecules spanning a ∼300-fold molecular weight range within a single field of view. We further demonstrate multiplexed profiling of tumor-associated microRNAs in pretreated supernatants from patient-derived breast cancer cells across 24 clinical samples. Dynamic plasmonic nano-oscillators provide a scalable architecture for multiplex molecular diagnostics.