Plasmonic Nanoprobes for Multiplexed Fluorescence‐Free Super‐Resolution Imaging

Abstract Noble metal nanoparticles (NPs), owing to their unique optical and physicochemical properties, are routinely used for optical imaging and labeling of biological specimens. Even though they can provide vital information for studying multiple cellular events and their interplays at the same time, optically multiplexing and resolving specific NPs within a diffraction‐limited region labeled in complex biological specimens remains a fundamental challenge. By introducing and manipulating plasmonic resonance assisted saturable scattering effects, multiplexed fluorescence‐free super‐resolution imaging of gold NPs in tumor cells with remarkable subdiffraction resolution is demonstrated. The saturable scattering allows fluorescence‐free resolving single plasmonic nanoprobes with significantly improved resolution down to ≈100 nm. The revealed plasmonic resonance assisted saturation effect as well as the associated spectral flexibility to variant sizes provides access to multiplexing capability in complex bioenvironments. The demonstrated feasibility of two‐color super‐resolution cellular imaging is achieved at ultralow suppression powers ≈0.28 MW cm⁻², corresponding to a two‐order of magnitude improvement compared to the state‐of‐the‐art of stimulated emission depletion (STED) nanoscopy.