Imaging and Tracking Single Plasmonic Nanoparticles in 3D Background-Free with Four-Wave Mixing Interferometry

Abstract

Imaging and tracking single nanoparticles using optical microscopy are powerful techniques with many applications in biology, chemistry, and material sciences. Despite significant advances, imaging single particles in a scattering environment as well as localizing objects with nanometric position precision remains challenging. Applied methods to achieve contrast are dominantly fluorescence based, with fundamental limits in the emitted photon fluxes arising from the excited-state lifetime as well as photobleaching. Here, we show a new four-wave mixing interferometry technique, whereby single nonfluorescing gold nanoparticles are imaged background-free even inside biological cells, and their position determined with nanometric precision in 3D. The technique is also uniquely sensitive to particle asymmetries of only 0.5% ellipticity, corresponding to a single atomic layer of gold, as well as particle orientation. This method opens new ways of unravelling single-particle trafficking within complex 3D architectures.