Imaging and tracking single plasmonic nanoparticles in 3D background-free with four-wave mixing interferometry

Abstract

We present a four-wave mixing interferometry technique recently developed by us, whereby single non-fluorescing gold nanoparticles are imaged background-free even inside highly heterogeneous cellular environments, owing to their specific nonlinear plasmonic response. The setup enables correlative four-wave mixing/confocal fluorescence imaging, opening the prospect to study the fate of nanoparticle-biomolecule-fluorophore conjugates and their integrity inside cells. Beyond imaging, the technique features the possibility to track single particles with nanometric position localisation precision in 3D from rapid single-point measurements at 1 ms acquisition time, by exploiting the optical vortex field pattern in the focal plane of a high numerical aperture objective lens. These measurements are also uniquely sensitive to the particle in-plane asymmetry and orientation. The localisation precision in plane is found to be consistent with the photon shot-noise, while axially it is limited to about 3 nm by the nano-positioning sample stage, with an estimated photon shot-noise limit of below 1 nm. As a proofof-principle, the axial localisation is exploited to track single gold nanoparticles of 25 nm radius while diffusing across aqueous pockets in a dense agarose gel, mimicking a relevant biological environment.