Four-wave mixing of gold nanoparticles for three-dimensional cell microscopy

Optical microscopy is an indispensable tool for obtaining spatial and temporal resolution within living cells and tissues. In this paper, a novel multiphoton microscopy technique which exploits the third-order nonlinearity called four-wave mixing and applied to gold nanoparticles in resonance with their surface plasmon is developed. The coherent, transient and resonant nature of this signal allows the interferometric time-resolved detection of four-wave mixing specifically originating from GNPs, with particle diameters down to 5nm. This paper demonstrate high-contrast, background-free imaging of gold-labelled Golgi structures in HepG2 cells with a sub-diffraction-limit lateral (axial) resolution of 140nm (470nm) at excitation powers corresponding to less than 3K photothermal heating, compatible to live cell imaging. These results pave the way towards photostable non-toxic and highly sensitive in-vivo optical imaging with sub-micron three-dimensional resolution.