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

Optical microscopy is an indispensable tool that is driving progress in cell biology, and is still the only practical means of obtaining spatial and temporal resolution within living cells and tissues. Much effort is being devoted recently to achieve intrinsic three-dimensional (3D) spatial resolution by exploiting optical nonlinear effects which can only take place in the small focal volume where high photon densities are reached. Presently, the most important multiphoton (ie nonlinear) microscopy technique for cell imaging is two-photon fluorescence [1] where the biomolecules of interest are labelled with fluorophores, which are optically excited via simultaneous absorption of two photons. Two-photon fluorescence is however limited by photobleaching of organic fluorophores or toxicity effects when using inorganic quantum dots [2].