Resonant four-wave mixing of gold nanoparticles for three-dimensional cell microscopy

By detecting the transient four-wave mixing from gold nanoparticles in resonance with their surface plasmon, we demonstrate a multiphoton imaging modality suited for cell microscopy. Four-wave mixing is measured free from background using a three-beam excitation geometry and heterodyne detection. We achieve a spatial resolution of 140 nm in-plane and 470 nm in the axial direction, surpassing the one-photon diffraction limit. With this technique, high-contrast photostable imaging of Golgi structures is demonstrated in HepG2 cells labeled with gold nanoparticles of 10 nm and 5 nm diameter.