We have developed a novel multiphoton microscopy technique not relying on (and hence not limited by) fluorescence emission, which exploits the third-order nonlinearity called four-wave mixing of gold nanoparticles in resonance with their surface Plasmon. The coherent, transient and resonant nature of this signal allows its detection free from backgrounds that limit other contrast methods for gold nanoparticles. We show detection of single 10nm gold nanoparticles with low excitation intensities, corresponding to negligible average thermal heating. Owing to the the third-order nonlinearity we measure a transversal and axial resolution of 140nm and 470nm respectively, better than the one-photon diffraction limit. We also show high-contrast imaging of gold-labels down to 5nm size in Golgi structures of HepG2 cells at useful imaging speeds (10 kHz pixel rate). Thermal dissociation of gold nanoparticles from their bonding sites when varying the excitation intensity is also investigated.

Date Published: 12 February 2011
PDF: 7 pages
Proc. SPIE 7911, Plasmonics in Biology and Medicine VIII, 79110Y (12 February 2011); doi: 10.1117/12.873883

Published in SPIE Proceedings Vol. 7911:
Plasmonics in Biology and Medicine VIII
Tuan Vo-Dinh; Joseph R. Lakowicz, Editor(s)