Resonance-enhanced functional third harmonic optical microscopy

For the purpose of functional third harmonic optical microscopy, it is necessary to find a method to locally enhance third harmonic generation at specific cellular site. We have demonstrated that by matching the third harmonic generation frequency of a Cr:forsterite laser and the surface plasmon resonance frequency of <50-nm silver nanoparticles, localized enhancement of third harmonic intensity of more than 100-folds can be achieved both in phantom and in real biological tissues. This strongly enhanced third harmonic signal can then be applied to specific molecule imaging by attaching the nanoparticles to the target molecule with the advantages of noninvasiveness and deep penetration capability.