Second-harmonic nanoparticles for deep tissue in vivo imaging

Deep tissue in vivo imaging remains a great challenge and we propose to use second-harmonic radiation imaging probes (SHRIMPs) as long-term non bleaching biomarkers. We show that the contrast of SHRIMPs with autofluorescence and endogenous second-harmonic generation (SHG) signal is strong enough for imaging as deep as 100 um in the tail of a living rodent. Currently, optical microscopy often uses fluorescent markers such as green fluorescent proteins (GFPs) and quantum dots to specifically enhance the contrast of selected targets [1]. Such fluorescent agents, however, are limited by photobleaching, blinking, and phototoxicity.