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. Such fluorescent agents, however, are limited by photobleaching, blinking, and phototoxicity.