Coherent anti-Stokes Raman scattering microscopy of single nanodiamonds.

Abstract

Nanoparticles have attracted enormous attention for biomedical applications as optical labels, drug delivery vehicles, and contrast agents in vivo. In the quest for superior photostability and bio-compatibility, nanodiamonds (NDs) are considered one of the best choices due to their unique structural, chemical, mechanical, and optical properties. So far, mainly fluorescent NDs have been utilized for cell imaging. However, their use is limited by the efficiency and costs in reliably producing fluorescent defect centers with stable optical properties. Here, we show that single non-fluorescing NDs exhibit strong coherent anti-Stokes Raman scattering (CARS) at the sp3 vibrational resonance of diamond. Using correlative light and electron microscopy, the relationship between CARS signal strength and ND size is quantified. The calibrated CARS signal in turn enables the analysis of the number and size of NDs internalized in living cells in situ, which opens the exciting prospect of following complex cellular trafficking pathways quantitatively.