In this study, we report on the remarkable two-photon excited fluorescence efficiency in the "biological window" of CaF2:Tm3+,Yb3+ nanoparticles. On the basis of the strong Tm3+ ion emission (at around 800 nm), tissue penetration depths as large as 2 mm have been demonstrated, which are more than 4 times those achievable based on the visible emissions in comparable CaF2:Er3+,Yb3+ nanoparticles. The outstanding penetration depth, together with the fluorescence thermal sensitivity demonstrated here, makes CaF2:Tm3+,Yb3+ nanoparticles ideal candidates as multifunctional nanoprobes for high contrast and highly penetrating in vivo fluorescence imaging applications.

NIR-to-NIR Two-Photon Excited CaF2:Tm3+,Yb3+ Nanoparticles: Multifunctional Nanoprobes for Highly Penetrating Fluorescence Bio-Imaging