Band Gap Engineering Improves Three-Photon Luminescence of Quantum Dots for Deep Brain Imaging

Three-photon fluorescence microscopy (3PFM) has emergedas a promisingtool in monitoring the structures and functions of the brain. Comparedto the various imaging technologies, 3PFM enables a deep-penetratingdepth attributed to tighter excitation confinement and suppressedphoton scattering. However, the shortage of three-photon probes witha large absorption cross section (& sigma;(3)) substantiallylimits its uses. Herein, CdSe/CdS/ZnS quantum dots (QDs) with enhanced3PF performance were synthesized via the band gap engineering strategy.The introduction of a CdS interlayer with optimized thickness betweenthe emitting CdSe core and the ZnS shell significantly enhanced the3P absorption cross section of QDs, which originated from the intrinsicpiezoelectric polarization effect and the change of the core/shellstructure from type-I to quasi-type-II. In addition, the outer ZnSlayer compensated the poor electronic passivation of CdS, providinga high level of passivation for the improvement of quantum yield aswell as the 3P action cross section of QDs. Under the excitation ofa 1600 nm femtosecond laser, PEGylated CdSe/CdS/ZnS QDs were usedfor in vivo 3PFM imaging of cerebral vessels with high resolution.A tiny capillary with a diameter of 0.8 & mu;m could be resolvedat the imaging depth of 1550 & mu;m in a mouse brain with an openedskull. A penetration depth of 850 & mu;m beneath the skull was alsoachieved using a mouse model with an intact skull.