Architecting Sub-2 nm Organosilica Nanohybrids for Far-field Super-resolution Imaging.

Stimulated emission depletion (STED) microscopy enables ultrastructural imaging of biological samples with high spatiotemporal resolution. Herein, we report a new class of STED nanoprobes based on fluorescent organosilica nanohybrids featuring sub-2 nm physical dimension and near-unity quantum yield. Corroborated by theoretical calculations, we experimentally demonstrate that the detrimental spin-orbit coupling (SOC) effect of heavy-atom-rich organic fluorophores can be effectively mitigated through a silane-molecule-mediated hydrolysis-condensation/dehalogenation process, resulting in bright fluorescent organosilica nanohybrids integrating with multiple emitters in one hybrid nanodot. When harnessed as STED nanoprobes, these sub-2 nm fluorescent nanohybrids show intense photoluminescence, high biocompatibility, and satisfactory long-term photostability. By taking advantages of the low-power excitation (0.5 uW), prolonged singlet-state lifetime, and negligible depletion-induced re-excitation, these fluorescent STED nanohybrids present high depletion efficiency (> 96%), extremely low saturation intensity (PSat = 0.54 mW, ~0.188 MW/cm2), and eventually ultra-high lateral resolution of sub-20 nm (~Wavelength em/28). We believe that this approach may facilitate the expansion of the nanoprobe toolbox across imaging and biological disciplines.