Measuring Solvent Exchange in Silica Nanoparticles with Rotor‐Based Fluorophore

Measuring the diffusivity of molecules is the first step toward understanding their dependence and controlling diffusion, but the challenge increases with the decrease of molecular size, particularly for non-fluorescent and non-reactive molecules such as solvents. Here, the capability to monitor the solvent exchange process within the micropores of silica with millisecond time resolution is demonstrated, by simply embedding a rotor-based fluorophore (thioflavin T) in colloidal silica nanoparticles. Basically, the silica provides an extreme case of viscous microenvironment, which is affected by the polarity of the solvents. The fluorescence intensity traces can be well fitted to the Fickian diffusion model, allowing analytical solution of the diffusion process, and revealing the diffusion coefficients. The validation experiments, involving the water-to-ethanol and ethanol-to-water solvent exchange, the comparison of different drying conditions, and the variation in the degree of cross-linking in silica, confirmed the effectiveness and sensitivity of this method for characterizing diffusion in silica micropores. This work focuses on the method development of measuring diffusivity and the high temporal resolution in tracking solvent exchange dynamics over a short distance (within 165 nm) opens enormous possibilities for further studies.