Insights into shell formation mechanism and semi-scale preparation of radially porous SiO2@SiO2 core-shell microspheres in a biphasic system for fast separation in ultra-performance liquid chromatography

The biphasic method is commonly used to prepare SiO₂@SiO₂ core-shell microspheres (CSSMs) with pores perpendicular to the surface of the SiO₂ core. However, this method often results in incomplete shell coverage during scale-up preparation, which severely hinders the commercial application of this method. In this paper, the formation mechanism of the silica shell layer during the preparation of CSSMs using the biphasic method was investigated. The degree of interface disturbance in the biphasic system was found to affect the type and size distribution of emulsion droplets containing TEOS. Mild disturbance led to small O/W emulsion droplets around 2 μm in size, while strong disturbance resulted in both small O/W emulsion droplets around 2 μm and larger W/O/W emulsion droplets larger than 5 μm in the aqueous phase. Due to their mass differences, the droplets exhibit distinct inertial motion in the reaction system, leading to different wetting behaviors on the SiO₂ core surface. Specifically, the larger 5 μm droplets can partially wet the SiO₂ core interface when the silicate oligomer density on the droplet surface is low and hydrophobicity is high, whereas the smaller 2 μm droplets only wet the SiO₂ core interface when the silicate oligomer density is high and hydrophilicity is strong. When both droplet sizes coexist in the aqueous phase and participate in interfacial wetting, the residues with varying silicate oligomer densities further hydrolyze and condense, leading to shell structures with varying integrity. By reducing the stirrer diameter and agitation speed to maintain weak interfacial disturbance and generate only approximately 2 μm emulsion droplets, this study successfully resolved the issue of incomplete shell coverage during scale-up, achieving a CSSMs yield of 50 g. Furthermore, CSSMs modified with C18 were employed as the stationary phase in reversed phase liquid chromatography (RPLC) for the fast separation of small molecules and peptides. The superior separation efficiency indicates that the biphasic method has the potential to be utilized in the large-scale production of CSSMs.