Tailored Mesoporous Silica Microspheres as HPLC Column Materials by a Hard-Templating Method

The targeted design of monodisperse, mesoporous silica microspheres (MPSMs) as HPLC separation phases is still a challenge. The MPSMs can be generated via a multi-step template-assisted method. However, this method and the factors affecting the individual process steps and resulting material properties are scarcely understood, and specific control of the complex multi-step process has been hardly discussed. In this work, the key synthesis steps were systematically investigated by means of statistical Design of Experiment (DoE). In particular, three steps were considered in detail: 1) the synthesis of porous poly(glycidyl methacrylate-co-ethylene glycol dimethacrylate) (p(GMA-co-EDMA)) particles, which as template particles, determine the structure for the final MPSMs. In this context, functional models were generated, which allow the control of the template properties pore volume, pore size and specific surface area. 2) In the presence of amino-functionalized template particles, the sol-gel process was carried out under Stöber process conditions. The water to tetraethyl orthosilicate (TEOS) ratio, as well as the concentration of ammonia as basic catalyst were varied according to a face-centered central composite design (FCD). The incorporation of silica nanoparticles (SNPs) into the pore network of the porous polymers was investigated by scanning electron microscopy (SEM), evaluation of the pore properties assessed by nitrogen sorption measurements and determination of the inorganic content by thermogravimetric analysis (TGA). Here, the material properties, such as the amount of attached silica, can be specifically controlled in the resulting organic/silica hybrid material (hybrid beads, HBs). Furthermore, depending on the sol-gel conditions three, potentially four, reaction regimes were identified, leading to different HBs. These range from porous polymer particles coated with a thin protective silica layer, to interpenetrating networks of polymer and silica, to potential particles consisting of a porous polymer core coated with a silica shell. Also, the effects of the use of different precursors and solvents on silica incorporation were investigated. 3) To obtain MPSMs from the HBs, the organic polymer template was removed by calcination. The effects of sol-gel process conditions on the resulting MPSMs were evaluated and relationships between process conditions and material properties were shown in predictive models. Fully porous, spherical, monodisperse silica particles with sizes ranging from 0.5 µm to 7.8 µm and pore sizes from 3.5 nm to 72.4 nm can be prepared specifically. Subsequent to organo-functionalization, prepared MPSMs were applied as reversed-phase HPLC column materials. Here, the columns were successfully applied for the separation of proteins and amino acids. The separation performance of the materials depends largely on the property profile of the MPSMs, which is predetermined during the preparation of the HBs