Diglycerylsilane (DGS), a member of the family of sugar-based silanes, is converted into monolithic silica at low temperatures and at mild pH. These materials are suitable for the entrapment of proteins under conditions that generally offer protection against denaturation, particularly when compared to analogous silicas prepared from tetraethoxysilane (TEOS). However, the resulting monoliths did not have sufficient porosity to permit flow and, thus, could not be utilized as monolithic chromatographic supports for frontal affinity chromatography (FAC). It was demonstrated that poly(ethylene oxide) can be used to induce spinodal decomposition of the DGS-derived sol, prior to gelation, leading to a meso- and macroporous silica monolith after cure, as demonstrated by nitrogen sorption analysis. High molecular weight PEO is required for effective phase separation to take place: below 10000 MW, no such phase separation occurs under the conditions employed. The amount and molecular weight of PEO is critical to the timing of gelation. If too much PEO is present, or ionic strength is increased, gelation occurs before it is possible to fill the chromatography column with the sol, while too little results in a lack of macropores. Proteins entrapped in this material are shown to be of comparable stability to those prepared in the absence of PEO, and can be used to chromatographically screen, with MS detection, potential drug candidates by changes in retention resulting from ligand binding.