Silica-based monoliths

The basic studies dealing with the preparation of continuous porous silica materials date back to 1991 [76-78]. Two years later, Nakanishi and Saga applied for a patent describing the fabrication of monolithic silica rods for chromatographic application [79-81], whereas a second protocol for the preparation of continuous silica rods was independently filed by Merck KGaA in Germany [82]. 

First comprehensive investigations with respect to the properties of continuous porous silica rods were, however, carried out by Tanaka and Fields in 1996 [33,34,83], who reported on two different methods for the preparation of silica monoliths. 

FIGURE 1.4 Morphology and porosity of a typical monolithic rod, prepared by copolymerization of silane precursors, (a) SEM micrograph of the fractured surface of a monolithic silica gel rod. (b) Pore size distribution of a representative monolithic silica rod. (Reprinted from Guiochon, G., J. Chromatogr. A, 1168, 101, 2007. Copyright 2007, with permission from Elsevier.) 

Although inorganic, monolithic columns attracted considerable attention in the last 10 years, the preparation of silica-based monoliths does not yet offer the broad chemical variety of precursors and porogens for specific adjustment of separation compared with their organic counterpart. The preparation of silica monoliths uses the classical sol-gel process of hydrolysis and polycondensation of organosilicium compounds. 

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Cabrera, K. Applications of silica-based monolithic HPLC columns./. Sep. Sci. 2004, 27, 843-852. 

Bushey, M.M., Jorgenson, J.W. (1990). Automated instrumentation for comprehensive two-dimensional high-performance liquid chromatography of proteins. Anal. Chem. 62,161-167. Cabrera, K. (2004). Applications of silica-based monolithic HPLC columns. J. Sep. Sci. 27, 843-852. 

Leinweber, F.C., Lubda, D., Cabrera, K., Tallarek, U. (2002). Characterization of silica-based monoliths with bimodal pore size distribution. Anal. Chem. 74, 2470-2477. 

Reproducibility of monolithic columns has also been cited as a major concern because the monoliths are manufactured individually.34-35 An extensive study by Kele and Guiochon indicates that the reproducibility results of Chromolith columns were almost comparable to those from different batches of particle-packed columns.37 Other drawbacks of monolithic columns include weak reten-tivity for polar analytes,38 efficiency loss at high flow rates for larger (800 MW) molecules,39 and peak tailing, even for neutral non-ionizable compounds.36-38-40 Furthermore, silica-based monolithic... 

FIGURE 13.7 Scanning electron micrograph showing flow-through channels in silica-based monolithic rods. 

Excellent performance for the elution of another peptide, insulin (molecular weight 5800 g/mol), was also observed using silica-based monoliths. The efficiency of the monolithic column was much better than that of a column packed with beads, and did not change much even at high flow rates. 

The promise of monolith is the achievement of a higher performance at a lower backpressure than a packed bed. While this is true in principle, current implementations are limited by the fact that the external wall to the structure is made from PEEK. At the time of this writing, the commercially available monoliths can only be used up to a pressure of 20MPa (200 atm, 3000 psi), while packed bed steel columns can be used up to double this pressure and higher. Also, the preparation of the monolith appears to be cumbersome. At the current time, the silica-based monoliths are available only with an internal diameter of 4.6mm. The speed is thus also limited by the flow rate achievable by the HPLC instrument. At the same time, the detector of choice today is the mass spectrometer, which can tolerate only much... 

Silica-based monolithic columns (Figure 9) are generally prepared using sol-gel technology. This involves the preparation of a sol solution and the gelation of the sol to form a network in a continuous liquid phase within the capillary. The precursors for the synthesis of these monoliths are normally metal alkoxides that react readily with water. The most widely used are alkoxysilanes such as tetramethoxysilane (TMOS) and TEOS. 

The sol-gel process for the preparation of silica-based monoliths involves heat treatment at lower temperatures for gelation and aging and the formation of mesopores by heating at high temperatures. 

Smith, J. H. McNair, H. M. Fast HPLC with a Silica-Based Monolithic ODS Column. J Chromatogr Sci 2003, 41, 209-214. 

Depending on the postpolymerization derivatization procedure, silica-based monolithic columns have been employed for NPC [95] (see also Merck KGaA Darmstadt, Germany), RPC [189-193,196,197,200] (see also Merck KGaA Darmstadt, Germany), lEX [194], and HILIC [84,194,198] application. Additionally, their use as efficient bioreactors has recently been reported [86,195]. 

During the past 10 years, in addition to silica-based monoliths [12], a broad range of organic polymeric monoliths has been studied. Their most advantageous attribute is their chemical stability over a wide pH range. The most common organic monoliths were the results of methacrylate [13] and styrene [14] monomers. Some examples that confirm the utility of monolithic columns in IPC are described below. 

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