(406h) Development of a Realistic 3D Model of Silica Monoliths for Cfd Simulations

Vasudevan, V., National University of Singapore
Loh, K. C., National University of Singapore

One of the critical steps in the production of therapeutic biomolecules is their isolation and purification (downstream processing) which accounts for more than 50% of the total production cost. The full potential of therapeutic agents can be realized only if large quantities are available for testing, characterization and quantitative structure?activity analysis. The crucial factors for a successful and fast separation of large complex biomolecules are a reduced mass transfer resistance within large open-ended pores / channels and a small residence time within the chromatographic column to preserve their bio-activity. This has traditionally been carried out using particulate HPLC columns in which separation efficiency increases with decreasing particle diameter. High pressures associated with smaller particles, however, impose a practical limit on the improvements possible in separation efficiencies. This trade-off between column backpressure and efficiency has resulted in the use of short columns or low flow rates, often sacrificing one for the other. Monolithic columns, cast in the form of tubes, rods or disks as a single and co-continuous porous and permeable block, generally provide higher performance than conventional particulate HPLC columns. The regular structure of macroporous channels is less constricted and less tortuous than in packed beds and imparts a high external porosity. The stationary phase skeleton, made up of a network of small, thin threads of porous silica or polymers, has no effect on hydraulic resistance and hence can be tuned to speed up the mass transfer of analyte molecules. The reduced backpressure, minimal unspecific binding and low product degradation, without loss of resolution, make monoliths ideal candidates as chromatographic matrices for purification of large bio-macromolecules.

Direct visualization, believed to be the only way to capture the true morphology of porous materials, has traditionally been conducted using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Rapid advances in non?invasive 3D scanning techniques have led to the use of nuclear magnetic resonance imaging (MRI), laser scanning confocal microscopy (LSCM), x-ray computerized tomography (CT) and electron tomography to capture ?as is? the inherent morphologies of porous materials. Direct use of reconstructed 3D images as bounding geometries in an environment amenable to solving fundamental transport equations has obviated the need for fitting parameters in transport models, which limit the predictive value of the models. This research is aimed at elucidating the pore structure and transport mechanism characteristics of a silica monolith through CFD simulations by developing a realistic 3D model through image analysis of non-invasive scans of a monolith sample.

Reconstructed images from micro-CT scans of a silica monolith sample were processed to extract a representative pore volume. The flow domain within the pore volume was imported into an environment amenable to using the processed geometry as physical boundaries for flow simulations. Simulations of flow hydrodynamics as well as dispersion characteristics of the porous sample were performed using the commercial CFD software ? FLUENT. The simulations were verified for grid independence and other geometry-related parameters. The scanned geometry was validated by comparing simulations with experimental data obtained from commercially available monoliths. The efficacy of 3D morphology capture from micro-CT scans as well as simulation results will be discussed.