Evaluation of a structural mechanics model to predict the effect of inserts in the bed support of chromatographic columns

Abstract

Inserts are placed within chromatography columns to enhance wall support. The impact of column inserts is captured by structural mechanics models.Simulations are shown to be in good agreement with experimental data. The model helps selecting dimensions of inserts to increase column linear velocity. a b s t r a c tCell culture titres are expected to increase still further over the forthcoming years. This imposes challenges for downstream processing including the potential need to use larger volumes of chromatography resins. Such a move could create throughput bottlenecks because of the compressible nature of many commercially available resins, which makes the operation of columns with diameters beyond 2 m infeasible due to resin collapse. The use of cylindrical inserts of negligible thickness has been proposed in the literature as a way to enhance the level of wall support, allowing higher superficial flow velocities to be applied and hence larger diameter columns to be used. In this study, a structural mechanics model has been developed to evaluate the effect of inserts on the column pressure drop and flow characteristics. Simulations were shown to be in good agreement with published experimental data. The model was then used to predict the effect of insert number, diameter, height and roughness on critical velocity of manufacturing scale columns.

Assessing the wall effects of packed concentric cylinders and angular walls on granular bed porosity

“…McCarthy et al [29] and Lovregio et al [30] showed that porosity values of spheres confined in annular and cylindrical cells, respectively, obtained through DEM and experimental methods can agree well quantitatively. Meanwhile, Gerontas et al [31] successfully developed a structural mechanics model of resin compression in a liquid chromatography column, which used the finite element method to simulate the effect of wall support inside the column on the process in agreement with the experimental data of Lan et al [20]. This consequently allowed the model to predict previously untested scenarios, thereby providing a convenient case study method.…”

Progression of continuous downstream processing of monoclonal antibodies: Current trends and challenges

“…Chromatography column scale-up typically involves increasing the diameter of the column to process a higher quantity of load at a constant bed height and flow velocity (Carta & Jungbauer, 2010). The diameters of manufacturing scale columns can go above 1 m with corresponding aspect ratios >5 (Gerontas, Lan, Micheletti, & Titchener-Hooker, 2015). Such changes in the column aspect ratio increases media compression and destabilizes the bed due to the loss of wall support and pressure drop (Stickel & Fotopoulos, 2001).…”

Size Separation of Silica Particles Using a Magnetite-Containing Gel-Packed Column

“…Compared with that of the Mag gel-packed column, the pressure drop of the gel-packed column was larger because of the smaller deformation of Mag gel relative to that of the reference gel in the column. This is because magnetite in the gel particles disturbed the free deformation at the contacting surfaces of the gel particles, resulting in a smaller pressure drop [6,14].…”