Abstract
In recent papers we have discussed the use of cuboid packed-bed devices as alternative to columns for chromatographic separations. These devices address some of the major flow distribution challenges faced by preparative columns used for process-scale purification of biologicals. Our previous studies showed that significant improvements in separation metrics such as the number of theoretical plates, peak shape, and peak resolution in multi-protein separation could be achieved. However, the length-to-width aspect ratio of a cuboid packed-bed device could potentially affect its performance. A systematic comparison of six cuboid packed-bed devices having different length-to-width aspect ratios showed that it had a significant effect on separation performance. The number of theoretical plates per meter in the best-performing cuboid packed-bed device was about 4.5 times higher than that in its equivalent commercial column. On the other hand, the corresponding number in the worst-performing cuboid-packed bed was lower than that in the column. A head-to-head comparison of the best-performing cuboid packed bed and its equivalent column was carried out. Performance metrics compared included the widths and dispersion indices of flow-through and eluted protein peaks. The optimized cuboid packed-bed device significantly outperformed its equivalent column with regards to all these attributes.
Highlights
Column chromatography is widely used for both analytical and preparative purification of biopharmaceuticals [1,2,3,4]
Preparative columns used in large-scale biopharmaceutical purification processes typically have low bed height-to-diameter ratios
Cuboid packed-bed devices examined in this study were designed to provide superior flow distribution and thereby better separation than equivalent preparative columns
Summary
Column chromatography is widely used for both analytical and preparative purification of biopharmaceuticals [1,2,3,4]. Preparative columns, especially those used for large-scale bioseparation (which have small bed-height to diameter ratios) and are packed with larger resin particles (>30 microns) do not [3,6]. In multi-protein length-to-width aspect ratios of a cuboid packed-bed device of a given bed height and bed volume could separations. We have attempted to optimize the performance of a 5 mL cuboid packed-bed device by systematically examining 6 different cuboid devices having identical bed height and bed volume, but different length-to-width ratios. A head-to-head comparison of the best-performing cuboid packed-bed device and its equivalent column was carried out Performance metrics such as the widths, and dispersion indices of flow-through and eluted protein peaks were compared.
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