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Low speed, low capacity, and poor scalability make size-exclusion chromatography (SEC) unattractive for use in the preparative separation of proteins. We discuss a novel z2 cuboid SEC device that addresses these challenges. A z2 cuboid SEC device (~24 mL volume) was systematically compared with a conventional SEC column having the same volume and packed with the same resin. The primary objective of this study was to use the same volume of SEC medium in a much more efficient way by using the novel device. At any given flow rate, the pressure drop across the z2 cuboid SEC device was lower by a factor of 6 to 8 due to its shorter bed height and greater cross-sectional area. Under overloaded conditions, the peaks obtained during protein separation with the conventional column were poorly resolved and showed significant fronting, while those obtained with the z2 cuboid SEC device were much better resolved and showed no fronting. At any given flow rate, better resolution was obtained with the z2 cuboid SEC device, while for obtaining a comparable resolution, the flow rate that could be used with the z2 cuboid SEC device was higher by a factor of 2 to 3. Hence, productivity in SEC could easily be increased by 200 to 300% using the z2 cuboid SEC device. The scalability of the z2 cuboid SEC device was also demonstrated based on a device with a 200 mL bed volume.

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Conventional hollow fiber hemodialyzers have a cylindrical shell-and-tube design. Due to their circular cross-section and radial flow distribution and collection in the headers, the flow of blood in the header as well as in the hollow fiber membranes is non-uniform. The creation of high shear stress and high shear rate zones or stagnation zones could result in problems, such as cell lysis and blood clotting. In this paper, a novel cuboid hemodialyzer design is proposed as an alternative to the conventional cylindrical hemodialyzer. The primary motivation behind the proposed design is to create uniform flow conditions and thereby minimize some of the above-mentioned adverse effects. The most salient feature of the proposed design is a cuboid shell within which the hollow fiber membrane bundle is potted. The lumen of the fibers is fed from one side using a flow distributor consisting of embedded primary and secondary channels, while the fibers are drained from the other side using a flow collector, which also has embedded primary and secondary channels. The flow characteristics of the lumen side of the cuboid hemodialyzer were compared with those of a conventional hemodialyzer based on computational fluid dynamics (CFD) simulations. The results of CFD simulations clearly indicated that the flow of liquid within the cuboid dialyzer was significantly more uniform. Consequently, the shear rate and shear stress were also more uniform. By adopting this new design, some of the problems associated with the conventional hemodialyzer design could potentially be addressed.

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