Title: Translation between rotating disc and a capillary flow device for the ultra scale-down prediction of protein precipitate particle break-up
Authors: Papantoniou, Ioannis ×
Hoare, Mike #
Issue Date: 2011
Publisher: Elsevier
Series Title: Chemical Engineering Science
Abstract: Intense flow conditions are present in almost all bioprocesses and are particularly associated with operations involving agitation, pumping and flow and continuous flow high-speed centrifugation. The ability to predict the impact of such conditions on the properties of process materials, such as the size of suspended solids, using ultra scale-down methods which mimic large-scale processes is of considerable importance in the successful development of bioprocesses. This paper examines the impact of intense flow conditions on a microbial protein precipitate; this was chosen as it is known to be sensitive to flow conditions during processing especially during pumping and during recovery in continuous centrifugation.
The target of this work was to conduct experiments by using ultra scale-down (USD) shear devices which could mimic the flow conditions in the large-scale process while needing just a few millilitres of test material. In this study, two ultra scale-down devices, a rotating disk shear device and a capillary device, have been used to produce very intense flow conditions ie maximum shear rates >105 s-1 or maximum energy dissipation rates >100 W/mL. The use of the former device has been demonstrated for bench-scale studies as a mimic of industrial-scale operations especially for high stress regions in the feed zone of continuous-flow industrial centrifuges. The capillary flow device can operate with up to 50-fold less material and is suited for use in a robotic platform particularly for early studies of the impact of fluid stress in a material. The flow field within both devices was mapped using computational fluid dynamics (CFD). The effect of shear in an ultra scale-down rotating disc device was compared and correlated with that in a capillary device. A method is presented to correlate the extent of precipitate break up with flow conditions in the capillary and in terms of equilibrium sizes appropriate to specific combinations of stress and time and under extremes of stress. A series of first order rate constants were established to relate size changes with extent of shear and number of passes in the capillary and it was discussed how the flow conditions in a rotating disc device could be equated to an equivalent number of passes through a capillary of set length operating at a velocity to give the same maximum energy dissipation rate as that for a rotating disc. A preliminary fluid dynamic analysis of the flow patterns in a rotating disc device showed how the math with capillary flow conditions may be justified in terms of the mean frequency of exposure to high stresses at the disc tip and the mean time of exposure in that region.The use of an ultra scale-down capillary device within the laboratory or on a robotic platform is discussed. Such a device would allow the characterisation of the effect of shear on a process material and predict the performance of large-scale operations. As such the ultra scale-down method would be applicable at the early discovery stage of a new therapy when, until clinical efficacy is demonstrated, only limited amounts of material are available for bioprocess development.
ISSN: 0009-2509
Publication status: submitted
KU Leuven publication type: IT
Appears in Collections:Non-KU Leuven Association publications
× corresponding author
# (joint) last author

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