Ranking bioprocess variables using global sensitivity analysis: a case study in centrifugation |
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Authors: | J M P King N J Titchener-Hooker Y Zhou |
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Institution: | (1) The Advanced Centre for Biochemical Engineering, Department of Biochemical Engineering, University College London, Torrington Place, London, WC1E 7JE, UK |
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Abstract: | The selection of appropriate operating conditions for bioprocessing is complex due to the large number of interacting stages
and variables. Bioprocesses also operate under tight regulation and therefore tools to assist bioprocess design are of significant
utility. Conventional approaches for the analysis of variable sensitivities are inadequate. We propose the use of global sensitivity
analysis to determine the level of importance of each variable and their interactions. Once key variables have been determined,
the designer may focus on the most significant subset. Two case studies are used to demonstrate the applicability of the approach.
Each is based on centrifugation and determines the impact of flow-rate, feed viscosity, density difference and particle size,
while performance is assessed by supernatant clarification. Significant differences in sensitivities were found between the
two studies due to the different feed material properties. Variable sensitivities were found to be system-specific and provide
insight for potential operating strategies. |
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Keywords: | Bioprocessing Simulation Global sensitivity analysis Interactions |
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