dynamic optimization of bioprocesses动态优化的生物过程.pdfVIP

Applied Mathematics, 2012, 3, 1487-1495 /10.4236/am.2012.330208 Published Online October 2012 (http://www.SciRP.org/journal/am) Dynamic Optimization of Bioprocesses 1 2 George Koumpouras , Cleo Kontoravdi 1 Nexant Limited, 1 King’s Arms Yard, London, UK 2Centre for Process Systems Engineering, Department of Chemical Engineering, Imperial College London, South Kensington Campus, London, UK Email: cleo.kontoravdi@imperial.ac.uk Received July 10, 2012; revised August 10, 2012; accepted August 17, 2012 ABSTRACT The Bioprocessing industry delivers high-value protein-based pharmaceutical products produced using microbial or animal cells. Animal cell culture, the only method currently available for the production of proteins with human-like post-translational modifications, is an expensive and labor-intensive process, as animal cells have complex nutrient re- quirements. Optimization studies have typically been limited to experimental studies, although there has recently been increased interest in combined experimental and computational approaches. In this work, we present the results of a dynamic optimization approach to improving animal cell bioprocesses. We have based this on a model validated over batch and fed-batch conditions and have examined four possible objective functions. Our results indicate that the maxi- mization of the product concentration or the integral of viable cell concentration over time give equivalent results and can improve the product titer up to 70% over non-optimized fed-batch cultures. Keywords: