title: Continuous hybridoma bioreactor: sensitivity analysis and optimal control.
abstract: Animal cell culture has already established itself as a mature technology able to make a wide range of valuable products, the actual focus being to find the competitive bioreactor design and operating conditions for increasing production. A complex analysis, implying sensitivity calculus and optimal control computation, is done for a system composed of a continuous perfectly mixed bioreactor, with cell recirculation, a cell separator, a mixer and a purge. The bioreactor's sensitivity to the control parameters is measured by a new concept, entropic density, developed from the notion of Shannon entropy. An optimization procedure based on a genetic-algorithms approach is applied for the computation of the inlet flow profile in time, which guarantees optimum monoclonal-antibody production. Our studies, including the present one, proved that the best approach to obtain high production is to use a hybrid operating sequence: fed-batch mode followed by the continuous mode.
authors.affiliation: Chemical Engineering Department, University Politehnica of Bucharest, Polizu 1-7, 011061 Bucharest, Romania. vasile_lavric@webmail.pub.ro
authors.forename: Vasile
authors.initials: V
authors.lastname: Lavric
authors.forename: Irina Dana
authors.initials: ID
authors.lastname: Ofiţeru
authors.forename: Alexandru
authors.initials: A
authors.lastname: Woinaroschy
mesh_terms: D000911:Antibodies, Monoclonal / Q000096:biosynthesis*; D019149:Bioreactors; D018929:Cell Culture Techniques / Q000295:instrumentation / Q000379:methods; D005246:Feedback; D006825:Hybridomas / Q000378:metabolism*; D008962:Models, Theoretical
chemical_list: D000911:Antibodies, Monoclonal