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Continuous hybridoma bioreactor: sensitivity analysis and optimal control
Author(s) -
Lavric Vasile,
Ofiţeru Irina Dana,
Woinaroschy Alexandru
Publication year - 2006
Publication title -
biotechnology and applied biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 70
eISSN - 1470-8744
pISSN - 0885-4513
DOI - 10.1042/ba20050222
Subject(s) - bioreactor , sensitivity (control systems) , computation , process engineering , operating point , computer science , separator (oil production) , control theory (sociology) , biochemical engineering , biological system , algorithm , control (management) , engineering , chemistry , biology , physics , electronic engineering , organic chemistry , artificial intelligence , thermodynamics
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.