Improving cultivation processes for recombinant protein production |
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Authors: | A Kuprijanov S Schaepe M Aehle R Simutis A Lübbert |
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Institution: | 1.Center for Bioprocess Engineering,Martin-Luther-University Halle Wittenberg,Halle/Saale,Germany;2.Institute of Automation and Control Systems,Kaunas University of Technology,Kaunas,Lithuania |
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Abstract: | An new cascade control system is presented that reproducibly keeps the cultivation part of recombinant protein production
processes on its predetermined track. While the system directly controls carbon dioxide production mass and carbon dioxide
production rates along their setpoint profiles in fed-batch cultivation, it simultaneously keeps the specific biomass growth
rates and the biomass profiles on their desired paths. The control scheme was designed and tuned using a virtual plant environment
based on the industrial process control system SIMATIC PCS 7 (Siemens AG). It is shown by means of validation experiments
that the simulations in this straightforward approach directly reflect the experimentally observed controller behaviour. Within
the virtual plant environment, it was shown that the cascade control is considerably better than previously used control approaches.
The controller significantly improved the batch-to-batch reproducibility of the fermentations. Experimental tests confirmed
that it is particularly suited for cultivation processes suffering from long response times and delays. The performance of
the new controller is demonstrated during its application in Escherichia coli fed-batch cultivations as well as in animal cell cultures with CHO cells. The technique is a simple and reliable alternative
to more sophisticate model-supported controllers. |
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