Frahm Björn, Lane Paul, Atzert Hendrik, Munack Axel, Hoffmann Martin, Hass Volker C, Pörtner Ralf
Technische Universität Hamburg-Harburg, Bioprozess- und Bioverfahrenstechnik, Denickestrasse 15, 21071 Hamburg, Germany.
Biotechnol Prog. 2002 Sep-Oct;18(5):1095-103. doi: 10.1021/bp020035y.
Although fed-batch suspension culture of animal cells continues to be of industrial importance for the large scale production of pharmaceutical products, existing control concepts are still insufficient. Changes in cell metabolism during cultivation and between similar cultivations, the complexity of the cell metabolism, and the lack of on-line state variables restrict the transfer of available control strategies established in bioprocess engineering. A process control strategy designed to achieve optimized process control must account for all these difficulties and fit sophisticated requirements toward adaptability and flexibility. The combination of a fed-batch process and an Open-Loop-Feedback-Optimal (OLFO) control provides a new approach for cell culture process control that couples an efficient cultivation concept to a capable process control strategy. The application of an adaptive, model-based OLFO controller to a hybridoma cultivation and experimental results are presented.
尽管动物细胞的补料分批悬浮培养对于大规模生产药品仍具有工业重要性，但现有的控制理念仍存在不足。培养过程中以及相似培养之间细胞代谢的变化、细胞代谢的复杂性以及缺乏在线状态变量，限制了生物过程工程中已建立的可用控制策略的转移。旨在实现优化过程控制的过程控制策略必须考虑到所有这些困难，并满足对适应性和灵活性的复杂要求。补料分批过程与开环-反馈-最优（OLFO）控制相结合，为细胞培养过程控制提供了一种新方法，该方法将高效的培养理念与有效的过程控制策略相结合。本文介绍了一种自适应、基于模型的OLFO控制器在杂交瘤培养中的应用及实验结果。
