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重组蛋白生产过程中补料分批培养中溶解氧浓度的先进控制

Advanced control of dissolved oxygen concentration in fed batch cultures during recombinant protein production.

作者信息

Kuprijanov A, Gnoth S, Simutis R, Lübbert A

机构信息

Center for Bioprocess Engineering, Martin-Luther-University, Halle Wittenberg, Germany.

出版信息

Appl Microbiol Biotechnol. 2009 Feb;82(2):221-9. doi: 10.1007/s00253-008-1765-y. Epub 2008 Nov 13.

DOI:10.1007/s00253-008-1765-y
PMID:19005652
Abstract

Design and experimental validation of advanced pO(2) controllers for fermentation processes operated in the fed-batch mode are described. In most situations, the presented controllers are able to keep the pO(2) in fermentations for recombinant protein productions exactly on the desired value. The controllers are based on the gain-scheduling approach to parameter-adaptive proportional-integral controllers. In order to cope with the most often appearing distortions, the basic gain-scheduling feedback controller was complemented with a feedforward control component. This feedforward/feedback controller significantly improved pO(2) control. By means of numerical simulations, the controller behavior was tested and its parameters were determined. Validation runs were performed with three Escherichia coli strains producing different recombinant proteins. It is finally shown that the new controller leads to significant improvements in the signal-to-noise ratio of other key process variables and, thus, to a higher process quality.

摘要

本文描述了用于补料分批发酵过程的先进pO₂控制器的设计与实验验证。在大多数情况下,所提出的控制器能够将重组蛋白生产发酵中的pO₂精确地维持在期望值上。这些控制器基于增益调度方法应用于参数自适应比例积分控制器。为了应对最常出现的干扰,基本的增益调度反馈控制器补充了一个前馈控制组件。这种前馈/反馈控制器显著改善了pO₂控制。通过数值模拟,测试了控制器的行为并确定了其参数。使用三种生产不同重组蛋白的大肠杆菌菌株进行了验证实验。最终表明,新控制器显著提高了其他关键过程变量的信噪比,从而提高了过程质量。

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