Center for Bioprocess Engineering, Martin-Luther-University Halle Wittenberg, Kurt-Mothes-Straße 3, Halle/Saale, Germany.
Bioprocess Biosyst Eng. 2012 Mar;35(3):333-40. doi: 10.1007/s00449-011-0571-6. Epub 2011 Jul 22.
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.
一种新的级联控制系统可重现性地将重组蛋白生产过程的培养部分保持在预定的轨道上。该系统在补料分批培养中直接控制二氧化碳生成质量和二氧化碳生成速率沿其设定点曲线，同时保持比生长速率和生物质曲线在期望路径上。该控制方案是使用基于工业过程控制系统 SIMATIC PCS 7（西门子 AG）的虚拟植物环境设计和调整的。通过验证实验表明，该直接方法的模拟直接反映了实验观察到的控制器行为。在虚拟植物环境中，级联控制明显优于以前使用的控制方法。该控制器显著提高了发酵的批间重现性。实验测试证实，它特别适用于响应时间和延迟较长的培养过程。该新控制器在大肠杆菌补料分批培养以及 CHO 细胞的动物细胞培养中的应用中展示了其性能。该技术是一种简单可靠的替代更复杂的模型支持控制器的方法。
