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采用先进控制器方案在大肠杆菌中生产重组蛋白的过程分析技术实施。

Implementing Process Analytical Technology for the Production of Recombinant Proteins in Escherichia coli Using an Advanced Controller Scheme.

机构信息

Department of Chemical Engineering, Indian Institute of Technology Delhi, Hauz Khas, New Delhi, 110016, India.

Kusuma School of Biological Sciences, Indian Institute of Technology Delhi, Hauz Khas, New Delhi, 110016, India.

出版信息

Biotechnol J. 2019 Nov;14(11):e1800556. doi: 10.1002/biot.201800556. Epub 2019 Aug 21.

DOI:10.1002/biot.201800556
PMID:31329337
Abstract

The performance of a bioreactor in meeting process goals is affected by the microorganism used, medium composition, and operating conditions. A typical bioreactor uses a supervisory control and data acquisition (SCADA) system for control, and a combination of software and hardware tools for real-time data analysis. However, when the process is disrupted by utility or instrumentation failure, typical process controllers may be unable to reinstate normal operating conditions before the cells in the reactor shift to unfavorable metabolic regimes. The objective of this study is to examine how the response of a controller affects process recovery when disruptive incidences occur under a process analytical technology (PAT) framework. The process used for this investigation is the production of lethal toxin-neutralizing factor (LTNF) by Escherichia coli (E. coli), which is controlled by a decoupled input-output-linearizing controller (DIOLC). The performance of the DIOLC is compared to a proportional integral derivative (PID) controller subjected to the same conditions. The disruptions are introduced manually and the effect of controller action on process recovery and LTNF synthesis is measured in terms of peak purity and concentration. It is observed that DIOLC performs better after reinstating operating conditions and results in a meaningful improvement in performance.

摘要

生物反应器的性能是否能满足工艺目标受到所使用的微生物、培养基组成和操作条件的影响。典型的生物反应器使用监控和数据采集 (SCADA) 系统进行控制,并结合软件和硬件工具进行实时数据分析。然而,当过程受到公用设施或仪器故障的干扰时,典型的过程控制器可能无法在反应器中的细胞转向不利的代谢状态之前恢复正常运行条件。本研究的目的是研究在过程分析技术 (PAT) 框架下发生破坏性事件时,控制器的响应如何影响过程恢复。本研究中使用的过程是大肠杆菌 (E. coli) 产生致死毒素中和因子 (LTNF),该过程由解耦输入输出线性化控制器 (DIOLC) 控制。将 DIOLC 的性能与受到相同条件的比例积分微分 (PID) 控制器进行比较。破坏性事件是手动引入的,根据峰纯度和浓度来衡量控制器作用对过程恢复和 LTNF 合成的影响。结果表明,在恢复操作条件后,DIOLC 的性能更好,并且在性能方面有明显的提高。

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