发酵过程多水平问题及其生物反应器装置技术研究——基于过程参数相关的发酵过程优化与放大技术  

Study on the Fermentation Processes at Multi-levels in Bioreactor and Its Application for Special Purposes——? ptimization and Scaling Up of the Fermentation Process Based on the Parameter Correlation Method

作　　者：张嗣良[1] 

机构地区：[1]华东理工大学生物反应器国家重点实验室国家生化工程技术研究中心,上海200237

出　　处：《中国工程科学》2001年第8期37-45,共9页Strategic Study of CAE

基　　金：国家自然科学基金资助项目 ( 2 9976 0 13)

摘　　要：回顾了发酵过程优化与放大所依据的基本思想和方法 ,认为采用以动力学为基础的最佳工艺控制点为依据的静态操作方法 ,实质上只是化学工程宏观动力学概念在发酵工程上的延伸 ,往往忽视细胞代谢流的存在。以细胞代谢流的分析与控制为核心的生物反应工程学的观点 ,通过实验研究 ,提出了基于参数相关的发酵过程多水平问题研究的优化技术和发酵过程多参数调整的放大技术。随着过程传感技术和计算机技术的发展 ,设计了一种定型为FUS 5 0L (A)的新概念生物反应器。这种新型生物反应器是以物料流检测为手段 ,过程优化与放大为目标 ,成功地应用在青霉素、红霉素、金霉素、肌苷、鸟苷发酵和Pichia酵母表达系统的基因工程人血清白蛋白 (rh SA)、疟疾疫苗等高密度高表达培养 ,大幅度提高发酵水平 ,并直接放大到几百升 ,甚至 10 0m3After reviewing the basic idea, methods of optimization and scale up for fermentation process adopted by many researchers for quite a long time, the author believes that the static optimizing method based on the kinetic conception with conventional optimum operating condition, in fact, is only an extension of kinetic conception of chemical engineering to the fermentation process.Such being the case, the existence of cellular metabolic flux is often neglected. Thus, the viewpoint to emphasize the metabolic flux analysis and control in bioreactor is put forward in this paper. Through several further experiments, the optimization technology of fermentation process at multi levels based on the parameter correlation methodology and scaling up strategy with multi parameters modulation have been realized. With the development of process sensing and computer technology, the new concept bioreactor (FUS 50L(A)) is used for fermentation processes optimization and scale up. This new bioreactor aimed at the measurement of material flux has been successfully applied to the fermentation of penicillin, erythromycin,aureomycin, inosine, guanosine, as well as the cultivation of recombinant human serum albumin, malaria vaccine, etc. As a result, thirty percent to several folds increase in titers were achieved. The process can be directly used for the scale up of Permentor from 50 liters to several hundred liters, even to 100 m 3. [

关 键 词：生物反应器 发酵 放大 过程优化 细胞培养 

分 类 号：TQ92[轻工技术与工程—发酵工程] TQ052