State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China,
Adv Biochem Eng Biotechnol. 2010;122:105-50. doi: 10.1007/10_2010_70.
Along with the rapid development of life science, great attention has been increasingly given to the biotechnological products of cell cultivation technology. In the course of industrialization, bioreactor and bioproduct separation techniques are the two essential technical platforms. In this chapter, the current situation and development prospects of bioreactor techniques in China are systematically discussed, starting with the elucidation of bioreactor processes and the principle of process optimization. Separation technology for biological products is also briefly introduced.At present, a series of bioreactors made by Chinese enterprises have been widely used for laboratory microbial cultivation, process optimization studies, and large-scale production. In the course of bioprocess optimization studies, the complicated bioprocesses in a bioreactor could be resolved into different reaction processes on three scales, namely genetic, cellular, and bioreactor scales. The structural varieties and nonlinear features of various scales of bioprocess systems was discussed through considering the mutual effects of different scale events, namely material flux, energy flux, and information flux, and the optimization approach for bioprocesses was proposed by taking the analysis of metabolic flux and multiscale consideration as a core strategy.In order to realize such an optimization approach, a bioreactor system based on association analysis of multiscale parameters was elaborated, and process optimization of many biological products were materialized, which resulted in great improvement in production efficiency. In designing and manufacturing large-scale bioreactors, the principle of scaling up a process incorporated with flow field study and physiological features in a bioreactor was suggested according to the criterion for the scale-up of cellular physiological and metabolic traits. The flow field features of a bioreactor were investigated through computational fluid dynamics (CFD), and the design of a bioreactor configuration was carried out depending on multiscale studies of parameters correlation in a bioprocess. With respect to the development trend of bioreactor studies in China, the significance of the development of microbioreactors for high throughput strain screening and large-scale bioreactors for animal cell cultivation were put forward. Finally, the importance of studies of systems biology for bioprocesses based on bioinformation processing was raised, and the necessity of establishing a bioprocess information database and local area network (LAN) were emphasized as well.Bioseparation engineering plays a key role in biotechnology production. At present, many difficulties need to be resolved in the area. Scientists of China have made considerable progress in bioseparation engineering. This progress includes chromatography media, recycling aqueous two-phase systems (ATPS), affinity precipitation, molecular imprinting, renaturation and modification of proteins, protein fractionation using ultrafiltration (UF), ion liquid separation of bioproducts, reverse micellar extraction, etc. The preparation of bioseparation materials, as well as part of bioseparation process research development in the past 5 years, are introduced here.
随着生命科学的快速发展，细胞培养技术的生物技术产品越来越受到重视。在产业化过程中，生物反应器和生物产品分离技术是两个必不可少的技术平台。本章从生物反应器过程的阐明和过程优化的原理出发，系统地讨论了中国生物反应器技术的现状和发展前景。简要介绍了生物产品的分离技术。目前，中国企业生产的一系列生物反应器已广泛应用于实验室微生物培养、工艺优化研究和大规模生产。在生物过程优化研究过程中，可以将生物反应器中的复杂生物过程分解为三个尺度上的不同反应过程，即遗传、细胞和生物反应器尺度。通过考虑不同尺度事件之间的相互作用，即物质通量、能量通量和信息流，讨论了各种生物过程系统的结构多样性和非线性特征，并提出了以代谢通量分析和多尺度考虑为核心策略的生物过程优化方法。为了实现这种优化方法，阐述了一种基于多尺度参数关联分析的生物反应器系统，并实现了许多生物产品的过程优化，大大提高了生产效率。在设计和制造大型生物反应器时，根据细胞生理和代谢特性的放大准则，提出了结合流场研究和生物反应器生理特征的放大过程原理。通过计算流体动力学（CFD）研究生物反应器的流场特性，根据生物过程中参数相关性的多尺度研究，进行生物反应器结构设计。关于中国生物反应器研究的发展趋势，提出了发展高通量筛选用微生物生物反应器和动物细胞培养用大规模生物反应器的意义。最后，提出了基于生物信息处理的生物过程系统生物学研究的重要性，并强调了建立生物过程信息数据库和局域网（LAN）的必要性。生物分离工程在生物技术生产中起着关键作用。目前，该领域还需要解决许多困难。中国科学家在生物分离工程方面取得了相当大的进展。这一进展包括色谱介质、回收双水相体系（ATPS）、亲和沉淀、分子印迹、蛋白质复性和修饰、超滤（UF）分离蛋白质、离子液体分离生物产物、反胶束萃取等。本文介绍了过去 5 年生物分离材料的制备以及部分生物分离过程研究的进展。
