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Bioprocess 2023
哺乳动物细胞培养中搅拌系统的研究进展
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Abstract:
近年来，全球肿瘤发病率逐年上升，以单克隆抗体为代表的重组蛋白受到越来越多的关注和应用，推动了搅拌釜式生物反应器在哺乳动物细胞培养工艺开发中的研究和发展。搅拌釜式生物反应器是以通过鼓泡分布器供氧，通过搅拌装置加速传质及实现微环境均一性为特征的一类反应器，广泛应用于重组蛋白生产，反应规模从10 mL到25,000 L不等。其中搅拌系统作为细胞培养中最关键的部分之一，其引导的流体混合特性及带来的剪切应力与细胞表现、代谢产品产量及质量息息相关。针对哺乳动物细胞培养工艺中搅拌系统的选择与设计目前已取得许多研究成果，故本文从常见叶轮类型、桨叶数量、桨叶安装方式、搅拌辅助配件、搅拌转速设计等方面展开论述，综述了搅拌系统的研究现状，以期为细胞培养工艺的反应器优化和规模缩放提供参考。
In recent years, with the rising of the global tumor incidence rate, recombinant proteins, represented by monoclonal antibodies, are gaining more and more attention and clinical application, which has promoted the research and development of the stirred tank bioreactor in mammalian cell culture. The stirred tank bioreactor, a type of reactor featured with a stirring device for enhancing mass transfer and achieving micro environment uniformity, and bubbling spargers for oxygen supply, has been widely used in the production of recombinant proteins, with reaction scales ranging from 10 mL to 25,000 L. The mix-ing system is one of the most critical parts of culture. Cell performance, yield and quality of meta-bolic products are closely related to this system and the fluid mixing characteristics and shear stress induced by it. Achievements have been made in the selection and design of stirring system in mammalian cell culture process. Here, the types, number, installation modes of impellers, auxiliary accessories, and stirring speed setting were reviewed and discussed to provide reference for the bioreactor optimization, and scaling up and down of the cell culture process.
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