【作者】 赵晓伟；

【导师】 宋博岩；

【作者基本信息】 哈尔滨工业大学 ， 机械制造及其自动化， 2010， 硕士

【摘要】 随着生物技术由实验室研究向实用化和产业化的不断转化,细胞培养作为其重要的手段已成为许多国家争先研究的领域。目前,国内外对于细胞培养的研究不仅仅只停留在实验室规模,而是迈向工业级别的大规模培养,这就对细胞体外培养技术的核心装置生物反应器提出了更高的要求。通过对细胞大规模培养的影响因素进行分析,发现反应器内流场混合的均匀性和搅拌剪切力是制约细胞大规模培养的主要原因,因此把这两个因素作为研究方向,进行一系列的仿真计算,为细胞大规模培养生物反应器的研究设计提供资料和理论依据。首先,采用CFD数值模拟方法分析一种新型的Elephant Ear桨叶,把它和三种常用的搅拌桨叶在流场混合均匀性和剪切力这两方面进行了仿真对比,得出该桨叶不仅产生的剪切力较小而且流场的混合也比较均匀,采用该桨叶作为大规模生物反应器的搅拌桨叶。在此基础上,使用FLUENT仿真软件对采用Elephant Ear桨叶的100L生物反应器进行了结构优化,优化了反应器的高径比、反应器罐底半径、桨叶安装高度、挡板数量;同时对Elephant Ear桨叶也进行了仿真分析。然后,运用有限元分析软件ABAQUS从宏观角度对CHO细胞在流场内的力学特性进行了仿真分析,得到了在剪切力作用下细胞产生的应力和变形规律;分析了培养液压力和剪切力复合作用下的细胞力学特性,认为剪切力是引起细胞变形破坏的主要原因。最后,把CHO细胞在不同转速下的培养实验和仿真分析结合起来,得出最适合CHO细胞生长的流场剪切力为0.3Pa,对细胞在该剪切力作用下进行了仿真分析,得出细胞在U方向的最大变形位移为8.5μm。更多还原

【Abstract】 With the continuous transformation of biotechnology from laboratory research to practical and industrial, cell culture technology which is the important means of it has become a rushed field of study in many countries. Currently cell culture studies does not just stop at the laboratory scale, but develops towards the large-scale industrial-level training both at home and abroad, therefore, the bioreactor which is the core device of cell culture technology is required higher. In this paper, based on the analysis of affected factors of large-scale cultivation of cells, we found the main reason for restricting cell mass culture, which is mixed flow reactor uniformity and mixing shear force, therefore, making the two factors as research directions, we carried out a series of simulation calculations and provide information and theoretical basis for the research and design of the large-scale cell culture bioreactor.Firstly, using CFD simulation to analyze a new type of Elephant Ear impeller, and make a simulation comparison on it and the three commonly used impeller in the mixed flow uniformity and shear force, as a result, it founds that it not only produces less shear force but also produces more uniform flow mixing field, therefore, the impeller was used for the bioreactor.On this basis, using the simulation software FLUENT to optimize the structure of 100L bioreactor which is use Elephant Ear impeller, optimization of the reactor diameter ratio, bottom of the tank radius, impeller mounting height and the number of baffles; simultaneously, Elephant Ear impeller is analyzed too.Secondly, using the finite element analysis software ABAQUS simulation analysis the mechanical properties of CHO cells in the flow field from a broad perspective, as a result, obtained the law of cells stress and deformation by Shear force; Analysis of the mechanical properties of cells which is in the medium pressure and shear stress, and get the conclusion that the shear stress is the main reason for deformation and damage of cell.Finally, we combine the CHO cells cultured experiment under different speed test and simulation analysis, get the result that the most suitable shear stress for the growth of CHO cells in the shear flow field is 0.3Pa, simultaneously, simulate the effect of the shear stress on cells and get the result that the maximum deformation of cell in the U direction is 8.5μm.更多还原