大规模微载体细胞培养技术研究—微载体回收、细胞迁移、灌注培养及过程放大
文献类型：学位论文
| 作者 | 王玉树 |
| 学位类别 | 博士 |
| 答辩日期 | 1999-04-26 |
| 授予单位 | 中国科学院研究生院 |
| 导师 | 欧阳藩 |
| 关键词 | 微载体回收 微载体间细胞迁移 重力沉降 灌注培养 过程放大 |
| 其他题名 | Large Scale Microcarrier Cell Culture Technology--Microcarrier Reeycling, Cell Transfer, Perfusion Culture and Scale-up |
| 中文摘要 | 本论文对大规模微载体细胞培养中的一些关键技术环节进行探索与研究，旨在简化微载体细胞扩大培养工艺，提高细胞反应器的单位体积生产能力，降低生产成本，同时对微载体细胞培养过程放大规律进行了初步理论探索。首次系统研究了回收利用Cytodex-3微载体的可行性。发现经4 ℃低温搅拌处理和-30 ℃冷冻处理后的微载体仍能支持Vero细胞的贴壁生长，其生长代谢特征与在新微载体上的十分相似，可用于在疫苗或其它生物制品生产中最后阶段的微载体的回收。首先实验验证了细胞在微载体间迁移的主要机制，并对微载体间细胞迁移传代技术的可行性进行试验。可望简化微载体细胞培养的过程放大工艺。设计出结构简单、操作方便的灌注装置，可较长时间地使细胞处于较高的活性状态（大于80％）并达到10~7/ml的密度。提出以培养系统可能产生的最小旋涡的特征长度与微载体大小的比值η/d作为微载体细胞培养过程放大设计合理性的评价标准及微载体细胞培养过程放大的主要程序步骤。 |
| 英文摘要 | Present research was mainly concerned with some key parts of the microcarrier cell culture technology, trying to simplify the scale-up process of anchorage-dependent animal cell culture, to increase the volumetric productivity of bioreactors, and to improve the economic efficiency of the production process. Investigations were also conducted to the scale-up mechanism of microcarrier cell culture process. The feasibility of recycle Cytodex-3 microcarrier for Vero cell culture was examined systematically. It was found that Vero cells could grow well on microcarriers recycled by cold treatment with high speed agitation at 4 ℃ and by freezing treatment at -30 ℃ with similar growth features to that of on new ones. Such a method can be applied in recycle microcarriers from the final stage of the production process of animal virus vaccines and other bio-therapeutic proteins. The main mechanism of bead-to-bead cell transfer was also identified and the applicability of subculturing technique by bead-to-bead cell transfer was examined. in order to simplify the scale-up process of animal cell culture. Perfusion cell culture based on gravitational setting was successfully applied, which was simple and easy to run, and of high scale-up potential. Cells on the microcarriers in the perfusion culture system could be kept with high viability (above 80%) and the cell density reached 10~7/ml. The ratio of smallest eddy length and the microcarrier diameter η/d, a critical parameter to the cell culture process, was proposed for examination of the scale-up design. The program of microcarrier culture scale-up process was outlined based on the criteria of η/d > 1. |
| 语种 | 中文 |
| 公开日期 | 2013-09-27 |
| 页码 | 90 |
| 源URL | [http://ir.ipe.ac.cn/handle/122111/1986]  |
| 专题 | 过程工程研究所_研究所（批量导入） |
| 推荐引用方式 GB/T 7714 | 王玉树. 大规模微载体细胞培养技术研究—微载体回收、细胞迁移、灌注培养及过程放大[D]. 中国科学院研究生院. 1999. |
入库方式： OAI收割
来源：过程工程研究所
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