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新型生物人工肝反应器悬浮培养参数的优化测定

The optimization for suspension culture parameters in a novel bioreactor of bio-artificial liver

作者: 曹越  段梅梅  霍小林  吴昌哲  李明 
单位:中国科学院电工研究所(北京100190)
关键词: 生物反应器;人工肝;悬浮;Fluent;微载体 
分类号:
出版年·卷·期(页码):2012·31·4(331-337)
摘要:

目的 对新型生物人工肝反应器进行参数的优化测定,以寻找更适合肝细胞生长的工作条件。方法 从实验和仿真两方面优化运行参数。通过调节生物反应器旋转速度、培养液流速,寻找能使细胞微载体均匀悬浮于反应器的合理运行参数。利用流体动力学仿真软件Fluent对新型生物反应器进行仿真,将仿真结果与实验结果进行对比得出合理工作范围。结果 生物反应器的旋转往复周期Z越大,反应器内细胞微载体达到均匀悬浮状态时所需的培养液流速就越大,即控制培养液流动的蠕动泵转速L越大。在确保细胞微载体均匀悬浮分布下,往复周期Z=0.5min时,没有合适的L值满足要求;往复周期Z=0.4min时,L的工作范围为120~160r/min;往复周期Z=0.3min时,L的工作范围为80~160r/min。结论 合理的运行参数优化了生物人工肝的工作方式,为动物实验及临床实验奠定了基础。

Objective In order to find more suitable working conditions for the growth of liver cells, bioreactor parameters of a novel bio-artificial liver are optimized. Methods The study of optimization of culture parameters is divided into two parts: experiment and simulation. We control the rotational speed of bioreactor and the flow rate of culture medium to make micro-carriers suspend evenly in the bioreactor. We use the fluid dynamics software—Fluent to simulate this novel bioreactor and to obtain the reasonable working scope of the novel bioreactor by comparing the simulation results with the experimental results. Results With the increasing of the reciprocating cycle Z of the bioreactor, we need higher flow rate of culture medium to make sure micro-carriers suspend evenly in the bioreactor. The speed of the peristaltic pump L which controls the flow rate of culture medium should also be higher. In the evenly suspending condition of micro-carriers, when the reciprocating cycle Z is 0.5min, we cannot find a suitable value of L to meet the requirement. When the reciprocating cycle Z is 0.4min, the operating range of L is 120—160r/min. When Z is 0.3min, the value of L is 80—160r/min. Conclusions The acquisition of the reasonable operation parameters is useful for improving the efficiency of bio-artificial liver and has laid the foundation for further animal experiments and clinical trials.

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