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使用振动搅拌器的实验室规模生物反应器的机械和几何因素对哺乳动物细胞培养指标影响的定量研究。

Quantitative investigation of the effect of mechanical and geometrical factors of a laboratory-scale bioreactor using a vibrating agitator on mammalian cell culture indices.

作者信息

Govara Sepehr, Hosseinalipour S M, Soleimani Masoud

机构信息

School of Mechanical Engineering, Iran University of Science and Technology, Resalat Square, Hengam Street, Tehran, Tehran, Iran.

Department of Hematology, Faculty of Medical Science, Tarbiat Modares University, Tehran, Tehran, Iran.

出版信息

Bioprocess Biosyst Eng. 2025 Jan;48(1):85-101. doi: 10.1007/s00449-024-03095-0. Epub 2024 Oct 7.

Abstract

Mammalian cell cultures in laboratories are performed in static and dynamic methods, and cell growth indices are higher in dynamic mode. In this study, a lab-scale stirred bioreactor using a vibrating disc and a suitable setup has been introduced for dynamic cell culture, which creates proper mixing at low shear stress. 15 experiments have been done by Raji cell in batch mode using Box-Behnken design to quantitatively investigate the effect of mechanical and geometrical factors of this bioreactor on cell culture indices. Three structural factors, including disc diameter, vibration amplitude, and the height of the disc placement have been selected as the main factors. Three cell growth indices including the specific growth rate, the maximum cell concentration, and productivity have been considered as biological responses. Resulting models predict the value of each index under different settings of the factors with good accuracy. Results show that the disc diameter has the greatest effect among the investigated factors. Also, the specific growth rate, the natural logarithm of the maximum cell concentration, and productivity are about 0.033 (1/h), 13.2, and 5133 (cells/hmL), respectively by using a 25 (mm) disc with a vibration amplitude of 2.5 up to 3 (mm), and a placement height of 40 up to 60 (mm).

摘要

实验室中的哺乳动物细胞培养采用静态和动态方法进行,动态模式下细胞生长指数更高。在本研究中,引入了一种使用振动盘的实验室规模搅拌生物反应器及合适的装置用于动态细胞培养,该装置能在低剪切应力下实现良好的混合。使用Box-Behnken设计,以Raji细胞在分批模式下进行了15次实验,以定量研究该生物反应器的机械和几何因素对细胞培养指标的影响。选择了三个结构因素,包括盘直径、振动幅度和盘放置高度作为主要因素。将三个细胞生长指标,包括比生长速率、最大细胞浓度和生产率作为生物学响应。所得模型能以良好的精度预测不同因素设置下各指标的值。结果表明,在所研究的因素中,盘直径的影响最大。此外,使用直径为25(mm)、振动幅度为2.5至3(mm)、放置高度为40至60(mm)的盘时,比生长速率、最大细胞浓度的自然对数和生产率分别约为0.033(1/h)、13.2和5133(细胞/hmL)。

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