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过程工程学报 ›› 2022, Vol. 22 ›› Issue (9): 1192-1202.DOI: 10.12034/j.issn.1009-606X.221364CSTR: 32067.14.jproeng.221364

• 研究论文 • 上一篇    下一篇

鼓泡塔细胞反应器流体力学与传质特性

徐胜楠1,2， 刘宏斐1,2， 李雪良1,2， 堵国成1,2， 陈坚1,2*
  

  1. 1. 江南大学生物工程学院，江苏 无锡 214122 2. 江南大学未来食品科学中心，江苏 无锡 214122
  • 收稿日期:2021-11-12 修回日期:2021-12-22 出版日期:2022-09-28 发布日期:2022-10-09
  • 通讯作者: 徐胜楠 shengnanxu68@163.com
  • 作者简介:徐胜楠(1997-)，女，山东省日照市人，硕士研究生，发酵工程专业，E-mail: 1925281933@qq.com；通讯联系人，陈坚，E-mail: jchen@jiangnan.edu.cn.
  • 基金资助:
    中央高校基本科研业务费专项资金资助;中央高校基本科研业务费专项资金资助

Hydrodynamics and mass transfer in a three-phase bubble column cell culture bioreactor

Shengnan XU1,2,  Hongfei LIU1,2,  Xueliang LI1,2,  Guocheng DU1,2,  Jian CHEN1,2*   

  1. 1. School of Biotechnology, Jiangnan University, Wuxi, Jiangsu 214122, China 2. Science Center for Future Foods, Jiangnan University, Wuxi, Jiangsu 214122, China
  • Received:2021-11-12 Revised:2021-12-22 Online:2022-09-28 Published:2022-10-09

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摘要： 以超大规模细胞培养为目的，构建了与细胞培养体系十分接近的冷模实验体系，系统地研究了微载体(Cytodex I)、细胞保护剂(Pluronic F68)和消泡剂(Antifoam C)对鼓泡塔反应器中气、固、液三相流流体力学和氧传质特性的影响。在0.04~0.17 cm/s表观气速范围内采用50 μm孔径的烧结金属滤芯曝气时，在含有0.5和1.0 g/L的Pluronic F68的磷酸盐缓冲溶液冷模体系中，气含率与表观气速成线性增加关系，而气泡直径受表观气速影响较小；相同气速下的冷模体系与空气-水体系相比，气含率显著提高，气泡直径明显减小。在所研究的表观气速范围内微载体均可全悬浮，对气含率有一定增强，但微载体浓度为14%~20%时对气泡大小几乎无影响。消泡剂用量在1.60×10-4时，可以有效抑制泡沫的形成。添加剂对液膜传质系数kL有较大负面作用，抵消了小气泡带来的传质面积增加，总的体积传质系数kLa变化不大。Euler-Euler多相流计算流体力学模型与拟稳态实验数据吻合较好，可用于指导反应器放大设计。

关键词: 鼓泡塔, 微载体, 细胞培养, 气泡, 气含率, 传质, 计算流体力学

Abstract: Pneumatic bioreactors, including bubble columns and air-lift reactors, were once considered the most suitable for large scale cell culture. However, their applications quickly declined and research interests diminished when it was suspected that the bubbles bursting at the gas-liquid interface could cause damage to certain cells. Stirred tank reactors, limited to 1~2 m3 working volume, became the industry standard. In recent year, the emergence of new cell-based technology, such as cultured meat, has led people to reconsider the bubble column reactor technology, as such products required reactors in the order of 100 m3 to be economically viable. However, there was generally a lack of up-to-date understanding of the performance of pneumatic reactors in the context of cell culture due to the lack of interest from the industry in the past four decades or so. In this study, cold flow experiments were conducted and CFD simulations were performed to investigate the effect of microcarriers and cell culture media additives such as Pluronic F68 and Antifoam C on the hydrodynamics and mass transfer characteristics of a bench-top bubble column. Foaming and foam control were also investigated. It was found that in the presence of 0.5 and 1.0 g/L Pluronic F68, the bubble size in a simulated culture medium remained almost unchanged as the superficial gas velocity increased from 0.04 cm/s to 0.17 cm/s, dissimilar to the air-water system where the bubble size increased significantly with gas flow due to coalescence. Microcarriers of 14%~20% volumetric fractions were not found to impact the bubble size and Antifoam C of up to 1.60×10-4 was required to suppress the foam, without affecting the bubble size in the column. Despite the smaller bubble size and higher gas holdup, the overall volumetric mass transfer coefficient, kLa was on par with the air-water system, as the medium additives negatively affected the liquid side mass transfer coefficient, kL. In all the experiments, the microcarriers could all be completely suspended. The gas holdup and solid distribution in the three-phase system could be adequately described by an Euler-Euler CFD model.

Key words: bubble column, microcarrier, cell culture, bubbles, gas holdup, mass transfer, CFD