Zhu Li-Kuan, Song Bo-Yan, Wang Zhen-Long, Monteil Dominique T, Shen Xiao, Hacker David L, De Jesus Maria, Wurm Florian M
School of Mechatronics Engineering, Harbin Institute of Technology, Harbin, Heilongjiang, People's Republic of China.
Laboratory of Cellular Biotechnology (LBTC), Faculty of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, CH-1015, Switzerland.
Biotechnol Prog. 2017 Jan;33(1):192-200. doi: 10.1002/btpr.2375. Epub 2016 Oct 31.
Orbitally shaken cylindrical bioreactors [OrbShake bioreactors (OSRs)] without an impeller or sparger are increasingly being used for the suspension cultivation of mammalian cells. Among small volume OSRs, 50-mL tubes with a ventilated cap (OSR50), originally derived from standard laboratory centrifuge tubes with a conical bottom, have found many applications including high-throughput screening for the optimization of cell cultivation conditions. To better understand the fluid dynamics and gas transfer rates at the liquid surface in OSR50, we established a three-dimensional simulation model of the unsteady liquid forms (waves) in this vessel. The studies verified that the operating conditions have a large effect on the interfacial surface. The volumetric mass transfer coefficient (k a) was determined experimentally and from simulations under various working conditions. We also determined the liquid-phase mass transfer coefficient (k ) and the specific interfacial area (a) under different conditions to demonstrate that the value of a affected the gas transfer rate more than did the value of k . High oxygen transfer rates, sufficient for supporting the high-density culture of mammalian cells, were found. Finally, the average axial velocity of the liquid was identified to be an important parameter for maintaining cells in suspension. Overall these studies provide valuable insights into the preferable operating conditions for the OSR50, such as those needed for cell cultures requiring high oxygen levels. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 33:192-200, 2017.
无搅拌器或气体分布器的轨道振荡圆柱形生物反应器[轨道振荡生物反应器（OSR）]越来越多地用于哺乳动物细胞的悬浮培养。在小体积的OSR中，带有通风帽的50毫升试管（OSR50），最初源自底部为锥形的标准实验室离心管，已发现有许多应用，包括用于优化细胞培养条件的高通量筛选。为了更好地理解OSR50中液体表面的流体动力学和气体传递速率，我们建立了该容器中非稳态液体形态（波浪）的三维模拟模型。研究证实操作条件对界面表面有很大影响。通过实验并在各种工作条件下进行模拟确定了体积传质系数（k a）。我们还确定了不同条件下的液相传质系数（k）和比界面面积（a），以证明a的值对气体传递速率的影响大于k的值。发现了足以支持哺乳动物细胞高密度培养的高氧传递速率。最后，确定液体的平均轴向速度是将细胞维持在悬浮状态的一个重要参数。总体而言，这些研究为OSR50的优选操作条件提供了有价值的见解，例如对于需要高氧水平的细胞培养所需的条件。©2016美国化学工程师学会生物技术进展，33:192 - 200，2017。
