CFD支持的生物制药灌注生物反应器的放大

IF 2.5 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Frontiers in chemical engineering Pub Date : 2023-01-18 DOI:10.3389/fceng.2023.1076509
M. Kuschel, J. Wutz, Mustafa Salli, D. Monteil, T. Wucherpfennig
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引用次数: 1

摘要

灌注系统的稳健规模需要在所有规模上具有可比性的条件,以确保等效的细胞培养性能。由于细胞在连续过程中在生物反应器外循环,如果射流和搅拌导致灌注进料和回流之间的直接联系,则可能产生性能损失。计算流体动力学可以用来识别这种短路流动,评估混合效率,并最终适应灌注设置。本研究调查了从2升玻璃生物反应器到100升和500升一次性中试规模系统的规模。在单相条件下进行了高分辨晶格玻尔兹曼大涡模拟,并在2l体系中进行了混合效率(Emix)的实验验证。该评价提供了深入了解流动模式,混合行为和生物反应器内细胞停留时间的信息。在中试规模系统中不需要进行几何调整,因为Emix在所有测试条件下都大于90%。两种不同的设置在2升的规模下进行了评估,其中流动方向改变,产生10%的混合效率差异。尽管如此,由于Emix在两种2升设置中也被确认为bbb90 %,并且确定的混合时间在所有比例下都在相似的范围内,因此2升系统被认为是合适的比例缩小模型。结果表明,计算流体动力学模型可以用于生物制药工业强化生产过程的合理工艺设计。
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CFD supported scale up of perfusion bioreactors in biopharma
The robust scale up of perfusion systems requires comparable conditions over all scales to ensure equivalent cell culture performance. As cells in continuous processes circulate outside the bioreactor, performance losses may arise if jet flow and stirring cause a direct connection between perfusion feed and return. Computational fluid dynamics can be used to identify such short circuit flows, assess mixing efficiencies, and eventually adapt the perfusion setup. This study investigates the scale up from a 2 L glass bioreactor to 100 L and 500 L disposable pilot scale systems. Highly resolved Lattice Boltzmann Large Eddy simulations were performed in single phase and mixing efficiencies (Emix) furthermore experimentally validated in the 2 L system. This evaluation gives insight into the flow pattern, the mixing behavior and information on cell residence time inside the bioreactors. No geometric adaptations in the pilot scale systems were necessary as Emix was greater than 90% for all conditions tested. Two different setups were evaluated in 2 L scale where the direction of flow was changed, yielding a difference in mixing efficiency of 10%. Nevertheless, since Emix was confirmed to be >90% also for both 2 L setups and the determined mixing times were in a similar range for all scales, the 2 L system was deemed to be a suitable scale down model. The results demonstrate how computational fluid dynamic models can be used for rational process design of intensified production processes in the biopharmaceutical industry.
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来源期刊
CiteScore
3.50
自引率
0.00%
发文量
0
审稿时长
13 weeks
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