Characterization and comparison of ATF and TFF in stirred bioreactors for continuous mammalian cell culture processes
Characterization and comparison of ATF and TFF in stirred bioreactors for continuous mammalian cell culture processes
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DOI：
10.1016/j.bej.2016.02.003
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发表时间：
2016-06-15
影响因子：
3.9
通讯作者：
Morbidelli, Massimo
中科院分区：
文献类型：
--
作者：
Karst, Daniel J.;Serra, Elisa;Morbidelli, Massimo
在这项工作中，两个外部过滤装置的细胞保留，商业交替切向流（ATF）系统和切向流过滤（TFF）设置驱动的无轴承离心泵进行了比较。生物反应器流体动力学的物理表征显示，在类似的混合和氧气传质速率在ATF的最大应力值显着较小。确定了通风、搅拌和保留装置操作方面的合适操作参数。对于两种设置，以每天一个反应器体积的固定收获率，在灌注中以20、40和60 × 10（6）个细胞/mL的浓度稳定培养中国仓鼠卵巢（CHO）细胞至少一周。与ATF相反，观察到TFF中产生的单克隆抗体的相当大的保留（高达50%），然而在产品质量上没有显著差异。物理和细胞培养表征的整合可以全面评估细胞培养性能。所提出的方法可以作为一个通用的程序来开发一个可扩展的哺乳动物细胞灌注培养。(C)2016爱思唯尔B. V.保留所有权利。
In this work, two external filtration devices for cell retention, the commercial alternating tangential flow (ATF) system and a tangential flow filtration (TFF) setup driven by a bearingless centrifugal pump were compared. Physical characterization of the bioreactor hydrodynamics revealed significantly smaller maximum stress values in the ATF at similar mixing and oxygen mass transfer rates. Suitable operating parameters in terms of aeration, stirring and operation of the retention device were determined. Steady culture of Chinese hamster ovary (CHO) cells at 20, 40 and 60 x 10(6) cells/mL for at least one week was achieved in perfusion at a fixed harvest rate of one reactor volume per day for both setups. Contrary to the ATF, considerable retention (up to 50%) of the produced monoclonal antibody in the TFF was observed, however without significant difference in product quality. The integration of physical and cell culture characterization allows the comprehensive assessment of cell culture performance. The presented approach can serve as a general procedure to develop a scalable mammalian cell perfusion culture. (C) 2016 Elsevier B.V. All rights reserved.