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Wave characterization for mammalian cell culture: residence time distribution

机译：哺乳动物细胞培养的波表征：停留时间分布

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The high dose requirements of biopharmaceutical products led to the development of mammalian cell culture technologies that increase biomanufacturing capacity. The disposable Wave bioreactor is one of the most promising technologies, providing ease of operation and no cross-contamination, and using an innovative undulation movement that ensures good mixing and oxygen transfer without cell damage. However, its recentness demands further characterization. This study evaluated the residence time distribution (RTD) in Wave, allowing the characterization of mixing and flow and the comparison with ideal models and a Stirred tank reactor (STR) used for mammalian cell culture. RTD was determined using methylene blue with pulse input methodology, at three flow rates common in mammalian cell culture (3.3 × 10~(-5)m~3/h, 7.9 × 10~(-5)m~3/h, and 1.25 × 10~(-4)m~3/h) and one typical of microbial culture (5 × 10~(-3) m~3/h). Samples were taken periodically and the absorbance read at 660 nm. It was observed that Wave behavior diverted from ideal models, but was similar to STR. Therefore, the deviations are not related to the particular Wave rocking mechanism, but could be associated with the inadequacy of these reactors to operate in continuous mode or to a possible inability of the theoretical models to properly describe the behavior of reactors designed for mammalian cell culture. Thus, the development of new theoretical models could better characterize the performance of these reactors.
机译：生物制药产品的高剂量要求导致了哺乳动物细胞培养技术的发展，该技术增加了生物制造能力。一次性Wave生物反应器是最有前途的技术之一，操作简便且无交叉污染，并采用创新的起伏运动，可确保良好的混合和氧气传输而不会损坏细胞。但是，其最新性需要进一步表征。这项研究评估了Wave中的停留时间分布（RTD），从而可以表征混合和流动，并与理想模型和用于哺乳动物细胞培养的搅拌罐反应器（STR）进行比较。 RTD使用亚甲基蓝和脉冲输入法在哺乳动物细胞培养中常见的三种流速下进行测定（3.3×10〜（-5）m〜3 / h，7.9×10〜（-5）m〜3 / h和1.25×10〜（-4）m〜3 / h）和一种典型的微生物培养（5×10〜（-3）m〜3 / h）。定期采集样品，并在660 nm处读取吸光度。观察到波浪行为偏离了理想模型，但与STR类似。因此，偏差与特定的Wave摇摆机制无关，而可能与这些反应器不能以连续模式运行或理论模型可能无法正确描述为哺乳动物细胞培养设计的反应器的行为有关。 。因此，新理论模型的开发可以更好地表征这些反应堆的性能。

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