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首页> 外文期刊>Biotechnology Progress >Understanding and Modeling Retention of Mammalian Cells in Fluidized Bed Centrifuges
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Understanding and Modeling Retention of Mammalian Cells in Fluidized Bed Centrifuges

机译：了解和建模流化床离心机中的哺乳动物细胞。

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Within the last decade, fully disposable centrifuge technologies, fluidized-bed centrifuges (FBC), have been introduced to the biologics industry. The FBC has found a niche in cell therapy where it is used to collect, concentrate, and then wash mammalian cell product while continuously discarding centrate. The goal of this research was to determine optimum FBC conditions for recovery of live cells, and to develop a mathematical model that can assist with process scaleup. Cell losses can occur during bed formation via flow channels within the bed. Experimental results with the kSep400 centrifuge indicate that, for a given volume processed: the bed height (a bed compactness indicator) is affected by RPM and flowrate, and dead cells are selectively removed during operation. To explain these results, two modeling approaches were used: (i) equating the centrifugal and inertial forces on the cells (i.e., a force balance model or FBM) and (ii) a two-phase computational fluid dynamics (CFD) model to predict liquid flow patterns and cell retention in the bowl. Both models predicted bed height vs. time reasonably well, though the CFD model proved more accurate. The flow patterns predicted by CFD indicate a Coriolis-driven flow that enhances uniformity of cells in the bed and may lead to cell losses in the outflow over time. The CFD-predicted loss of viable cells and selective removal of the dead cells generally agreed with experimental trends, but did over-predict dead cell loss by up to 3-fold for some of the conditions. (C) 2016 American Institute of Chemical Engineers
机译：在过去的十年中，将完全一次性的离心技术，即流化床离心机（FBC）引入了生物制剂行业。 FBC在细胞疗法中发现了一个利基市场，可用于收集，浓缩然后洗涤哺乳动物细胞产物，同时不断丢弃离心液。这项研究的目的是确定用于回收活细胞的最佳FBC条件，并开发可以帮助扩大工艺规模的数学模型。通过床内的流道在床形成期间会发生细胞损失。 kSep400离心机的实验结果表明，对于给定的处理体积，床高（床紧密度指示器）受RPM和流速的影响，并且在运行过程中选择性去除死细胞。为了解释这些结果，使用了两种建模方法：（i）等效于单元上的离心力和惯性力（即力平衡模型或FBM）和（ii）两相计算流体动力学（CFD）模型来预测液体流动模式和细胞在碗中的保留。两种模型都可以较好地预测床高与时间的关系，尽管事实证明CFD模型更准确。 CFD预测的流动模式表明科里奥利驱动的流动增强了床中细胞的均匀性，并可能导致流出物中的细胞随时间流失。 CFD预测的活细胞损失和死细胞的选择性清除通常与实验趋势一致，但在某些情况下确实将死细胞损失高估了多达3倍。 （C）2016美国化学工程师学会

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