During the scale‐up of a bioprocess, not all characteristics of the process can be kept constant throughout the different scales. This typically results in increased mixing times with increasing reactor volumes. The poor mixing leads in turn to the formation of concentration gradients throughout the reactor and exposes cells to varying external conditions based on their location in the bioreactor. This can affect process performance and complicate process scale‐up. Scale‐down simulators, which aim at replicating the large‐scale environment, expose the cells to changing environmental conditions. This has the potential to reveal adaptation mechanisms, which cells are using to adjust to rapidly fluctuating environmental conditions and can identify possible root causes for difficulties maintaining similar process performance at different scales. This understanding is of utmost importance in process validation. Additionally, these simulators also have the potential to be used for selecting cells, which are most robust when encountering changing extracellular conditions. The aim of this review is to summarize recent work in this interesting and promising area with the focus on mammalian bioprocesses, since microbial processes have been extensively reviewed.

中文翻译：

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用于哺乳动物细胞培养的缩小模拟器作为工具来了解大型生物反应器中发生的不均匀性的影响


在生物过程的放大过程中，并非该过程的所有特征都可以在不同的规模中保持恒定。这通常导致混合时间随着反应器体积的增加而增加。混合不良进而导致整个反应器中浓度梯度的形成，并使细胞根据其在生物反应器中的位置而暴露于不同的外部条件。这可能会影响工艺性能并使工艺放大变得复杂。缩小规模的模拟器旨在复制大规模环境，将细胞暴露在不断变化的环境条件下。这有可能揭示适应机制，细胞利用这些机制来适应快速波动的环境条件，并可以识别在不同规模下维持相似过程性能困难的可能根本原因。这种理解对于过程验证至关重要。此外，这些模拟器还具有用于选择细胞的潜力，这些细胞在遇到变化的细胞外条件时最稳健。本综述的目的是总结这个有趣且有前途的领域的最新工作，重点关注哺乳动物生物过程，因为微生物过程已被广泛综述。