Hybrid-model-based design of fill-freeze-thaw processes for human induced pluripotent stem cells considering productivity and quality
Hybrid-model-based design of fill-freeze-thaw processes for human induced pluripotent stem cells considering productivity and quality
复制标题
DOI：
10.1016/j.compchemeng.2021.107566
复制
发表时间：
2022-01
期刊：
影响因子：
--
通讯作者：
Y. Hayashi;M. Kino‐oka;H. Sugiyama
中科院分区：
文献类型：
--
作者：
Y. Hayashi;M. Kino‐oka;H. Sugiyama
本工作提出了一种基于混合模型的人诱导多能干细胞（hiPS）填充-冻融过程的设计。对于冷冻，我们应用了我们以前提出的单细胞模型，该模型描述了冷冻过程中的传热，脱水和结晶。已经开发了用于填充和解冻的新模型。在灌装和解冻过程中细胞内活性氧的积累被定义为质量指标，并被描述为黑箱模型。实验结果提供了必要的参数值。基于物理模型，将灌装和解冻的持续时间定义为生产率指标。总体灌装-冻融模型计算给定工艺质量标准的质量和生产率指标，如小瓶直径和解冻温度。在解冻的案例研究中，小瓶直径在很大程度上影响生产率。对于整个灌装-冻融工艺，根据可接受的质量标准和细胞需求，生产率的最佳解冻温度和小瓶直径发生了显著变化。
This work presents a hybrid-model-based design of a fill-freeze-thaw processes for human induced pluripotent stem (hiPS) cells. For freezing, we applied our previously presented single-cell model, which describes heat transfer, dehydration, and crystallization during freezing. New models have been developed for filling and thawing. The accumulation of intracellular reactive oxygen species during filling and thawing was defined as the quality indicator and was described as a black-box model. Experimental results provided the necessary parameter values. The time duration for filling and thawing was defined as the productivity indicator based on physical models. The overall fill-freeze-thaw model calculates the quality and productivity indicators given the process specifications, such as vial diameter and thawing temperature. In the case study for thawing, vial diameter largely affected the productivity. For the overall fill-freeze-thaw process, the optimal thawing temperature and vial diameter for productivity changed significantly, depending on the acceptable quality specifications and cell demand.