This work presents a model-based assessment of temperature profiles in slow freezing for human induced pluripotent stem (hiPS) cells. It is based on our single-cell model that can quantify temperature distribution in a vial, cell volume change through transmembrane water transport, and intracellular ice formation during freezing. This mechanistic model was extended to cover the cell survival rate through statistical modeling. Freeze/thaw experiments using hiPS cells provided the necessary parameter values. Given a temperature profile of freezing, the hybrid single-cell model could estimate the cell survival rate and required freezing time as the quality and productivity objectives, respectively. The model was applied to assess 16,206 temperature profiles. The simulation results suggested fast, slow, and fast cooling in the dehydration, nucleation-promoting, and further cooling zones, respectively. The work can be the first step toward establishing a design space of slow freezing of hiPS cells with an awareness of productivity and quality.

这项工作提出了基于模型的慢速冷冻过程中人类诱导的多能干（hiPS）细胞温度曲线的评估。它基于我们的单细胞模型，可以量化小瓶中的温度分布，通过跨膜水运输引起的细胞体积变化以及冷冻过程中细胞内冰的形成。通过统计模型扩展了该机制模型以涵盖细胞存活率。使用hiPS单元进行冻结/解冻实验可提供必要的参数值。给定冻结的温度曲线，混合单细胞模型可以分别估计细胞存活率和所需的冻结时间作为质量和生产率的目标。该模型用于评估16,206个温度曲线。仿真结果表明脱水过程中的快速，缓慢和快速冷却，分别促进成核和进一步的冷却区。这项工作可能是朝着建立具有生产力和质量意识的hiPS细胞缓慢冷冻的设计空间迈出的第一步。