Abstract
This work presents multiobjective and dynamic optimization of temperature profile for the slow freezing of human induced pluripotent stem (hiPS) cells. A single-cell model was developed that can quantify (i) temperature distribution in a container that causes intracontainer conditional variation, (ii) cell volume change through transmembrane water transport, (iii) intracellular ice formation during freezing, and (iv) cell survival rate after thawing. The phenomena (i) to (iii) were described by white-box (ODE/PDE) models. The phenomenon (iv) was statistically modeled, for which experiments using hiPS cells provided the necessary parameter values. The overall hybrid model can produce cell survival rate and required freezing time as the quality and the productivity objectives, respectively. Multiobjective dynamic optimization was performed on the freezer temperature profile. Among the Pareto optimal solutions, a specific profile was identified that maximized the joint objective of quality and productivity.
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