Integrated white-box models for designing freezing processes of human induced pluripotent stem cells considering diversity within a container

Abstract

Abstract This work presents a novel combination of white-box models that describes heat transfer, mass transfer, and intracellular ice formation during freezing of human induced pluripotent stem (hiPS) cells. The models can be applied to the design of freezing processes for hiPS cells considering the diversity in cell quality within a container. In the case study, two design variables were defined, i.e., the cooling rate of a programmed freezer as an element of {1.0, 1.2, …, 3.8, 4.0 K/min} and the diameter of a vial as an element of {5, 50, 150 mm}. The objective functions were defined as the maxima of cell volume change and intracellular ice crystal volume as the proxy for the cell survival rate. The Pareto optimal solutions were obtained as 5 mm as the vial diameter with all considered cooling rates; given a threshold of the ice crystal volume, the feasible range of the cooling rate was strongly influenced by the diameter of the vial.