Design space determination of freezing processes for human induced pluripotent stem cell-derived spheroids using hybrid modeling

Abstract

This work presents the design space determination of freezing processes for human induced pluripotent stem (hiPS) cell-derived spheroids using hybrid modeling. First, a mechanistic model was developed considering spheroid characteristics and freezing phenomena. The developed model was then extended to calculate the cell recovery ratio after thawing using statistical modeling. The hybrid model parameters were estimated based on freezing experiments using hiPS cell-derived spheroids. The extension enabled the calculation of the cell recovery ratio and the number of living cells in the spheroid after thawing, as a function of the cooling rate and the average radius of spheroids. The application of the hybrid model was demonstrated in a case study. The design space of the freezing process was obtained under given constraints related to both quality and productivity. In this way, we could determine design spaces considering both quality and productivity toward industrial manufacturing of hiPS cell-derived spheroids.