A population balance approach for the description of water osmosis and intracellular ice formation during cryopreservation

A novel model capable of quantitatively describing and predicting Intracellular Ice Formation (IIF) as a function of temperature in a cell population during the cooling stage of a cryopreservation protocol, without Cryo-Protective Agent (CPA) is proposed. The model accounts for water osmosis and IIF occurrence during freezing of the cell population, whose size distribution dynamics is simulated by means of a suitable population balance approach. It is found that IIF temperature depends upon the cell size, i.e. it is higher for larger cells. Correspondingly, the Probability of IIF (PIIF) results to be dependent on the initial size distribution of the cell population. Model reliability is successfully verified by predicting experimental data available in the literature of PIIF at different, constant cooling rates with better accuracy as compared to previous theoretical approaches.