Development and optimization of cell based cryopreservation models

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Cryopreservation is a foundational technology based in interdisciplinary fundamental science. It facilitates basic research through genetic resource repositories and cell-line distribution, enables animal and plant endangered species conservation, is crucial to billion dollar industries in animal and plant agriculture, and plays a critical role in veterinary and human transplantation and transfusion medicine. However, in spite of these myriad applications and nearly a century of research, few cells, fewer tissues, and no organs thrive after cryopreservation.******My research is guided by the accepted central hypothesis that cryopreservation can be well understood as a series of heat and mass transport systems in non-ideal and non-physiologic conditions. The governing multiscale transport models and their controls provide a rich subject at the intersection of mathematical, engineering, and biological research.******Successful cryopreservation of biological samples in liquid nitrogen requires high concentrations of cryoprotective agents (CPAs) that typically include cell-membrane-permeable solutes such as DMSO, membrane-impermeable solutes like sugars, or modern ice-blocking chemicals. After equilibration with CPAs, cells are cooled to -196\degC and stored indefinitely. When needed, samples are warmed and then equilibrated with CPA-free media. Critically, each step of this process is associated with a number of mechanisms of damage. Consequently, my long term research goal is to develop and optimize computational cryopreservation damage models. This will enable rapid cell, tissue, and organ cryopreservation protocol design. My approach is integrative and interdisciplinary, and in the next five years, I will focus on the following three objectives: 1) build cell-level damage models using innovative iterative optimization and machine learning approaches as well as novel feedback control to separate volume effects from concentration effects; 2) build upon existing cell-based heat and mass transport tissue models to facilitate modeling of cell-level cryopreservation damage in tissues; 3) develop computational tools for optimization of cell based cryopreservation and damage models from Objectives 1 and 2. These objectives provide a number of interdisciplinary training opportunities at the intersection of mathematics and biology.