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Updated: Apr 20, 2026

Optimizing Sample Preparation for Cryogenic Electron Microscopy
Published on: April 11, 2025
Modeling and optimization of cryopreservation
1Department of Mathematical Sciences, Northern Illinois University, DeKalb, IL, 60115, USA, benson@math.niu.edu.
Abstract:
Modeling plays a critical role in understanding the biophysical processes behind cryopreservation. It facilitates understanding of the biophysical and some of the biochemical mechanisms of damage during all phases of cryopreservation including CPA equilibration, cooling, and warming. Modeling also provides a tool for optimization of cryopreservation protocols and has yielded a number of successes in this regard. While modern cryobiological modeling includes very detailed descriptions of the physical phenomena that occur during freezing, including ice growth kinetics and spatial gradients that define heat and mass transport models, here we reduce the complexity and approach only a small but classic subset of these problems. Namely, here we describe the process of building and using a mathematical model of a cell in suspension where spatial homogeneity is assumed for all quantities. We define the models that describe the critical cell quantities used to describe optimal and suboptimal protocols and then give an overview of classical methods of how to determine optimal protocols using these models.

