Thermodynamic principles of emerging cryopreservation technologies

Abstract

Modern cryopreservation exists at the convergence of diverse disciplines--materials science, physical chemistry, mechanical engineering, biological engineering, etc.--and emerging technologies often draw from many of these disciplines simultaneously. Thermodynamics, as one of the foundational theories underlying both physical and biological science, provides a framework through which to understand these interdisciplinary technologies, yet the full kit of requisite thermodynamic tools is not housed within any one discipline. This Chapter aims to articulate a foundational thermodynamic approach to the description, interrogation, and design of modern cryopreservation technologies, and to review the state of the art in emerging cryopreservation technologies through the lens of this approach. We focus in particular on the management of phase change across equilibrium-driven techniques (e.g., liquidus tracking, partial freezing, isochoric freezing), kinetics-driven techniques (e.g. supercooling, ice seeding), and transport-driven techniques (e.g. directional freezing, droplet approaches), and we hope to equip the reader with a self-consistent theoretical toolkit that enables meaningful comparison of these techniques from a thermodynamic perspective.

Figures (17)

• Figure 1: Equilibrium melting points. a) Chemical potential of water in solution with NaCl and in ice as a function of temperature and b) corresponding liquidus curve. Intersections of the ice and water curves denote the coexistence temperature (i.e., $T_{\mathrm{m}}$). Melting point as a function of mole fraction for a typical b) permeating solute (glycerol) and c) non-permeating solute (sucrose).
• Figure 2: Eutectic phase diagrams for binary aqueous solutions generated via size-dependent and ideal predictive models. Experimental data from the literature is shown in gray markers for a) glycerol and b) sucrose. Both models require only pure component properties, and do not require empirical information on the solution itself.
• Figure 3: Isochoric equilibrium: a) Convex hull construction for determination of phase equilibria. b) Isochoric T-V phase diagram for pure water. Adapted with permission from Consiglio et al. r19.
• Figure 4: Isobaric Ice-liquid phase fractions and solute ripening processes. a) Construction of the lever rule for a binary solution T-x phase diagram, which enables calculation of the fraction of the system that remains in the frozen or unfrozen state at a given temperature. b) Unfrozen phase fraction versus temperature for various starting concentrations of DMSO in a water-DMSO solution. c) According concentration of the liquid phase during progressive freezing, for the same starting concentrations indicated by the color bar in panel (b).
• Figure 5: Isochoric ice-liquid phase fractions for pure water. a) Construction of the isochoric lever rule from the water/ice Ih temperature-specific volume phase diagram derived by Powell-Palm et al. r20. b) Fraction of isochoric system that remains liquid during isochoric freezing as a function of system specific volume.