Thermodynamics Explains How Solution Composition Affects the Kinetics of Stochastic Ice Nucleation

Area of Science:

• Physical Chemistry
• Materials Science
• Chemical Engineering

Background:

• Ice nucleation is critical in freezing processes, particularly for biopharmaceuticals.
• Current understanding often relies on microdroplet studies, limiting applicability to larger volumes.

Purpose of the Study:

• To investigate ice nucleation kinetics in milliliter-scale aqueous solutions.
• To determine if solute type and concentration affect nucleation kinetics.
• To validate findings for biopharmaceutical manufacturing.

Main Methods:

• Studied ice nucleation in 10 aqueous solutions at the milliliter scale.
• Collected data from approximately 6,000 nucleation events.
• Statistically analyzed nucleation kinetics and estimated kinetic parameters.

Main Results:

• Ice nucleation kinetics proved independent of solute nature and concentration.
• A single set of kinetic parameters quantitatively described nucleation behavior across all tested solutions.
• This independence held true irrespective of the thermodynamic driving force used (chemical potential, water activity, or supercooling).

Conclusions:

• Solute effects on ice nucleation kinetics are negligible at the milliliter scale.
• Findings support the generalization of microdroplet nucleation data to larger volumes.
• Simplified expressions for nucleation rate can be used in pharmaceutical freezing models.