Open-Microcombinatorial Analysis of Critical Points of Crystal Growth and Nucleation for Small Molecules in Organic Solvents

Abstract Obtaining phase diagrams to know the critical points of crystal growth and nucleation is essential for reducing trial-and-error processes and enabling systematic fabrication. However, conventional methods require gram-scale sample volumes and long equilibration times (weeks to months) and allow only limited parallel measurements, making them unsuitable for early-stage material development. Here, we report an open microfluidic system that enables rapid and quantitative phase diagram construction of small-molecule solutions in volatile organic solvents by using nanoliter-scale volumes. Unlike conventional approaches that suppress solvent evaporation using closed configurations, our method quantitatively monitors evaporation in real-time, allowing analysis under open conditions. This enables the simultaneous evaluation of both phase behavior and evaporation kinetics. The system achieves approximately 10-fold faster measurements than conventional methods, and allows high-throughput analysis through dense integration. In addition to reproducing results comparable to those of bulk methods, we observe microscale-specific behavior, including an expanded supersaturation region arising from reduced liquid volumes. This approach provides a versatile platform for rapid phase diagram analysis and is broadly applicable to crystallization and phase separation processes in materials science and chemical engineering.