Fluorocarbon Nanodroplets: Their Formation and Stability in Complex Solution Systems

Perfluorocarbon (PFC) nanodroplets (NDs) are expanding in a wide range of applications in biotechnology and nanotechnology. Their efficacy in biological systems is significantly influenced by their size uniformity and stability within bioelectrolyte contexts. Presently, methods for creating monodisperse, highly concentrated, and well-stabilized PFC NDs under harsh conditions using low energy consumption methods have not been thoroughly developed, and their stability has not been sufficiently explored. This gap restricts their applicability for advanced medical interventions in tissues with high pH levels and various electrolytic conditions. To tackle these challenges and to circumvent potential toxicity from surface stabilizers, we have conducted an in-depth investigation into the formation and stability of uncoated perfluorohexane (PFH) NDs, which were synthesized by using a low-energy consumption solvent exchange technique, across complex electrolyte compositions or a broad spectrum of pH levels. The results indicated that low concentrations of low-valent electrolyte ions facilitate the nucleation of NDs and consistently accelerate Ostwald ripening over an extended period. Conversely, high concentrations of highly valent electrolyte ions inhibit nucleation and decelerate the ripening process over time. Given the similarities between the properties of NDs and nanobubbles, we propose a potential stabilization mechanism. Electrolytes influence the Ostwald ripening of NDs by adjusting the adsorption and distribution of ions on the NDs' surface, modifying the thickness of the electric double layer, and fine-tuning the energy barrier between droplets. These insights enable precise control over the stability of PFC NDs through the meticulous adjustment of the surrounding electrolyte composition. This offers an effective preparation method and a theoretical foundation for employing bare PFC NDs in physiological settings.