Controllable formation of bulk perfluorohexane nanodroplets by solvent exchange

Perfluorocarbon (PFC) nanodroplets have rapidly developed into useful ultrasound imaging agents in modern medicine due to their non-toxic and stable chemical properties that facilitate disease diagnosis and targeted therapy. In addition, with the good capacity for carrying breathing gases and the anti-infection ability, they are employed as blood substitutes and are the most ideal liquid respirators. However, it is still a challenge to prepare stable PFC nanodroplets of uniform size and high concentration for their efficient use. Herein, we developed a simple and highly reproducible method, i.e., propanol-water exchange, to prepare highly homogeneous and stable perfluorohexane (PFH) bulk nanodroplets. Interestingly, the size distribution and concentration of formed nanodroplets could be regulated by controlling the volume fraction of PFH and percentage of propanol in the propanol-water mixture. We demonstrated good reproducibility in the formation of bulk nanodroplets with PFH volume fractions of 1/2000-1/200 and propanol percentage of 5-40%, with uniform particle size distribution and high droplet concentration. Also, the prepared nanodroplets were very stable and could survive for several hours. We constructed a ternary phase diagram to describe the relationship between the PFH volume ratio, propanol concentration, and the size distribution and concentration of the formed PFH nanodroplets. This study provides a very useful method to prepare uniform size, high concentration and stable PFC nanodroplets for their medical applications.