Facile fabrication of uniform nanoscale perfluorocarbon droplets as ultrasound contrast agents

Perfluorocarbon (PFC) nanodroplets have emerged as a novel phase-change contrast agent, remotely triggered by ultrasound in situ, which holds great potential for ultrasound imaging, early cancer diagnosis, and ultrasound-mediated cancer treatment. As the characteristics of PFC nanodroplets are highly size dependent, it is crucial to tightly control the size and uniformity of PFC nanodroplets, which remain a challenge using current available emulsification techniques. To meet this niche, we developed a novel method to produce monodisperse PFC nanodroplets by the Ouzo effect using a staggered herringbone micromixer. With this method, we fabricated PFC nanodroplets from 200 to 700nm in diameter with a narrow size distribution (PDI<0.1) and the throughput of nanodroplet production could be as high as 0.48ml/h. The stability and biocompatibility of the prepared PFC nanodroplets were verified. Finally, the acoustic characterization of PFC nanodroplets was conducted to demonstrate the feasibility of PFC nanodroplets as ultrasound contrast agents via acoustic direct vaporization.