Cavitation behavior in a coaxial ultrasonic microreactor and its effects on mixing performance and liposomes preparation

Microfluidics have been widely used for the preparation of small and monodisperse liposomes but it still suffered from the challenges with fouling-free, velocity independent and steadily flash mixing. Herein, we developed a novel ultrasonic microreactor with an adjustable tube-in-tube structure (USM-AT) for robust preparation of uniform liposomes with narrow distribution via antisolvent method. Within the USM-AT, different cavitation behaviors could be tuned by altering inner tube position, manifesting four distinct cavitation patterns. The bubble clusters pattern exhibited a superior mixing performance even at low total flow rate ( t mix =22 ms at TFR=1.0 mL/min), which was further enhanced with increasing TFR, ultrasonic power and gas content. Additionally, by adjusting the operation parameters, the USM-prepared liposomes exhibited small size and low polydispersity index (PDI<0.1), superior to that of liposome prepared by traditional ethanol injection. The results from the present work may pave an avenue for the efficient and robust fabrication of monodisperse nanomaterials.