Optical and Acoustic Characterization of Phase-Shift Droplets with Varying Shell Compositions

Shell-stabilized, phase-shift droplets of perfluorocarbon have shown promising potential in diagnostic and therapeutic ultrasound applications. While the role of shell composition has been well-studied for conventional gas-filled microbubbles, its influence on bubbles generated via acoustic droplet vaporization (ADV) remains understudied. This study investigates the effect of shell composition─lipid, protein, and polymer─on the stability, ADV dynamics, growth behavior, release kinetics, and acoustic response of perfluorohexane phase-shift droplets. Payload-carrying, micron-sized droplets were produced using a microfluidic platform. Both optical, including ultrahigh-speed and timelapse confocal microscopy, and acoustic characterizations of the generated droplets were investigated in fibrin-based, tissue-mimicking hydrogels. Fluorescent markers were used to selectively label fibrin, payload, and droplet shells. Following insonation at 2.5 and 9.6 MHz, lipid-coated droplets had a maximum expansion ratio up to 20% lower than protein- and polymer-coated droplets. Payload release rates were an order of magnitude faster than the bubble growth rate post ADV, with minimal dependence on shell composition. Additionally, lipid shell fluorescence retained up to 40% of its initial intensity 120 s after ADV, while protein shell fluorescence was completely diminished. Acoustic characterization indicated that the ADV and inertial cavitation thresholds were similar across all shell types, suggesting that shell composition has a negligible effect on acoustic characteristics at high driving pressures.