Toward monodisperse ultrasound-triggered phase-shift emulsions using differential centrifugation

Acoustic droplet vaporization (ADV) is a process that enables the in situ production of microbubbles from an injected perfluorocarbon emulsion and it has been investigated for imaging and therapeutic applications. High-speed mechanical shaking rapidly produces a polydisperse emulsion (~1010 droplets/mL) with droplets ranging from less than 400 nm to greater than 15 μm. The ADV pressure amplitude threshold is higher and fraction of transitioned droplets lower for droplets smaller than approximately 2 μm in diameter. Droplets greater than approximately 8 μm in diameter are not suitable for systemic administration. Therefore, high-speed mechanical shaking produces many droplets of limited utility. Differential centrifugation has been used as a size isolation technique for polydisperse ultrasound contrast agents. By applying a similar technique to a perfluorocarbon emulsion, the volume-weighted fraction of droplets between 2 and 5 μm was increased from 29±2% to 93±3%. The transition efficiency of the droplets between 2and 5 μm was the same regardless of whether a polydisperse or monodisperse distribution was insonfied with 2 MHz ultrasound. The ADV pressure threshold of differentially centrifuged droplets was similar to non-centrifuged droplets. [Supported in part by NIH grant KL2 TR000078.]