Ultrasound-induced nanofragmentation of bubbles

Micron-sized bubbles are of considerable interest for use in biomedical imaging and drug delivery. Lipid-coated bubbles have been reported to rapidly shrink in the presence of short (3 $\mu$s) ultrasound pulses, purportedly by shedding of the coat during compression. Loss of coat would increase the internal pressure, enhancing diffusive gas loss long after the pulse. Note that during such a short pulse, diffusive gas loss is insignificant. If lipid-shedding is the mechanism for bubble shrinkage, a coated bubble in ultrasound may shrink no faster than a quiescent uncoated bubble; the shrinkage rate is entirely dominated by diffusive loss between pulses. Remarkably, we find that most insonated lipid-coated bubbles do shrink faster than quiescent uncoated bubbles. If bubbles cannot shrink by diffusive gas loss, they must fragment, though no fragmentation was observed. The results are consistent with ``nanofragmentation,'' where sub-micron fragments (which entrap gas) are lost from the bubble. Entrapment of gas in fragments may have important consequences for their efficacy in ultrasound-mediated drug delivery, and could affect their ability to transfer drugs to cells.