Ultra high speed observations of cavitation derived microjetting phenomena

Ultrasound mediated molecular delivery (sonoporation) is a highly attractive route for cancer- and gene-therapy. This has been demonstrated, both in vitro and in animal trials, to achieve a number of critical bioeffects such as apoptosis, lysis and tumour regression. Moreover, it is now accepted that the clinical potential is enhanced when ultrasound contrast agent (UCA) microbubbles are present during insonation. However, the fundamental mechanism of interaction between cell and microbubble during US exposure remains elusive and this hampers attempts to optimise the approach. In addressing this deficiency in our understanding, we designed and constructed a unique apparatus that can optically guide an individual UCA microbubble to a predefined displacement relative to a planar substrate. In parallel with this, we undertook direct observations, via high speed imaging at MHz frame rates. We demonstrate how this approach has allowed us to observe a dynamic microscopic interaction during insonation, that may give rise to membrane permeabilization in biological cells.