Violent cavitation from optically configured microbubble pairs

Contrast agent microbubble cavitation has received increased attention in recent years, since it has been recognised as significantly enhancing the bio-effects of ultrasound mediated intra-cellular drug delivery, the technique better known as sonoporation. However, whilst the empirical credentials underscoring the potential of sonoporation to usefully load the full gamut of biological cells and tissues continues to grow, there remains a distinct lack of clarity in relation to the underlying mechanism of action. Here, we have adopted the viewpoint that this aspect will only become elucidated by imaging the interaction of individual ultrasound stimulated microbubbles with nearby cells, and corroborating subsequent damage or disruption to that specific modes of bubble activity. Previous studies that have used time lapse photomicrography to image free microbubbles have demonstrated their vigorous interaction with pressure pulses, especially at mechanical indices greater than circa 0.5. For the purposes of the present paper, we extend that approach and use corroborative cell imaging by both electron- and force microscopies to illuminate an unusual mode for membrane disruption from violent microbubble cavitation.