High-speed photography of microbubbles

Ultrasound contrast agents consist of encapsulated bubbles in the micrometer size range. At low acoustic amplitudes these microbubbles pulsate linearly, but at high amplitudes they demonstrate highly nonlinear, destructive behaviour. Cellular drug uptake and lysis are increased under sonication, and even more so when a contrast agent is present, owing to the formation of transient porosities in the cell membrane (sonoporation). An overview is given of the physical mechanisms of microbubble behaviour, supported by high-speed photographs through a microscope. The ultrasound-induced formation of bubble clusters may be of interest as a therapeutic means. If the clusters behave as one entity, i.e., one mega-bubble, its ultrasonic manipulation towards a boundary is straightforward and quick. If the clusters can be forced to accumulate to a microfoam, entire vessels might be blocked on purpose using an ultrasound contrast agent and a sound source. We analyse how ultrasound contrast agent clusters are formed in a capillary and what happens to the clusters if sonication is continued, using continuous driving frequencies in the range 1–10 MHz. Furthermore, we show high-speed camera footage of microbubble clustering phenomena. We observed the following stages of microfoam formation within a dense population of microbubbles before ultrasound arrival, shown in Figure 1. After sonication started, contrast microbubbles collided, forming small clusters, owing to secondary radiation forces. These clusters coalesced within the space of a quarter of the ultrasonic wavelength, owing to primary radiation forces. The resulting microfoams translated in the direction of the ultrasound field, hitting the capillary wall, also owing to primary radiation forces