Acoustic radiation force induced accumulation and dynamics of microbubbles on compliant surfaces

Ultrasound stimulated microbubbles have been shown to be capable of breaking up blood clots through micro-scale interactions occurring near the clot surface. However, only a small fraction of bubbles circulating in the bloodstream will be in close proximity to such boundaries, where they must be to elicit therapeutic effects. Here, the accumulation and subsequent behavior of microbubbles displaced from an overlying flow channel to a boundary under radiation forces were examined. Experimental data were acquired using a novel high speed microscopy configuration and simulations were conducted to provide insight into the accumulation process. There was broad agreement between experiments and simulations, both indicating that the size distribution and number of bubbles arriving at the boundary depended on channel flow rate, applied pressure, and bubble concentration. For example, higher flow rates and lower pressures favored the accumulation of larger bubbles relative to the native agent distribution. Moreover, bubble dynamics were dependent on the surface type, exhibiting rapid translation along agarose gel surfaces whereas on fibrin surfaces, they accumulated in localized regions inducing repetitive strain cycles. The results indicate that the process of bringing bubbles from within a vessel to a boundary is complex and should be an important consideration in the development of therapeutic applications such as sonothrombolysis.