Temporal effect of inertial cavitation with and without microbubbles on surface deformation of agarose S gel in the presence of 1-MHz focused ultrasound.

Sonoporation has the potential to deliver extraneous molecules into a target tissue non-invasively. There have been numerous investigations of cell membrane permeabilization induced by microbubbles, but very few studies have been carried out to investigate sonoporation by inertial cavitation, especially from a temporal perspective. In the present paper, we show the temporal variations in nano/micro-pit formations following the collapse of inertial cavitation bubbles, with and without Sonazoid® microbubbles. Using agarose S gel as a target material, erosion experiments were conducted in the presence of 1-MHz focused ultrasound applied for various exposure times, Tex (0.002-60 s). Conventional microscopy was used to measure temporal variations in micrometer-scale pit numbers, and atomic force microscopy utilized to detect surface roughness on a nanometer scale. The results demonstrated that nanometer-scale erosion was predominantly caused by Sonazoid® microbubbles and C4F10 gas bubbles for 0.002 s<Tex<1 s, while the number of micrometer-scale pits, caused mainly by inertial cavitation bubbles such as C4F10 gas bubbles and vapor bubbles, increased exponentially with increasing Tex in the range 0.1 s<Tex<10 s. The results of the present study suggest that cavitation-induced sonoporation can produce various pore sizes in membranes, enabling the delivery of external molecules of differing sizes into cells or tissues.