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

• Cavitation-induced sonoporation can produce various pore sizes in membranes.
• For US exposure times less than 0.1 s, erosion was produced only by microbubbles.
• Nanometer-scale pits were caused by Sonazoid® microbubbles and C4F10 gas bubbles.
• Micrometer-scale pits were caused by inertial vapor bubbles and C4F10 gas bubbles.
• Micrometer-scale pit numbers increased with increasing US exposure time.

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.