Adjustment of Ultrasound Exposure Duration to Microbubble Sonodestruction Kinetics for Optimal Cell Sonoporation In Vitro

Cell sonoporation enables the delivery of various exogenous molecules into the cells. To maximize the percentage of reversibly sonoporated cells and to increase cell viability we propose a model for implicit dosimetry for adjustment of ultrasound (US) exposure duration. The Chinese hamster ovary cell suspension was supplemented with microbubbles (MB) and exposed to US, operating at the frequency of 880 kHz, with a 100% duty cycle and with an output peak negative pressure (PNP) of 500 kPa for durations ranging from 0.5 to 30 s. Using diagnostic B-scan imaging we showed that the majority of the MB at 500 kPa US peak negative pressure undergo sonodestruction in less than a second. During this time maximal number of reversibly sonoporated cells was achieved. Increase of US exposure duration did not increase sonoporated cell number, however it induced additional cell viability decrease. Therefore aiming to achieve the highest level of reversibly sonoporated cells and also to preserve the highest level of cell viability, the duration of US exposure should not exceed the duration needed for complete MB sonodestruction.