Microbubbles interact with ultrasound to induce transient microscopic pores in the cellular plasma membrane in a highly localized thermo-mechanical process called sonoporation. The objective of this study was to advance in vitro and in vivo sonoporation through the development of novel devices and methodologies to precisely characterize the effects of microbubble size on suspended cell and blood-brain barrier sonoporation. The three core findings of our study were: 1) microbubble size allows for control over sonoporation power and energy, 2) the previously cited "soft" limit on in vitro sonoporation efficiency can be overcome utilizing sequential, low-energy sonoporation with small-diameter microbubbles, and 3) microbubble volume, not size, is the unifying parameter representing microbubble dose in blood-brain barrier (BBB) sonoporation. These findings greatly simplify the planning of future in vivo sonoporation studies, which benefit from a unified microbubble dose parameter, and provide precise methods to measure BBB permeabilization efficiency both in vitro and in vivo..
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