Ultra-fast mechanics and bioeffects of acoustic droplet vaporization in tissue-mimicking hydrogels

Abstract

Acoustic droplet vaporization (ADV) enables phase-shift droplets to respond to focused ultrasound in a spatiotemporal manner, offering a versatile platform for theranostic applications. To better understand the ADV-inducedmechanics and resulting bioeffects in real-time, we integrated ultra-high-speed microscopy (up to 10 million frames per second), time-lapse confocal microscopy, and focused ultrasound. Three monodispersed phase-shift droplets—containing perfluoropentane (PFP), perfluorohexane (PFH), or perfluorooctane (PFO)—with an average diameter of ∼12 μm were studied in fibrin-based, tissue-mimicking hydrogels. To assess cellular bioeffects and mechanical changes resulting from ADV, we co-encapsulated fibroblasts and tracer particles within the hydrogel. Tracking the displacement of tracer particles during and after ADV indicated a hyper-local region of influence by an ADV-generated bubble, correlating inversely with the bulk boiling point of the phase-shift droplets. Additionally, cell membrane permeabilization significantly depended on the distance between the droplet and cell (d), decreasing rapidly with increasing d. We will discuss and compare ADV dynamics, including maximum radial expansion, expansion velocity, and induced radial strain, as well as the critical distance for cell membrane permeabilization in fibrin-based hydrogels containing three different phase-shift droplets. The findings here provide useful information to optimize ADV for more tailored theranostic applications.