Excessive noise exposure damages sensory hair cells, leading to permanent hearing loss. Zebrafish are a highly tractable model that have advanced our understanding of drug-induced hair cell death, yet no comparable model exists for noise exposure research. We demonstrate the utility of zebrafish as model to increase understanding of hair cell damage from acoustic trauma and develop protective therapies. We created an acoustic trauma system using underwater cavitation to stimulate lateral line hair cells. We found that acoustic stimulation resulted in exposure time- and intensity-dependent lateral line and saccular hair cell damage that is maximal at 48-72h post-trauma. The number of TUNEL positive lateral line hair cells increased 72h post-exposure whereas no increase was observed in TUNEL positive supporting cells, demonstrating that acoustic stimulation causes hair cell-specific damage. Lateral line hair cells damaged by acoustic stimulation regenerate within three days, consistent with prior regeneration studies utilizing ototoxic drugs. Acoustic stimulation-induced hair cell damage is attenuated by pharmacological inhibition of protein synthesis or caspase activation, suggesting a requirement for translation and activation of apoptotic signaling cascades. Surviving hair cells exposed to acoustic stimulation showed signs of synaptopathy, consistent with mammalian studies. Finally, we demonstrate the feasibility of this platform to identify compounds that prevent acoustic trauma by screening a small redox library for protective compounds. Our data suggest that acoustic stimulation results in lateral line hair cell damage consistent with acoustic trauma research in mammals, providing a highly tractable model for high-throughput genetic and drug discovery studies. Significance Statement Noise overexposure damages hair cells, leading to permanent hearing loss. A critical step in understanding and preventing noise-induced hearing loss is establishing an accessible in vivo model to test for genetic and chemical modulators of noise damage. We developed a novel acoustic trauma system, using cavitation, to stimulate and damage zebrafish lateral line hair cells. We demonstrate that acoustic stimulation damages zebrafish lateral line hair cells in an exposure time- and intensity-dependent manner, consistent with acoustic trauma research in mammals. This novel system provides a model for in vivo, real-time studies of noise exposure, and for rapid discovery of chemical and genetic modulators of acoustic trauma-induced hair cell damage.

The model of a droplet squeezed through a narrow-constricted channel has many applications in pathology, chip/filter/membrane design, drug delivery, etc. Understanding the transient physics of the squeezing process is important in the design and optimization of many micro flow systems. However, available models often ignore the influence of droplet viscosity, and they usually feature low numerical efficiency by solving Navier-Stokes equations. In the present research, we developed a low-dimension analytical model to predict the pressure of squeezing a viscous droplet through a circular constricted channel with acceptable fidelity and low computational cost. Our approach is as follows. We first adapt the Hagen–Poiseuille law to predict the viscosity effect of droplet squeezing. Next, we obtain an analytical expression for the extra pressure caused by only the curvature change obtained. Finally, the general expression of squeezing pressure taking consideration of viscosity and surface tension is expressed. The analytical model we developed is in great agreement with the numerical solutions of the Navier-Stokes equation at a low Reynolds number and low capillary number. These findings have fundamental significance for future applications in engineering and industry.

Oscillating bubbles have proven to be a versatile tool for various microfluidic applications. Despite the existence of the extensive literature on the behavior of acoustically actuated bubbles, a ready-to-use approach, capable of predicting the oscillatory motion for the bubbles trapped in the circular microcavities, is still missing. In this study, we propose a theoretical model to quantify the resonant frequencies and viscous dissipation factors for a single trapped bubble and verify it experimentally. We further investigate an interaction of two coupled bubbles of equal and different radii. For the identical bubble pair, coupling results in controllable frequency shift from the modes of a single bubble, whereas the non-identical one can operate as a flow switch.