One of the earliest events in cellular mechanotransduction is often an increase in intracellular calcium concentration associated with intracellular calcium waves (ICWs) in various physiologic or pathophysiologic processes. Although cavitation-induced calcium responses are believed to be important for modulating downstream bioeffects such as cell injury and mechanotransduction in ultrasound therapy, the fundamental mechanisms of these responses have not been elucidated. In this study, we investigated mechanistically the ICWs elicited in single HeLa cells by the tandem bubble-induced jetting flow in a microfluidic system. We identified two distinct (fast and slow) types of ICWs at varying degrees of flow shear stress-induced membrane deformation, as determined by different bubble standoff distances. We showed that ICWs were initiated by an extracellular calcium influx across the cell membrane nearest to the jetting flow, either primarily through poration sites for fast ICWs or opening of mechanosensitive ion channels for slow ICWs, which then propagated in the cytosol via a reaction−diffusion process from the endoplasmic reticulum. The speed of ICW (C_ICW) was found to correlate strongly with the severity of cell injury, with C_ICW in the range of 33 μm/s to 93 μm/s for fast ICWs and 1.4 μm/s to 12 μm/s for slow ICWs. Finally, we demonstrated that micrometer-sized beads attached to the cell membrane integrin could trigger ICWs under mild cavitation conditions without collateral injury. The relation between the characteristics of ICW and cell injury, and potential strategies to mitigate cavitation-induced injury while evoking an intracellular calcium response, may be particularly useful for exploiting ultrasound-stimulated mechanotransduction applications in the future.

We report about an intriguing boiling regime occurring for small heaters embedded on the boundary in subcooled water. The microheater is realized by focusing a continuous wave laser beam to about $10\mu \mathrm{m}$ in diameter onto a 165-nm-thick layer of gold, which is submerged in water. After an initial vaporous explosion a single bubble oscillates continuously and repeatedly at several $100\mathrm{kHz}$ albeit with constant laser power input. The microbubble's oscillations are accompanied with bubble pinch-off, leading to a stream of gaseous bubbles in the subcooled water. The self-driven bubble oscillation is explained with a thermally kicked oscillator caused by surface attachment and by the nonspherical collapses. Additionally, Marangoni stresses induce a recirculating streaming flow which transports cold liquid towards the microheater, reducing diffusion of heat along the substrate and therefore stabilizing the phenomenon to many million cycles. We speculate that this oscillate boiling regime may overcome the heat transfer thresholds observed during the nucleate boiling crisis and offers a new pathway for heat transfer under microgravity conditions.

The complex structure of the blood–brain barrier (BBB), which blocks nearly all large biomolecules, hinders drug delivery to the brain and drug assessment, thus decelerating drug development. Conventional in vitro models of BBB cannot mimic some crucial features of BBB in vivo including a shear stress environment and the interaction between different types of cells. There is a great demand for a new in vitro platform of BBB that can be used for drug delivery studies. Compared with in vivo models, an in vitro platform has the merits of low cost, shorter test period, and simplicity of operation. Microfluidic technology and microfabrication are good tools in rebuilding the BBB in vitro. During the past decade, great efforts have been made to improve BBB penetration for drug delivery using biochemical or physical stimuli. In particular, compared with other drug delivery strategies, sonoporation is more attractive due to its minimized systemic exposure, high efficiency, controllability, and reversible manner. BBB on chips (BOC) holds great promise when combined with sonoporation. More details and mechanisms such as trans-endothelial electrical resistance (TEER) measurements and dynamic opening of tight junctions can be figured out when using sonoporation stimulating BOC, which will be of great benefit for drug development. Herein, we discuss the recent advances in BOC and sonoporation for BBB disruption with this in vitro platform.

Therapeutic ultrasound or shockwave has shown its great potential to stimulate neural and muscle tissue, where cavitation microbubble induced Ca²⁺ signaling is believed to play an important role. However, the pertinent mechanisms are unknown, especially at the single-cell level. Particularly, it is still a major challenge to get a comprehensive understanding of the effect of potential mechanosensitive molecular players on the cellular responses, including mechanosensitive ion channels, purinergic signaling and integrin ligation by extracellular matrix.

The flow driven by a rapidly expanding and collapsing cavitation bubble in a narrow cylindrical gap is studied with the volume of fluid method. The simulations reveal a developing plug flow during the early expansion followed by flow reversal at later stages. An adverse pressure gradient leads to boundary layer separation and flow reversal, causing large shear stress near the boundaries. Analytical solution to a planar pulsating flow shows qualitative agreement with the CFD results. The shear stress close to boundaries has implications to deformable objects located near the bubble: Experiments reveal that thin, flat biological cells entrained in the boundary layer become stretched, while cells with a larger cross section are mainly transported with the flow.