Published papers

Ultrasound-triggered drug delivery has been widely researched for its potential to improve the therapeutic efficacy of drugs. This paper presents drug release using hydrogel microbeads with release enhancer for efficient ultrasound-triggered drug delivery. By using a centrifuge-based microfluidic device, drug-model-encapsulating calcium alginate hydrogel microbeads containing tungsten particles with high acoustic impedance were fabricated. Because the tungsten particles work as release enhancer, the hydrogel microbeads become to have high sensitivity to ultrasound with localized variation in acoustic impedance so that the release rate of drug models improves. By applying ultrasound at 20 kHz to the hydrogel microbeads, the release of fluorescent silica nanoparticles that are a drug model for virus vectors, micelles, and proteins was tested. Importantly, the proposed hydrogel microbeads released the drug model even under a cavitation-suppressed environment. Furthermore, the additional coating on the hydrogel microbeads with poly-L-lysine enabled us to adjust the release rate of the drug model. The proposed ultrasound-triggered drug release system using release enhancer is expected to be an effective approach for expanding the varieties of applicable treatments using on-demand drug delivery systems.

This research focuses on the heat transfer of laminar water flow in a square channel under 28–120 kHz and 60–120 W ultrasonic waves, irradiated along the streamwise direction. The experiment was conducted at Reynolds numbers of 400–2000, and the uniform surface heat flux of the pipe was set as 3.1–12.9 kW/m2. In this study, ultrasound-induced streaming was investigated using a particle image velocimetry (PIV) technique, and cavitation bubbles were detected using a digital camera. From the results, the maximum heat transfer enhancement was 155% with 28 kHz and 120 W ultrasound at q = 12.9 kW/m2, Re = 400, and x/D_h = 2.58. The Nu ratio, which represents the capability of ultrasound-induced heat transfer enhancement, was also determined. A maximum Nu ratio of 2.017 was achieved with 28 kHz and 120 W ultrasound at q = 7.2 kW/m2 and Re = 400 or St = 28.16 × 10^4. With a relatively low Re, the poorest heat transfer was observed at St values ranging from 40 × 10^4 to 120 × 10^4. This study provides a predictive formula for the Nu ratio, with deviations ranging from 6.89 to 13.2%. Furthermore, the PIV analysis suggested that acoustic streaming of Eckart type appears under the ultrasound irradiation and its velocity enhancement effect becomes maximal under the conditions for the maximum Nu ratio. It is also confirmed that the ultrasound irradiation can enhance the nucleation of bubbles at the pipe wall; ultrasound-induced dynamics of these nucleated bubbles are expected to further disturb near-wall liquid motion and contribute to heat transfer enhancement.

We experimentally study viscous effects on spherical shock waves in glycerol-water solution. A spherical shock wave is generated through rapid expansion of plasma by focusing a nanosecond laser pulse (532 nm) of energy fixed at 1.66 ± 0.22 mJ into the solution with varying glycerol concentration. In the near field, the shock propagation is recorded by an ultra-high-speed camera with temporal resolution of 10 ns. The recorded images are used to obtain the shock evolution, allowing for constructing the shock pressure evolution with the Rankine-Hugoniot relation. It turns out that the plasma pressure is reduced as the solution gets more viscous with increasing the glycerol concentration; wave steepening effect is deemphasized in the more viscous solution, leading to slower decay of the near-field shock pressure. In the far field, the shock pressure is recorded by a hydrophone at 2 mm to 10 mm from the laser focus and compared to linear acoustic theories with or without viscous absorption. The comparison shows that for the case of higher glycerol concentration (say, beyond 80 wt%), the inviscid assumption will fail, meaning that the viscous theory needs to be used for more accurate prediction of the far-field shock pressure.

Sonochemistry has become increasingly important in bioengineering research, and many in vitro and in vivo bioapplications have been developed. Cytotoxicity is always a concern in its implementation. For in vivo treatments and studies, mechanical index (MI) is known to ensure biocompatibility, and even in vitro MI has been used. Because cell characteristics and acoustic phenomena differ in vitro and in vivo, we questioned using MI in vitro. The in vitro cytotoxicity of ultrasound exposure should be investigated to support the development of cutting-edge sonochemistry. In this study, a system for irradiating cultured cells with 1–2 MHz-range ultrasound was developed to demonstrate the invalidity of employing MI alone in vitro. The results showed that cell damage is defined by the MI, ultrasound frequency, and exposure time, which are new indices for quantifying cell damage. Furthermore, cavitation and acoustic streaming are shown to be the main scientific factors that injure cells.

This study experimentally investigated heat transfer and flow characteristics under natural convection in a closed rectangular chamber filled with HFE-7100 fluid, employing megasonic waves. Experiments using parallel heated plates with varying megasonic source distances and inter-plate spacings demonstrated a maximum heat transfer enhancement of 755 %. Particle image velocimetry (PIV) analysis revealed a megasonic wave-induced streaming effect that homogenized temperature differences within the chamber to <1 % under natural convective conditions, effectively addressing the problem of heat accumulation in localized regions. The optimal inter-plate distance between parallel heaters is critical; a reduced inter-plate distance enhances flow interactions between the heater surfaces, allowing confined streaming flow to impinge on and sweep across both boundary layers, thereby augmenting the cooling effect. In contrast, the spacing between the heaters increased, the acoustic streaming beam expanded, and its maximum velocity decreased due to the transformation of acoustic energy into beam enlargement, requiring a greater drive force to overcome acoustic energy attenuation and fluid viscosity. Additionally, the heat transfer effectiveness by megasonic waves is heat-flux dependent; strong acoustic streaming significantly reduces the thermal boundary layer at relatively low heat fluxes, resulting in more uniform temperatures. However, at higher fluxes, the waves' disruptive effect still sweeps away the thermal boundary layer with a relatively high-velocity stream, despite its thickness and vigorous natural convection, further improving heat transfer. These findings suggest that combining megasonic waves with dielectric liquids in two-phase immersion cooling systems could substantially improve thermal management in small electronic components and batteries.

An experimental technique was developed for two-dimensional Particle Image Velocimetry (PIV) measurement of wall shear flow around a bubble growing under dissolved gas supersaturation. Carbonated water was used as dissolved-gas-supersaturated liquid, and its flow was created in a small container with a tube pump. An isolated CO2 bubble nucleated from an intentionally created scratch on the glass surface was placed in the flow. The mass-diffusion-driven growth of the bubble (from nucleation to detachment from the surface) was recorded using a video camera with backlighting; the radius of the detached bubble was below 1 mm in the present experimental conditions. The velocity field without and with the wall-attached bubble was obtained through PIV with the water (seeded with fluorescent particles) and with a planar laser sheet, which enables one to obtain local shear flow. With the measured liquid velocity at the bubble center, the particle Reynolds number was found to be below 1. The proposed PIV measurement technique allows for careful examination of bubble detachment dynamics and convective mass transfer around attached bubbles.

The elasticity of Tetra-PEG chemical gel deformed by the oscillation of a laser-induced microbubble was obtained through comparison to a bubble dynamics model. An infrared nanosecond laser pulse was focused into the gel to nucleate a spherical microbubble was recorded using a high-speed camera. The evolution of the bubble radius is found to be symmetric between the growth and shrinkage phases, suggesting that the gel structure is not damaged by finite-amplitude oscillations of the bubble. The radius evolution in the first collapse phase (from the maximal to the minimal size) was compared with the Rayleigh–Plesset (RP) equation equipped with neo-Hookean and quadratic Kelvin–Voigt (qKV) constitutive models, allowing for the determination of the shear modulus under high-frequency deformation. When the maximum radius of the bubble is sufficiently small, the measured shear modulus agrees with values from previous conventional rheometer studies, indicating frequency-independent behavior of the chemical gel above a certain deformation rate threshold. On the other hand, when the maximum radius exceeds a threshold, the neo-Hookean model fails to capture the elastic response, and comparison with the RP equation with the qKV model, reveals pronounced stiffening under large deformation.

This study experimentally investigates heat transfer enhancement in single-phase KF-96 silicone fluid immersion cooling subjected to 2.4 MHz megasonic irradiation. A vertically immersed symmetric two-sided heated plate with one instrumented face was employed under heat fluxes ranging from 2.21 to 6.86 kW/m2, while the piezoelectric disk diameter (16–25 mm) and fluid kinematic viscosity (1–50 cSt) were systematically varied. Particle Image Velocimetry (PIV) resolved near-wall acoustic streaming to elucidate convective mechanisms. The results show that megasonic excitation reduced surface temperature by up to 13.5% relative to natural convection. Among all configurations, the 20 mm transducer yielded the highest performance, achieving a maximum heat transfer enhancement of 60% at 2.21 kW/m2 in 1 cSt fluid and a peak enhancement per watt metric of 0.84 at 6.86 kW/m2 in 10 cSt fluid. The enhancement exhibited a non-monotonic dependence on transducer diameter, governed by an optimal dimensionless acoustic parameter window of 153 to 167 and an area coverage ratio of 0.11. Furthermore, the enhancement trend decreases with increasing heat flux in low-viscosity fluids but conversely increases in highly viscous fluids due to localized, thermally induced viscosity reduction. PIV revealed that low-viscosity fluids generate wide, divergent shear layers promoting macro-recirculation and high turbulent intensity. Conversely, high-viscosity fluids produce narrow, collimated streams constrained by internal friction, despite velocity increment ratios reaching up to 164 times those of natural convection. An empirical correlation was developed to predict the overall Nusselt number ratio, yielding a mean absolute error of 3.67%. These findings demonstrate that optimal megasonic-assisted immersion cooling requires aligning transducer geometry with fluid rheology to overcome viscous damping.

Cleaning tests with ultrasound-superposed water jets are performed to explore the optimal injection distance from the jet nozzle to a glass plate spin-coated with small silica particles (as a cleaning sample). The cleaning performance is evaluated based on particle removal efficiency (PRE) that is calculated using the haze method. Visualization of the water jet and liquid film flow over the cleaning target shows that the jet flow with short injection distance tends to be in a steady state, while the water jet shape instability grows for long injection distance, leading to atomization of the jet. The cleaning tests with varying the injection distance suggest that there exists an optimal injection distance at which the PRE becomes maximal.

In this paper, we apply aeration with oxygen microbubbles to tap water; the intent is to quantitatively evaluate whether nitrogen gas originally dissolved in the water under the atmosphere is purged by the aeration with oxygen microbubbles. Oxygen microbubbles are continuously injected into the circulation system of tap water open to the atmosphere. While the concentration of dissolved oxygen (DO) can be detected by a commercial DO meter, that of dissolved nitrogen (DN) is unavailable. To detect the DN level, we observe the growth of millimetre-sized gas bubbles nucleated at glass surfaces in contact with the aerated water and compare it with the multi-species theory of Epstein and Plesset where the (unknown) DN concentration is treated as a fitting parameter. In the theory, we solve binary diffusion of each gas species (oxygen or nitrogen) in the water independently, under the assumption that the dissolved gases are sufficiently dilute. Comparisons between the experiment and the theory suggest that the DN in the water is effectively purged by the oxygen aeration. The supplemental experiment of aeration with nitrogen microbubbles is also documented to show that the DO can be effectively purged as well.

The process of quickly removing abrasive particles of silica and ceria slurries is important in the use of CMP equipment. Megasonic cleaning of nozzle injection type is one of a variety of post-CMP cleaning methods and its performance including cleaning efficiency and erosion was explored experimentally with parametric studies. In the cleaning process, it is favorable to achieve both high efficiency and low damage. The cleaning efficiency was defined by particle removal efficiency (PRE) with a glass sample spin-coated with small silica particles; the damage was detected from mass loss of aluminum foils after the cleaning. The cleaning tests show that the performance of nozzle injection megasonic cleaning depends significantly on ultrasound frequency and water temperature. Toward more efficient and less erosive cleaning, the nozzle injection angle is also expected to play a key role.

The problem of predicting the moments of the distribution of bubble radius in bubbly flows is considered. The particular case where bubble oscillations occur due to a rapid (impulsive or step change) change in pressure is analyzed, and it is mathematically shown that in this case, inviscid bubble oscillations reach a stationary statistical equilibrium, whereby phase cancellations among bubbles with different sizes lead to time-invariant values of the statistics. It is also shown that at statistical equilibrium, moments of the bubble radius may be computed using the period-averaged bubble radius in place of the instantaneous one. For sufficiently broad distributions of bubble equilibrium (or initial) radius, it is demonstrated that bubble statistics reach equilibrium on a time scale that is fast compared to physical damping of bubble oscillations due to viscosity, heat transfer, and liquid compressibility. The period-averaged bubble radius may then be used to predict the slow changes in the moments caused by the damping. A benefit is that period averaging gives a much smoother integrand, and accurate statistics can be obtained by tracking as few as five bubbles from the broad distribution. The period-averaged formula may therefore prove useful in reducing computational effort in models of dilute bubbly flow wherein bubbles are forced by shock waves or other rapid pressure changes, for which, at present, the strong effects caused by a distribution in bubble size can only be accurately predicted by tracking thousands of bubbles. Some challenges associated with extending the results to more general (nonimpulsive) forcing and strong two-way coupled bubbly flows are briefly discussed.

The theory of the acoustics of dilute bubbly liquids is reviewed, and the dispersion relation is modified by including the effect of liquid compressibility on the natural frequency of the bubbles. The modified theory is shown to more accurately predict the trend in measured attenuation of ultrasonic waves. The model limitations associated with such high-frequency waves are discussed.

Shock propagation through a bubbly liquid contained in a deformable tube is considered. Quasi-one-dimensional mixture-averaged flow equations that include fluid–structure interaction are formulated. The steady shock relations are derived and the nonlinear effect due to the gas-phase compressibility is examined. Experiments are conducted in which a free-falling steel projectile impacts the top of an air/water mixture in a polycarbonate tube, and stress waves in the tube material and pressure on the tube wall are measured. The experimental data indicate that the linear theory is incapable of properly predicting the propagation speeds of finite-amplitude waves in a mixture-filled tube; the shock theory is found to more accurately estimate the measured wave speeds.

A method for on-demand droplet fusion in a microfluidic channel is presented using the flow created from a single explosively expanding cavitation bubble. We test the technique for water-in-oil droplets, which are produced using a T-junction design in a microfluidic chip. The cavitation bubble is created with a pulsed laser beam focused into one droplet. High-speed photography of the dynamics reveals that the droplet fusion can be induced within a few tens of microseconds and is caused by the rapid thinning of the continuous phase film separating the droplets. The cavitation bubble collapses and re-condenses into the droplet. Droplet fusion is demonstrated for static and moving droplets, and for droplets of equal and unequal sizes. Furthermore, we reveal the diffusion dominated mixing flow and the transport of a single encapsulated cell into a fused droplet. This laser-based droplet fusion technique may find applications in micro-droplet based chemical synthesis and bioassays.

When a droplet impacts a solid surface at high speed, the contact periphery expands very quickly and liquid compressibility plays an important role in the initial dynamics and the formation of lateral jets. The high speed impact results in high pressures that can account for the surface erosion. In this study, we numerically investigated a high speed droplet impacts on a solid wall. The multicomponent Euler equations with the stiffened equation of state are computed using a FV-WENO scheme with an HLLC Riemann solver that accurately captures shocks and interfaces. In order to compare the available theories and experiments, 1D, 2D and axisymmetric solutions are obtained. The generated pressures, shock speeds, and differences in the dimensionality are investigated. In addition, the effect of target compliance is evaluated.

The effect of distributed bubble nuclei sizes on shock propagation in a bubbly liquid is numerically investigated. An ensemble-averaged technique is employed to derive the statistically averaged conservation laws for polydisperse bubbly flows. A finite-volume method is developed to solve the continuum bubbly flow equations coupled to a single-bubble-dynamic equation that incorporates the effects of heat transfer, liquid viscosity and compressibility. The one-dimensional shock computations reveal that the distribution of equilibrium bubble sizes leads to an apparent damping of the averaged shock dynamics due to phase cancellations in oscillations of the different-sized bubbles. If the distribution is sufficiently broad, the phase cancellation effect can dominate over the single-bubble-dynamic dissipation and the averaged shock profile is smoothed out.

High speed spray cleaning which utilize droplets impact has been used for removing contaminants from wafer surface. When a droplet impacts a solid surface at high speed, the contact periphery expands very quickly and liquid compressibility plays an important role in the initial dynamics and the formation of lateral jets. Impact results in high pressures that can clean or damage the surface. In this study, we numerically investigated a high speed droplet impacts on a solid wall. In order to compare the available theory and experiments, 1D, 2D and axisymmetric solutions are obtained. The generated pressures, shock speeds, and the lateral jetting mechanism are investigated; especially the effect of target compliance is focused.

It has been an experimental challenge to test the rupture of liquids with homogeneous nucleation of vapor bubbles. Many prior studies suffered from the ubiquitous presence of impurities in liquids or at container surfaces that spontaneously nucleate and grow under tension. Here, we propose a microfluidic approach to eliminate such impurities and obtain homogeneous bubble nucleation. We stretch the liquid dynamically via the interaction between a laser-induced shock and an air-liquid interface in a microchannel. Reproducible observations of the nucleation of vapor bubbles are obtained, supporting our claim of homogeneous nucleation. From comparisons of the distribution of vapor cavities with Euler flow simulations, the nucleation threshold for water at room temperature is predicted to be −60 MPa.

Laser-induced optical breakdown at two spatial locations in ultrapure water saturated with ambient gas is used to nucleate microscopic bubble clouds with lifetimes of tens of nanoseconds. The liquid is ruptured via the interaction of a pair of laser-induced shocks and bubbles. We find that the acoustically nucleated micro-bubbles appear in a localized region defined by the plane that bisects the pair of foci, where rarefaction waves (reflected from the laser-induced bubbles) merge. We measure the probability for acoustic nucleation as a function of the separation between the foci, and the minimum pressures for each separation are calculated with Euler flow simulations. The simulations show that the liquid is exposed to negative pressures for 3–17 ns. A statistical threshold pressure for cavitation inception (0.5 probability) of -20.1 MPa is extracted from the measured probabilities and the calculated minimum pressures.