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Introduction: It is now known that capillary waves driven upon a fluid interface by high frequency (> 1 MHz) ultrasound exhibit capillary wave turbulence: the appearance of waves with phase and wavelength far removed from the excitation signal that drives them. These waves are responsible in significant part for atomization, a useful application for ultrasound, though the physics responsible for their appearance is poorly understood. Methods: We use high-speed digital holographic microscopy to observe these capillary waves, an important step towards understanding their generation and atomization phenomena. Results: We observe Zakharov-Kolmogorov weak wave turbulence for a limited range of input power, and find broader turbulence phenomena outside this range. We see discrete thresholds as the input power is increased, where higher and higher frequency responses are driven in the capillary waves with sudden onset between regimes. Discussion: We employed spatial analysis to find extensions of the capillary wave response to higher frequencies, suggesting there is additional information in the spatial distribution of the capillary wave that is rarely if ever measured. We verified via frequency modulation that nonlinear resonance broadening is present, which undermines the use of Faraday wave or parametric wave theories to characterize these waves, important in the context of atomization which is now, definitively, not a Faraday wave process. [ABSTRACT FROM AUTHOR]

Acoustofluidics is a promising technology that leverages acoustic waves for precise manipulation of micro/nano‐scale flows and suspended objects within microchannels. Despite many advantages, the practical applicability of conventional acoustofluidic platforms is limited by irreversible bonding between the piezoelectric actuator and the microfluidic chip. Recently, reconfigurable acoustofluidic platforms are enabled by reversible bonding between the reusable actuator and the replaceable polydimethylsiloxane (PDMS) microfluidic chip by incorporating a PDMS membrane for sealing the microchannel and coupling the acoustic waves with the fluid inside. However, a quantitative guideline for selecting a suitable PDMS membrane for various acoustofluidic applications is still missing. Here, a design rule for reconfigurable acoustofluidic platforms is explored based on a thorough investigation of the PDMS thickness effect on acoustofluidic phenomena: acousto–thermal heating (ATH), acoustic radiation force (ARF), and acoustic streaming flow (ASF). These findings suggest that the relative thickness of the PDMS membrane (t) for acoustic wavelength (λPDMS) determines the wave attenuation in the PDMS and the acoustofluidic phenomena. For t/λPDMS ≈ O(1), the transmission of acoustic waves through the membrane leads to the ARF and ASF phenomena, whereas, for t/λPDMS ≈ O(10), the acoustic waves are entirely absorbed within the membrane, resulting in the ATH phenomenon. [ABSTRACT FROM AUTHOR]

Acoustic manipulation has emerged as a valuable tool for precision controls and dynamic programming of cells and particles. However, conventional acoustic manipulation approaches lack the finesse necessary to form intricate, configurable, continuous, and 3D patterning of particles. Here, this study reports acoustography by Beam Engineering and Acoustic Control Node (BEACON), which delivers intricate, configurable patterns by guiding particles along custom paths with independent phase modulation. Leveraging analytical methods of orbital angular momentum beam via iterative Wirtinger hologram algorithm, this study accomplish acoustography by facilitating orbital angular momentum traps, enabling continuous 2D and 3D acoustic manipulation of microparticles in any desired geometry, with phase modulation independent of intensity. Utilizing on‐chip acoustography, the BEACON platform markedly increases the space‐bandwidth product to 31 000 while attaining an enhanced resolution with a pixel size of ≈25 µm, surpassing the typical resolution of over 200 µm in previous holographic particle manipulation methods. The capabilities of BEACON are demonstrated in creating intricate triple helical tracing structures using microdroplets (20 µm in diameter) and those carrying DNA to validate the effectiveness of the acoustography and phase control methods. This study offers new particle manipulation opportunities, paving the way for next‐generation biomedical systems and the future of contact‐free precision manufacturing. [ABSTRACT FROM AUTHOR]

The small dimensions of microfluidic channels allow for fast diffusive or passive mixing, which is beneficial for time-sensitive applications such as chemical reactions, biological assays, and the transport of to-be-detected species to sensors. In microfluidics, the need for fast mixing within milliseconds arises primarily because these devices are often used in fields where rapid and efficient mixing significantly impacts the performance and outcome of the processes. Active mixing with acoustics in microfluidic devices involves using acoustic waves to enhance the mixing of fluids within microchannels. Using sharp corners and wall patterns in acoustofluidic devices significantly enhances the mixing by acoustic streaming around these features. The streaming patterns around the sharp edges are particularly effective for the mixing because they can produce strong lateral flows that rapidly homogenize liquids. This work presents extensive characterizations of the effect of sharp-edged structures on acoustic mixing in bulk acoustic wave (BAW) mode in a silicon microdevice. The effect of side wall patterns in different angles and shapes, their positions, the type of piezoelectric transducer, and its amplitude and frequency have been studied. Following the patterning of the channel walls, a mixing time of 25 times faster was reached, compared to channels with smooth side walls exhibiting conventional BAW behavior. The average locally determined acoustic streaming velocity inside the channel becomes 14 times faster if sharp corners of 10° are added to the wall. [ABSTRACT FROM AUTHOR]

Micro- and nanoplastics have become increasingly relevant as contaminants to be monitored due to their potential health effects and environmental impact. Nanoplastics, in particular, have been shown to be difficult to detect in drinking water, requiring new capture technologies. In this work, we applied the acoustofluidic seed particle method to capture nanoplastics in an optimized, tilted grid of silica clusters even at the high flow rate of 5 mL/min. Moreover, we achieved, using this technique, the enrichment of nanoparticles ranging from 500 nm to 25 nm as a first in the field. We employed fluorescence to observe the enrichment profiles according to size, using a washing buffer flow at 0.5 mL/min, highlighting the size-dependent nature of the silica seed particle release of various sizes of nanoparticles. These results highlight the versatility of acoustic trapping for a wide range of nanoplastic particles and allow further study into the complex dynamics of the seed particle method at these size ranges. Moreover, with reproducible size-dependent washing curves, we provide a new window into the rate of nanoplastic escape in high-capacity acoustic traps, relevant to both environmental and biomedical applications. [ABSTRACT FROM AUTHOR]

[Display omitted] SERS measurements for monitoring bactericides in dairy products are highly desired for food safety problems. However, the complicated preparation process of SERS substrates greatly impedes the promotion of SERS. Here, we propose acoustofluidic one-step synthesis of Ag nanoparticles on paper substrates for SERS detection. Our method is economical, fast, simple, and eco-friendly. We adopted laser cutting to cut out appropriate paper shapes, and aldehydes were simultaneously produced at the cutting edge in the pyrolysis of cellulose by laser which were leveraged as the reducing reagent. In the synthesis, only 5 μL of Ag precursor was added to complete the reaction, and no reducing agent was used. Our recently developed acoustofluidic device was employed to intensely mix Ag+ ions and aldehydes and spread the reduced Ag nanoparticles over the substrate. The SERS substrate was fabricated in 1 step and 3 min. The standard R6G solution measurement demonstrated the excellent signal and prominent uniformity of the fabricated SERS substrates. SERS detection of the safe concentration of three bactericides, including tetracycline hydrochloride, thiabendazole, and malachite green, from food samples can be achieved using fabricated substrates. We take the least cost, time, reagents, and steps to fabricate the SERS substrate with satisfying performance. Our work has an extraodinary meaning for the green preparation and large-scale application of SERS. [ABSTRACT FROM AUTHOR]

Droplet generation is crucial in various scientific and industrial fields, such as drug delivery, diagnostics, and inkjet printing. While microfluidic platforms enable precise droplet formation, traditional methods often require costly and complex setups, limiting their accessibility. This study introduces a simple, low-cost approach using an off-the-shelf unit and a 3D-printed reservoir. The device, equipped with a driver board, piezo-ring transducer, and a metal sheet with holes, generates oil-in-water (O/W) droplets with an average diameter of 4.62 ± 0.67 µm without external fluid pumps. Its simplicity, cost-effectiveness, and scalability make it highly suitable for both lab-on-chip and industrial applications, demonstrating the feasibility of large-scale uniform droplet production. [ABSTRACT FROM AUTHOR]

The small dimensions of microfluidic channels allow for fast diffusive or passive mixing, which is beneficial for time-sensitive applications such as chemical reactions, biological assays, and the transport of to-be-detected species to sensors. In microfluidics, the need for fast mixing within milliseconds arises primarily because these devices are often used in fields where rapid and efficient mixing significantly impacts the performance and outcome of the processes. Active mixing with acoustics in microfluidic devices involves using acoustic waves to enhance the mixing of fluids within microchannels. Using sharp corners and wall patterns in acoustofluidic devices significantly enhances the mixing by acoustic streaming around these features. The streaming patterns around the sharp edges are particularly effective for the mixing because they can produce strong lateral flows that rapidly homogenize liquids. This work presents extensive characterizations of the effect of sharp-edged structures on acoustic mixing in bulk acoustic wave (BAW) mode in a silicon microdevice. The effect of side wall patterns in different angles and shapes, their positions, the type of piezoelectric transducer, and its amplitude and frequency have been studied. Following the patterning of the channel walls, a mixing time of 25 times faster was reached, compared to channels with smooth side walls exhibiting conventional BAW behavior. The average locally determined acoustic streaming velocity inside the channel becomes 14 times faster if sharp corners of 10° are added to the wall.

Abstract Hepatic spheroids are of high interest in basic research, drug discovery and cell therapy. Existing methods for spheroid culture present advantages and drawbacks. An alternative technology is explored: the hepatic spheroid formation and culture in an acoustofluidic chip, using HepaRG cell line. Spheroid formation and morphology, cell viability, genetic stability, and hepatic functions are analyzed after 6 days of culture in acoustic levitation. They are compared to 2D culture and non-levitated 3D cultures. Sizes of the 25 spheroids created in a single acoustofluidic microphysiological system are homogeneous. The acoustic parameters in our system do not induce cell mortality nor DNA damage. Spheroids are cohesive and dense. From a functional point of view, hepatic spheroids obtained by acoustic levitation exhibit polarity markers, secrete albumin and express hepatic genes at higher levels compared to 2D and low attachment 3D cultures. In conclusion, this microphysiological system proves not only to be suitable for long-term culture of hepatic spheroids, but also to favor differentiation and functionality within 6 days of culture.

Microplastics have emerged as ubiquitous contaminants, attracting increasing global attention. Recent evidence confirms the presence of microplastics in human blood, suggesting their potential to interact with cells and induce adverse physiological reactions in various organs as blood circulates. To quantify the distribution of microplastics and assess their potential effects on human health, the effective separation of microplastics from blood is crucial. However, current methods for separating microplastics from blood are limited in effectiveness and simplicity. This study proposes a microfluidic device that utilizes traveling surface acoustic waves to separate microplastics from blood. While traveling surface acoustic waves have been employed to separate various particles, a systematic study on the separation of microplastics from blood samples has not been previously reported. Specifically, the theoretical values of the acoustic radiation factor for various types of microplastics and blood cells were investigated. The significant differences in resonant frequencies indicated the feasibility of separating microplastics of different sizes and types from blood cells. Experimental validation was performed using a polydimethylsiloxane microfluidic device on a piezoelectric lithium niobate substrate. The device successfully separated 5- and 10-micrometer polystyrene microplastics from blood samples. The effects of power and flow rate on separation efficiency were also systematically investigated. This study provides a novel approach for the effective separation of microplastics from blood, contributing to the assessment of their distribution and potential health impacts.

Cytopathology, crucial in disease diagnosis, commonly uses microscopic slides to scrutinize cellular abnormalities. However, processing high volumes of samples often results in numerous negative diagnoses, consuming significant time and resources in healthcare. To address this challenge, a surface acoustic wave‐enhanced multi‐view acoustofluidic rotation cytometry (MARC) technique is developed for pre‐cytopathological screening. MARC enhances cellular morphology analysis through comprehensive and multi‐angle observations and amplifies subtle cell differences, particularly in the nuclear‐to‐cytoplasmic ratio, across various cell types and between cancerous and normal tissue cells. By prioritizing MARC‐screened positive cases, this approach can potentially streamline traditional cytopathology, reducing the workload and resources spent on negative diagnoses. This significant advancement enhances overall diagnostic efficiency, offering a transformative vision for cytopathological screening. [ABSTRACT FROM AUTHOR]

Hepatic spheroids are of high interest in basic research, drug discovery and cell therapy. Existing methods for spheroid culture present advantages and drawbacks. An alternative technology is explored: the hepatic spheroid formation and culture in an acoustofluidic chip, using HepaRG cell line. Spheroid formation and morphology, cell viability, genetic stability, and hepatic functions are analyzed after 6 days of culture in acoustic levitation. They are compared to 2D culture and non-levitated 3D cultures. Sizes of the 25 spheroids created in a single acoustofluidic microphysiological system are homogeneous. The acoustic parameters in our system do not induce cell mortality nor DNA damage. Spheroids are cohesive and dense. From a functional point of view, hepatic spheroids obtained by acoustic levitation exhibit polarity markers, secrete albumin and express hepatic genes at higher levels compared to 2D and low attachment 3D cultures. In conclusion, this microphysiological system proves not only to be suitable for long-term culture of hepatic spheroids, but also to favor differentiation and functionality within 6 days of culture. [ABSTRACT FROM AUTHOR]

Microplastics have emerged as ubiquitous contaminants, attracting increasing global attention. Recent evidence confirms the presence of microplastics in human blood, suggesting their potential to interact with cells and induce adverse physiological reactions in various organs as blood circulates. To quantify the distribution of microplastics and assess their potential effects on human health, the effective separation of microplastics from blood is crucial. However, current methods for separating microplastics from blood are limited in effectiveness and simplicity. This study proposes a microfluidic device that utilizes traveling surface acoustic waves to separate microplastics from blood. While traveling surface acoustic waves have been employed to separate various particles, a systematic study on the separation of microplastics from blood samples has not been previously reported. Specifically, the theoretical values of the acoustic radiation factor for various types of microplastics and blood cells were investigated. The significant differences in resonant frequencies indicated the feasibility of separating microplastics of different sizes and types from blood cells. Experimental validation was performed using a polydimethylsiloxane microfluidic device on a piezoelectric lithium niobate substrate. The device successfully separated 5- and 10-micrometer polystyrene microplastics from blood samples. The effects of power and flow rate on separation efficiency were also systematically investigated. This study provides a novel approach for the effective separation of microplastics from blood, contributing to the assessment of their distribution and potential health impacts. [ABSTRACT FROM AUTHOR]

Cancer immunotherapy shows promising potential for treating breast cancer. While patients may have heterogeneous treatment responses for adjuvant therapy, it is challenging to predict an individual patients response to cancer immunotherapy. Here, we report primary tumor-derived organotypic cell clusters (POCCs) for rapid and reliable evaluation of cancer immunotherapy. By using a label-free, contactless, and highly biocompatible acoustofluidic method, hundreds of cell clusters could be assembled from patient primary breast tumor dissociation within 2 min. Through the incorporation of time-lapse living cell imaging, the POCCs could faithfully recapitulate the cancer-immune interaction dynamics as well as their response to checkpoint inhibitors. Superior to current tumor organoids that usually take more than two weeks to develop, the POCCs can be established and used for evaluation of cancer immunotherapy within 12 h. The POCCs can preserve the cell components from the primary tumor due to the short culture time. Moreover, the POCCs can be assembled with uniform fabricate size and cell composition and served as an open platform for manipulating cell composition and ratio under controlled treatment conditions with a short turnaround time. Thus, we provide a new method to identify potentially immunogenic breast tumors and test immunotherapy, promoting personalized cancer therapy.

Lateral flow membrane microdevices are widely used for chromatographic separation processes and diagnostics. The separation performance of microfluidic lateral membrane devices is determined by mass transfer limitations in the membrane, and in the liquid phase, mass transfer resistance is dependent on the channel dimensions and transport properties of the species separated by the membrane. We present a novel approach based on an active bulk acoustic wave (BAW) mixing method to enhance lateral transport in micromachined silicon devices. BAWs have been previously applied in channels for mixing and trapping cells and particles in single channels, but this is, to the best of our knowledge, the first instance of their application in membrane devices. Our findings demonstrate that optimal resonance is achieved with minimal influence of the pore configuration on the average lateral flow. This has practical implications for the design of microfluidic devices, as the channels connected through porous walls under the acoustic streaming act as 760 µm-wide channels rather than two 375 µm-wide channels in the context of matching the standing pressure wave criteria of the piezoelectric transducer. However, the roughness of the microchannel walls does seem to play a significant role in mixing. A roughened (black silicon) wall results in a threefold increase in average streaming flow in BAW mode, suggesting potential avenues for further optimization. [ABSTRACT FROM AUTHOR]

Today, microfluidics has become a revolutionary interdisciplinary topic with considerable attention in a wide range of biotechnology applications. In this research work, a numerical investigation of a microfluidic micromixer is carried out using a hybrid actuation approach with different micropillar shapes and gaps. For this purpose, COMSOL Multiphysics v.5.2. is used with three different physics, such as thermoviscous acoustic physics to solve acoustic governing equations, laminar physics to solve fluid flow governing equations, and diluted transport species to solve mixing governing equations. The simulations were carried out at different Reynolds numbers such as 2, 4, 6, 8, 10, and 12 with an oscillation frequency of 15 kHz. The results were in the form of acoustic characteristics such as acoustic pressure, acoustic velocity, acoustic stream, mixing index, and fluid flow behaviour at various Reynolds numbers. The results revealed that the inclusion of micropillars improved the mixing performance and strength of the acoustic field, resulting in an improvement of the mixing performance compared to the case without micropillars. In addition, the mixing performance is also investigated at different Reynolds numbers, and a higher mixing index is investigated at lower Reynolds numbers. Moreover, it was also investigated that blade-shaped micropillars with 0.150 mm gaps deliver the best results compared to the other cases, and the maximum and minimum values of the mixing index are 0.97 and 0.72, respectively, at Reynolds number 2. The main reason behind this larger mixing index at low Reynolds numbers is due to the inclusion of micropillars that enhance the diffusion rate and contact area, leading to the homogenisation of the heterogeneous fluids in the microchamber. The obtained results can be extremely helpful for the design and modifications of a hybrid microfluidics micromixer. [ABSTRACT FROM AUTHOR]

Acoustic streaming enabled by a Lamb wave resonator (LWR) is efficient for particle trapping and enrichment in microfluidic channels. However, because Lamb waves combine the features of bulk acoustic waves and surface acoustic waves, the resulting acoustic streaming in the LWR occurs in multiple planes, and the particle flow behavior in this acoustofluidic system is largely unknown. Reported here are numerical simulations and laboratory experiments conducted to investigate the boundary conditions for particle motion inside a microvortex induced by an LWR. Upon dynamic capture, the particles' trajectories become orbital paths within an acoustic vortex. The suspended particles encounter two distinct acoustic phenomena, i.e., the drag force resulting from acoustic streaming and the acoustic radiation force, which exert forces in various directions on the particles. When the acoustic radiation force and the fluid drag force are dominant for large and small particles in a mixed solution, respectively, the large particles reside within the vortex while the small particles remain at its periphery. Conversely, when the acoustic radiation force is dominant for both types of particles, the distribution pattern is reversed. ARTICLE HIGHLIGHTS: HIGHLIGHTS • A Lamb wave resonator (LWR) was fabricated and used for particle manipulation, and upon analyzing the forces acting on the particles, two distinct distribution patterns are found. • Particles in the acoustic streaming are dominated by different forces depending on their size and the frequency of the LWR. • An LWR with a frequency of 370 MHz was used, and this frequency induces a potent acoustic flow in the LWR that is suitable for particle manipulation. [ABSTRACT FROM AUTHOR]

We studied the effects of vertical vibrations on a water drop that was pinned to the sharp edges of a rectangular post. By varying the frequency and amplitude of the vertical displacement, distinct resonance peaks were observed using a simple optical technique. The vibrational spectra of the first two modes exhibited two closely spaced peaks, which corresponded to standing waves that exist along the major and minor contour lengths of the drops. The values of the resonance frequencies can be explained rather well by a simple model, which was originally proposed for axially symmetric drops. [ABSTRACT FROM AUTHOR]

Acoustic focusing of particle flow in microfluidics has been shown to be an efficient tool for particle separation for various chemical and biomedical applications. The mechanism behind the method is the selective effect of the acoustic radiation force on distinct particles. In this way, they can be selectively focused and separated. The technique can also be applied under stationary conditions, i.e., in the absence of fluid flows. In this study, the manipulation of self-propelled particles, such as Janus particles, in an acoustofluidic setup was investigated. In experiments with self-propelled Janus particles and passive beads, we explored the interplay between self-propulsion and the acoustic radiation force. Our results demonstrated unusual and potentially useful effects such as selective trapping, escape, and assisted escape in binary mixtures of active and passive particles. We also analyzed various aspects related to the behavior of Janus particles in acoustic traps in the presence and absence of flows.

Micro- and nanoplastics have become increasingly relevant as contaminants to be monitored due to their potential health effects and environmental impact. Nanoplastics, in particular, have been shown to be difficult to detect in drinking water, requiring new capture technologies. In this work, we applied the acoustofluidic seed particle method to capture nanoplastics in an optimized, tilted grid of silica clusters even at the high flow rate of 5 mL/min. Moreover, we achieved, using this technique, the enrichment of nanoparticles ranging from 500 nm to 25 nm as a first in the field. We employed fluorescence to observe the enrichment profiles according to size, using a washing buffer flow at 0.5 mL/min, highlighting the size-dependent nature of the silica seed particle release of various sizes of nanoparticles. These results highlight the versatility of acoustic trapping for a wide range of nanoplastic particles and allow further study into the complex dynamics of the seed particle method at these size ranges. Moreover, with reproducible size-dependent washing curves, we provide a new window into the rate of nanoplastic escape in high-capacity acoustic traps, relevant to both environmental and biomedical applications.

Droplet generation is crucial in various scientific and industrial fields, such as drug delivery, diagnostics, and inkjet printing. While microfluidic platforms enable precise droplet formation, traditional methods often require costly and complex setups, limiting their accessibility. This study introduces a simple, low-cost approach using an off-the-shelf unit and a 3D-printed reservoir. The device, equipped with a driver board, piezo-ring transducer, and a metal sheet with holes, generates oil-in-water (O/W) droplets with an average diameter of 4.62 ± 0.67 µm without external fluid pumps. Its simplicity, cost-effectiveness, and scalability make it highly suitable for both lab-on-chip and industrial applications, demonstrating the feasibility of large-scale uniform droplet production.

Acoutofluidics is an increasingly developing and maturing technical discipline. With the advantages of being label-free, non-contact, bio-friendly, high-resolution, and remote-controllable, it is very suitable for the operation of living cells. After decades of fundamental laboratory research, its technical principles have become increasingly clear, and its manufacturing technology has gradually become popularized. Presently, various imaginative applications continue to emerge and are constantly being improved. Here, we introduce the development of acoustofluidic actuation technology from the perspective of related manipulation applications on living cells. Among them, we focus on the main development directions such as acoustofluidic sorting, acoustofluidic tissue engineering, acoustofluidic microscopy, and acoustofluidic biophysical therapy. This review aims to provide a concise summary of the current state of research and bridge past developments with future directions, offering researchers a comprehensive overview and sparking innovation in the field. [ABSTRACT FROM AUTHOR]

The effects of helical flow in a blood vessel are investigated in a dynamic flow generator using surface acoustic wave (SAW) in the microfluidic device. The SAW, generated by an interdigital transducer (IDT), induces acoustic streaming, resulting in a stable and consistent helical flow pattern in microscale channels. This approach allows rapid development of helical flow within the channel without directly contacting the medium. The precise design of the window enables the creation of distinct unidirectional vortices, which can be controlled by adjusting the amplitude of the SAW. Within this device, optimal operational parameters of the dynamic flow generator to preserve the integrity of endothelial cells are found, and in such settings, the actin filaments within the cells are aligned to the desired state. Our findings reveal that intracellular Ca2+ concentrations vary in response to flow conditions. Specifically, comparable maximum intensity and graphical patterns were observed between low-flow rate helical flow and high-flow rate Hagen-Poiseuille flow. These suggest that the cells respond to the helical flow through mechanosensitive ion channels. Finally, adherence of monocytes is effectively reduced under helical flow conditions in an inflammatory environment, highlighting the atheroprotective role of helical flow. Helical flow in blood vessels is well known to prevent atherosclerosis. However, despite efforts to replicate helical flow in microscale channels, there is still a lack of in vitro models which can generate helical flow for analyzing its effects on the vascular system. In this study, we developed a method for generating steady and constant helical flow in microfluidic channel using acoustofluidic techniques. By utilizing this dynamic flow generator, we were able to observe the atheroprotective aspects of helical flow in vitro, including the enhancement of calcium ion flux and reduction of monocyte adhesion. This study paves the way for an in vitro model of dynamic cell culture and offers advanced investigation into helical flow in our circulatory system. [Display omitted] [ABSTRACT FROM AUTHOR]

Acoustic focusing of particle flow in microfluidics has been shown to be an efficient tool for particle separation for various chemical and biomedical applications. The mechanism behind the method is the selective effect of the acoustic radiation force on distinct particles. In this way, they can be selectively focused and separated. The technique can also be applied under stationary conditions, i.e., in the absence of fluid flows. In this study, the manipulation of self-propelled particles, such as Janus particles, in an acoustofluidic setup was investigated. In experiments with self-propelled Janus particles and passive beads, we explored the interplay between self-propulsion and the acoustic radiation force. Our results demonstrated unusual and potentially useful effects such as selective trapping, escape, and assisted escape in binary mixtures of active and passive particles. We also analyzed various aspects related to the behavior of Janus particles in acoustic traps in the presence and absence of flows. [ABSTRACT FROM AUTHOR]

Acoustofluidics is an emerging research field wherein either mixing or (bio)-particle separation is conducted. High-power acoustic streaming can produce more intense and rapid flow patterns, leading to faster and more efficient liquid mixing. However, without cooling, the temperature of the piezoelectric element that is used to supply acoustic power to the fluid could rise above 50% of the Curie point of the piezomaterial, thereby accelerating its aging degradation. In addition, the supply of excessive heat to a liquid may lead to irreproducible streaming effects and gas bubble formation. To control these phenomena, in this paper, we present a feedback temperature control system integrated into an acoustofluidic setup using bulk acoustic waves (BAWs) to elevate mass transfer and manipulation of particles. The system performance was tested by measuring mixing efficiency and determining the average velocity magnitude of acoustic streaming. The results show that the integrated temperature control system keeps the temperature at the set point even at high acoustic powers and improves the reproducibility of the acoustofluidic setup performance when the applied voltage is as high as 200 V. [ABSTRACT FROM AUTHOR]

Acoustic propulsion system presents a novel underwater propulsion approach in small scale swimmer. This study introduces a submerged surface acoustic wave (SAW) propulsion system based on the SiO2/Al/LiNbO 3 structure. At 19.25 MHz, the SAW propulsion system is proposed and investigated by the propulsion force calculation, PIV measurements and propulsion measurements. 3.3 mN propulsion force is measured at 27.6 Vpp. To evaluate the miniature swimmer, the SAW propulsion systems with multiple frequencies are studied. At 2.2 W, the submerged SAW propulsion system at 38.45 MHz demonstrates 0.83 mN/mm2propulsion characteristics. At 96.13 MHz and 24 Vpp, the movements of miniature swimmer with a fully submerged SAW propulsion system are recorded and analyzed to a maximum of 177 mm/s. Because of miniaturization, high power density, and simple structure, the SAW propulsion system can be expected for some microrobot applications, such as underwater drone, pipeline robot and intravascular robot.

Three-dimensional cell agglomerates are broadly useful in tissue engineering and drug testing. We report a well-free method to form large (1.4-mm) multicellular clusters using 100-MHz surface acoustic waves (SAW) without direct contact with the media or cells. A fluid couplant is used to transform the SAW into acoustic streaming in the cell-laden media held in a petri dish. The couplant transmits longitudinal sound waves, forming a Lamb wave in the petri dish that, in turn, produces longitudinal sound in the media. Due to recirculation, human embryonic kidney (HEK293) cells in the dish are carried to the center of the coupling location, forming a cluster in less than 10 min. A few minutes later, these clusters may then be translated and merged to form large agglomerations, and even repeatedly folded to produce a roughly spherical shape of over 1.4 mm in diameter for incubation-without damaging the existing intercellular bonds. Calcium ion signaling through these clusters and confocal images of multiprotein junctional complexes suggest a continuous tissue construct: intercellular communication. They may be formed at will, and the method is feasibly useful for formation of numerous agglomerates in a single petri dish.

The field of ultrasound neuromodulation has rapidly developed over the past decade, a consequence of the discovery of strain-sensitive structures in the membrane and organelles of cells extending into the brain, heart, and other organs. Notably, clinical trials are underway for treating epilepsy using focused ultrasound to elicit an organized local electrical response. A key limitation to this approach is the formation of standing waves within the skull. In standing acoustic waves, the maximum ultrasound intensity spatially varies from near zero to double the mean in one half a wavelength, and has lead to localized tissue damage and disruption of normal brain function while attempting to evoke a broader response. This phenomenon also produces a large spatial variation in the actual ultrasound exposure in tissue, leading to heterogeneous results and challenges with interpreting these effects. One approach to overcome this limitation is presented herein: transducer-mounted diffusers that result in spatiotemporally incoherent ultrasound. Herein, we numerically and experimentally quantified the effect of a diffuser in an enclosed domain, and show that adding the diffuser leads to a two-fold increase in ultrasound responsiveness of hsTRPA1 transfected HEK cells. Furthermore, we demonstrate the diffuser allow us to produce an uniform spatial distribution of pressure in the rodent skull. Collectively, we propose that our approach leads to a means to deliver uniform ultrasound into irregular cavities for sonogenetics.

Ultrasound has been used to manipulate cells in both humans and animal models. While intramembrane cavitation and lipid clustering have been suggested as likely mechanisms, they lack experimental evidence. Here, high-speed digital holographic microscopy (kiloHertz order) is used to visualize the cellular membrane dynamics. It is shown that neuronal and fibroblast membranes deflect about 150 nm upon ultrasound stimulation. Next, a biomechanical model that predicts changes in membrane voltage after ultrasound exposure is developed. Finally, the model predictions are validated using whole-cell patch clamp electrophysiology on primary neurons. Collectively, it is shown that ultrasound stimulation directly defects the neuronal membrane leading to a change in membrane voltage and subsequent depolarization. The model is consistent with existing data and provides a mechanism for both ultrasound-evoked neurostimulation and sonogenetic control.

Nowadays, lipid nanoparticles have gained profound interest in chemical and biomedical engineering. The rapid development of therapeutic nanosystems has led to a need to design suitable approaches to synthesize bio-carriers for efficient drug delivery. Microfluidic methods provide an excellent opportunity to acquire desirable nanoparticle properties, including stability, size, shape, and size distribution, which are often challenging to obtain using conventional bulk synthesis methods. Rapid mixing is a crucial factor in the nanoprecipitation process as it influences the size and size distribution of the nanoparticles. Within this regard, in this work, we report an ultrafast acoustofluidic micromixer to synthesize liposome nanoparticles, which have been widely investigated in the literature as drug carriers due to their biocompatibility and biodegradability. This research has also investigated the influence of glycerol addition to the solvent to control the size of the liposomes. Our findings indicate that utilizing the acoustofluidic platform resulted in the production of nanoscale liposomes with small mean sizes compared to the hydrodynamic flow-focusing (HFF) method. Furthermore, the inclusion of glycerol led to a significant reduction in liposome size. These results emphasize the potential of the proposed approach for the efficient and precise synthesis of liposome nanoparticles with improved characteristics, which can be utilized in various biomedical and drug delivery applications.

With the development of in vitro diagnostics, extracting submicron scale particles from mixed body fluids samples is crucial. In recent years, microfluidic separation has attracted much attention due to its high efficiency, label-free, and inexpensive nature. Among the microfluidic-based separation, the separation based on ultrasonic standing waves has gradually become a powerful tool. A microfluid environment containing a tilted-angle ultrasonic standing surface acoustic wave (taSSAW) field has been widely adapted and designed to separate submicron particles for biochemical applications. This paper investigated submicron particle defection in microfluidics using taSSAWs analytically. Particles with 0.1–1 μm diameters were analyzed under acoustic pressure, flow rate, tilted angle, and SSAW frequency. According to different acoustic radiation forces acting on the particles, the motion of large-diameter particles was more likely to deflect to the direction of the nodal lines. Decreasing the input flow rate or increasing acoustic pressure and acoustic wave frequency can improve particle deflection. The tilted angle can be optimized by analyzing the simulation results. Based on the simulation analysis, we experimentally showed the separation of polystyrene microspheres (100 nm) from the mixed particles and exosomes (30–150 nm) from human plasma. This research results can provide a certain reference for the practical design of bioparticle separation utilizing acoustofluidic devices.

Acoustofluidics is an emerging interdisciplinary research field that involves the integration of acoustics and microfluidics to address challenges in various scientific areas. This technology has proven to be a powerful tool for separating biological targets from complex fluids due to its label-free, biocompatible, and contact-free nature. Considering a careful designing process and tuning the acoustic field particles can be separated with high yield. Recently the advancement of acoustofluidics led to the development of point-of-care devices for separations of micro particles which address many of the limitations of conventional separation tools. This review article discusses the working principles and different approaches of acoustofluidic separation and provides a synopsis of its traditional and emerging applications, including the theory and mechanism of acoustofluidic separation, blood component separation, cell washing, fluorescence-activated cell sorting, circulating tumor cell isolation, and exosome isolation. The technology offers great potential for solving clinical problems and advancing scientific research. [ABSTRACT FROM AUTHOR]

Controllable manipulation and effective mixing of fluids and colloids at the nanoscale is made exceptionally difficult by the dominance of surface and viscous forces. The use of megahertz (MHz)-order vibration has dramatically expanded in microfluidics, enabling fluid manipulation, atomization, and microscale particle and cell separation. Even more powerful results are found at the nanoscale, with the key discovery of new regimes of acoustic wave interaction with 200 fL droplets of deionized water. It is shown that 40 MHz-order surface acoustic waves can manipulate such droplets within fully transparent, high-aspect ratio, 100 nm tall, 20-130 micron wide, 5-mm long nanoslit channels. By forming traps as locally widened regions along such a channel, individual fluid droplets may be propelled from one trap to the next, split between them, mixed, and merged. A simple theory is provided to describe the mechanisms of droplet transport and splitting.

Today, microfluidics has become a revolutionary interdisciplinary topic with considerable attention in a wide range of biotechnology applications. In this research work, a numerical investigation of a microfluidic micromixer is carried out using a hybrid actuation approach with different micropillar shapes and gaps. For this purpose, COMSOL Multiphysics v.5.2. is used with three different physics, such as thermoviscous acoustic physics to solve acoustic governing equations, laminar physics to solve fluid flow governing equations, and diluted transport species to solve mixing governing equations. The simulations were carried out at different Reynolds numbers such as 2, 4, 6, 8, 10, and 12 with an oscillation frequency of 15 kHz. The results were in the form of acoustic characteristics such as acoustic pressure, acoustic velocity, acoustic stream, mixing index, and fluid flow behaviour at various Reynolds numbers. The results revealed that the inclusion of micropillars improved the mixing performance and strength of the acoustic field, resulting in an improvement of the mixing performance compared to the case without micropillars. In addition, the mixing performance is also investigated at different Reynolds numbers, and a higher mixing index is investigated at lower Reynolds numbers. Moreover, it was also investigated that blade-shaped micropillars with 0.150 mm gaps deliver the best results compared to the other cases, and the maximum and minimum values of the mixing index are 0.97 and 0.72, respectively, at Reynolds number 2. The main reason behind this larger mixing index at low Reynolds numbers is due to the inclusion of micropillars that enhance the diffusion rate and contact area, leading to the homogenisation of the heterogeneous fluids in the microchamber. The obtained results can be extremely helpful for the design and modifications of a hybrid microfluidics micromixer.

Lateral flow membrane microdevices are widely used for chromatographic separation processes and diagnostics. The separation performance of microfluidic lateral membrane devices is determined by mass transfer limitations in the membrane, and in the liquid phase, mass transfer resistance is dependent on the channel dimensions and transport properties of the species separated by the membrane. We present a novel approach based on an active bulk acoustic wave (BAW) mixing method to enhance lateral transport in micromachined silicon devices. BAWs have been previously applied in channels for mixing and trapping cells and particles in single channels, but this is, to the best of our knowledge, the first instance of their application in membrane devices. Our findings demonstrate that optimal resonance is achieved with minimal influence of the pore configuration on the average lateral flow. This has practical implications for the design of microfluidic devices, as the channels connected through porous walls under the acoustic streaming act as 760 µm-wide channels rather than two 375 µm-wide channels in the context of matching the standing pressure wave criteria of the piezoelectric transducer. However, the roughness of the microchannel walls does seem to play a significant role in mixing. A roughened (black silicon) wall results in a threefold increase in average streaming flow in BAW mode, suggesting potential avenues for further optimization.

We studied the effects of vertical vibrations on a water drop that was pinned to the sharp edges of a rectangular post. By varying the frequency and amplitude of the vertical displacement, distinct resonance peaks were observed using a simple optical technique. The vibrational spectra of the first two modes exhibited two closely spaced peaks, which corresponded to standing waves that exist along the major and minor contour lengths of the drops. The values of the resonance frequencies can be explained rather well by a simple model, which was originally proposed for axially symmetric drops.

The propagation of acoustic waves in fluids and solids produces fascinating phenomena that have been studied since the late 1700s and through to today, where it is finding broad application in manipulating fluids and particles at the micro to nano-scale. Due to the recent and rapid increase in application frequencies and reduction in the scale of devices to serve this new need, discrepancies between theory and reality have driven new discoveries in physics that are underpinning the burgeoning discipline. While many researchers are continuing to explore the use of acoustic waves in microfluidics, some are exploring vastly smaller scales, to nanofluidics and beyond. Because many of the applications incorporate biological material--organelles, cells, tissue, and organs--substantial effort is also being invested in understanding how ultrasound interacts with these materials. Surprisingly, there is ample evidence that ultrasound can be used to directly drive cellular responses, producing a new research direction beyond the established efforts in patterning and agglomerating cells to produce tissue. We consider all these aspects in this mini-review after a brief introduction to acoustofluidics as an emerging research discipline. [ABSTRACT FROM AUTHOR]

The integration of high-frequency acoustic waves with microfluidics has been gaining popularity as a method of separating cells/particles. A standing surface acoustic wave (sSAW) device produces constructive interference of the stationary waves, demonstrating an increase in cell separating efficiency without damaging/altering the cell structure. The performance of an sSAW device depends on the applied input signal, design of the IDT, and piezoelectric properties of the substrate. This work analyzes the characteristics of a validated 3D finite element model (FEM) of LiNbO3 and the effect on the displacement components of the mechanical waves under the influence of sSAWs by considering XY-, YX-, and 1280 YX-cut LiNbO3 with varying electrode length design. We demonstrated that device performance can be enhanced by the interference of multiple waves under a combination of input signals. The results suggest that 1280 YX-cut LiNbO3 is suitable for generating higher-amplitude out-of-plane waves which can improve the effectiveness of acoustofluidics-based cell separation. Additionally, the findings showed that the length of the electrode impacts the formation of the wavefront significantly. [ABSTRACT FROM AUTHOR]

This comprehensive review paper focuses on the intricate physics of microfluidics and their application in micromixing techniques. Various methods for enhancing mixing in microchannels are explored, with a keen emphasis on the underlying fluid dynamics principles. Geometrical micromixers employ complex channel designs to induce fluid–fluid interface distortions, yielding efficient mixing while retaining manufacturing simplicity. These methods synergize effectively with external techniques, showcasing promising potential. Electrohydrodynamics harnesses electrokinetic phenomena like electroosmosis, electrophoresis, and electrothermal effects. These methods offer dynamic control over mixing parameters via applied voltage, frequency, and electrode positioning, although power consumption and heating can be drawbacks. Acoustofluidics leverages acoustic waves to drive microstreaming, offering localized yet far-reaching effects. Magnetohydrodynamics, though limited in applicability to certain fluids, showcases potential by utilizing magnetic fields to propel mixing. Selecting an approach hinges on trade-offs among complexity, efficiency, and compatibility with fluid properties. Understanding the physics of fluid behavior and rationalizing these techniques aids in tailoring the most suitable micromixing solution. In a rapidly advancing field, this paper provides a consolidated understanding of these techniques, facilitating the informed choice of approach for specific microfluidic mixing needs. [ABSTRACT FROM AUTHOR]

Size sorting, line focusing, and isolation of microparticles or cells are fundamental ingredients in the improvement of disease diagnostic tools adopted in biology and biomedicine. Microfluidic devices are exploited as a solution to transport and manipulate (bio)particles via a liquid flow. Use of acoustic waves traveling through the fluid provides non-contact solutions to the handling goal, by exploiting the acoustophoretic phenomenon. In this paper, a finite element model of a microfluidic surface acoustic wave-based device for the manipulation of microparticles is reported. Counter-propagating waves are designed to interfere inside a PDMS microchannel and generate a standing surface acoustic wave which is transmitted to the fluid as a standing pressure field. A model of the cross-section of the device is considered to perform a sensitivity analysis of such a standing pressure field to uncertainties related to the geometry of the microchannel, especially in terms of thickness and width of the fluid domain. To also assess the effects caused by possible secondary waves traveling in the microchannel, the PDMS is modeled as an elastic solid material. Remarkable effects and possible issues in microparticle actuation, as related to the size of the microchannel, are discussed by way of exemplary results. [ABSTRACT FROM AUTHOR]

Advances in gene editing are leading to new medical interventions where patients' own cells are used for stem cell therapies and immunotherapies. One of the key limitations to translating these treatments to the clinic is the need for scalable technologies for engineering cells efficiently and safely. Toward this goal, microfluidic strategies to induce membrane pores and permeability have emerged as promising techniques to deliver biomolecular cargo into cells. As these technologies continue to mature, there is a need to achieve efficient, safe, nontoxic, fast, and economical processing of clinically relevant cell types. We demonstrate an acoustofluidic sonoporation method to deliver plasmids to immortalized and primary human cell types, based on pore formation and permeabilization of cell membranes with acoustic waves. This acoustofluidic-mediated approach achieves fast and efficient intracellular delivery of an enhanced green fluorescent protein-expressing plasmid to cells at a scalable throughput of 200,000 cells/min in a single channel. Analyses of intracellular delivery and nuclear membrane rupture revealed mechanisms underlying acoustofluidic delivery and successful gene expression. Our studies show that acoustofluidic technologies are promising platforms for gene delivery and a useful tool for investigating membrane repair.

High frequency (MHz-order) surface acoustic waves (SAW) are able to generate intense fluid flow from the attenuation of acoustic radiation in viscous fluids as acoustic streaming. Though such flows are known to produce a force upon the fluid and an equivalent and opposing force upon the object producing the acoustic radiation, there is no convenient method for measuring this force. We describe a new method to accomplish this aim, noting the potential of these devices in providing essentially silent underwater propulsion by virtue of their use of the sound itself to generate fluid momentum flux. Our example employs a 40 MHz SAW device as a pendulum bob while immersed in a fluid, measuring a 1.5 mN propulsion force from an input power of 5 W power to the SAW device. Supporting details regarding the acoustic streaming profile via particle image velocimetry and an associated theoretical model are provided to aid in the determination of the propulsion force knowing the applied power and fluid characteristics. Finally, a simple model is provided to aid the selection of the acoustic device size to maximize the propulsion force per unit device area, a key figure of merit in underwater propulsion devices. Using this model, a maximum force of approximately 10 mN/cm 2 was obtained from 1 W input power using 40 MHz SAW in water and producing a power efficiency of approximately 50%. Given the advantages of this technology in silent propulsion with such large efficiency and propulsion force per unit volume, it seems likely this method will be beneficial in propelling small autonomous submersibles.

Both powerful and unstable, practical lithium metal batteries have remained a difficult challenge for over 50 years. With severe ion depletion gradients in the electrolyte during charging, they rapidly develop porosity, dendrites, and dead Li that cause poor performance and, all too often, spectacular failure. Remarkably, incorporating a small, 100 MHz surface acoustic wave device (SAW) solves this problem. Providing acoustic streaming electrolyte flow during charging, the device enables dense Li plating and avoids porosity and dendrites. SAW-integrated Li cells can operate up to 6 mA cm-2 in a commercial carbonate-based electrolyte; omitting the SAW leads to short circuiting at 2 mA cm-2 . The Li deposition is morphologically dendrite-free and close to theoretical density when cycling with the SAW. With a 245 µm thick Li anode in a full Li||LFP (LiFePO4 ) cell, introducing the SAW increases the uncycled Li from 145 to 225 µm, decreasing Li consumption from 41% to only 8%. A closed-form model is provided to explain the phenomena and serve as a design tool for integrating this chemistry-agnostic approach into batteries whatever the chemistry within.

Abstract Cancer immunotherapy shows promising potential for treating breast cancer. While patients may have heterogeneous treatment responses for adjuvant therapy, it is challenging to predict an individual patient’s response to cancer immunotherapy. Here, we report primary tumor-derived organotypic cell clusters (POCCs) for rapid and reliable evaluation of cancer immunotherapy. By using a label-free, contactless, and highly biocompatible acoustofluidic method, hundreds of cell clusters could be assembled from patient primary breast tumor dissociation within 2 min. Through the incorporation of time-lapse living cell imaging, the POCCs could faithfully recapitulate the cancer-immune interaction dynamics as well as their response to checkpoint inhibitors. Superior to current tumor organoids that usually take more than two weeks to develop, the POCCs can be established and used for evaluation of cancer immunotherapy within 12 h. The POCCs can preserve the cell components from the primary tumor due to the short culture time. Moreover, the POCCs can be assembled with uniform fabricate size and cell composition and served as an open platform for manipulating cell composition and ratio under controlled treatment conditions with a short turnaround time. Thus, we provide a new method to identify potentially immunogenic breast tumors and test immunotherapy, promoting personalized cancer therapy.