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Liposomes are widely utilized in therapeutic nanosystems as promising drug carriers for cancer treatment, which requires a meticulous synthesis approach to control the nanoprecipitation process. Acoustofluidic platforms offer a favorable synthesis environment by providing robust agitation and rapid mixing. Here, a novel high-throughput acoustofluidic micromixer is presented for a solvent and solvent-free synthesis of ultra-small and size-tunable liposomes. The size-tunability is achieved by incorporating glycerol as a new technique into the synthesis reagents, serving as a size regulator. The proposed device utilizes the synergistic effects of vibrating trapped microbubbles and an oscillating thin elastic membrane to generate vigorous acoustic microstreaming. The working principle and mixing mechanism of the device are explored numerically and experimentally. The platform exhibits remarkable mixing efficacy for aqueous and viscous solutions at flow rates up to 8000 µL/h, which makes it unique for high-throughput liposome formation and preventing aggregation. As a proof of concept, this study investigates the impact of phospholipid type and concentration, flow rate, and glycerol on the size and size distribution of liposomes. The results reveal a significant size reduction, from ≈900 nm to 40 nm, achieved by merely introducing 75% glycerol into the synthesis reagents, highlighting an innovative approach toward size-tunable liposomes., (© 2024 The Author(s). Small published by Wiley‐VCH GmbH.)

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., (© 2024. The Author(s).)

Point-of-care testing (POCT) has played important role in clinical diagnostics, environmental assessment, chemical and biological analyses, and food and chemical processing due to its faster turnaround compared to laboratory testing. Dedicated manipulations of solutions or particles are generally required to develop POCT technologies that achieve a "sample-in-answer-out" operation. With the development of micro- and nanotechnology, many tools have been developed for sample preparation, on-site analysis and solution manipulations (mixing, pumping, valving, etc.). Among these approaches, the use of acoustic waves to manipulate fluids and particles (named acoustofluidics) has been applied in many researches. This review focuses on the recent developments in acoustofluidics for POCT. It starts with the fundamentals of different acoustic manipulation techniques and then lists some of representative examples to highlight each method in practical POC applications. Looking toward the future, a compact, portable, highly integrated, low power, and biocompatible technique is anticipated to simultaneously achieve precise manipulation of small targets and multimodal manipulation in POC applications., (© 2023 Wiley-VCH GmbH.)

We report a label-free acoustic microfluidic method to confine single, cilia-driven swimming cells in space without limiting their rotational degrees of freedom. Our platform integrates a surface acoustic wave (SAW) actuator and bulk acoustic wave (BAW) trapping array to enable multiplexed analysis with high spatial resolution and trapping forces that are strong enough to hold individual microswimmers. The hybrid BAW/SAW acoustic tweezers employ high-efficiency mode conversion to achieve submicron image resolution while compensating for parasitic system losses to immersion oil in contact with the microfluidic chip. We use the platform to quantify cilia and cell body motion for wildtype biciliate cells, investigating effects of environmental variables like temperature and viscosity on ciliary beating, synchronization, and three-dimensional helical swimming. We confirm and expand upon the existing understanding of these phenomena, for example determining that increasing viscosity promotes asynchronous beating. Motile cilia are subcellular organelles that propel microorganisms or direct fluid and particulate flow. Thus, cilia are critical to cell survival and human health. The unicellular alga Chlamydomonas reinhardtii is widely used to investigate the mechanisms underlying ciliary beating and coordination. However, freely swimming cells are difficult to image with sufficient resolution to capture cilia motion, necessitating that the cell body be held during experiments. Acoustic confinement is a compelling alternative to use of a micropipette, or to magnetic, electrical, and optical trapping that may modify the cells and affect their behavior. Beyond establishing our approach to studying microswimmers, we demonstrate a unique ability to mechanically perturb cells via rapid acoustic positioning.

Acoustofluidic devices becomes one of the emerging and versatile tools for many biomedical applications. Most of the previous acoustofluidic devices are used for cells manipulation, and the few devices for cell phenotyping with a limitation in throughput. In this study, an enhanced tilted-angle (ETA) acoustofluidic device is developed and applied for mechanophenotyping of live cells. The ETA Device consists of an interdigital transducer which is positioned along a microfluidic channel. An inclination angle of 5° is introduced between the interdigital transducer and the liquid flow direction. The pressure nodes formed inside the acoustofluidic field in the channel deflect the biological cells from their original course in accordance with their mechanical properties, including volume, compressibility, and density. The threshold power for fully converging the cells to the pressure node is used to calculate the acoustic contrast factor. To demonstrate the ETA device in cell mechanophenotyping, and distinguishing between different cell types, further experimentation is carried out by using A549 (lung cancer cells), MDB-MA-231 (breast cancer cells), and leukocytes. The resulting acoustic contrast factors for the lung and breast cancer cells are different from that of the leukocytes by 27.9% and 21.5%, respectively. These results suggest this methodology can successfully distinguish and phenotype different cell types based on the acoustic contrast factor., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Surface acoustic wave (SAW)-based acoustofluidics has shown significant promise to manipulate micro/nanoscale objects for biomedical applications, e.g. cell separation, enrichment, and sorting. A majority of the acoustofluidic devices utilize microchannels with rectangular cross-section where the acoustic waves propagate in the direction perpendicular to the sample flow. A region with weak acoustic wave intensity, termed microchannel anechoic corner (MAC), is formed inside a rectangular microchannel of the acoustofluidic devices where the ultrasonic waves refract into the fluid at the Rayleigh angle with respect to the normal to the substrate. Due to the absence of a strong acoustic field within the MAC, the microparticles flowing adjacent to the microchannel wall remain unaffected by a direct SAW-induced acoustic radiation force (ARF). Moreover, an acoustic streaming flow (ASF) vortex produced within the MAC pulls the particles further into the corner and away from the direct ARF influence. Therefore, a residue of particles continues to flow past the SAWs without intended deflection, causing a decrease in microparticle manipulation efficiency. In this work, we introduce a cross-type acoustofluidic device composed of a half-circular microchannel, fabricated through a thermal reflow of a positive photoresist mold, to overcome the limitations associated with rectangular microchannels, prone to the MAC formation. We investigated the effects of different microchannel cross-sectional shapes with varying contact angles on the microparticle deflection in a continuous flow and found three distinct regimes of particle deflection. By systematically removing the MAC out of the microchannel cross-section, we achieved residue-free acoustofluidic microparticle manipulation via SAW-induced ARF inside a half-circular microchannel. The proposed method was applied to efficient fluorescent coating of the microparticles in a size-selective manner without any residue particles left undeflected in the MAC., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

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., (© 2022. The Author(s).)

There is an increasing interest in acoustics for microfluidic applications. This field, commonly known as acoustofluidics involves the interaction of ultrasonic standing waves with fluids and dispersed microparticles. The combination of microfluidics and the so-called acoustic standing waves (ASWs) led to the development of integrated systems for contact-less on-chip cell and particle manipulation where it is possible to move and spatially localize these particles based on the different acoustophysical properties. While it was initially suggested that the acoustic forces could be harmful to the cells and could impact cell viability, proliferation, or function via phenotypic or even genotypic changes, further studies disproved such claims. This review is summarizing some interesting applications of acoustofluidics in the manipulations of biomaterials, such as cells or subcellular vesicles, in works published mainly within the last 5 years., (© 2021 Wiley-VCH GmbH.)

Aquatic organisms within the Cephalopoda family (e.g., octopuses, squids, cuttlefish) exist that draw the surrounding fluid inside their bodies and expel it in a single jet thrust to swim forward. Like cephalopods, several acoustically powered microsystems share a similar process of fluid expulsion which makes them useful as microfluidic pumps in lab-on-a-chip devices. Herein, an array of acoustically resonant bubbles are employed to mimic this pumping phenomenon inside an untethered microrobot called CeFlowBot. CeFlowBot contains an array of vibrating bubbles that pump fluid through its inner body thereby boosting its propulsion. CeFlowBots are later functionalized with magnetic layers and steered under combined influence of magnetic and acoustic fields. Moreover, acoustic power modulation of CeFlowBots is used to grasp nearby objects and release it in the surrounding workspace. The ability of CeFlowBots to navigate remote environments under magneto-acoustic fields and perform targeted manipulation makes such microrobots useful for clinical applications such as targeted drug delivery. Lastly, an ultrasound imaging system is employed to visualize the motion of CeFlowBots which provides means to deploy such microrobots in hard-to-reach environments inaccessible to optical cameras., (© 2021 The Authors. Small published by Wiley-VCH GmbH.)

Acoustofluidics inside the microchannel has already found its wide applications recently. Acoustic streaming and radiation force are two underlying mechanisms that determine the trajectory of microparticles and cells in the manipulation. Critical particle size of viscous effects is found to be about 1.6 µm in the conventional rectangular microchannel (W × H = 380 m × 160 m) at the frequency of 2 MHz, below which the acoustic streaming dominants, and is independent of the driving voltage. In order to effectively adjust such a critical size, a approach is proposed and evaluated numerically to enhance the acoustic streaming by adding some protrusions (i.e., in the shape of a wedge, rod, half-ellipse) to the middle of the top or bottom wall. It is found that the resonant frequency and acoustic pressure will decrease and the acoustic streaming velocity will increase significantly, respectively, with the increase of protrusion height (up to 30 µm while keeping the width the same as 8 µm). Subsequently, trajectory motion patterns of microparticles have apparent changes in comparison to those inside the rectangular microchannel, and acoustic streaming can even dominate the motion of large microparticles (i.e., 10 µm). As a result, the critical particle size could be increased up to 72.5 µm. Furthermore, different protrusion shapes (i.e., wedge, rod, half-ellipse) on the top wall were compared. The sharpness of protrusion at its tip seems to determine the acoustic streaming velocity. The wedge attached to the bottom wall had higher resonant frequency and lower acoustic streaming velocity compared with the top wedge in the same dimension. The patterns of acoustic streaming and microparticle trajectory motion in the microchannel with dual wedges on the top and bottom walls are not the superposition of those of the top and bottom wedge individually. In summary, the geometry of the microchannel has a significant effect on the induced acoustofluidics by the bulk acoustic waves. A much larger acoustic streaming velocity is produced at the tip of the protrusion to change the critical size of microparticles between acoustic streaming and radiation force. It suggests that more applications of acoustofluidics (i.e., mixing and sonoporation) to microparticles and cells in various sizes are feasible by designing an appropriate geometry of the microchannel., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The manipulation of microscale bioentities is desired in many biological and biomedical applications. However, the potential unobservable damage to bioparticles due to rigid contact has always been a source of concern. Herein, a soft-contact acoustic microgripper to handle microparticles to improve the interaction safety is introduced. The system takes advantage of the acoustic-enhanced adhesion of flexible gas-liquid interfaces to capture-release, transport, and rotate the target, such as microbeads (20-65 µm) and zebrafish embryos (from 950 µm to 1.4 mm). The gas-liquid interface generated at the tip of a microcapillary can be precisely controlled by a pneumatic pressure source. The gas-liquid interface oscillation excited by acoustic energy imposes coupled radiation force and drag force on the microparticles, enabling multidimensional movements. Experiments with the microbeads are conducted to evaluate the claimed function and quantify the key parameters that influence the manipulation result. Additionally, 250 zebrafish embryos are captured, transported, and rotated. The hatching rate of the 250 manipulated embryos is approximately 98% similar to that of the nonmanipulated group, which proves the noninvasiveness of the method. The derived theories and experimental data indicate that the developed soft-contact microgripper is functional and beneficial for biological and medical applications., (© 2021 Wiley-VCH GmbH.)

Although ultrasound tools for manipulating and permeabilizing suspended cells have been available for nearly a century, accurate prediction of the distribution of acoustic radiation force (ARF) continues to be a challenge. We therefore developed an analytical model of the acoustic radiation force (ARF) generated by a focused Gaussian ultrasound beam incident on a eukaryotic cell immersed in an ideal fluid. The model had three layers corresponding to the nucleus, cytoplasm, and membrane, of a eukaryotic cell. We derived an exact expression for the ARF in relation to the geometrical and acoustic parameters of the model cell components. The mechanics of the cell membrane and nucleus, the relative width of the Gaussian beam, the size, position and aspect ratio of the cell had significant influence on the ARF. The model provides a theoretical basis for improved acoustic control of cell trapping, cell sorting, cell assembly, and drug delivery., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Acoustofluidic methods, with advantages including simplicity of device design, biocompatible manipulation, and low power consumption, have been touted as promising tools for point-of-care (POC) testing. Here, we report a cell-phone-based acoustofluidic platform that uses acoustic radiation forces to enrich nanoscale analytes and red and green fluorescence nanoparticles (SiO 2 @R and G@SiO 2 ) as probes for POC visual testing. Thus, the color signals from the fluorescent probes are enhanced, and colorimetric sensitivity is significantly improved. As a POC demonstration, the acoustofluidic platform is used to detect hemoglobin (Hb) from human blood, resulting in a rapid and straightforward measurement of normal blood Hb levels. Combining an acoustofluidic-based nanoparticle-concentration platform with cell-phone-based colorimetry, our method introduces a potential pathway toward practical POC testing.

The interaction of a sound or ultrasound wave with an elastic object, such as a microbubble, can give rise to a steady-state microstreaming flow in its surrounding liquid. Many microfluidic strategies for cell and particle manipulation, and analyte mixing, are based on this type of flow. In addition, there are reports that acoustic streaming can be generated in biological systems, for instance, in a mammalian inner ear. Here, new observations are reported that individual cells are able to induce microstreaming flow, when they are excited by controlled acoustic waves in vitro. Single adherent cells are exposed to an acoustic field inside a microfluidic device. The cell-induced microstreaming is then investigated by monitoring flow tracers around the cell, while the structure and extracellular environment of the cell are altered using different chemicals. The observations suggest that the maximum streaming flow induced by an MDA-MB-231 breast cancer cell can reach velocities on the order of mm s -1 , and this maximum velocity is primarily governed by the overall cell stiffness. Therefore, such cell-induced microstreaming measurements, including flow pattern and velocity magnitude, may be used as label-free proxies of cellular mechanical properties, such as stiffness., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Bubbles locating in microfluidic chamber can produce acoustic streaming vortices by applying travelling surface acoustic wave oscillation in an ultrasonic range, which can be used to drive bio-samples to move within the flow field. In this paper, a strategy of bubble array configured in a large number of regularly arranged horseshoe structures is proposed to capture and rotate cells simultaneously. By modifying the geometric parameters of the horseshoe structure and microfluidic setting, high bubble homogeneity and cell trapping percentage was achieved. The simulation and experimental results of the bubble-induced streaming vortices were confirmed to be consistent. Through experiments, we achieved both in-plane and out-of-plane rotation of arrayed HeLa cells trapped by the bubbles. Out-of-plane rotation was used to reconstruct the 3D (three-dimensional) cell morphology, which was demonstrated to be useful in calculating cell geometry related parameters. We believe that this bubble array based cell rotation method is expected to be a promising tool for the investigation of bioengineering, biophysics, medicine, and cell biology.

Bead-based ELISA in microfluidics is a promising platform for reducing the reagent consumption and improving assay throughput due to its fast binding kinetics and low reagent consumption. Current microfluidic bead-based immunoassay mainly relies on magnetic and centrifugal forces to manipulate microparticles to complete an assay protocol. Here we report an acoustic streaming-based microfluidic method that can perform all the fluid and particle operations of bead-based ELISA. A series of sharp-edge structures are used to generate a long-range coupled acoustic streaming that enables simultaneous particle trapping and active molecular exchange in a dead-end microchannel. The device achieved >99% of molecular exchange in 4 min, while maintaining a particle trapping efficiency of 85%. This acoustofluidic-based method demonstrates all three key operations in a bead-based immunoassay: (1) Beads "immobilization"; (2) Active mixing of fluid for bead/target binding; (3) Active molecular exchange for reagent loading and washing. Finally, on-chip quantitative detection of biomarker IL-6 with a limit of detection ∼50 pg/mL is achieved using this platform including an enzymatic signal amplification step. The small footprint, simple setup, and continuous flow operation of the acoustic streaming-based method makes it an attractive platform for continuous flow bead-based immunoassay., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The study of circulating tumor cells (CTCs) offers pathways to develop new diagnostic and prognostic biomarkers that benefit cancer treatments. In order to fully exploit and interpret the information provided by CTCs, the development of a platform is reported that integrates acoustics and microfluidics to isolate rare CTCs from peripheral blood in high throughput while preserving their structural, biological, and functional integrity. Cancer cells are first isolated from leukocytes with a throughput of 7.5 mL h -1 , achieving a recovery rate of at least 86% while maintaining the cells' ability to proliferate. High-throughput acoustic separation enables statistical analysis of isolated CTCs from prostate cancer patients to be performed to determine their size distribution and phenotypic heterogeneity for a range of biomarkers, including the visualization of CTCs with a loss of expression for the prostate specific membrane antigen. The method also enables the isolation of even rarer, but clinically important, CTC clusters., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Acoustophoresis is rapidly gaining prominence in the field of cell manipulation. In recent years, researchers have extensively used this method for separating different types of cells from the bulk fluid. In this paper, we propose a novel acoustophoresis-based technique to capture infected or abnormal erythrocytes from blood plasma. A typical acoustic device consisting of a transducer assembly, microfluidic cavity, and a reflector is considered. Based on the concept of impedance matching, a pair of antibody-coated polystyrene layers is placed in the nodal regions of an acoustic field within the cavity. This technique allows bi-directional migration of the suspended cells to the biofunctionalized surfaces. Therefore, simultaneous capture of infected erythrocytes on both the layers is feasible. Finite element method is used to model the pressure field as well as the motion of erythrocytes under the influence of acoustic radiation, drag, and gravitational forces. A parametric analysis is done by varying the excitation frequency, driving voltage, and the thickness of the polystyrene layers. The resulting changes in the pressure amplitude and field pattern are investigated. The erythrocyte collection efficiency, rate of collection, and the cell distribution on the layer surfaces are also determined under different field conditions. The occurrence of transient cavitation in the blood plasma-filled cavity at the chosen frequency is taken into account by using its threshold pressure value as the limiting factor of pressure amplitude. The study provides an insight into the phenomenon and serves as a guideline to fabricate low-cost, multifunctional rapid diagnostic devices based on acoustophoretic separation., (Copyright © 2017 John Wiley & Sons, Ltd.)

A polydimethylsiloxane microchannel featuring sidewall sharp-edge structures and bare channels, and a piezoelement transducer is attached to a thin glass slide. When an external acoustic field is applied to the microchannel, the oscillation of the sharp-edge structures and the thin glass slide generate acoustic streaming flows which in turn rotate single cells and C. elegans in-plane and out-of-plane., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Nucleation and growth methods offer scalable means of synthesizing colloidal particles with precisely specified size for applications in chemical research, industry, and medicine. These methods have been used to prepare a class of silicone gel particles that display a range of programmable properties and narrow size distributions. The acoustic contrast factor of these particles in water is estimated and can be tuned such that the particles undergo acoustophoresis to either the pressure nodes or antinodes of acoustic standing waves. These particles can be synthesized to display surface functional groups that can be covalently modified for a range of bioanalytical and acoustophoretic sorting applications., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We report an on-chip acoustofluidic method for sequential trapping and transporting of microparticles via acoustically oscillating bubbles. The size and location of bubbles were precisely controlled by lithography. When the acoustic waves were turned off, particles followed the streamlines dictated by laminar flow. When the acoustic waves were turned on, particles were attracted to and trapped in a vortex near the surface of bubble. Therefore, particles could move across the microfluidic channel with programmed trajectories. Additionally, a theoretical model based on acoustic radiation force and drag force due to acoustic microstreaming was established to help design this particle-trapping and -transporting system.

Acoustofluidic technology combines acoustic and microfluidic technologies to realize particle manipulation in microchannels driven by acoustic waves, and the acoustic radiation force (ARF) with boundaries is important for particle manipulation in an acoustofluidic device. In the work reported here, the ARF on a free cylinder immersed in a viscous fluid with an incident plane wave between two impedance boundaries is derived analytically and calculated numerically. The influence of multiple scattering between the particle and the impedance boundaries is described by means of image theory, the finite-series method, and the translational addition theorem, and multiple scattering is included partly in image theory. The ARF on a free rigid cylinder in a viscous fluid is analyzed by numerical calculation, with consideration given to the effects of the distances from cylinder edge to boundaries, fluid viscosity, cylinder size, and boundary reflectivity. The results show that the interaction between the two boundaries and the cylinder makes the ARF change more violently with different frequencies, while increasing the viscosity can reduce the amplitude of the ARF in boundary space. This study provides a theoretical basis for particle manipulation by the ARF in acoustofluidics. HIGHLIGHTS: •The acoustic radiation force due to plane-wave incidence is derived for a free cylinder immersed in a viscous fluid between two boundaries. •A larger negative acoustic radiation force can be obtained when two impedance boundaries exist. •Theoretical guidance is provided for applying the acoustic radiation force in particle manipulation. [ABSTRACT FROM AUTHOR]

We have developed a hybrid device that fuses the techniques of acoustofluidic localization and resonator-based mass sensing of particles in liquid-phase for in-situ analysis in a $\mu \text{L}$ droplet. An elliptic plate resonator (EPR) was used in this work to verify the capability of acoustofluidic manipulation on a resonator chip. Particles were focused on the EPR by the acoustic tweezers to increase the effectiveness of detection. The EPR has a reasonably high liquid-phase quality factor (${Q}$) and low motional resistance (${R}_{m}$) to allow the detection of focused particles in liquid. Moreover, the resonator chip can be detached from the acoustic tweezing device without damage. This allows replacement of just the chip when required. A potential application of this work is organizing and sensing cells on-chip using the concepts herein. [ABSTRACT FROM AUTHOR]

A surge of research in intracellular delivery technologies is underway with the increased innovations in cell‐based therapies and cell reprogramming. Particularly, physical cell membrane permeabilization techniques are highlighted as the leading technologies because of their unique features, including versatility, independence of cargo properties, and high‐throughput delivery that is critical for providing the desired cell quantity for cell‐based therapies. Amongst the physical permeabilization methods, sonoporation holds great promise and demonstrates to deliver a variety of functional cargos, such as biomolecular drugs, proteins, and plasmids, to various cells including cancer, immune, and stem cells. However, traditional bubble‐based sonoporation methods usually require special contrast agents. Bubble‐based sonoporation methods also have high chances of inducing irreversible damage to critical cell components, lowering the cell viability, and reducing the effectiveness of delivered cargos. To overcome these limitations, several novel non‐bubble‐based sonoporation mechanisms are under development. This review will cover both the bubble‐based and non‐bubble‐based sonoporation mechanisms being employed for intracellular delivery, the technologies being investigated to overcome the limitations of traditional platforms, as well as perspectives on the future sonoporation mechanisms, technologies, and applications. [ABSTRACT FROM AUTHOR]

Particles and cells can be patterned and moved (i.e., manipulated) precisely using acoustically driven techniques. To date, application of acoustic particle manipulation has been limited to plain surfaces. There is much potential for applying acoustic manipulation techniques to surfaces with microfabricated structures for high-throughput sensing. But adding thin film structures could alter manipulation characteristics compared to a plain surface. Using a two-chip setup that allows the wave generating device to be reused, we study the feasibility of acoustofluidic micro-manipulation on a surface-micromachined silicon (SMS) chip. The SMS chip is a complex superstrate with generic thin-film structures fabricated by patterning and etching multiple layers of thin films, with properties meant to represent a broad range of microfabricated devices. We report notable alterations in the particle separation distances on the SMS chip compared to a bare silicon superstrate, which we attribute to a change in wave type through a comparison of different superstrates prepared. We demonstrate a high cell viability after acoustic manipulation of live cells on the SMS chip. The results herein demonstrate the possibility of integrating a suite of microfabricated sensors on a chip with acoustically driven manipulation capabilities for multiplexed sensing and analysis for bio-applications. [ABSTRACT FROM AUTHOR]

In recent years, surface acoustic wave (SAW) devices have demonstrated great potentials and increasing applications in the manipulation of nano- and micro-particles including biological cells with the advantages of label-free, high sensitivity and accuracy. In this letter, we introduce a novel tilted-angle SAW devices to optimise the acoustic pressure inside a microchannel for cancer-cell manipulation. The SAW generation and acoustic radiation force are improved by seamlessly patterning electrodes in the space surrounding the microchannel. Comparisons between this novel SAW device and a conventional device show a 32% enhanced separation efficiency while the input power, manufacturing cost and fabrication effort remain the same. Effective separation of HeLa cancer cells from peripheral blood mononuclear cells is demonstrated. This novel SAW device has the advantages in minimizing device power consumption, lowering component footprint and increasing device density. [ABSTRACT FROM AUTHOR]

Microalgae play a key role in aquatic ecology, and methods providing species determination and enumeration can provide critical information about—for instance—harmful algae blooms (HABs) or spreading of invasive species. A crucial step in current methods is the use of sedimentation. This provides the enrichment needed to achieve statistical counts of sometimes rare species within reasonable timeframes, but it comes with the drawback of aggregating the sample. This is a real challenge for computer-aided identification as particle aggregates can often be erroneously classified. In this paper, we propose an alternative method based on flow-through imaging aided by acoustic-focussing, as this provides better input-data for automated counting-methods while simultaneously removing the need for manual sample preparation. We demonstrate that by acoustically focussing microalgae and other particulates in a fast-flowing water sample, it is possible to analyse up to 8 mL sample per minute with sufficient image quality to discriminate the invasive species Ostreopsis ovata from other particulates in samples taken directly from the Mediterranean. We also showcase the ability to achieve sharp images in flow-through at magnifications up to × 50. [ABSTRACT FROM AUTHOR]

One of the challenges in directed energy deposition via powder feeding (DED-PF) is the powder stream divergence that results in low catchment efficiency (i.e., the fraction of particles added to the melt pool). This article introduces a new ultrasound-based powder focusing method referred to as ultrasound particle lensing (UPL), tailored for powder used in DED-PF. The method uses an ultrasound phased array to produce a small volume of high-intensity ultrasound with the required period averaged sound intensity profile. UPL was used to acoustically focus streams of Ti64 and SS 316L particles with an average size of 89 μ m and a particle speed of 0.6 m/s, exiting from a DED-PF nozzle analog. The e − 1 powder stream widths downstream of the resulting force fields for both materials were reduced by 30%. The experimental results closely match Lagrangian and Eulerian simulations of the process. This novel setup offers the possibility of fast control of the powder stream divergence angle and effective diameter in the process zone during the DED-PF process. This will in turn improve the feature resolution and catchment efficiency of the process. • Simulation and experiments on new powder stream focusing method are presented. • The method is used to focus metal powder using an ultrasound phased array. • A new particle stream model is used to model particle stream/force field interaction. [ABSTRACT FROM AUTHOR]