Acoustofluidic manipulation for submicron to nanoparticles.

Particles, ranging from submicron to nanometer scale, can be broadly categorized into biological and non-biological types. Submicron-to-nanoscale bioparticles include various bacteria, viruses, liposomes, and exosomes. Non-biological particles cover various inorganic, metallic, and carbon-based particles. The effective manipulation of these submicron to nanoparticles, including their separation, sorting, enrichment, assembly, trapping, and transport, is a fundamental requirement for different applications. Acoustofluidics, owing to their distinct advantages, have emerged as a potent tool for nanoparticle manipulation over the past decade. Although recent literature reviews have encapsulated the evolution of acoustofluidic technology, there is a paucity of reports specifically addressing the acoustical manipulation of submicron to nanoparticles. This article endeavors to provide a comprehensive study of this topic, delving into the principles, apparatus, and merits of acoustofluidic manipulation of submicron to nanoparticles, and discussing the state-of-the-art developments in this technology. The discourse commences with an introduction to the fundamental theory of acoustofluidic control and the forces involved in nanoparticle manipulation. Subsequently, the working mechanism of acoustofluidic manipulation of submicron to nanoparticles is dissected into two parts, dominated by the acoustic wave field and the acoustic streaming field. A critical analysis of the advantages and limitations of different acoustofluidic platforms in nanoparticles control is presented. The article concludes with a summary of the challenges acoustofluidics face in the realm of nanoparticle manipulation and analysis, and a forecast of future development prospects.

Design and numerical study of a bidirectional acoustic microfluidic pump enabled by microcantilever arrays.

Microfluidics offers a versatile and promising platform for various applications in biomedical and other fields, boasting cost-effectiveness, rapid analysis time, and a compact equipment footprint. However, achieving controlled and versatile microfluidic motion within implantable devices presents a significant challenge. In this study, we propose a novel bidirectional micro-pump design that leverages two sharp-edge microcantilever arrays, driven by ultrasound, to enable selective flow direction by manipulating the ultrasound frequency. Through systematic numerical simulation, we demonstrate the feasibility of this design and further optimize its performance through comprehensive parametric analysis. This work provides valuable guidance for the practical development of sharp-edge-based acoustic micro-pumps, particularly for potential implantable applications such as controlled drug release and in vivo sampling for advanced diagnostics.

Study on the Characteristics of Trackside Acoustic Flow Field of High-Speed Train under the Influence of Crosswind.

During the on-track acoustic detection process, a potential flow model and an acoustic finite element mathematical model based on synthetic wind are utilized, taking into account the combined effects of vehicle speed, wind direction angle, and crosswind speed. Simulation and modeling are achieved using Automatic Matching of Acoustic Radiation Boundary Conditions (AML) technology, enabling obtaining a distribution map and sound pressure frequency response curve of the trackside acoustic field under crosswind conditions by setting up field point grids. It is found that sound pressure values at the same location gradually increase as the vehicle speed increases in the frequency range of 10 Hz to 70 Hz, at different vehicle speeds. The sound pressure values and distribution area of the trackside acoustic field are the largest when the crosswind speed is 10 m/s (wind force at level five), allowing for easier location of the sound source when a fault occurs. The study also reveals that under different wind direction angles, the same location's sound pressure value on the trackside gradually decreases as the wind direction angle increases, to lower than that of the non-crosswind condition, severely hindering the reception and diagnosis of acoustic signals.

Effect of microchannel protrusion on the bulk acoustic wave-induced acoustofluidics: numerical investigation.

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.

Focusing surface acoustic waves assisted electrochemical detector in microfluidics.

This article demonstrates a novel electrochemical detection device. The device is composed by two focusing interdigital transducers for exciting focused surface acoustic waves by applying an AC signal, a three-electrode system for electrochemical measurement, and a liquid pool for holding liquid on a LiNbO3 wafer. The amperometry current of ferrocenecarboxylic acid and potassium phosphate buffer solution is used to characterize the detection sensitivity. Two experiments are carried out to optimize the device design. The result shows that the two focusing interdigital transducers with arc degree 30° and distance 5 mm can remarkably enhance the liquid mixing rate. Under this condition, the oxidation current is about 27 times larger than that without surface acoustic wave stirring.

Programmable multi-DNA release from multilayered polyelectrolytes using gigahertz nano-electromechanical resonator.

BACKGROUND: Controllable and multiple DNA release is critical in modern gene-based therapies. Current approaches require complex assistant molecules for combined release. To overcome the restrictions on the materials and environment, a novel and versatile DNA release method using a nano-electromechanical (NEMS) hypersonic resonator of gigahertz (GHz) frequency is developed. RESULTS: The micro-vortexes excited by ultra-high frequency acoustic wave can generate tunable shear stress at solid-liquid interface, thereby disrupting molecular interactions in immobilized multilayered polyelectrolyte thin films and releasing embedded DNA strands in a controlled fashion. Both finite element model analysis and experiment results verify the feasibility of this method. The release rate and released amount are confirmed to be well tuned. Owing to the different forces generated at different depth of the films, release of two types of DNA molecules with different velocities is achieved, which further explores its application in combined gene therapy. CONCLUSIONS: Our research confirmed that this novel platform based on a nano-electromechanical hypersonic resonator works well for controllable single and multi-DNA release. In addition, the unique features of this resonator such as miniaturization and batch manufacturing open its possibility to be developed into a high-throughput, implantable and site targeting DNA release and delivery system.

Controlled and Tunable Loading and Release of Vesicles by Using Gigahertz Acoustics.

Controllable exchange of molecules between the interior and the external environment of vesicles is critical in drug delivery and micro/nano-reactors. While many approaches exist to trigger release from vesicles, controlled loading remains a challenge. Herein, we show that gigahertz acoustic streaming generated by a nanoelectromechanical resonator can control the loading and release of cargo into and from vesicles. Polymer-shelled vesicles showed loading and release of molecules both in solution and on a solid substrate. We observed deformation of individual giant unilamellar vesicles and propose that the shear stress generated by gigahertz acoustic streaming induces the formation of transient nanopores, with diameters on the order of 100 nm, in the vesicle membranes. This provides a non-invasive method to control material exchange across membranes of different types of vesicles, which could allow site-specific release of therapeutics and controlled loading into cells, as well as tunable microreactors.

Investigation into the Effect of Acoustic Radiation Force and Acoustic Streaming on Particle Patterning in Acoustic Standing Wave Fields.

Acoustic standing waves have been widely used in trapping, patterning, and manipulating particles, whereas one barrier remains: the lack of understanding of force conditions on particles which mainly include acoustic radiation force (ARF) and acoustic streaming (AS). In this paper, force conditions on micrometer size polystyrene microspheres in acoustic standing wave fields were investigated. The COMSOL® Mutiphysics particle tracing module was used to numerically simulate force conditions on various particles as a function of time. The velocity of particle movement was experimentally measured using particle imaging velocimetry (PIV). Through experimental and numerical simulation, the functions of ARF and AS in trapping and patterning were analyzed. It is shown that ARF is dominant in trapping and patterning large particles while the impact of AS increases rapidly with decreasing particle size. The combination of using both ARF and AS for medium size particles can obtain different patterns with only using ARF. Findings of the present study will aid the design of acoustic-driven microfluidic devices to increase the diversity of particle patterning.

Recent progress in transdermal sonophoresis.

Transdermal drug administration has a number of advantages that cannot be leveraged for therapeutic benefits because of the robust barrier provided by the stratum corneum. One of the promising techniques for circumventing the stratum corneum is sonophoresis - the use of ultrasound for facilitating transdermal drug delivery. In this review, the mechanisms underlying sonophoresis and the utilization of the technique for transdermal delivery are discussed. The challenges of this mode of drug administration have also been highlighted and insight from a number of toxicological studies is described.

Probing Cell Deformability via Acoustically Actuated Bubbles.

An acoustically actuated, bubble-based technique is developed to investigate the deformability of cells suspended in microfluidic devices. A microsized bubble is generated by an optothermal effect near the targeted cells, which are suspended in a microfluidic chamber. Subsequently, acoustic actuation is employed to create localized acoustic streaming. In turn, the streaming flow results in hydrodynamic forces that deform the cells in situ. The deformability of the cells is indicative of their mechanical properties. The method in this study measures mechanical biomarkers from multiple cells in a single experiment, and it can be conveniently integrated with other bioanalysis and drug-screening platforms. Using this technique, the mean deformability of tens of HeLa, HEK, and HUVEC cells is measured to distinguish their mechanical properties. HeLa cells are deformed upon treatment with Cytochalasin. The technique also reveals the deformability of each subpopulation in a mixed, heterogeneous cell sample by the use of both fluorescent markers and mechanical biomarkers. The technique in this study, apart from being relevant to cell biology, will also enable biophysical cellular diagnosis.

Acoustic micro-vortexing of fluids, particles and cells in disposable microfluidic chips.

We demonstrate an acoustic platform for micro-vortexing in disposable polymer microfluidic chips with small-volume (20 µl) reaction chambers. The described method is demonstrated for a variety of standard vortexing functions, including mixing of fluids, re-suspension of a pellet of magnetic beads collected by a magnet placed on the chip, and lysis of cells for DNA extraction. The device is based on a modified Langevin-type ultrasonic transducer with an exponential horn for efficient coupling into the microfluidic chip, which is actuated by a low-cost fixed-frequency electronic driver board. The transducer is optimized by numerical modelling, and different demonstrated vortexing functions are realized by actuating the transducer for varying times; from fractions of a second for fluid mixing, to half a minute for cell lysis and DNA extraction. The platform can be operated during 1 min below physiological temperatures with the help of a PC fan, a Peltier element and an aluminum heat sink acting as the chip holder. As a proof of principle for sample preparation applications, we demonstrate on-chip cell lysis and DNA extraction within 25 s. The method is of interest for automating and chip-integrating sample preparation procedures in various biological assays.

Characterizing Acoustic Behavior of Silicon Microchannels Separated by a Porous Wall.

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.

Enhanced Performance of an Acoustofluidic Device by Integrating Temperature Control.

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.

A Microflow Cytometer Enabled by Monolithic Integration of a Microreflector with an Acoustic Resonator.

Current microflow cytometers suffer from complicated fluidic integration and low fluorescence collection efficiency, resulting in reduced portability and sensitivity. Herein, we demonstrated a new flow cell design based on an on-chip monolithically integrated microreflector with a bulk acoustic wave resonator (MBAW). It enables simultaneous 3D particle focusing and fluorescence enhancement without using shear flow. Benefited by the on-chip microreflector, the captured fluorescence intensity was 1.8-fold greater than that of the Si substrate and 8.3-fold greater than that of the SiO2 substrate, greatly improving the detection sensitivity. Combined with the contactless acoustic streaming-based focusing, particle sensing with a coefficient of variation as low as 6.1% was achieved. We also demonstrated the difference between live and dead cells and performed a cell cycle assay using the as-developed microflow cytometry. This monolithic integrated MBAW provides a new type of opto-acoustofluidic system and has the potential to be a highly integrated, highly sensitive flow cytometer for applications such as in vitro diagnostics and point of care.

Remote control of fluid motion in a channel by acoustic holography.

A new method for manipulating fluid movement using sound waves is presented in this paper. The method relies on acoustic streaming near the free surface of the fluid in a channel with an open top. The sound waves are modulated in phase using acoustic phase holography, which creates a periodic phase pattern from 0 to 2π along a straight path on a target plane. The paper also describes an experimental design to study the main factors influencing the method, such as frequency, number of phase patterns in the path, and sound pressure amplitude. The paper shows that phase pitch and voltage significantly affects fluid speed and that there is a good match between the theoretical and experimental results. Furthermore, the article reports additional experiments with different channel shapes to demonstrate the versatility of the method in controlling fluid motion. The highest fluid speed observed was 0.4 mm/s at a frequency of 1300 kHz and a phase pitch of 5. The paper also investigates the effect of changing the frequency on reversing the flow direction in a U-shaped channel, both experimentally and theoretically. The paper concludes that this method could be a suitable alternative to other acoustic devices for inducing fluid motion because of its simple and flexible design, fabrication, accuracy, and ability to handle complex channels.

Three-dimensional array of microbubbles sonoporation of cells in microfluidics.

Sonoporation is a popular membrane disruption technique widely applicable in various fields, including cell therapy, drug delivery, and biomanufacturing. In recent years, there has been significant progress in achieving controlled, high-viability, and high-efficiency cell sonoporation in microfluidics. If the microchannels are too small, especially when scaled down to the cellular level, it still remains a challenge to overcome microchannel clogging, and low throughput. Here, we presented a microfluidic device capable of modulating membrane permeability through oscillating three-dimensional array of microbubbles. Simulations were performed to analyze the effective range of action of the oscillating microbubbles to obtain the optimal microchannel size. Utilizing a high-precision light curing 3D printer to fabricate uniformly sized microstructures in a one-step on both the side walls and the top surface for the generation of microbubbles. These microbubbles oscillated with nearly identical amplitudes and frequencies, ensuring efficient and stable sonoporation within the system. Cells were captured and trapped on the bubble surface by the acoustic streaming and secondary acoustic radiation forces induced by the oscillating microbubbles. At a driving voltage of 30 Vpp, the sonoporation efficiency of cells reached 93.9% ± 2.4%.

Integrated Rayleigh wave streaming-enhanced sensitivity of shear horizontal surface acoustic wave biosensors.

Shear horizontal surface acoustic wave (SH-SAW) sensors are regarded as a promising alternative for label-free, sensitive, real time and low-cost detection. Nevertheless, achieving high sensitivity with SH-SAW has approached its limit imposed by the mass transport and probe-target affinity. We present here an SH-SAW biosensor accompanied by a unique Rayleigh wave-based actuator. The platform assembled on an ST-quartz substrate consists of dual-channel SH-SAW delay lines fabricated along a 90°-rotated direction, whilst another interdigital electrode (IDT) is orthogonally placed to generate Rayleigh waves so as to induce favourable streaming in the bio-chamber, enhancing the binding efficiency of the bio-target. Theoretical foundation and simulation have shown that Rayleigh acoustic streaming generates a level of agitation that accelerates the mass transport of the biomolecules to the surface. A fourfold improvement in sensitivity is achieved compared with conventional SH-SAW biosensors by means of complementary DNA hybridization with the aid of the Rayleigh wave device, giving a sensitivity level up to 6.15 Hz/(ng/mL) and a limit of detection of 0.617 ng/mL. This suggests that the proposed scheme could improve the sensitivity of SAW biosensors in real-time detection.

Study on the Cooling Performance of a Focused Ultrasonic Radiator for Electrical Heating Elements.

In this work, a focused ultrasonic radiator is proposed for cooling the electrical heating elements in the focal region, and its working characteristics are investigated. The analyses of the FEM computational and flow field visualization test results indicate that focused ultrasound can generate forced convective heat transfer by the acoustic streaming in the focal region, which can cool the heating elements effectively. Experiments show that when the input voltage is 30Vp-p and the ambient temperature is 25 °C, the focused ultrasonic radiator can cause the surface temperature of the heating element (high-temperature alumina ceramic heating plate with a diameter of 5 mm) in the focal region to drop from 100 °C to about 55 °C. When the diameter of the electrical heating element is changed from 5 mm to 30 mm, the cooling effect is similar in the focal region. Compared with a fan, the focused ultrasound radiator has a shorter cooling time and a more concentrated cooling area. The focused ultrasonic radiator proposed in this work is suitable for some special environments.

Integration of acoustic micromixing with cyclic olefin copolymer microfluidics for enhanced lab-on-a-chip applications in nanoscale liposome synthesis.

The integration of acoustic wave micromixing with microfluidic systems holds great potential for applications in biomedicine and lab-on-a-chip technologies. Polymers such as cyclic olefin copolymer (COC) are increasingly utilized in microfluidic applications due to its unique properties, low cost, and versatile fabrication methods, and incorporating them into acoustofluidics significantly expands their potential applications. In this work, for the first time, we demonstrated the integration of polymer microfluidics with acoustic micromixing utilizing oscillating sharp edge structures to homogenize flowing fluids. The sharp edge mixing platform was entirely composed of COC fabricated in a COC-hydrocarbon solvent swelling based microfabrication process. As an electrical signal is applied to a piezoelectric transducer bonded to the micromixer, the sharp edges start to oscillate generating vortices at its tip, mixing the fluids. A 2D numerical model was implemented to determine the optimum microchannel dimensions for experimental mixing assessment. The system was shown to successfully mix fluids at flow rates up to 150µl h-1and has a modest effect even at the highest tested flow rate of 600µl h-1. The utility of the fabricated sharp edge micromixer was demonstrated by the synthesis of nanoscale liposomes.

Study of liquid-phase mass transfer and residual stress in jet electrodeposition process with coaxial megasonic agitation.

The electrodeposition process confronts significant challenges arising from mass transfer limitation and residual stress. To address these issues, an innovative method, combining megasonic agitation with coaxial jet electrodeposition, is introduced. This approach aims to enhance mass transfer and mitigate residual stress. First, an electrodeposition nozzle device was designed, and the liquid-phase mass transfer during electrodeposition was analyzed through finite element simulation. Simulation results indicate that the mass transfer coefficient increases with rising megasonic power density. Notably, when the megasonic power density reached 20 W/cm2, the mass transfer coefficient increased from 0.45 × 10-7 m/s to 18.63 × 10-7 m/s, compared to electrodeposition without megasonic agitation. Secondly, electrodeposition experiments were conducted both with and without megasonic assistance. X-ray diffraction (XRD) was employed to measure the residual stress values of the electrodeposited layers. The results reveal that samples processed with megasonic assistance exhibit lower residual stress values compared to those without. Specifically, at a megasonic power density of 10 W/cm2, the residual stress was 94.3 MPa, representing a 37.7 % reduction compared to the residual stress of 151.5 MPa observed in samples without megasonic agitation. Overall, the findings demonstrate that coaxial megasonic agitation can effectively enhance the liquid-phase mass transfer capability during electrodeposition and reduce the residual stress of the electroplated layer. This innovative method presents a promising avenue for improving electrodeposition processes and achieving superior material properties.