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Microscale acoustic streaming for biomedical and bioanalytical applications
Abstract
Over the past few decades, acoustofluidics, one of the branches of microfluidics, has rapidly developed as a multidisciplinary cutting edge research topic, covering many biomedical and bioanalytical applications. Acoustofluidics usually utilizes acoustic pressure and acoustic streaming effects to manipulate liquids and bioparticles. Acoustic manipulation using acoustic radiation force has been widely studied; however, with the recent development of new piezoelectric devices that enable faster acoustic streaming, particle manipulations using drag force induced by acoustic streaming have attracted more attention. Despite many review articles on acoustic radiation force-based acoustophoresis, acoustic streaming is less frequently covered. Here, we review the recent development of microscale acoustic streaming, especially high-frequency transducer-induced high-speed streaming, confinement and programed streaming, and acoustic streaming tweezers, which combine the acoustic radiation force and drag force to tackle the size limitations of conventional acoustic manipulations. A brief review of acoustic streaming theory and its generation is summarized. Recent progress in applying acoustic streaming for fluidic handling and bioparticle manipulations is reviewed. Representative applications of micro acoustic streaming are provided, and the key issues in these applications are analyzed. Finally, the future prospects of micro acoustic streaming in bioanalytical and biomedical applications are discussed.
... • Micro-patterning of magnetic microsources to establish localized, high magnetic fields [54][55][56][57] • Magnetic microtweezers for single cell manipulation [57] • Negative selection of non-targeted cells [60] • Magnetomicrofluidic circuits for spatial single cell control [254,255] • Use of alternating magnetic fields for advanced particle movement [62] Acoustophoresis • Label-free, contact-free separation [63] • Large operation/penetration distances [21] • Large volume and high-throughput processing [63] • Application independent of properties like pH, ionic strength, or charge [64] • Bulk piezoelectric transducers pose geometric limitations to integration [68] • Less sensitive sample discrimination than on dielectric polarizability [21] • Cell manipulation efficiency influenced by the properties of the medium and the microfluidic channel geometry [65,66] • Requires the use materials with high specific acoustic impedances relative to the fluid [70] • Most effective for the manipulation of spherical cells [75] • Applications of acoustophoretic principles in polymer-based platforms. [66,[70][71][72] • Size-independent cell separation via isoacoustic focusing [75] • Generation of 2D acoustic standing waves in microchannels to focus non-spherical cells [76] • Acoustic cell washing [77,78] • Use of secondary acoustic radiation forces or acoustic streaming to manipulate single-cell motion [81,82,84] Optical Tweezers • Label-free, contact-free separation [86,95,256] • High force resolution [86] • Application possible both in flow and static conditions [91,256] • Photo, thermal and mechanical influence on cells might be utilized for cellular and molecular analyses (e.g., light scalpels, intracellular deliveries, membrane fusion) [259] • Handling often limited to small, single cells, therefore low throughput and scalability [90,91,257] • Limited speed of the manipulated particles [257] • Sophisticated and expensive equipment [90,91,95] • Large power needed to create reasonable trapping forces [91] • Potential for photo, thermal and mechanical damage to cells [90,91,259] • Trapping in crowded environments challenging [257,260] • 3D trapping via optical setups that enhance the stiffness of optical traps [89] • Miniaturization of optical elements and their integration into microfluidic systems [91,94,95,258] • Optoelectronic tweezers [90] Passive cell separation method Advantages Drawbacks Novel applications Inertial and hydrodynamic focusing ...
... precise single-cell manipulations, including rotation, selective trapping, controllable release, and particle pairing. [79][80][81][82] Secondary acoustic radiation forces, which are responsible for particle-particle interactions in an acoustic field, are also explored to manipulate single-cell motion in microfluidic channels. [83] The magnitude and direction of secondary acoustic radiation forces have been found to strongly depend on the orientation of the particle pair relative to the wave propagation direction. ...
From deciphering infection and disease mechanisms to identifying novel bio-markers and personalizing treatments, the characteristics of individual cells canprovide significant insights into a variety of biological processes and facilitatedecision-making in biomedical environments. Conventional single-cell analysismethods are limited in terms of cost, contamination risks, sample volumes,analysis times, throughput, sensitivity, and selectivity. Although microfluidicapproaches have been suggested as a low-cost, information-rich, and high-throughput alternative to conventional single-cell isolation and analysis methods,limitations such as necessary off-chip sample pre- and post-processing as well assystems designed for individual workflows have restricted their applications. Inthis review, a comprehensive overview of recent advances in integrated micro-fluidics for single-cell isolation and on-chip analysis in three prominentapplication domains are provided: investigation of somatic cells (particularlycancer and immune cells), stem cells, and microorganisms. Also, the use ofconventional cell separation methods (e.g., dielectrophoresis) in unconventionalor novel ways, which can advance the integration of multiple workflows inmicrofluidic systems, is discussed. Finally, a critical discussion related to currentlimitations of integrated microfluidic single-cell workflows and how they could beovercome is provided.
... The development of microfluidic chips has solved the problem of cell sorting by using expensive equipment and harsh experimental environments. Some of the most common principles to achieve cell sorting are filtration [9], optics [10,11], magnetic sorting [12] and dielectrophoresis [13] and acoustophoresis [14]; dielectrophoresis' separation technology does not require the labeling of cells, in comparison to other methods, but also allows for rapid and continuous sorting and simpler chip fabrication processes and operation methods. In addition, dielectrophoresis enables the rapid and continuous separation of proteins, which is one of the reasons for the rapid development of dielectrophoresis. ...
... After numerical simulation, if the CM factor is calculated by using the cell as a model without membrane spheres, the value of Re[K cm ] will change from negative to positive, at which time the cell will receive a positive dielectrophoretic force, contrary to the actual physical phenomenon. In order to restore the dielectrophoresis of the cell in a solution to a higher degree, the cell can be equated to a single-shell model [14], which is shown in Figure 1b. ...
Dielectrophoresis technology is applied to microfluidic chips to achieve microscopic control of cells. Currently, microfluidic chips based on dielectrophoresis have certain limitations in terms of cell sorting species, in order to explore a microfluidic chip with excellent performance and high versatility. In this paper, we designed a microfluidic chip that can be used for continuous cell sorting, with the structural design of a curved channel and curved double side electrodes. CM factors were calculated for eight human healthy blood cells and cancerous cells using the software MyDEP, the simulation of various blood cells sorting and the simulation of the joule heat effect of the microfluidic chip were completed using the software COMSOL Multiphysics. The effect of voltage and inlet flow velocity on the simulation results was discussed using the control variables method. We found feasible parameters from simulation results under different voltages and inlet flow velocities, and the feasibility of the design was verified from multiple perspectives by measuring cell movement trajectories, cell recovery rate and separation purity. This paper provides a universal method for cell, particle and even protein sorting.
... In acoustic manipulation within standing wave fields, the particle movement range is limited between pressure nodes; even for traveling waves, the non-zero time-averaged value of pressure is of second order, which is low, causing particles to mainly exhibit harmonic fluctuating motion. On the other hand, due to the continuity of fluid motion, acoustic streaming can produce directional flow that spans multiple pressure nodes, driving continuous particle motion [91,92]. This continuity also allows for acoustic streaming to extend over a longer range or to change direction [93,94], forming circulating flows or vortices [95]. ...
... ARF is a sort of mechanical force that can be generated by the focused ultrasound, which, when applied to the biological tissue, would cause low-frequency micrometer-scale displacement for the dynamic scatterers. 53,54 The displacement field generated by the ARF is shown to be unipolar and concentrated near the focal point. 55 On the other hand, DCS is an ideal modality that uses the diffused light to assess the scatterer motions enhanced by ARF. ...
In field of diffuse optics for biomedical applications, the spatial sensitivity (SS) is a key parameter to evaluate or optimize the adopted modalities, such as penetration depth, signal-to-noise ratio as well as sensor distribution. Nevertheless, SS is usually estimated via computer simulations (e.g., photon Monte Carlo simulation), rather than being quantified experimentally, due to the technical difficulty. In this study, we report the experimental measurement and visualization of optical SS through combination of acoustic radiation force (ARF) and the scanning diffuse correlation spectroscopy (DCS). By spatially varying the location of ARF focal spot within liquid phantom, the enhanced particle flow, which represents the most spatial sensitive location, was identified by DCS. The experimental outcomes were cross-validated with the photon Monte Carlo simulation, thus demonstrating its accuracy, feasibility, and potential for guiding clinical usage.
... Alternatively, optical methods could offer an approach to measure the stiffness of tissues, meanwhile providing additional optical information about the tissue, such as light absorption and scattering, which is associated with impedance is mismatches, ultrasound intensity will be attenuated. This phenomenon is caused by the momentum transfer between the acoustic wave and the medium, inducing resonance at a low frequency within the medium and thereby the acoustic radiation force (ARF) [39,40]. As for the focused ultrasound, a few studies have demonstrated that the medium motion caused by the ARF is primarily concentrated near the focal spot, at dimensions ranging from nanometers to micrometers [41]. ...
Many diseases, such as inflammation, dropsy, or tumors, often cause alterations in the mechanical stiffness of human tissues. Ultrasound-based techniques are commonly adopted in clinics for stiffness assessment, whereas optical methodologies hold promise for sensing strain changes and providing optical information pertaining to the microcirculatory network, thereby facilitating comprehensive measurements of tissue physiopathology. Diffuse correlation spectroscopy (DCS), an emerging dynamic light scattering technique, has been used to capture the enhanced motion of light scatterers induced by acoustic radiation force (ARF). Theoretically, the amplitude of this enhanced scatterers motion is related to the medium stiffness. Based on this relationship, we report a light coherent technique that combines ARF and DCS to qualitatively evaluate changes in the stiffness of medium. We experimentally demonstrate the accuracy and feasibility of this technique for probing stiffness in homogeneous phantom by comparing it with independent ultrasound methods. Additionally, we explore a potential application of this technique in distinguishing between fluid filled lesion and homogeneous tissue through heterogeneous phantom experiments. This unique combination of ARF and DCS, namely, acoustomotive DCS (AM-DCS), would provide an alternative way to measure particle-motion related stiffness, thereby assisting in the diagnosis and treatment of diseases.
... The acoustic approach, as an active method in microfluidic centrifugation, offers a highly efficient and flexible solution to the challenge of vortex generation at the microfluidic scale [18]. It boasts several advantages, such as non-invasive biocompatibility, precise control through multi-parameter adjustments, strong penetration, compatibility with various microfluidic control materials, and highly localized generation of acoustic streaming [19][20][21][22][23].Due to the transferability of vibrations, various waveguides [24] and acoustic black hole effects [25] can be combined to further generate acoustic fluid effects with multiple modes through wave modulation. ...
The µTAS/LOC, a highly integrated microsystem, consolidates multiple bioanalytical functions within a single chip, enhancing efficiency and precision in bioanalysis and biomedical operations. Microfluidic centrifugation, a key component of LOC devices, enables rapid capture and enrichment of tiny objects in samples, improving sensitivity and accuracy of detection and diagnosis. However, microfluidic systems face challenges due to viscosity dominance and difficulty in vortex formation. Acoustic-based centrifugation, particularly those using surface acoustic waves (SAWs), have shown promise in applications such as particle concentration, separation, and droplet mixing. However, challenges include accurate droplet placement, energy loss from off-axis positioning, and limited energy transfer from low-frequency SAW resonators, restricting centrifugal speed and sample volume. In this work, we introduce a novel ring array composed of eight Lamb wave resonators (LWRs), forming an Ultra-Fast Centrifuge Tunnel (UFCT) in a microfluidic system. The UFCT eliminates secondary vortices, concentrating energy in the main vortex and maximizing acoustic-to-streaming energy conversion. It enables ultra-fast centrifugation with a larger liquid capacity (50 μL), reduced power usage (50 mW) that is one order of magnitude smaller than existing devices, and greater linear speed (62 mm/s), surpassing the limitations of prior methods. We demonstrate successful high-fold enrichment of 2 μm and 10 μm particles and explore the UFCT’s potential in tissue engineering by encapsulating cells in a hydrogel-based micro-organ with a ring structure, which is of great significance for building more complex manipulation platforms for particles and cells in a bio-compatible and contactless manner.
... In some scenarios, when acoustic waves propagate in a fluid medium, it causes the fluid to undergo stable flow motion, that is, acoustic streaming [21][22][23][24][25]. In the acoustofluidic field, the forces acting on particles' movement mainly come from the interaction between acoustic waves and the streaming. ...
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.
... Acoustofluidics focuses on phenomena and physics of acoustic waves interacting with fluid medium (either in sessile droplets or micro-channels), including state-of-the-art applications in diagnostic systems [1,2], bioanalytical chemistry and biomedical technology [3,4]. Acoustofluidics has already drawn widespread attention of scientists from all over the world in recent years and has been increasingly used in many frontier fields such as life science [5] and advanced manufacturing [6]. ...
In this study, a series of Sierpiński-type structural plates have been artificially introduced to generate diversified acoustofluidic distributions in the originally-static microfluidic chambers, which are stimulated under the oscillation of incident acoustic waves at different input frequency points. The complicated interactions between quasi/pseudo-Sierpiński-carpet shaped structural plates and incident ultrasonic waves, including acoustic reflection and diffraction, can initiate sophisticated spatio-temporal discrepancies along the sound propagation path and induce heterogeneous acoustic streaming vortices. In comparison with the existing construction strategies of microfluidic lab-on-a-chip devices, the introduction of fractalized elements like quasi/pseudo-Sierpiński-carpet shaped structural components can provide remarkable insights and expand application scenarios of unconventional acoustofluidic approaches, which is conducive to driving ultrasonic micro/nano manipulation technology from monotonousness to diversification. The preliminary research demonstrates the feasibility of considering Sierpiński-type structural features as tunable ingredients to customize acoustofluidic apparatuses for the exploration of topographical manipulation of micro/nano-scale particles and orientational operation of biological specimens.
... In microfluidic systems, acoustic streaming can be used to generate and control flow patterns, and manipulate particulate matters, including particles, cells, bubbles, and droplets. The acoustic techniques have been also widely utilized for lab-on-a-chip applications for cell sorting and separation, and chemical synthesis [106]. Acoustic waves can be used to levitate small particles and droplets in a fluid by producing an ARF [100]. ...
... 86 The sample solution is subjected to acoustic streaming effects when acoustic waves are applied, allowing the acoustic radiation force and acoustic drag force to act on particles. [91][92][93] Nanostructures such as microtips, microcolumns, and filter membranes have been paired with acoustic waves to achieve EV separation functionality. Chen et al. 94 developed an ultrafast EV separation device called EXO-DUS by combining piezoelectric transducers (PZTs) with porous alumina (AAO) membranes. ...
Extracellular vesicles (EVs) have recently attracted significant research attention owing to their important biological functions, including cell-to-cell communication. EVs are a type of membrane vesicles that are secreted into the extracellular space by most types of cells. Several biological biomolecules found in EVs, such as proteins, microRNA, and DNA, are closely related to the pathogenesis of human malignancies, making EVs valuable biomarkers for disease diagnosis, treatment, and prognosis. Therefore, EV separation and detection are prerequisites for providing important information for clinical research. Conventional separation methods suffer from low levels of purity, as well as the need for cumbersome and prolonged operations. Moreover, detection methods require trained operators and present challenges such as high operational expenses and low sensitivity and specificity. In the past decade, platforms for EV separation and detection based on nanostructures have emerged. This article reviews recent advances in nanostructure-based EV separation and detection techniques. First, nanostructures based on membranes, nanowires, nanoscale deterministic lateral displacement, and surface modification are presented. Second, high-throughput separation of EVs based on nanostructures combined with acoustic and electric fields is described. Third, techniques combining nanostructures with immunofluorescence, surface plasmon resonance, surface-enhanced Raman scattering, electrochemical detection, or piezoelectric sensors for high-precision EV analysis are summarized. Finally, the potential of nanostructures to detect individual EVs is explored, with the aim of providing insights into the further development of nanostructure-based EV separation and detection techniques.
... By integrating the acoustic device with the micro-channel, the sound waves generated by devices suffer energy dissipation when crossing the solid-liquid interface, which drives local and highly controllable streaming, named acoustic streaming (AS). This kind of AS is superior in solution mixing and pumping, which has been successfully implemented in microfluidic and applied for sample separation, concentration and manipulation [26][27][28]. However, besides these biological and chemical analysis applications, few studies have been devoted to on chip surface modification and analysis applications [29,30]. ...
Developing effective strategies for the flexible control of fluid is vital for microfluidic electrochemical biosensing. In this study, a gigahertz (GHz) acoustic streaming (AS) based sonoelectrochemical system was developed to realize an on-chip surface modification and sensitive hydrogen peroxide (H2O2) detection from living cells. The flexible and controlled fluid surrounding the electrochemical chip was optimized theoretically and applied in the sonoelectrochemical deposition of Au nanoparticles (AuNPs) first. Under the steady and fast flow stimulus of AS, AuNPs could be synthesized with a smaller and evener size distribution than the normal condition, allowing AuNPs to show an excellent peroxidase-like activity. Moreover, the AS also accelerated the mass transport of target molecules and improved the catalytic rate, leading to the enhancement of H2O2 detection, with an extremely low detection limit of 32 nM and a high sensitivity of 4.34 μA/ (mM·mm²). Finally, this system was successfully applied in tracking H2O2 release from different cell lines to distinguish the cancer cells from normal cells. This study innovatively integrated the surface modification and molecules detection process on a chip, and also proposed a simple but sensitive platform for microfluidic biosensing application.
... The Rayleigh-Schlichting streaming is induced by the boundary-driven streaming resulting from the wave attenuation near the no-slip solid boundary regime. The boundary streaming within the viscous boundary layer induces counter-rotating flow in the outer boundary region, consecutively resulting in periodic patterns of micro-vortices within the fluid [28]. These micro-vortices of acoustic streaming require high power consumption as the loss of acoustic energy is relatively greater near the viscous boundary, and the vortex regime is small, typically less than the acoustic wavelength, which could be unfavorable for fluid mixing [23,29]. ...
Ultrasonic surface acoustic wave (SAW)-induced acoustic streaming flow (ASF) has been utilized for microfluidic flow control, patterning, and mixing. Most previous research employed cross-type SAW acousto-microfluidic mixers, in which the SAWs propagated perpendicular to the flow direction. In this configuration, the flow mixing was induced predominantly by the horizontal component of the acoustic force, which was usually much smaller than the vertical component, leading to energy inefficiency and limited controllability. Here, we propose a vertical-type ultrasonic SAW acousto-microfluidic mixer to achieve rapid flow mixing with improved efficiency and controllability. We conducted in-depth numerical and experimental investigations of the vertical-type SAW-induced ASF to elucidate the acousto-hydrodynamic phenomenon under varying conditions of total flow rate, acoustic wave amplitude, and fluid viscosity conditions. We conducted computational fluid dynamics simulations for numerical flow visualization and utilized micro-prism-embedded microchannels for experimental flow visualization for the vertical SAW-induced ASF. We found that the SAW-induced vortices served as a hydrodynamic barrier for the co-flow streams for controlled flow mixing in the proposed device. For proof-of-concept application, we performed chemical additive-free rapid red blood cell lysis and achieved rapid cell lysis with high lysis efficiency based on the physical interactions of the suspended cells with the SAW-induced acoustic vortical flows. We believe that the proposed vertical-type ultrasonic SAW-based mixer can be broadly utilized for various microfluidic applications that require rapid, controlled flow mixing.
... The prediction model of the acoustic streaming with flow velocity and flow field morphology should be established, and the movement behavior of objects within complex flow fields should be analyzed. 6 Due to the difficulty and complexity of obtaining the 3D acoustic streaming flow field through experiments, numerical simulation methods have received widespread attention in order to obtain comprehensive flow field information. The method based on the spatial variation of the Reynolds stress for deriving the driving force of the acoustic streaming that can efficiently calculate the inside and outside the boundary layer is widely used in the simulation of acoustic streaming in 2D cross sections under traveling and standing acoustic waves. ...
As an effective tool for contactless manipulation of submicrometer scale objects, the controllability of acoustic streaming velocity and flow field morphology determines the accuracy of object migration and the completeness of three dimensional (3D) imaging. This paper proposes an equivalent acoustic streaming driving force model that is applicable to both two dimensional (2D) and 3D calculations and constructs a numerical method for submicrometer microsphere migration and rotation velocity in acoustic streaming. The results show that the relationship between the peripheral vortex size Lp/wc and the relative acoustic streaming velocity vas/vf satisfies Lp/wc = 0.125vas/vf0.36 under certain geometrical conditions. Reducing the spatial confinement and increasing the inter-vortex distance will increase the energy release efficiency, reduce the pressure gradient distribution and convective dissipation rates, increase the vortex intensity and radiation range, and consequently, increase the vortex characteristic size. In complex 3D vortex flow fields, suspended objects are affected by velocity distributions and exhibit motions such as cross-flow lines and rotation. For larger vortex structure sizes, full 3D imaging is more favorable due to the increased rotation speed and period of motion along the orbit of the submicrometer microspheres. This study helps us to reveal the modulation mechanism of acoustic streaming field flow characteristics, enrich the basic theory of alternating orbital motion and forces on objects in vortex structures, and provide guidance for acoustic flow-based contactless object manipulation.
Acoustic microfluidic is an important technology in particle manipulations in biomedical analyses and detections. However, the particle-movement manipulations achieved by the standing surface acoustic wave is suitable for particles in a thin layer of fluids, however it is difficult to manipulate particles in deeper solutions due to the energy loss of surface acoustic waves. The traditional standing bulk wave method can realize the particle manipulation in deep solutions, but it cannot work properly for particle manipulation within a long distance due to the energy loss. In this work, the topological rainbow defect-state trapping is realized, the results show that an effect of point accumulation of acoustic pressure in the waveguide path exists, the position of maximum acoustic pressure can be adjusted flexibly by changing the frequency of the incident acoustic wave, based on which, long-distance movement and capture manipulations of particles in deep solution have been realized. The phenomenon presented in this work can provide a reliable method for manipulations of continuous long-distance particle movement and capture to meet the demand of multiple processing steps in biochemical analyses and detections. The experiment verification results will be presented in the near future.
Background: Cutaneous leishmaniasis is one of the endemic diseases in Iraq. Both types of cutaneous leishmaniasis that cause different ulcers are present, namely Leishmania major and Leishmania tropica, The disease also represents a major public and global health problem all over the world, objective: Investigation of the relationship between parasitic infection with cutaneous leishmaniasis and some antioxidants Superoxide, Nitric oxide and immune cytokines tumor necrosis factor-alpha, Interferon-gamma. Materials and Methods: The demographic and epidemiological study included 55 cases suspected of being infected with cutaneous leishmaniasis. They visited Ramadi Teaching Hospital, with 25 volunteers. After obtaining their consent, they were used as control samples, where blood serum samples were obtained from both study groups. After that, work was done in laboratories. Department of Biology-College of Education for Pure Sciences-Anbar University. Results: The patients and healthy people were of different genders, and among the 55 samples from the infected, the number of males was 36 (65.5)% and females 19 (34.5)%, with statistically significant differences p<0.05, and the age groups of the patients were from one year to 60 years. With an average age of (31 years), they were distributed into 6 groups. Also, among the 25 samples from the control group, the number of males was 12 (48%) and females were 13 (52%), Their ages also ranged from one year to 60 years, with an average age of (13) years, the enzyme-linked immunoabsorbent assay (ELISA) technique was used to detect the level of immunological indicators TNF-α, IFN-γ, SOD, NO, where the results showed High levels in the serum of cutaneous leishmaniasis patients (120.00 ± 52.11, 123.00 ± 44.21, 3.10 ± 1.21 and 121.93 ± 33.22), respectively compared to healthy subjects (72.86 ± 14.94, 21.91 ± 45.40, 0.88 ± 0.12, and 81.46 ± 4.50) respectively With statistically significant differences at the level of p < 0.05, p < 0.001. Conclusions: The inflammatory cytokines TNF-α, IFN-γ play a vital role in increasing or decreasing the severity in the pathogenesis of the disease and eliminating it.
The rapid and accurate analysis of micro-samples is a crucial foundation for precision medicine, particularly for early screening and monitoring of cancer, where it holds significant importance. Ultrasound-based multifunctional biocompatible manipulation techniques have been extensively applied in a variety of biomedical fields, providing insights for the development of rapid, cost-effective, and accurate biomarker detection strategies. In this chapter, we combine ultrasound-based gradient pressure fields with functionalized microsphere enrichment to develop a biosensing method for ultra-trace miRNA enrichment in nanoliter samples without PCR. This system relies on inexpensive capillaries, enabling simultaneous visual imaging and trace sample detection.
We investigate the effect of ultrasound on the evaporation and crystallization of sessile NaCl solution droplets which were positioned in traveling or standing wave ultrasound field. The experimental results indicated that the ultrasound field can significantly accelerate the evaporation rate of the sessile droplets and refine the crystal grains. By adjusting the distance between the sessile droplets and the ultrasound emitter, it is found that, in traveling wave ultrasound field, the sessile droplet evaporation time and the time for the appearance of NaCl grains exhibited a fluctuating increase as the droplet-emitter distance increased. While in the standing wave ultrasound, the sessile droplet evaporation rate increases with the increasing droplet-emitter distance. Overall, the traveling wave ultrasound field has a stronger effect on grain refinement of the sessile droplets than the standing wave ultrasound field. The grain refinement is attributed to the decrease of critical nucleation radius caused by ultrasound energy and the increase of the nucleation rate caused by the accelerated evaporation rate. In addition, the breakage of grains caused by ultrasonic cavitation would also lead to grain refinement.
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.
Liposomes have garnered significant attention owing to their favorable characteristics as promising carriers. Microfluidic based hydrodynamic flow focusing, or micro-mixing approaches enable precise control of liposome size during their synthesis...
Gigahertz acoustic streaming enables the synthesis of localized microjets reaching speeds of up to meters per second, offering tremendous potential for precision micromanipulation. However, theoretical and numerical investigations of acoustic streaming at these frequencies remain so far relatively scarce due to significant challenges including: (i) the inappropriateness of classical approaches, rooted in asymptotic development, for addressing high-speed streaming with flow velocities comparable to the acoustic velocity; and (ii) the numerical cost of direct numerical simulations generally considered as prohibitive. In this paper, we investigate high-frequency bulk streaming using high-order finite difference direct numerical simulations. First, we demonstrate that high-speed micrometric jets of several meters per second can only be obtained at high frequencies, due to diffraction limits. Second, we establish that the maximum jet streaming speed at a given actuation power scales with the frequency to the power of 3/2 in the low attenuation limit and linearly with the frequency for strongly attenuated waves. Last, our analysis of transient regimes reveals a dramatic reduction in the time required to reach the maximum velocity as the frequency increases (power law in –5/2), leading to characteristic time on the order of μs at gigahertz frequencies, and hence accelerations within the Mega-g range.
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.
This research developed a high-frequency, high-power ultrasonic transducer. Operating at 1.54 MHz, the transducer generated plane waves through the excitation of the thickness mode of a piezoelectric ring. These waves are subsequently focused by a parabolic reflector, exciting the bending mode of a circular plate and yielding substantial mechanical output at the center. Under a driving voltage of 48 Vpp, the transducer achieved a saturation velocity of 11.7 mpp/s. The mechanical quality factor (Q_m) of the resonant mode is calculated using the half-power bandwidth method, resulting in a value of approximately 1250. The proposed transducer exhibits outstanding performance and holds promising applications in the fields of biology, medicine, and sonochemistry.
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.
The generation and dispensing of microdroplets is a vital process in various fields such as biomedicine, medical diagnosis and chemistry. However, most methods still require the structures of nozzles or microchannels to assist droplet generation, which leads to limitations on system flexibility and restrictions on the size range of the generated droplets. In this paper, we propose a nozzle-free acoustic-based method for generating droplets using a gigahertz (GHz) bulk acoustic wave (BAW). Unlike most of the acoustofluidic approaches, the proposed method produces the droplet by pinching-off the liquid column generated by the acoustic body force at the oil-water interface. Benefitting from the focused acoustic energy and small footprint of the device, four orders of magnitude (ranging from 2 μm to 1800 μm) of droplet size could be produced by controlling the working time and power of the device. We also demonstrated cell encapsulation in the droplet and a high cell viability was achieved. The proposed acoustic-based droplet generation method exhibits capacity for generating droplets with a wide size range, versatility toward different viscosities, as well as biocompatibility for handling viable samples, which shows potential in miniaturization and scalability.
Acoustofluidic systems often employ prefabricated acoustic scatterers that perturb the imposed acoustic field to realize the acoustophoresis of immersed microparticles. We present a numerical study to investigate the time-averaged streaming and radiation force fields around a scatterer. Based on the streaming and radiation force field, we obtain the trajectories of the immersed microparticles with varying sizes and identify a critical transition size at which the motion of immersed microparticles in the vicinity of a prefabricated scatterer shifts from being streaming dominated to radiation dominated. We consider a range of acoustic frequencies to reveal that the critical transition size decreases with increasing frequency; this result explains the choice of acoustic frequencies in previously reported experimental studies. We also examine the impact of scatterer material and fluid properties on the streaming and radiation force fields, as well as on the critical transition size. Our results demonstrate that the critical transition size decreases with an increase in acoustic contrast factor: a nondimensional quantity that depends on material properties of the scatterer and the fluid. Our results provide a pathway to realize radiation force based manipulation of small particles by increasing the acoustic contrast factor of the scatterer, lowering the kinematic viscosity of the fluid, and increasing the acoustic frequency.
Trace biological sample detection is critical for the analysis of pathologies in biomedicine. Integration of microfluidic manipulation techniques typically strengthens biosensing performance. For instance, using isothermal amplification reactions to sense trace miRNA in peripheral circulation lacks a sufficiently complex pretreatment process that limits the sensitivity of on-chip detection. Herein we propose an orthogonal tunable acoustic tweezer (OTAT) to simultaneously actuate the transportation and centrifugation of μ-droplets on a single device. The OTAT enables diversified modes of droplet transportation such as unidirectional transport, multi-direction transport, round-trip transport, tilt angle movement, multi-droplet fusion, and continuous centrifugation of the dynamic droplets simultaneously. The multiplicity of modalities enables the focusing of a loaded analyte at the center of the droplet or constant rotation about the center axis of the droplet. We herein demonstrate the OTAT's ability to actuate transportation, fusion, and centrifugation-based pretreatment of two biological sample droplets loaded with miRNA biomarkers and multiple mixtures, as well as facilitating the increase of fluorescence detection sensitivity by an order of magnitude compared to traditional tube reaction methods. The results herein demonstrate the OTAT-based droplet acoustofluidic platform's ability to combine a wide range of biosensing mechanisms and provide a higher accuracy of detection for one-stop point-of-care disease diagnosis.
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 acoustoflu-idic 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.
Interdigitated transducers (IDTs) were originally designed as delay lines for radars. Half a century later, they have found new life as actuators for microfluidic systems. By generating strong acoustic fields, they trigger nonlinear effects that enable pumping and mixing of fluids, and moving particles without contact. However, the transition from signal processing to actuators comes with a range of challenges concerning power density and spatial resolution that have spurred exciting developments in solid-state acoustics and especially in IDT design. Assuming some familiarity with acoustofluidics, this paper aims to provide a tutorial for IDT design and characterization for the purpose of acoustofluidic actuation. It is targeted at a diverse audience of researchers in various fields, including fluid mechanics, acoustics, and microelectronics.
At the single-cell level, cellular parameters, gene expression and cellular function are assayed on an individual but not population-average basis. Essential to observing and analyzing the heterogeneity and behavior of these cells/clusters is the ability to prepare and manipulate individuals. Here, we demonstrate a versatile microsystem, a stereo acoustic streaming tunnel, which is triggered by ultrahigh-frequency bulk acoustic waves and highly confined by a microchannel. We thoroughly analyze the generation and features of stereo acoustic streaming to develop a virtual tunnel for observation, pretreatment and analysis of cells for different single-cell applications. 3D reconstruction, dissociation of clusters, selective trapping/release, in situ analysis and pairing of single cells with barcode gel beads were demonstrated. To further verify the reliability and robustness of this technology in complex biosamples, the separation of circulating tumor cells from undiluted blood based on properties of both physics and immunity was achieved. With the rich selection of handling modes, the platform has the potential to be a full-process microsystem, from pretreatment to analysis, and used in numerous fields, such as in vitro diagnosis, high-throughput single-cell sequencing and drug development.
The transport, enrichment, and purification of nanoparticles are fundamental activities in the fields of biology, chemistry, material science, and medicine. Here, we demonstrate an approach for manipulating nanospecimens in which a virtual channel with a diameter that can be spontaneously self-adjusted from dozens to a few micrometers based on the concentration of samples is formed by acoustic waves and streams that are triggered and stabilized by a gigahertz bulk acoustic resonator and microfluidics, respectively. By combining a specially designed arc-shaped resonator and lateral flow, the in situ enrichment, focusing, displacement, and continuous size-based separation of nanoparticles were achieved, with the ability to capture 30-nm polystyrene nanoparticles and continuously focus 150-nm polystyrene nanoparticles. Furthermore, exosome separation was also demonstrated. This technology overcomes the limitation of continuously manipulating particles under 200 nm and has the potential to be useful for a wide range of applications in chemistry, life sciences, and medicine.
Contactless acoustic manipulation of micro/nanoscale particles has attracted considerable attention owing to its near independence of the physical and chemical properties of the targets, making it universally applicable to almost all biological systems. Thin-film bulk acoustic wave (BAW) resonators operating at gigahertz (GHz) frequencies have been demonstrated to generate localized high-speed microvortices through acoustic streaming effects. Benefitting from the strong drag forces of the high-speed vortices, BAW-enabled GHz acoustic streaming tweezers (AST) have been applied to the trapping and enrichment of particles ranging in size from micrometers to less than 100 nm. However, the behavior of particles in such 3D microvortex systems is still largely unknown. In this work, the particle behavior (trapping, enrichment, and separation) in GHz AST is studied by theoretical analyses, 3D simulations, and microparticle tracking experiments. It is found that the particle motion in the vortices is determined mainly by the balance between the acoustic streaming drag force and the acoustic radiation force. This work can provide basic design principles for AST-based lab-on-a-chip systems for a variety of applications.
This paper demonstrates that surface acoustic wave (SAW) atomization can produce suitable aerosol concentration and size distribution for efficient inhaled lung drug delivery and is a potential atomization device for asthma treatment. Using the SAW device, we present comprehensive experimental results exploring the complexity of the acoustic atomization process and the influence of input power, device frequency, and liquid flow rate on aerosol size distribution. It is hoped that these studies will explain the mechanism of SAW atomization aerosol generation and how they can be controlled. The insights from the high-speed flow visualization studies reveal that it is possible by setting the input power above 4.17 W, thus allowing atomization to occur from a relatively thin film, forming dense, monodisperse aerosols. Moreover, we found that the aerosol droplet size can be effectively changed by adjusting the input power and liquid flow rate to change the film conditions. In this work, we proposed a method to realize drug atomization by a microfluidic channel. A SU-8 flow channel was prepared on the surface of a piezoelectric substrate by photolithography technology. Combined with the silicon dioxide coating process and PDMS process closed microfluidic channel was prepared, and continuous drug atomization was provided to improve the deposition efficiency of drug atomization by microfluidic.
Acoustic black holes offer superior capabilities for slowing down and trapping acoustic waves for various applications such as metastructures, energy harvesting, and vibration and noise control. However, no studies have considered the linear and nonlinear effects of acoustic black holes on micro/nanoparticles in fluids. This study presents acoustofluidic black holes (AFBHs) that leverage controlled interactions between AFBH-trapped acoustic wave energy and particles in droplets to enable versatile particle manipulation functionalities, such as translation, concentration, and patterning of particles. We investigated the AFBH-enabled wave energy trapping and wavelength shrinking effects, as well as the trapped wave energy–induced acoustic radiation forces on particles and acoustic streaming in droplets. This study not only fills the gap between the emerging fields of acoustofluidics and acoustic black holes but also leads to a class of AFBH-based in-droplet particle manipulation toolsets with great potential for many applications, such as biosensing, point-of-care testing, and drug screening.
Acoustic manipulation of microparticles and cells has attracted growing interest in biomedical applications. In particular, the use of acoustic waves to concentrate particles plays an important role in enhancing the detection process by biosensors. Here, we demonstrated microparticle concentration within sessile droplets placed on the hydrophobic surface using the flexural wave. The design benefits from streaming flow induced by the Lamb wave propagated in the glass waveguide to manipulate particles in the droplets. Microparticles will be concentrated at the central area of the droplet adhesion plane based on the balance among the streaming drag force, gravity, and buoyancy at the operating frequency. We experimentally demonstrated the concentration of particles of various sizes and tumor cells. Using numerical simulation, we predicted the acoustic pressure and streaming flow pattern within the droplet and characterized the underlying physical mechanisms for particle motion. The design is more suitable for micron-sized particle preparation, and it can be valuable for various biological, chemical, and medical applications.
Separation of micro- and nano-sized biological particles, such as cells, proteins, and nucleotides, is at the heart of most biochemical sensing/analysis, including in vitro biosensing, diagnostics, drug development, proteomics, and genomics. However, most of the conventional particle separation techniques are based on membrane filtration techniques, whose efficiency is limited by membrane characteristics, such as pore size, porosity, surface charge density, or biocompatibility, which results in a reduction in the separation efficiency of bioparticles of various sizes and types. In addition, since other conventional separation methods, such as centrifugation, chromatography, and precipitation, are difficult to perform in a continuous manner, requiring multiple preparation steps with a relatively large minimum sample volume is necessary for stable bioprocessing. Recently, microfluidic engineering enables more efficient separation in a continuous flow with rapid processing of small volumes of rare biological samples, such as DNA, proteins, viruses, exosomes, and even cells. In this paper, we present a comprehensive review of the recent advances in microfluidic separation of micro-/nano-sized bioparticles by summarizing the physical principles behind the separation system and practical examples of biomedical applications.
Acoustophoretic microfluidic devices have been developed for accurate, label-free, contactless, and non-invasive manipulation of bioparticles in different biofluids. However, their widespread application is limited due to the need for the use of high quality microchannels made of materials with high specific acoustic impedances relative to the fluid (e.g., silicon or glass with small damping coefficient), manufactured by complex and expensive microfabrication processes. Soft polymers with a lower fabrication cost have been introduced to address the challenges of silicon- or glass-based acoustophoretic microfluidic systems. However, due to their small acoustic impedance, their efficacy for particle manipulation is shown to be limited. Here, we developed a new acoustophoretic microfluid system fabricated by a hybrid sound-hard (aluminum) and sound-soft (polydimethylsiloxane polymer) material. The performance of this hybrid device for manipulation of bead particles and cells was compared to the acoustophoretic devices made of acoustically hard materials. The results show that particles and cells in the hybrid material microchannel travel to a nodal plane with a much smaller energy density than conventional acoustic-hard devices but greater than polymeric microfluidic chips. Against conventional acoustic-hard chips, the nodal line in the hybrid microchannel could be easily tuned to be placed in an off-center position by changing the frequency, effective for particle separation from a host fluid in parallel flow stream models. It is also shown that the hybrid acoustophoretic device deals with smaller temperature rise which is safer for the actuation of bioparticles. This new device eliminates the limitations of each sound-soft and sound-hard materials in terms of cost, adjusting the position of nodal plane, temperature rise, fragility, production cost and disposability, making it desirable for developing the next generation of economically viable acoustophoretic products for ultrasound particle manipulation in bioengineering applications.
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.
A high‐throughput non‐viral intracellular delivery platform is introduced for the transfection of large cargos with dosage‐control. This platform, termed Acoustic‐Electric Shear Orbiting Poration (AESOP), optimizes the delivery of intended cargo sizes with poration of the cell membranes via mechanical shear followed by the modulated expansion of these nanopores via electric field. Furthermore, AESOP utilizes acoustic microstreaming vortices wherein up to millions of cells are trapped and mixed uniformly with exogenous cargos, enabling the delivery of cargos into cells with targeted dosages. Intracellular delivery of a wide range of molecule sizes (<1 kDa to 2 MDa) with high efficiency (>90%), cell viability (>80%), and uniform dosages (<60% coefficient of variation (CV)) simultaneously into 1 million cells min⁻¹ per single chip is demonstrated. AESOP is successfully applied to two gene editing applications that require the delivery of large plasmids: i) enhanced green fluorescent protein (eGFP) plasmid (6.1 kbp) transfection, and ii) clustered regularly interspaced short palindromic repeats (CRISPR)‐Cas9‐mediated gene knockout using a 9.3 kbp plasmid DNA encoding Cas9 protein and single guide RNA (sgRNA). Compared to alternative platforms, this platform offers dosage‐controlled intracellular delivery of large plasmids simultaneously to large populations of cells while maintaining cell viability at comparable delivery efficiencies.
Radiation force is a universal phenomenon in any wave motion where the wave energy produces a static or transient force on the propagation medium. The theory of acoustic radiation force (ARF) dates back to the early 19th century. In recent years, there has been an increasing interest in the biomedical applications of ARF. Following a brief history of acoustic radiation force, this paper describes a concise theory of ARF under four physical mechanisms of radiation force generation in tissue-like media. These mechanisms are primarily based on the dissipation of acoustic energy of propagating waves, the reflection of the incident wave, gradients of the compressional wave speeds, and the spatial variations of energy density in standing acoustic waves. Examples describing some of the practical applications of ARF under each mechanism are presented. This paper concludes with a discussion on selected ideas for potential future applications of ARF in biomedicine.
Precise manipulations for micro/nano targets of synthetic particles and bio‐cells hold great promise for the next generation of nano robotic systems and micro‐machines. Although considerable efforts have been devoted to developing propulsion protocols for micro/nano‐manipulation, the limited intelligence without effective control for current microrobots prohibits them away from most sophisticated applications. Here, a novel approach integrating the vision feedback control (VFC) is presented into a microrobotic platform powered by acoustic fields to accomplish autonomous targets identification and optimization of the locomotion resolution. Driven by local enhanced acoustic streaming, microparticles in the vicinity of the linear manipulator could be transported along the given pathway. Via vision feedback control, the targets of microparticles are automatically recognized in the acousto‐microrobotic interface and driven toward the exact user‐defined destinations. The VFC integrated interface is also adoptable to multiple particle manipulations, where each particle is distinguished with unique index numbers for a convenient on‐demand selection. At last, this closed‐loop interface is validated to control the motion of bio‐cells, illustrating the good robustness and biological compatibility. The VFC based control strategy for acousto‐microrobotic interface is featured with favorable controllability and thus will have great potentials in myriad scenarios for smart micro/nano systems.
Here, we present a novel approach for the transient permeabilization of cells. We combined laminar shear flow in a microchannel with chaotic advection employing surface acoustic waves. First, as a fundamental result on the one hand, and as a kind of reference measurement for the more complex acoustofluidic approach on the other hand, we studied the permeabilization of cells in pure shear flow in a microchannel with Y-geometry. As a proof of principle, we used fluorescent dyes as model drugs and investigated their internalization into HeLa cells. We found that drug uptake scaled non-linearly with flow rate and thus shear stress. For calcein, we obtained a maximal enhancement factor of about 12 at an optimum flow rate of Q = 500 µL/h in the geometry used here compared to static incubation. This result is discussed in the light of structural phase transitions of lipid membranes accompanied by non-linear effects, as the plasma membrane is the main barrier to overcome. Second, we demonstrated the enhanced permeabilization of acoustically trapped cells in surface acoustic wave induced vortices in a microchannel, with an enhancement factor of about 18 compared to quasi-static incubation. Moreover, we optimized the trapping conditions regarding flow rate, the power level of the surface acoustic wave, and trapping time. Finally, we showed that our method is not limited to small molecules but can also be applied to compounds with higher molecular weight.
Surface acoustic waves (SAWs) have the potential to become the basis for a wide gamut of lab-on-a-chips (LoCs). These mechanical waves are among the most promising physics that can be exploited for fulfilling all the requirements of commercially appealing devices that aim to replace-or help-laboratory facilities. These requirements are low processing cost of the devices, scalable production, controllable physics, large flexibility of tasks to perform, easy device miniaturization. To date, SAWs are among the small set of technologies able to both manipulate and analyze biological liquids with high performance. Therefore, they address the main needs of microfluidics and biosensing. To this purpose, the use of high-frequency SAWs is key. In the ultra-high-frequency regime (UHF, 300 MHz - 3 GHz) SAWs exhibit large sensitivities to molecule adsorption and unparalleled fluid manipulation capabilities, together with overall device miniaturization. The UHF-SAW technology is expected to be the realm for the development of complex, reliable, fully automated, high-performance LoCs. In this review, we present the most recent works on UHF-SAWs for microfluidics and biosensing, with particular focus on the LoC application. We derive the relevant scale laws, useful formulas, fabrication guidelines, current limitations of the technology, and future developments.
Traumatic brain injury (TBI) is a global cause of morbidity and mortality. Initial management and risk stratification of patients with TBI is made difficult by the relative insensitivity of screening radiographic studies as well as by the absence of a widely available, noninvasive diagnostic biomarker. In particular, a blood-based biomarker assay could provide a quick and minimally invasive process to stratify risk and guide early management strategies in patients with mild TBI (mTBI). Analysis of circulating exosomes allows the potential for rapid and specific identification of tissue injury. By applying acoustofluidic exosome separation—which uses a combination of microfluidics and acoustics to separate bioparticles based on differences in size and acoustic properties—we successfully isolated exosomes from plasma samples obtained from mice after TBI. Acoustofluidic isolation eliminated interference from other blood components, making it possible to detect exosomal biomarkers for TBI via flow cytometry. Flow cytometry analysis indicated that exosomal biomarkers for TBI increase in the first 24 h following head trauma, indicating the potential of using circulating exosomes for the rapid diagnosis of TBI. Elevated levels of TBI biomarkers were only detected in the samples separated via acoustofluidics; no changes were observed in the analysis of the raw plasma sample. This finding demonstrated the necessity of sample purification prior to exosomal biomarker analysis. Since acoustofluidic exosome separation can easily be integrated with downstream analysis methods, it shows great potential for improving early diagnosis and treatment decisions associated with TBI.
Modern biomedical research and preclinical pharmaceutical development rely heavily on the phenotyping of small vertebrate models for various diseases prior to human testing. In this article, we demonstrate an acoustofluidic rotational tweezing platform that enables contactless, high-speed, 3D multispectral imaging and digital reconstruction of zebrafish larvae for quantitative phenotypic analysis. The acoustic-induced polarized vortex streaming achieves contactless and rapid (~1 s/rotation) rotation of zebrafish larvae. This enables multispectral imaging of the zebrafish body and internal organs from different viewing perspectives. Moreover, we develop a 3D reconstruction pipeline that yields accurate 3D models based on the multi-view images for quantitative evaluation of basic morphological characteristics and advanced combinations of metrics. With its contactless nature and advantages in speed and automation, our acoustofluidic rotational tweezing system has the potential to be a valuable asset in numerous fields, especially for developmental biology, small molecule screening in biochemistry, and pre-clinical drug development in pharmacology.
Acoustics-based tweezers provide a unique toolset for contactless, label-free, and precise manipulation of bioparticles and bioanalytes. Most acoustic tweezers rely on acoustic radiation forces; however, the accompanying acoustic streaming often generates unpredictable effects due to its nonlinear nature and high sensitivity to the three-dimensional boundary conditions. Here, we demonstrate acoustohydrodynamic tweezers, which generate stable, symmetric pairs of vortices to create hydrodynamic traps for object manipulation. These stable vortices enable predictable control of a flow field, which translates into controlled motion of droplets or particles on the operating surface. We built a programmable droplet-handling platform to demonstrate the basic functions of planar-omnidirectional droplet transport, merging droplets, and in situ mixing via a sequential cascade of biochemical reactions. Our acoustohydrodynamic tweezers enables improved control of acoustic streaming and demonstrates a previously unidentified method for contact-free manipulation of bioanalytes and digitalized liquid handling based on a compact and scalable functional unit.
Liquid droplets have been studied for decades and have recently experienced renewed attention as a simplified model for numerous fascinating physical phenomena occurring on size scales from the cell nucleus to stellar black holes. Here, we present an acoustofluidic centrifugation technique that leverages an entanglement of acoustic wave actuation and the spin of a fluidic droplet to enable nanoparticle enrichment and separation. By combining acoustic streaming and droplet spinning, rapid (<1 min) nanoparticle concentration and size-based separation are achieved with a resolution sufficient to identify and isolate exosome subpopulations. The underlying physical mechanisms have been characterized both numerically and experimentally, and the ability to process biological samples (including DNA segments and exosome subpopulations) has been successfully demonstrated. Together, this acoustofluidic centrifuge overcomes existing limitations in the manipulation of nanoscale (<100 nm) bioparticles and can be valuable for various applications in the fields of biology, chemistry, engineering, material science, and medicine.
Acoustic manipulation of submicron particles in a controlled manner has been challenging to date because of the increased contribution of acoustic streaming which leads to fluid mixing and homogenization. This article describes the patterning of submicron particles and the migration of their patterned locations from pressure nodes to antinodes in non-ionic surfactant (Tween 20) aqueous solution at a conventional standing surface acoustic wave field with the wavelength of 150 µm. Phase separation of the aqueous surfactant solution occurs when they are exposed to acoustic waves probably due to the “clouding behavior” of non-ionic surfactant. The generated surfactant precipitates are pushed to the pressure antinodes due to the negative acoustic contrast factor relative to water. Comparing with the mixing appearance in pure water media, acoustic radiation force dominant patterning behavior of submicron particles with a diameter of 300 nm is readily apparent in the aqueous solution with 2% volumetric concentration of Tween 20 surfactant, thanks to the suppression effect of acoustic streaming at inhomogeneous fluids. These submicron particles are first pushed to acoustic pressure nodes and then are migrated to antinodes where the surfactant precipitates stay. More attractively, the migration of acoustically patterned locations is not only limited to submicron particles and it also occurs to micrometer sized particles at solutions with higher surfactant concentrations. These findings open up a novel avenue for the controllable acoustic manipulation.
Hydrodynamic force loading platforms for controllable cell mechanical deformation play an essential role in modern cell technologies. Current systems require assistance from specific microstructures thus limiting the controllability and flexibility in cell shape modulation, and studies on real‐time 3D cell morphology analysis are still absent. This article presents a novel platform based on acoustic streaming generated from a gigahertz device for cell shape control and real‐time cell deformation analysis. Details in cell deformation and the restoration process are thoroughly studied on the platform, and cell behavior control at the microscale is successfully achieved by tuning the treating time, intensity, and wave form of the streaming. The application of this platform in cell membrane permeability modulation and analysis is also exploited. Based on the membrane reorganization during cell deformation, the effects of deformation extent and deformation patterns on membrane permeability to micro‐ and macromolecules are revealed. This technology has shown its unique superiorities in cell mechanical manipulation such as high flexibility, high accuracy, and pure fluid force operation, indicating its promising prospect as a reliable tool for cell property study and drug therapy development.
Extracellular vesicles (EVs) are lipid membrane-enclosed, cell-secreted nanovesicles that have attracted significant attentions in recent years in view of their potential as non-invasive cancer diagnostic biomarkers. However, isolation and analysis of EVs from biofluids remain a challenging field due to their small size, heterogeneous marker expression, and co-existence with non-vesicular contaminants. Microfluidic techniques provide a promising approach for isolating and analyzing EVs with advantages of small sample consumption, precise fluid control, high resolution and yield, short processing time, and cost effectiveness. In this review, we summarize recent efforts in developing label-free and affinity-based microfluidic methods for isolation of EVs according to their physical and biological characteristics, and their applications in cancer diagnostics. We conclude this review with key challenges and directions for microfluidic methods for EV isolation and analysis in clinical settings.
Cellular heterogeneity is prevalent in all cell populations. Single-cell analysis (SCA) could unveil the heterogeneity and thus gain unique insights into complex biological processes. SCA has been widely used in various fields of life sciences and medicine, providing discerning information inaccessible by conventional population-based experiments. In drug development, SCA shows attractive power in revealing the origin of drug resistance, identifying new targets for drug intervention, accelerating the process of drug screening, as well as predicting drug response. In this article, we summarize the major advances in SCA technology and its applications for drug development over the past five years, and discuss the challenges and future research opportunities in this field.
Self-contained microfluidic platforms with on-chip integration of flow control units, microreactors, (bio)sensors, etc. are ideal systems for point-of-care (POC) testing. However, current approaches such as micropumps and microvalves, increase the cost and the control system, and it is rather difficult to integrate into a single chip. Herein, we demonstrated a versatile acoustofluidic platform actuated by a Lamb wave resonator (LWR) array, in which pumping, mixing, fluidic switching, and particle trapping are all achieved on a single chip. The high-speed microscale acoustic streaming triggered by the LWR in the confined microchannel can be utilized to realize a flow resistor and switch. Variable unidirectional pumping was realized by regulating the relative position of the LWR in various custom-designed microfluidic structures and adoption of different geometric parameters for the microchannel. In addition, to realize quantitative biomarker detection, the on-chip flow resistor, micropump, micromixer and particle trapper were also integrated with a CMOS photo sensor and electronic driver circuit, resulting in an automated handheld microfluidic system with no moving parts. Finally, the acoustofluidic platform was tested for prostate-specific antigen (PSA) sensing, which demonstrates the biocompatibility and applied potency of this proposed self-contained system in POC biomedical applications.
Acoustofluidic micromixers have attracted considerable attention in recent years due to their unique features in terms of flexible control, contactless operation, and short mixing distance. However, optimizing geometry in acoustic micromixers to achieve robust mixing performance towards practical chemical engineering is still a great challenge. Herein, we first propose flower-like sharp-edge acoustic micromixers for developing functional 3D ZnO nanorod array. Numerical simulation and experimental validation are conducted to investigate the effect of petal numbers, spreading angles, and tip angles on the mixing performance. Generally, more petals need a larger spreading angle to achieve better mixing while a large spreading angle is unfavorable, and the mixing performance decreases with the increase of tip angles. Compared to single sharp-edge devices, flower-like sharp-edge ones always perform better mixing efficiency. The optimized device is utilized to synthesize well-defined 3D ZnO nanorod array inside a glass capillary and the excellent capabilities of photodegradation of dye and enrichment of heavy metal ions are examined. The photodegradation and enrichment efficiencies can be well regulated by adjusting the flow rates, and superior reusability of the engineered ZnO nanorod array is validated. These results not only provide important guidelines for the rational design of lab-on-a-chip devices, but also shed light on controllable synthesis of functional nanomaterials and other chemical engineering fields.
The behaviours of microparticles inside a sessile droplet actuated by surface acoustic waves (SAWs) were investigated, where the SAWs produced an acoustic streaming flow and imparted an acoustic radiation force on the microparticles. The Rayleigh waves formed by a comb-like interdigital transducer were made to propagate along the surface of a LiNbO3 substrate in order to allow the manipulation of microparticles in a label-free and non-contact manner. Polystyrene microparticles were first employed to describe the behaviours inside a sessile droplet. The influence of the volume of the sessile droplet on the behaviours of the microparticles was examined by changing the contact angle of the droplet. Next, cancer cells were suspended in a sessile droplet, and the influence of contact angle on the behaviours of the cancer cells was investigated. A long gelation time was afforded by using a PEGylated fibrin gel. A primary tumour was mimicked by patterning the cancer cells to be concentrated in the middle of the sessile droplet. The non-contact manipulation property of acoustic waves was indicated to be biocompatible and enabled a structure-free platform configuration. Three-dimensional aggregated culture models were observed to make the cancer cells display an elevated expression of E-cadherin. The efficacy of the anticancer drug tirapazamine increased in the aggregated cancer cells, attributed to the low levels of oxygen in this formation of cancer cells.
Acoustic microreactors that function with acoustics to drive reactant fluids at the microscale make a comprehensive lab-on-a-chip revolution in chemical engineering. Compared to passive microreactors, acoustics-enabled active microreactors offer many outstanding merits such as flexible control, short mixing distance, and intensive reaction kinetics. Herein, we provide an overview of the state-of-the-art of acoustic microreactors for chemical process intensification and reaction engineering. We firstly discuss the established bulk acoustic wave and surface acoustic wave microreactors and highlight their underlying working principles. Next, we present the achievements of acoustic microreactors for the engineering of chemicals and materials from both confined microchannels and sessile microdrops. Finally, we outline emerging challenges and opportunities facing acoustic microfluidics for inspiring future directions in this area. This review article aims not only to elucidate the state-of-the-art acoustic microfluidics for chemical engineering, but also to inspire more advanced lab-on-a-chip systems for facilitating process intensification applications of both scientific and industrial interest.
The development of microfluidic devices for lab-on-a-chip applications has largely been limited by a lack of flexible control and intensive mixing. The fusion of acoustics and microfluidics, termed acoustofluidics, has been demonstrated to be a promising tool for precisely manipulating micro-/nanoscale fluids and objects. When introducing sharp-edges inside the microchannel of acoustofluidic devices, the sound waves can drive highly controllable streaming flows via oscillating these microsolid structures. Considering its precise fluid control, simple device design, greatly reduced reaction duration, contactless operation, and good biocompatibility, sharp-edge acoustofluidics has demonstrated superior on-chip mixing and pumping performance for many application fields. Herein, we provide a comprehensive overview of the research and development of sharp-edge acoustofluidics. In particular, we discuss the design principles and underlying physics of sharp-edges, summarize the existing different types of sharp-edge microreactors (including sidewall wedge, sidewall rod, off-sidewall sharp-edges, and inlet conjunction needle), and highlight established applications of sharp-edge acoustofluidic technology in materials synthesis, bioliquefaction, enzyme bioassay, biomanipulation, and cell lysis. Finally, we point out the current challenges and future directions for inspiring further research in this field. The scope of this work is not only to provide an in-depth understanding of the state-of-the-art sharp-edge acoustofluidics, but also to inspire research efforts on the development of advanced on-chip platforms to satisfy the demanding needs of both academic and industrial communities.
Extracellular vesicles (EVs) represent a promising biomarker source in several medical areas. Flow cytometry (FC) is one of the most widely-used methods to characterize EVs, providing quantitative information and determination of EV subtypes. EV evaluation represents a challenge as no standardized methods are available to facilitate assessment across different research centers. This is principally because their size falls below the detection limit of most standard flow cytometers and a thorough optimization process must be done to ensure instrument-specific sensitivity.
We provide an overview of a standardized method to evaluate large EVs using the Attune™ Nxt Acoustic Focusing Flow Cytometer system (ThermoFisher Scientific).
Increasing the efficiency of aerobic greywater treatment is crucial to ensure that greywater recycling can be effectively implemented in individual and community households. In this work, we demonstrate that exposing greywater samples to low intensity high frequency (MHz-order) surface acoustic waves (SAWs) during the aerobic treatment process can result in increases in the total suspended solids (TSS), chemical oxygen demand (COD) and biochemical oxygen demand (BOD) removal efficiencies by 24%, 24% and 21%, respectively, over a 2 h aerobic digestion period, and up to 37% (TSS removal efficiency) over a 4 h period compared to the unexposed controls. These values are considerably higher than that typically obtained with lower frequency (kHz-order) bulk ultrasound, particularly because the SAW does not cause denaturation of bacteria in the greywater suspension unlike its low frequency counterpart. The SAW enhancement in removal efficiencies can primarily be attributed to the acoustic radiation pressure and acoustic streaming that it generates, which act to efficiently deagglomerate the bacterial flocculates in addition to promoting more uniform mixing of the suspended waste, bacteria and dissolved oxygen in the sample. Also, the results indicate that in the presence of air bubbles in the greywater, the MHz-order SAW treatment remains effective. Additionally, we show that it is possible to further increase the TSS removal efficiency by about twofold through a hybrid process. This ability to significantly accelerate the rate of aerobic digestion to achieve a given removal efficiency level highlights the potential of this novel low-cost technology for improving domestic greywater treatment.
This paper investigates the mechanism of a new acoustic micro-ejector using a Lamb wave transducer array, which can stably generate picoliter (pL) droplet jetting without nozzles. With eight transducers arranged as an octagon array, droplets are ejected based on the mechanism of combined acoustic pressure waves and acoustic streaming. The acoustic focusing area is designed as a line at the liquid center, which is the key factor for a large working range of liquid height. The experimental results show that the ejector can produce uniform water droplets of 22 μm diameter (5.6 pL in volume) continuously at a rate of 0.33 kHz with high ejection stability, owing to a large liquid height window and high acoustic wave frequency. By delivering precise ∼pL droplets without clogging issues, the acoustic ejector has great potential for demanding biochemical applications.
An efficient and accurate antibiotic susceptibility test (AST) is indispensable for measuring the antimicrobial resistance of pathogenic bacteria. A minimal inhibitory concentration (MIC) can be obtained without performing repeated dilutions of the antibiotic by forming a linear antibiotic concentration gradient in a microfluidic channel. We demonstrated a device designed to use travelling surface acoustic waves (TSAWs) to enable a rapid formation of an antibiotic gradient in a few seconds. The TSAWs produced by a focused interdigital transducer deposited on the surface of a piezoelectric (LiNbO3) substrate generated an acoustic streaming flow inside a microfluidic channel, which mixed confluent streams of antibiotics in a controlled fashion. The growth of bacteria exposed to the antibiotic gradient was determined by measuring the MIC, which was used as an indicator of the effectiveness of the AST. The concentration gradient produced using our device was linear, a feature that enhanced the reliability of measurements throughout the microchannel. Two ASTs, namely Pseudomonas aeruginosa against gentamicin and levofloxacin were chosen for the case of slowly proliferating bacteria, and one AST, namely Escherichia coli against gentamicin, were chosen for the rapidly proliferating case. Appropriate antibiotic doses for Pseudomonas aeruginosa and Escherichia coli were each obtained in an efficient manner.
Cell lysis is a crucial process for the detection of intracellular secrets, which is important in various areas, such as biochemical detection, biomechanical analysis and biophysics. Typically, the acoustic method induced cell lysis relies on acoustic cavitation, which requires high acoustic power and may damage the important cell contents, such as DNA, RNA, and mRNA. We introduce herein an efficient microfluidic cell lysis approach based on nanowires collision induced by acoustic streaming using surface acoustic wave in a gentle and controllable manner. The magnetic Ag-nanowires were introduced to the cell suspension, and rotational acoustic streaming induced strong drag and the shear stress result in the collision between the cells and nanowires, leading to the cell lysis. The maximum velocity of the streaming could reach 3 mm/s Cell-lysis was obtained between 10 s, and more than 97 % lysis efficiency was achieved at just 1 W power. The experimental results show that this method has the advantage of high efficiency, very low consumption of power, ultrafast, reusability and tiny sample consumption, also Ni coated Ag-Nanowires provide reusability and highly applicable in point of care diagnostics.
The development of rapid and efficient tools to modulate neurons is vital for the treatment of nervous system diseases. Here, a novel non-invasive neurite outgrowth modulation method based on a controllable acoustic streaming effect induced by an electromechanical gigahertz resonator microchip is reported. The results demonstrate that the gigahertz acoustic streaming can induce cell structure changes within a 10 min period of stimulation, which promotes a high proportion of neurite bearing cells and encourages longer neurite outgrowth. Specifically, the resonator stimulation not only promotes outgrowth of neurites, but also can be combined with chemical mediated methods to accelerate the direct entry of nerve growth factor (NGF) into cells, resulting in higher modulation efficacy. Owing to shear stress caused by the acoustic streaming effect, the resonator microchip mediates stress fiber formation and induces the neuron-like phenotype of PC12 cells. We suggest that this method may potentially be applied to precise single-cell modulation, as well as in the development of non-invasive and rapid disease treatment strategies.
Biological research and many cell-based therapies rely on the successful delivery of cargo materials into cells. Intracellular delivery in an in vitro setting refers to a variety of physical and biochemical techniques developed for conducting rapid and efficient transport of materials across the plasma membrane. Generally, the techniques that are time-efficient (e.g., electroporation) suffer from heterogeneity and low cellular viability, and those that are precise (e.g., microinjection) suffer from low-throughput and are labor-intensive. Here, we present a novel in vitro microfluidic strategy for intracellular delivery, which is based on the acoustic excitation of adherent cells. Strong mechanical oscillations, mediated by Lamb waves, inside a microfluidic channel facilitate the cellular uptake of different size (e.g., 3-500 kDa, plasmid encoding EGFP) cargo materials through endocytic pathways. We demonstrate successful delivery of 500 kDa dextran to various adherent cell lines with unprecedented efficiency in the range of 65-85% above control. We also show that actuation voltage and treatment duration can be tuned to control the dosage of delivered substances. High viability (≥91%), versatility across different cargo materials and various adherent cell lines, scalability to hundreds of thousands of cells per treatment, portability, and ease-of-operation are among the unique features of this acoustofluidic strategy. Potential applications include targeting through endocytosis-dependant pathways in cellular disorders, such as lysosomal storage diseases, which other physical methods are unable to address. This novel acoustofluidic method achieves rapid, uniform, and scalable delivery of material into cells, and may find utility in lab-on-a-chip applications.
In this paper, an annular array consisting of 64 piezoelectric ceramics was established to make acoustic vortices. The trapped particles and streaming lines in the fluid chamber were theoretically designed and manipulated in experiment. The acoustic field was simulated by Bessel functions and the principle of Huygens by a hydrophone with the annular array excitation. An fast Fourier transform comparison method was proposed in experiments to get the acoustic vortices and phase patterns. The results showed that the patterns of the acoustic field were much different from each other with the variation of excitation phases and the phase patterns implied the vortices in fluid of the chamber, which were affected by the annular arrays of piezoelectric slice excitation. The research concluded that the trapped area and streaming lines can be manipulated by adjusting the phase of piezoelectric slices and the experimental data were helpful to guide the design of acoustic tweezers.
Asymmetric surface acoustic waves have been shown useful in separating particles and cells in many microfluidics designs, mostly notably sessile microdroplets. However, no one has successfully extracted target particles or cells for later use from such samples. We present a novel omnidirectional spiral surface acoustic wave (OSSAW) design that exploits a new cut of lithium niobate, 152 Y-rotated, to rapidly rotate a microliter sessile drop to 10g, producing efficient multi-size particle separation. We further extract the separated particles for the first time, demonstrating the ability to target specific particles, for example, platelets from mouse blood for further integrated point-of-care diagnostics. Within about 5 s of surface acoustic wave actuation, particles with diameter of 5 µm and 1 µm can be separated into two portions with a numerical purity of 83% and 97%, respectively. Murine red blood cells and platelets within are further demonstrated to be separated with a purity of 93% and 84%, respectively. These advancements potentially provide an effective platform for whole blood separation and point-of-care diagnostics without need for micro or nanoscale fluidic enclosures.
3D printing has attracted the attention of analytical chemists. 3D printing possesses the merits of fast and low-cost fabrication of geometrically complex 3D structures and has been employed in the fields of microfluidic devices, electrochemical sensors and biosensors, separation sciences, sample pretreatment, and wearable sensors. We focus on the applications and materials of 3D printing in microfluidic devices, separation sciences, and extraction over the last three years and we offer outlook. It is clear that the 3D printing in separation science is here to stay and with new materials development, to develop to on demand fabrication of separation tools.
Over the past decades, nanoparticles have increased in implementation to a variety of applications ranging from high-efficiency electronics to targeted drug delivery. Recently, microfluidic techniques have become an important tool to isolate and enrich populations of nanoparticles with uniform properties (
e.g.
, size, shape, charge) due to their precision, versatility, and scalability. However, due to the large number of microfluidic techniques available, it can be challenging to identify the most suitable approach for isolating or enriching a nanoparticle of interest. In this review article, we survey microfluidic methods for nanoparticle isolation and enrichment based on their underlying mechanisms, including acoustofluidics, dielectrophoresis, filtration, deterministic lateral displacement, inertial microfluidics, optofluidics, electrophoresis, and affinity-based methods. We discuss the principles, applications, advantages, and limitations of each method. We also provide comparisons with bulk methods, perspectives for future developments and commercialization, and next-generation applications in chemistry, biology, and medicine.
The introduction of surface acoustic wave (SAW) technology on microfluidics has shown its powerfully controlling and actuating fluid and particle capability in a micro-nano scale, such as fluid mixing, fluid translation, microfluidic pumping, microfluidic rotational motor, microfluidic atomization, particle or cell concentration, droplet or cell sorting, reorientation of nano-objects, focusing and separation of particles, and droplet jetting. The SAW-driven droplet jetting technology enjoys the advantages of simple structure to fabricate with little hindrance, compact size to integrate with other components, high biocompatibility with biological cells or other molecule samples, large force in realizing fast fluidic actuation, and contact-free manipulation with fluid. The realization of this technology can effectively overcome some bottleneck problems in the current micro-injection technology, such as mechanical swear, complicated and bulky structure, and strict limitation of requirements on fluidic characteristics. This article reviews and reorganizes SAW-microfluidic jetting technology from decades of years, referring to the interaction mechanism theory of SAW and fluid, experimental methods of SAW-microfluidic jetting, effects of related parameters on objected pinch-off droplets, and applications of individual structures. Finally, we made a summary of the research results of the current literature and look forward and appraise where this discipline of SAW-microfluidic jetting could go in the future.
Giant unilamellar vesicles (GUVs) are a useful platform for reconstituting and studying membrane-bound biological systems, offering reduced complexity compared to living cells. Several techniques exist to form GUVs and populate them with biomolecules of interest. However, a persistent challenge is the ability to efficiently and reliably load solutions of biological macromolecules, organelle-like membranes, and/or micrometer-scale particles with controlled stoichiometry in the encapsulated volume of GUVs. Here, we demonstrate the use of acoustic streaming from high-intensity focused ultrasound to make and load GUVs from bulk solutions, without the need for nozzles that can become clogged or otherwise alter the solution composition. In this method, a compact acoustic lens is focused on a planar lipid bilayer formed between two aqueous solutions. The actuation of a planar piezoelectric material coupled to the lens accelerates a small volume of liquid, deforming the bilayer and forming a GUV containing the solution on the transducer side of the bilayer. As demonstrated here, acoustic jetting offers an alternative method for the generation of GUVs for biological and biophysical studies.
We study the nozzle-free ejection of liquid droplets at controlled angles from a sessile drop actuated from two, mutually opposed directions by focused surface acoustic waves with dissimilar parameters. Previous researchers assumed that jets formed in this way are limited by the Rayleigh angle. However, when we carefully account for surface tension in addition to the driving force, acoustic streaming, we find a quantitative model that reduces to the Rayleigh angle only when inertia is dominant, and suggests larger ejection angles are possible in many practical situations. We confirm this in demonstrating ejection at more than double the Rayleigh angle. Our model explains the effects of both fluid and input parameters on experiments with a range of liquids. We extract, from this model, a dimensionless number that serves as an analog for the typical Weber number for predicting single droplet events.
The dynamic control of the chemical concentration within droplets is required in numerous droplet microfluidic applications. Here, we propose an acoustofluidic method for the generation of a library of aqueous droplets with the desired chemical concentrations in a continuous oil phase. Surface acoustic waves produced by a focused interdigital transducer interact with two parallel laminar streams with different chemical compositions. Coupling the acoustic waves with the flow streams results in the controlled acoustofluidic mixing of the aqueous solutions through the formation of acoustic streaming flow-induced microvortices. The mixed streams are split at a bifurcation, and one of the streams with a precisely controlled chemical concentration is fed into a T-junction to produce droplets with tunable chemical concentrations. The periodic acoustofluidic mixing of the aqueous streams enables the generation of a droplet library with a well-defined inter-droplet concentration gradient. The proposed method is a promising tool for the on-chip dynamic control of in-droplet chemical concentrations and for next-generation droplet microfluidic applications.
Here, we present a high performance uncooled near-infrared (NIR) detector comprising of a giga hertz (GHz) solidly mounted resonator (SMR) and gold nanorods (GNRs) arrays. By coupling the localized surface plasmon resonances of GNRs, the resonator system exhibits optimized optical response to vis-NIR region. Both simulation and experiments demonstrate the hybrid GNRs-SMR exhibit significantly enhanced optical responsive sensitivity of NIR, the tunable aspect ratios (AR) of GNRs enable resonator respond sensitively to selected light. Specially, taking advantage of the acoustofluidic effect of SMR, the GNRs can be controllably and precisely modified on the microchip surface in an ultra-short time, which addresses one of the most fundamental challenges in the localized functionalization of micro/nano scale surface. The presented work opens new directions in development of novel miniaturized, tunable NIR detector.
Acoustofluidics have been widely used for particle and cell manipulations. Given the scaling of acoustic radiation forces and acoustic streaming flow velocities with increasing frequency, existing acoustofluidic manipulation of submicron particles require actuation at MHz and even GHz frequencies. In this work, we explore a novel acoustofluidic phenomenon, where an ultra-low frequency (800 Hz) acoustic vibration is capable of concentrating and patterning submicron particles at two poles of each pillar in an array embedded in a microfluidic device. This unprecedented phenomenon is attributed to a collective effect of acoustic streaming induced drag force and non-Newtonian fluid induced elastic lift force, arising from symmetric acoustic microstreaming flows around each pillar uniformly across the entire pillar array. To our knowledge, this is the first demonstration that particles can be manipulated by an acoustic wave with a wavelength that is six orders of magnitude larger than the particle size. This ultra-low frequency acoustofluidics will enable a simple and cost-effective solution to effective and uniform manipulation of submicron biological particles in large scales, which has the potential to be widely exploited in clinical and biomedical fields.