Search

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.

The tilted-angle standing surface acoustic wave (taSSAW) microfluidic device has become a powerful tool for biosample separation due to its biocompatibility and non-contact, label-free, and high-efficiency nature. Studying and modeling particle deflection in a microfluid environment containing a taSSAW field is essential in the design of robust taSSAW-based microfluidic devices. Here, we present a numerical model taking into consideration fluid viscous drag force and the acoustic radiation force induced by scattering of acoustic waves for the study of particle deflection. The reliability of the model is validated by comparing our predictions with data from existing literature. In order to support our prediction experimentally, we fabricated a taSSAW microfluidic chip using 128° YX LiNbO3, and the deflection results for 3- and 7-μm polystyrene microspheres concur with the numerical estimation. The effects on particle deflection by parameters such as pre-focusing, pre-focusing width, average flow velocity, acoustic pressure amplitude, tilted angle, and surface acoustic wave frequency on particle deflection are then analyzed. This model could be used to optimize the design and better understand the mechanism of taSSAW microfluidic devices.

Blood coagulation is a process involving several chemical reactions governed by coagulation factors, during which the shear elastic coefficient, μ , varies as the medium transitions from liquid to gel phase. This work used ultrasound to measure μ during the clotting of human plasma samples by tracking the motion of a glass sphere located inside a cuvette filled with the plasma. A 2.03 MHz ultrasonic system generated an impulsive acoustic radiation force acting on the sphere, and a 4.89 MHz pulse-echo ultrasonic system tracked the sphere displacement induced by that force. Measurements of μ were determined by fitting a μ -dependent theoretical model to the motion waveform of the sphere immersed in clotting normal plasma and plasma samples with fibrinogen (FI) concentrations of 1.2 (FI-deficiency) and 3.6 (FI-normal) g/L. For normal plasma, μ started at 14.22 Pa and increased rapidly until 2 min, then slowly until it reached 210.23 Pa at 35 min after the clotting process started. A similar trend was exhibited in plasma samples with FI concentrations of 1.2 and 3.6 g/L, with μ reaching 120.55 and 679.42 Pa, respectively. A theoretical model, related to the kinetics of clot-structure formation, describes the time changes of μ for the clotting plasma samples. The sphere-motion-based acoustic-radiation-force approach allowed us to measure the shear elastic coefficient during the coagulation process of plasma samples with normal and deficient FI concentrations. Our results suggest that the method used in this study is capable of being used to detect bleeding disorders.

Biomechanical properties of corneal scar are strongly correlated with many corneal diseases and some types of corneal surgery, however, there is no elasticity information available about corneal scar to date. Here, we proposed an acoustic radiation force optical coherence elastography system to evaluate corneal scar elasticity. Elasticity quantification was first conducted on ex vivo rabbit corneas, and the results validate the efficacy of our system. Then, experiments were performed on an ex vivo human scarred cornea, where the structural features, the elastic wave propagations, and the corresponding Young’s modulus of both the scarred region and the normal region were achieved and based on this, 2D spatial distribution of Young’s modulus of the scarred cornea was depicted. Up to our knowledge, we realized the first elasticity quantification of corneal scar, which may provide a potent tool to promote clinical research on the disorders and surgery of the cornea.

Shear wave elastography (SWE) is a method of evaluating mechanical properties of soft tissues. Most current implementations of SWE report the group velocity for shear wave velocity, which assumes an elastic, isotropic, homogenous and incompressible tissue. Local Phase Velocity Imaging (LPVI) is a novel method of phase velocity reconstruction that allows for accurate evaluation of shear wave velocity at specified frequencies. This method’s robustness was evaluated in 11 elastic and 8 viscoelastic phantoms using linear and curvilinear arrays. We acquired data with acoustic radiation force push beams with different focal depths and F-numbers and reconstructed phase velocity images over a wide range of frequencies. Regardless of phantom, push beam focal depth, and reconstruction frequency, using an F-number around 3.0 was found to produce the largest usable area in the phase velocity reconstructions. For elastic phantoms scanned with a linear array, the optimal focal depth, frequency range, and maximum region-of interest (ROI) were 20–30 mm, 100–400 Hz, and 2.70 cm(2), respectively. For viscoelastic phantoms scanned with a linear array, the optimal focal depth, frequency, and maximum ROI were 20–30 mm, 100–300 Hz, 1.54 cm(2), respectively. For the curvilinear array in the same phantoms; optimal focal depth, frequency range, and maximum ROIs were 45–60 mm, 100–400 Hz and 100–300 Hz, and 1.54 cm(2), respectively. Further work will be done to evaluate LPVI reconstructions from inclusion phantoms to simulate nonhomogeneous tissues. Additionally, LPVI will be evaluated in larger volume phantoms to account for wave reflection from the containers when using the curvilinear array.

In this work, we explored the potential of measuring shear wave propagation using optical coherence elastography (OCE) in an inhomogeneous phantom and carotid artery samples based on a sweptsource optical coherence tomography (OCT) system. Shear waves were generated using a piezoelectric transducer transmitting sine-wave bursts of 400 μs duration, applying acoustic radiation force (ARF) to inhomogeneous phantoms and carotid artery samples, synchronized with a swept-source OCT (SS-OCT) imaging system. The phantoms were composed of gelatin and titanium dioxide whereas the carotid artery samples were embedded in gel. Differential OCT phase maps, measured with and without the ARF, detected the microscopic displacement generated by shear wave propagation in these phantoms and samples of different stiffness. We present the technique for calculating tissue mechanical properties by propagating shear waves in inhomogeneous tissue equivalent phantoms and carotid artery samples using the ARF of an ultrasound transducer, and measuring the shear wave speed and its associated properties in the different layers with OCT phase maps. This method lays the foundation for future in-vitro and in-vivo studies of mechanical property measurements of biological tissues such as vascular tissues, where normal and pathological structures may exhibit significant contrast in the shear modulus.

The visualization and analysis of a novel acoustic-particulate system is the objective of this study. The system is composed of rice-husk fired smoke particulates (36.7 nm–840 μm) and one annular resonant circular-tube waveguide contrarily coupled with two sound sources. The collective interaction behavior process of smoke particulates in an inhomogeneous acoustic field is displayed during an experiment and a simulation. The result shows that the aggregation and fragmentation of particles under a change in resonant frequencies and sound pressure amplitude is extremely complex. This complex process consists of dynamically tuning the particle characteristics to attain stripes shaped like thin-films/umbrellas and clusters with volume-change/fragmentation. The balanced modulation of the acoustic radiation force and secondary radiation force to alter the particle characteristics (size and stack density) is verified to be the control mechanism of the particle system. The intermediate variable of the process control is the acoustic contrast factor (Ф) related to the physical characteristics of the growing particulates. The value plus-minus alternation of Ф results in different particulate processes. This study can enhance the application of aerodynamic acoustic-particulate-fluid systems for environment protection, energy fuel conversion, and industrial production.

Shear wave elastography (SWE) is an ultrasonic technique able to quantitatively assess the mechanical properties of tissues, combining acoustic radiation force and ultrafast imaging. While utilizing coherent plane wave compounding enhances echo and shear wave motion signal-to-noise ratio (SNR), it also reduces the effective pulse repetition frequency (PRF(e)), affecting the accuracy of the measurements of the motion and, consequently, of the material properties. It is important to maintain both high motion SNR and PRF(e), particularly for the characterization of (material and/or geometrical) dispersive tissues such as arteries. This work proposes a method for SWE measurements with high SNR, while maintaining a high PRF(e), using conventional clinical ultrasound scanners. A time alignment process is applied, after acquiring data from plane wave transmissions at different angles. The time alignment uses interpolation to obtain data points at higher frame rates, and the time-aligned data is compounded to increase the SNR. The method is used for SWE in tissue-mimicking phantoms of various stiffness and is compared to traditional plane wave compounding. An increase of 58% and of 36% in spatial and temporal bandwidth compared to conventional plane wave compounding, respectively, can be achieved for SWE measurements of representative arterial stiffness values. Improvements on phase velocity accuracy and bandwidth in an arterial phantom are also presented, to emphasize the beneficial advantage in dispersive cases.

A variable focus optical lens using a thixotropic gel and ultrasonic vibration is discussed. The surface profile of the gel could be deformed via acoustic radiation force generated by ultrasound. A thixotropic gel in which the viscosity was changed by shear stress was employed as a transparent lens material. The thixotropic gel allowed the lens to maintain shape deformation in the absence of continuous ultrasound excitation. The lens had a simple structure with no mechanical moving parts and included an annular piezoelectric transducer, a glass disk, and the thixotropic gel film. The axisymmetric concentric flexural vibration mode was generated on the lens at 71 kHz, which resulted in static surface deformation of the gel via the acoustic radiation force. The preservation rate was investigated after switching off the ultrasonic excitation. There was a trade-off between the preservation rate of the lens deformation and the response time for focusing. The focal length could be controlled via the input voltage to the lens, and a variable-focus convex lens could be realized; the change in the focal length with 4.0 Vpp was 0.54 mm. The optical transmittance of the lens was measured and the transmittance ranged 70%–80% in the visible spectral region.

A method is proposed of fabricating tubular constructs from tissue spheroids (conglomerates of cells up to 200 μm in size) in a nutrient fluid using the acoustic radiation force. The source of the acoustic field is a hollow piezoceramic cylinder with a resonant frequency of 800 kHz. Keeping the obtained structure at 37°C for 24 h fuses the spheroids into a solid tubular viable tissue construct.

Standing surface acoustic waves (SSAWs) have been widely utilized in microfluidic devices to manipulate various cells and micro/nano-objects. Despite widespread application, a time-/cost-efficient versatile 3D model that predicts particle behavior in such platforms is still lacking. Herein, a fully-coupled 3D numerical simulation of boundary-driven acoustic streaming in the acoustofluidic devices utilizing SSAWs has been conducted based on the limiting velocity finite element method. Through this efficient computational method, the underlying physical interplay from the electromechanical fields of the piezoelectric substrate to different acoustofluidic effects (acoustic radiation force and streaming-induced drag force), fluid–solid interactions, the 3D influence of novel on-chip configuration like tilted-angle SSAW (taSSAW) based devices, required boundary conditions, meshing technique, and demanding computational cost, are discussed. As an experimental validation, a taSSAW platform fabricated on YX 128 $$^\circ $$ ∘ LiNbO3 substrate for separating polystyrene beads is simulated, which demonstrates acceptable agreement with reported experimental observations. Subsequently, as an application of the presented 3D model, a novel sheathless taSSAW cell/particle separator is conceptualized and designed. The presented 3D fully-coupled model could be considered a powerful tool in further designing and optimizing SSAW microfluidics due to the more time-/cost-efficient performance than precedented 3D models, the capability to model complex on-chip configurations, and overcome shortcomings and limitations of 2D simulations.

Ultrasound shear wave elastography (SWE) is a technique used to measure mechanical properties to evaluate healthy and pathological soft tissues. SWE typically employs an acoustic radiation force (ARF) to generate laterally propagating shear waves that are tracked in the spatiotemporal domains, and algorithms are used to estimate the wave velocity. The tissue viscoelasticity is often examined through analyzing the shear wave phase velocity dispersion curves, which is the variation of phase velocity with frequency or wavelength. A number of available methods to estimate dispersion exist, which can differ in resolution and variance. Moreover, most of these techniques reconstruct dispersion curves for a limited frequency band. In this work, we propose a novel method used for dispersion curve calculation. Our unique approach uses a generalized Stockwell transformation combined with a slant frequency-wavenumber analysis (GST-SFK). We tested the GST-SFK method on numerical phantom data generated using a finite-difference-based method in tissue-mimicking viscoelastic media. In addition, we evaluated the method on numerical shear wave motion data with different amounts of white Gaussian noise added. Additionally, we performed tests on data from custom-made tissue-mimicking viscoelastic phantom experiments, ex vivo porcine liver measurements, and in vivo liver tissue experiments. We compared results from our method with two other techniques used for estimating shear wave phase velocity: the two-dimensional Fourier transform (2D-FT) and the eigenvector (EV) method. Tests carried out revealed that the GST-SFK method provides dispersion curve estimates with lower errors over a wider frequency band in comparison to the 2D-FT and EV methods. In addition, the GST-SFK provides expanded bandwidth by a factor of two or more to be used for phase velocity estimation, which is meaningful for a tissue dispersion analysis in vivo .

Acoustic radiation force (ARF) might improve the distribution of nanoparticles (NPs) in tumors. To study this, tumors growing subcutaneously in mice were exposed to focused ultrasound (FUS) either 15 min or 4 h after the injection of NPs, to investigate the effect of ARF on the transport of NPs across the vessel wall and through the extracellular matrix. Quantitative analysis of confocal microscopy images from frozen tumor sections was performed to estimate the displacement of NPs from blood vessels. Using the same experimental exposure parameters, ARF was simulated and compared to the experimental data. Enhanced interstitial transport of NPs in tumor tissues were observed when FUS (10 MHz, acoustic power 234 W/cm2, 3.3 % duty cycle) was given either 15 min or 4 h after NP administration. According to acoustic simulations, the FUS generated an ARF per unit volume of 2.0 x 106 N/m3. The displacement of NPs was larger when FUS was applied 4h after NP injection compared to after 15 min. This study shows that ARF might contribute to a modest improved distribution of NPs into the tumor interstitium. © 2020 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works.

Gaseous hydrogen/liquid oxygen turbulent shear coaxial flames were subjected experimentally to both pressure antinode (PAN) and pressure node (PN) transverse acoustic forcing as a function of the g...

Acoustophoresis is the technology to separate the microparticles and cells from suspending fluid. This research focuses on the separation of nanoparticles from water by using macro-scale fluidic separator which works based on gravity-aided ultrasonic standing wave technology. Titanium dioxide particles of 40 nm diameter were concentrated by the combination of ultrasonic standing wave field at 2.2 MHz and gravity-aided sedimentation. The purpose of this study is to investigate the performance of gravity-aided ultrasonic particle to concentrate nanoparticles. It was found that the separation efficiency is 83% at a flow rate of 0.1 mL/min. FEM simulations were also conducted to evaluate characteristics of variation of acoustic energy inside the fluidic channel. Results indicate that nanoparticles can be concentrated using gravity-aided ultrasonic standing wave field, however optimization of the design of the fluidic channel is required for increasing throughput of the separator.

Transcranial focused ultrasound (tFUS) is an emerging neuromodulation technique to modulate brain activity non-invasively with high spatial specificity and focality. Given the influence of tFUS on brain activity, combining tFUS with multi-channel intracranial electrophysiological recordings enables monitoring of the activity of large populations of neurons with high temporal resolution. However, the physical interactions between tFUS and the electrode may affect a reliable assessment of neuronal activity, which remains poorly understood. In this article, high-frequency ultrasound (HFUS) system was developed and integrated into the tFUS neuromodulation system. The performance of the HFUS-based displacement tracking and analysis was evaluated by the theoretical analysis in the literature. The effects of various pressure levels on the displacements of the silicon-based microelectrode array in ex vivo brain tissue were investigated. The developed approach was capable of tracking and measuring the motion of a solid sphere in a tissue-mimicking phantom and measured displacements were comparable to theoretical predictions. The significant changes in the averaged peak displacements of the microelectrode array in ex vivo brain were observed with a pulse duration of 200 $\mu \text{s}$ and a peak-to-peak pressure from 131 kPa at a center frequency of 500 kHz compared with the values from the negative control group. The present results demonstrate the relationship between several pressure levels and displacements of the microelectrode array in ex vivo brain through the developed approach. This approach can be used to determine a vibration-free threshold of ultrasound parameters in multi-channel intracranial recordings for a reliable assessment of electrophysiological activities of living neurons.

Shear wave elastography (SWE) has the potential to determine cardiac tissue stiffness from non-invasive shear wave speed measurements, important, e.g., for predicting heart failure. Previous studies showed that waves traveling in the interventricular septum (IVS) may display Lamb-like dispersive behaviour, introducing a thickness-frequency dependency in the wave speed. However, the IVS tapers across its length, which complicates wave speed estimation by introducing an additional variable to account for. The goal of this work is to assess the impact of tapering thickness on SWE. The investigation is performed by combining in vitro experiments with acoustic radiation force (ARF) and 2D finite element simulations, to isolate the effect of the tapering curve on ARF-induced and natural waves in the heart. The experiments show a 11% deceleration during propagation from the thick to the thin end of an IVS-mimicking tapered phantom plate. The numerical analysis shows that neglecting the thickness variation in the wavenumber-frequency domain can introduce errors of more than 30% in the estimation of the shear modulus, and that the exact tapering curve, rather than the overall thickness reduction, determines the dispersive behaviour of the wave. These results suggest that septal geometry should be accounted for when deriving cardiac stiffness with SWE.

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 a non-ionic surfactant (Tween 20) aqueous solution in a conventional standing surface acoustic wave field with a 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. Compared with the mixing appearance in pure water media, the patterning behavior of submicron particles with a diameter of 300 nm dominated by acoustic radiation force is readily apparent in an aqueous solution with 2% volumetric concentration of Tween 20 surfactant, thanks to the suppression effect of acoustic streaming in 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, but also occurs to micrometer-sized particles in solutions with higher surfactant concentrations. These findings open up a novel avenue for controllable acoustic manipulation.

Mechanical effects of microbubbles on tissues are central to many emerging ultrasound applications. Here, we investigated the acoustic radiation force a microbubble exerts on tissue at clinically relevant therapeutic ultrasound parameters. Individual microbubbles administered into a wall-less hydrogel channel (diameter: 25–100 µm, Young's modulus: 2–8.7 kPa) were exposed to an acoustic pulse (centre frequency: 1 MHz, pulse length: 10 ms, peak-rarefactional pressures: 0.6–1.0 MPa). Using high-speed microscopy, each microbubble was tracked as it pushed against the hydrogel wall. We found that a single microbubble can transiently deform a soft tissue-mimicking material by several micrometres, producing tissue loading–unloading curves that were similar to those produced using other indentation-based methods. Indentation depths were linked to gel stiffness. Using a mathematical model fitted to the deformation curves, we estimated the radiation force on each bubble (typically tens of nanonewtons) and the viscosity of the gels. These results provide insight into the forces exerted on tissues during ultrasound therapy and indicate a potential source of bio-effects. This study was supported by Alzheimer's Research UK (Grant ARUK-IRG2017 A-7). J.H.B. was funded by the King's College London and Imperial College London Engineering and Physical Sciences Research Council (EPSRC) Centre for Doctoral Training in Medical Imaging (Grant EP/L015226/1 ). We also acknowledge support from the Wellcome Trust (Grant 212490/Z/18/Z ), EPSRC (Grant EP/S016538/1 ), Biotechnology and Biological Sciences Research Council (BBSRC Grant BB/T011947/1 ) and Imperial College Excellence Fund for Frontier Research. Equipment from the Facility for Imaging by Light Microscopy (FILM) at Imperial College London was supported by funding from the Wellcome Trust (Grant 104931/Z/14/Z ) and BBSRC (Grant BB/L015129/1 ) WOS:000581178900016 2-s2.0-85090738507 PMID: 32919812 Science Citation Index Expanded Q1 Article Uluslararası işbirliği ile yapılan - EVET Aralık 2020 YÖK - 2020-21

BACKGROUND: Simultaneous magnetic resonance (MR) acoustic radiation force imaging (ARFI) and MR thermometry (MRT) (STARFI) based on coherent echo-shifted (cES) sequence was proposed and comprehensively compared to radiofrequency (RF)-spoiled gradient echo (spGRE) STARFI. METHODS: Through use of delicately designed gradients, a collection of echoes was delayed by one repetition time (TR) cycle. The crusher gradient after readout (RO) was used as the displacement encoding gradient (DEG). The sequence was intrinsically sensitive to temperature. High-intensity focused ultrasound (HIFU) pulses were interleaved ON/OFF in successive TRs to separate the phase changes induced by displacement due to acoustic radiation force (ARF) impulses and temperature. Bloch simulation was performed to study the phase sensitivity to displacement of the proposed cES STARFI and spGRE STARFI. The proposed cES sequence was evaluated and compared to spGRE STARFI in ex vivo porcine muscle and ex vivo porcine brain. RESULTS: The minimally achievable TR of cES STARFI was shorter than that of spGRE STARFI, indicating that the cES sequence was more time efficient. It was verified through Bloch simulation and ex vivo experiments that the phase sensitivity to displacement of cES STARFI was higher than that of spGRE STARFI. The optimal trigger delays of cES STARFI and spGRE STARFI in ex vivo porcine muscle were t(offset) =–2 and –1 ms, respectively. The displacement-induced phase change to acoustic pressure slopes of cES STARFI were 0.079, 0.079, and 0.047 rad/Mpa across the three muscle samples, while the slopes of spGRE STARFI were only 0.047, 0.052, and 0.027 rad/Mpa. The maximum temperature difference between cES STARFI and spGRE STARFI was 1.1 °C. In ex vivo porcine brain, both the displacement-induced phase-to-noise ratio (PNRd) and the temperature uncertainty of cES STARFI were better than those of spGRE STARFI (P

This paper investigates the use of shear wave elastography (SWE) in deep tissues with a two-dimensional (2D) transducer array. A 130-element 800-kHz 2D array for SWE in regions deeper than 100 mm is designed, fabricated, and characterized. SWE simulations are performed with the proposed 2D array in a tissue-like medium. The pressure field of the proposed transducer was recorded and utilized to simulate the generation of acoustic radiation force in deep tissues. The elasticity map of the tissue was successfully reconstructed by tracking the speed of shear wave propagation at 120 mm depth. This study suggests that a 2D transducer with proper parameters may provide a means for extending the depth range of SWE.

Intravascular acoustic radiation force impulse (IV-ARFI) imaging has the potential to identify vulnerable atherosclerotic plaques and improve clinical treatment decisions and outcomes for patients with coronary heart disease. Our long-term goal is to develop a thin, flexible catheter probe that does not require mechanical rotation to achieve high-resolution IV-ARFI imaging. In this work, we propose a novel cylindrical transducer array design for IV-ARFI imaging and investigate the feasibility of this approach. We present the construction of a 2.2-mm-long, 4.6-Fr cylindrical prototype transducer to demonstrate generating large ARFI displacements from a small toroidal beam, and we also present simulations of the proposed IV-ARFI cylindrical array design using Field II and a cylindrical finite-element model of vascular tissues and soft plaques. The prototype transducer was found to generate peak radial displacements of over $10~\mu \text{m}$ in soft gelatin phantoms, and simulations demonstrate the ability of the array design to obtain ARFI images and distinguish soft plaque targets from surrounding, stiffer vessel wall tissue. These results suggest that high-resolution IV-ARFI imaging is possible using a cylindrical transducer array.

Ultrasound shear wave elastography (SWE) is an increasingly used noninvasive modality for quantitative evaluation of tissue mechanical properties. SWE typically uses an acoustic radiation force to produce laterally propagating shear waves that are tracked in the spatial and temporal domains, in order to obtain the wave velocity. One of the ways to study the viscoelasticity is through studying the shear wave phase velocity dispersion curves. Shear wave attenuation can be also characterized in viscoelastic tissues with methods that use multiple lateral data samples. In this article, we present an alternative method for measuring the shear wave attenuation without using a rheological model two-point frequency shift (2P-FS). The technique uses information related to the amplitude spectra FS of shear waves measured at only two lateral locations. The theoretical basis for the 2P-FS is derived and validated. We examined how the first signal position and the distance between the two locations affect the shear wave attenuation estimation in the 2P-FS method. We tested this new method on digital phantom data created using the local interaction simulation approach (LISA) in viscoelastic media. Moreover, we tested data acquired from custom-made tissue-mimicking viscoelastic phantom experiments and ex vivo porcine liver measurements. We compared results from the 2P-FS method with the other two techniques used for assessing a shear wave attenuation: the FS-based method and the attenuation-measuring ultrasound shear wave elastography (AMUSE) technique. In addition, we evaluated the 2P-FS algorithm with different levels of added white Gaussian noise to the shear wave particle velocity using numerical phantoms. Tests conducted showed that the 2P-FS method gives robust results based on only two measurements and can be used to measure attenuation of viscoelastic soft tissues.

The acoustic radiation force, originating from ultrasonic standing waves and utilized in numerous cell oriented acoustofluidic applications, is dependent on the acoustic contrast factor which describes the relationship between the acousto-mechanical properties of a particle and its surrounding medium. The acousto-mechanical properties of a cell population are known to be heterogeneously distributed but are often assumed to be constant over time. In this paper, we use microchannel acoustophoresis to show that the cell state within a cell population, in our case living and dead cells, influences the mechanical phenotype. By investigating the trapping location of viable and dead K562, MCF-7 and A498 cells as a function of the suspension medium density, we observed that beyond a specific medium density the viable cells were driven to the pressure anti-node while the dead cells were retained in the pressure node. Using this information, we were able to calculate the effective acoustic impedance of viable K562 and MCF-7 cells. The spatial separation between viable and dead cells along the channel width demonstrates a novel acoustophoresis approach for binary separation of viable and dead cells in a cell-size independent and robust manner.

The ability to construct core-shell microcapsules has the potential to shift the paradigm in the development of new delivery systems for nutrients, cosmetics, and drugs. In this work, we demonstrate an application of focused surface acoustic wave (FSAW) microfluidics to produce microcapsules with a core-shell structure using one or two focused interdigital transducers (FIDTs) on the microfluidic device. Solid particles or liquid microdroplets without any special modification in multiphase laminar flow are driven by the acoustic radiation force arising from the FSAW, and cross the oil/water interface back and forth, which is not only suitable for generation of core-shell microcapsules with solid cores but also used for coating an aqueous microdroplet core with an oil shell. On this basis, more FIDTs can be added to the device to manufacture more layers of microcapsules if needed. Single-layer, two-layer, or even multi-layer microcapsules can be selectively fabricated. This work provides a promising and robust platform to construct core-shell microcapsules via FSAW microfluidics, which are suitable for a wide range of applications.

Quantitative assessment of myocardial stiffness is crucial to understand and evaluate cardiac biomechanics and function. Despite the recent progresses of ultrasonic shear wave elastography, quantitative evaluation of myocardial stiffness still remains a challenge because of strong elastic anisotropy. In this paper we introduce a smart ultrasound approach for non-invasive real-time quantification of shear wave velocity (SWV) and elastic fractional anisotropy (FA) in locally transverse isotropic elastic medium such as the myocardium. The approach relies on a simultaneous multidirectional evaluation of the SWV without a prior knowledge of the fiber orientation. We demonstrated that it can quantify accurately SWV in the range of 1.5 to 6 m/s in transverse isotropic medium (FA0.7) using numerical simulations. Experimental validation was performed on calibrated phantoms and anisotropic ex vivo tissues. A mean absolute error of 0.22 m/s was found when compared to gold standard measurements. Finally, in vivo feasibility of myocardial anisotropic stiffness assessment was evaluated in four healthy volunteers on the antero-septo basal segment and on anterior free wall of the right ventricle (RV) in end-diastole. A mean longitudinal SWV of 1.08 ± 0.20 m/s was measured on the RV wall and 1.74 ± 0.51 m/s on the septal wall with a good intra-volunteer reproducibility (±0.18 m/s). This approach has the potential to become a clinical tool for the quantitative evaluation of myocardial stiffness and diastolic function.

In this study, we demonstrate an acoustofluidic device that enables single-file focusing of submicron particles and bacteria using a two-dimensional (2D) acoustic standing wave. The device consists of a 100 µm ✕ 100 µm square channel that supports 2D particle focusing in the channel center at an actuation frequency of 7.39 MHz. This higher actuation frequency compared with conventional bulk acoustic systems enables radiation-force-dominant motion of submicron particles and overcome the classical size limitation (≈ 2 µm) of acoustic focusing. We present acoustic radiation force-based focusing of particles with diameters less than 0.5 µm at a flow rate of 12 µL min-1, and 1.33 µm particles at flow rates up to 80 µL min-1. The device focused 0.25 µm particles by the 2D acoustic radiation force while undergoing a channel cross-section centered, single-vortex acoustic streaming. A suspension of bacteria was also investigated to evaluate the biological relevance of the device, which demonstrated the alignment of bacteria in the channel at a flow rate of up to 20 µL min-1. The developed acoustofluidic device can align submicron particles within a narrow flow stream in a highly robust manner, validating its use as a flow-through focusing chamber to perform high-throughput and accurate flow cytometry of submicron objects.

Comprehensive integration of process steps into a miniaturised version of synthetic biology workflows remains a crucial task in automating the design of biosystems. However, each of these process steps has specific demands with respect to the environmental conditions, including in particular the composition of the surrounding fluid, which makes integration cumbersome. As a case in point, transformation, i.e. reprogramming of bacteria by delivering exogenous genetic material (such as DNA) into the cytoplasm, is a key process in molecular engineering and modern biotechnology in general. Transformation is often performed by electroporation, i.e. creating pores in the membrane using electric shocks in a low conductivity environment. However, cell preparation for electroporation can be cumbersome as it requires the exchange of growth medium (high-conductivity) for low-conductivity medium, typically performed via multiple time-intensive centrifugation steps. To simplify and miniaturise this step, we developed an acoustofluidic device capable of trapping the bacterium Escherichia coli non-invasively for subsequent exchange of medium, which is challenging in acoustofluidic devices due to detrimental acoustic streaming effects. With an improved etching process, we were able to produce a thin wall between two microfluidic channels, which, upon excitation, can generate streaming fields that complement the acoustic radiation force and therefore can be utilised for trapping of bacteria. Our novel design robustly traps Escherichia coli at a flow rate of 10 μL min−1 and has a cell recovery performance of 47 ± 3% after washing the trapped cells. To verify that the performance of the medium exchange device is sufficient, we tested the electrocompetence of the recovered cells in a standard transformation procedure and found a transformation efficiency of 8 × 105 CFU per μg of plasmid DNA. Our device is a low-volume alternative to centrifugation-based methods and opens the door for miniaturisation of a plethora of microbiological and molecular engineering protocols., Lab on a Chip, 21 (22), ISSN:1473-0197, ISSN:1473-0189

Transition between stream and droplet regimes in a coflow is typically achieved by adjusting the capillary numbers (Ca) of the phases. Remarkably, we experimentally evidence a reversible transition between the two regimes by controlling exposure of the system to acoustic standing waves, with Ca fixed. By satisfying the ratio of acoustic radiation force to the interfacial tension force, ${\mathrm{Ca}}_{\mathrm{ac}}g1$, experiments reveal a reversible stream drop transition for $\mathrm{Ca}l1$, and stream relocation for $\mathrm{Ca}\ensuremath{\ge}1$. We explain the phenomenon in terms of the pinching, advection, and relocation timescales and a transition between convective and absolute instability from a linear stability analysis [P. Guillot et al., Phys. Rev. Lett. 99, 104502 (2007)].

Acoustic radiation force (ARF) induced Shear wave elasticity imaging (SWEI) is a noninvasive method to characterize pathological tissues. Conventionally, ARF is generated by focused beam with limited depth of focus. Supersonic shear imaging (SSI) uses multiple push-beam foci to achieve larger depth of field (DoF) elastograms. Here, we propose a SWEI method based on Bessel apodized ARF to generate larger DoF with lower energy. As a result, Bessel elastogram in gel phantom shows 19% higher contrast-to-noise ration (CNR) and 95% lower energy than SSI. Furthermore, Bessel elastogram in porcine liver shows 61% higher signal-to-noise ratio (SNR) and 56% lower energy than SSI.

Single frequency acoustic traps are widely applied to microparticle trapping, filtering, sorting and manipulation. This work considers how additional frequencies can be used to achieve better trapping. The acoustic radiation force on a small (sub-wavelength) particle in a rigid walled cavity vibrating at multiple harmonic frequencies is calculated analytically and applied to developing a trap with large regions of near constant force and a stiff local trap at the cavity center. A 1D transmission line model is used to demonstrate that these multi-frequency traps should be realizable in a straight forward acoustic system and that the trap stiffness can be increased more than 2.5 times compared to a single frequency trap without increasing power requirements or the acoustic intensity in the chamber.

At a water-air interface, the acoustic radiation pressure (ARP), generates a deformation of the interface. In this work, we propose to study the interface deformation for non-continuous excitations. A particular attention is given to the maximum height at the center of the deformation. An experimental setup has been developed to evaluate the height of the deformation for different durations and amplitudes of the transient acoustic radiation pressure. The results are compared to a numerical approach using the Finite-Element Method (FEM). Finally, the numerical and experimental results for a transient excitation have been compared to results obtained for continuous excitation in order to propose a pertinent optimization of the excitation parameters. Results are in good agreement with the theory for a continuous excitation, and encouraging for further improvement on both numerical and experimental methods.

The difference in residence time spent by particles in acoustic separator devices correlates to the values of the efficiency and purity coefficients. Although the particle trajectories and the required flow speeds have been investigated in theoretical and numerical studies, most of the existing studies overlook the effect of transverse flow profiles. More complex sorter methods, such as tilted-angle or frequency-modulated methods however can be better understood by applying analysis based on flow profiles. A numerical integration scheme is used here to obtain axial particle trajectories for arbitrary flow profiles with residence time differences of up to 20% for simple time-of-flight sorting. For more complex phase modulated techniques, a non-monotonous dependence of residence time on particle size is observed, with differences up to 27%.

The stiffening of soft tissues has been demonstrated to be associated with different disease processes such as cancer. In the last decades several devices and techniques have been developed to provide 2D maps of elasticity in order to help in diagnosis. 3D shear elasticity imaging was recently implemented with matrix arrays using the acoustic radiation force of ultrasound as shear wave source. However, matrix arrays require large number of channels and data to be processed. Row Column Arrays (RCAs) are a cheaper alternative to volume imaging since they require lower number of channels. However, at present RCAs are unable to generate acoustic radiation force due to their design and manufacturing process. To overcome the need of acoustic radiation force for elasticity imaging, in this work we implemented a passive elastography approach based on noise correlation of a complex elastic wave field to conduct 3D shear elasticity imaging using RCAs. Experiments were conducted on a tissue mimicking phantom demonstrate the feasibility of this approach.

The most common neurostimulation method is the stimulation of the focal point by using a focused ultrasound transducer. In the field of particle manipulation using ultrasound, research using acoustic vortices is ongoing and presents promising characteristics. In neurostimulation using ultrasound, the acoustic radiation force is a leading candidate for a physical mechanism. In this study, the acoustic radiation forces generated by a general-focused transducer and a vortex transducer were compared. For the experiment, a 70 mm diameter transducer with a center frequency of 1 MHz was fabricated using a piezoceramic plate. The ultrasound transducer frame was made of aluminum, and air backing was used to maximize the output pressure. A large-scale Fresnel focused lens and focused vortex lens were fabricated using polydimethylsiloxane (PDMS). A mold of an 8-step Fresnel lens with a diameter of 70 mm was developed using 3-D printing. We compared the pressure field and radiation force according to the two manufactured lenses to determine whether there was any difference in neurostimulation.

A finite element method with perturbation theory for calculating the secondary acoustic radiation force between cells and solid particles is implemented and simulated results were compared with experimental results. To do so, two sets of particles, including polystyrene particles...

Highlights • Manipulation of particles (bubbles) with acoustic radiation force (Bjerknes force). • Implementation of multi particle manipulation. • Study of the change of particle position with operating frequency. • Visualization of acoustic field by Schlieren imaging method., This paper reports a method to generate tunable bottle beams using an ultrasonic lens, by which the bottle position can be precisely adjusted with the change of the acoustic frequency. Therefore, the position of a single particle or bubble in liquid can be manipulated without using phased array which is costly and huge with complex circuits. Furthermore, we introduced this method to multiple bubble manipulation using acoustic holography. The bottle properties against frequency are theoretically and experimentally analyzed. It is shown that the bottle position depends almost linearly on the operating frequency, which provides a basis for the precise manipulation of bubbles and particles. In addition, the relationship between the acoustic radiation force and the drag force under different incident acoustic pressures is considered, establishing a limit on the moving velocity of the trapped particles. The ultrasonic field observation is further demonstrated by Schlieren imaging system. The proposed method has potential biomedical applications, such as more flexible cell manipulation and targeted drug delivery in vivo, as well as potential applications in the study of chemical reactions between micro objects.

To achieve precise and untethered clinical therapeutics, microrobots have been widely researched. However, because conventional microrobot actuation is based on magnetic forces generated by a magnetic field and magnetic particles, unexpected side effects caused by additional magnetic ingredients could induce clinical safety issues. In this paper, as an alternative to an untethered actuator, we present a novel ultrasonic actuation mechanism that enables drug particle/cell manipulation and micro/nano-robot actuation in clinical biology and medicine. Firstly, characteristics of the acoustic field in the vessel mimic circular tube, formed from particles emerging through a submerged ultrasonic transducer, are mathematically analyzed and modeled. Thereafter, a control method is proposed for trapping and moving the micro-particles by using acoustic radiation force (ARF) in a standing wave of a tangential standing wave. The feasibility of the proposed method could be demonstrated with the help of experiments conducted using a single transducer with a resonance frequency of 950 kHz and a motorized linear stage, which were used in a water tank. The micro-particles in the tube were trapped via ultrasound and the position of the micro-particles could be controlled by frequency manipulation of the transducer and motor control. This study shows that ultrasonic manipulation can be used for specific applications, such as the operation of a micro robot inserted in a peripheral blood vessel and targeted for drug delivery.

The aim of this study was to improve the sensitivity of magnetic resonance-acoustic radiation force imaging (MR-ARFI) to minimize pressures required to localize focused ultrasound (FUS) beams, and to establish safe FUS localization parameters for ongoing ultrasound neuromodulation experiments in living non-human primates. We developed an optical tracking method to ensure that the MR-ARFI motion-encoding gradients (MEGs) were aligned with a single-element FUS transducer and that the imaged slice was prescribed at the optically tracked location of the acoustic focus. This method was validated in phantoms, which showed that MR-ARFI-derived displacement sensitivity is maximized when the MR-ARFI MEGs were maximally aligned with the FUS propagation direction. The method was then applied in vivo to acquire displacement images in two healthy macaque monkeys (M fascicularis) which showed the FUS beam within the brain. Temperature images were acquired using MR thermometry to provide an estimate of in vivo brain temperature changes during MR-ARFI, and pressure and thermal simulations of the acoustic pulses were performed using the k-Wave package which showed no significant heating at the focus of the FUS beam. The methods presented here will benefit the multitude of transcranial FUS applications as well as future human applications.

We have developed a unique particle-separation technique based on size that uses kHz-band ultrasound irradiation in water. Dispersed-millimeter-size particles in dissolved-gases water form themselves into a spherically flocculated particle swarm (SFPS). With the changes of ultrasound irradiation properties, the particles are separated according to their sizes. We previously investigated the characteristics of an SFPS and elucidated its formation mechanism. To achieve an efficient and precise particle-separation technique, the forces acting on the particles during the transition state of the ultrasound modulation must be determined, but it is difficult to clarify the forces acting on each particle. Herein, we experimentally and systematically investigated the forces acting on a single particle trapped in the sound pressure field. We discuss nine types of forces acting on the particle and the bubble adhering to its surface. Under the static state, the particle buoyancy was counterbalanced with the acoustic radiation force acting on the acoustic cavitation-oriented bubbles (ACOBs). We examined two types of amplitude change: a gradual amplitude change of the input power of a transducer, and a step-like amplitude change. The results revealed that the particle motion depends on a subtle balance between the acoustic radiation force acting on the ACOBs and unsteady fluid-dynamical forces acting on the particle. We also demonstrate the classification of particles by diameter by controlling the transition state of the amplitude change of the ultrasound input power. We conclude that the gradual amplitude change provided an efficient and precise classification of particles by their diameters.

In this report, a method is proposed to quantify the translation of ultrasound contrast agent (UCA) microbubbles driven by acoustic radiation for the detection of channels filled with stationary fluid. The authors subjected UCA microbubbles in a channel with diameters of 0.1 and 0.5 mm to ultrasound pulses with a center frequency of 14.4 MHz. The translational velocity of the UCA microbubbles increased with the sound pressure and pulse repetition frequency (PRF) of the transmitted ultrasound. The mean translational velocity reached 0.75 mm/s at a negative peak sound pressure of 2.76 MPa and a PRF of 2 kHz. This trend agreed with the theoretical prediction, which indicated that the translational velocity was proportional to the square of the sound pressure and the PRF. Furthermore, an experiment was carried out with a phantom that mimics tissue and found that the proposed method aided in detection of the channel, even in the case of a low contrast-echo to tissue-echo ratio. The authors expect to develop the proposed method into a technique for detecting lymph vessels.

Magnetic Drug Targeting (MDT) is a cancer treatment technique that enables a local chemotherapy. In MDT, chemotherapeutic drugs are bound to magnetic nanoparticles and are accumulated in the tumor area by means of an external magnetic field. Unfortunately, a single magnet can only generate a pulling magnetic force. However, in some applications a pushing force on the nanoparticles could be advantageous. One way to realize pushing forces is to exploit the acoustic radiation force based on the nonlinearity of sound propagation in fluid media generated by a high intensity focused ultrasonic transducer. In this context, we built a test setup was built to investigate the utility of High Intensity Focused Ultrasound (HIFU) to generate a pushing force on the magnetic nanoparticles. The results show that the acoustic radiation force can be employed for particle guidance to achieve concentration differences similar to those obtained by using an electromagnet.

Recovery of fine coal particles by flotation has always been difficult due to the low collision efficiency between air bubbles and fine coal particles. One method to improve the flotation recovery of fine coal particles is the aggregation of these particles prior to the flotation process. This paper introduces a new method for the aggregation of fine coal particles by utilizing an ultrasonic standing-wave treatment. Under a 200 kHz ultrasonic standing-wave, cavitation bubbles formed on the hydrophobic coal particle surfaces. The bubble-laden coal particles moved to the nodes of the ultrasonic standing wave by the acoustic radiation force if the size of the cavitation bubbles were larger than the resonance radius, resulting in rapid aggregation of the fine coal particles. Micro-flotation results indicated that the flotation rate significantly increased after the ultrasonic standing-wave treatment. This study demonstrated an efficient ultrasonic standing-wave method for improving the flotation rate of fine coal particles without addition of chemicals or collectors.

We demonstrate a novel microdroplets generation method by using focused surface acoustic waves (FSAW). The method differs from previous work in the mechanism and the geometry structure of the chip, which is depend on FSAW rather than flow shearing. The acoustic radiation force arising from FSAW acts on the oil-water interface, breaking up the water into microdroplets whose size can be controlled by tuning the driving voltage and frequency of FSAW. This approach overcomes the limitation of microchannel structure and capillary number of the traditional microfluidic droplets formation methods, which enables a fully electrical control of microdroplets size, with a good uniformity. Further, the FSAW-induced microdroplets are used as templates to prepare microgels with uniform size, offering a new platform for the design and synthesis of monodispersed functional microspheres.

Purpose The capability of microparticle/objects patterning in the three-dimensional (3D) printing structure could improve its performance and functionalities. This paper aims to propose and evaluate a novel acoustic manipulation approach. Design/methodology/approach A novel method to accumulate the microparticles in the cylindrical tube during the 3D printing process is proposed by acoustically exciting the structural vibration of the cylindrical tube at a specific frequency, and subsequently, focusing the 50-μm polystyrene microparticles at the produced pressure node toward the center of the tube by the acoustic radiation force. To realize this solution, a piezoceramic plate was glued to the outside wall of a cylindrical glass tube with a tapered nozzle. The accumulation of microparticles in the tube and printing structure was monitored microscopically and the accumulation time and width were quantitatively evaluated. Furthermore, the application of such technology was also evaluated in the L929 and PC-12 cells suspended in the sodium alginate and gelatin methacryloyl. Findings The measured location of pressure and the excitation frequency of the cylindrical glass tube (172 kHz) agreed quite well with our numerical simulation (168 kHz). Acoustic excitation could effectively and consistently accumulate the microparticles. It is found that the accumulation time and width of microparticles in the tube increase with the concentration of sodium alginate and microparticles in the ink. As a result, the microparticles are concentrated mostly in the central part of the printing structure. In comparison to the conventional printing strategy, acoustic excitation could significantly reduce the width of accumulated microparticles in the printing structure (p Originality/value This paper proves that the proposed acoustic approach is able to increase the accuracy of printing capability at a low cost, easy configuration and low power output.

The kidney is an anisotropic organ, with higher elasticity along versus across nephrons. The degree of mechanical anisotropy in the kidney may be diagnostically relevant if properly exploited; however, if improperly controlled, anisotropy may confound stiffness measurements. The purpose of this study is to demonstrate the clinical feasibility of acoustic radiation force (ARF)-induced peak displacement (PD) measures for both exploiting and obviating mechanical anisotropy in the cortex of human kidney allografts, in vivo . Validation of the imaging methods is provided by preclinical studies in pig kidneys, in which ARF-induced PD values were significantly higher ( $p , Wilcoxon) when the transducer executing asymmetric ARF was oriented across versus along the nephrons. The ratio of these PD values obtained with the transducer oriented across versus along the nephrons strongly linearly correlated ( $R^{2} = 0.95$ ) to the ratio of shear moduli measured by shear wave elasticity imaging. On the contrary, when a symmetric ARF was implemented, no significant difference in PD was observed ( $p > 0.01$ ). Similar results were demonstrated in vivo in the kidney allografts of 14 patients. The symmetric ARF produced PD measures with no significant difference ( $p > 0.01$ ) between along versus across alignments, but the asymmetric ARF yielded PD ratios that remained constant over a six-month observation period post-transplantation, consistent with stable serum creatinine level and urine protein-to-creatinine ratio in the same patient population ( $p> 0.01$ ). The results of this pilot in vivo clinical study suggest the feasibility of 1) implementing symmetrical ARF to obviate mechanical anisotropy in the kidney cortex when anisotropy is a confounding factor and 2) implementing asymmetric ARF to exploit mechanical anisotropy when mechanical anisotropy is a potentially relevant biomarker.

Precise manipulation of microparticles in microchannels is a primary technique for numerous lab-on-a-chip bioengineering research and applications, as it determines the chip’s functions and analytical results. Acoustic manipulation, using the acoustic radiation force, is a compact, versatile and contactless manipulation technique, which can be easily integrated with other microfluidic components. It is our main purpose to report the effect of boundary condition of a cylindrical microfluidic cavity on the acoustic particles’ manipulation. A device consisting of a cylindrical cavity in a silicon wafer with three kinds of top boundary conditions (rigid, soft, and imperfect rigid boundary) has been built. The corresponding distributions of acoustic radiation force are analyzed analytically and numerically. Experiments are performed with 2.5 μm radius polystyrene microspheres in the cavity covered by three reflective layers (340 μm-thick glass, 400 μm-thick PDMS, and 660 μm-thick glass film), respectively, which specify the three different boundary conditions at the top of the cavity. It is demonstrated that the boundary condition of a cavity influences the acoustic radiation force and the stable positions of particles, and this is in agreement with the theoretical predictions. Thus, the effects of boundary conditions need to be considered for precise acoustic manipulation.