Acoustic Tweezers Research Articles

Acoustic manipulation of microparticles using a piezoelectric phononic crystal plate

Acoustic tweezer is a promising device for manipulating particles, which does not need contact does not cause damage, or requires transparent materials. They have diverse applications in cell separation, tissue engineering, and material assembly. To control particle movement, this technology relies on the exchange of momentum between the particle and the acoustic field, generating an acoustic radiation force. Achieving high-performance acoustic tweezers necessitates the precise shaping of the acoustic fields. Traditionally, there are mainly two types of acoustic tweezers: bulk acoustic wave (BAW) and surface acoustic wave (SAW). The SAW-based acoustic tweezer operates at high frequencies, realizing precise manipulation. The BAW-based acoustic tweezer operates at lower frequencies and requires artificial structure on the transducer surface to shape the field. However, the separation of the artificial structure from the transducer brings complexity and instability into the manipulation process. In this study, we propose a novel approach to overcoming these challenges, that is, using piezoelectric phononic crystal plates to integrate the transducer and acoustic artificial structure. By designing the thickness, periodicity, and electrode width of the piezoelectric phononic crystal plate, we can excite the <i>A</i><sub>0</sub> Lamb wave mode and the periodic resonant mode, resulting in a periodic gradient field and a periodic weak gradient field, respectively. These fields enable particle to be trapped or levitated on the surface. To validate this approach, an experimental device is constructed, and successful particle manipulation is achieved by using Lamb wave mode or periodic resonant mode through using the piezoelectric phononic crystal plate. This technological breakthrough serves as a crucial foundation and experimental validation for developing the compact, low-energy and high-precision acoustic tweezers.

Super-Resolution Ultrasound Imaging for Analysis of Microbubbles Cluster by Acoustic Vortex Tweezers.

Using acoustic vortex tweezers (AVT) to spatially accumulate microbubbles (MBs) shows promise for enhancing drug delivery efficiency and reducing off-target effects. The strong echogenicity of accumulated MBs also improves diagnostics via conventional ultrasound (US) B-mode imaging. However, the annular high-pressure distribution of AVT inhibits MBs inflow at the inlet, reducing MBs collection. The spatial resolution of US B-mode imaging further limits theranostic applications of AVT-mediated MBs accumulation. To address these challenges, we integrated an AVT waveform with volumetric super-resolution imaging (VSRI) to monitor the dynamic growth of MBs cluster during accumulation. We used a 5-MHz 2D array transducer for VSRI, employing plane wave pulses interleaved with accumulating pulses to retain MBs at a flow rate of 0.023-0.047 mL/s in a 3-mm vessel phantom. An asymmetrical AVT waveform (AVT*) was produced by modulating the pressure at the MBs inlet compared to the outlet. The effectiveness was validated in rat cerebral vessels for real-time volumetric tracking of MBs clusters. Microscopy observations showed that AVT* could quickly gather flowing MBs into cluster without repelling them at a flow rate of 0.023 mL/s. Statistical results indicated that microscopic data correlated better with VSRI than with B-mode images, suggesting VSRI suffices to detect the dynamics of AVT*-actuated MBs accumulation in real-time. Additionally, VSRI detected a significant increase in MBs cluster size over time during AVT* in the superior sagittal sinus of the rat brain. These findings demonstrate that the proposed strategy can accumulate the flowing MBs at a desired location and simultaneously observe this phenomenon.

Acoustophoresis-driven particle focusing and separation with standard/inverse Chladni patterns

The classical standard/inverse Chladni patterns are reproduced in an aqueous environment for the first time. Sinking particles and suspended particles are separated by standard/inverse Chladni patterns, paving the way for advanced acoustic tweezers.

A localized approximation approach for the calculation of beam shape coefficients of acoustic and ultrasonic Bessel beams

The description of acoustical waves can be achieved using an expansion over basic functions with weighting coefficients which may be called beam shape coefficients (BSCs). There is a strong analogy between the scalar formalism of acoustical waves and the vectorial electromagnetic formalism, known as generalized Lorenz–Mie theory (GLMT), describing the interaction between a homogeneous sphere and an arbitrary illuminating beam. In particular, BSCs have been introduced as well in GLMT and the mathematical arsenal to evaluate them, developed since several decades, can be used mutatis mutandis to evaluate BSCs in acoustics. In particular, the present paper introduces a method named localized approximation to the evaluation of the acoustical BSCs, similar to the localized approximation used to evaluate electromagnetic BSCs, in the case of Bessel beams. Such a formalism akin to the electromagnetic GLMT may be viewed as an acoustical GLMT and should allow a renewal of the calculation of various properties of acoustical wave scattering, in particular to the design of acoustical tweezers similar to optical tweezers.

Numerical Beamforming and Parametric Descriptions of Laguerre-Gaussian Vortex Beams

Vortex beams are beams with a helical wavefront that have found applications in optical or acoustic tweezers to manipulate microscopic particles. Vortex beam imposes torque or force to particles, allowing them to trap the object within the beam's field and induce motion or displacement in a non-contact manner. One type of such beam is a Laguerre-Gaussian beam, where the solution of a Gaussian wave is modified by the Laguerre polynomial term that determines the pattern and helical characteristic of the beam. In this paper, a numerical method based on the mathematical expression of the Laguerre-Gaussian beam is implemented to describe how the parameters change the physical behavior of the beam. This work has shown that a straightforward numerical method is capable of producing this kind of beam. Therefore, this approach can be used for generating vortex beams for physical emissions, complex numerical simulations, or demonstrations for teaching purposes

Filtered Lebedev quadrature method for robust and efficient beam shape coefficient estimation in acoustic tweezers calibration.

Acoustic tweezers offer a contactless, three-dimensional, and selective approach to trapping objects by harnessing the acoustic radiation force. Precise control of this technique requires accurate calibration of the force, which depends on the object's properties and the spherical harmonics expansion of the incident field through the beam shape coefficients. Previous studies showed that these coefficients can be determined using either the Lebedev quadrature or the angular spectrum methods. However, the former is highly susceptible to noise, while the latter demands extensive implementation time due to the number of required measurement points. A filtered method with a reduced number of points is introduced to address these limitations. Initially, we emphasize the implicit filtering in the angular spectrum method, allowing relative noise insensitivity. Subsequently, we present its unfiltered version, enabling force estimation of a standing field. Finally, we develop a filtered method based on the Lebedev quadrature, requiring fewer points, and apply it to focused vortex beams. Numerical evaluation of the radiation force demonstrates the method's resilience to noise and a reduced need for points compared to previous methods. The filtered Lebedev method paves the way for characterizing high-frequency acoustic tweezers, where measurement constraints necessitate rapid and robust beam shape coefficient estimation techniques.

Born approximation of trapping forces by acoustical Bessel and vortex fields.

Acoustic radiation forces have been used to trap various objects for fundamental studies and practical applications. Born approximation method, originally introduced to solve quantum scattering problems, is herein extended to analyze trapping forces exerted by two- and three-dimensional acoustic Bessel and vortex fields on spherical and nonspherical objects of arbitrary size. The results are compared with the conventional models like the partial wave expansion and Gorkov force potential. It is shown that for weakly scattering objects (such as common soft biological particles surrounded by fluids), the Born approximation can make predictions for the trapping forces on objects whose characteristic lengths are even up to multiple wavelengths of the sound beams. With the aid of the approximation, the Gorkov force potential is applied to analyze and gain insights into trapping forces on large objects far beyond the original Rayleigh scattering regime. The effects caused by the beam parameters, object shape, and orientation on the trapping behaviors are revealed. This work is useful for the further study of acoustic radiation forces and will guide the experiment of simplified acoustic tweezers on arbitrary-shaped particles.

Acoustic-propelled micro/nanomotors and nanoparticles for biomedical research, diagnosis, and therapeutic applications.

Acoustic manipulation techniques have gained significant attention across various fields, particularly in medical diagnosis and biochemical research, due to their biocompatibility and non-contact operation. In this article, we review the broad range of biomedical applications of micro/nano-motors that use acoustic manipulation methods, with a specific focus on cell manipulation, targeted drug release for cancer treatment and genetic disease diagnosis. These applications are facilitated by acoustic-propelled micro/nano-motors and nanoparticles which are manipulated by acoustic tweezers. Acoustic systems enable high precision positioning and can be effectively combined with magnetic manipulation techniques. Furthermore, acoustic propulsion facilitates faster transportation speeds, making it suitable for tasks in blood flow, allowing for precise positioning and in-body manipulation of cells, microprobes, and drugs. By summarizing and understanding these acoustic manipulation methods, this review aims to provide a summary and discussion of the acoustic manipulation methods for biomedical research, diagnostic, and therapeutic applications.

Red blood cell trapping using single-beam acoustic tweezers in the Rayleigh regime

Acoustic tweezers (ATs) are a promising technology that can trap and manipulate microparticles or cells with the focused ultrasound beam without physical contact. Unlike optical tweezers, ATs may be used for invivo studies because they can manipulate cells through tissues. However, in previous non-invasive microparticle trapping studies, ATs could only trap spherical particles, such as beads. Here, we present a theoretical analysis of how the acoustic beam traps red blood cells (RBCs) with experimental demonstration. The proposed modeling shows that the trapping of a non-spherical, biconcave-shaped RBC could be successfully done by single-beam acoustic tweezers (SBATs). We demonstrate this by trapping RBCs using SBATs in the Rayleigh regime, where the cell size is smaller than the wavelength of the beam. Suggested SBAT is a promising tool for cell transportation and sorting.

Single focused-beam acoustical tweezers: Trapping cells in 3-D

Single focused beams have shown great potential in acoustofluidics and medical ultrasound because of their large pressure gradient and acoustic-thermal effect, such as acoustical tweezers and high-intensity focused ultrasound (HIFU) technique. However, the three-dimensional trapping of typical cells is still challenging since cells in water have a positive acoustic contrast factor and will be repulsive from the focus [Gong and Baudoin, Phys. Rev. Applied 18, 044033 (2022)]. In this work, to reverse this positive acoustic contrast factor into negative, we propose to use a cell-friendly medium (made of iodixanol with water) [Augustsson et al., Nat. Commun. 7, 11556 (2016)]. This enables a single focused beam to selectively trap and control cells in 3-D, and more importantly, keeps the manipulated cells with good viability. This work will extend the applications of acoustical tweezers, which may be beneficial to single cell analysis, cellular phenotyping, precise assembly of different cells in tissue engineering, and controlled drug delivery.

Scheme of negative acoustic radiation force based on a multiple-layered spherical structure

Acoustic radiation force (ARF), as an important particle manipulation method, has been extensively studied in recent years. With the introduction of the concept of “acoustic tweezers”, negative acoustic radiation has become a research hotspot. In this paper, a scheme of realizing negative ARF based on the multiple-layered spherical structure design is proposed. The specific structure and design idea are presented. Detailed theoretical calculation analysis is carried out. Numerical simulations have been performed to verify the correctness of this prediction. The conjecture that the suppression of backscattering can achieve negative ARF is verified concretely, which greatly expands the application prospect and design ideas of the ARF. This work has laid a theoretical foundation for realizing precise control of the structure.

Broadband high-efficiency acoustic vortices via a topology-optimized space-coiling-cavity metasurface

Acoustic vortices carrying orbital angular momentum are significant in wave-matter interactions, allowing for versatile devices with promising applications. However, current metasurface-based vortex generators have limited bandwidth, operating within a narrow frequency range. Here, we propose a broadband acoustic metasurface with four space-coiling-cavity units through the bottom-up topology optimization. These units have constant phase differences with high-efficiency transmission (>0.8) over a desired frequency range [3.0, 4.0] kHz, indicating the unique wideband vortex response of their assembled metasurfaces. Our simulations and experiments further demonstrate this excellent performance. This breakthrough in broadband vortices allows for the development of devices like acoustic tweezers, antennas, and spanners.

Calibration of the axial stiffness of a single-beam acoustic tweezers.

Single-beam acoustic tweezers have recently been demonstrated to be capable of selective three-dimensional trapping. This new contactless manipulation modality has great potential for many scientific applications. Its development as a scientific tool requires precise calibration of its radiation force, specifically its axial component. The lack of calibration for this force is mainly due to its weak magnitude compared to competing effects such as weight. We investigate an experimental method for the calibration of the axial stiffness of the radiation force by observing the axial oscillations of a trapped bead in a microgravity environment. The stiffness exhibits a linear relationship with the acoustic intensity and is of the mN/m order. Then, a predictive model, loaded with the experimental acoustic field, is compared to the measured stiffness with very good agreement, within a single amplitude coefficient. This study paves the way for the development of calibrated acoustic tweezers.

Acoustic tweezers for high-throughput single-cell analysis.

Acoustic tweezers provide an effective means for manipulating single cells and particles in a high-throughput, precise, selective and contact-free manner. The adoption of acoustic tweezers in next-generation cellular assays may advance our understanding of biological systems. Here we present a comprehensive set of instructions that guide users through device fabrication, instrumentation setup and data acquisition to study single cells with an experimental throughput that surpasses traditional methods, such as atomic force microscopy and micropipette aspiration, by several orders of magnitude. With acoustic tweezers, users can conduct versatile experiments that require the trapping, patterning, pairing and separation of single cells in a myriad of applications ranging across the biological and biomedical sciences. This procedure is widely generalizable and adaptable for investigations in materials and physical sciences, such as the spinning motion of colloids or the development of acoustic-based quantum simulations. Overall, the device fabrication requires ~12 h, the experimental setup of the acoustic tweezers requires 1-2 h and the cell manipulation experiment requires ~30 min to complete. Our protocol is suitable for use by interdisciplinary researchers in biology, medicine, engineering and physics.

Single-channel acoustic vortex tweezer with attachable fan-shaped holographic lens

The utilization of acoustic vortices presents a promising technique for contactless particle manipulation. However, existing methods for generating acoustic vortices typically rely on complex active driving systems and array ultrasound transducers. Therefore, more simplified and robust approaches to inducing acoustic vortices should be considered. With inspiring the fact that acoustic vortices can be generated by the differences in the height of adjacent sectors in conventional four-panel transducers, we aim to develop a single-channel acoustic vortex tweezer with a simplified driving system by incorporating attachable fan-shaped polydimethylsiloxane (PDMS) holographic lens. This passive lens structure with different heights in adjacent sectors can generate phase-modulated ultrasonic waves. Therefore, the interaction of phase-modulated waves passing through the lens is expected to result in a vortex-like beam. The available materials of fan-shaped lens are not limited to the PDMS. This lens type can be appropriately fabricated with an understanding of the sound of speed within the desired material and predetermined thickness, inducing π/2 phase difference in the adjacent lobes. As a result, the excited acoustic waves propagated through the lens were under mutual interaction without any active electrical setup, forming a null pressure region enveloped by four distinct acoustic lobes. We systemically investigated the tweezing potential using vortex-like waves. Several types of bioparticles were utilized in these investigations: microbubbles, polystyrene (PS) beads, and cancer cells. Our findings demonstrate that the transducer with lens is sufficiently capable of spatial manipulation of bioparticles. Remarkably, the microbubbles traveling at a flow velocity of 32 cm/s in a blood vessel-mimicking phantom were feasibly trapped in the proposed transducer. Furthermore, the spatial control of PS and cells with higher acoustic impedance was also feasible in static conditions. Consequently, the proposed transducer offers an economically and practically viable solution for various biomedical applications, such as drug delivery and cell-based bioengineering.

Robust acoustic trapping and perturbation of single-cell microswimmers illuminate three-dimensional swimming and ciliary coordination

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

In-vivo programmable acoustic manipulation of genetically engineered bacteria

Acoustic tweezers can control target movement through the momentum interaction between an acoustic wave and an object. This technology has advantages over optical tweezers for in-vivo cell manipulation due to its high tissue penetrability and strong acoustic radiation force. However, normal cells are difficult to acoustically manipulate because of their small size and the similarity between their acoustic impedance and that of the medium. In this study, we use the heterologous expression of gene clusters to generate genetically engineered bacteria that can produce numerous sub-micron gas vesicles in the bacterial cytoplasm. We show that the presence of the gas vesicles significantly enhances the acoustic sensitivity of the engineering bacteria, which can be manipulated by ultrasound. We find that by employing phased-array-based acoustic tweezers, the engineering bacteria can be trapped into clusters and manipulated in vitro and in vivo via electronically steered acoustic beams, enabling the counter flow or on-demand flow of these bacteria in the vasculature of live mice. Furthermore, we demonstrate that the aggregation efficiency of engineering bacteria in a tumour is improved by utilizing this technology. This study provides a platform for the in-vivo manipulation of live cells, which will promote the progress of cell-based biomedical applications.

Phase-Optimized Multi-Step Phase Acoustic Metasurfaces for Arbitrary Multifocal Beamforming.

Focused ultrasound featuring non-destructive and high sensitivity has attracted widespread attention in biomedical and industrial evaluation. However, most traditional focusing techniques focus on the design and improvement of single-point focusing, neglecting the need to carry more dimensions of multifocal beams. Here we propose an automatic multifocal beamforming method, which is implemented using a four-step phase metasurface. The metasurface composed of four-step phases improves the transmission efficiency of acoustic waves as a matching layer and enhances the focusing efficiency at the target focal position. The change in the number of focused beams does not affect the full width at half maximum (FWHM), revealing the flexibility of the arbitrary multifocal beamforming method. Phase-optimized hybrid lenses reduce the sidelobe amplitude, and excellent agreement is observed between the simulation and experiments for triple-focusing beamforming metasurface lenses. The particle trapping experiment further validates the profile of the triple-focusing beam. The proposed hybrid lens can achieve flexible focusing in three dimensions (3D) and arbitrary multipoint, which may have potential prospects for biomedical imaging, acoustic tweezers, and brain neural modulation.

Numerical Simulation of the Radiation Force from Transient Acoustic Fields: Application to Laser-Guided Acoustic Tweezers

Using pulsed acoustic waves could provide a superior selectivity for microscale acoustic tweezers. However, the theory for the radiation force of pulsed acoustic waves has only been recently derived and no numerical implementations are available. In this paper, we present a finite-element implementation of this model to simulate the transient acoustic radiation force on small spheres. We use the model to simulate laser-guided acoustic tweezers and optimize their performance. By enabling numerical simulations of the transient radiation force, this work may accelerate the rational design of pulse-based high-selectivity acoustic tweezer devices.

A Multifunctional Acoustic Tweezer for Heterogenous Assembloids Patterning

Acoustic Tweezer for Heterogenous Assembloids Patterning Heterogeneous assembloids with predesigned patterns can be constructed sequentially to explore polarized tissue development or disease metastasis in multi-organs. In article 2200288, Hairong Zheng, Xiao Zhang, Teng Ma, and co-workers present a multifunctional acoustic tweezer system that manipulates single organoid to construct assembloids non-invasively and free-label—this pioneering study demonstrates the possibility of bulk-wave acoustic tweezer application in tissue engineering.