![Mixing in acoustofluidics. (a) Schematic drawing of a bubble‐assisted PZT mixer, which may produce fast‐switching chaotic flows for multiplexed detection of cancer biomarkers. Reproduced from ref. [18] Copyright (2018), with permission from Royal Society of Chemistry. (b) Schematic of a PZT mixer with sharp‐edges. Reproduced from ref. [19] Copyright (2021), with permission from Royal Society of Chemistry. (c) Schematic illustration of a PZT mixer using an array of PDMS micropillars in a ship‐shaped microchannel for thrombin detection. Reproduced from ref. [20] Copyright (2021), with permission from Elsevier. (d) SMR‐based acoustofluidic device with sub‐milliseconds mixing performance. Reproduced from ref. [21] Copyright (2016), with permission from AIP Publishing. (e) A POC biosensing device with SAW‐induced mixing for the detection of viruses. Reproduced from ref. [22] Copyright (2022), with permission from Wiley‐VCH. (f) LWR‐induced acoustic streaming for microscale efficient mixing in the solid−liquid heterogeneous immunoassay. Reproduced from ref. [23] Copyright (2021), with permission from American Chemical Society.](https://www.researchgate.net/publication/375381656/figure/fig1/AS:11431281243902876@1715770161223/Mixing-in-acoustofluidics-a-Schematic-drawing-of-a-bubble-assisted-PZT-mixer-which_Q320.jpg)
![Pumping in acoustofluidics. (a) Schematic diagram of a unidirectional pumping by collecting the upwards net flow in the cavitational microstreaming of PZT. Reproduced from ref. [25] Copyright (2010), with permission from Society for Laboratory Automation and Screening. (b) Schematic illustration of a bidirectional pumping based on bubbles in opposite directions. Reproduced from ref. [26] Copyright (2020), with permission from Springer Nature. (c) A global bulk flow generated by an array of oscillated air/liquid interfaces under the actuation of PZT. Reproduced from ref. [27] Copyright (2019), with permission from Royal Society of Chemistry. (d) A continuous flow pumping between external reservoirs with consideration given to the direction of SAW attenuation. Reproduced from ref. [29] Copyright (2014), with permission from Royal Society of Chemistry. (e) Schematic of digital acoustofluidic pump powered by SAW‐induced streaming. Reproduced from ref. [30] Copyright (2019), with permission from American Chemical Society. (f) LWR‐based unidirectional pumping device in an “L‐shaped” microchannel. Reproduced from ref. [31] Copyright (2022), with permission from Royal Society of Chemistry.](https://www.researchgate.net/publication/375381656/figure/fig2/AS:11431281243922690@1715770161595/Pumping-in-acoustofluidics-a-Schematic-diagram-of-a-unidirectional-pumping-by_Q320.jpg)
![Valving in acoustofluidics. (a) Schematic diagram showing the acoustic flow switch powered by SAW in a “H‐shaped” microchannel. Reproduced from ref. [32] Copyright (2018), with permission from Royal Society of Chemistry. (b) A dynamic flow switch by regulating the applied power of LWRs. Reproduced from ref. [31] Copyright (2022), with permission from Royal Society of Chemistry.](https://www.researchgate.net/publication/375381656/figure/fig3/AS:11431281243859563@1715770161876/Valving-in-acoustofluidics-a-Schematic-diagram-showing-the-acoustic-flow-switch_Q320.jpg)
![Separation in acoustofluidics. (a) Schematic diagram of an “out‐of‐plane” plastic‐based platelet separation device under the actuation of PZT. Reproduced from ref. [33] Copyright (2019), with permission from Royal Society of Chemistry. (b) Schematic of acoustofluidic separation of proteins using traveling SAW. Reproduced from ref. [34] Copyright (2021), with permission from American Chemical Society. (c) Two separation modules with parallel IDT group for exosomes separation. Reproduced from ref. [35] Copyright (2021), with permission from Springer Nature. (d) Acoustic nanoscale separation via ANSWER phenomenon. Reproduced from ref. [36] Copyright (2022), with permission from American Association for the Advancement of Science.](https://www.researchgate.net/publication/375381656/figure/fig4/AS:11431281243859564@1715770162098/Separation-in-acoustofluidics-a-Schematic-diagram-of-an-out-of-plane-plastic-based_Q320.jpg)
![Trapping in acoustofluidics. (a) The different mode of acoustic trapping using a focusing PZT and a 96‐well microplate. Reproduced from ref. [37] Copyright (2004), with permission from AIP Publishing. (b) Photo of the acoustofluidic trapping device based on PZT and illustration of nanoparticle trapping performance. Reproduced from ref. [38] Copyright (2020), with permission from American Chemical Society. (c) Schematic presentation of 2D trapping using two orthogonally placed PZTs. Reproduced from ref. [39] Copyright (2020), with permission from AIP Publishing. (d) Schematic of probe trapping based on acoustic streaming tweezers generated by SMR. Reproduced from ref. [41] Copyright (2023), with permission from American Chemical Society. (e) Schematic illustration of a single acoustic vortex in a capillary tube for nanoparticle trapping. Reproduced from ref. [43] Copyright (2017), with permission from American Chemical Society. (f) A schematic of the sound wave activated nano‐sieve using SAW excited packed bed of microparticles. Reproduced from ref. [45] Copyright (2020), with permission from Royal Society of Chemistry.](https://www.researchgate.net/publication/375381656/figure/fig5/AS:11431281243859566@1715770162454/Trapping-in-acoustofluidics-a-The-different-mode-of-acoustic-trapping-using-a-focusing_Q320.jpg)
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Recent Advances in Acoustofluidics for Point‐of‐Care Testing
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Abstract and Figures
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.
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... Looking towards the future, SAW devices are poised to be highly promising candidates for lab-on-chip applications across various fields, including clinical diagnosis, laboratory research, food safety, and environmental monitoring. This technology is anticipated to enable precise, high throughput, and continuous manipulation of small targets and multimodal operations in point-of-care applications [94]. For instance, Husseini et al. demonstrated the potential to create portable point-of-care DNA testing, allowing for rapid and accurate DNA testing in diverse settings [95]. ...
Surface acoustic wave (SAW)-based microfluidics has emerged as a promising technology for precisely manipulating particles and cells at the micro- and nanoscales. Acoustofluidic devices offer advantages such as low energy consumption, high throughput, and label-free operation, making them suitable for particle manipulation tasks including pumping, mixing, sorting, and separation. In this review, we provide an overview and discussion of recent advancements in SAW-based microfluidic devices for micro- and nanoparticle manipulation. Through a thorough investigation of the literature, we explore interdigitated transducer designs, materials, fabrication techniques, microfluidic channel properties, and SAW operational modes of acoustofluidic devices. SAW-based actuators are mainly based on lithium niobate piezoelectric transducers, with a plethora of wavelengths, microfluidic dimensions, and transducer configurations, applied for different fluid manipulation methods: mixing, sorting, and separation. We observed the accuracy of particle sorting across different size ranges and discussed different alternative device configurations to enhance sensitivity. Additionally, the collected data show the successful implementation of SAW devices in real-world applications in medical diagnostics and environmental monitoring. By critically analyzing different approaches, we identified common trends, challenges, and potential areas for improvement in SAW-based microfluidics. Furthermore, we discuss the current state-of-the-art and opportunities for further research and development in this field.
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.
Magnetic beads manipulation in microfluidic chips is a promising research field for biological application, especially in the detection of biological targets. In this review, we intend to present a thorough and in-depth overview of recent magnetic beads manipulation in microfluidic chips and its biological application. First, we introduce the mechanism of magnetic manipulation in microfluidic chip, including force analysis, particle properties, and surface modification. Then, we compare some existing methods of magnetic manipulation in microfluidic chip and list their biological application. Besides, the suggestions and outlook for future developments in the magnetic manipulation system are also discussed and summarized.
Multiplex detection of protein post‐translational modifications (PTMs), especially at point‐of‐care, is of great significance in cancer diagnosis. Herein, we report a machine learning‐assisted photonic crystal hydrogel (PCH) sensor for multiplex detection of PTMs. With closely‐related PCH sensors microfabricated on a single chip, our design achieved not only rapid screening of PTMs at specific protein sites by using only naked eyes/cellphone, but also the feasibility of real‐time monitoring of phosphorylation reactions. By taking advantage of multiplex sensor chips and a neural network algorithm, accurate prediction of PTMs by both their types and concentrations was enabled. This approach was ultimately used to detect and differentiate up/down regulation of different phosphorylation sites within the same protein in live mammalian cells. Our developed method thus holds potential for POC identification of various PTMs in early‐stage diagnosis of protein‐related diseases.
Diffusion limitations and nonspecific surface absorption are great challenges for developing micro-/nanoscale affinity biosensors. There are very limited approaches that can solve these issues at the same time. Here, an acoustic streaming approach enabled by a gigahertz (GHz) resonator is presented to promote mass transfer of analytes through the jet mode and biofouling removal through the shear mode, which can be switched by tuning the deviation angle, α, between the resonator and the sensor. Simulations show that the jet mode (α ≤ 0) drives the analytes in the fluid toward the sensing surface, overcomes the diffusion limitation, and enhances the binding; while the shear mode (0 < α < π/4) provides a scouring action to remove the biofouling from the sensor. Experimental studies were performed by integrating this GHz resonator with optoelectronic sensing systems, where a 34-fold enhancement for the initial binding rate was obtained. Featuring high efficiency, controllability, and versatility, we believe that this GHz acoustic streaming approach holds promise for many kinds of biosensing systems as well as lab-on-chip systems.
Acoustofluidics is a technique that utilizes the forces produced by ultrasonic waves and fluid flows to manipulate cells or nano-/microparticles within microfluidic systems. In this study, we demonstrate the feasibility of performing the Raman analysis of living human erythrocytes (Erys) within a 3D-printed acoustofluidic device designed as a half-wavelength multilayer resonator. Experiments show that a stable and orderly Ery aggregate can be formed in the pressure nodal plane at the resonator's mid-height. This has a significant potential for improving the applicability of Raman spectroscopy in single Ery analysis, as evidenced by the acquisition of the spectrum of healthy and pre-heated Erys without substrate interference. Moreover, principal component analysis applied on the obtained spectra confirms the correct Ery group identification. Our study demonstrates that 3D-printed acoustofluidic devices can improve the accuracy and sensitivity of Raman spectroscopy in blood investigations, with potential clinical applications for noninvasive disease diagnosis and treatment monitoring.
With extensive and widespread uses of miniaturized and intelligent wearable devices, continuously monitoring subtle spatial and temporal changes in human physiological states becomes crucial for daily healthcare and professional medical diagnosis. Wearable acoustical sensors and related monitoring systems can be comfortably applied onto human body with a distinctive function of non-invasive detection. This paper reviews recent advances in wearable acoustical sensors for medical applications. Structural designs and characteristics of the structural components of wearable electronics, including piezoelectric and capacitive micromachined ultrasonic transducer (i.e., pMUT and cMUT), surface acoustic wave sensors (SAW) and triboelectric nanogenerators (TENGs) are discussed, along with their fabrication techniques and manufacturing processes. Diagnostic applications of these wearable sensors for detection of biomarkers or bioreceptors and diagnostic imaging have further been discussed. Finally, main challenges and future research directions in these fields are highlighted.
Flexible and wearable acoustic wave technology has recently attracted tremendous attention due to their wide-range applications in wearable electronics, sensing, acoustofluidics, and lab-on-a-chip, attributed to its advantages such as low power consumption, small size, easy fabrication, and passive/wireless capabilities. Great effort has recently been made in technology development, fabrication, and characterization of rationally designed structures for next-generation acoustic wave based flexible electronics. Herein, advances in fundamental principles, design, fabrication, and applications of flexible and wearable acoustic wave devices are reviewed. Challenges in material selections (including both flexible substrate and piezoelectric film) and structural designs for high-performance flexible and wearable acoustic wave devices are discussed. Recent advances in fabrication strategies, wave mode theory, working mechanisms, bending behavior, and performance/evaluation are reviewed. Key applications in wearable and flexible sensors and acoustofluidics, as well as lab-on-a-chip systems, are discussed. Finally, major challenges and future perspectives in this field are highlighted.
Acoustofluidics offers contact-free manipulation of particles and fluids, enabling their uses in various life sciences, such as for biological and medical applications. Recently, there have been extensive studies on acoustic streaming-based acoustofluidics, which are formed inside a liquid agitated by leaky surface acoustic waves (SAWs) through applying radio frequency signals to interdigital transducers (IDTs) on a piezoelectric substrate. This paper aims to describe acoustic streaming-based acoustofluidics and provide readers with an unbiased perspective to determine which IDT structural designs and techniques are most suitable for their research. This review, first, qualitatively and quantitatively introduces underlying physics of acoustic streaming. Then, it comprehensively discusses the fundamental designs of IDT technology for generating various types of acoustic streaming phenomena. Acoustic streaming-related methodologies and the corresponding biomedical applications are highlighted and discussed, according to either standing surface acoustic waves or traveling surface acoustic waves generated, and also sessile droplets or continuous fluids used. Traveling SAW-based acoustofluidics generate various physical phenomena including mixing, concentration, rotation, pumping, jetting, nebulization/atomization, and droplet generation, as well as mixing and concentration of liquid in a channel/chamber. Standing SAWs induce streaming for digital and continuous acoustofluidics, which can be used for mixing, sorting, and trapping in a channel/chamber. Key challenges, future developments, and directions for acoustic streaming-based acoustofluidics are finally discussed.
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.
Aggregation-dependent brightness (ADB) indirectly limits the in vitro performance of a pure aggregation-induced emission (AIE) probe in many ways; thus, controlling the aggregation state of the AIE probe is helpful for detecting an object of interest. Many studies are focused on the molecule design of the AIE probes, while less efforts have been made for the control of the aggregation of the AIEs. Here, an acoustic streaming tweezer (AST) generated using a gigahertz bulk acoustic wave resonator was applied to manipulate the aggregation status of the AIE probe and further enhance their performance for human serum albumin (HSA) detection. As the trapping size of the AST matches the working size of the AIE probe, the streaming can enrich and accumulate AIE nanoparticles, which then further trigger larger aggregates. Due to the ADB effect, the fluorescence intensity strongly increased, and thus, the detection limit of HSA was reduced to 0.5 μg/mL, which is low enough for kidney disease detection. Such an AST-assisted ADB strategy is potentially applicable to other AIE probes and can work as a portable choice for the biomedical detection.