Search

Acoustofluidics is a promising technology that leverages acoustic waves for precise manipulation of micro/nano‐scale flows and suspended objects within microchannels. Despite many advantages, the practical applicability of conventional acoustofluidic platforms is limited by irreversible bonding between the piezoelectric actuator and the microfluidic chip. Recently, reconfigurable acoustofluidic platforms are enabled by reversible bonding between the reusable actuator and the replaceable polydimethylsiloxane (PDMS) microfluidic chip by incorporating a PDMS membrane for sealing the microchannel and coupling the acoustic waves with the fluid inside. However, a quantitative guideline for selecting a suitable PDMS membrane for various acoustofluidic applications is still missing. Here, a design rule for reconfigurable acoustofluidic platforms is explored based on a thorough investigation of the PDMS thickness effect on acoustofluidic phenomena: acousto–thermal heating (ATH), acoustic radiation force (ARF), and acoustic streaming flow (ASF). These findings suggest that the relative thickness of the PDMS membrane (t) for acoustic wavelength (λPDMS) determines the wave attenuation in the PDMS and the acoustofluidic phenomena. For t/λPDMS ≈ O(1), the transmission of acoustic waves through the membrane leads to the ARF and ASF phenomena, whereas, for t/λPDMS ≈ O(10), the acoustic waves are entirely absorbed within the membrane, resulting in the ATH phenomenon. [ABSTRACT FROM AUTHOR]

Acoustic manipulation has emerged as a valuable tool for precision controls and dynamic programming of cells and particles. However, conventional acoustic manipulation approaches lack the finesse necessary to form intricate, configurable, continuous, and 3D patterning of particles. Here, this study reports acoustography by Beam Engineering and Acoustic Control Node (BEACON), which delivers intricate, configurable patterns by guiding particles along custom paths with independent phase modulation. Leveraging analytical methods of orbital angular momentum beam via iterative Wirtinger hologram algorithm, this study accomplish acoustography by facilitating orbital angular momentum traps, enabling continuous 2D and 3D acoustic manipulation of microparticles in any desired geometry, with phase modulation independent of intensity. Utilizing on‐chip acoustography, the BEACON platform markedly increases the space‐bandwidth product to 31 000 while attaining an enhanced resolution with a pixel size of ≈25 µm, surpassing the typical resolution of over 200 µm in previous holographic particle manipulation methods. The capabilities of BEACON are demonstrated in creating intricate triple helical tracing structures using microdroplets (20 µm in diameter) and those carrying DNA to validate the effectiveness of the acoustography and phase control methods. This study offers new particle manipulation opportunities, paving the way for next‐generation biomedical systems and the future of contact‐free precision manufacturing. [ABSTRACT FROM AUTHOR]

Cytopathology, crucial in disease diagnosis, commonly uses microscopic slides to scrutinize cellular abnormalities. However, processing high volumes of samples often results in numerous negative diagnoses, consuming significant time and resources in healthcare. To address this challenge, a surface acoustic wave‐enhanced multi‐view acoustofluidic rotation cytometry (MARC) technique is developed for pre‐cytopathological screening. MARC enhances cellular morphology analysis through comprehensive and multi‐angle observations and amplifies subtle cell differences, particularly in the nuclear‐to‐cytoplasmic ratio, across various cell types and between cancerous and normal tissue cells. By prioritizing MARC‐screened positive cases, this approach can potentially streamline traditional cytopathology, reducing the workload and resources spent on negative diagnoses. This significant advancement enhances overall diagnostic efficiency, offering a transformative vision for cytopathological screening. [ABSTRACT FROM AUTHOR]

Ultrasound has been used to manipulate cells in both humans and animal models. While intramembrane cavitation and lipid clustering have been suggested as likely mechanisms, they lack experimental evidence. Here, high-speed digital holographic microscopy (kiloHertz order) is used to visualize the cellular membrane dynamics. It is shown that neuronal and fibroblast membranes deflect about 150 nm upon ultrasound stimulation. Next, a biomechanical model that predicts changes in membrane voltage after ultrasound exposure is developed. Finally, the model predictions are validated using whole-cell patch clamp electrophysiology on primary neurons. Collectively, it is shown that ultrasound stimulation directly defects the neuronal membrane leading to a change in membrane voltage and subsequent depolarization. The model is consistent with existing data and provides a mechanism for both ultrasound-evoked neurostimulation and sonogenetic control.

Controllable manipulation and effective mixing of fluids and colloids at the nanoscale is made exceptionally difficult by the dominance of surface and viscous forces. The use of megahertz (MHz)-order vibration has dramatically expanded in microfluidics, enabling fluid manipulation, atomization, and microscale particle and cell separation. Even more powerful results are found at the nanoscale, with the key discovery of new regimes of acoustic wave interaction with 200 fL droplets of deionized water. It is shown that 40 MHz-order surface acoustic waves can manipulate such droplets within fully transparent, high-aspect ratio, 100 nm tall, 20-130 micron wide, 5-mm long nanoslit channels. By forming traps as locally widened regions along such a channel, individual fluid droplets may be propelled from one trap to the next, split between them, mixed, and merged. A simple theory is provided to describe the mechanisms of droplet transport and splitting.

Tumor microenvironment crosstalk, in particular interactions between cancer cells, T cells, and myeloid‐derived suppressor cells (MDSCs), mediates tumor initiation, progression, and response to treatment. However, current patient‐derived models such as tumor organoids and 2D cultures lack some essential niche cell types (e.g., MDSCs) and fail to model complex tumor‐immune interactions. Here, the authors present the novel acoustically assembled patient‐derived cell clusters (APCCs) that can preserve original tumor/immune cell compositions, model their interactions in 3D microenvironments, and test the treatment responses of primary tumors in a rapid, scalable, and user‐friendly manner. By incorporating a large array of 3D acoustic trappings within the extracellular matrix, hundreds of APCCs can be assembled within a petri dish within 2 min. Moreover, the APCCs can preserve sensitive and short‐lived (≈1 to 2‐day lifespan in vivo) tumor‐induced MDSCs and model their dynamic suppression of T cell tumor toxicity for up to 24 h. Finally, using the APCCs, the authors succesully model the combinational therapeutic effect of a multi‐kinase inhibitor targeting MDSCs (cabozantinib) and an anti‐PD‐1 immune checkpoint inhibitor (pembrolizumab). The novel APCCs may hold promising potential in predicting treatment response for personalized cancer adjuvant therapy as well as screening novel cancer immunotherapy and combinational therapy. [ABSTRACT FROM AUTHOR]

Sperm motility is a significant predictor of male fertility potential and is directly linked to fertilization success in both natural and some forms of assisted reproduction. Sperm motility can be impaired by both genetic and environmental factors, with asthenozoospermia being a common clinical presentation. Moreover, in the setting of assisted reproductive technology clinics, there is a distinct absence of effective and noninvasive technology to increase sperm motility without detriment to the sperm cells. Here, a new method is presented to boost sperm motility by increasing the intracellular rate of metabolic activity using high frequency ultrasound. An increase of 34% in curvilinear velocity (VCL), 10% in linearity, and 32% in the number of motile sperm cells is shown by rendering immotile sperm motile, after just 20 s exposure. A similar effect with an increase of 15% in VCL treating human sperm with the same setting is also identified. This cell level mechanotherapy approach causes no significant change in cell viability or DNA fragmentation index, and, as such, has the potential to be applied to encourage natural fertilization or less invasive treatment choices such as in vitro fertilization rather than intracytoplasmic injection. [ABSTRACT FROM AUTHOR]

Abstract Ultrasound has been used to manipulate cells in both humans and animal models. While intramembrane cavitation and lipid clustering have been suggested as likely mechanisms, they lack experimental evidence. Here, high‐speed digital holographic microscopy (kiloHertz order) is used to visualize the cellular membrane dynamics. It is shown that neuronal and fibroblast membranes deflect about 150 nm upon ultrasound stimulation. Next, a biomechanical model that predicts changes in membrane voltage after ultrasound exposure is developed. Finally, the model predictions are validated using whole‐cell patch clamp electrophysiology on primary neurons. Collectively, it is shown that ultrasound stimulation directly defects the neuronal membrane leading to a change in membrane voltage and subsequent depolarization. The model is consistent with existing data and provides a mechanism for both ultrasound‐evoked neurostimulation and sonogenetic control.

Abstract Controllable manipulation and effective mixing of fluids and colloids at the nanoscale is made exceptionally difficult by the dominance of surface and viscous forces. The use of megahertz (MHz)‐order vibration has dramatically expanded in microfluidics, enabling fluid manipulation, atomization, and microscale particle and cell separation. Even more powerful results are found at the nanoscale, with the key discovery of new regimes of acoustic wave interaction with 200 fL droplets of deionized water. It is shown that 40 MHz‐order surface acoustic waves can manipulate such droplets within fully transparent, high‐aspect ratio, 100 nm tall, 20–130 micron wide, 5‐mm long nanoslit channels. By forming traps as locally widened regions along such a channel, individual fluid droplets may be propelled from one trap to the next, split between them, mixed, and merged. A simple theory is provided to describe the mechanisms of droplet transport and splitting.

Abstract Acoustic fields are capable of manipulating biological samples contained within the enclosed and highly controlled environment of a microfluidic chip in a versatile manner. The use of acoustic streaming to alter fluid flows and radiation forces to control cell locations has important clinical and life science applications. While there have been significant advances in the fundamental implementation of these acoustic mechanisms, there is a considerable lack of understanding of the associated biological effects on cells. Typically a single, simple viability assay is used to demonstrate a high proportion of living cells. However, the findings of this study demonstrate that acoustic exposure can inhibit cell attachment, decrease cell spreading, and most intriguingly increase cellular metabolic activity, all without any impact upon viability rates. This has important implications by showing that mortality studies alone are inadequate for the assessment of biocompatibility, but further demonstrates that physical manipulation of cells can also be used to influence their biological activity.

Abstract Synthesis of nanoparticles and particulate nanomaterials with tailored properties is a central step toward many applications ranging from energy conversion and imaging/display to biosensing and nanomedicine. While existing microfluidics‐based synthesis methods offer precise control over the synthesis process, most of them rely on passive, partial mixing of reagents, which limits their applicability and potentially, adversely alter the properties of synthesized products. Here, an acoustofluidic (i.e., the fusion of acoustic and microfluidics) synthesis platform is reported to synthesize nanoparticles and nanomaterials in a controllable, reproducible manner through acoustic‐streaming‐based active mixing of reagents. The acoustofluidic strategy allows for the dynamic control of the reaction conditions simply by adjusting the strength of the acoustic streaming. With this platform, the synthesis of versatile nanoparticles/nanomaterials is demonstrated including the synthesis of polymeric nanoparticles, chitosan nanoparticles, organic–inorganic hybrid nanomaterials, metal–organic framework biocomposites, and lipid‐DNA complexes. The acoustofluidic synthesis platform, when incorporated with varying flow rates, compositions, or concentrations of reagents, will lend itself unprecedented flexibility in establishing various reaction conditions and thus enable the synthesis of versatile nanoparticles and nanomaterials with prescribed properties.

Abstract: A particle suspended in a fluid within a microfluidic channel experiences a direct acoustic radiation force (ARF) when traveling surface acoustic waves (TSAWs) couple with the fluid at the Rayleigh angle, thus producing two components of the ARF. Most SAW‐based microfluidic devices rely on the horizontal component of the ARF to migrate prefocused particles laterally across a microchannel width. Although the magnitude of the vertical component of the ARF is more than twice the magnitude of the horizontal component, it is long ignored due to polydimethylsiloxane (PDMS) microchannel fabrication limitations and difficulties in particle focusing along the vertical direction. In the present work, a single‐layered PDMS microfluidic chip is devised for hydrodynamically focusing particles in the vertical plane while explicitly taking advantage of the horizontal ARF component to slow down the selected particles and the stronger vertical ARF component to push the particles in the upward direction to realize continuous particle separation. The proposed particle separation device offers high‐throughput operation with purity >97% and recovery rate >99%. It is simple in its fabrication and versatile due to the single‐layered microchannel design, combined with vertical hydrodynamic focusing and the use of both the horizontal and vertical components of the ARF. [ABSTRACT FROM AUTHOR]

Acoustic fields are capable of manipulating biological samples contained within the enclosed and highly controlled environment of a microfluidic chip in a versatile manner. The use of acoustic streaming to alter fluid flows and radiation forces to control cell locations has important clinical and life science applications. While there have been significant advances in the fundamental implementation of these acoustic mechanisms, there is a considerable lack of understanding of the associated biological effects on cells. Typically a single, simple viability assay is used to demonstrate a high proportion of living cells. However, the findings of this study demonstrate that acoustic exposure can inhibit cell attachment, decrease cell spreading, and most intriguingly increase cellular metabolic activity, all without any impact upon viability rates. This has important implications by showing that mortality studies alone are inadequate for the assessment of biocompatibility, but further demonstrates that physical manipulation of cells can also be used to influence their biological activity. [ABSTRACT FROM AUTHOR]

Synthesis of nanoparticles and particulate nanomaterials with tailored properties is a central step toward many applications ranging from energy conversion and imaging/display to biosensing and nanomedicine. While existing microfluidics‐based synthesis methods offer precise control over the synthesis process, most of them rely on passive, partial mixing of reagents, which limits their applicability and potentially, adversely alter the properties of synthesized products. Here, an acoustofluidic (i.e., the fusion of acoustic and microfluidics) synthesis platform is reported to synthesize nanoparticles and nanomaterials in a controllable, reproducible manner through acoustic‐streaming‐based active mixing of reagents. The acoustofluidic strategy allows for the dynamic control of the reaction conditions simply by adjusting the strength of the acoustic streaming. With this platform, the synthesis of versatile nanoparticles/nanomaterials is demonstrated including the synthesis of polymeric nanoparticles, chitosan nanoparticles, organic–inorganic hybrid nanomaterials, metal–organic framework biocomposites, and lipid‐DNA complexes. The acoustofluidic synthesis platform, when incorporated with varying flow rates, compositions, or concentrations of reagents, will lend itself unprecedented flexibility in establishing various reaction conditions and thus enable the synthesis of versatile nanoparticles and nanomaterials with prescribed properties. [ABSTRACT FROM AUTHOR]