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The latest advances in topological physics have yielded a rich toolset to design highly robust wave transfer systems, for overcoming issues like beam steering and lateral diffraction in surface acoustic waves (SAWs). However, presently used designs for topologically protected SAWs have been largely limited to spin or valley-polarized phases, which rely on non-zero Berry curvature effects. Here we propose and experimentally demonstrate a highly robust SAW waveguide on lithium niobate (LiNbO3), based on a line defect within a true triangular phononic lattice, which instead employs an intrinsic chirality of phase vortices and maintains a zero Berry curvature. The guided SAW mode spans a wide bandwidth and shows confinement in the lateral direction with 3 dB attenuation within half of the unit-cell length. SAW routing around sharp bends has been demonstrated in such waveguide, with less than ~4% reflection per bend. The waveguide has also been found robust for defect lines with different configurations. The fully on-chip system permits unidirectional SAW modes that are tightly bound to the waveguide, which provides a compact footprint ideal for miniaturization of practical applications and offers insight into the possibility of manipulating highly focused SAW propagation.

Infant breastfeeding diagnostics remain subjective due to the absence of instrumentation to objectively measure and understand infant oral motor skills and suckling characteristics. Qualitative diagnostic exams, such as the digital suck assessment which relies upon a clinician’s gloved finger inserted into the infant’s mouth, produce a diversity of diagnoses and intervention pathways due to their subjective nature. In this paper, we report on the design of a non-nutritive suckling (NNS) system which quantifies and analyzes quantitative intraoral vacuum and sucking patterns of full-term neonates in real time. In our study, we evaluate thirty neonate suckling profiles to demonstrate the technical and clinical feasibility of the system. We successfully extract the mean suck vacuum, maximum suck vacuum, frequency, burst duration, number of sucks per burst, number of sucks per minute, and number of bursts per minute. In addition, we highlight the discovery of three intraoral vacuum profile shapes that are found to be correlated to different levels of suckling characteristics. These results establish a framework for future studies to evaluate oromotor dysfunction that affect the appearance of these signals based on established normal profiles. Ultimately, with the ability to easily and quickly capture intraoral vacuum data, clinicians can more accurately perform suckling assessments to provide timely intervention and assist mothers and infants towards successful breastfeeding outcomes.

Materials under vibration experience internal stress waves that can cause material failure or energy loss due to inelastic vibration. Traditionally, failure is defined in terms of material acceleration, yet this approach has many drawbacks, principally because it is not invariant with respect to scale, type of vibration, or material choice. Here, the likelihood of failure is instead considered in terms of the maximum vibration or particle velocity for various metals, polymers, and structural materials. The exact relationship between the maximum particle velocity and the maximum induced stress may be derived, but only if one knows the details of the vibration, material, flaws, and geometry. Statistical results with over thousands of individual trials are presented here to demonstrate a wide variety of vibrations across a sufficient variety of these choices. Failure in this context is defined as either fracture or plastic yield, the latter associated with inelastic deformation and energy loss during vibration. If the maximum permissible cyclical stress in material vibration is known, to at least an order of magnitude, the probability of this type of failure may be computed for a range of vibration velocities in each material. The results support the notion that a maximum particle velocity on the order of 1 m/s is a universal and critical limit that, upon exceeding, causes the probability of failure to become significant regardless of the details of the material, geometry, or vibration. We illustrate this in a specific example relevant to acoustofluidics, a simple surface acoustic wave device. The consequences of particle velocity limit analysis can effectively be used in materials and structural engineering to predict when dynamic material particle velocity can cause inelastic losses or failure via brittle fracture, plastic deformation, or fatigue failure.

“Zero drift” behavior of an optical intraocular pressure sensor is studied using an analytical model based on the deflection of a circular membrane. Results from the analytical model were verified with experimental results from “bulge” testing. The analytical model was used to study the zero drift of the sensor as a function of changes in membrane thickness, geometry of the sensor and amount of gas inside the cavity of the sensor. The results show that dissolution of the membrane, swelling of the spacer layer and oxidative aging can contribute significantly to zero drift of the sensor over time. The results are useful in guiding design and fabrication optimization to minimize drift in intraocular pressure sensors used for long term implantation.

Acoustofluidics has promised to enable lab-on-a-chip and point-of-care devices in ways difficult to achieve using other methods. Piezoelectric ultrasonic transducers-as small as the chips they actuate-provide rapid fluid and suspended object transport. Acoustofluidic lab-on-chip devices offer a vast range of benefits in early disease identification and noninvasive drug delivery. However, their potential has long been undermined by the need for benchtop or rack-mount electronics. The piezoelectric ultrasonic transducers within require these equipment and thus acoustofluidic device implementation in a bedside setting has been limited. Here we detail a general process to enable the reader to produce battery or mains-powered microcircuits ideal for driving 1-300 MHz acoustic devices. We include the general design strategy for the circuit, the blocks that collectively define it, and suitable, specific choices for components to produce these blocks. We furthermore illustrate how to incorporate automated resonance finding and tracking, sensing and feedback, and built-in adjustability to accommodate devices' vastly different operating frequencies and powers in a single driver, including examples of fluid and particle manipulation typical of the needs in our discipline. With this in hand, the many groups active in lab-on-a-chip acoustofluidics can now finally deliver on the promise of handheld, point-of-care technologies.

Asymmetric surface acoustic waves have been shown useful in separating particles and cells in many microfluidics designs, mostly notably sessile microdroplets. However, no one has successfully extracted target particles or cells for later use from such samples. We present a novel omnidirectional spiral surface acoustic wave (OSSAW) design that exploits a new cut of lithium niobate, 152 Y-rotated, to rapidly rotate a microliter sessile drop to ∼10 g, producing efficient multi-size particle separation. We further extract the separated particles for the first time, demonstrating the ability to target specific particles, for example, platelets from mouse blood for further integrated point-of-care diagnostics. Within ∼5 s of surface acoustic wave actuation, particles with diameter of 5 μm and 1 μm can be separated into two portions with a purity of 83% and 97%, respectively. Red blood cells and platelets within mouse blood are further demonstrated to be separated with a purity of 93% and 84%, respectively. These advancements potentially provide an effective platform for whole blood separation and point-of-care diagnostics without need for micro or nanoscale fluidic enclosures.

Three-dimensional cell agglomerates are broadly useful in tissue engineering and drug testing. We report a well-free method to form large (1.4-mm) multicellular clusters using 100-MHz surface acoustic waves (SAW) without direct contact with the media or cells. A fluid couplant is used to transform the SAW into acoustic streaming in the cell-laden media held in a petri dish. The couplant transmits longitudinal sound waves, forming a Lamb wave in the petri dish that, in turn, produces longitudinal sound in the media. Due to recirculation, human embryonic kidney (HEK293) cells in the dish are carried to the center of the coupling location, forming a cluster in less than 10 min. A few minutes later, these clusters may then be translated and merged to form large agglomerations, and even repeatedly folded to produce a roughly spherical shape of over 1.4 mm in diameter for incubation—without damaging the existing intercellular bonds. Calcium ion signaling through these clusters and confocal images of multiprotein junctional complexes suggest a continuous tissue construct: intercellular communication. They may be formed at will, and the method is feasibly useful for formation of numerous agglomerates in a single petri dish.

The field of ultrasound neuromodulation has rapidly developed over the past decade, a consequence of the discovery of strain-sensitive structures in the membrane and organelles of cells extending into the brain, heart, and other organs. Notably, clinical trials are underway for treating epilepsy using focused ultrasound to elicit an organized local electrical response. A key limitation to this approach is the formation of standing waves within the skull. In standing acoustic waves, the maximum ultrasound intensity spatially varies from near zero to double the mean in one half a wavelength, and can lead to localized tissue damage and disruption of normal brain function while attempting to evoke a broader response. This phenomenon also produces a large spatial variation in the actual ultrasound exposure in tissue, leading to heterogeneous results and challenges with interpreting these effects. One approach to overcome this limitation is presented herein: transducer-mounted diffusers that result in spatiotemporally incoherent ultrasound. The signal is numerically and experimentally quantified in an enclosed domain with and without the diffuser. Specifically, we show that adding the diffuser leads to a two-fold increase in ultrasound responsiveness of hsTRPA1 transfected HEK cells. Furthermore, we demonstrate the diffuser allow us to produce an uniform spatial distribution of pressure in the rodent skull. Collectively, we propose that our approach leads to a means to deliver uniform ultrasound into irregular cavities for sonogenetics.

We describe a novel mathematical method to supplant the classic approach and properly treat the spatiotemporal scale disparities present between the acoustics and remaining fluid dynamics. The method is applied in this work to well-known problems of semi-infinite extent defined by the Navier-Stokes equations, and preserves unsteady fluid behavior driven by the acoustic wave. The separation of the governing equations between the fast (acoustic) and slow (hydrodynamic) spatiotemporal scales are shown to naturally arise from the intrinsic properties of the fluid under forcing, not by arbitrary assumption beforehand. Solution of the unsteady streaming field equations provides physical insight into observed temporal evolution of bulk streaming flows that, to date, have not been modeled. A Burgers equation is derived from the new method to represent unsteady flow. By then assuming steady flow, a Riccati equation is found to represent it. Solving these equations produces direct, concise insight into the nonlinearity of the acoustic streaming phenomenon alongside an absolute, universal upper bound of 50\% for the energy efficiency in transducing acoustic energy input to the acoustic streaming energy output. Rigorous validation with respect to experimental and theoretical results from the classic literature is presented to connect this work to past efforts by many authors., main article: 19 pages, 9 figures; new version: changed article formatting, changed article title, revised for clarity, general editorial tasks

Tumor cells express a unique cell surface glycocalyx with upregulation of sulfated glycosaminoglycans and charged glycoproteins. Little is known about how electromagnetic fields interact with this layer, particularly with regard to harnessing unique properties for therapeutic benefit. We applied a pulsed 20-millitesla (mT) magnetic field with rate of rise (dB/dt) in the msec range to cultured tumor cells to assess whether this affects membrane integrity as measured using cytolytic assays. A 10-min exposure of A549 human lung cancer cells to sequential 50- and 385-Hz oscillating magnetic fields was sufficient to induce intracellular protease release, suggesting altered membrane integrity after the field exposure. Heparinase treatment, which digests anionic sulfated glycan polymers, before exposure rendered cells insensitive to this effect. We further examined a non-neoplastic human primary cell line (lung lymphatic endothelial cells) as a typical normal host cell from the lung cancer microenvironment and found no effect of field exposure on membrane integrity. The field exposure was also sufficient to alter proliferation of tumor cells in culture, but not that of normal lymphatic cells. Pulsed magnetic field exposure of human breast cancer cells that express a sialic-acid rich glycocalyx also induced protease release, and this was partially abrogated by sialidase pretreatment, which removes cell surface anionic sialic acid. Scanning electron microscopy showed that field exposure may induce unique membrane "rippling" along with nanoscale pores on A549 cells. These effects were caused by a short exposure to pulsed 20-mT magnetic fields, and future work may examine greater magnitude effects. The proof of concept herein points to a mechanistic basis for possible applications of pulsed magnetic fields in novel anticancer strategies.

Acoustofluidics is a burgeoning field that applies ultrasound to micro-scale to nano-scale fluidic systems. The discovery of the ability to effectively manipulate fluids and particles at small scales has yielded results that are superior to other approaches and has been built into a diverse range of research. Recasting the fundamentals of acoustics from the past to include new phenomena observed in recent years has allowed acoustical systems to impact new areas, such as drug delivery, diagnostics, and enhanced chemical processes. The contributions in this special issue address a diverse range of research topics in acoustofluidics. Topics include acoustic streaming, flows induced by bubbles, manipulation of particles using acoustic radiation forces, fluid and structural interactions, and contributions suggesting a natural limit to the particle velocity, the ability to deliver molecules to human immune T cells, and microdroplet generation via nozzle-based acoustic atomization.

Over the years, a diverse range of physical and chemical phenomena have been explored and applied to devise reliable, small thrusters for stationkeeping and orientation of spacecraft. Commercial space flight is accelerating this need. Here, we consider acoustically driven melting of a frozen working fluid in the nozzle of an acoustic device, followed by acoustofluidic atomization from the nozzle to produce thrust. Fifty-five MHz acoustic waves generated by piezoelectric transducers couple into liquid and transfer energy in the form of both acoustic radiation and streaming, producing a directed atomized spray. A challenge in this system, as with most liquid-thrust systems, is the risk of phase change due to the extreme thermal environment in space, particularly in the freezing of the working fluid. Though acoustic energy is known to produce rapid and controllable heating, it so far has not been used to produce phase changes. The atomization produces capillary pressure sufficient to draw in fluid from a reservoir, though we do use a simple pressure-driven pump to support greater atomization rates. We provide a simple energy conservation model to explain the acoustothermal interaction and validate this with experiments. The specific impulse and thrust of this type of thruster are quite modest at 0.1–0.4 s and 12.3 μN, respectively, but the thruster component is small, light, and is without moving parts, a fascinating potential alternative to current technologies.

Three-dimensional cell agglomerates are broadly useful in tissue engineering and drug testing. We report a well-free method to form large (1-mm) multicellular clusters using 100-MHz surface acoustic waves (SAW) without direct contact with the media or cells. A fluid couplant is used to transformthe SAW into acoustic streaming in the cell-laden media held in a petri dish. The couplant transmits longitudinal sound waves, forming a Lamb wave in the petri dish that, in turn, produces longitudinal sound in the media. Due to recirculation, human embryonic kidney (HEK293) cells in the dish are carried to the center of the coupling location, forming a cluster in less than 10 min. A few minutes later, these clusters may then be translated and merged to form large agglomerations, and even repeatedly folded to produce a roughly spherical shape of over 1 mm in diameter for incubation—without damaging the existing intercellular bonds. Calcium ion signaling through these clusters and confocal images of multiprotein junctional complexes suggest a continuous tissue construct: intercellular communication. They may be formed at will, and the method is feasibly useful for formation of numerous agglomerates in a single petri dish.

Ultrasound has been shown to affect the function of both neurons and non-neuronal cells. However, the underlying molecular machinery has been poorly understood. Here, we show that at least two mechanosensitive proteins act in parallel to generate C. elegans behavioral responses to ultrasound stimuli. We first show that these animals generate reversals in response to a single 10 msec pulse from a 2.25 MHz ultrasound transducer. Next, we show that the pore-forming subunit of the mechanosensitive channel TRP-4, and a DEG/ENaC/ASIC ion channel MEC-4, are both required for this ultrasound-evoked reversal response. Further, the trp-4 mec-4 double mutant shows a stronger behavioral deficit compared to either single mutant. Finally, overexpressing TRP-4 in specific chemosensory neurons can rescue the ultrasound-triggered behavioral deficit in the mec-4 null mutant, suggesting that these two pathways act in parallel. Together, we demonstrate that multiple mechanosensitive proteins likely cooperate to transform ultrasound stimuli into behavioral changes.

Ultrasound has been shown to affect the function of both neurons and non-neuronal cells, but, the underlying molecular machinery has been poorly understood. Here, we show that at least two mechanosensitive proteins act together to generate C. elegans behavioral responses to ultrasound stimuli. We first show that these animals generate reversals in response to a single 10 msec pulse from a 2.25 MHz ultrasound transducer. Next, we show that the pore-forming subunit of the mechanosensitive channel TRP-4, and a DEG/ENaC/ASIC ion channel MEC-4, are both required for this ultrasound-evoked reversal response. Further, the trp-4;mec-4 double mutant shows a stronger behavioral deficit compared to either single mutant. Finally, overexpressing TRP-4 in specific chemosensory neurons can rescue the ultrasound-triggered behavioral deficit in the mec-4 null mutant, suggesting that both TRP-4 and MEC-4 act together in affecting behavior. Together, we demonstrate that multiple mechanosensitive proteins likely cooperate to transform ultrasound stimuli into behavioral changes.

Stimuli-responsive hydrogels with programmable shapes produced by defined patterns of particles are of great interest for the fabrication of small-scale soft actuators and robots. Patterning the particles in the hydrogels during fabrication generally requires external magnetic or electric fields, thus limiting the material choice for the particles. Acoustically driven particle manipulation, however, solely depends on the acoustic impedance difference between the particles and the surrounding fluid, making it a more versatile method to spatially control particles. Here, an approach is reported by combining direct acoustic force to align photothermal particles and photolithography to spatially immobilize these alignments within a temperature-responsive poly(N-isopropylacrylamide) hydrogel to trigger shape deformation under temperature change and light exposure. The spatial distribution of particles can be tuned by the power and frequency of the acoustic waves. Specifically, changing the spacing between the particle patterns and position alters the bending curvature and direction of this composite hydrogel sheet, respectively. Moreover, the orientation (i.e., relative angle) of the particle alignments with respect to the long axis of laser-cut hydrogel strips governs the bending behaviors and the subsequent shape deformation by external stimuli. This acousto-photolithography provides a means of spatiotemporal programming of the internal heterogeneity of composite polymeric systems.

Vibrating materials experience internal stress waves that can cause material failure or energy loss due to inelastic vibration. Failure is traditionally defined in terms of acceleration, yet this approach has many drawbacks, principally because it is not invariant with respect to scale, type of vibration, or material choice. Here, the likelihood of failure is instead defined in terms of the maximum particle velocity. While the exact dependence of the internal stress on the particle velocity may be determined for specific cases, here we take a statistical approach in seeking a universal maximum particle velocity correlated to a specific risk of material failure. Our Monte Carlo-based analysis on a variety of materials, vibration types and frequencies, structures with flaws, and vibration velocities produced results in support of the notion that a maximum particle velocity on the order of 1 m/s is a universal and critical limit. Upon exceeding this limit, we find the probability of failure or excessive acoustic loss in suppression of the vibration to become significant, regardless of the details of the material, geometry, or vibration. We illustrate this in a specific example relevant to acoustofluidics, a simple surface acoustic wave device with fluid sample, and point out the value of using the maximum particle velocity as a design invariant.

When an otherwise quiescent minuscule (O(≤10−6) μl) basin of water is driven by ultrasonic vibrations at high frequencies (O(≥106)Hz) and with nanoscale (O(≤10−9)m) amplitudes, turbulent capillary waves that are visible by eye (O(10−2)m amplitudes and O(10−1)s periods) form at the air-water interface. Classical mechanisms typically attributed to such instabilities—such as Faraday wave theory—are absent. Contemporary wave turbulence studies have been mainly limited to weakly nonlinear regimes. In this talk, we present detailed measurements of strongly nonlinear, microscopic capillary wave turbulence. We show that this regime is reliably statistically characterized as an alpha-stable Lévy flight with a varying tail parameter. Our results demonstrate that as input power is increased, the heaviness of distribution tails also increases so that rogue events play an increasingly prevalent role in the overall wave system. Implications for future study and potential applications within the area of controlled atomization are discussed.

Having accurate data to represent hyperelastic materials that underpin soft robotics would facilitate their analysis, design, and validation. We seek to provide the reader with a useful tool to overcome a mundane but crucially important problem in determining the hyperelastic material properties. We show how to employ first dimensionless and then dimensional comparisons between experimental data and the classic theoretical model representing this system to produce C(1) and C(2) for the Mooney–Rivlin model, closely representing a variety of soft polymers.

Catheters used for endovascular navigation in interventional procedures lack dexterity at the distal tip. Neurointerventionists, in particular, encounter challenges in up to 25% of aneurysm cases largely due to the inability to steer and navigate the tip of the micro-catheters through tortuous vasculature to access aneurysms. We overcome this problem with sub-millimeter diameter, hydraulically-actuated hyperelastic polymer devices at the distal tip of micro-catheters to enable active steerability. Controlled by hand, the devices offer complete 3D orientation of the tip. Using saline as a working fluid, we demonstrate guidewire-free navigation, access, and coil deployment in vivo, offering safety, ease of use, and design flexibility absent in other approaches to endovascular intervention. We demonstrate the ability of our device to navigate through vessels and to deliver embolization coils to the cerebral vessels in a live porcine model. This indicates the potential for microhydraulic soft robotics to solve difficult access and treatment problems in endovascular intervention.

Catheters used for endovascular navigation in interventional procedures lack dexterity at the distal tip. Neurointerventionists, in particular, encounter challenges in up to 25% of aneurysm cases largely due to the inability to steer and navigate the tip of the micro-catheters through tortuous vasculature to access aneurysms. We overcome this problem with sub-millimeter diameter, hydraulically-actuated hyperelastic polymer devices at the distal tip of micro- catheters to enable active steerability. Controlled by hand, the devices offer complete 3D orientation of the tip. Using pressures up to 400 kPa (4 atm) we demonstrate guidewire-free navigation, access, and coil deploymentin vivo, offering safety, ease of use, and design flexibility absent in other approaches to endovascular intervention. We demonstrate the ability of our device to navigate through vessels and to deliver embolization coils to the cerebral vessels in a live porcine model. This indicates the potential for microhydraulic soft robotics to solve difficult access and treatment problems in endovascular intervention.

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., With the help of a new method for imaging cell membrane motion, high‐speed digital holographic microscopy, membrane deformation responsible for the direct depolarization of membranes that lead to action potential generation in nerve cells is observed. A complete model of the phenomena has been devised, producing voltage spiking and oscillation predictions similar to patch clamp measurements.

International audience; A major challenge for negative-index acoustic metamaterials is increasing their operational frequency to the MHz range in water for applications such as biomedical ultrasound. Herein, a novel technology to realize acoustic metamaterials in water using microstructured silicon chips as unit cells that incorporate silicon nitride membranes and Helmholtz resonators with dimensions below 100 μm fabricated using clean-room microfabrication technology is presented. The silicon chip unit-cells are then assembled to form periodic structures that result in a negative-index metamaterial. Finite-element method (FEM) simulations of the metamaterial show a negative-index branch in the dispersion relation in the 0.25–0.35 MHz range. The metamaterial is characterized experimentally using laser-doppler vibrometry, showing opposite phase and group velocities, a signature of negative-index materials, and is in close agreement with FEM simulations. The experimental measurements also show that the magnitude of phase and group velocities increase as the frequency increases within the negative-index band, confirming the negative-index behavior of the material. Acoustic indices from –1 to –5 are reached with respect to water in the 0.25–0.35 MHz range. The use of silicon technology microfabrication to produce acoustic metamaterials for operation in water opens a new road to reach frequencies relevant for biomedical ultrasound applications.

Past forms of acoustic streaming, named after their progenitors Eckart (1948), Schlichting (1932), and Rayleigh (1884), serve to describe fluid and particle transport phenomena from the macro to micro-scale. Governed by the fluid viscosity, traditional acoustic streaming arises from second-order nonlinear coupling between the fluid's density and particle velocity, with the first-order acoustic wave time averaging to zero. We describe a form of acoustogeometric streaming that has a nonzero first-order contribution. Experimentally discovered in nanochannels of a height commensurate with the viscous penetration depth of the fluid in the channel, it arises from nonlinear interactions between the surrounding channel deformation and the leading order acoustic pressure field, generating flow pressures three orders of magnitude greater than any known acoustically mediated mechanism. It enables the propulsion of fluids against significant Laplace pressure, sufficient to produce 6 mm/s flow in a 130-150nm tall nanoslit. We find quantitative agreement between theory and experiment across a variety of fluids and conditions, and identify the maximum flow rate with a channel height 1.59 times the viscous penetration depth.

Regenerative medicine and drug development require large numbers of high-quality cells, usually delivered from in vitro culturing. During culturing, the appearance of unwanted cells and an inability to remove them without damaging or losing most if not all the surrounding cells in the culture reduce the overall quality of the cultured cells. This is a key problem in cell culturing, as is the inability to sample cells from a culture as desired to verify the quality of the culture. Here, we report a method to locally remove cells from an adherent cell culture using a 100.4 MHz focused surface acoustic wave (SAW) device. After exposing a plated C2C12 mouse myoblast cell culture to phosphate buffered solution (PBS), ultrasound from the SAW device transmitted into the cell culture via a coupling water droplet serves to detach a small grouping of cells. The cells are removed from an area 6 × 10-3 mm2, equivalent to about 12 cells, using a SAW device-Petri dish water gap of 1.5 mm, a PBS immersion time of 300 s, and an input voltage of 75 V to the SAW device. Cells were released as desired 90% of the time, releasing the cells from the target area nine times out of ten runs. In the one trial in ten that fails, the cells partially release and remain attached due to inter-cellular binding. By making it possible to target and remove small groups of cells as desired, the quality of cell culturing may be significantly improved. The small group of cells may be considered a colony of iPS cells. This targeted cell removal method may facilitate sustainable, contamination-free, and automated refinement of cultured cells.

Acoustic metamaterials with negative index of refraction offer great potential for improving resolution and signal transmission in biomedical ultrasound. Their potential has remained unrealized, however, for the lack of a fabrication technology that can create metamaterials compatible with biomedical imaging and operating at frequencies near 1 MHz. The authors report the simulation, fabrication, and characterization of integrated Helmholtz and membrane resonators with characteristic lengths less than 1 mm, produced by silicon-based clean-room microfabrication. Their work finally realizes a negative-index acoustic metamaterial that can be applied in ultrasound imaging and therapeutics.

The vacuum-exhausted isolation locker (VEIL) provides a safety barrier during the care of COVID-19 patients. The VEIL is a 175-L enclosure with exhaust ports to continuously extract air through viral particle filters connected to hospital suction. Our experiments show that the VEIL contains and exhausts exhaled aerosols and droplets.

Ultrasound has been used to non-invasively manipulate neuronal functions in humans and other animals1–4. However, this approach is limited as it has been challenging to target specific cells within the brain or body5–8. Here, we identify human Transient Receptor Potential A1 (hsTRPA1) as a candidate that confers ultrasound sensitivity to mammalian cells. Ultrasound-evoked gating of hsTRPA1 specifically requires its N-terminal tip region and cholesterol interactions; and target cells with an intact actin cytoskeleton, revealing elements of the sonogenetic mechanism. Next, we use calcium imaging and electrophysiology to show that hsTRPA1 potentiates ultrasound-evoked responses in primary neurons. Furthermore, unilateral expression of hsTRPA1 in mouse layer V motor cortical neurons leads to c-fos expression and contralateral limb responses in response to ultrasound delivered through an intact skull. Collectively, we demonstrate that hsTRPA1-based sonogenetics can effectively manipulate neurons within the intact mammalian brain, a method that could be used across species.

We present a technique to fabricate simple thickness mode piezoelectric devices using lithium niobate (LN). Such devices have been shown to atomize liquid more efficiently, in terms of flow rate per power input, than those that rely on Rayleigh waves and other modes of vibration in LN or lead zirconate titanate (PZT). The complete device is composed of a transducer, a transducer holder, and a fluid supply system. The fundamentals of acoustic liquid atomization are not well known, so techniques to characterize the devices and to study the phenomena are also described. Laser Doppler vibrometry (LDV) provides vibration information essential in comparing acoustic transducers and, in this case, indicates whether a device will perform well in thickness vibration. It can also be used to find the resonance frequency of the device, though this information is obtained more quickly via impedance analysis. Continuous fluid atomization, as an example application, requires careful fluid flow control, and we present such a method with high-speed imaging and droplet size distribution measurements via laser scattering.

Endovascular procedures are limited by an absence of effective actuation methods for navigation and precise device positioning. The existing panoply of passive guidewires and catheters for the treatment of cerebral aneurysms, in particular, leaves neurointerventionists without a treatment option in at least 25% of patients. A key reason is the inability to steer the tip of the microcatheters in vivo. We overcome this problem with sub-millimeter diameter hydraulically-actuated hyperelastic polymer devices connected over a 160 cm length. These provide controlled 3D orientation of acute tip curvatures beyond 180 degrees at pressures of 400kPa that achieves stable coil deployment in vivo. This method uses saline as the working fluid, and forms a closed system from the steerable tip to the hydraulic actuator offering safety, ease of use, and design flexibility absent in approaches that require external actuation. Disclosures T. Gopesh: None. J. Wen: None. D. Santiago-Dieppa: None. B. Yan: None. J. Scott-Pannell: None. A. Khalessi: None. A. Norbash: None. J. Friend: None.

Author(s): Girgis, Alexander M; Aziz, Merna N; Gopesh, Tilvawala C; Friend, James; Grant, Alex M; Sandubrae, Jeffrey A; Banks, Dalia A

The COVID‐19 pandemic has produced critical shortages of ventilators worldwide. There is an unmet need for rapidly deployable, emergency‐use ventilators with sufficient functionality to manage COVID‐19 patients with severe Acute Respiratory Distress Syndrome. Here we show the development and validation of a simple, portable, and low‐cost ventilator that may be rapidly manufactured with minimal susceptibility to supply chain disruptions. This single‐mode continuous, mandatory, closed‐loop, pressure‐controlled, time‐terminated emergency ventilator offers robust safety and functionality absent in existing solutions to the ventilator shortage. Validated using certified test lungs over a wide range of compliances, pressures, volumes and resistances to meet U.S. Food and Drug Administration standards of safety and efficacy, an Emergency Use Authorization is in review for this system. This emergency ventilator could eliminate controversial ventilator rationing or splitting to serve multiple patients. All design and validation information is provided to facilitate ventilator production even in resource‐limited settings.

Manipulation of fluids and particles by acoustic actuation at small scale is aiding the rapid growth of lab-on-a-chip applications. Megahertz-order surface acoustic wave (SAW) devices generate enormous accelerations on their surface, up to 108 m/s2, in turn responsible for many of the observed effects that have come to define acoustofluidics: acoustic streaming and acoustic radiation forces. These effects have been used for particle, cell, and fluid handling at the microscale-and even at the nanoscale. In this paper we explicitly demonstrate two major fabrication methods of SAW devices on lithium niobate: the details of lift-off and wet etching techniques are described step-by-step. Representative results for the electrode pattern deposited on the substrate as well as the performance of SAW generated on the surface are displayed in detail. Fabrication tricks and troubleshooting are covered as well. This procedure offers a practical protocol for high frequency SAW device fabrication and integration for future microfluidics applications.