Cavity-agnostic acoustofluidic manipulations enabled by guided flexural waves on a membrane acoustic waveguide actuator.

This article presents an in-depth exploration of the acoustofluidic capabilities of guided flexural waves (GFWs) generated by a membrane acoustic waveguide actuator (MAWA). By harnessing the potential of GFWs, cavity-agnostic advanced particle manipulation functions are achieved, unlocking new avenues for microfluidic systems and lab-on-a-chip development. The localized acoustofluidic effects of GFWs arising from the evanescent nature of the acoustic fields they induce inside a liquid medium are numerically investigated to highlight their unique and promising characteristics. Unlike traditional acoustofluidic technologies, the GFWs propagating on the MAWA's membrane waveguide allow for cavity-agnostic particle manipulation, irrespective of the resonant properties of the fluidic chamber. Moreover, the acoustofluidic functions enabled by the device depend on the flexural mode populating the active region of the membrane waveguide. Experimental demonstrations using two types of particles include in-sessile-droplet particle transport, mixing, and spatial separation based on particle diameter, along with streaming-induced counter-flow virtual channel generation in microfluidic PDMS channels. These experiments emphasize the versatility and potential applications of the MAWA as a microfluidic platform targeted at lab-on-a-chip development and showcase the MAWA's compatibility with existing microfluidic systems.

Quantum Oscillations in Graphene Using Surface Acoustic Wave Resonators.

Surface acoustic waves (SAWs) provide a contactless method for measuring wave-vector-dependent conductivity. This technique has been used to discover emergent length scales in the fractional quantum Hall regime of traditional, semiconductor-based heterostructures. SAWs would appear to be an ideal match for van der Waals heterostructures, but the right combination of substrate and experimental geometry to allow access to the quantum transport regime has not yet been found. We demonstrate that SAW resonant cavities fabricated on LiNbO_{3} substrates can be used to access the quantum Hall regime of high-mobility, hexagonal boron nitride encapsulated, graphene heterostructures. Our work establishes SAW resonant cavities as a viable platform for performing contactless conductivity measurements in the quantum transport regime of van der Waals materials.

GHz ultrasonic sensor for ionic content with high sensitivity and localization.

Sensing the ionic content of a solution at high spatial and temporal resolution and sensitivity is a challenge in nanosensing. This paper describes a comprehensive investigation of the possibility of GHz ultrasound acoustic impedance sensors to sense the content of an ionic aqueous medium. At the 1.55 GHz ultrasonic frequency used in this study, the micron-scale wavelength and the decay lengths in liquid result in a highly localized sense volume with the added potential for high temporal resolution and sensitivity. The amplitude of the back reflected pulse is related to the acoustic impedance of the medium and a function of ionic species concentration of the KCl, NaCl, and CaCl2 solutions used in this study. A concentration sensitivity as high as 1 mM and concentration detection range of 0 to 3 M was achieved. These bulk acoustic wave pulse-echo acoustic impedance sensors can also be used to record dynamic ionic flux.

Microfabricated acoustofluidic membrane acoustic waveguide actuator for highly localized in-droplet dynamic particle manipulation.

Precision manipulation techniques in microfluidics often rely on ultrasonic actuators to generate displacement and pressure fields in a liquid. However, strategies to enhance and confine the acoustofluidic forces often work against miniaturization and reproducibility in fabrication. This study presents microfabricated piezoelectric thin film membranes made via silicon diffusion for guided flexural wave generation as promising acoustofluidic actuators with low frequency, voltage, and power requirements. The guided wave propagation can be dynamically controlled to tune and confine the induced acoustofluidic radiation force and streaming. This provides for highly localized dynamic particle manipulation functionalities such as multidirectional transport, patterning, and trapping. The device combines the advantages of microfabrication and advanced acoustofluidic capabilities into a miniature "drop-and-actuate" chip that is mechanically robust and features a high degree of reproducibility for large-scale production. The membrane acoustic waveguide actuators offer a promising pathway for acoustofluidic applications such as biosensing, organoid production, and in situ analyte transport.

Ultrasonically actuated neural probes for reduced trauma and inflammation in mouse brain.

Electrical neural recordings measured using direct electrical interfaces with neural tissue suffer from a short lifespan because the signal strength decreases over time. The inflammatory response to the inserted microprobe can create insulating tissue over the electrical interfaces, reducing the recorded signal below noise levels. One of the factors contributing to this inflammatory response is the tissue damage caused during probe insertion. Here, we explore the use of ultrasonic actuation of the neural probe during insertion to minimize tissue damage in mice. Silicon neural microprobes were designed and fabricated with integrated electrical recording sites and piezoelectric transducers. The microprobes were actuated at ultrasonic frequencies using integrated piezoelectric transducers. The microprobes were inserted into mouse brains under a glass window over the brain surface to image the tissue surrounding the probe using two-photon microscopy. The mechanical force required to penetrate the tissue was reduced by a factor of 2-3 when the microprobe was driven at ultrasonic frequencies. Tissue histology at the probe insertion site showed a reduced area of damage and decreased microglia counts with increasing ultrasonic actuation of the probes. Two-photon imaging of the microprobe over weeks demonstrated stabilization of the inflammatory response. Recording of electrical signals from neurons over time suggests that microprobes inserted using ultrasound have a higher signal-to-noise ratio over an extended time period.

Polymer interdigitated pillar electrostatic (PIPE) actuators.

This work reports a three-dimensional polymer interdigitated pillar electrostatic actuator that can produce force densities 5-10× higher than those of biological muscles. The theory of operation, scaling, and stability is investigated using analytical and FEM models. The actuator consists of two high-density arrays of interdigitated pillars that work against a restoring force generated by an integrated flexure spring. The actuator architecture enables linear actuation with higher displacements and pull-in free actuation to prevent the in-use stiction associated with other electrostatic actuators. The pillars and springs are 3D printed together in the same structure. The pillars are coated with a gold-palladium alloy layer to form conductive electrodes. The space between the pillars is filled with liquid dielectrics for higher breakdown voltages and larger electrostatic forces due to the increase in the dielectric constant. We demonstrated a prototype actuator that produced a maximum work density of 54.6 µJ/cc and an electrical-to-mechanical energy coupling factor of 32% when actuated at 4000 V. The device was operated for more than 100,000 cycles with no degradation in displacements. The flexible polymer body was robust, allowing the actuator to operate even after high mechanical force impact, which was demonstrated by operation after drop tests. As it is scaled further, the reported actuator will enable soft and flexible muscle-like actuators that can be stacked in series and parallel to scale the resulting forces. This work paves the way for high-energy density actuators for microrobotic applications.

Femtometer-amplitude imaging of coherent super high frequency vibrations in micromechanical resonators.

Dynamic measurement of femtometer-displacement vibrations in mechanical resonators at microwave frequencies is critical for a number of emerging high-impact technologies including 5G wireless communications and quantum state generation, storage, and transfer. However, the resolution of continuous-wave laser interferometry, the method most commonly used for imaging vibration wavefields, has been limited to vibration amplitudes just below a picometer at several gigahertz. This is insufficient for these technologies since vibration amplitudes precipitously decrease for increasing frequency. Here we present a stroboscopic optical sampling approach for the transduction of coherent super high frequency vibrations. Phase-sensitive absolute displacement detection with a noise floor of 55 fm/√Hz for frequencies up to 12 GHz is demonstrated, achieving higher bandwidth and significantly lower noise floor simultaneously compared to previous work. An acoustic microresonator with resonances above 10 GHz and displacements smaller than 70 fm is measured using the presented method to reveal complex mode superposition, dispersion, and anisotropic propagation.

GHz Ultrasound and Electrode Chip-Scale Arrays Stimulate and Influence Morphology of Human Neural Cells.

This study describes the effects of chip-scale gigahertz (GHz) ultrasound (US) and electrical stimulus on the morphology, functionality, and viability of neural cells in vitro. The GHz frequency stimulation is achieved using aluminum nitride piezoelectric transducers fabricated on a silicon wafer, operating at 1.47 GHz, corresponding to the film's thickness mode resonance. These devices are used to stimulate SH-SY5Y neural cells in vitro and observe effects on the morphology and viability of the stimulated cells. It is possible to use these devices to deliver either ultrasonic stimulus alone or US stimulus in conjunction with electrical stimulus. Viability tests demonstrated that the neurons retained structural integrity and viability across a wide range of GHz US stimulus intensities (0-1.2 W/cm2), validating that measurements occur at nontoxic doses of US. Neural stimulation is validated with these devices following the outputs of a previous study, with the normalized fluorescence intensity of activated cells between 1.9 and 2.4. The 300-s ultrasonic stimulation at 1.47 GHz and 0.05 W/cm2 peak intensity led to a decrease in nuclear elongation by 17.5% and a cross-sectional area decrease by 17.8% across three independent trials of over 150 cells per category ( ). The F-actin governed cellular elongation increased in length by up to 16.3% in cells exposed to an ultrasonic stimulus or costimulus ( ). Neurite length increased following ultrasonic stimulation compared with control by 75.8% ( ). This article demonstrates new GHz US and electrical chip-scale arrays with apparent effects in both neural excitation and cell morphology.

Palliative vertical vein stenting in a critical neonate with obstructed infradiaphragmatic total anomalous pulmonary venous connection.

Neonatal total anomalous pulmonary venous connection has an incidence of about ∼1-2%.1 The clinical presentation of total anomalous pulmonary venous connection in the neonatal period is dependent on the presence or absence of pulmonary venous obstruction, which is usual when the veins connect to the umbilicovitelline system, as in infradiaphragmatic total anomalous pulmonary venous connection. Obstructed total anomalous pulmonary venous connection presents with severe respiratory distress, metabolic acidosis, and cyanosis and requires urgent surgical intervention. However, critically ill neonates with obstructed total anomalous pulmonary venous connection have a higher surgical morbidity and mortality, and pre-operative stabilisation can improve outcomes in them. We present a case of a septic term neonate with obstructed infradiaphragmatic total anomalous pulmonary venous connection who underwent emergency palliative stent placement for immediate relief of pulmonary venous obstruction.

Non-contact ultrasound oocyte denudation.

Cumulus removal (CR) is a central prerequisite step for many protocols involved in the assisted reproductive technology (ART) such as intracytoplasmic sperm injection (ICSI) and preimplantation genetic testing (PGT). The most prevalent CR technique is based upon laborious manual pipetting, which suffers from inter-operator variability and therefore a lack of standardization. Automating CR procedures would alleviate many of these challenges, improving the odds of a successful ART or PGT outcome. In this study, a chip-scale ultrasonic device consisting of four interdigitated transducers (IDT) on a lithium niobate substrate has been engineered to deliver megahertz (MHz) range ultrasound to perform denudation. The acoustic streaming and acoustic radiation force agitate COCs inside a microwell placed on top of the LiNbO3 substrate to remove the cumulus cells from the oocytes. This paper demonstrates the capability and safety of the denudation procedure utilizing surface acoustic wave (SAW), achieving automation of this delicate manual procedure and paving the steps toward improved and standardized oocyte manipulation.

GHz Ultrasonic Chip-Scale Device Induces Ion Channel Stimulation in Human Neural Cells.

Emergent trends in the device development for neural prosthetics have focused on establishing stimulus localization, improving longevity through immune compatibility, reducing energy re-quirements, and embedding active control in the devices. Ultrasound stimulation can single-handedly address several of these challenges. Ultrasonic stimulus of neurons has been studied extensively from 100 kHz to 10 MHz, with high penetration but less localization. In this paper, a chip-scale device consisting of piezoelectric Aluminum Nitride ultrasonic transducers was engineered to deliver gigahertz (GHz) ultrasonic stimulus to the human neural cells. These devices provide a path towards complementary metal oxide semiconductor (CMOS) integration towards fully controllable neural devices. At GHz frequencies, ultrasonic wavelengths in water are a few microns and have an absorption depth of 10-20 µm. This confinement of energy can be used to control stimulation volume within a single neuron. This paper is the first proof-of-concept study to demonstrate that GHz ultrasound can stimulate neurons in vitro. By utilizing optical calcium imaging, which records calcium ion flux indicating occurrence of an action potential, this paper demonstrates that an application of a nontoxic dosage of GHz ultrasonic waves [Formula: see text] caused an average normalized fluorescence intensity recordings >1.40 for the calcium transients. Electrical effects due to chip-scale ultrasound delivery was discounted as the sole mechanism in stimulation, with effects tested at α = 0.01 statistical significance amongst all intensities and con-trol groups. Ionic transients recorded optically were confirmed to be mediated by ion channels and experimental data suggests an insignificant thermal contributions to stimulation, with a predicted increase of 0.03 oC for [Formula: see text] This paper paves the experimental framework to further explore chip-scale axon and neuron specific neural stimulation, with future applications in neural prosthetics, chip scale neural engineering, and extensions to different tissue and cell types.

A frequency domain SIM reconstruction algorithm using reduced number of images.

Conventional two-dimensional structured illumination microscopy (SIM) requires 9 raw images to reconstruct a super-resolved image. In order to increase the frame rate of 2DSIM, attempts are being made to reduce the number of raw SIM images. However, all the proposed SIM reconstruction algorithms (SIM-RA) capable of reconstructing super-resolution (SR) image with a reduced number of raw SIM images operate in the spatial domain. Here, we present a frequency domain SIM-RA based on ordinary least squares technique, which enables reconstruction of SR image using 4 raw SIM images. Unlike the spatial domain RA, which produces the SR image through iterative convergence, the presented RA provides a single step solution. It also reveals the fundamental limitation of least number of raw images required for resolution doubling in SIM.

UV-Triggered Transient Electrospun Poly(propylene carbonate)/Poly(phthalaldehyde) Polymer Blend Fiber Mats.

This work reports the first transient electrospun nanofiber mat triggered by UV-irradiation using poly(propylene carbonate) (PPC)/poly(phthalaldehyde) (cPPA) polymer blends. The ability to trigger room temperature transience of nanofiber mats without the need for additional heat or solvent expands its utility in nonbiological fields, especially for transient electronic devices. The addition of a photo-acid-generator to the system, working in combination with UV light, provides an acid source to enhance degradation because both polymer backbones are acid-sensitive. Electrospinning enables the production of PPC/cPPA composite nanofiber mats capable of significant degradation upon exposure to UV radiation while maintaining relatively high mechanical properties. An acid amplifier, an autocatalytically decomposing compound triggered by acid, was used to generate more acid and accelerate nanofiber degradation. The electrospun fiber mats can be post-annealed to achieve an improved mat with a mechanical strength of ∼170 MPa.

Fast, long-term, super-resolution imaging with Hessian structured illumination microscopy.

To increase the temporal resolution and maximal imaging time of super-resolution (SR) microscopy, we have developed a deconvolution algorithm for structured illumination microscopy based on Hessian matrixes (Hessian-SIM). It uses the continuity of biological structures in multiple dimensions as a priori knowledge to guide image reconstruction and attains artifact-minimized SR images with less than 10% of the photon dose used by conventional SIM while substantially outperforming current algorithms at low signal intensities. Hessian-SIM enables rapid imaging of moving vesicles or loops in the endoplasmic reticulum without motion artifacts and with a spatiotemporal resolution of 88 nm and 188 Hz. Its high sensitivity allows the use of sub-millisecond excitation pulses followed by dark recovery times to reduce photobleaching of fluorescent proteins, enabling hour-long time-lapse SR imaging of actin filaments in live cells. Finally, we observed the structural dynamics of mitochondrial cristae and structures that, to our knowledge, have not been observed previously, such as enlarged fusion pores during vesicle exocytosis.

Transient Fiber Mats of Electrospun Poly(Propylene Carbonate) Composites with Remarkable Mechanical Strength.

Polymers with a triggered decomposition are attractive for an array of applications ranging from patterning to transient packaging materials, as well as for environmental protection. This work showed for the first time UV and thermally triggered transience in fiber mats using poly(propylene carbonate) (PPC) composites. The electrospun PPC-composite fiber mats combine excellent decomposition performance (because of the high surface to volume ratio) with high stiffness and thus represent a new class of materials enabling innovative applications, such as transient filter materials and short-time plant protection materials, as well as temporary lightweight materials for aerospace engineering. Thermally and UV-triggerable additives (protected acids or base) have been used in different concentrations to tune the transience performance of the fiber mats over a wide range (75-212 °C). The addition of organo-modified clay (OMMT) enhanced mechanical stability and prevented shrinkage at room temperature. Different annealing methods have been used to improve the mechanical properties even further (tensile strength = 2-12 MPa, Young's modulus = 55-747 MPa) making these fiber mats attractive for a broad field of applications. An Ashby plot of Young's modulus versus degradation temperature for electrospun fiber mats is shown, revealing much lower degradation temperatures with higher moduli for PPC composites compared to other electrospun polymers.

An optically-gated AuNP-DNA protonic transistor.

Bio-interface transistors, which manipulate the transportation of ions (i.e. protons), play an important role in bridging physical devices with biological functionalities, because electrical signals are carried by ions/protons in biological systems. All available ionic transistors use electrostatic gates to tune the ionic carrier density, which requires complicated interconnect wires. In contrast, an optical gate, which offers the advantages of remote control as well as multiple light wavelength selections, has never been explored for ionic devices. Here, we demonstrate a light-gated protonic transistor fabricated from an Au nanoparticle and DNA (AuNP-DNA) hybrid membrane. The device can be turned on and off completely by using light, with a high on/off current ratio of up to 2 orders of magnitude. Moreover, the device only responds to specific light wavelengths due to the plasmonic effect from the AuNPs, which enables the capability of wavelength selectivity. Our results open up new avenues for exploring remotely controlled ionic circuits, in vivo protonic switches, and other biomedical applications.

Emergent Network Topology within the Respiratory Rhythm-Generating Kernel Evolved In Silico.

We hypothesize that the network topology within the pre-Bötzinger Complex (preBötC), the mammalian respiratory rhythm generating kernel, is not random, but is optimized in the course of ontogeny/phylogeny so that the network produces respiratory rhythm efficiently and robustly. In the present study, we attempted to identify topology of synaptic connections among constituent neurons of the preBötC based on this hypothesis. To do this, we first developed an effective evolutionary algorithm for optimizing network topology of a neuronal network to exhibit a 'desired characteristic'. Using this evolutionary algorithm, we iteratively evolved an in silico preBötC 'model' network with initial random connectivity to a network exhibiting optimized synchronous population bursts. The evolved 'idealized' network was then analyzed to gain insight into: (1) optimal network connectivity among different kinds of neurons-excitatory as well as inhibitory pacemakers, non-pacemakers and tonic neurons-within the preBötC, and (2) possible functional roles of inhibitory neurons within the preBötC in rhythm generation. Obtained results indicate that (1) synaptic distribution within excitatory subnetwork of the evolved model network illustrates skewed/heavy-tailed degree distribution, and (2) inhibitory subnetwork influences excitatory subnetwork primarily through non-tonic pacemaker inhibitory neurons. Further, since small-world (SW) network is generally associated with network synchronization phenomena and is suggested as a possible network structure within the preBötC, we compared the performance of SW network with that of the evolved model network. Results show that evolved network is better than SW network at exhibiting synchronous bursts.

Low-concentration mechanical biosensor based on a photonic crystal nanowire array.

The challenge for new biosensors is to achieve detection of biomolecules at low concentrations, which is useful for early-stage disease detection. Nanomechanical biosensors are promising in medical diagnostic applications. For nanomechanical biosensing at low concentrations, a sufficient resonator device surface area is necessary for molecules to bind to. Here we present a low-concentration (500 aM sensitivity) DNA sensor, which uses a novel nanomechanical resonator with ordered vertical nanowire arrays on top of a Si/SiO(2) bilayer thin membrane. The high sensitivity is achieved by the strongly enhanced total surface area-to-volume ratio of the resonator (10(8) m(-1)) and the state-of-the-art mass-per-area resolution (1.8×10(-12) kg m(-2)). Moreover, the nanowire array forms a photonic crystal that shows strong light trapping and absorption over broad-band optical wavelengths, enabling high-efficiency broad-band opto-thermo-mechanical remote device actuation and biosensing on a chip. This method represents a mass-based platform technology that can sense molecules at low concentrations.

In vivo electrochemical characterization of tissue-electrode interface during metamorphic growth.

The domestication of insect locomotion has been recently investigated through microelectrode based systems implanted in the insect to tap into its neuromuscular system. Benefiting from developmental changes, the idea of performing such surgical implantation during metamorphic development enabled the fusion of engineered constructs to these living biological organisms. This study uses electrochemical analysis to provide a preliminary quantitative comparison of tissue-electrode coupling over the course of metamorphic development and after eclosion, where PEDOT:PSS coated gold electrodes are implanted in the insect during the early pupal stages and right after emergence. An average 1 kHz impedance of 8.9 k was obtained with pupal stage inserted electrodes, with a stored charge of 52 mC/cm2 at the interface as characterized by cyclic voltammetry 10 days after emergence. 5.1 mC/cm2 of this charge was successfully injected into the tissue through charge balanced biphasic pulses. In comparison, implanted electrodes in the adult state caused a 1 kHz impedance of 12.1 k, where the stored charge was 38 mC/cm2 with an injectable charge amount of 3.5 mC/cm2. Finally, to shed light on possible reasons for improvement in the bioelectrical coupling, equivalent circuit models were formed and the extracted parameters were correlated with metamorphic development of pupal tissue.