Microfabricated Nitinol Stent Retrievers with a Micro-Patterned Surface.

Stent retrievers are medical devices that are designed to physically remove blood clots from within the blood vessels of the brain. This paper focuses on microfabricated nitinol (nickel-titanium alloy) stent retrievers, which feature micro-patterns on their surface to enhance the effectiveness of mechanical thrombectomy. A thick film of nitinol, which was 20 µm in thickness, was sputtered onto a substrate with a micro-patterned surface, using electroplated copper as the sacrificial layer. The nitinol film was released from the substrate and then thermally treated while folded into a cylindrical shape. In vitro experiments with pig blood clots demonstrated that the micro-patterns on the surface improved the efficacy of blood clot retrieval.

Real-time quantitative characterization of ion channel activities for automated control of a lipid bilayer system.

This paper describes a novel signal processing method to characterize the activity of ion channels on a lipid bilayer system in a real-time and quantitative manner. Lipid bilayer systems, which enable single-channel level recordings of ion channel activities against physiological stimuli in vitro, are gaining attention in various research fields. However, the characterization of ion channel activities has heavily relied on time-consuming analyses after recording, and the inability to return the quantitative results in real time has long been a bottleneck to incorporating the system into practical products. Herein, we report a lipid bilayer system that integrates real-time characterization of ion channel activities and real-time response based on the characterization result. Unlike conventional batch processing, an ion channel signal is divided into short segments and processed during the recording. After optimizing the system to maintain the same characterization accuracy as conventional operation, we demonstrated the usability of the system with two applications. One is quantitative control of a robot based on ion channel signals. The velocity of the robot was controlled every second, which was around tens of times faster than the conventional operation, in proportion to the stimulus intensity estimated from changes in ion channel activities. The other is the automation of data collection and characterization of ion channels. By constantly monitoring and maintaining the functionality of a lipid bilayer, our system enabled continuous recording of ion channels over 2 h without human intervention, and the time of manual labor has been reduced from conventional 3 h to 1 min at a minimum. We believe the accelerated characterization and response in the lipid bilayer systems presented in this work will facilitate the transformation of lipid bilayer technology toward a practical level, finally leading to its industrialization.

Easily Attach/Detach Reattachable EEG Headset with Candle-like Microneedle Electrodes.

To expand the applications of the electroencephalogram (EEG), long-term measurement, a short installation time, and little stress on the participants are needed. In this study, we designed, fabricated, and evaluated an EEG headset with three candle-like microneedle electrodes (CMEs). The user is able to detach and reattach the electrodes, enabling long-term measurement with little stress. The design of the CMEs was experimentally determined by considering the skin-to-electrode impedance and user comfort. An EEG was successfully measured from areas with a high hair density without any preparation. The installation time was shorter than 60 s and the electrodes could be detached and reattached. The headset was designed such that the discomfort caused by its ear pads was higher than that caused by the electrodes. In 1 h experiments, the participants did not feel pain and the detachment of the CMEs was found to improve the comfort level of the participants in most cases. A successful demonstration of the long-term measurement of EEGs while watching a whole movie verified that the developed EEG headset with CMEs is applicable for EEG measurement in a variety of applications.

Stretchable Strain Sensor with Small but Sufficient Adhesion to Skin.

Stretchable strain sensors that use a liquid metal (eutectic gallium-indium alloy; E-GaIn) and flexible silicone rubber (Ecoflex) as the support and adhesive layers, respectively, are demonstrated. The flexibility of Ecoflex and the deformability of E-GaIn enable the sensors to be stretched by 100%. Ecoflex gel has sufficiently large adhesion force to skin, even though the adhesion force is smaller than that for commercially available adhesives. This enables the sensor to be used for non-invasive monitoring of human motion. The mechanical and electrical properties of the sensor are experimentally evaluated. The effectiveness of the proposed sensors is demonstrated by monitoring joint movements, facial expressions, and respiration.

Micromanufactured Tactile Samples for Characterization of Rough and Dry Tactile Perception.

The quantitative characterization of tactile perception, which is crucial in the design of tactile devices, requires the tested samples to have individually and precisely controlled properties associated with the senses. In this work, we microfabricated such tactile samples and then quantitatively characterized tactile perception with a focus on roughness and dryness. In the roughness perception experiments, the tactile samples had a stripe pattern with ridge and groove widths that were individually controlled. The experimental results revealed that the feeling of roughness was more dominated by the width of the groove than that of the ridge and that conventionally used roughness parameters such as Sa and Sq were not sufficient for predicting roughness perception. In the dryness perception experiments, the tactile samples had a micropattern formed by dry etching and an array of squares. The experimental results revealed that dry perception had different properties when the feature sizes were below and above 30 µm, which may have been due to the effect of adhesion on friction. The proposed tactile samples were suitable for the quantitative and precise characterization of tactile perception.

Machine-Learning-Based Fine Tuning of Input Signals for Mechano-Tactile Display.

Deducing the input signal for a tactile display to present the target surface (i.e., solving the inverse problem for tactile displays) is challenging. We proposed the encoding and presentation (EP) method in our prior work, where we encoded the target surface by scanning it using an array of piezoelectric devices (encoding) and then drove the piezoelectric devices using the obtained signals to display the surface (presentation). The EP method reproduced the target texture with an accuracy of over 80% for the five samples tested, which we refer to as replicability. Machine learning is a promising method for solving inverse problems. In this study, we designed a neural network to connect the subjective evaluation of tactile sensation and the input signals to a display; these signals are described as time-domain waveforms. First, participants were asked to touch the surface presented by the mechano-tactile display based on the encoded data from the EP method. Then, the participants recorded the similarity of the surface compared to five material samples, which were used as the input. The encoded data for the material samples were used as the output to create a dataset of 500 vectors. By training a multilayer perceptron with the dataset, we deduced new inputs for the display. The results indicate that using machine learning for fine tuning leads to significantly better accuracy in deducing the input compared to that achieved using the EP method alone. The proposed method is therefore considered a good solution for the inverse problem for tactile displays.

Study Effect of nAg Particle Size on the Properties and Antibacterial Characteristics of Polysulfone Membranes.

Polysulfone ultrafiltration membranes were fabricated using various sizes (20, 40, and 90-210 nm) of silver nanoparticles (nAg) blended in a dope solution. To characterize the performance and properties of the prepared membranes, scanning electron microscopy (SEM), water contact angle, protein separation, water flux, and antibacterial tests were conducted. The characterization results revealed that when nAg particles (20 nm) were blended into the base polymer PSF, the PSF/nAg blended membrane had the lowest contact angle (58.5°) and surface energy (110.7 mN/m). When experimenting with ultrafiltration using protein solutions, bare PSF and PSF/nAg-20 blended membranes gave similar values of protein rejection: 93% of bovine serum albumin (BSA) and 70% of lysozyme rejection. Furthermore, SEM studies showed that the surface pore size was reduced by adding 20 nm nAg particles in the casting solution. Most importantly, the introduction of 40 nm nAg particles reduced the growth of bacterial colonies on the membrane surface by up to 72%. These findings revealed that nAg particles are expected to be a potential modifier for the fabrication of an ultrafiltration membrane.

Direct Wiring of Liquid Metal on an Ultrasoft Substrate Using a Polyvinyl Alcohol Lift-off Method.

In recent years, wiring and system construction on ultrasoft materials such as biological tissues and hydrogels have been proposed for advanced wearable devices, implantable devices, and soft robotics. Among the soft conductive materials, Ga-based liquid metals (LMs) are both biocompatible and ultrasoft, making them a good match for electrodes on the ultrasoft substrates. However, gels and tissues are softer and less wettable to the LMs than conventional soft substrates such as Ecoflex and polydimethylsiloxane. In this study, we demonstrated the transfer of LM paste composed of Ga-based LM and Ni nanoparticles onto ultrasoft substrates such as biological tissue and gels using sacrificial polyvinyl alcohol (PVA) films. The LM paste pattern fabricated on the PVA film adhered to the ultrasoft substrate along surface irregularities and was transferred without being destroyed by the PVA film before the PVA's dissolution in water. The minimum line width that could be wired was approximately 165 µm. Three-dimensional wiring, such as the helical structure on the gel fiber surface, is also possible. Application of this transfer method to tissues using LM paste wiring allowed the successful stimulation of the vagus nerve in rats. In addition, we succeeded in transferring a temperature measurement system fabricated on a PVA film onto the gel. The connection between the solid-state electrical element and the LM paste was stable and maintained the functionality of the temperature-sensing system. This fundamental study of wiring fabrication and system integration can contribute to the development of advanced electric devices based on ultrasoft substrates.

The effect of haptic stimulation simulating heartbeats on the regulation of physiological responses and prosocial behavior under stress: The influence of interoceptive accuracy.

Research has discovered the modulatory effect of peripheral stimulation simulating altered bodily signals on emotion. Whether such an effect varies depending on one's interoceptive accuracy (IAc) remains unclear. Therefore, we provided haptic stimulation simulating participants' slowed-down heartbeats or no stimulation while they engaged in socially stressful tasks to examine whether participants reacted differently depending on their IAc. Results showed that haptic stimulation exhibited the opposite effect on participants with different levels of IAc for both heart rate and heart rate variability (HRV). When receiving the stimulation, participants with higher IAc showed less increased heart rate and more elevated HF than participants with lower IAc. In contrast, in the absence of stimulation, an opposite pattern of response depending on participants' IAc was observed. The modulatory effect of stimuli and IAc on prosocial behavior was not significant. Individual differences in IAc were shown to affect how one perceives/responds to altered bodily signals.

Pump-Free Microfluidic Hemofiltration Device.

Hemofiltration removes water and small molecules from the blood via nanoporous filtering membranes. This paper discusses a pump-free hemofiltration device driven by the pressure difference between the artery and the vein. In the design of the filtering device, oncotic pressure needs to be taken into consideration. Transmembrane pressure (TMP) determines the amount and direction of hemofiltration, which is calculated by subtracting the oncotic pressure from the blood pressure. Blood pressure decreases as the channels progress from the inlet to the outlet, while oncotic pressure increases slightly since no protein is removed from the blood to the filtrate in hemofiltration. When TMP is negative, the filtrate returns to the blood, i.e., backfiltration takes place. A small region of the device with negative TMP would thus result in a small amount of or even zero filtrates. First, we investigated this phenomenon using in vitro experiments. We then designed a hemofiltration system taking backfiltration into consideration. We divided the device into two parts. In the first part, the device has channels for the blood and filtrate with a nanoporous membrane. In the second part, the device does not have channels for filtration. This design ensures TMP is always positive in the first part and prevents backfiltration. The concept was verified using in vitro experiments and ex vivo experiments in beagle dogs. Given the simplicity of the device without pumps or electrical components, the proposed pump-free hemofiltration device may prove useful for either implantable or wearable hemofiltration.

A Lipid-Bilayer-On-A-Cup Device for Pumpless Sample Exchange.

Lipid-bilayer devices have been studied for on-site sensors in the fields of diagnosis, food and environmental monitoring, and safety/security inspection. In this paper, we propose a lipid-bilayer-on-a-cup device for serial sample measurements using a pumpless solution exchange procedure. The device consists of a millimeter-scale cylindrical cup with vertical slits which is designed to steadily hold an aqueous solution and exchange the sample by simply fusing and splitting the solution with an external solution. The slit design was experimentally determined by the capabilities of both the retention and exchange of the solution. Using the optimized slit, a planar lipid bilayer was reconstituted with a nanopore protein at a microaperture allocated to the bottom of the cup, and the device was connected to a portable amplifier. The solution exchangeability was demonstrated by observing the dilution process of a blocker molecule of the nanopore dissolved in the cup. The pumpless solution exchange by the proposed cup-like device presents potential as a lipid-bilayer system for portable sensing applications.

Rapid and Resilient Detection of Toxin Pore Formation Using a Lipid Bilayer Array.

An artificial cell membrane is applied to study the pore formation mechanisms of bacterial pore-forming toxins for therapeutic applications. Electrical monitoring of ionic current across the membrane provides information on the pore formation process of toxins at the single pore level, as well as the pore characteristics such as dimensions and ionic selectivity. However, the efficiency of pore formation detection largely depends on the encounter probability of toxin to the membrane and the fragility of the membrane. This study presents a bilayer lipid membrane array that parallelizes 4 or 16 sets of sensing elements composed of pairs of a membrane and a series electrical resistor. The series resistor prevents current overflow attributed to membrane rupture, and enables current monitoring of the parallelized membranes with a single detector. The array system shortens detection time of a pore-forming protein and improves temporal stability. The current signature represents the states of pore formation and rupture at respective membranes. The developed system will help in understanding the toxic activity of pore-forming toxins.

Ion concentration measurement using synthetic microfluidic papers.

Non-invasive diagnosis on biological liquid samples, such as urine, sweat, saliva, and tears, may allow patients to evaluate their health by themselves. To obtain accurate diagnostic results, target liquid must be precisely sampled. Conventionally, urine sampling using filter paper can be given as an example sampling, but differences in the paper structure can cause variations in sampling volume. This paper describes precise liquid sampling using synthetic microfluidic papers, which are composed of obliquely combined micropillars. Sampling volume accuracy was investigated using different designs and collection methods to determine the optimal design and sample collecting method. The optimized protocol was followed to accurately measure potassium concentration using synthetic microfluidic paper and a commercially available densitometer, which verified the usefulness of the synthetic microfluidic papers for precision sampling.

Design and Characterization of an EEG-Hat for Reliable EEG Measurements.

In this study, a new hat-type electroencephalogram (EEG) device with candle-like microneedle electrodes (CMEs), called an EEG-Hat, was designed and fabricated. CMEs are dry EEG electrodes that can measure high-quality EEG signals without skin treatment or conductive gels. One of the challenges in the measurement of high-quality EEG signals is the fixation of electrodes to the skin, i.e., the design of a good EEG headset. The CMEs were able to achieve good contact with the scalp for heads of different sizes and shapes, and the EEG-Hat has a shutter mechanism to separate the hair and ensure good contact between the CMEs and the scalp. Simultaneous measurement of EEG signals from five measurement points on the scalp was successfully conducted after a simple and brief setup process. The EEG-Hat is expected to contribute to the advancement of EEG research.

Capturing Human Perceptual and Cognitive Activities via Event-Related Potentials Measured with Candle-Like Dry Microneedle Electrodes.

We demonstrate capture of event-related potentials (ERPs) using candle-like dry microneedle electrodes (CMEs). CMEs can record an electroencephalogram (EEG) even from hairy areas without any skin preparation, unlike conventional wet electrodes. In our previous research, we experimentally verified that CMEs can measure the spontaneous potential of EEG from the hairy occipital region without preparation with a signal-to-noise ratio as good as that of the conventional wet electrodes which require skin preparation. However, these results were based on frequency-based signals, which are relatively robust compared to noise contamination, and whether CMEs are sufficiently sensitive to capture finer signals remained unclear. Here, we first experimentally verified that CMEs can extract ERPs as good as conventional wet electrodes without preparation. In the auditory oddball tasks using pure tones, P300, which represent ERPs, was extracted with a signal-to-noise ratio as good as that of conventional wet electrodes. CMEs successfully captured perceptual activities. Then, we attempted to investigate cerebral cognitive activity using ERPs. In processing the vowel and prosody in auditory stimuli such as /itta/, /itte/, and /itta?/, laterality was observed that originated from the locations responsible for the process in near-infrared spectroscopy (NIRS) and magnetoencephalography experiments. We simultaneously measured ERPs with CMEs and NIRS in the oddball tasks using the three words. Laterality appeared in NIRS for six of 10 participants, although laterality was not clearly shown in the results, suggesting that EEGs have a limitation of poor spatial resolution. On the other hand, successful capturing of MMN and P300 using CMEs that do not require skin preparation may be readily applicable for real-time applications of human perceptual activities.

Microfluidic screening system based on boron-doped diamond electrodes and dielectrophoretic sorting for directed evolution of NAD(P)-dependent oxidoreductases.

We report the development of a micro total analysis system (µTAS) based on electrochemical measurements and dielectrophoretic sorting for screening of NAD(P)-dependent oxidoreductases. In this system, the activity of enzymes immobilized on microbeads, together with their encoding DNA, can be measured with a boron-doped diamond (BDD) electrode in each compartment (∼30 nL) of the microfluidic system. The 30 nL droplets containing microbead-displayed genes of enzymes with higher activity can then be recovered by dielectrophoretic sorting. Previously, we developed the NAD(P)H-measuring device containing the BDD electrode for high-throughput measurement of the activity of NAD(P)-dependent oxidoreductases. In this study, we fabricated an encapsulating device and a droplet-sorting device for nanoliter-size droplets, for the first time, and then combined these three devices to construct a µTAS for directed evolution of NAD(P)-dependent oxidoreductases. We confirmed that this system works by proof-of-principle experiments and successfully applied this system for screening of randomized libraries of NAD-dependent dehydrogenases.

Synthesis of sub-micrometer biphasic Au-AuGa2/liquid metal frameworks.

A novel biphasic sub-micrometer Au-AuGa2/liquid metal framework, consisting of solid nanoparticles encapsulating liquid metal (LM) droplets, is introduced. By utilizing oxide-free galvanic replacement of a Ga-alloy LM with alkaline KAuBr4, the controllable process of gold-based encapsulation of individual sub-micrometer LM droplets capped with polyvinylpyrrolidone, lysozyme or sodium alginate is demonstrated. The morphology, structure and composition of the encapsulated droplets are characterized in-depth via scanning electron microscopy, energy-dispersive X-ray spectroscopy, and X-ray diffraction. For the first time, the existence of two kinetic regimes leading to the controllable synthesis of either intermetallic AuGa2 or Au nanoparticles to encapsulate LM droplets is highlighted via the study of the evolution of the pH of the reaction medium. The as-formed biphasic sub-micrometer Au-LM frameworks demonstrate moderate stability in an aqueous environment and formidable structural and chemical stability in ambient air at room temperature. The encapsulation process can be adapted to the micro-patterning of LM droplet surfaces to produce conductive Au-encapsulated LM droplets then sintered to recover LM lines, while the sub-micrometer Au-LM droplets can be reintegrated onto larger LM surfaces and volumes to create multi-metallic and multi-scale biphasic structures with controllable electrical properties. The adaptability of the encapsulation process to the macro-, micro- and nanoscale of liquid metal features with a wide range of surfactants could in principle allow its use in various systems and applications.

Editorial for the Special Issue of Selected Papers from the 9th Symposium on Micro-Nano Science and Technology on Micromachines.

The Micro-Nano Science and Technology Division of the JSME (Japan Society of Mechanical Engineers) promotes academic activities to pioneer novel research topics on microscopic mechanics [...].

Connecting Mechanism for Artificial Blood Vessels with High Biocompatibility.

This paper proposes a connecting mechanism for artificial vessels, which can be attached/detached with ease and does not deteriorate the biocompatibility of the vessels at the joint. The inner surface of the artificial vessels is designed to have high biocompatibility. In order to make the best of the property, the proposed connecting mechanism contacts and fixes the two artificial vessels whose contacting edges are turned inside out. In this manner, blood flowing inside the vessels only has contact with the biocompatible surface. The biocompatibility, or biofouling at the joint was investigated after in vitro blood circulation tests for 72 h with scanning electron microscopy. Blood coagulation for a short term (120 min) was evaluated by activated partial thromboplastin time (APTT). A decrease of APTT was observed, although it was too small to conclude that the connector augmented the blood coagulation. The micro dialysis device which our group has developed as the artificial kidney was inserted into the blood circulation system with the connector. Decrease of APTT was similarly small. These experiments verified that the proposed connector can be readily applicable for implantable medical devices.

A Thermal Tactile Sensation Display with Controllable Thermal Conductivity.

We demonstrate a thermal tactile sensation display that can present various thermal sensations, namely cold/cool/warm/hot feelings, by varying the effective thermal conductivity of the display. Thermal sensation is one of the major tactile sensations and needs to be further investigated for advanced virtual reality/augmented reality (VR/AR) systems. Conventional thermal sensation displays present hot/cold sensations by changing the temperature of the display surface, whereas the proposed display is the first one that controls its effective thermal conductivity. The device contains an air cavity and liquid metal that have low and high thermal conductivity, respectively. When the liquid metal is introduced to fill up the air cavity, the apparent thermal conductivity of the device increases. This difference in the thermal conductivity leads to the users experiencing different thermal tactile sensations. Using this device, the threshold to discriminate the effective thermal conductivity was experimentally deduced for the first time. This thermal tactile display can be a good platform for further study of thermal tactile sensation.