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Recent nano-scale fabrication has realized the progress of integrated circuits, where current density increases with the downscaling of each electronic component, leading to failure due to electromigration. Electromigration is the transport of materials via momentum exchange from high-density conducting electrons to metal atoms. Defects of atoms result in the disconnection of the circuits and the accumulation of atoms causes the short circuit. Therefore, electromigration due to highly dense current flow has been studied for long years. However, it is difficult to non-destructively evaluate the structural and physical property changes due to the electromigration in an in-situ and microscopic measurement. In this study, we develop a real-time monitoring method of structural and mechanical property changes of a single nanowire using picosecond ultrasonics. Picosecond ultrasonics is ultrafast pump-probe laser ultrasonics using femtosecond pulse laser to excite and detect sub-THz ultrasound. We can focus the laser light within 1-micrometer diameter, enabling us to evaluate the mechanical property changes in a single nanowire from the ultrasound propagation. By applying direct current and observing ultrasound, we discuss the relationship among mechanical, electrical, and structural changes due to electromigration.

Protein aggregation causes intractable diseases such as Alzheimer’s disease. In these diseases, crystal-like protein aggregates, so-called amyloid fibrils, form in vivo and induce severe malfunction of biological tissues. Amyloid fibril formation comprises primary nucleation from a supersaturated solution of protein monomers and subsequent fibril growth. Within them, primary nucleation possesses an extremely high energy barrier, resulting in a long induction time for nucleation, typically over a decade in vivo and several days even in a test tube. Our previous study (1) revealed that ultrasonic irradiation to supersaturated protein solution drastically accelerates amyloid formation because of the effects of ultrasonic cavitation, which is applicable to clinical diagnosis (2). However, the degree of acceleration has not been controlled yet. Furthermore, the reproducibility of the induction time for nucleation highly depends on ultrasonic-irradiation conditions and the degree of supersaturation of initial protein solutions. Herein, we systematically investigate the optimized condition to accurately control amyloid formation using an originally developed sonoreactor (3) and discuss the underlying mechanism governing ultrasonic induction of amyloid formation. (1) K. Nakajima et al., Ultrason. Sonochem. 36, 206-211 (2017). (2) K. Nakajima et al., Nat. Commun. 13, 5689 (2022). (3) K. Nakajima et al., Ultrason. Sonochem. 73 105508 (2022).

Living cells sense various mechanical stimuli and respond to them by adjusting their tissue morphogenesis, self-renewal, and differentiation. Because stem cells seem to be more sensitive to the stimuli, many studies have been conducted to control their behavior. However, many of these mechanisms remain unexplored, because stimulus extends throughout the cells or causes cell-damaging. In this study, we have developed a focused ultrasound spectroscopic technique for noninvasively applying local mechanical stimulation in a single cell and combined it with an optical microscopy to systematically investigate its effects on the function and morphology of the cell. Our original system allows ultrasonically monitoring living cells for longer than 24 h. Appling this technique for human iPS cells, we find out an ultrasound absorption band at ∼160 MHz, which we attribute to the resonance of the nucleus. This indicates that we can stimulate cell nucleus selectively and effectively. Furthermore, we have established a method to evaluate the height distribution of cell colonies and revealed that human iPS cell colonies show very characteristic changes in height distribution during their growth.

α-Synuclein inclusions are a pathological hallmark of several neurodegenerative diseases. Although it has been demonstrated a relationship between fibril polymorphism and different pathologies, the molecular origins of polymorphism are not understood. Employing biophysical approaches, we revealed that the conformational state of the monomeric αSyn is responsible for fibril polymorphism: αSyn adopts specific conformations at high NaCl that produce rod fibrils, and different conformations at low NaCl that generate twisted fibrils. Using NMR, we found that the high NaCl conformations establish a polar interaction between the initial part of the NAC region and a wide section of the C-terminus domain. These high NaCl conformations can be commonly promoted by changes in the chemical environment, like NaCl, the presence of Ca2+or cellular components, like endotoxins, that alter the interaction NAC/C-terminus domain. Our results provide mechanistic insights that explain how the behavior of the C-terminus domain imparts polymorphism during the fibril formation.Significance StatementThe accumulation of the protein α-Synuclein into amyloid aggregates in the brain is a key characteristic of neurodegenerative disorders like Parkinson’s disease and multiple system atrophy. Intensive research has demonstrated that structurally different amyloid fibrils are related to the development of different diseases; however, the molecular mechanisms that originate such fibril diversity from the same protein remain unknown. In this work, we discovered that the conformational state of the monomeric αSyn, regulated by an intramolecular polar interaction NAC region/C-terminus domain, is crucial for the generation of different fibrils. Our results represent the monomeric molecular events behind the diversity of fibrils and open the conformational state of αSyn as a target to understand how the fibrils get formed in the brain.

The dynamics of magnetization is important in spintronics, where the coupling between phonon and magnon attracts much attention. In this work, we study the angular dependence of the coupling between longitudinal-wave phonon and magnon. We investigated the magnetization dynamics using the time-resolved magneto-optical Kerr effect, which allows measuring spin-wave resonances and the magnetic echo signal. The frequency, mode number, and amplitude of the spin-wave resonance change with the out-of-plane angle of the external magnetic field. The amplitude of the magnetic echo signal caused by the strain pulse also changes with the angle. We calculate these angular dependences based on the Landau–Lifshitz–Gilbert equation and find that the angles of the external field and magnetic moment are important factors for the phonon–magnon coupling when phonon propagates in the thickness direction under the out-of-plane magnetic field.

We acoustically measured the energy level for thermally activated conduction (TAC) in high-resistivity Fe-doped GaN using the non-contacting antenna-transmission acoustic-resonance method. The acoustic attenuation takes a maximum at a specific temperature, where the TAC is accelerated with the help of phonon energy. The Debye-type relaxation is thus observed for acoustic attenuation, and its activation energy (0.54 ± 0.04 eV) was determined with attenuation measurements at various frequencies and temperatures. This value agrees with the E3 level in GaN, indicating that thermally associated conduction originates from the E3 trap level. We also measured the five independent elastic constants at high temperatures.

The adsorbed structure of 1-pyrenebutanoic acid succinimidyl ester (PASE) on graphene was investigated based on density functional theory. We found two locally stable structures: a straight structure with the chainlike part of butanoic acid succinimidyl ester (BSE) lying down and a bent structure with the BSE part directed away from graphene, keeping the pyrene (Py) part adsorbed on graphene. Then, to elucidate the adsorption mechanism, we separately estimated the contributions of the Py and BSE parts to the entire PASE adsorption, and the adsorption effect of the BSE part was found to be secondary in comparison to the contribution of the Py. Next, the mobility of the BSE part at room temperature was confirmed by the activation energy barrier between straight and bent structures. To take account of the external environment, we considered the presence of amino acids and the hydration effect by a three-dimensional reference interaction site model. The contributions of glycine molecules and the solvent environment to stabilizing the bent PASE structure relative to the straight PASE structure were found. Therefore, the effect of the external environment around PASE is of importance when the standing-up process of the BSE part from graphene is considered., Comment: 21 pages, 5 figures, accepted for publication in ACS Omega

Nakamura Nobutomo, Matsuura Koji, Ishii Akio and Ogi Hirotsugu. Restructuring in bimetallic core-shell nanoparticles: Real-time observation. Physical Review B, 105, 125401, 2022. https://doi.org/10.1103/PhysRevB.105.125401., The formation process of core-shell bimetallic nanoparticles synthesized by sputtering onto a substrate is observed in real time using an originally developed acoustic technique. The technique enables us to evaluate the structural change of nanoparticles at room temperature without contacting the nanoparticles or substrate. In the experiments, the sputtering of metal A followed by metal B tended to form B-shell/A-core nanoparticles. However, in Pd-Au alloy system, notable restructuring occurred during synthesis, resulting in the formation of A-shell/B-core nanoparticles. The formation process is analyzed using the molecular dynamics simulation, revealing that this restructuring occurs on a short timescale, and high diffusivity of Au plays an important role.

We propose a high sensitivity biosensor based on a GHz phononic crystal (PnC) waveguide, and demonstrate its operation by numerical simulations. The geometry consists of a micron-scale freestanding PnC silica waveguide plate with embedded Au nanopillars for bioparticle attachment, the PnC plate lying between two groups of periodic metal strips for GHz Lamb-wave acoustic generation and detection with ultrashort light pulses. By precise choice of the waveguide defect width, this biosensor is designed to work using a single, isolated waveguide mode. We study the influence of the waveguide defect width on the acoustic dispersion and transmission of this mode. Bioparticle attachment is simulated by investigation of the Au nanopillar mass loading, and is shown to shift the waveguide transmission peak to lower frequencies. We thereby demonstrate femtogram detection, showing that our approach provides a new methodology for label-free ultra-sensitive biosensing.

The hydrogen energy, which is environmentally friendly and does not emit carbon dioxide, has been attracting attention as an alternative fuel to the fossil fuel. In the shift to a hydrogen energy society, the highly sensitive hydrogen gas sensor has been required for the storage and management of hydrogen gas. In this study, we propose a film deposition method to induce the in-plane plastic deformation in the thin film and apply it to a hydrogen gas sensor, where the palladium film formed by this method is deposited on a thin quartz resonator. It is found that the sensor chip with the plastically deformed palladium film is about 1.5 times more sensitive than the conventional sensor chip and has high-speed response. The developed sensor is a novel device that can be used in an oxygen-free environment without any temperature compensation and constant heating.

Weng H.K., Nagakubo A., Ogi H., et al. "Phonon propagation in isotopic diamond superlattices", Physical Review B, 104(5), 054112, 2021. https://doi.org/10.1103/physrevb.104.054112., The out-of-plane thermal conductivity and elastic constant of epitaxial [100] C12/C13 superlattice diamonds with layer thicknesses of 1, 30, and 100 nm are evaluated by picosecond ultrasound spectroscopy. The measured elastic constants of the superlattices are equivalent to those of single-layer diamond thin films. This result confirms our success in synthesizing superlattice specimens with few defects at the interfaces. Therefore, the phonon transport behavior is governed by the mass difference, not the interfacial defects. The measured thermal conductivity of the superlattices is lower than that of a pure C12 isotope diamond thin film. We estimated the lattice thermal conductivity using the lattice dynamics calculation, attributing the lowered thermal conductivity to the decrease in the phonon group velocity in superlattices. We further consider the effect of mini-umklapp scattering in the superlattice, which explains the dependence of the thermal conductivity on the layer thickness. We reveal that the mini-umklapp scattering effect becomes significant only for an isotope diamond superlattice because of the high Debye temperature and large relative mass difference.

Amyloid fibrils are formed from various proteins, some of which cause the corresponding neurodegenerative disorders, such as Alzheimer's and Parkinson's diseases. It has been reported that many compounds inhibit the formation of amyloid fibrils. Anthocyanins are flavonoid pigments present in fruits and vegetables, which are known to suppress symptoms related with Alzheimer's disease. However, the influence of anthocyanins on the amyloid fibril remains unclear. Here, we succeeded in the direct monitoring of the disaggregation reaction of single amyloid β (Aβ) fibrils by anthocyanins using total-internal-reflection-fluorescence microscopy with a quartz-crystal microbalance (TIRFM-QCM). It is found that the disassembly activity to the Aβ fibrils depends on the number of hydroxyl groups in six-membered ring B of anthocyanin, and only delphinidin-3-galactoside, possessing three hydroxyl groups there, shows high disassembly activity. Our results show the importance of the number of hydroxyl groups and demonstrate the usefulness of TIRFM-QCM as a powerful tool in studying interactions between amyloid fibrils and compounds.

Quartz-crystal-microbalance (QCM) biosensor is a mass-sensitive biosensor, and its sensitivity in detecting target proteins can be improved with weighted detection antibodies. In this communication, we propose a mass-amplified detection of biomarkers by bio-nanocapsules (BNCs) in wireless high-frequency multichannel QCM biosensor. BNC exhibits molecular mass of 6.57 MDa and possesses many immunoglobulin-G (IgG) Fc-binding Z domains on its surface, making it possible to display ∼60 antibodies in an oriented immobilization manner. We find that by reinforcing the bond strength between the Z domain and the Fc part of antibody with the cross-linker, a high sensitive detection of biomarkers with QCM is realized. We used multichanel wireless QCM system with fundamental resonance frequencies above 54 MHz and performed detection of C-reactive protein. The detection limit is lower than 10 pg/mL, confirming that combination of BNC and wireless high-frequency QCM allows high sensitivity detection of biomarkers.

A novel label-free biosensor array is proposed, which uses the ultrafast heat transport from a metallic nano-plate into surrounding solution across proteins captured on the nano-plate. Using electron-beam lithography, 2500 gold nano-plates of 30 nm thick with 5 × 5 μm2 area were fabricated on a fused silica substrate, on which receptor proteins were immobilized. Thermal phonons were induced on the back surface of a single nano-plate by focusing ultrafast light pulses from the substrate side, which propagated toward surrounding solution through surface proteins. Because the ultrafast heat-transport behavior, which is completed within ∼1 ns, is affected by existence of target proteins on the nano-plate, each nano-plate works as a single label-free biosensor. A theoretical calculation was made for predicting the cooling-down behavior of the nano-plate after an impulsive heating, and a pump–probe optics was developed for monitoring the ultrafast temperature change after excitation with a femtosecond fiber laser. We then confirm that each nano-plate acts as a single label-free biosensor by performing antigen–antibody binding reactions, indicating that a large scale number of multichannel measurement is made possible with this phenomenon.

Nucleation by sedimentation of colloidal particles on a flat surface is experimentally observed, and effect of attractive depletion force generated by polymers on nucleation is investigated. Sedimentation forms polycrystalline colloidal crystal on a flat surface, and above the threshold polymer concentration, ratio of the spontaneous nucleation increases, resulting in a decrease in the grain size, whereas dependence of the contact angle on the polymer concentration was not observed. We show that the interaction between particles and the flat surface mainly affects the spontaneous nucleation, not the interaction between the particles, and it is demonstrated that the nucleation process can be numerically reproduced using the rate equations.

The formation of amyloid fibrils of various amyloidogenic proteins is dramatically enhanced by ultrasound irradiation. To apply this phenomenon to the study of protein aggregation science and diagnosis of neurodegenerative diseases, a multichannel ultrasound irradiation system with individually adjustable ultrasound irradiation conditions is necessary. Here, we develop a sonochemical reaction system, where an ultrasonic transducer is placed in each well of a 96-well microplate to perform ultrasonic irradiation of sample solutions under various conditions with high reproducibility, and applied it to study the amyloid fibril formation of amyloid β, α-synuclein, β2-microglobulin, and lysozyme. The results clearly show that our instrument is superior to the conventional shaking method in terms of the degree of acceleration and reproducibility of fibril formation reaction. The acceleration degree is controllable by controlling the driving voltage applied to each transducer. We have thus succeeded in developing a useful tool for the study of amyloid fibril formation in various proteins.

Since surface acoustic waves (SAW) are often generated on substrates to which nanostrips are periodically attached, it is very important to consider the effect of interface between the deposited strip and the substrate surface, which is an unavoidable issue in manufacturing. In this paper, we propose a theoretical model that takes into account the interface damping and calculate the dispersion relationships both for frequency and attenuation of SAW resonance. This results show that the interface damping has an insignificant effect on resonance frequency, but, interestingly, attenuation of the SAW can decrease significantly in the high frequency region as the interface damping increases. Using picosecond ultrasound spectroscopy, we confirm the validity of our theory; the experimental results show similar trends both for resonant frequency and attenuation in the SAW resonance. Furthermore, the resonant behavior of the SAW is simulated using the finite element method, and the intrinsic cause of interface damping on the vibrating system is discussed. These findings strongly indicate the necessity of considering interfacial damping in the design of SAW devices.

We study the lattice thermal conductivity of isotope diamond superlattices consisting of 12C and 13C diamond layers at various superlattice periods. It is found that the thermal conductivity of a superlattice is significantly deduced from that of pure diamond because of the reduction of the phonon group velocity near the folded Brillouin zone. The results show that asymmetric superlattices with a different number of layers of 12C and 13C diamonds exhibit higher thermal conductivity than symmetric superlattices even with the same superlattice period, and we find that this can be explained by the trade-off between the effects of phonon specific heat and phonon group velocity. Furthermore, impurities and imperfect superlattice structures are also found to significantly reduce the thermal conductivity, suggesting that these effects can be exploited to control the thermal conductivity over a wide range.

Nakajima K., Yamazaki T., Kimura Y., et al. "Time-Resolved Observation of Evolution of Amyloid-β Oligomer with Temporary Salt Crystals", Journal of Physical Chemistry Letters, 11(15), 6176-6184, July 20, 2020. Copyright © 2020 American Chemical Society. https://doi.org/10.1021/acs.jpclett.0c01487., The aggregation behavior of amyloid-β (Aβ) peptides remains unclarified despite the fact that it is closely related to the pathogenic mechanism of Alzheimer's disease. Aβ peptides form diverse oligomers with various diameters before nucleation, making clarification of the mechanism involved a complex problem with conventional macroscopic analysis methods. Time-resolved single-molecule level analysis in bulk solution is thus required to fully understand their early stage aggregation behavior. Here, we perform time-resolved observation of the aggregation dynamics of Aβ oligomers in bulk solution using liquid-state transmission electron microscopy. Our observations reveal previously unknown behaviors. The most important discovery is that a salt crystal can precipitate even with a concentration much lower than its solubility, and it then dissolves in a short time, during which the aggregation reaction of Aβ peptides is significantly accelerated. These findings will provide new insights in the evolution of the Aβ oligomer.

Amyloid fibrils involved in amyloidoses are crystal-like aggregates, which are formed by breaking supersaturation of denatured proteins. Ultrasonication is an efficient method of agitation for breaking supersaturation and thus inducing amyloid fibrils. By combining an ultrasonicator and a microplate reader, we developed the HANABI (HANdai Amyloid Burst Inducer) system that enables high-throughput analysis of amyloid fibril formation. Among high-throughput approaches of amyloid fibril assays, the HANABI system has advantages in accelerating and detecting spontaneous amyloid fibril formation. HANABI is also powerful for amplifying a tiny amount of preformed amyloid fibrils by seeding. Thus, HANABI will contribute to creating therapeutic strategies against amyloidoses by identifying their biomarkers.

The interplanar bond strength in graphite has been identified to be very low owing to the contribution of the van der Waals interaction. However, in this study, we use microscopic picosecond ultrasound to demonstrate that the elastic constant, $C_{33}$, along the $c$ axis of defect-free monocrystalline graphite exceeds 45 GPa, which is higher than reported values by 20\%. Existing theories fail to reproduce this strongly correlated interplanar system, and our results, thus, indicate the necessity for improvement. Since the LDA+U+RPA method, including both random phase approximation correlation and short-range correlation in $p$ Wannier orbitals, shows better agreement with the observation than LDA or even than ACFDT-RPA, the experimental results indicate non-negligible electron correlation effects with respect to both the short-range and long-range interactions., (Main text) 5 pages, 3 figures, (Supplementary material A) 2 pages, 2 figures, (Supplementary material B) 12 pages, 1 figure

Thermal mode spectroscopy (TMS) has been recently proposed for accurately measuring thermal diffusivity of solids from a temperature decay rate of a specific thermal mode selected by three- dimensional (anti)nodal information [Phys. Rev. Lett., 117, 195901 (2016)]. In this paper, we find out the following advantages of TMS by use of perturbation analyses. First, TMS is applicable to the measurement of high thermal diffusivity with a small size specimen. Second, it is less affected by thermally resistive films on a specimen in the sense that the resistance at the interface does not affect the first-order correction of thermal diffusivity. Third, it can perform doubly accurate measurement of the thermal diffusivity specified at a thermal equilibrium state even if the diffusivity depends on temperature in the sense that the measurement can be performed within tiny temperature difference from the given state and that the decay rate of the slowest decaying mode is not affected by the dependence., Comment: 17 pages, 6 figures

Yen-Ting Lai, Hirotsugu Ogi, Kentaro Noi, and Fumihito Kato. Viscoelasticity Response during Fibrillation of Amyloid β Peptides on a Quartz-Crystal-Microbalance Biosensor. Langmuir, 2018, 34(19), 5474-5479. ©2018 American Chemical Society. https://doi.org/10.1021/acs.langmuir.8b00639., Unlike previous in vitro measurements where Amyloid β (Aβ) aggregation was studied in bulk solutions, we detect the structure change of the Aβ aggregate on the surface of a wireless quartz-crystal-microbalance biosensor, which resembles more closely the aggregation process on the cell membrane. Using a 58 MHz quartz crystal, we monitored changes in the viscoelastic properties of the aggregate formed on the quartz surface from monomers to oligomers and then to fibrils, involving up to the 7th overtone mode (406 MHz). With atomic-force microscopy observations, we found a significant stiffness increase as well as thinning of the protein layer during the structure change from oligomer to fibrils at 20 h, which indicates that the stiffness of the fibril is much higher. Viscoelasticity can provide a significant index of fibrillation and can be useful for evaluating inhibitory medicines in drug development.

This research was originally published in the Journal of Biological Chemistry. Ayame Nitani, Hiroya Muta, Masayuki Adachi, Masatomo So, Kenji Sasahara, Kazumasa Sakurai, Eri Chatani, Kazumitsu Naoe, Hirotsugu Ogi, Damien Hall, and Yuji Goto. Heparin-dependent aggregation of hen egg white lysozyme reveals two distinct mechanisms of amyloid fibrillation. J. Biol. Chem. 2017; 292, 21219-21230 © the American Society for Biochemistry and Molecular Biology, Heparin, a biopolymer possessing high negative charge density, is known to accelerate amyloid fibrillation by various proteins. Using hen egg white lysozyme, we studied the effects of heparin on protein aggregation at low pH, raised temperature, and applied ultrasonic irradiation, conditions under which amyloid fibrillation was promoted. Heparin exhibited complex bimodal concentration-dependent effects, either accelerating or inhibiting fibrillation at pH 2.0 and 60 °C. At concentrations lower than 20 μg/ml, heparin accelerated fibrillation through transient formation of hetero-oligomeric aggregates. Between 0.1 and 10 mg/ml, heparin rapidly induced amorphous heteroaggregation with little to no accompanying fibril formation. Above 10 mg/ml, heparin again induced fibrillation after a long lag time preceded by oligomeric aggregate formation. Compared with studies performed using monovalent and divalent anions, the results suggest two distinct mechanisms of heparin-induced fibrillation. At low heparin concentrations, initial hen egg white lysozyme cluster formation and subsequent fibrillation is promoted by counter ion binding and screening of repulsive charges. At high heparin concentrations, fibrillation is caused by a combination of salting out and macromolecular crowding effects probably independent of protein net charge. Both fibrillation mechanisms compete against amorphous aggregation, producing a complex heparin concentration–dependent phase diagram. Moreover, the results suggest an active role for amorphous oligomeric aggregates in triggering fibrillation, whereby breakdown of supersaturation takes place through heterogeneous nucleation of amyloid on amorphous aggregates.

Summary Background Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a member of the EGF family and is involved in various diseases including cancers. Aptamers are synthetic oligonucleotides (RNA or DNA) that fold into unique three-dimensional structures and specifically bind to their targets with high affinity. We aimed to generate an aptamer with high affinity and specificity for HB-EGF. Methods Recombinant human HB-EGF (rhHB-EGF), comprised of the extracellular EGF-like and heparin-binding domains of HB-EGF, was used as the target. The aptamer against HB-EGF (the anti-HB-EGF aptamer) was obtained by systematic evolution of ligands by exponential enrichment (SELEX). Results After the 10th round of SELEX, aptamers were reverse-transcribed and PCR-amplified. Within obtained forty-six clones, twenty-three were identical (the anti-HB-EGF aptamer). The analysis using wireless-electrodeless quartz crystal microbalance revealed that the anti-HB-EGF aptamer had high affinity for rhHB-EGF (KD value: 12.2 ± 1.1 nmol/L). The dot-blot analysis revealed that the anti-HB-EGF aptamer specifically bound to rhHB-EGF. The analysis using confocal microscopy indicated that the anti-HB-EGF aptamer also bound to membrane-bound HB-EGF. Western-blot assay indicated that the anti-HB-EGF aptamer inhibited the phosphorylation of rhHB-EGF-mediated EGF receptor (EGFR). Conclusion We identified a novel RNA aptamer that bound with high affinity and specificity to rhHB-EGF and potently inhibited the rhHB-EGF-mediated phosphorylation of EGFR. The anti-HB-EGF aptamer may be a promising therapeutic agent for specifically neutralizing HB-EGF signaling.

Nakajima K., Nishioka D., Hirao M., et al. Drastic acceleration of fibrillation of insulin by transient cavitation bubble. Ultrasonics Sonochemistry, 36, 206, 2016. https://doi.org/10.1016/j.ultsonch.2016.11.034., Amyloid-fibril formation of proteins can be accelerated by ultrasonic irradiation to the peptide solutions. Although this phenomenon contributes to understanding pathogenic behavior of amyloidosis, its physical mechanism has not been clarified, because several factors (cavitation, temperature increase, stirring effect, and so on) related to ultrasonic irradiation can participate in the fibrillation reaction. Here, we independently study contributions of the possible factors, using insulin, which is extremely stable and then suitable for the mechanism clarification. We find that the optimized ultrasonic irradiation can drastically accelerate the fibrillation reaction; the time for completing the reaction is shortened compared with the high-speed (1200 rpm) stirring agitation by a factor of 430. The fibrillation reaction proceeds only when the subharmonic-mode intensity exceeds a threshold, indicating generation of the transient cavitation bubbles. Our results reveal that not the temperature increase but the transient cavitation bubbles work as the dominant accelerator of the fibrillation reaction.

We developed a pitch-catch system based on electromagnetic acoustic transducers (EMATs) for pipe inspection, which moves inside the pipe in the axial direction. The first higher mode, T(0,2), of the torsional guided wave is transmitted and detected, and variations of amplitude and phase are measured while moving the EMATs. Several aluminum pipes containing dish-shaped defects are inspected, and the amplitude and phase show enough detection sensitivity. It is found that the phase measurement has better potential as a tool for quantitative inspection. The applicability of the technique for steel pipe is also confirmed.

Oligomer species of amyloid β (Aβ) peptides are intensively investigated because of their relevance to Alzheimer’s disease (AD), and a stable oligomer will be a cause of AD. In this article, we investigate the structural stability of two representative Aβ1–40 oligomers, which are with and without the β-sheet structure, denoted by β and non-β oligomers, respectively, using optimized ultrasonic irradiation (OUI). Recent studies reveal that OUI significantly accelerates the fibril formation in Aβ1–40 monomers; it is capable of transforming any unstable oligomers into fibrils (the dead-end products) in a short time. First, we find that β oligomers can be produced under high-speed stirring agitation; their β-sheet structures are evaluated by the circular-dichroism spectrum measurement, by the immunoassay using the fibril-specific OC antibody, and by the seeding experiment, showing identical characteristics to those formed in previous reports. Second, we form non-β oligomers in a high-concentration NaCl solutio...

Kentaro Noi, Arihiro Iwata, Fumihito Kato, and Hirotsugu Ogi. Ultrahigh-frequency, wireless mems qcm biosensor for direct, label-free detection of biomarkers in a large amount of contaminants. Analytical Chemistry, 2019, 91(15), 9398-9402. ©2019 American Chemical Society. https://doi.org/10.1021/acs.analchem.9b01414., Label-free biosensors, including conventional quartz-crystal-microbalance (QCM) biosensors, are seriously affected by nonspecific adsorption of contaminants involved in analyte solution, and it is exceptionally difficult to extract the sensor responses caused only by the targets. In this study, we reveal that this difficulty can be overcome with an ultrahigh-frequency, wireless QCM biosensor. The sensitivity of a QCM biosensor dramatically improves when the quartz resonator is thinned, which also makes the resonance frequency higher, causing high-speed surface movement. Contaminants weakly (nonspecifically) interact with the quartz surface, but they fail to follow the fast surface movement and cannot be detected as the loaded mass. The targets are, however, tightly captured by the receptor proteins immobilized on the surface, and they can move with the surface, contributing to the loaded mass and decreasing the resonant frequency. We have developed a MEMS QCM biosensor in which an AT-cut quartz resonator, 26 μm thick, is packaged without fixing, and we demonstrate this phenomenon by comparing the frequency changes of the fundamental (∼64 MHz) and ninth (∼576 MHz) modes. At ultrahigh-frequency operation with the ninth mode, the sensor response is independent of the amount of impurity proteins, and the binding affinity is unchanged. We then applied this method to the label-free and sandwich-free, direct detection of C-reactive protein (CRP) in serum and confirmed its applicability.

This is the Accepted Manuscript version of an article accepted for publication in Japanese Journal of Applied Physics. IOP Publishing Ltd are not responsible for any errors or omissions in this version of the manuscript or any version derived from it. The Version of Record is available online at https://doi.org/10.35848/1347-4065/abea50., We present a wireless quartz crystal microbalance (QCM) biosensor fabricated using MEMS technology. The MEMS QCM biosensor contains a 125 MHz AT-cut quartz resonator embedded in the microchannel. Because of the compact design, the MEMS QCM biosensor is suitable for mass production and device miniaturization. We performed immunoglobulin G (IgG) detection measurements with different concentrations of IgG. The detection limit was 1 ng ml-1 or less, which is superior to that of the gold-standard surface plasma resonance method. Furthermore, we studied the binding affinity between protein A and IgG by studying the frequency response of the QCM biosensor. We found good agreement with reported values. Therefore, the presented MEMS QCM biosensor has the advantages of compactness, low cost, low power consumption, high sensitivity, and reliability.

This is the Accepted Manuscript version of an article accepted for publication in Japanese Journal of Applied Physics. IOP Publishing Ltd are not responsible for any errors or omissions in this version of the manuscript or any version derived from it. The Version of Record is available online at https://doi.org/10.35848/1347-4065/abec5a., Elastic constants and sound velocities of nm order thin films are essential for designing acoustic filters. However, it is difficult to measure them for dielectric thin films. In this study, we use a three-layer structure where a dielectric nano-thin film is sandwiched between thicker metallic films to measure the longitudinal elastic constant of the dielectric film. We propose an efficiency function to estimate the optimal thicknesses of the components. We use Pt/NiO/Pt three-layer films for confirming our proposed method. The determined elastic constant of NiO deposited at room temperature is smaller than the bulk value by ∼40%. However, it approaches the bulk value as the deposition temperature increases. We also reveal that the uncertainty of the elastic constant of the Pt film insignificantly affects the accuracy of the determined elastic constant of NiO in this structure.

This paper studies the structural design of the wireless-electrodeless quartz crystal microbalance (QCM) sensor, which has a rectangular AT-cut quartz oscillator installed in the microchannel fabricated by nanoimprint lithography. The quartz oscillator was supported by the micropillars in the microchannel, and by optimizing the micropillar arrangement, it was found that the structural damping could be significantly reduced by performing the finite elemental piezoelectric analysis. This behavior was then confirmed by the experiments using the evaluation chips. By supporting the four corners of the quartz oscillator with the micropillars, the structural damping could be reduced, achieving a high-quality factor (Q-factor) of about 24700. This high Q-factor was also realized in the experiments, and we investigated its application to a hydrogen-gas sensor. We succeeded in detecting hydrogen gas with an extremely low concentration of 10 ppm.

A highly sensitive hydrogen-gas sensor fabricated using MEMS technology is presented. The sensor chip consists of glass substrates, silicon substrate, and an AT-cut quartz crystal resonator, which is embedded in the microchannel constructed on the substrates. The quartz resonator has a fundamental resonant frequency of 165 MHz and a 200 nm palladium film deposited on its single surface as the hydrogen-gas sensing material. The MEMS hydrogen-gas sensor operates in a wireless manner by exciting and detecting the resonator vibration using the non-contacting antennas. The curvature induced resonant frequency change of the resonator plate caused by the expansion of the palladium film is used for the detection of the hydrogen gas. We succeeded in improving the hydrogen absorption rate and then the sensitivity for the hydrogen-gas detection by applying the air-plasma treatment method, and clarified the role of palladium oxide in lowering the energy barrier for the hydrogen-atom migration from surface to subsurface with the X-ray photoelectron spectroscopy. Thus sensitivity enhanced MEMS hydrogen-gas sensor exhibits a detection limit of 10 ppm or less at room temperature both in nitrogen and air.

Point-focusing electromagnetic-acoustic transducers (PF-EMATs) for shear-vertical (SV) waves were developed for crack inspection of stainless-steel pipes. The transducer has improved defect detectability by accumulating SV waves generated by concentric line sources at a focal point in phase. An optimum frequency for defect detection was found to be 2 MHz, with which a crack of 0.5 mm depth near a weld was clearly detected. The EMAT exhibited defect detectability comparable to that of a conventional phased-array piezoelectric transducer, indicating that this new EMAT is highly practical for the non-contacting evaluation of stress-corrosion cracking in stainless steels.

This is the Accepted Manuscript version of an article accepted for publication in Japanese Journal of Applied Physics. IOP Publishing Ltd are not responsible for any errors or omissions in this version of the manuscript or any version derived from it. The Version of Record is available online at https://doi.org/10.35848/1347-4065/abea50., For visualizing propagation of an acoustic wave and evaluating the local sound velocity in micro/nano-meter structures, confocal picosecond ultrasonics is developed. In conventional picosecond ultrasonics, the measurement of local sound velocity was difficult, and macroscopic sound velocity and elastic properties were measured. However, in confocal picosecond ultrasonics, a confocal laser-scanning microscope is embedded in the optics of the picosecond ultrasonics, and the depth resolution is improved. Using the developed optics, we successfully observed propagation of an acoustic wave in thin film. In this paper, the optics we developed and the experimental results on silica film are reported.