Investigating the efficacy of nasal administration for delivering magnetic nanoparticles into the brain for magnetic particle imaging.

This study explored the effectiveness of nasal administration in delivering magnetic nanoparticles into the brain for magnetic particle imaging of target regions. Successful delivery of iron oxide nanoparticles, which serve as contrast agents, to specific sites within the brain is crucial for achieving magnetic particle imaging. Nasal administration has gained attention as a method to bypass the blood-brain barrier and directly deliver therapeutics to the brain. In this study, we investigated surface modification techniques for administering magnetic nanoparticles into the nasal cavity, and provided experimental validation through in vivo studies. By compositing magnetic nanoparticles with gold nanoparticles, we enabled additional surface modification via AuS bonds without compromising their magnetic properties. The migration of the designed PEGylated magnetic nanoparticles into the brain following nasal administration was confirmed by magnetization measurements. Furthermore, we demonstrated the accumulation of these nanoparticles at specific target sites using probe molecules immobilized on the PEG terminus. Thus, the efficacy of delivering magnetic nanoparticles to the brain via nasal administration was demonstrated in this study. The findings of this research are expected to contribute significantly to the realization of magnetic particle imaging of target regions within the brain.

Ultrathin Platinum Film Hydrogen Sensors with a Twin-T Type Notch Filter Circuit.

In recent years, hydrogen energy has garnered attention as a potential solution for mitigating greenhouse gas emissions. However, concerns regarding the inherent risk of hydrogen gas leakage and potential explosions have necessitated the development of advanced sensors. Within our research group, we have innovated an ultrathin platinum (Pt) film hydrogen sensor that gauges resistance changes in Pt thin films when exposed to hydrogen gas. Notably, the sensitivity of each sensor is contingent upon the thickness of the Pt film. To address the challenge of detecting hydrogen using multiple sensors, we integrated the ultrathin Pt film as a resistance element within a twin-T type notch filter. This filter exhibits a distinctive reduction in output signals at a specific frequency. The frequency properties of the notch filter dynamically alter with changes in the resistance of the Pt film induced by hydrogen exposure. Consequently, the ultrathin Pt film hydrogen sensor monitors output signal variations around the notch frequency, responding to shifts in frequency properties. This innovative approach enables the electrical control of sensor sensitivity by adjusting the operating frequency in proximity to the notch frequency. Additionally, the simultaneous detection of hydrogen by multiple sensors was successfully achieved by interconnecting sensors with distinct notch frequencies in series.

Multifunctional terahertz microscopy for biochemical and chemical imaging and sensing.

Laser-excited terahertz emission microscopy (LTEM) has exhibited great potential for studying the dynamic physical properties of various materials and device evaluation. In this study, an up-to-date version of LTEM, the terahertz chemical microscopy, was developed for biochemical and chemical imaging and sensing. By functionalizing a terahertz semiconductor emitter with an ion-sensitive membrane, a DNA aptamer, and a specific polymer, the change in the terahertz signal amplitude attributed to the surface electrical potential change was successfully detected. Accordingly, the measurement of calcium ions (Ca2+), stress biomarker cortisol, and 2, 4, 6-trinitrotoluene (TNT) explosive was achieved. Measured of charged Ca2+ was via the change in the electrical potential of the ion-sensitive membrane with ion accumulation. For non-charged cortisol and TNT measurements, the surface potential change was recorded by the conformational change of the negatively charged DNA aptamer bound to cortisol and the charge-transfer complex formation between TNT and polyethylenimine polymer, respectively. Moreover, the specificity of this sensing approach was demonstrated by molecular docking and measuring the interfering substances such as sodium ions, potassium ions, brain chemicals histamine and dopamine, and TNT analogues. The results showed that the developed multifunctional terahertz microscopy technique can be used for trace biochemical and chemical sensing via visualization of the terahertz amplitude distribution.

Optimization of Microchannels and Application of Basic Activation Functions of Deep Neural Network for Accuracy Analysis of Microfluidic Parameter Data.

The fabrication of microflow channels with high accuracy in terms of the optimization of the proposed designs, minimization of surface roughness, and flow control of microfluidic parameters is challenging when evaluating the performance of microfluidic systems. The use of conventional input devices, such as peristaltic pumps and digital pressure pumps, to evaluate the flow control of such parameters cannot confirm a wide range of data analysis with higher accuracy because of their operational drawbacks. In this study, we optimized the circular and rectangular-shaped microflow channels of a 100 µm microfluidic chip using a three-dimensional simulation tool, and analyzed concentration profiles of different regions of the microflow channels. Then, we applied a deep learning (DL) algorithm for the dense layers of the rectified linear unit (ReLU), Leaky ReLU, and Swish activation functions to train and test 1600 experimental and interpolation of data samples which obtained from the microfluidic chip. Moreover, using the same DL algorithm, we configured three models for each of these three functions by changing the internal middle layers of these models. As a result, we obtained a total of 9 average accuracy values of ReLU, Leaky ReLU, and Swish functions for a defined threshold value of 6×10-5 using the trial-and-error method. We applied single-to-five-fold cross-validation technique of deep neural network to avoid overfitting and reduce noises from data-set to evaluate better average accuracy of data of microfluidic parameters.

Rational Design of Peptides Derived from Odorant-Binding Proteins for SARS-CoV-2-Related Volatile Organic Compounds Recognition.

Peptides are promising molecular-binding elements and have attracted great interest in novel biosensor development. In this study, a series of peptides derived from odorant-binding proteins (OBPs) were rationally designed for recognition of SARS-CoV-2-related volatile organic compounds (VOCs). Ethanol, nonanal, benzaldehyde, acetic acid, and acetone were selected as representative VOCs in the exhaled breath during the COVID-19 infection. Computational docking and prediction tools were utilized for OBPs peptide characterization and analysis. Multiple parameters, including the docking model, binding affinity, sequence specification, and structural folding, were investigated. The results demonstrated a rational, rapid, and efficient approach for designing breath-borne VOC-recognition peptides, which could further improve the biosensor performance for pioneering COVID-19 screening and many other applications.

Thickness Measurement at High Lift-Off for Underwater Corroded Iron-Steel Structures Using a Magnetic Sensor Probe.

Infrastructure facilities that were built approximately half a century ago have rapidly aged. Steel sheet piles, the inspection object in this study, are severely corroded, resulting in cave-in damages at wharfs. To solve such a problem, non-destructive inspection techniques are required. We previously demonstrated plate thickness measurement using extremely low-frequency eddy current testing. However, when the steel sheet piles are located in water, shellfish adhere to their surface, causing a lift-off of several tens of millimeters. Therefore, this large lift-off hinders the thickness measurement owing to fluctuations of magnetic signals. In this study, sensor probes with different coil diameters were prototyped and the optimum size for measuring steel sheet piles at high lift-off was investigated. Using the probes, the magnetic field was applied with a lift-off range from 0 to 80 mm, and the intensity and phase of the detected magnetic field were analyzed. Subsequently, by increasing the probe diameter, a good sensitivity was obtained for the thickness estimation with a lift-off of up to 60 mm. Moreover, these probes were used to measure the thickness of actual steel sheet piles, and measurements were successfully obtained at a high lift-off.

Detection of Lung Cancer Cells in Solutions Using a Terahertz Chemical Microscope.

Cancer genome analysis has recently attracted attention for personalized cancer treatment. In this treatment, evaluation of the ratio of cancer cells in a specimen tissue is essential for the precise analysis of the genome. Conventionally, the evaluation takes at least two days and depends on the skill of the pathologist. In our group, a terahertz chemical microscope (TCM) was developed to easily and quickly measure the number of cancer cells in a solution. In this study, an antibody was immobilized on a sensing plate using an avidin-biotin reaction to immobilize it for high density and to improve antibody alignment. In addition, as the detected terahertz signals vary depending on the sensitivity of the sensing plate, the sensitivity was evaluated using pH measurement. The result of the cancer cell detection was corrected using the result of pH measurement. These results indicate that a TCM is expected to be an excellent candidate for liquid biopsies in cancer diagnosis.

Noninvasive, label-free, and quantitative monitoring of lipase kinetics using terahertz emission technology.

Enzymes catalyze chemical transformations of great importance in many fields, and analysis of the rate of these transformations is equally important. The latter are typically monitored using surrogate substrates that produce quantifiable optical signals, owing to limitations associated with "label-free" techniques that could be used to monitor the transformation of original substrate molecules. In this study, terahertz (THz) emission technology is used as a noninvasive and label-free technique to monitor the kinetics of lipase-induced hydrolysis of several substrate molecules (including the complex substrate whole cow's milk) and horseradish peroxidase-catalyzed oxidation of o-phenylenediamine in the presence of H2 O2 . This technique was found to be quantitative, and kinetic parameters are compared to those obtained by proton NMR spectroscopy or UV/Vis spectroscopy. This study sets the stage for investigating THz emission technology as a tool for research and development involving enzymes, and for monitoring industrial processes in the food, cosmetic, detergent, pharmaceutical, and biodiesel sectors.

Liquid-like dielectric response is an origin of long polaron lifetime exceeding 10 µs in lead bromide perovskites.

Lead halide perovskites are promising materials for optoelectronic applications because of their exceptional performances in carrier lifetime and diffusion length; however, the microscopic origins of their unique characteristics remain elusive. The organic-inorganic hybrid perovskites show unique dielectric functions, i.e., ferroelectric-like phonon responses in the 0.1-10 THz region and liquid-like rotational relaxation in the 1-100 GHz range. To reveal the role of the dielectric responses is of primal importance because the dielectric screening is a key to understanding the optoelectronic properties governed by polarons in the perovskites. Here, we conducted comparative studies of broadband dielectric spectroscopy on both all-inorganic CsPbBr3 and organic-inorganic hybrid (CH3NH3)PbBr3 single crystals to uncover the origin of the liquid-like dielectric relaxation in the 1-100 GHz range. We confirmed the absence of the dielectric response in the range of 106-1010 Hz in CsPbBr3, which was clearly present in the hybrid (CH3NH3)PbBr3. This suggests that the response is almost purely due to the rotational motions of the organic dipoles in the hybrid perovskites. We evaluated the lifetimes of the polarons using surface-free transient photoluminescence. The lifetime in CsPbBr3 was up to 1.6 µs, while the lifetime in (CH3NH3)PbBr3 was 18 µs. The lifetime in the hybrid (CH3NH3)PbBr3 was significantly longer than in CsPbBr3, also confirmed by transient infrared spectroscopy. We concluded that the liquid-like dielectric response inhibits polaron recombination due to the efficient separation of opposite charges by the additional dynamic disorder.

Extraction Method of Crack Signal for Inspection of Complicated Steel Structures Using A Dual-Channel Magnetic Sensor.

Conventional eddy current testing (ECT) using a pickup coil probe is widely employed for the detection of structural cracks. However, the inspection of conventional ECT for steel structures is difficult because of the magnetic noise caused by the nonuniform permeability of steel. To combat this challenge, we have developed a small magnetic sensor probe with a dual-channel tunneling magnetoresistance sensor that is capable of reducing magnetic noise. Applying this probe to a complicated component of steel structures-such as the welds joining a U-shaped rib and deck plate together-requires the reduction of signal fluctuation caused by the distance (liftoff) variations between the sensor probe and the subject. In this study, the fundamental crack signal and the liftoff signal were investigated with the dual-channel sensor. The results showed that the liftoff signals could be reduced and differentiated from the crack signals by the differential parameters of the dual-channel sensor. In addition, we proposed an extraction technique for the crack signal using the Lissajous curve of the differential parameters. The extraction technique could be applied to the inspections not only for flat plates but also for welded angles to detect cracks without the influence of the liftoff signal.

pH measurements in 16-nL-volume solutions using terahertz chemical microscopy.

Terahertz chemical microscopy has been developed for measuring the pH of a solution using only a small volume. The microsolution wells were fabricated on the surface of the sensing plate using a conventional photolithograph technique. Because the pH value can be calculated from the amplitude of a terahertz wave directly radiated from a sensing plate by a femtosecond laser irradiation, this method does not require any reference electrode in the solution. Thus, pH measurement can be achieved with a volume as small as 16 nL.

Stabilization method for signal drifts in terahertz chemical microscopy.

A stabilization method for signal drifts in terahertz chemical microscopy (TCM) due to unexpected chemical potential changes in sample solutions was proposed and developed. The sensing plate was separated into two areas: a detection area and a control area. The detection area radiated a THz pulse whose amplitude was related to both the chemical reactions in the sample solutions and unexpected potential changes. The THz pulse from the control area was related only to unexpected potential changes. In the proposed system, the THz pulse from each area was interfered and detected. By adjusting the timing of the positive peak of the THz pulse from the detection area and the negative peak of the THz pulse from the control area, we detected the difference in both peaks as the interference signal. Thus, the signal deviation of 390 when the environmental condition changes in the temperature range of 38 °C and the pH range of 8.33 was stabilized to be the signal deviation of 31. As the result, the TCM with stabilization method could detect the signal shift of 121 when the 275-nmol/L immunoglobulin G was immobilized on the sensing plate.

Work function shifts of catalytic metals under hydrogen gas visualized by terahertz chemical microscopy.

Terahertz chemical microscopy (TCM) was applied to visualize the distribution of the work function shift of catalytic metals under hydrogen gas. TCM measures the chemical potential on the surface of a SiO(2)/Si/sapphire sensing plate without any contact with the plate. By controlling the bias voltage between an electrode on the SiO(2)/ surface and the Si layer, the relationship between the voltage and the THz amplitude from the sensing plate can be obtained. As a demonstration, two types of structures were fabricated on the sensing plate, and the work function shifts due to catalytic reactions were visualized.

Chemical sensing plate with a laser-terahertz monitoring system.

A new type of laser-terahertz emission system for noncontact investigations of chemical solutions has been developed. The system monitors terahertz emission from a sensing plate, which consists of silicon oxide and silicon thin film layers on a sapphire substrate. Sensing of chemical solutions with pH values between 1.68 and 10.01 was demonstrated. The amplitude of the terahertz emission from the sensing plate increased with increasing pH value. This change in the amplitude was caused by a change in the depletion layers of the silicon thin film when protons were adsorbed on the surface of the sensing plate. This study demonstrates that full noncontact monitoring of chemical solutions is possible using the laser-terahertz emission system.

Imaging of large-scale integrated circuits using laser-terahertz emission microscopy.

We present the redesign and improved performance of the laser terahertz emission microscope (LTEM), which is a potential tool for locating electrical failures in integrated circuits. The LTEM produces an image of the THz waves emitted when the circuit is irradiated by a femtosecond laser; the amplitude of the THz emission is proportional to the local electric field. By redesigning the optical setup and improving the spatial resolution of the system to below 3 microm, we could extend its application to examining of large-scale integration circuits. As example we show the THz emission pattern of the electric field in an 8-bit microprocessor chip under bias voltage.

Laser terahertz-emission microscope for inspecting electrical faults in integrated circuits.

A laser terahertz-emission microscope (LTEM) system is proposed and developed for inspecting electrical faults in integrated circuits (IC). We test a commercial operational amplifier while the system is operating. Two-dimensional terahertz-emission images of the IC chip are clearly observed while the chip is scanned with a femtosecond laser. When one of the interconnection lines is cut, the damaged chip has a LTEM image different from that of normal chips. The results indicate that the LTEM system is a potential tool for IC inspection.