Exosomal membrane proteins analysis using a silicon nanowire field effect transistor biosensor.

Exosomes are of great significance in clinical diagnosis, due to their high homology with parental generation, which can reflect the pathophysiological status. However, the quantitative and classification detection of exosomes is still faced with the challenges of low sensitivity and complex operation. In this study, we develop an electrical and label-free method to directly detect exosomes with high sensitivity based on a Silicon nanowire field effect transistor biosensor (Si-NW Bio-FET). First, the impact of Debye length on Si-NW Bio-FET detection was investigated through simulation. The simulation results demonstrated that as the Debye length increased, the electrical response to Si-NW produced by charged particle at a certain distance from the surface of Si-NW was greater. A Si-NW Bio-FET modified with specific antibody CD81 on the nanowire was fabricated then used for detection of cell line-derived exosomes, which achieved a low limit of detection (LOD) of 1078 particles/mL in 0.01 × PBS. Furthermore, the Si-NW Bio-FETs modified with specific antibody CD9, CD81 and CD63 respectively, were employed to distinguish exosomes derived from human promyelocytic leukemia (HL-60) cell line in three different states (control group, lipopolysaccharide (LPS) inflammation group, and LPS + Romidepsin (FK228) drug treatment group), which was consistent with nano-flow cytometry. This study provides a highly sensitive method of directly quantifying exosomes without labeling, indicating its potential as a tool for disease surveillance and medication instruction.

Acoustofluidics-enhanced biosensing with simultaneously high sensitivity and speed.

Simultaneously achieving high sensitivity and detection speed with traditional solid-state biosensors is usually limited since the target molecules must passively diffuse to the sensor surface before they can be detected. Microfluidic techniques have been applied to shorten the diffusion time by continuously moving molecules through the biosensing regions. However, the binding efficiencies of the biomolecules are still limited by the inherent laminar flow inside microscale channels. In this study, focused traveling surface acoustic waves were directed into an acoustic microfluidic chip, which could continuously enrich the target molecules into a constriction zone for immediate detection of the immune reactions, thus significantly improving the detection sensitivity and speed. To demonstrate the enhancement of biosensing, we first developed an acoustic microfluidic chip integrated with a focused interdigital transducer; this transducer had the ability to capture more than 91% of passed microbeads. Subsequently, polystyrene microbeads were pre-captured with human IgG molecules at different concentrations and loaded for detection on the chip. As representative results, ~0.63, 2.62, 11.78, and 19.75 seconds were needed to accumulate significant numbers of microbeads pre-captured with human IgG molecules at concentrations of 100, 10, 1, and 0.1 ng/mL (~0.7 pM), respectively; this process was faster than the other methods at the hour level and more sensitive than the other methods at the nanomolar level. Our results indicated that the proposed method could significantly improve both the sensitivity and speed, revealing the importance of selective enrichment strategies for rapid biosensing of rare molecules.

Directional surface plasmon polariton scattering using single magnetic nanoparticles.

Directional surface plasmon polaritons (SPPs) are expected to promote the energy efficiency of plasmonic devices, via limiting the energy in a given spatial domain. The directional scattering of dielectric nanoparticles induced by the interference between electric and magnetic responses presents a potential candidate for directional SPPs. Magnetic nanoparticles can introduce permeability as an extra manipulation, whose directional scattered SPPs have not been investigated yet. In this work, we demonstrated the directional scattered SPPs by using single magnetic nanoparticles via simulation and experiment. By increasing the permeability and particle size, the high-order TEM modes are excited inside the particle and induce more forward directional SPPs. It indicated that the particle size manifests larger tuning range compared with the permeability. Experimentally, the maximum forward-to-backward (F-to-B) SPP scattering intensity ratio of 118.52:1 is visualized by using a single 1 µm Fe3O4 magnetic nanoparticle. The directional scattered SPPs of magnetic nanoparticles are hopeful to improve the efficiency of plasmonic devices and pave the way for plasmonic circuits on-chip.

A Surface Electromyography (sEMG) System Applied for Grip Force Monitoring.

Muscles play an indispensable role in human life. Surface electromyography (sEMG), as a non-invasive method, is crucial for monitoring muscle status. It is characterized by its real-time, portable nature and is extensively utilized in sports and rehabilitation sciences. This study proposed a wireless acquisition system based on multi-channel sEMG for objective monitoring of grip force. The system consists of an sEMG acquisition module containing four-channel discrete terminals and a host computer receiver module, using Bluetooth wireless transmission. The system is portable, wearable, low-cost, and easy to operate. Leveraging the system, an experiment for grip force prediction was designed, employing the bald eagle search (BES) algorithm to enhance the Random Forest (RF) algorithm. This approach established a grip force prediction model based on dual-channel sEMG signals. As tested, the performance of acquisition terminal proceeded as follows: the gain was up to 1125 times, and the common mode rejection ratio (CMRR) remained high in the sEMG signal band range (96.94 dB (100 Hz), 84.12 dB (500 Hz)), while the performance of the grip force prediction algorithm had an R2 of 0.9215, an MAE of 1.0637, and an MSE of 1.7479. The proposed system demonstrates excellent performance in real-time signal acquisition and grip force prediction, proving to be an effective muscle status monitoring tool for rehabilitation, training, disease condition surveillance and scientific fitness applications.

Curved and Annular Diaphragm Coupled Piezoelectric Micromachined Ultrasonic Transducers for High Transmit Biomedical Applications.

In this paper, we present a novel three-dimensional (3D) coupled configuration of piezoelectric micromachined ultrasound transducers (pMUTs) by combing a curved and an annular diaphragm for transmit performance optimization in biomedical applications. An analytical equivalent circuit model (EQC) is developed with varied excitation methods to incorporate the acoustic-structure coupling of the curved and annular diaphragm-coupled pMUTs (CAC-pMUTs). The model-derived results align well with the reference simulated by the finite element method (FEM). Using this EQC model, we optimize the key design parameters of the CAC-pMUTs in order to improve the output sound pressure, including the width of the annular membrane, the thickness of the passive layer, and the phase difference of the driving voltage. In the anti-phase mode, the designed CAC-pMUTs demonstrate a transmit efficiency 285 times higher than that of single annular pMUTs. This substantial improvement underscores the potential of CAC-pMUTs for large array applications.

Cardiac Multi-Frequency Vibration Signal Sensor Module and Feature Extraction Method Based on Vibration Modeling.

Cardiovascular diseases pose a long-term risk to human health. This study focuses on the rich-spectrum mechanical vibrations generated during cardiac activity. By combining Fourier series theory, we propose a multi-frequency vibration model for the heart, decomposing cardiac vibration into frequency bands and establishing a systematic interpretation for detecting multi-frequency cardiac vibrations. Based on this, we develop a small multi-frequency vibration sensor module based on flexible polyvinylidene fluoride (PVDF) films, which is capable of synchronously collecting ultra-low-frequency seismocardiography (ULF-SCG), seismocardiography (SCG), and phonocardiography (PCG) signals with high sensitivity. Comparative experiments validate the sensor's performance and we further develop an algorithm framework for feature extraction based on 1D-CNN models, achieving continuous recognition of multiple vibration features. Testing shows that the recognition coefficient of determination (R2), mean absolute error (MAE), and root mean square error (RMSE) of the 8 features are 0.95, 2.18 ms, and 4.89 ms, respectively, with an average prediction speed of 60.18 us/point, meeting the re-quirements for online monitoring while ensuring accuracy in extracting multiple feature points. Finally, integrating the vibration model, sensor, and feature extraction algorithm, we propose a dynamic monitoring system for multi-frequency cardiac vibration, which can be applied to portable monitoring devices for daily dynamic cardiac monitoring, providing a new approach for the early diagnosis and prevention of cardiovascular diseases.

Volatile carbonyl metabolites analysis of nanoparticle exposed lung cells in an organ-on-a-chip system.

The evaluation of nanoparticles (NPs) cytotoxicity is crucial for advancing nanotechnology and assessing environmental pollution. However, existing methods for NPs cytotoxicity evaluation suffer from limited accuracy and inadequate information content. In the study, we developed a novel detection platform that enables the identification of cellular carbonyl metabolites at the organ level. The platform is integrated with a cell co-culture lung organ chip (LOC) and a micropillar concentrator. Notably, our work represents the successful measurement of the amounts of cellular metabolites on LOC system. The volatile carbonyl metabolites (VCMs) generated by cells exposure to various types of NPs with different concentrations were captured and detected by high-resolution mass spectrometry (MS). Compared with conventional cell viability and reactive oxygen species (ROS) analysis, our method discerns the toxicological impact of NPs at low concentrations by analyzed VCM at levels as low as ppb level. The LOC system based metabolic gas detection confirmed that low concentrations of NPs have a toxic effect on the cell model, which was not reflected in the fluorescence detection, and the effect of NP material is more significant than the size effect. Furthermore, this method can distinguish different NPs acting on cell models through cluster analysis of multiple VCMs.

Oriented bouncing of droplets with a small Weber number on inclined one-dimensional nanoforests.

Asymmetric superhydrophobic structures with anisotropic wettability can achieve directional bouncing of droplets and thus can have applications in directional self-cleaning, liquid transportation, and heat transfer. To achieve convenient large-scale preparation of asymmetric superhydrophobic surfaces, inclined nanoforests are prepared in this work using a technique of competitive ablation polymerization, which allows the control of the inclined angles, diameters, and heights of the nanostructures. In this study, such asymmetric structures with the smallest dimension (230 nm diameter) known are achieved by a simple etching method to guide droplet unidirectional bouncing. With such nanoforests, the mechanism of droplet bouncing on their surface is investigated, and controllable droplet bouncing over a long distance is achieved using droplets with a low Weber number. The proposed structure has a promising future in directional self-cleaning, liquid transportation and heat transfer.

Nanophotonic Enhanced Chiral Sensing and Its Biomedical Applications.

Chiral sensing is crucial in the fields of biology and the pharmaceutical industry. Many naturally occurring biomolecules, i.e., amino acids, sugars, and nucleotides, are inherently chiral. Their enantiomers are strongly associated with the pharmacological effects of chiral drugs. Owing to the extremely weak chiral light-matter interactions, chiral sensing at an optical frequency is challenging, especially when trace amounts of molecules are involved. The nanophotonic platform allows for a stronger interaction between the chiral molecules and light to enhance chiral sensing. Here, we review the recent progress in nanophotonic-enhanced chiral sensing, with a focus on the superchiral near-field and enhanced circular dichroism (CD) spectroscopy generated in both the dielectric and in plasmonic structures. In addition, the recent applications of chiral sensing in biomedical fields are discussed, including the detection and treatment of difficult diseases, i.e., Alzheimer's disease, diabetes, and cancer.

Reconstruction Filters Improving the Spatial Resolution and Signal-to-Noise Ratio of Surface Plasmon Resonance Microscopy.

Benefitting from high sensitivity, real-time, and label-free imaging, surface plasmon resonance microscopy (SPRM) has become a powerful tool for dynamic detection of nanoparticles. However, the evanescent propagation of surface plasmon polaritons (SPPs) induces interference between scattered and launched SPPs, which deteriorates the spatial resolution and signal-to-noise ratio (SNR). Due to the simplicity and fast processing, image reconstruction based on deconvolution has shown the feasibility of improving the spatial resolution of SPRM imaging. Retrieving the particle scattering from SPRM interference imaging by filters is crucial for reconstruction. In this work, we illustrate the effect of filters extracting SPP scattering of nanoparticles with different sizes and shapes for reconstruction. The results indicate that the optimum filters are determined by the material of nanoparticles instead of particle sizes. The reconstruction of single Au and PS nanospheres as well as Ag nanowires with optimum filters is achieved. The reconstructed spatial resolution is improved to 254 nm, and the SNR is increased by 8.1 times. Our research improves the quality of SPRM imaging and provides a reliable method for fast detection of particles with diverse sizes and shapes.

Au doped metal organic frameworks as di-functional photocatalysts for clearing organics in wastewater.

Along with the development of productive forces, the use of organic compounds including diversified dyes and multiple drugs has become more and more commonly, resulting in the accelerating water contamination. Herein in this paper, Au doped PCN 224 are designed as bi-functional wastewater treatment agents to absorb and decompose organics molecules efficiently under light irradiation. After inserted with Au, the PCN 224 nanoparticles, which is kind of porous, stable and photosensitive metal-organic framework, show enhanced photodegradeability. Because the Au inserted could inhibit the re-combination of electrons and holes by absorbing photo-electrons; decrease the nanoparticles' band gap, and finally produce much more free radicals. In the meanwhile, due to the lower binding energy between S and Au, the Au modified PCN 224 perform better in absorbing organic compounds consisted of S contained heterocyclic ring (such as methylene blue). This work provides new insights into the precious design of materials in clearing organic compounds.

Carpal bone replacement using personalized 3D printed tantalum prosthesis.

Objective: Scaphoid and lunate fractures have a relatively high incidence rate. Traditional carpectomy and carpal arthrodesis in the treatment of carpal osteonecrosis will lead to many complications. Three-dimensional (3D) printed tantalum has good biocompatibility and can be designed to match the patient's personalized anatomical carpal structure. This study aims to investigate carpal function and prosthesis-related conditions after carpal bone replacement using 3D printed tantalum prostheses. Methods: From July 2020 to January 2022 at our center, seven patients with osteonecrosis of the carpus received carpal bone replacement using 3D printed tantalum prosthesis. The Disability of the Arm, Shoulder and Hand (DASH) score and patient satisfaction, as well as the Mayo Wrist Scores (Cooney method, modified Green, and O'Brien wrist score), were used to evaluate the preoperative and postoperative wrist function of patients. The Visual Analog Scale (VAS) pain scores were also recorded before and after surgery. The angles of flexion, dorsiflexion, ulnar deviation, and radial deviation were measured using an arthrometer. The grip strength and pinch strength of the operated hand after carpal bone replacement and the contralateral healthy carpus were measured using a dynamometer. Radiographs were taken to confirm the condition and complications of the tantalum prosthesis. Results: All seven patients were followed for 19.6 ± 2.7 months. At the last follow-up, the grip strength of the operated wrist joint after carpal bone replacement was 33.4 ± 2.3 kg, the pinch strength was 8.9 ± 0.7 kg, the flexion was 54.6° ± 0.8°, the dorsiflexion was 54.7° ± 1.7°, the ulnar deviation was 34.6° ± 1.9°, and the radial deviation was 25.9° ± 0.8°, all of which showed no statistically significant difference with the contralateral healthy carpus (p > 0.05). There were significant differences in the VAS, DASH, and MAYO scores between the preoperative and the last follow-up (p < 0.01). Patients had reduced postoperative pain and improved wrist function and range of motion (ROM), and the tantalum prostheses were stable. Conclusion: The 3D printed tantalum brings us new hope, not only for hip or knee replacement, but also for joint replacement of other complex anatomical structures, and patients with other irregular bone defects such as bone tumors and deformity, which could realize personalized treatment and precise medicine.

Sensitivity Analysis of CMAP Scan Step Index to Different Stimulation Parameters and Examination of Muscles Affected by Spinal Cord Injury.

Step index (STEPIX) is a recently developed compound muscle action potential (CMAP) scan method for evaluating motor unit loss and remodeling changes. This study investigates the influence of different stimulation parameters during CMAP scan on STEPIX and its examination of muscles affected by spinal cord injury (SCI). CMAP scan of the first dorsal interosseous (FDI) muscle was performed using different stimulus pulse widths (0.1 ms, 0.2 ms) and different numbers of stimuli (500, 1000) in 12 neurologically intact subjects. STEPIX was derived from each CMAP scan of all subjects. A significantly higher STEPIX was obtained using 1000 stimuli than 500 stimuli, while no significant difference in STEPIX was observed using 0.1 and 0.2 ms stimulus pulse widths. STEPIX was further applied to process CMAP scans of the FDI muscle from 13 tetraplegia and 13 healthy control subjects using the same stimulation parameter setting (0.1 ms, 500 stimuli), along with other methods including MScanFit motor unit number estimation (MUNE) and D50. STEPIX was significantly lower for the SCI subjects compared with the healthy control subjects. STEPIX was significantly correlated with MscanFit MUNE and D50, but had a smaller relative width of the overlapping zone (WOZ%) between tetraplegic and healthy control groups compared with MScanFit MUNE and D50. The findings of the study highlight the importance of maintaining a consistent stimulation parameter setting in CMAP scan studies and confirm the usefulness of STEPIX as a convenient CMAP scan parameter for examination of motor unit number changes.

Knockdown of microRNA-96-5p resists oxidative stress-induced apoptosis in nucleus pulposus cells.

BACKGROUND: Intervertebral disc degeneration (IVDD) often leads to low back pain, which severely affects people's quality of life. Oxidative stress (OS) can accelerate nucleus pulposus cell (NPCs) senescence and apoptosis. Exploring the mechanism underlying OS-induced apoptosis is of utmost importance to aid in the development of IVDD treatment. METHODS: In the current study, we tested the function of microRNA-96-5p in H2O2-treated NPCs. Apoptosis and mitophagy-related proteins were examined by western blot. Reactive oxygen species (ROS) generation, mitochondrial membrane potential, and apoptosis of NPCs were evaluated by flow cytometry. A luciferase reporter assay was conducted to confirm the interaction between microRNA-96-5p and Forkhead Box Protein O1 (FOXO1). RESULTS: H2O2 treatment enhanced apoptosis in NPCs and upregulated the microRNA-96-5p expression. It was shown that knockdown of microRNA-96-5p attenuated H2O2-induced OS and apoptosis. FOXO1 is a direct target of microRNA-96-5p, and knockdown of microRNA-96-5p enhanced PINK1/Parkin-mediated mitophagy by up-regulating FOXO1. CONCLUSIONS: Collectively, knockdown of microRNA-96-5p enhanced PINK1/Parkin-mediated mitophagy by up-regulating FOXO1. Our results facilitate the understanding of the role of microRNA-96-5p in IVDD and the mechanism of H2O2-induced oxidative damage.

Wafer-Level, High-Performance, Flexible Sensors Based on Organic Nanoforests for Human-Machine Interactions.

High-performance flexible sensors are essential for real-time information analysis and constructing noncontact communication modules for emerging human-machine interactions. In these applications, batch fabrication of sensors that exhibit high performance at the wafer level is in high demand. Here, we present organic nanoforest-based humidity sensor (NFHS) arrays on a 6 in. flexible substrate prepared via a facile, cost-effective manufacturing approach. Such an NFHS achieves state-of-the-art overall performance: high sensitivity and fast recovery time; the best properties are at a small device footprint. The high sensitivity (8.84 pF/% RH) and fast response time (5 s) of the as-fabricated organic nanoforests are attributed to the abundant hydrophilic groups, the ultra-large surface area with a huge number of nanopores, and the vertically distributed structures beneficial to the transfer of molecules up and down. The NFHS also exhibits excellent long-term stability (90 days), superior mechanical flexibility, and good performance repeatability after bending. With these superiorities, the NFHS is further applied as a smart noncontact switch, and the NFHS array is used as the motion trajectory tracker. The wafer-level batch fabrication capability of our NFHS provides a potential strategy for developing practical applications of such humidity sensors.

piRT-IFC: Physics-informed real-time impedance flow cytometry for the characterization of cellular intrinsic electrical properties.

Real-time transformation was important for the practical implementation of impedance flow cytometry. The major obstacle was the time-consuming step of translating raw data to cellular intrinsic electrical properties (e.g., specific membrane capacitance Csm and cytoplasm conductivity σcyto). Although optimization strategies such as neural network-aided strategies were recently reported to provide an impressive boost to the translation process, simultaneously achieving high speed, accuracy, and generalization capability is still challenging. To this end, we proposed a fast parallel physical fitting solver that could characterize single cells' Csm and σcyto within 0.62 ms/cell without any data preacquisition or pretraining requirements. We achieved the 27000-fold acceleration without loss of accuracy compared with the traditional solver. Based on the solver, we implemented physics-informed real-time impedance flow cytometry (piRT-IFC), which was able to characterize up to 100,902 cells' Csm and σcyto within 50 min in a real-time manner. Compared to the fully connected neural network (FCNN) predictor, the proposed real-time solver showed comparable processing speed but higher accuracy. Furthermore, we used a neutrophil degranulation cell model to represent tasks to test unfamiliar samples without data for pretraining. After being treated with cytochalasin B and N-Formyl-Met-Leu-Phe, HL-60 cells underwent dynamic degranulation processes, and we characterized cell's Csm and σcyto using piRT-IFC. Compared to the results from our solver, accuracy loss was observed in the results predicted by the FCNN, revealing the advantages of high speed, accuracy, and generalizability of the proposed piRT-IFC.

Dynamic Detection of Specific Membrane Capacitance and Cytoplasmic Resistance of Neutrophils After Ischemic Stroke.

Peripheral blood is the most readily available resource for stroke patient prognosis, but there is a lack of methods to detect dynamic changes of neutrophils in peripheral blood that can be used in the clinic. Herein, we developed a procedure to characterize dynamic changes of neutrophils based on their electrical properties in rats after transient middle cerebral artery occlusion (MCAO). We characterized the specific membrane capacitance (Csm) and cytoplasmic resistance (σcyto) of approximately 27,600 neutrophils from MCAO rats 24 h after ischemia/reperfusion. We found that the Csm and σcyto of neutrophils in the MCAO group were significantly higher compared to the sham group. Furthermore, we observed a monotonically upward shift in neutrophil Csm in the MCAO group during the four 5-minute test cycles. Our findings suggest that the dynamic changes of cellular electrical properties could reflect neutrophil activity and serve as a prognostic indicator for ischemic stroke in the clinical setting.

Spatial Dependence of Log-Transformed Electromyography-Force Relation: Model-Based Sensitivity Analysis and Experimental Study of Biceps Brachii.

This study investigated electromyography (EMG)-force relations using both simulated and experimental approaches. A motor neuron pool model was first implemented to simulate EMG-force signals, focusing on three different conditions that test the effects of small or large motor units located more or less superficially in the muscle. It was found that the patterns of the EMG-force relations varied significantly across the simulated conditions, quantified by the slope (b) of the log-transformed EMG-force relation. b was significantly higher for large motor units, which were preferentially located superficially rather than for random depth or deep depth conditions (p < 0.001). The log-transformed EMG-force relations in the biceps brachii muscles of nine healthy subjects were examined using a high-density surface EMG. The slope (b) distribution of the relation across the electrode array showed a spatial dependence; b in the proximal region was significantly larger than the distal region, whereas b was not different between the lateral and medial regions. The findings of this study provide evidence that the log-transformed EMG-force relations are sensitive to different motor unit spatial distributions. The slope (b) of this relation may prove to be a useful adjunct measure in the investigation of muscle or motor unit changes associated with disease, injury, or aging.

Muscle innervation zone estimation from monopolar high-density M-waves using principal component analysis and radon transform.

This study examined methods for estimating the innervation zone (IZ) of a muscle using recorded monopolar high density M waves. Two IZ estimation methods based on principal component analysis (PCA) and Radon transform (RT) were examined. Experimental M waves, acquired from the biceps brachii muscles of nine healthy subjects were used as testing data sets. The performance of the two methods was evaluated by comparing their IZ estimations with manual IZ detection by experienced human operators. Compared with manual detection, the agreement rate of the estimated IZs was 83% and 63% for PCA and RT based methods, respectively, both using monopolar high density M waves. In contrast, the agreement rate was 56% for cross correlation analysis using bipolar high density M waves. The mean difference in estimated IZ location between manual detection and the tested method was 0.12 ± 0.28 inter-electrode-distance (IED) for PCA, 0.33 ± 0.41 IED for RT and 0.39 ± 0.74 IED for cross correlation-based methods. The results indicate that the PCA based method was able to automatically detect muscle IZs from monopolar M waves. Thus, PCA provides an alternative approach to estimate IZ location of voluntary or electrically-evoked muscle contractions, and may have particular value for IZ detection in patients with impaired voluntary muscle activation.

[Research progress of transcription activating factor 3 in regulating the alveolar macrophages in acute respiratory distress syndrome].

Acute respiratory distress syndrome (ARDS) refers to acute diffuse lung injury caused by a variety of intrapulmonary and/or extrapulmonary factors such as infection and trauma. Uncontrolled inflammatory response is the main pathological feature. Different functional states of alveolar macrophages have different effects on inflammatory response. Transcription activating factor 3 (ATF3) is a fast response gene in the early stage of stress. In recent years, it has been found that ATF3 plays an important role in regulating the inflammatory response of ARDS by regulating the function of macrophages. This paper reviews the regulatory effects of ATF3 on alveolar macrophage polarization, autophagy and endoplasmic reticulum stress and its effects on the inflammatory process of ARDS, aiming to provide a new research direction for the prevention and treatment of ARDS.