Biosensing Intestinal Alkaline Phosphatase by Pregnancy Test Strips Based on Target-Triggered CRISPR-Cas12a Activity to Monitor Intestinal Inflammation.

With an increasing incidence worldwide, inflammatory bowel disease (IBD) is a chronic inflammatory disease affecting the gastrointestinal tract, which impairs the life quality of patients. Therefore, it is of great significance to construct a sensitive, simple, and convenient biosensor to analyze IBD-associated biomarkers for an auxiliary diagnosis of IBD. Intestinal alkaline phosphatase (IAP), expressed by the intestinal epithelium, is an endogenous protein that is thought to play a vital role in maintaining intestinal homeostasis and is considered a potential biomarker for IBD. Here, an IAP detection method was developed using pregnancy test strips by dephosphorylation. Initially, a double-stranded DNA (dsDNA) was designed to respond to IAP and acted as an activator of Cas12a. In the presence of IAP, the designed dsDNA was not digested by lambda exonuclease (λ exo), which hybridized to the Cas12a-crRNA duplex and resulted in the activation of the trans-cleavage of Cas12a. Further, the activated Cas12a cleaved the single-strand DNA (ssDNA) linker in the MBs-ssDNA-hCG probe, triggering the release of hCG. With magnetic separation, the released hCG could be quantitatively detected by pregnancy test strips. IAP levels were analyzed in feces from colitis and healthy mice by pregnancy test strips. The results showed that the IAP level of colitis mice (3.89 ± 1.92 U/L) was much lower than that of healthy mice (39.64 ± 24.93 U/L), indicating the correlation between IAP and intestinal inflammation. Taken together, a sensitive, user-friendly detection assay based on pregnancy test strips was constructed to monitor IAP and used as an auxiliary diagnostic approach for IBD in a clinical scene.

Identifying, Resolving, and Quantifying Anisotropy in ReS2 Nanomechanical Resonators.

As an emerging two-dimensional semiconductor, rhenium disulfide (ReS2 ) is renowned for its strong in-plane anisotropy in electrical, optical, and thermal properties. In contrast to the electrical, optical, optoelectrical, and thermal anisotropies that are extensively studied in ReS2 , experimental characterization of mechanical properties has largely remained elusive. Here, it is demonstrated that the dynamic response in ReS2 nanomechanical resonators can be leveraged to unambiguously resolve such disputes. Using anisotropic modal analysis, the parameter space for ReS2 resonators in which mechanical anisotropy is best manifested in resonant responses is determined. By measuring their dynamic response in both spectral and spatial domains using resonant nanomechanical spectromicroscopy, it is clearly shown that ReS2 crystal is mechanically anisotropic. Through fitting numerical models to experimental results, it is quantitatively determined that the in-plane Young's moduli are 127 and 201 GPa along the two orthogonal mechanical axes. In combination with polarized reflectance measurements, it is shown that the mechanical soft axis aligns with the Re-Re chain in the ReS2 crystal. These results demonstrate that dynamic responses in nanomechanical devices can offer important insights into intrinsic properties in 2D crystals and provide design guidelines for future nanodevices with anisotropic resonant responses.

Acoustics-Controlled Microdroplet and Microbubble Fusion and Its Application in the Synthesis of Hydrogel Microspheres.

Droplet fusion technology is a key technology for many droplet-based biochemical medical applications. By integrating a symmetrical flow channel structure, we demonstrate an acoustics-controlled fusion method of microdroplets using surface acoustic waves. Different kinds of microdroplets can be staggered and ordered in the symmetrical flow channel, proving the good arrangement effect of the microfluidic chip. This method can realize not only the effective fusion of microbubbles but also the effective fusion of microdroplets of different sizes without any modification. Further, we investigate the influence of the input frequency and peak-to-peak value of the driving voltage on microdroplets fusion, giving the effective fusion parameter conditions of microdroplets. Finally, this method is successfully used in the preparation of hydrogel microspheres, offering a new platform for the synthesis of hydrogel microspheres.

A Compact Optical MEMS Pressure Sensor Based on Fabry-Pérot Interference.

Pressure sensors have important prospects in wind pressure monitoring of transmission line towers. Optical pressure sensors are more suitable for transmission line towers due to its anti-electromagnetic interference. However, the fiber pressure sensor is not a suitable choice due to expensive and bulky. In this paper, a compact optical Fabry-Pérot (FP) pressure sensor for wind pressure measurement was developed by MEMS technology. The pressure sensor consists of a MEMS sensing chip, a vertical-cavity surface-emitting laser (Vcsel), and a photodiode (PD). The sensing chip is combined with an FP cavity and a pressure sensing diaphragm which adopts the square film and is fabricated by Silicon on Insulator (SOI) wafer. To calibrate the pressure sensor, the experimental platform which consists of a digital pressure gauge, a pressure loading machine, a digital multimeter, and a laser driver was set up. The experimental results show that the sensitivity of the diaphragm is 117.5 nm/kPa. The measurement range and sensitivity of the pressure sensor are 0-700 Pa and 115 nA/kPa, respectively. The nonlinearity, repeatability, and hysteresis of the pressure sensor are 1.48%FS, 2.23%FS, and 1.59%FS, respectively, which lead to the pressure accuracy of 3.12%FS.

Thermal conductivity and interfacial thermal resistance in the heterostructure of silicon/amorphous silicon dioxide: the strain and temperature effect.

This article reports the thermal conduction properties of Si/a-SiO2 heterostructure with two different interfaces: weak and strong coupling strength through molecular dynamics simulation. The size and temperature dependencies on the interfacial thermal resistance of the weak coupling interface are larger than those of the strong coupling interface. The thermal conduction in Si/a-SiO2 shows strong anisotropy. The thermal conductivity, interfacial thermal resistance, and enhancement of the anisotropy can be modulated by changing the strains applied to the heterostructures. This work provides an optional way to design the silicon-based heterostructures considering heat insulation and heat dissipation.

A Novel Single-Axis MEMS Tilt Sensor with a High Sensitivity in the Measurement Range from 0∘ to 360∘.

In this paper, a novel single-axis MEMS tilt sensor is presented. It contains a hexagonal proof mass, six micro-lever force amplifiers and three double-ended-tuning fork (DETF) resonant strain gauges. The proof mass is placed in the center with the micro-levers and the DETFs radially arrayed around. The variation of gravity acceleration applied on the proof mass will result in frequency shifts of the DETFs. Angular tilt can be got by analyzing the frequency outputs. The structural design of the tilt sensor is optimized by finite element simulation and the device is microfabricated using a silicon-on-insulator process, followed by open-loop and closed-loop characterizations. Results show that the scale factor of such sensor is at least 11.53 Hz/degree. Minimum Allan deviation of the DETF oscillator is 220 ppb (parts per billion) of the resonant frequency for an 5 s integration time. Resolution of the tilt sensor is 0.002 ∘ in the whole measurement range from 0 ∘ to 360 ∘ .

A Manganin Thin Film Ultra-High Pressure Sensor for Microscale Detonation Pressure Measurement.

With the development of energetic materials (EMs) and microelectromechanical systems (MEMS) initiating explosive devices, the measurement of detonation pressure generated by EMs in the microscale has become a pressing need. This paper develops a manganin thin film ultra-high pressure sensor based on MEMS technology for measuring the output pressure from micro-detonator. A reliable coefficient is proposed for designing the sensor's sensitive element better. The sensor employs sandwich structure: the substrate uses a 0.5 mm thick alumina ceramic, the manganin sensitive element with a size of 0.2 mm × 0.1 mm × 2 µm and copper electrodes of 2 µm thick are sputtered sequentially on the substrate, and a 25 µm thick insulating layer of polyimide is wrapped on the sensitive element. The static test shows that the piezoresistive coefficient of manganin thin film is 0.0125 GPa-1. The dynamic experiment indicates that the detonation pressure of micro-detonator is 12.66 GPa, and the response time of the sensor is 37 ns. In a word, the sensor developed in this study is suitable for measuring ultra-high pressure in microscale and has a shorter response time than that of foil-like manganin gauges. Simultaneously, this study could be beneficial to research on ultra-high-pressure sensors with smaller size.

Study of ZnS Nanostructures Based Electrochemical and Photoelectrochemical Biosensors for Uric Acid Detection.

Uric acid (UA) is a kind of purine metabolism product and important in clinical diagnosis. In this work, we present a study of ZnS nanostructures-based electrochemical and photoelectrochemical biosensors for UA detection. Through a simple hydrothermal method and varying the ratio of reaction solvents, we obtained ZnS nanomaterials of one-dimensional to three-dimensional morphologies and they were characterized using field emission scanning electron microscopy (FESEM) and X-ray diffraction (XRD). To fabricate the UA biosensor and study the effect of material morphology on its performance, ZnS nanomaterials were deposited on indium tin oxide (ITO) conducting glass and then coated with uricase by physical absorption. Three kinds of working electrodes were characterized by cyclic voltammetry method. The effect of material morphology on performance of UA detection was investigated via amperometric response based electrochemical method based on enzymatic reaction. The ZnS urchin-like nanostructures electrode shows better sensitivity compared with those made of nanoparticles and nanoflakes because of its high surface-area-to-volume ratio. The photoelectrochemical method for detection of UA was also studied. The sensitivity was increased 5 times after irradiation of 300 nm UV light. These results indicate that ZnS nanostructures are good candidate materials for developing enzyme-based UA biosensors.

Plastic Deformation of Micromachined Silicon Diaphragms with a Sealed Cavity at High Temperatures.

Single crystal silicon (SCS) diaphragms are widely used as pressure sensitive elements in micromachined pressure sensors. However, for harsh environments applications, pure silicon diaphragms are hardly used because of the deterioration of SCS in both electrical and mechanical properties. To survive at the elevated temperature, the silicon structures must work in combination with other advanced materials, such as silicon carbide (SiC) or silicon on insulator (SOI), for improved performance and reduced cost. Hence, in order to extend the operating temperatures of existing SCS microstructures, this work investigates the mechanical behavior of pressurized SCS diaphragms at high temperatures. A model was developed to predict the plastic deformation of SCS diaphragms and was verified by the experiments. The evolution of the deformation was obtained by studying the surface profiles at different anneal stages. The slow continuous deformation was considered as creep for the diaphragms with a radius of 2.5 mm at 600 °C. The occurrence of plastic deformation was successfully predicted by the model and was observed at the operating temperature of 800 °C and 900 °C, respectively.

Structural design of microfluidic channels for blood plasma separation.

Microfluidics devices for separation of plasma from whole blood can be applied to numerous clinical laboratory and point-of-care diagnostics, since over 90% of blood diagnosis tests are conducted using plasma. This paper proposed a structural design of microfluidic channels for blood plasma separation. The Euler-Euler Laminar Flow Model in COMSOL Multiphysics has been utilized to simulate the blood flow behavior in microchannels. Micro chips with separating microchannels of different designs were fabricated and tested. The geometrical effect of microchannels on plasma separation was investigated. Simulation results show that curved channel contributes little in lateral migration of cells in low flow rate and becomes a difficult choice in the case of high flow rate due to the coupling of centrifugal migration and Dean Vortex. Studies on the bifurcation corner radius and the angle between main channel and side channel show that an abrupt change in flow direction of cell free layer helps to get more plasma with higher purity. An optimal design of multi-bifurcation separator has been achieved by balancing the flow resistances of the side channels and the main channels.

Synchronization bandwidth enhancement induced by a parametrically excited oscillator.

The synchronization phenomenon in nature has been utilized in sensing and timekeeping fields due to its numerous advantages, including amplitude and frequency stabilization, noise reduction, and sensitivity improvement. However, the limited synchronization bandwidth hinders its broader application, and few techniques have been explored to enhance this aspect. In this paper, we conducted theoretical and experimental studies on the unidirectional synchronization characteristics of a resonator with phase lock loop oscillation. A novel enhancement method for the synchronization bandwidth using a parametrically excited MEMS oscillator is proposed, which achieves a remarkably large synchronization bandwidth of 8.85 kHz, covering more than 94% of the hysteresis interval. Importantly, the proposed method exhibits significant potential for high-order synchronization and frequency stabilization compared to the conventional directly excited oscillator. These findings present an effective approach for expanding the synchronization bandwidth, which has promising applications in nonlinear sensing, fully mechanical frequency dividers, and high-precision time references.

Nonlinearity-Induced Asymmetric Synchronization Region in Micromechanical Oscillators.

Synchronization in microstructures is a widely explored domain due to its diverse dynamic traits and promising practical applications. Within synchronization analysis, the synchronization bandwidth serves as a pivotal metric. While current research predominantly focuses on symmetric evaluations of synchronization bandwidth, the investigation into potential asymmetries within nonlinear oscillators remains unexplored, carrying implications for sensor application performance. This paper conducts a comprehensive exploration employing straight and arch beams capable of demonstrating linear, hardening, and softening characteristics to thoroughly scrutinize potential asymmetry within the synchronization region. Through the introduction of weak harmonic forces to induce synchronization within the oscillator, we observe distinct asymmetry within its synchronization range. Additionally, we present a robust theoretical model capable of fully capturing the linear, hardening, and softening traits of resonators synchronized to external perturbation. Further investigation into the effects of feedback strength and phase delay on synchronization region asymmetry, conducted through analytical and experimental approaches, reveals a consistent alignment between theoretical predictions and experimental outcomes. These findings hold promise in providing crucial technical insights to enhance resonator performance and broaden the application landscape of MEMS (Micro-Electro-Mechanical Systems) technology.

Nanotoxicity of tungsten trioxide nanosheets containing oxygen vacancy to human umbilical vein endothelial cells.

Because of the excellent performance in photochemistry, WO3 is increasingly applied in the field of biology and medicine. However, little is known about the mechanism of WO3 cytotoxicity. In this work, WO3 nanosheets with oxygen vacancy are synthesized by solvothermal method, then characterized and added to culture medium of human umbilical vein endothelial cells (HUVECs) with different concentrations. We characterized and analyzed the morphology of nano-WO3 by transmission electron microscopy and calculated the specific data of oxygen vacancy by XPS. It is the first time the effect of WO3-x on cells that WO3-x can cause oxidative stress in HUVEC cells, resulting in DNA damage and thus promoting apoptosis. Transcriptome sequencing is performed on cells treated with low and high concentrations of WO3-x, and a series of key signals affecting cell proliferation and apoptosis are detected in differentially expressed genes, which indicates the research direction of nanotoxicity. The expression levels of key genes are also verified by quantitative PCR after cell treatment with different concentrations of WO3-x. This work fills the gap between the biocompatibility of nano WO3-x materials and molecular cytology and paves the way for investigating the mechanism and risks of oxygen vacancy in cancer therapy.

Advances in heart failure monitoring: Biosensors targeting molecular markers in peripheral bio-fluids.

Cardiovascular diseases (CVDs), especially chronic heart failure, threaten many patients' lives worldwide. Because of its slow course and complex causes, its clinical screening, diagnosis, and prognosis are essential challenges. Clinical biomarkers and biosensor technologies can rapidly screen and diagnose. Multiple types of biomarkers are employed for screening purposes, precise diagnosis, and treatment follow-up. This article provides an up-to-date overview of the biomarkers associated with the six main heart failure etiology pathways. Plasma natriuretic peptides (BNP and NT-proBNP) and cardiac troponins (cTnT, cTnl) are still analyzed as gold-standard markers for heart failure. Other complementary biomarkers include growth differentiation factor 15 (GDF-15), circulating Galactose Lectin 3 (Gal-3), soluble interleukin (sST2), C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-α). For these biomarkers, the electrochemical biosensors have exhibited sufficient sensitivity, detection limit, and specificity. This review systematically summarizes the latest molecular biomarkers and sensors for heart failure, which will provide comprehensive and cutting-edge authoritative scientific information for biomedical and electronic-sensing researchers in the field of heart failure, as well as patients. In addition, our proposed future outlook may provide new research ideas for researchers.

Advances in biosensors for major depressive disorder diagnostic biomarkers.

Depression is one of the most common mental disorders and is mainly characterized by low mood or lack of interest and pleasure. It can be accompanied by varying degrees of cognitive and behavioral changes and may lead to suicide risk in severe cases. Due to the subjectivity of diagnostic methods and the complexity of patients' conditions, the diagnosis of major depressive disorder (MDD) has always been a difficult problem in psychiatry. With the discovery of more diagnostic biomarkers associated with MDD in recent years, especially emerging non-coding RNAs (ncRNAs), it is possible to quantify the condition of patients with mental illness based on biomarker levels. Point-of-care biosensors have emerged due to their advantages of convenient sampling, rapid detection, miniaturization, and portability. After summarizing the pathogenesis of MDD, representative biomarkers, including proteins, hormones, and RNAs, are discussed. Furthermore, we analyzed recent advances in biosensors for detecting various types of biomarkers of MDD, highlighting representative electrochemical sensors. Future trends in terms of new biomarkers, new sample processing methods, and new detection modalities are expected to provide a complete reference for psychiatrists and biomedical engineers.

Analysis of Acousto-Optic Phenomenon in SAW Acoustofluidic Chip and Its Application in Light Refocusing.

This paper describes and analyzes a common acousto-optic phenomenon in surface acoustic wave (SAW) microfluidic chips and accomplishes some imaging experiments based on these analyses. This phenomenon in acoustofluidic chips includes the appearance of bright and dark stripes and image distortion. This article analyzes the three-dimensional acoustic pressure field and refractive index field distribution induced by focused acoustic fields and completes an analysis of the light path in an uneven refractive index medium. Based on the analysis of microfluidic devices, a SAW device based on a solid medium is further proposed. This MEMS SAW device can refocus the light beam and adjust the sharpness of the micrograph. The focal length can be controlled by changing the voltage. Moreover, the chip is also proven to be capable of forming a refractive index field in scattering media, such as tissue phantom and pig subcutaneous fat layer. This chip has the potential to be used as a planar microscale optical component that is easy to integrate and further optimize and provides a new concept about tunable imaging devices that can be attached directly to the skin or tissue.

Multiple virus sorting based on aptamer-modified microspheres in a TSAW device.

Due to the overlapping epidemiology and clinical manifestations of flaviviruses, differential diagnosis of these viral diseases is complicated, and the results are unreliable. There is perpetual demand for a simplified, sensitive, rapid and inexpensive assay with less cross-reactivity. The ability to sort distinct virus particles from a mixture of biological samples is crucial for improving the sensitivity of diagnoses. Therefore, we developed a sorting system for the subsequent differential diagnosis of dengue and tick-borne encephalitis in the early stage. We employed aptamer-modified polystyrene (PS) microspheres with different diameters to specifically capture dengue virus (DENV) and tick-borne encephalitis virus (TBEV), and utilized a traveling surface acoustic wave (TSAW) device to accomplish microsphere sorting according to particle size. The captured viruses were then characterized by laser scanning confocal microscopy (LSCM), field emission scanning electron microscopy (FE-SEM) and reverse transcription-polymerase chain reaction (RT‒PCR). The characterization results indicated that the acoustic sorting process was effective and damage-free for subsequent analysis. Furthermore, the strategy can be utilized for sample pretreatment in the differential diagnosis of viral diseases.

Low-noise fluorescent detection of cardiac troponin I in human serum based on surface acoustic wave separation.

Acute myocardial infarction (AMI) is a life-threatening disease when sudden blockage of coronary artery occurs. As the most specific biomarker, cardiac troponin I (cTnI) is usually checked separately to diagnose or eliminate AMI, and achieving the accurate detection of cTnI is of great significance to patients' life and health. Compared with other methods, fluorescent detection has the advantages of simple operation, high sensitivity and wide applicability. However, due to the strong fluorescence interference of biological molecules in body fluids, it is often difficult to obtain high sensitivity. In order to solve this problem, in this study, surface acoustic wave separation is designed to purify the target to achieve more sensitive detection performance of fluorescent detection. Specifically, the interference of background noise is almost completely removed on a microfluidic chip by isolating microbeads through acoustic radiation force, on which the biomarkers are captured by the immobilized detection probe. And then, the concentration of cTnI in human serum is detected by the fluorescence intensity change of the isolated functionalized beads. By this way, the detection limit of our biosensor calculated by 3σ/K method is 44 pg/mL and 0.34 ng/mL in PBS buffer and human serum respectively. Finally, the reliability of this method has been validated by comparison with clinical tests from the nephelometric analyzer in hospital.

Frequency unlocking-based MEMS bifurcation sensors.

MEMS resonators exhibit rich dynamic behaviors under the internal resonance regime. In this work, we present a novel MEMS bifurcation sensor that exploits frequency unlocking due to a 1:3 internal resonance between two electrostatically coupled micro-resonators. The proposed detection mechanism allows the sensor to operate in binary (digital) and analog modes, depending on whether the sensor merely detects a significant jump event in the peak frequency upon unlocking or measures the shift in the peak frequency after unlocking and uses it in conjunction with a calibration curve to estimate the corresponding change in stimulus. We validate the success of this sensor paradigm by experimentally demonstrating charge detection. High charge resolutions are achieved in binary mode, up to 0.137 fC, and in analog mode, up to 0.01 fC. The proposed binary sensor enables extraordinarily high detection resolutions due to the excellent frequency stability under internal resonance and the high signal-to-noise ratio of the shift in peak frequency. Our findings offer new opportunities for high-performance ultrasensitive sensors.

Fast frequency relocking for synchronization enhanced resonant accelerometer.

Synchronization, as a unique phenomenon, has been extensively studied in biology, chaotic systems, nonlinear dynamics, quantum information, and other fields. Benefiting from the characteristics of frequency amplification, noise suppression, and stability improvement, synchronization has been gradually applied in sensing, communication, time keeping, and other applications. In the sensing field, synchronization provides a new strategy to improve the performance of sensors. However, the performance improvement is only effective within the synchronization range, and the narrow synchronization range has become a great challenge for the wide application of synchronization-enhanced sensing mechanism. Here, we propose a frequency automatic tracking system (FATS) to widen the synchronization range and track the periodic acceleration signals by adjusting the frequency of the readout oscillator in real time. In addition, a high-precision frequency measurement system and fast response control system based on FPGA (Field Programmable Gate Array) are built, and the tracking performance of the FATS for static and dynamic external signals is analyzed to obtain the optimal control parameters. Experimental results show that the proposed automatic tracking system is capable of static acceleration measurement, the synchronization range can be expanded to 975 Hz, and the relocking time is shortened to 93.4 ms at best. By selecting the optimal PID parameters, we achieve a faster relocking time to meet the requirements of low-frequency vibration measurements, such as seismic detection and tidal monitoring.