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.

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.

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.

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.

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.

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.

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.

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.

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.

A rapid fluorescent aptasensor for point-of-care detection of C-reactive protein.

In this paper, we report on a novel fluorescent aptasensor based on aptamers modified by both nitrogen-doped graphene quantum dots (N-GQDs) and gold nanoparticles (AuNPs) for the detection of C-reactive protein (CRP). FRET effect is utilized in our aptasensor by the change of aptamers conformation when binding with the target. An obvious fluorescence quench of the N-GQDs can be observed when CRP appears in the assay due to electron transfer between the donor and accepter. A detection limit of 0.2 ng/mL can be achieved by our sensor in PBS buffer which is much lower than the physiological CRP level in human serum. Also, CRP levels in different patients' serum are tested with our assay. Since our aptasensor is rapid (detection time less than 40 min), one-step and very simple to operate, we believe it has great potential to apply for point-of-care testing (POCT).

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.

Graded Interlocks for Iontronic Pressure Sensors with High Sensitivity and High Linearity over a Broad Range.

Flexible pressure sensors that have high sensitivity, high linearity, and a wide pressure-response range are highly desired in applications of robotic sensation and human health monitoring. The challenge comes from the incompressibility of soft materials and the stiffening of microstructures in the device interfaces that lead to gradually saturated response. Therefore, the signal is nonlinear and pressure-response range is limited. Here, we show an iontronic flexible pressure sensor that can achieve high sensitivity (49.1 kPa-1), linear response (R2 > 0.995) over a broad pressure range (up to 485 kPa) enabled by graded interlocks of an array of hemispheres with fine pillars in the ionic layer. The high linearity comes from the fact that the pillar deformation can compensate for the effect of structural stiffening. The response-relaxation time of the sensor is <5 ms, allowing the device to detect vibration signals with frequencies up to 200 Hz. Our sensor has been used to recognize objects with different weights based on machine learning during the gripper grasping tasks. This work provides a strategy to make flexible pressure sensors that have combined performances of high sensitivity, high linearity, and wide pressure-response range.

Robot-aided fN∙m torque sensing within an ultrawide dynamic range.

In situ scanning electron microscope (SEM) characterization have enabled the stretching, compression, and bending of micro/nanomaterials and have greatly expanded our understanding of small-scale phenomena. However, as one of the fundamental approaches for material analytics, torsion tests at a small scale remain a major challenge due to the lack of an ultrahigh precise torque sensor and the delicate sample assembly strategy. Herein, we present a microelectromechanical resonant torque sensor with an ultrahigh resolution of up to 4.78 fN∙m within an ultrawide dynamic range of 123 dB. Moreover, we propose a nanorobotic system to realize the precise assembly of microscale specimens with nanoscale positioning accuracy and to conduct repeatable in situ pure torsion tests for the first time. As a demonstration, we characterized the mechanical properties of Si microbeams through torsion tests and found that these microbeams were five-fold stronger than their bulk counterparts. The proposed torsion characterization system pushes the limit of mechanical torsion tests, overcomes the deficiencies in current in situ characterization techniques, and expands our knowledge regarding the behavior of micro/nanomaterials at various loads, which is expected to have significant implications for the eventual development and implementation of materials science.

Acoustic valves in microfluidic channels for droplet manipulation.

A novel concept of using acoustic valves in microfluidic channels is reported in this work for the first time. An acoustic valve is a controllable virtual barrier constructed with focused acoustic fields, which can control droplets into different branch channels or block and then release them to specific target channels. Compared with other droplet sorting devices using a surface acoustic wave, acoustic valves do not use an acoustic field to drive droplets but only block branch channels. Compared with other sorting methods, such as using dielectric and magnetic forces, acoustic valves do not need a high voltage or target sample modification. As a non-contact and low-damage manipulation method with minimal requirements for target samples, the use of acoustic valve is suitable for microfluidic applications like sorting and manipulation in biochemical experiments, especially those involving optical observation, fluorescence testing, and chemical reactions.

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.

Effects of strain on thermal conductivity of silicon dioxide thin films using test method based on 3-ω technique and uniaxial strain setup.

We propose a test method to study the effects of strain on the thermal conductivity of thin films. First, a strain setup was designed to apply stress to a thin film, and a test system was built to measure its thermal conductivity by combining the strain setup with the 3-ω method. The strain setup can apply stress to the specimen by adjusting load weights, while the strain of a thin film was obtained by measuring the applied stress with a force sensor. Second, the effects of strain on the resistance and temperature coefficients of a metal thin film were studied using the strain setup and the four-wire resistance measurement method; the results show that the resistance and temperature coefficients of metal thin films decrease with strain. Finally, the effects of strain on the thermal conductivity of a silicon dioxide thin film and silicon substrate were studied using the proposed method and test system. As the strain increased from 0% to 0.072%, the thermal conductivity of the 300-nm thick silicon dioxide thin film decreased from 0.907 W/(m K) to 0.817 W/(m K). The thermal conductivity of the 0.5-mm thick silicon substrate fluctuated in the range of 130.6 W/(m K) to 118.8 W/(m K) and then tended to stabilize around 126.4 W/(m K).

Construction of core-shell microcapsules via focused surface acoustic wave microfluidics.

The ability to construct core-shell microcapsules has the potential to shift the paradigm in the development of new delivery systems for nutrients, cosmetics, and drugs. In this work, we demonstrate an application of focused surface acoustic wave (FSAW) microfluidics to produce microcapsules with a core-shell structure using one or two focused interdigital transducers (FIDTs) on the microfluidic device. Solid particles or liquid microdroplets without any special modification in multiphase laminar flow are driven by the acoustic radiation force arising from the FSAW, and cross the oil/water interface back and forth, which is not only suitable for generation of core-shell microcapsules with solid cores but also used for coating an aqueous microdroplet core with an oil shell. On this basis, more FIDTs can be added to the device to manufacture more layers of microcapsules if needed. Single-layer, two-layer, or even multi-layer microcapsules can be selectively fabricated. This work provides a promising and robust platform to construct core-shell microcapsules via FSAW microfluidics, which are suitable for a wide range of applications.