Pre-enrichment-free detection of hepatocellular carcinoma-specific ctDNA via PDMS and MEMS-based microfluidic sensor.

The growing interest in microfluidic biosensors has led to improvements in the analytical performance of various sensing mechanisms. Although various sensors can be integrated with microfluidics, electrochemical ones have been most commonly employed due to their ease of miniaturization, integration ability, and low cost, making them an established point-of-care diagnostic method. This concept can be easily adapted to the detection of biomarkers specific to certain cancer types. Pathological profiling of hepatocellular carcinoma (HCC) is heterogeneous and rather complex, and biopsy samples contain limited information regarding the tumor and do not reflect its heterogeneity. Circulating tumor DNAs (ctDNAs), which can contain information regarding cancer characteristics, have been studied tremendously since liquid biopsy emerged as a new diagnostic method. Recent improvements in the accuracy and sensitivity of ctDNA determination also paved the way for genotyping of somatic genomic alterations. In this study, three-electrode (Au-Pt-Ag) glass chips were fabricated and combined with polydimethylsiloxane (PDMS) microchannels to establish an electrochemical microfluidic sensor for detecting c.747G > T hotspot mutations in the TP53 gene of ctDNAs from HCC. The preparation and analysis times of the constructed sensor were as short as 2 h in total, and a relatively high flow rate of 30 µl/min was used during immobilization and hybridization steps. To the best of our knowledge, this is the first time a PDMS-based microfluidic electrochemical sensor has been developed to target HCC ctDNAs. The system exhibited a limit of detection (LOD) of 24.1 fM within the tested range of 2-200 fM. The sensor demonstrated high specificity in tests conducted with fully noncomplementary and one-base mismatched target sequences. The developed platform is promising for detecting HCC-specific ctDNA at very low concentrations without requiring pre-enrichment steps.

Multisensor Integrated Platform Based on MEMS Charge Variation Sensing Technology for Biopotential Acquisition.

We propose a new methodology for long-term biopotential recording based on an MEMS multisensor integrated platform featuring a commercial electrostatic charge-transfer sensor. This family of sensors was originally intended for presence tracking in the automotive industry, so the existing setup was engineered for the acquisition of electrocardiograms, electroencephalograms, electrooculograms, and electromyography, designing a dedicated front-end and writing proper firmware for the specific application. Systematic tests on controls and nocturnal acquisitions from patients in a domestic environment will be discussed in detail. The excellent results indicate that this technology can provide a low-power, unexplored solution to biopotential acquisition. The technological breakthrough is in that it enables adding this type of functionality to existing MEMS boards at near-zero additional power consumption. For these reasons, it opens up additional possibilities for wearable sensors and strengthens the role of MEMS technology in medical wearables for the long-term synchronous acquisition of a wide range of signals.

An electromechanical stimulation regulating model with flexoelectric effect of piezoelectric laminated micro-beam for cell bionic culture.

Cell bionic culture requires the construction of cell growth microenvironments. In this paper, mechanical force and electrical stimulations are applied to the cells cultured on the surface of the piezoelectric laminated micro-beam driven by an excitation voltage. Based on the extended dielectric theory, the electromechanical microenvironment regulating model of the current piezoelectric laminated micro-beam is established. The variational principle is used to obtain the governing equations and boundary conditions. The differential quadrature method and the iterative method are used to solve two boundary value problems for cantilever beams and simply supported beams. In two cases, the mechanical force and electrical stimulations applied to the cells are analyzed in detail and the microscale effect is investigated. This study is meaningful for improving the quality of cell culture and promoting the cross-integration of mechanics and biomedicine.

MEMS strapdown inertial attitude measurement system using rotational modulation technology.

Attitude determination involves the integration of methodologies and systems for estimating the time varying attitude of moving objects. Strapdown Inertial Attitude Measurement System (SIAMS) is among the most widely used navigation systems. The development of cost effective Micro Electro Mechanic System (MEMS) based inertial sensors has made attitude measurement system more affordable. However, MEMS sensors suffer from various errors that have to be calibrated and compensated to get acceptable attitude results. Given the auto-compensation of inertial sensor bias in rotation error modulation, the objective of this paper is to develop a MEMS-based rotary SIAMS, in which the significant sensor bias is automatically compensated by rotating the IMU, to offer comparable performance with respect to a tactical-grade Inertial Measurement Unit (IMU). With the analysis of the relationship between the MEMS error and misalignment, a MEMS calibration model is derived, and a combined calibration method of multi position rotation is applied to estimate the deterministic sensor errors such as bias, scale factor, and misalignment. Simulation and experiment results indicate that the proposed method can further modulate and compensate the MEMS errors, thereby improving the MEMS attitude accuracy.

Representing Fine Texture of Pencil Hardness by High-Frequency Vibrotactile Equivalence Conversion Using Ultra-Thin PZT-MEMS Vibrators.

This study aims to represent fine texture differences in pencil hardness using intensity segment modulation (ISM), a sensory equivalent conversion method of vibration from high to low frequencies. This method enables the presentation of delicate tactile sensations even with small transducers. We integrated this approach in the world's thinnest ultra-thin PZT-MEMS vibrator with a stylus-type device. The vibration waveforms of four types of pencil hardness were captured under the same conditions, and the differences in the frequency components were confirmed. We compared the fine texture feelings under raw signal, ISM, and ISM below 1 kHz conditions by conducting discrimination tests and subjective similarity evaluations. The results showed that ISM could reproduce similar feelings of the pencil hardness.

Ultrasensitive detection of vital biomolecules based on a multi-purpose BioMEMS for Point of care testing: digoxin measurement as a case study.

Rapid and label-free detection of very low concentrations of biomarkers in disease diagnosis or therapeutic drug monitoring is essential to prevent disease progression in Point of Care Testing. For this purpose, we propose a multi-purpose optical Bio-Micro-Electro-Mechanical-System (BioMEMS) sensing platform which can precisely measure very small changes of biomolecules concentrations in plasma-like buffer samples. This is realized by the development of an interferometric detection method on highly sensitive MEMS transducers (cantilevers). This approach facilitates the precise analysis of the obtained results to determine the analyte type and its concentrations. Furthermore, the proposed multi-purpose platform can be used for a wide range of biological assessments in various concentration levels by the use of an appropriate bioreceptor and the control of its coating density on the cantilever surface. In this study, the present system is prepared for the identification of digoxin medication in its therapeutic window for therapeutic drug monitoring as a case study. The experimental results represent the repeatability and stability of the proposed device as well as its capability to detect the analytes in less than eight minutes for all samples. In addition, according to the experiments carried out for very low concentrations of digoxin in plasma-like buffer, the detection limit of LOD = 300 fM and the maximum sensitivity of S = 5.5 × 1012 AU/M are achieved for the implemented biosensor. The present ultrasensitive multi-purpose BioMEMS sensor can be a fully-integrated, cost-effective device to precisely analyze various biomarker concentrations for various biomedical applications.

Bionanotechnology and bioMEMS (BNM): state-of-the-art applications, opportunities, and challenges.

The development of micro- and nanotechnology for biomedical applications has defined the cutting edge of medical technology for over three decades, as advancements in fabrication technology developed originally in the semiconductor industry have been applied to solving ever-more complex problems in medicine and biology. These technologies are ideally suited to interfacing with life sciences, since they are on the scale lengths as cells (microns) and biomacromolecules (nanometers). In this paper, we review the state of the art in bionanotechnology and bioMEMS (collectively BNM), including developments and challenges in the areas of BNM, such as microfluidic organ-on-chip devices, oral drug delivery, emerging technologies for managing infectious diseases, 3D printed microfluidic devices, AC electrokinetics, flexible MEMS devices, implantable microdevices, paper-based microfluidic platforms for cellular analysis, and wearable sensors for point-of-care testing.

Strengthening Privacy and Data Security in Biomedical Microelectromechanical Systems by IoT Communication Security and Protection in Smart Healthcare.

Biomedical Microelectromechanical Systems (BioMEMS) serve as a crucial catalyst in enhancing IoT communication security and safeguarding smart healthcare systems. Situated at the nexus of advanced technology and healthcare, BioMEMS are instrumental in pioneering personalized diagnostics, monitoring, and therapeutic applications. Nonetheless, this integration brings forth a complex array of security and privacy challenges intrinsic to IoT communications within smart healthcare ecosystems, demanding comprehensive scrutiny. In this manuscript, we embark on an extensive analysis of the intricate security terrain associated with IoT communications in the realm of BioMEMS, addressing a spectrum of vulnerabilities that spans cyber threats, data manipulation, and interception of communications. The integration of real-world case studies serves to illuminate the direct repercussions of security breaches within smart healthcare systems, highlighting the imperative to safeguard both patient safety and the integrity of medical data. We delve into a suite of security solutions, encompassing rigorous authentication processes, data encryption, designs resistant to attacks, and continuous monitoring mechanisms, all tailored to fortify BioMEMS in the face of ever-evolving threats within smart healthcare environments. Furthermore, the paper underscores the vital role of ethical and regulatory considerations, emphasizing the need to uphold patient autonomy, ensure the confidentiality of data, and maintain equitable access to healthcare in the context of IoT communication security. Looking forward, we explore the impending landscape of BioMEMS security as it intertwines with emerging technologies such as AI-driven diagnostics, quantum computing, and genomic integration, anticipating potential challenges and strategizing for the future. In doing so, this paper highlights the paramount importance of adopting an integrated approach that seamlessly blends technological innovation, ethical foresight, and collaborative ingenuity, thereby steering BioMEMS towards a secure and resilient future within smart healthcare systems, in the ambit of IoT communication security and protection.

Micro Electromechanical System Navigation Assists Femoral Extramedullary Alignment Osteotomy in Total Knee Arthroplasty: A Single-Blind Randomizing Study.

OBJECTIVE: A micro-electromechanical system (MEMS) was developed based on spatial alignment and navigation technology to assist femoral extramedullary alignment osteotomy (FEAO) in total knee arthroplasty (TKA). The system can locate and adjust the femoral distal condylar osteotomy (FDCO) to obtain a better femoral prosthesis placement. It is a portable navigation device and provides an innovative approach for FDCO. METHODS: Sixty patients who suffered from severe knee osteoarthritis who underwent unilateral TKA from May 14, 2021 to May 30, 2022 were randomly divided into a MEMS-FEAO group and a conventional femoral intramedullary alignment osteotomy (FIAO) group, with 30 cases in each group for a controlled retrospective study. The hip-knee-ankle angle (HKAA) of the lower limb was measured before and after surgery, the femoral valgus angle (FVA) was measured preoperatively, and the femoral prosthesis valgus angle (FPVA) and the femoral prosthesis flexion angle (FPFA) were measured postoperatively following computed tomography imaging protocols. Measurement data is statistically described as mean ± standard deviation c. The count data is described by frequency (constituent ratio) using the rank sum test. RESULT: A total of 6.7% (2/30) of FEAO compared to 20.0% (6/30) of FIAO cases were postoperative deviations where the HKAA exceeded ±3° of neutral alignment (p < 0.05). The postoperative HKAA was 178.74° ± 1.56° versus 176.64° ± 3.39° (p < 0.05), the HKAA deviation was 1.25° ± 1.56° versus 3.36° ± 3.40° (p < 0.05), and the FPFA was 4.85° ± 2.46° versus 6.60° ± 1.86°(p < 0.05). Therefore, the differences were all statistically significant between the two groups. However, the FPVA was -0.59° ± 2.73° versus -0.80° ± 2.85° (p > 0.05), and there was no statistical significance between the two groups. CONCLUSION: The MEMS-FEAO system can improve the accurate alignment and can be utilized as a locator to obtain the best femoral prosthesis placement in TKA and significantly reduce the rate of poor force line of the lower limb.

Multiple-Degree-of-Freedom Modeling and Simulation for Seismic-Grade Sigma-Delta MEMS Capacitive Accelerometers.

The high-order mechanical resonances of the sensing element in a high-vacuum environment can significantly degrade the noise and distortion performance of seismic-grade sigma-delta MEMS capacitive accelerometers. However, the current modeling approach is unable to evaluate the effects of high-order mechanical resonances. This study proposes a novel multiple-degree-of-freedom (MDOF) model to evaluate the noise and distortion induced by high-order mechanical resonances. Firstly, the MDOF dynamic equations of the sensing element are derived using the principle of modal superposition and Lagrange's equations. Secondly, a fifth-order electromechanical sigma-delta system of the MEMS accelerometer is established in Simulink based on the dynamic equations of the sensing element. Then, the mechanism through which the high-order mechanical resonances degrade the noise and distortion performances is discovered by analyzing the simulated result. Finally, a noise and distortion suppression method is proposed based on the appropriate improvement in high-order natural frequency. The results show that the low-frequency noise drastically decreases from about -120.5 dB to -175.3 dB after the high-order natural frequency increases from about 130 kHz to 455 kHz. The harmonic distortion also reduces significantly.

Research on Dust Effect for MEMS Thermal Wind Sensors.

This communication investigated the dust effect on microelectromechanical system (MEMS) thermal wind sensors, with an aim to evaluate performance in practical applications. An equivalent circuit was established to analyze the temperature gradient influenced by dust accumulation on the sensor's surface. The finite element method (FEM) simulation was carried out to verify the proposed model using COMSOL Multiphysics software. In experiments, dust was accumulated on the sensor's surface by two different methods. The measured results indicated that the output voltage for the sensor with dust on its surface was a little smaller than that of the sensor without dust at the same wind speed, which can degrade the measurement sensitivity and accuracy. Compared to the sensor without dust, the average voltage was reduced by about 1.91% and 3.75% when the dustiness was 0.04 g/mL and 0.12 g/mL, respectively. The results can provide a reference for the actual application of thermal wind sensors in harsh environments.

What MEMS Research and Development Can Learn from a Production Environment.

The intricate interdependency of device design and fabrication process complicates the development of microelectromechanical systems (MEMS). Commercial pressure has motivated industry to implement various tools and methods to overcome challenges and facilitate volume production. By now, these are only hesitantly being picked up and implemented in academic research. In this perspective, the applicability of these methods to research-focused MEMS development is investigated. It is found that even in the dynamics of a research endeavor, it is beneficial to adapt and apply tools and methods deduced from volume production. The key step is to change the perspective from fabricating devices to developing, maintaining and advancing the fabrication process. Tools and methods are introduced and discussed, using the development of magnetoelectric MEMS sensors within a collaborative research project as an illustrative example. This perspective provides both guidance to newcomers as well as inspiration to the well-versed experts.

Advances in Silicon-Based Integrated Lidar.

Silicon-based Lidar is an ideal way to reduce the volume of the Lidar and realize monolithic integration. It removes the moving parts in the conventional device and realizes solid-state beam steering. The advantages of low cost, small size, and high beam steering speed have attracted the attention of many researchers. In order to facilitate researchers to quickly understand the research progress and direction, this paper mainly describes the research progress of silicon-based integrated Lidar, including silicon-based optical phased array Lidar, silicon-based optical switch array Lidar, and continuous frequency-modulated wave Lidar. In addition, we also introduced the scanning modes and working principles of other kinds of Lidar, such as the Micro-Electro-Mechanical System, mechanical Lidar, etc., and analyzed the characteristics of the Lidars above. Finally, we summarized this paper and put forward the future expectations of silicon-based integrated Lidar.

Terahertz Detectors Using Microelectromechanical System Resonators.

The doubly clamped microelectromechanical system (MEMS) beam resonators exhibit extremely high sensitivity to tiny changes in the resonance frequency owing to their high quality (Q-) factors, even at room temperature. Such a sensitive frequency-shift scheme is very attractive for fast and highly sensitive terahertz (THz) detection. The MEMS resonator absorbs THz radiation and induces a temperature rise, leading to a shift in its resonance frequency. This frequency shift is proportional to the amount of THz radiation absorbed by the resonator and can be detected and quantified, thereby allowing the THz radiation to be measured. In this review, we present an overview of the THz bolometer based on the doubly clamped MEMS beam resonators in the aspects of working principle, readout, detection speed, sensitivity, and attempts at improving the performance. This allows one to have a comprehensive view of such a novel THz detector.

Fabrication and Performance of a Ta2O5 Thin Film pH Sensor Manufactured Using MEMS Processes.

In this work, a capacitive pH sensor consisting of Ta2O5 functional film is designed and fabricated by employing MEMS-based procedures. The Ta2O5 thin film has an amorphous microstructure, and its surface roughness is less than 3.17 nm. A signal processing circuit and a software filtering algorithm are also designed to measure the pH value, thus improving the detection accuracy and anti-interference ability. Good linearity (R2 = 0.99904) and sensitivity (63.12 mV/pH) are recorded for the proposed sensing element in the range of pH 2~12. In addition, the sensor's drift and hysteresis are equal to 5.1 mV and 5.8 mV, respectively. The enhanced sensing performance in combination with the facile miniaturization process, low fabrication cost, and suitability for mass production render the fabricated sensor attractive for applications where pH change measurements in a water environment are required.

Feasibility study of MEMS-based stenosis detection using a prototypical catheter design with intravascular scanning probes (IVSPs).

X-ray coronary angiography (XRA) is a standard clinical method for diagnosing coronary artery disease (CAD). However, despite continuous improvements in XRA technology, it has limitations that include being visible only in color contrast, and the information it provides on coronary artery plaques is not comprehensive due to its low signal-to-noise ratio and limited resolution. In this study, we propose a novel diagnostic tool, a MEMS-based smart catheter with an intravascular scanning probe (IVSP), to complement XRA and verify its effectiveness and feasibility. The IVSP catheter uses Pt strain gauges embedded on the probe to examine the characteristics of a blood vessel, such as the degree of stenosis and morphological structures of the vessel walls, through physical contact. The feasibility test results showed that the output signals of the IVSP catheter reflected the morphological structure of the phantom glass vessel that mimicked stenosis. In particular, the IVSP catheter successfully assessed the morphology of the stenosis, which was only 17% of the cross-sectional diameter obstructed. In addition, the strain distribution on the probe surface was studied using finite element analysis (FEA), and a correlation between the experimental and FEA results was derived.

A Novel Packaging of the MEMS Gas Sensors Used for Harsh Outdoor and Human Exhale Sampling Applications.

Dust or condensed water present in harsh outdoor or high-humidity human breath samples are one of the key sources that cause false detection in Micro Electro-Mechanical System (MEMS) gas sensors. This paper proposes a novel packaging mechanism for MEMS gas sensors that utilizes a self-anchoring mechanism to embed a hydrophobic polytetrafluoroethylene (PTFE) filter into the upper cover of the gas sensor packaging. This approach is distinct from the current method of external pasting. The proposed packaging mechanism is successfully demonstrated in this study. The test results indicate that the innovative packaging with the PTFE filter reduced the average response value of the sensor to the humidity range of 75~95% RH by 60.6% compared to the packaging without the PTFE filter. Additionally, the packaging passed the High-Accelerated Temperature and Humidity Stress (HAST) reliability test. With a similar sensing mechanism, the proposed packaging embedded with a PTFE filter can be further employed for the application of exhalation-related, such as coronavirus disease 2019 (COVID-19), breath screening.

A Smart Active Phase-Change Micropump Based on CMOS-MEMS Technology.

The rational integration of many microfluidic chips and micropumps remains challenging. Due to the integration of the control system and sensors in active micropumps, they have unique advantages over passive micropumps when integrated into microfluidic chips. An active phase-change micropump based on complementary metal-oxide-semiconductor-microelectromechanical system (CMOS-MEMS) technology was fabricated and studied theoretically and experimentally. The micropump structure is simple and consists of a microchannel, a series of heater elements along the microchannel, an on-chip control system, and sensors. A simplified model was established to analyze the pumping effect of the traveling phase transition in the microchannel. The relationship between pumping conditions and flow rate was examined. Based on the experimental results, the maximum flow rate of the active phase-change micropump at room temperature is 22 µL/min, and long-term stable operation can be achieved by optimizing heating conditions.

A stochastic parabolic model of MEMS driven by fractional Brownian motion.

In this paper, we study a stochastic parabolic problem that emerges in the modeling and control of an electrically actuated MEMS (micro-electro-mechanical system) device. The dynamics under consideration are driven by an one dimensional fractional Brownian motion with Hurst index [Formula: see text]. We derive conditions under which the resulting SPDE has a global in time solution, and we provide analytic estimates for certain statistics of interest, such as quenching times and the corresponding quenching probabilities. Our results demonstrate the non-trivial impact of the fractional noise on the dynamics of the system. Given the significance of MEMS devices in biomedical applications, such as drug delivery and diagnostics, our results provide valuable insights into the reliability of these devices in the presence of positively correlated noise.