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This paper presents a MEMS electrochemical angular accelerometer with a silicon-based four-electrode structure, which was made of thousands of interconnected microchannels for electrolyte flow, anodes uniformly coated on structure surfaces and cathodes located on the sidewalls of flow holes. From the perspective of device fabrication, in this study, the previously reported multi-piece assembly was simplified into single-piece integrative manufacturing, effectively addressing the problems of complex assembly and manual alignment. From the perspective of the sensitive structure, in this study, the silicon-based four-electrode structure featuring with complete insulation layers between anodes and cathodes can enable fast electrochemical reactions with improved sensitivities. Numerical simulations were conducted to optimize the geometrical parameters of the silicon-based four-electrode structure, where increases in fluid resistance and cathode area were found to expand working bandwidths and improve device sensitivity, respectively. Then, the silicon-based four-electrode structure was fabricated by conventional MEMS processes, mainly composed of wafer-level bonding and wafer-level etching. As to device characterization, the MEMS electrochemical angular accelerometer with the silicon-based four-electrode structure exhibited a maximum sensitivity of 1458 V/(rad/s2) at 0.01 Hz and a minimum noise level of −164 dB at 1 Hz. Compared with previously reported electrochemical angular accelerometers, the angular accelerometer developed in this study offered higher sensitivities and lower noise levels, indicating strong potential for applications in the field of rotational seismology. [ABSTRACT FROM AUTHOR]

High mud content in the sand has a negative impact on cement mortar but there is little research on Alkali-activated slag (AAS) mortar. In order to explore the impacts of mud content in the sand on the performance of AAS mortar, this paper used sand that contains silt, clay, and a mixture of silt and clay; tested the setting time of AAS with different mud contents of 0%, 2%, 4%, 6%, 8%, and 10%; and measured the unconfined compressive strength and beam flexural strength of 3 d, 7 d, and 28 d AAS mortar specimens. The microstructure of AAS mortar with different kinds of mud was observed by scanning electron microscope (SEM), the elemental composition of the hydration product was tested by energy dispersive spectroscopy (EDS), and the AAS interaction mechanism with different kinds of mud was analyzed. The main conclusions are: the higher the mud content in the sand, the shorter the initial setting time and the longer the final setting time of AAS, mainly because the mud in the sand affects the hydration process; mud content above 4% causes a rapid decrease in the compressive and flexural strengths of AAS mortar, mainly because the mud affects the hydration process and hinders the bonding of the hydration product with the sand. When there is no mud in the sand, the main hydration product of AAS is dense calcium-alumina-silicate-hydrate (C-A-S-H) gel. When the sand contains silt, the hydration product of AAS is loose C-A-S-H gel. When the sand contains clay, the hydration products of AAS contain C-A-S-H gel and a small amount of sodium-aluminum-silicate-hydrate (N-A-S-H), and needle-like crystals. Loose gel and crystals have a negative effect on the AAS mortar strength. [ABSTRACT FROM AUTHOR]

The setting time of alkali-activated slag (AAS) binders is extremely short, while traditional retarders of Portland cement may be invalid for AAS. To find an effective retarder with a less negative impact on strength, borax (B), sucrose (S), and citric acid (CA) were selected as potential retarders. The setting time of AAS with different admixtures dosages of 0%, 2%, 4%, 6%, and 8%, and the unconfined compressive strength and beam flexural strength of 3 d, 7 d, and 28 d AAS mortar specimens were tested. The microstructure of AAS with different additives was observed by scanning using an electron microscope (SEM), and the hydration products were analyzed by energy dispersive spectroscopy (EDS), X-ray diffraction analysis (XRD), and thermogravimetric analysis (DT-TGA) to explain the retarding mechanism of AAS with different additives. The results showed that the incorporation of borax and citric acid could effectively prolong the setting time of AAS more than that of sucrose, and the retarding effect is more and more obvious with the increase in borax and citric acid dosages. However, sucrose and citric acid negatively influence AAS's unconfined compressive strength and flexural stress. The negative effect becomes more evident with the increase in sucrose and citric acid dosages. Borax is the most suitable retarder for AAS among the three selected additives. SEM-EDS analysis showed that the incorporation of borax does three things: produces gels, covers the surface of the slag, and slows down the hydration reaction rate. [ABSTRACT FROM AUTHOR]

In this paper, an all-Si resonant pressure microsensor based on eutectic bonding was developed, which can eliminate thermal expansion coefficient mismatches and residual thermal stresses during the bonding process. More specifically, the resonant pressure microsensor included an SOI wafer with a pressure-sensitive film embedded with resonators, which was eutectically bonded with a silicon cap for vacuum encapsulation. The all-Si resonant pressure microsensor was carefully designed and simulated numerically, where the use of the silicon cap was shown to effectively address temperature disturbances of the microsensor. The microsensor was then fabricated based on MEMS processes where eutectic bonding was adopted to link the SOI wafer and the silicon cap. The characterization results showed that the temperature disturbances of the resonant pressure microsensor encapsulated with the silicon cap were quantified as −0.82 Hz/°C of the central resonator and −2.36 Hz/°C of the side resonator within a temperature range from −40 °C to 80 °C, which were at least eight times lower than that of the microsensor encapsulated with the glass cap. Compared with the microsensor using the glass cap, the all-silicon microsensor demonstrated an accuracy improvement from 0.03% FS to 0.01% FS and a reduction in short-term frequency fluctuations from 3.2 Hz to 1.5 Hz. [ABSTRACT FROM AUTHOR]

This article first reviews scientific meanings of single-cell analysis by highlighting two key scientific problems: landscape reconstruction of cellular identities during dynamic immune processes and mechanisms of tumor origin and evolution. Secondly, the article reviews clinical demands of single-cell analysis, which are complete blood counting enabled by optoelectronic flow cytometry and diagnosis of hematologic malignancies enabled by multicolor fluorescent flow cytometry. Then, this article focuses on the developments of optoelectronic flow cytometry for the complete blood counting by comparing conventional counterparts of hematology analyzers (e.g., DxH 900 of Beckman Coulter, XN-1000 of Sysmex, ADVIA 2120i of Siemens, and CELL-DYN Ruby of Abbott) and microfluidic counterparts (e.g., microfluidic impedance and imaging flow cytometry). Future directions of optoelectronic flow cytometry are indicated where intrinsic rather than dependent biophysical parameters of blood cells must be measured, and they can replace blood smears as the gold standard of blood analysis in the near future. [ABSTRACT FROM AUTHOR]

This paper presented an electrochemical seismic micro sensor based on an integrated structure of four centrosymmetric electrodes. In this integrative structure, cathodes were not only distributed on wafer surfaces but also on the inner walls of the flow holes of the wafer, which increased the effective cathode areas and improved the sensitivity of the sensor. Numerical simulations were conducted to validate the feasibility of the integrated structure of four centrosymmetric electrodes in monitoring seismic vibrations where variations in the arrangements of the flow holes and anode width were investigated. The integrated structure of the four centrosymmetric micro electrodes was fabricated based on Micro-Electro-Mechanical Systems (MEMS) without the requirement of manual alignments. Experimental characterizations revealed that: (1) the maximum sensitivity of the electrochemical seismic sensor based on the integrated structure of four centrosymmetric electrodes was two orders of magnitude higher than that of the commercial counterpart of CME6011 and three times higher than the electrochemical seismic sensor based on the integrated structure of four planar micro electrodes; (2) the electrochemical seismic sensor based on the integrated structure of four centrosymmetric micro electrodes demonstrated comparable and even lower noise levels in comparison to CME6011. Thus, the electrochemical seismic micro sensor developed in this study may function as an enabling tool in future applications of seismic monitoring and geophysical explorations. [ABSTRACT FROM AUTHOR]

This paper developed an electrochemical angular micro-accelerometer using a silicon-based three-electrode structure as a sensitive unit. Angular acceleration was translated to ion changes around sensitive microelectrodes, and the adoption of the silicon-based three-electrode structure increased the electrode area and the sensitivity of the device. Finite element simulation was conducted for geometry optimization where the anode length, the orifice diameter, and the orifice spacing of the sensitive unit were determined as 200 μm, 80 μm, and 500 μm, respectively. Microfabrication was conducted to manufacture the silicon-based three-electrode structure, which then was assembled to form the electrochemical angular micro-accelerometer, leveraging mechanical compression. Device characterization was conducted, where the sensitivity, bandwidth, and noise level were quantified as 290.193 V/(rad/s2) at 1 Hz, 0.01–2 Hz, and 1.78 × 10−8 (rad/s2)/Hz1/2 at 1 Hz, respectively. Due to the inclusion of the silicon-based three-electrode structure, compared with previously reported electrochemical angular accelerometers, the angular accelerometer developed in this article was featured with a higher sensitivity and a lower self-noise level. Therefore, it could be used for the measurement of low-frequency seismic rotation signals and played a role in the seismic design of building structures. [ABSTRACT FROM AUTHOR]

Aiming at the development needs of low-frequency and high-sensitivity vector hydrophones, this paper has developed a micro-electro-mechanical system (MEMS) based co-oscillating electrochemical vector hydrophone. We obtained the optimized geometric parameters through simulation analysis of the diameter of the rubber membrane, the length of the flow channel and the diameter of the flow holes. Based on the simulation results, electrodes were fabricated using MEMS technology, and were then assembled and tested. Device characterization was conducted, where the sensitivity and bandwidth were quantified as 0.5–150 Hz, −187 dB ref. 1 V/μPa, respectively. Compared with a previously reported co-oscillating vector hydrophone, the co-oscillating vector hydrophone developed in this article featured a lower working frequency band. [ABSTRACT FROM AUTHOR]

This paper presents a micro-electromechanical systems (MEMS)-based integrated triaxial electrochemical seismometer, which can detect three-dimensional vibration. By integrating three axes, the integrated triaxial electrochemical seismometer is characterized by small volume and high symmetry. The numerical simulation results inferred that the integrated triaxial electrochemical seismometer had excellent independence among three axes. Based on the experimental results, the integrated triaxial electrochemical seismometer had the advantage of small axial crosstalk and could detect vibration in arbitrary directions. Furthermore, compared with the uniaxial electrochemical seismometer, the integrated triaxial electrochemical seismometer had similar sensitivity curves ranging from 0.01 to 100 Hz. In terms of random ground motion response, high consistencies between the developed integrated triaxial electrochemical seismometer and the uniaxial electrochemical seismometer could be easily observed, which indicated that the developed integrated triaxial electrochemical seismometer produced comparable noise levels to those of the uniaxial electrochemical seismometer. These results validated the performance of the integrated triaxial electrochemical seismometer, which has a good prospect in the field of deep geophysical exploration and submarine seismic monitoring. [ABSTRACT FROM AUTHOR]

In this paper, a piezoresistive pressure sensor based on silicon on insulator (SOI) was presented, which was composed of an SOI layer with sensing elements and a glass cap for a hermetic package. Different from its conventional counterparts, the position and thickness of the four piezoresistors was optimized based on numerical simulation, which suggests that two piezoresistors at the center while the other two at the edge of the pressure-sensitive diaphragm and a thickness of 2 μm can produce the maximum sensitivity and the minimum nonlinearity. Due to the use of silicon rather than metal for electrical connections, the piezoresistive pressure sensor was fabricated in a highly simplified process. From the experimental results, the fabricated piezoresistive pressure sensor demonstrated a high sensitivity of 37.79 mV·V−1·MPa−1, a high full-scale (FS) output of 472.33 mV, a low hysteresis of 0.09% FS, a good repeatability of 0.03% FS and a good accuracy of 0.06% FS at 20 °C. A temperature coefficient of sensitivity of 0.44 mV·MPa−1·°C−1 and a low zero drift were also shown at different temperatures. The piezoresistive pressure sensor developed in this study may function as an enabling tool in pressure measurements. [ABSTRACT FROM AUTHOR]

Ophiopogon japonicus is a commonly used Chinese medicine with multiple pharmacological effects. To increase the yield of O. japonicus, paclobutrazol is widely used during the cultivation, and residues of paclobutrazol cause undesired side effects of O. japonicus. In this study, the effect of different concentrations of paclobutrazol on O. japonicus was investigated, and the final residual amount of paclobutrazol in the plant sample was determined by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS); cell morphology was observed by transmission electron microscopy. The inhibitory effect of paclobutrazol on plant height and the stimulatory effect on root elongation were concentration-dependent from 0.6 to 11.3 g/L, reaching a maximum of about 28% and 67%, respectively. However, when the concentration was 22.5 g/L, these effects were significantly weakened, and the same trend was observed for the tuber root weight. Paclobutrazol caused the cell wall of O. japonicus to thicken, making the cells smaller and more densely arranged. Paclobutrazol also inhibited bacterial growth, irrespective of the concentration. Considering the residual concentration after application and the effects on growth, the application of 1.3 g/L or 2.8 g/L paclobutrazol can increase the accumulation of effective ingredients while promoting production, reducing application costs, and maximizing farmers' profit. [ABSTRACT FROM AUTHOR]

This paper presents a new process to fabricate a sensing unit of electrochemical seismometers using only one silicon–glass–silicon bonded wafer. By integrating four electrodes on one silicon–glass–silicon bonded wafer, the consistency of the developed sensing unit was greatly improved, benefiting from the high alignment accuracy. Parameter designs and simulations were carried out based on this sensing unit, which indicated that the sensitivities of the developed electrochemical seismometer decreased with the decrease in the number of flow holes in the sensing unit, and the initial stabilization time decreased gradually with the decrease in the thickness of the glass layer. Based on experimental results of four devices, the peak sensitivity was quantified as 5345.45 ± 43.78 V/(m/s) at 2 Hz, which proved high consistency of the fabricated electrochemical seismometer. In terms of the responses to random ground motions, high consistencies between the developed electrochemical seismometer and the commercial counterpart of CME6011 (R-sensors, Moscow, Russia) were found, where the developed electrochemical seismometer produced comparable noise levels to those of CME6011. These results validated the performance of the device and it may function as an effective tool for a variety of applications. [ABSTRACT FROM AUTHOR]

Electrochemical seismic sensors that employ liquid as their inertial masses have the advantages of high performances in the low-frequency domain and a large working inclination. However, the surrounding temperature changes have serious impacts on the sensitivities of the sensors, which makes them unable to work as expected. This paper studied the temperature characteristics of electrochemical seismic sensors based on MEMS (micro–electro–mechanical systems), and analyzed the influences of the temperature effects on the open-loop and closed-loop amplitude-frequency curves. Most importantly, the temperature compensation circuits based on thermistors were developed, which effectively adjusted pole frequencies and sensitivity coefficients, and finally realized the real-time temperature compensation for both open-loop and closed-loop measurements for the first time. The results showed that in the temperature range of −10 °C ~ +40 °C, and with the 3 dB bandwidth range of 0.01 Hz ~ 40 Hz, the change of the maximum sensitivity was reduced from about 25 dB before temperature compensation to less than 2 dB after temperature compensation. [ABSTRACT FROM AUTHOR]

This paper presents a resonant pressure microsensor with a wide range of pressure measurements. The developed microsensor is mainly composed of a silicon-on-insulator (SOI) wafer to form pressure-sensing elements, and a silicon-on-glass (SOG) cap to form vacuum encapsulation. To realize a wide range of pressure measurements, silicon islands were deployed on the device layer of the SOI wafer to enhance equivalent stiffness and structural stability of the pressure-sensitive diaphragm. Moreover, a cylindrical vacuum cavity was deployed on the SOG cap with the purpose to decrease the stresses generated during the silicon-to-glass contact during pressure measurements. The fabrication processes mainly contained photolithography, deep reactive ion etching (DRIE), chemical mechanical planarization (CMP) and anodic bonding. According to the characterization experiments, the quality factors of the resonators were higher than 15,000 with pressure sensitivities of 0.51 Hz/kPa (resonator I), −1.75 Hz/kPa (resonator II) and temperature coefficients of frequency of 1.92 Hz/°C (resonator I), 1.98 Hz/°C (resonator II). Following temperature compensation, the fitting error of the microsensor was within the range of 0.006% FS and the measurement accuracy was as high as 0.017% FS in the pressure range of 200 ~ 7000 kPa and the temperature range of −40 °C to 80 °C. [ABSTRACT FROM AUTHOR]

This study developed a MEMS-based electrochemical seismometer relying on a cathode–anode–cathode (CAC) integrated three-electrode structure where two cathodes were positioned on two surfaces of a silicon wafer, while one anode was positioned on the sidewalls of the through holes of the silicon wafer. Device design and numerical simulations were conducted to model the functionality of the three-electrode structure in detecting vibration signals with the key geometrical parameters optimized. The CAC integrated three-electrode structure was then manufactured by microfabrication, which demonstrated a simplified fabrication process in comparison with conventional four-electrode structures. Device characterization shows that the sensitivity of the CAC microseismometer was an order of magnitude higher than that of the CME6011 (a commercially available four-electrode electrochemical seismometer), while the noise level was comparable. Furthermore, in response to random vibrations, a high correlation coefficient between the CAC and the CME6011 (0.985) was located, validating the performance of the developed seismometer. Thus, the developed electrochemical microseismometer based on an integrated three-electrode structure may provide a new perspective in seismic observations and resource explorations. [ABSTRACT FROM AUTHOR]

This paper presents the analysis and characterization of a resonant pressure microsensor, which employs a temperature compensation method based on differential outputs and a temperature sensor. Leveraging a silicon-on-insulator (SOI) wafer, this microsensor mainly consists of a pressure-sensitive diagram and two resonant beams (electromagnetic driving and electromagnetic induction) to produce a differential output. The resonators were vacuum packaged with a silicon-on-glass (SOG) cap using anodic bonding and the wire interconnection was realized by sputtering an Au film on highly topographic surfaces using a hard mask. After the fabrication of the resonant pressure microsensor, systematic experiments demonstrated that the pressure sensitivity of the presented microsensor was about 0.33 kPa/Hz. Utilizing the differential frequency of the two resonators and the signal from a temperature sensor to replace the two-frequency signals by polynomial fitting, the temperature compensation method based on differential outputs aims to increase the surface fitting accuracy of these microsensors which have turnover points. Employing the proposed compensation approach in this study, the errors were less than 0.02% FS of the full pressure scale (a temperature range of −40 to 85 °C and a pressure range of 200 kPa to 2000 kPa). [ABSTRACT FROM AUTHOR]

(1) Background: Deep brain stimulation (DBS) is considered as an efficient treatment method for alleviating motor symptoms in Parkinson's disease (PD), while different stimulation frequency effects on the specific neuron patterns at the cellular level remain unknown. (2) Methods: In this work, nanocomposites-modified implantable microelectrode arrays (MEAs) were fabricated to synchronously record changes of dopamine (DA) concentration and striatal neuron firing in the striatum during subthalamic nucleus DBS, and different responses of medium spiny projecting neurons (MSNs) and fast spiking interneurons (FSIs) to DBS were analyzed. (3) Results: DA concentration and striatal neuron spike firing rate showed a similar change as DBS frequency changed from 10 to 350 Hz. Note that the increases in DA concentration (3.11 ± 0.67 μM) and neural spike firing rate (15.24 ± 2.71 Hz) were maximal after the stimulation at 100 Hz. The MSNs firing response to DBS was significant, especially at 100 Hz, while the FSIs remained stable after various stimulations. (4) Conclusions: DBS shows the greatest regulatory effect on DA concentration and MSNs firing rate at 100 Hz stimulation. This implantable MEA in the recording of the neurotransmitter and neural spike pattern response to DBS provides a new insight to understand the mechanism of PD at the cellular level. [ABSTRACT FROM AUTHOR]

Proteins play a significant role in the key activities of cells. Single-cell protein analysis provides crucial insights in studying cellular heterogeneities. However, the low abundance and enormous complexity of the proteome posit challenges in analyzing protein expressions at the single-cell level. This review summarizes recent advances of various approaches to single-cell protein analysis. We begin by discussing conventional characterization approaches, including fluorescence flow cytometry, mass cytometry, enzyme-linked immunospot assay, and capillary electrophoresis. We then detail the landmark advances of microfluidic approaches for analyzing single-cell protein expressions, including microfluidic fluorescent flow cytometry, droplet-based microfluidics, microwell-based assay (microengraving), microchamber-based assay (barcoding microchips), and single-cell Western blotting, among which the advantages and limitations are compared. Looking forward, we discuss future research opportunities and challenges for multiplexity, analyte, throughput, and sensitivity of the microfluidic approaches, which we believe will prompt the research of single-cell proteins such as the molecular mechanism of cell biology, as well as the clinical applications for tumor treatment and drug development. [ABSTRACT FROM AUTHOR]

As key bioelectrical markers, equivalent capacitance (Cne, i.e., capacitance per unit area) and resistance (Rne, i.e., resistivity multiply thickness) of nuclear envelopes have emerged as promising electrical indicators, which cannot be effectively measured by conventional approaches. In this study, single nuclei were isolated from whole cells and trapped at the entrances of microfluidic constriction channels, and then corresponding impedance profiles were sampled and translated into single-nucleus Cne and Rne based on a home-developed equivalent electrical model. Cne and Rne of A549 nuclei were first quantified as 3.43 ± 1.81 μF/cm2 and 2.03 ± 1.40 Ω·cm2 (Nn = 35), which were shown not to be affected by variations of key parameters in nuclear isolation and measurement. The developed approach in this study was also used to measure a second type of nuclei, producing Cne and Rne of 3.75 ± 3.17 μF/cm2 and 1.01 ± 0.70 Ω·cm2 for SW620 (Nn = 17). This study may provide a new perspective in single-cell electrical characterization, enabling cell type classification and cell status evaluation based on bioelectrical markers of nuclei. [ABSTRACT FROM AUTHOR]

This paper presents microelectromechanical system (MEMS)-based electrochemical seismometers with two pairs of electrodes integrated on one chip. Both theoretical analysis and numerical simulations were conducted to reveal the working principle of the proposed electrochemical seismometers, finding that flow holes distributed on cathodes rather than anodes can produce significantly higher sensitivities. The proposed electrochemical seismometers were fabricated based on conventional micromachined processes with high fabrication repeatability. Sensitivity measurements of the proposed seismometers and their commercial counterpart of CME6011 were conducted, indicating the sensitivities of the proposed seismometer with flow holes on cathodes were two orders higher than the counterpart with flow holes on anodes and one order higher than CME6011 at dominant frequencies. Measurements of random ground motions based on the proposed seismometer with flow holes on cathodes and CME6011 were conducted, producing comparable noise levels without observable ground motions and high correlations in response to random events of ground motions. These results validated the functionality of the proposed electrochemical seismometers, which may contribute to seismic monitoring in the near future. [ABSTRACT FROM AUTHOR]

This paper presents a temperature-insensitive resonant pressure sensor, which is mainly composed of a silicon-on-insulator (SOI) wafer for pressure measurements and a silicon-on-glass (SOG) cap for vacuum packaging. The variations of pressure under measurement bend the pressure sensitive diaphragm and regulate the intrinsic frequencies of the resonators in the device layer. While, variations of temperature cannot significantly change the intrinsic frequencies of the resonators, due to the SOG cap to offset generated thermal stress. Numerical simulations, based on finite element analysis, were conducted to calculate the residual thermal stress and optimize the sensing structures. Experimental results show that the Q-factors of the resonators are higher than 16,000, with a differential pressure sensitivity of 11.89 Hz/kPa, a nonlinearity of 0.01% F.S and a low fitting error of 0.01% F.S with the pressure varying from 100 kPa to 1000 kPa. In particular, a temperature sensitivity of ~1 Hz/°C was obtained in the range of −45 °C to 65 °C, which is one order of magnitude lower than the previously reported counterparts. [ABSTRACT FROM AUTHOR]

This paper presents resonant pressure micro sensors based on dual double ended tuning fork (DETF) resonators, which are electrostatically excited and piezoresistively detected. In operation, the barometric pressure under measurement bends the pressure sensitive diaphragm functioning as the anchor of DETF resonators and therefore produces eigenfrequency shifts of the resonators. Theoretical analyses and finite element analyses (FEA) were conducted to optimize the key geometries of the DETF resonators with enhanced signal to noise ratios (SNRs). In fabrications, key steps including deep reactive ion etching (DRIE) and anodic bonding were used, where sleeve holes were adopted to form electrical connections, leading to high-efficiency structure layout. Experimental results indicate that the presented micro sensors produced SNRs of 63.70 ± 3.46 dB in the open-loop characterizations and differential sensitivities of 101.3 ± 1.2 Hz/kPa, in the closed-loop characterizations. In addition, pressure cycling tests with a pressure range of 5 to 155 kPa were conducted, revealing that the developed micro sensors demonstrated pressure shifts of 83 ± 2 ppm, pressure hysteresis of 67 ± 3 ppm, and repeatability errors of 39 ± 2 ppm. Thus, the developed resonant pressure micro sensors may potentially function as an enabling tool for barometric pressure measurements. [ABSTRACT FROM AUTHOR]

This study proposes a microfabricated resonant pressure sensor in which a pair of double-ended tuning forks were utilized as resonators where comb electrodes and single-crystal silicon-based piezoresistors were used for electrostatic excitation and piezoresistive detection, respectively. In operations, pressures under measurements deform the pressure-sensitive diaphragm to cause stress variations of two resonators distributed on the central and side positions of the pressure-sensitive diaphragm, where the corresponding changes of the intrinsic resonant frequencies are then captured piezoresistively. The developed resonant pressure sensors were fabricated based on MEMS with open-loop and closed-loop characterizations conducted. Key sensing parameters including quality factors, differential pressure/temperature sensitivities and fitting errors were quantified as higher than 17,000, 48.24 Hz/kPa, 0.15 Hz/°C and better than 0.01% F.S. (140 kpa), respectively. In comparison to previously reported resonant pressure sensors driven by parallel-plate electrodes, the developed sensor in this study is featured with a lower temperature sensitivity and a higher stability. [ABSTRACT FROM AUTHOR]

This paper presents a resonant pressure microsensor with the measurement range of 1 MPa suitable for the soaring demands of industrial gas pressure calibration equipment. The proposed microsensor consists of an SOI layer as a sensing element and a glass cap for vacuum packaging. The sensing elements include a pressure-sensitive diaphragm and two resonators embedded in the diaphragm by anchor structures. The resonators are excited by a convenient Lorentz force and detected by electromagnetic induction, which can maintain high signal outputs. In operation, the pressure under measurement bends the pressure-sensitive diaphragm of the microsensor, producing frequency shifts of the two underlining resonators. The microsensor structures were designed and optimized using finite element analyses and a 4" SOI wafer was employed in fabrications, which requires only one photolithographic step. Experimental results indicate that the Q-factors of the resonators are higher than 25,000 with a differential temperature sensitivity of 0.22 Hz/°C, pressure sensitivities of 6.6 Hz/kPa, and −6.5 Hz/kPa, which match the simulation results of differential temperature sensitivity of 0.2 Hz/°C and pressure sensitivities of ±6.5 Hz/kPa. In addition, characterizations based on a closed-loop manner indicate that the presented sensor demonstrates low fitting errors within 0.01% FS, high accuracy of 0.01% FS in the pressure range of 20 kPa to 1 MPa and temperature range of −55 to 85 °C, and the long-term stability within 0.01% FS in a 156-day period under the room temperature. [ABSTRACT FROM AUTHOR]

This paper presents a microfluidic instrument capable of quantifying single-cell specific intracellular proteins, which are composed of three functioning modules and two software platforms. Under the control of a LabVIEW platform, a pressure module flushed cells stained with fluorescent antibodies through a microfluidic module with fluorescent intensities quantified by a fluorescent module and translated into the numbers of specific intracellular proteins at the single-cell level using a MATLAB platform. Detection ranges and resolutions of the analyzer were characterized as 896.78–6.78 × 105 and 334.60 nM for Alexa 488, 314.60–2.11 × 105 and 153.98 nM for FITC, and 77.03–5.24 × 104 and 37.17 nM for FITC-labelled anti-beta-actin antibodies. As a demonstration, the numbers of single-cell beta-actins of two paired oral tumor cell types and two oral patient samples were quantified as: 1.12 ± 0.77 × 106/cell (salivary adenoid cystic carcinoma parental cell line (SACC-83), ncell = 13,689) vs. 0.90 ± 0.58 × 105/cell (salivary adenoid cystic carcinoma lung metastasis cell line (SACC-LM), ncell = 15,341); 0.89 ± 0.69 × 106/cell (oral carcinoma cell line (CAL 27), ncell = 7357) vs. 0.93 ± 0.69 × 106/cell (oral carcinoma lymphatic metastasis cell line (CAL 27-LN2), ncell = 6276); and 0.86 ± 0.52 × 106/cell (patient I) vs. 0.85 ± 0.58 × 106/cell (patient II). These results (1) validated the developed analyzer with a throughput of 10 cells/s and a processing capability of ~10,000 cells for each cell type, and (2) revealed that as an internal control in cell analysis, the expressions of beta-actins remained stable in oral tumors with different malignant levels. [ABSTRACT FROM AUTHOR]

This paper presents a resonant pressure microsensor relying on electrostatic excitation and piezoresistive detection where two double-ended tuning forks were used as resonators, enabling differential outputs. Pressure under measurement caused the deformation of the pressure sensitive membrane, leading to stress buildup of the resonator under electrostatic excitation with a corresponding shift of the resonant frequency detected piezoresistively. The proposed microsensor was fabricated by simplified SOI-MEMS technologies and characterized by both open-loop and closed-loop circuits, producing a quality factor higher than 10,000, a sensitivity of 79.44 Hz/kPa and an accuracy rate of over 0.01% F.S. In comparison to the previously reported resonant piezoresistive sensors, the proposed device used single-crystal silicon as piezoresistors, which was featured with low DC biased voltages, simple sensing structures and fabrication steps. In addition, the two double-ended tuning forks were used as resonators, producing high quality factors and differential outputs, which further improved the sensor performances. [ABSTRACT FROM AUTHOR]

Semi-quantitative studies have located varied expressions of β-actin proteins at the population level, questioning their roles as internal controls in western blots, while the absolute copy numbers of β-actins at the single-cell level are missing. In this study, a polymeric microfluidic flow cytometry was used for single-cell analysis, and the absolute copy numbers of single-cell β-actin proteins were quantified as 9.9 ± 4.6 × 105, 6.8 ± 4.0 × 105 and 11.0 ± 5.5 × 105 per cell for A549 (ncell = 14,754), Hep G2 (ncell = 36,949), and HeLa (ncell = 24,383), respectively. High coefficients of variation (~50%) and high quartile coefficients of dispersion (~30%) were located, indicating significant variations of β-actin proteins within the same cell type. Low p values (≪0.01) and high classification rates based on neural network (~70%) were quantified among A549, Hep G2 and HeLa cells, suggesting expression differences of β-actin proteins among three cell types. In summary, the results reported here indicate significant variations of β-actin proteins within the same cell type from cell to cell, and significant expression differences of β-actin proteins among different cell types, strongly questioning the properties of using β-actin proteins as internal controls in western blots. [ABSTRACT FROM AUTHOR]

This paper presents an electrochemical seismic sensor in which paraylene was used as a substrate and insulating layer of micro-fabricated electrodes, enabling the detection of seismic signals with enhanced sensitivities in comparison to silicon-based counterparts. Based on microfabrication, paralene-based electrochemical seismic sensors were fabricated in which the thickness of the insulating spacer was 6.7 μm. Compared to silicon-based counterparts with ~100 μm insulating layers, the parylene-based devices produced higher sensitivities of 490.3 ± 6.1 V/(m/s) vs. 192.2 ± 1.9 V/(m/s) at 0.1 Hz, 4764.4 ± 18 V/(m/s) vs. 318.9 ± 6.5 V/(m/s) at 1 Hz, and 4128.1 ± 38.3 V/(m/s) vs. 254.5 ± 4.2 V/(m/s) at 10 Hz. In addition, the outputs of the parylene vs. silicon devices in response to two transit inputs were compared, producing peak responses of 2.97 V vs. 0.22 V and 2.41 V vs. 0.19 V, respectively. Furthermore, the self-noises of parylene vs. silicon-based devices were compared as follows: -82.3 ± 3.9 dB vs. -90.4 ± 9.4 dB at 0.1 Hz, -75.7 ± 7.3 dB vs. -98.2 ± 9.9 dB at 1 Hz, and -62.4 ± 7.7 dB vs. -91.1 ± 8.1 dB at 10 Hz. The developed parylene-based electrochemical seismic sensors may function as an enabling technique for further detection of seismic motions in various applications., Competing Interests: The authors declare no conflict of interest.

A monolithic electrochemical micro seismic sensor capable of monitoring three-axial vibrations was proposed in this paper. The proposed micro sensor mainly consisted of four sensing units interconnected within flow channels and by interpreting the voltage outputs of the sensing units, vibrations with arbitrary directions can be quantified. The proposed seismic sensors are fabricated based on MEMS technologies and characterized, which produced sensitivities along x , y , and z axes as 2473.2 ± 184.5 V/(m/s), 2261.7 ± 119.6 V/(m/s), and 3480.7 ± 417.2 V/(m/s) at 30 Hz. In addition, the vibrations in x - y , x - z , and y - z planes were applied to the developed seismic sensors, leading to comparable monitoring results after decoupling calculations with the input velocities. Furthermore, the results have shown its feasibilities for seismic data recording., Competing Interests: The authors declare no conflict of interest.

Electrochemical seismic sensors are key components in monitoring ground vibration, which are featured with high performances in the low-frequency domain. However, conventional electrochemical seismic sensors suffer from low repeatability due to limitations in fabrication and limited bandwidth. This paper presents a micro-fabricated electrochemical seismic sensor with a force-balanced negative feedback system, mainly composed of a sensing unit including porous sensing micro electrodes immersed in an electrolyte solution and a feedback unit including a feedback circuit and a feedback magnet. In this study, devices were designed, fabricated, and characterized, producing comparable performances among individual devices. In addition, bandwidths and total harmonic distortions of the proposed devices with and without a negative feedback system were quantified and compared as 0.005-20 (feedback) Hz vs. 0.3-7 Hz (without feedback), 4.34 ± 0.38% (without feedback) vs. 1.81 ± 0.31% (feedback)@1 Hz@1 mm/s and 3.21 ± 0.25% (without feedback) vs. 1.13 ± 0.19% (feedback)@5 Hz@1 mm/s (n device = 6, n represents the number of the tested devices), respectively. In addition, the performances of the proposed MEMS electrochemical seismometers with feedback were compared to a commercial electrochemical seismic sensor (CME 6011), producing higher bandwidth (0.005-20 Hz vs. 0.016-30 Hz) and lower self-noise levels (-165.1 ± 6.1 dB vs. -137.7 dB at 0.1 Hz, -151.9 ± 7.5 dB vs. -117.8 dB at 0.02 Hz (n device = 6)) in the low-frequency domain. Thus, the proposed device may function as an enabling electrochemical seismometer in the fields requesting seismic monitoring at the ultra-low frequency domain.

This paper presents the instrumentation of a microfluidic analyzer enabling the characterization of single-cell biophysical properties, which includes seven key components: a microfluidic module, a pressure module, an imaging module, an impedance module, two LabVIEW platforms for instrument operation and raw data processing, respectively, and a Python code for data translation. Under the control of the LabVIEW platform for instrument operation, the pressure module flushes single cells into the microfluidic module with raw biophysical parameters sampled by the imaging and impedance modules and processed by the LabVIEW platform for raw data processing, which were further translated into intrinsic cellular biophysical parameters using the code developed in Python. Based on this system, specific membrane capacitance, cytoplasm conductivity, and instantaneous Young's modulus of three cell types were quantified as 2.76 ± 0.57 μF/cm², 1.00 ± 0.14 S/m, and 3.79 ± 1.11 kPa for A549 cells ( n cell = 202); 1.88 ± 0.31 μF/cm², 1.05 ± 0.16 S/m, and 3.74 ± 0.75 kPa for 95D cells ( n cell = 257); 2.11 ± 0.38 μF/cm², 0.87 ± 0.11 S/m, and 5.39 ± 0.89 kPa for H460 cells ( n cell = 246). As a semi-automatic instrument with a throughput of roughly 1 cell per second, this prototype instrument can be potentially used for the characterization of cellular biophysical properties., Competing Interests: The authors declare no conflict of interest.

This article reviews recent developments in droplet microfluidics enabling high-throughput single-cell analysis. Five key aspects in this field are included in this review: (1) prototype demonstration of single-cell encapsulation in microfluidic droplets; (2) technical improvements of single-cell encapsulation in microfluidic droplets; (3) microfluidic droplets enabling single-cell proteomic analysis; (4) microfluidic droplets enabling single-cell genomic analysis; and (5) integrated microfluidic droplet systems enabling single-cell screening. We examine the advantages and limitations of each technique and discuss future research opportunities by focusing on key performances of throughput, multifunctionality, and absolute quantification.

This article reviews recent developments in microfluidic systems enabling high-throughput characterization of single-cell proteins. Four key perspectives of microfluidic platforms are included in this review: (1) microfluidic fluorescent flow cytometry; (2) droplet based microfluidic flow cytometry; (3) large-array micro wells (microengraving); and (4) large-array micro chambers (barcode microchips). We examine the advantages and limitations of each technique and discuss future research opportunities by focusing on three key performance parameters (absolute quantification, sensitivity, and throughput).

This paper presents the fabrication and characterization of a resonant pressure microsensor based on SOI-glass wafer-level vacuum packaging. The SOI-based pressure microsensor consists of a pressure-sensitive diaphragm at the handle layer and two lateral resonators (electrostatic excitation and capacitive detection) on the device layer as a differential setup. The resonators were vacuum packaged with a glass cap using anodic bonding and the wire interconnection was realized using a mask-free electrochemical etching approach by selectively patterning an Au film on highly topographic surfaces. The fabricated resonant pressure microsensor with dual resonators was characterized in a systematic manner, producing a quality factor higher than 10,000 (~6 months), a sensitivity of about 166 Hz/kPa and a reduced nonlinear error of 0.033% F.S. Based on the differential output, the sensitivity was increased to two times and the temperature-caused frequency drift was decreased to 25%.

Resonant pressure microsensors are widely used in the fields of aerospace exploration and atmospheric pressure monitoring due to their advantages of quasi-digital output and long-term stability, which, however, requires the use of additional temperature sensors for temperature compensation. This paper presents a resonant pressure microsensor capable of self-temperature compensation without the need for additional temperature sensors. Two doubly-clamped "H" type resonant beams were arranged on the pressure diaphragm, which functions as a differential output in response to pressure changes. Based on calibration of a group of intrinsic resonant frequencies at different pressure and temperature values, the functions with inputs of two resonant frequencies and outputs of temperature and pressure under measurement were obtained and thus the disturbance of temperature variations on resonant frequency shifts was properly addressed. Before compensation, the maximal errors of the measured pressure values were over 1.5% while after compensation, the errors were less than 0.01% of the full pressure scale (temperature range of -40 °C to 70 °C and pressure range of 50 kPa to 110 kPa).

This article reviews recent developments in microfluidic impedance flow cytometry for high-throughput electrical property characterization of single cells. Four major perspectives of microfluidic impedance flow cytometry for single-cell characterization are included in this review: (1) early developments of microfluidic impedance flow cytometry for single-cell electrical property characterization; (2) microfluidic impedance flow cytometry with enhanced sensitivity; (3) microfluidic impedance and optical flow cytometry for single-cell analysis and (4) integrated point of care system based on microfluidic impedance flow cytometry. We examine the advantages and limitations of each technique and discuss future research opportunities from the perspectives of both technical innovation and clinical applications.

This paper presents a microfluidics-based approach capable of continuously characterizing instantaneous Young's modulus (E(instantaneous)) and specific membrane capacitance (C(specific membrane)) of suspended single cells. In this method, cells were aspirated through a constriction channel while the cellular entry process into the constriction channel was recorded using a high speed camera and the impedance profiles at two frequencies (1 kHz and 100 kHz) were simultaneously measured by a lock-in amplifier. Numerical simulations were conducted to model cellular entry process into the constriction channel, focusing on two key parameters: instantaneous aspiration length (L(instantaneous)) and transitional aspiration length (L(transitional)), which was further translated to E(instantaneous). An equivalent distribution circuit model for a cell travelling in the constriction channel was used to determine C(specific membrane). A non-small-cell lung cancer cell line 95C (n = 354) was used to evaluate this technique, producing E(instantaneous) of 2.96 ± 0.40 kPa and Cspecific membrane of 1.59 ± 0.28 μF/cm2. As a platform for continuous and simultaneous characterization of cellular E(instantaneous) and C(specific membrane), this approach can facilitate a more comprehensive understanding of cellular biophysical properties.

This paper presents a high-Q resonant pressure microsensor with through-glass electrical interconnections based on wafer-level MEMS vacuum packaging. An approach to maintaining high-vacuum conditions by integrating the MEMS fabrication process with getter material preparation is presented in this paper. In this device, the pressure under measurement causes a deflection of a pressure-sensitive silicon square diaphragm, which is further translated to stress build up in "H" type doubly-clamped micro resonant beams, leading to a resonance frequency shift. The device geometries were optimized using FEM simulation and a 4-inch SOI wafer was used for device fabrication, which required only three photolithographic steps. In the device fabrication, a non-evaporable metal thin film as the getter material was sputtered on a Pyrex 7740 glass wafer, which was then anodically bonded to the patterned SOI wafer for vacuum packaging. Through-glass via holes predefined in the glass wafer functioned as the electrical interconnections between the patterned SOI wafer and the surrounding electrical components. Experimental results recorded that the Q-factor of the resonant beam was beyond 22,000, with a differential sensitivity of 89.86 Hz/kPa, a device resolution of 10 Pa and a nonlinearity of 0.02% F.S with the pressure varying from 50 kPa to 100 kPa. In addition, the temperature drift coefficient was less than -0.01% F.S/°C in the range of -40 °C to 70 °C, the long-term stability error was quantified as 0.01% F.S over a 5-month period and the accuracy of the microsensor was better than 0.01% F.S.

A resonant microbeam accelerometer of a novel highly symmetric structure based on MEMS bulk-silicon technology is proposed and some numerical modeling results for this scheme are presented. The accelerometer consists of two proof masses, four supporting hinges, two anchors, and a vibrating triple beam, which is clamped at both ends to the two proof masses. LPCVD silicon rich nitride is chosen as the resonant triple beam material, and parameter optimization of the triple-beam structure has been performed. The triple beam is excited and sensed electromagnetically by film electrodes located on the upper surface of the beam. Both simulation and experimental results show that the novel structure increases the scale factor of the resonant accelerometer, and ameliorates other performance issues such as cross axis sensitivity of insensitive input acceleration, etc.