Deep brain implantable microelectrode arrays for detection and functional localization of the subthalamic nucleus in rats with Parkinson’s disease

The subthalamic nucleus(STN)is considered the best target for deep brain stimulation treatments of Parkinson’s disease(PD).It is difficult to localize the STN due to its small size and deep location.Multichannel microelectrode arrays(MEAs)can rapidly and precisely locate the STN,which is important for precise stimulation.In this paper,16-channel MEAs modified with multiwalled carbon nanotube/poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate)(MWCNT/PEDOT:PSS)nanocomposites were designed and fabricated,and the accurate and rapid identification of the STN in PD rats was performed using detection sites distributed at different brain depths.These results showed that nuclei in 6-hydroxydopamine hydrobromide(6-OHDA)-lesioned brains discharged more intensely than those in unlesioned brains.In addition,the MEA simultaneously acquired neural signals from both the STN and the upper or lower boundary nuclei of the STN.Moreover,higher values of spike firing rate,spike amplitude,local field potential(LFP)power,and beta oscillations were detected in the STN of the 6-OHDA-lesioned brain,and may therefore be biomarkers of STN localization.Compared with the STNs of unlesioned brains,the power spectral density of spikes and LFPs synchronously decreased in the delta band and increased in the beta band of 6-OHDA-lesioned brains.This may be a cause of sleep and motor disorders associated with PD.Overall,this work describes a new cellular-level localization and detection method and provides a tool for future studies of deep brain nuclei.

Simulation and fabrication of in vitro microfluidic microelectrode array chip for patterned culture and electrophysiological detection of neurons

To enable the detection and modulation of modularized neural networks in vitro,this study proposes a microfluidic microelectrode array chip for the cultivation,compartmentalization,and control of neural cells.The chip was designed based on the specific structure of neurons and the requirements for detection and modulation.Finite-element analysis of the chip’s flow field was conducted using the COMSOL Multiphysics software,and the simulation results show that the liquid within the chip can flow smoothly,ensuring stable flow fields that facilitate the uniform growth of neurons within the microfluidic channels.By employing MEMS technology in combination with nanomaterial modification techniques,the microfluidic microelectrode array chip was fabricated successfully.Primary hippocampal neurons were cultured on the chip,forming a well-defined neural network.Spontaneous electrical activity of the detected neurons was recorded,exhibiting a 23.7%increase in amplitude compared to neuronal discharges detected on an open-field microelectrode array.This study provides a platform for the precise detection and modulation of patterned neuronal growth in vitro,potentially serving as a novel tool in neuroscience research.

Point-of-Care Testing Using Three Dimensional Optical Biosensor Based on Microfluidic Technology

We have presented a three dimensional optical protein chip that fulfills the demanding for point-of-care diagnostics in terms of ease-of-use (one step assay), miniaturization (5 μl). The artful combination of magnetic nanoparticles on chip and total internal reflection imaging (TIRI) technology permits the sensitive and rapid detection of hs-CRP (high-sensitivity C-reactive protein). The whole test was complete within 10 min using “all in one step” assay with a limit of detection of 0.1 ng/mL hs-CRP. The measuring range for hs-CRP could be extended to 10 ng/mL. The chip can also be used to detect more parameters in blood samples.

Exploration and mitigation of protrusion behavior in Ga-ion doped h-BN memristors

Using hexagonal boron nitride(h-BN)to prepare resistive switching devices is a promising strategy.Various doping methods have aroused great interest in the semiconductor field in recent years,but many researchers have overlooked the various repetitive anomalies that occur during the testing process.In this study,the basic electrical properties and additive protrusion behavior of Ga-ion-doped h-BN memristors at micro–nanoscale during the voltage scanning process are investigated via atomic force microscopy(AFM)and energy dispersive spectroscopy.The additive protrusion behavior is subjected to exploratory research,and it is concluded that it is caused by anodic oxidation.An approach is proposed that involves filling the AFM chamber with nitrogen gas to improve the stability of memristor testing,and this method provides a solution for enhanced testing stability of memristors.

Identification and quantification of the bioactive components in Osmanthus fragrans roots by HPLC-MS/MS

The roots of O. fragrans are also a valuable resource in addition to its flowers and fruits. In this study, the HPLC-MS/MS method used for analyzing the chemical constituents in O. fragrans roots extract was developed, which showed high sensitivity for both qualitative and quantitative analyses. Thirty-two compounds were first discovered in O. fragrans roots, one compound of which was reported for the first time. The simultaneous determination method for acteoside, isoacteoside, oleuropein and phillyrin was validated to be sensitive and accurate. Then it was applied to determine the content of bioactive components in O. fragrans roots from different cultivars. The content of oleuropein and phillyrin in the twelve batches was relatively stable, while the content of acteoside and isoacteoside varied greatly.Moreover, the therapeutic material basis and mechanism of O. fragrans roots exerting its traditional pharmacodynamics were analyzed by network pharmacology. The results showed that O. fragrans roots might be effective for the treatment of inflammation, cardiovascular diseases, cancer, and rheumatoid arthritis, which is consistent with the traditional pharmacodynamics of O. fragrans roots. This work can provide an analytical method for the comprehensive development of O. fragrans roots.

Determination of bioactive components in the fruits of Cercis chinensis Bunge by HPLC-MS/MS and quality evaluation by principal components and hierarchical cluster analyses

The fruits of leguminous plants Cercis Chinensis Bunge are still overlooked although they have been reported to be antioxidative because of the limited information on the phytochemicals of C.chinensis fruits.A simple,rapid and sensitive HPLC-MS/MS method was developed for the identification and quantitation of the major bioactive components in C.chinensis fruits.Eighteen polyphenols were identified,which are first reported in C.chinensis fruits.Moreover,ten components were simultaneously quantified.The validated quantitative method was proved to be sensitive,reproducible and accurate.Then,it was applied to analyze batches of C.chinensis fruits from different phytomorph and areas.The principal components analysis(PCA)realized visualization and reduction of data set dimension while the hierarchical cluster analysis(HCA)indicated that the content of phenolic acids or all ten components might be used to differentiate C.chinensis fruits of different phytomorph.

Screening for a new Streptomyces strain capable of efficient keratin degradation

Keratinous wastes could be degraded by some microorganisms in nature. Native human foot skin （NHFS） was used as sole nitrogen source to screen microorganisms with keratin-degrading capability. From approximately 200 strains, a strain of Streptomyces sp. strain No. 16 was found to possess the strongest keratinolytic activity, and the total activity in the culture was 110 KU/ml with specific activity of 2870 KU/mg protein （KU： keratinase unit）. Substrate specificity test indicated that the crude keratinase could degrade keratin azure, human hair, cock feathers and collagen. The optimal pH of the crude keratinase ranged from 7.5 to 10 and the temperature ranged from 40℃ to 55℃. Metal chelating agent ethylenediamine tetraacetic acid obviously stimulated the keratinolytic activity but suppressed the proteolytic activity. To our knowledge, this is the first report on specific induction of keratinases by NHFS from an actinomycete. Moreover, excellent characteristics of its crude keratinase may lead to the potential application in waste treatment and recovery, poultry and leather industry, medicine, and cosmetic development.

Integrated physics package of a chip-scale atomic clock

The physics package of a chip-scale atomic clock （CSAC） has been successfully realized by integrating vertical cavity surface emitting laser （VCSEL）, neutral density （ND） filter, λ/4 wave plate, 87Rb vapor cell, photodiode （PD）, and magnetic coil into a cuboid metal package with a volume of about 2.8 cm3. In this physics package, the critical component, 87Rb vapor cell, is batch-fabricated based on MEMS technology and in-situ chemical reaction method. Pt heater and thermistors are integrated in the physics package. A PTFE pillar is used to support the optical elements in the physics package, in order to reduce the power dissipation. The optical absorption spectrum of 87Rb D1 line and the microwave frequency correction signal are successfully observed while connecting the package with the servo circuit system. Using the above mentioned packaging solution, a CSAC with short-term frequency stability of about 7 × 10^-10τ-1/2 has been successfully achieved, which demonstrates that this physics package would become one promising solution for the CSAC.

Machine Learning Approach to Enhance the Performance of MNP?Labeled Lateral Flow Immunoassay

The use of magnetic nanoparticle(MNP)-labeled immunochromatography test strips(ICTSs) is very important for point-ofcare testing(POCT). However, common diagnostic methods cannot accurately analyze the weak magnetic signal from ICTSs, limiting the applications of POCT. In this study, an ultrasensitive multiplex biosensor was designed to overcome the limitations of capturing and normalization of the weak magnetic signal from MNPs on ICTSs. A machine learning model for sandwich assays was constructed and used to classify weakly positive and negative samples, which significantly enhanced the specificity and sensitivity. The potential clinical application was evaluated by detecting 50 human chorionic gonadotropin(HCG) samples and 59 myocardial infarction serum samples. The quantitative range for HCG was 1–1000 mIU mL^(-1) and the ideal detection limit was 0.014 mIU mL^(-1), which was well below the clinical threshold. Quantitative detection results of multiplex cardiac markers showed good linear correlations with standard values. The proposed multiplex assay can be readily adapted for identifying other biomolecules and also be used in other applications such as environmental monitoring, food analysis, and national security.

Recent Advances in Directed Assembly of Nanowires or Nanotubes

Nanowires and nanotubes of diverse material compositions,properties and/or functions have been produced or fabricated through various bottom-up or top-down approaches.These nanowires or nanotubes have also been utilized as potential building blocks for functional nanodevices.The key for the integration of those nanowire or nanotube based devices is to assemble these one dimensional nanomaterials to specific locations using techniques that are highly controllable and scalable.Ideally such techniques should enable assembly of highly uniform nanowire/nanotube arrays with precise control of density,location,dimension or even material types of nanowires/nanotubes.Numerous assembly techniques are being developed that can quickly align and assemble large quantities of one type or multiple types of nanowires through parallel processes,including flow-assisted alignment,Langmuir-Blodgett assembly,bubble-blown technique,electric/magnetic-field directed assembly,contact/roll printing,knocking-down,etc..With these assembling techniques,applications of nanowire/nanotube based devices such as flexible electronics and sensors have been demonstrated.This paper delivers an overall review of directed nanowire/nanotube assembling approaches and analyzes advantages and limitations of each method.The future research directions have also been discussed.

Rapid Isolation and Multiplexed Detection of Exosome Tumor Markers Via Queued Beads Combined with Quantum Dots in a Microarray

Tumor-derived exosomes are actively involved in cancer progression and metastasis and have emerged as a promising marker for cancer diagnosis in liquid biopsy.Because of their nanoscale size,complex biogenesis,and methodological limitations related to exosome isolation and detection,advancements in their analysis remain slow.Microfluidic technology offers a better analytic approach compared with conventional methods.Here,we developed a bead-based microarray for exosome isolation and multiplexed tumor marker detection.Using this method,exosomes are isolated by binding to antibodies on the bead surface,and tumor markers on the exosomes are detected through quantum dot(QD)probes.The beads are then uniformly trapped and queued among micropillars in the chip.This design benefits fluorescence observation by dispersing the signals into every single bead,thereby avoiding optical interference and enabling more accurate test results.We analyzed exosomes in the cell culture supernatant of lung cancer and endothelial cell lines,and different lung cancer markers labeled with three QD probes were used to conduct multiplexed detection of exosome surface protein markers.Lung cancer-derived samples showed much higher(~sixfold-tenfold)fluorescence intensity than endothelial cell samples,and different types of lung cancer samples showed distinctive marker expression levels.Additionally,using the chip to detect clinical plasma samples from cancer patients showed good diagnostic power and revealed a well consistency with conventional tests for serological markers.These results provide insight into a promising method for exosome tumor marker detection and early-stage cancer diagnosis.

Study on the spectral response of the Schottky photodetector of GaN

The Schottky photodetector was fabricated on GaN epilayers grown by metalorganic chemical vapour deposition （MOCVD）. The spectral response of the Schottky photodetector was characterized. A new model is proposed to interpret the characteristic of the spectral response curve of the Schottky photodetectors by introducing a penetrating distance of an incident light at a certain wavelength in the current continuity equation and the interface recombination at the metal-semiconductor rectifying contact. The expressions for the spectral response of the Schottky photodetector are deduced and used successfully to fit the experimental data.

Precision integration of grating-based polarizers onto focal plane arrays of near-infrared photovoltaic detectors for enhanced contrast polarimetric imaging

Polarimetric imaging enhances the ability to distinguish objects from a bright background by detecting their particular polarization status,which offers another degree of freedom in infrared remote sensing.However,to scale up by monolithically integrating grating-based polarizers onto a focal plane array(FPA)of infrared detectors,fundamental technical obstacles must be overcome,including reductions of the extinction ratio by the misalignment between the polarizer and the detector,grating line width fluctuations,the line edge roughness,etc.This paper reports the authors’latest achievements in overcoming those problems by solving key technical issues regarding the integration of large-scale polarizers onto the chips of FPAs with individual indium gallium arsenide/indium phosphide(In Ga As/In P)sensors as the basic building blocks.Polarimetric and photovoltaic chips with divisions of the focal plane of 540×4 pixels and 320×256 superpixels have been successfully manufactured.Polarimetric imaging with enhanced contrast has been demonstrated.The progress made in this work has opened up a broad avenue toward industrialization of high quality polarimetric imaging in infrared wavelengths.

Novel Graphene Biosensor Based on the Functionalization of Multifunctional Nano-bovine Serum Albumin for the Highly Sensitive Detection of Cancer Biomarkers

A simple,convenient,and highly sensitive bio-interface for graphene field-effect transistors(GFETs) based on multifunctional nano-denatured bovine serum albumin(nano-dBSA) functionalization was developed to target cancer bio-markers.The novel graphene–protein bioelectronic interface was constructed by heating to denature native BSA on the graphene substrate surface.The formed nano-d BSA film served as the cross-linker to immobilize monoclonal antibody against car-cinoembryonic antigen(anti-CEA mAb) on the graphene channel activated by EDC and Sulfo-NHS.The nano-dBSA film worked as a self-protecting layer of graphene to prevent surface contamination by lithographic processing.The improved GFETbiosensor exhibited good specificity and high sensitivity toward the target at an ultralow concentration of 337.58 fg mL-1.The electrical detection of the binding of CEA followed the Hill model for ligand–receptor interaction,indicating the negative binding cooperativity between CEA and anti-CEA mAb with a dissociation constant of 6.82×10-10M.The multifunctional nano-dBSA functionalization can confer a new function to graphene-like 2D nanomaterials and provide a promising bio-functionalization method for clinical application in biosensing,nanomedicine,and drug delivery.

FABRICATION AND TEST OF AN ELECTROMAGNETIC VIBRATING RING GYROSCOPE BASED ON SOI WAFER

Mode matching is the key to improve the performance of micro-machined vibrating ring gyroscopes.Mass and stiffness asymmetries can lend to normal modes badly mismatch for gyroscopes fabricated by single-crystal silicon.The mismatch of the normal nodes results in large normal mode frequency split and degraded sensitivity.To address this issue,a Silicon-On-Insulator(SOI) wafer is used to fabricate the sensor chips.Meanwhile,a compensate disk and the backside coated negative photo resist(AZ303) is employed to weaken the Lag and Footing effect during the Deep Reactive Ion Etching(DRIE) process.Test results reveal that frequency split between the normal modes is of less than 10 Hz before the following electronic tuning.Thus,the mode matching of the electromagnetic vibrating ring gyroscope is probable to be realized.

Self-Assembly of Micro-Parts onto Si Substrates at Liquid-Liquid Interface

We report a new approach for the self-assembly of cuboid micro-parts onto Si substrates to construct three-dimensional microstructures. To perform assembly, the Si substrates are prepared with a deep cavity array as binding sites. An aggregate composed of hundreds of uniformly aligned micro-parts is formed at the C10F18-H2O interface. The micro-parts are arranged by passing the substrate through the aggregate of micro-parts, thus the micro-parts are left on the substrate, and then the substrate is vibrated ultrasonically in the solution, making it possible for the micro-parts to fall into the cavities on the substrate. Finally the substrate is pulled out of the solution after assembly. This technique could give a high yield of up to 70%, providing a new method for micro-assembly.

SYSTEM-LEVEL SIMULATION OF VIBRATORY MICROMACHINED GYROSCOPE WITH FENCE STRUCTURE

An equivalent circuit model of a novel fence structure vibratory micromachined gy- roscope's oscillating properties is modeled by electrical equivalent circuits according to its dynamics equation.Equivalent circuit model of oscillating and differential detection capacitance model are im- plemented in the circuit simulation tool PSPICE,which is available in oscillating properties analysis such as oscillating's transient response,steady response and frequency response to angular rate to op- timize working mode of the gyroscope.The model also enables sensor simulation with the interfacing electronics to analyse the performances of the whole system.Behavioral simulation of the system is performed to prove the function of detection circuits.The simulation results and measurement results show that the design of circuits is feasible.

Demands and technical developments of clinical flow cytometry with emphasis in quantitative,spectral,and imaging capabilities

As the gold-standard method for single-cell analysis,flow cytometry enables high-throughput and multiple-parameter characterization of individual biological cells.This review highlights the demands for clinical flow cytometry in laboratory hematology(e.g.,diagnoses of minimal residual disease and various types of leukemia),summarizes state-of-the-art clinical flow cytometers(e.g.,FACSLyricTMby Becton Dickinson,DxFLEX by Beckman Coulter),then considers innovative technical improvements in flow cytometry(including quantitative,spectral,and imaging approaches)to address the limitations of clinical flow cytometry in hematology diagnosis.Finally,driven by these clinical demands,future developments in clinical flow cytometry are suggested.

Smooth Surface Morphology of Hydrogenated Amorphous Silicon Film Prepared by Plasma Enhanced Chemical Vapor Deposition

Influence of the parameters of plasma enhanced chemical vapor deposition （PECVD） on the surface morphology of hydrogenated amorphous silicon （α-Si：H） film was investigated. The root-mean-square （RMS） roughness of the film was measured by atomic force microscope （AFM） and the relevant results were analyzed using the surface smoothing mechanism of film deposition. It is shown that an α-Si：H film with smooth surface morphology can be obtained by increasing the PH3/N2 gas flow rate for 10% in a high frequency （HF） mode. For high power, however, the surface morphology of the film will deteriorate when the Sill4 gas flow rate increases. Furthermore, optimized parameters of PECVD for growing the film with smooth surface were obtained to be Sill4：25 sccm （standard cubic centimeters per minute）, At： 275 sccm, 10%PH3/N2：2 sccm, HF power： 15 W, pressure： 0.9 Torr and temperature： 350℃. In addition, for in thick fihn deposition on silicon substrate, a N20 and NH3 preprocessing method is proposed to suppress the formation of gas bubbles.

The effect of nozzle layout on droplet ejection of a piezo-electrically actuated micro-atomizer

We study here effects of nozzle layout on the droplet ejection of a micro atomizer, which was fabricated with the arrayed nozzles by the MEMS technology and actuated by a piezoelectric disc. A theoretical model was first built for this piezoelectric-liquid-structure coupling system to characterize the acoustic wave propagation in the liquid chamber, which determined the droplet formation out of nozzles. The modal analysis was carried out numerically to predict resonant frequencies and simulate the corresponding pressure wave field. By comparing the amplitude contours of pressure wave on the liquid-solid interface at nozzle inlets with the designed nozzle layout, behaviors of the device under different vibration modes can be predicted. Experimentally, an impedance analyzer was used to measure the resonant frequencies of the system. Three types of atomizers with different nozzle layouts were fabricated for measuring the effect of nozzle distribution on the ejection performance. The visualization experiment of droplet generation was carried out and volume flow rates of these devices were measured. The good agreement between the experiment and the prediction proved that only the increase of nozzles may not enhance the droplet generation and a design of nozzle distribution from a view-point of frequency is necessary for a resonant related atomizer.