Shengwei Xu

Highly sensitive detection of quantal dopamine secretion from pheochromocytoma cells using neural microelectrode array electrodeposited with polypyrrole graphene.

For the measurement of events of dopamine (DA) release as well as the coordinating neurotransmission in the nerve system, a neural microelectrode array (nMEA) electrodeposited directionally with polypyrrole graphene (PG) nanocomposites was fabricated. The deposited graphene significantly increased the surface area of working electrode, which led to the nMEA (with diameter of 20 μm) with excellent selectivity and sensitivity to DA. Furthermore, PG film modification exhibited low detection limit (4 nM, S/N = 3.21), high sensitivity, and good linearity in the presence of ascorbic acid (e.g., 13933.12 μA mM(-1) cm(-2) in the range of 0.8-10 μM). In particular, the nMEA combined with the patch-clamp system was used to detect quantized DA release from pheochromocytoma cells under 100 mM K(+) stimulation. The nMEA that integrates 60 microelectrodes is novel for detecting a large number of samples simultaneously, which has potential for neural communication research.

A wireless point-of-care testing system for the detection of neuron-specific enolase with microfluidic paper-based analytical devices

Neuron-specific enolase (NSE) had clinical significance on diagnosis, staging, monitoring effect and judging prognosis of small cell lung cancer. Thus, there had a growing demand for the on-site testing of NSE. Here, a wireless point-of-care testing (POCT) system with electrochemical measurement for NSE detection was developed and verified. The wireless POCT system consisted of microfluidic paper-based analytical devices (μPADs), electrochemical detector and Androids smartphone. Differential pulse voltammetry (DPV) measurement was adopted by means of electrochemical detector which including a potentiostat and current-to-voltage converter. μPADs were modified with nanocomposites synthesized by Amino functional graphene, thionine and gold nanoparticles (NH2-G/Thi/AuNPs) as immunosensors for NSE detection. Combined with μPADs, the performance of the wireless POCT system was evaluated. The peak currents showed good linear relationship of the logarithm of NSE concentration ranging from 1 to 500ngmL-1 with the limit of detection (LOD) of 10pgmL-1. The detection results were automatically stored in EEPROM memory and could be displayed on Androids smartphone through Bluetooth in real time. The detection results were comparable to those measured by a commercial electrochemical workstation. The wireless POCT system had the potential for on-site testing of other tumor markers.

Simultaneous recording of brain extracellular glucose, spike and local field potential in real time using an implantable microelectrode array with nano-materials.

Glucose is the main substrate for neurons in the central nervous system. In order to efficiently characterize the brain glucose mechanism, it is desirable to determine the extracellular glucose dynamics as well as the corresponding neuroelectrical activity in vivo. In the present study, we fabricated an implantable microelectrode array (MEA) probe composed of platinum electrochemical and electrophysiology microelectrodes by standard micro electromechanical system (MEMS) processes. The MEA probe was modified with nano-materials and implanted in a urethane-anesthetized rat for simultaneous recording of striatal extracellular glucose, local field potential (LFP) and spike on the same spatiotemporal scale when the rat was in normoglycemia, hypoglycemia and hyperglycemia. During these dual-mode recordings, we observed that increase of extracellular glucose enhanced the LFP power and spike firing rate, while decrease of glucose had an opposite effect. This dual mode MEA probe is capable of examining specific spatiotemporal relationships between electrical and chemical signaling in the brain, which will contribute significantly to improve our understanding of the neuron physiology.

A high-sensitive nano-modified biosensor for dynamic monitoring of glutamate and neural spike covariation from rat cortex to hippocampal sub-regions

BACKGROUND Hippocampus is a critical part of brain tissue involved in many cognitive neural activities. They are controlled by various neurotransmitters such as glutamate (Glu), and affected by electrophysiology. NEW METHOD Herein, we fabricated a 16-site (25μm in diameter) microelectrode array (MEA) biosensor applied in dual-mode tests including Glu and neural spike measurements. METHODS All the 16 recording sites were electrodeposited with platinum nanoparticles (PtNPs) and 8 sites were used for electrical recording. Glutamate oxidase enzyme (Gluox) and 1,3-Phenylenediamine (mPD) layer were specially modified on the other 8 sites for Glu recording. The dual-mode MEA was implanted from cortex to hippocampus of anesthetized rat to record Glu content and firing rate. RESULTS The electrical sites showed much lower impedance. The Glu sites showed much higher sensitivity(7.807 pA/μM), and ideal selectivity to the major molecules in brain. The post calibration sensitivity (3.935 pA/μM) maintained on a positive level. Different Glu content peaks including cortex (18.32μM) and hippocampal CA1 (4.39μM), CA3 (10.16μM), dentate gyrus (DG, two layers: 5.36μM and 10.34μM) have detected. The corresponded firing rate was recorded, too. COMPARISON WITH EXISTING METHODS This modification showed much lower impedance and much higher sensitivity. We obtained more neuron activities simultaneously by dual-mode recording. The covariation of Glu and neural spike signals was discovered in the specific hippocampus sub-region. CONCLUSIONS The covariation between Glu and firing rate changes were synchronous, and effected by regions. The dual-mode signals were useful to find the neurology disease mechanism.

An integrated system for synchronous detection of neuron spikes and dopamine activities in the striatum of Parkinson monkey brain

BACKGROUND Synchronous detecting neuron spikes and dopamine (DA) activities in the non-human primate brain play an important role in understanding of Parkinsons disease (PD). At present, most experiments are carried out by combing of electrodes and commercial instruments, which are inconvenient, time-consuming and inefficient. NEW METHOD Herein, this study describes a novel integrated system for monitoring neuron spikes and DA activities in non-human primate brain synchronously. This system integrates an implantable sensor, a dual-function head-stage and a low noise detection instrument. METHODS The system was developed efficiently by using the key technologies of noise reduction, interference protection and differential amplification. To demonstrate the utility of this system, synchronous recordings of electrophysiological signals and DA were in vivo performed in a monkey before and after treated as a Parkinson model monkey. RESULTS The system typically exhibited input-referred noise levels of only ∼ 3 μVRMS, input impedance levels of up to 5.1 GΩ, and a sensitivity of 14.075 pA/μM for DA and could detect electrophysiological signals and DA without mutual interference. In monkey experiments, lower DA concentrations in the striatum and more intensive spikes of the Parkinson model monkey than the normal one were synchronously recorded efficiently. COMPARISON WITH EXISTING METHODS This integrated system will not only significantly simplify the experimental operation and improve the experimental efficiency, but also improve the signal quality and synchronization performance. CONCLUSIONS This integrated system, which is practical, efficient and convenient, can be widely used for the study of PD and other neurological disorders.

Bio-electrochemical microelectrode arrays for glutamate and electrophysiology detection in hippocampus of temporal lobe epileptic rats

Temporal Lobe Epilepsy (TLE) is a chronic neurological disorder, characterized by sudden, repeated and transient central nervous system dysfunction. For better understanding of TLE, bio-nanomodified microelectrode arrays (MEA) are designed, for the achievement of high-quality simultaneous detection of glutamate signals (Glu) and multi-channel electrophysiological signals including action potentials (spikes) and local field potentials (LFPs). The MEA was fabricated by Micro-Electro-Mechanical System fabrication technology and all recording sites were modified with platinum black nano-particles, the average impedance decreased by nearly 90 times. Additionally, glutamate oxidase was also modified for the detection of Glu. The average sensitivity of the electrode in Glu solution was 1.999 ± 0.032 × 10-2pA/μM·μm2(n = 3) and linearity was R = 0.9986, with a good selectivity of 97.82% for glutamate and effective blocking of other interferents. In the in-vivo experiments, the MEA was subjected in hippocampus to electrophysiology and Glu concentration detection. During seizures, the fire rate of spikes increases, and the interspike interval is concentrated within 30 ms. The amplitude of LFPs increases by 3 times and the power increases. The Glu level (4.22 μM, n = 4) was obviously higher than normal rats (2.24 μM, n = 4). The MEA probe provides an advanced tool for the detection of dual-mode signals in the research of neurological diseases.

A rapid quantitative determination method of Luteinizing hormone with gold immunochromatographic strip

Measurement of Luteinizing hormone (LH) levels is of great importance in guidance for pregnancy, diagnosis of ovarian diseases and evaluation of clinical effect. Gold immunochromatographic strip(GICS) assay is a rapid, simple, low-costs, and on-site technology. Quantitative detection of GICS has advantage over the traditional qualitative or semi-quantitative strip assay. In this paper, we developed a novel quantitative detection method for GICS based on smart-phone. First, smart-phone was used to acquire GICS image. Then, we applied the canny edge detection operator to extract the reading window from GICS image, and the fuzzy c-means (FCM) clustering algorithm to locate the test and control lines in the reading window. In order to reduce environmental interference, luminance compensation based on color constancy algorithms was applied. Finally, the property of the developed quantitative method is demonstrated by the detection of LH sample and clinical serum sample. Experimental results revealed that this method could achieve a low detection limit of 1.0 mIU/mL in a linear range from 1.0 to 125.0 mIU/mL. Furthermore, the proposed method could be used for the determination of clinical serum samples and its corresponding correlation coefficients were 0.964. Results showed that this novel method could be an effective tool for the rapid quantitative determination of LH.Measurement of Luteinizing hormone (LH) levels is of great importance in guidance for pregnancy, diagnosis of ovarian diseases and evaluation of clinical effect. Gold immunochromatographic strip(GICS) assay is a rapid, simple, low-costs, and on-site technology. Quantitative detection of GICS has advantage over the traditional qualitative or semi-quantitative strip assay. In this paper, we developed a novel quantitative detection method for GICS based on smart-phone. First, smart-phone was used to acquire GICS image. Then, we applied the canny edge detection operator to extract the reading window from GICS image, and the fuzzy c-means (FCM) clustering algorithm to locate the test and control lines in the reading window. In order to reduce environmental interference, luminance compensation based on color constancy algorithms was applied. Finally, the property of the developed quantitative method is demonstrated by the detection of LH sample and clinical serum sample. Experimental results revealed that this method could achieve a low detection limit of 1.0 mIU/mL in a linear range from 1.0 to 125.0 mIU/mL. Furthermore, the proposed method could be used for the determination of clinical serum samples and its corresponding correlation coefficients were 0.964. Results showed that this novel method could be an effective tool for the rapid quantitative determination of LH.

Time-frequency distribution properties of event-related potentials in mental fatigue induced by visual memory tasks.

Prolonged periods of demanding cognitive tasks lead to an exhausted feeling known as mental fatigue. The neural underpinnings of mental fatigue are still under exploration. In the present study, we aimed to identify neurophysiological indicators of mental fatigue by studying the time–frequency distribution of the event-related potentials (ERPs) measured in N=26 adults in nonfatigued versus fatigued states. We were interested in the frontal theta and occipital alpha variations, which have shown consistent relationships with mental fatigue in previous studies. Furthermore, we expected differential changes in left and right electrodes, in line with previously detected lateralization effects in cognitive tasks. Mental fatigue was induced by a sustained two-back verbal visual memory task for 125 min and assessed using the Chalder Fatigue Scale. We applied a high-resolution time–frequency analysis method called smoothed pseudo Wigner Ville distribution and used regional integrals as indicators for changing trends of signal energy. Results showed an increase in ERP frontal theta energy (P=0.03) and a decrease in occipital alpha energy (P=0.028) when participants became mentally fatigued. The change in frontal theta was more pronounced in left electrode sites (P=0.032), hinting toward a differential fatigue effect in the two hemispheres. The results were discussed on the basis of previous lateralization studies with memory tasks and interpreted as an indicator of a causal relationship between the sustained task execution and the physiological changes. Our findings also suggest that the ERP signal energy variations in frontal theta and occipital alpha might be used as neural biomarkers to assess mental fatigue.

Microelectrode arrays studies of glutamate excitatory pathway in hippocampus CA3 by offside KCl and glutamate stimulating

In our central nervous system (CNS), glutamate is an excitatory neurotransmitter that can be accumulated remarkably by brain tissue. As is noticeable from previous studies, glutamate is somehow closely related with most ways of normal and abnormal cerebral activities. It was significant to monitor glutamate concentration changes in vivo real time. Therefore, we developed an enzyme-based microelectrode array with high sensitivity (7.34pA/µM) and perfect linearity (R2=0.999). Selectivity to normal neurotransmitters satisfied our in vivo demands. Ultimately, we applied the electrode into the brain specific tissue to study glutamate excitatory pathway in hippocampus CA3 by offside KCl and glutamate stimulating. The hippocampus CA3 glutamate was detected about 18.17µM and 13.19µM by twice KCl stimulating in the offside cortex, and 6.50µM, 4.55µM by twice glutamate stimulating. All peak current back to the base level later. The self-regulation ability reflects the glutamate excitatory pathway from hippocampus CA3 to cortex.

Inter-hemispheric frontal alpha synchronization of event-related potentials reflects memory-induced mental fatigue

Mental fatigue is often associated with continuous brain activities in our daily life. It can diminish efficiency and increase errors. However, the related physiological features are still not clear and under exploration. The present study investigated changes of inter-hemispheric synchronization in event-related potentials (ERPs) due to mental fatigue during sustained memory processing. Twenty-six participants performed a continuous two-back memory task for around 2.5h. Prefrontal and frontal synchronies in the alpha frequency band (8-13Hz) were analyzed because of their close relationships with memory functions. Coherence was used to examine bilateral synchronization changes of ERP power and phase. We compared ERP coherences in both non-fatigued and fatigued states. We also observed the variation of ERP coherences during the continuous task. High overlaps of inter-hemispheric ERP waveforms were observed at prefrontal and frontal cortex in both non-fatigued and fatigued conditions. During the whole experimental procedure, ERP alpha coherences at frontal regions (FP1-FP2 and F3-F4) were significantly higher than at central (C3-C4), parietal (P3-P4) and occipital (O1-O2) regions. Alpha synchronization in anterior electrode pairs showed significant declines with increasing mental fatigue during the memory task. Our findings about changes in frontal ERP alpha synchronization might be used as biomarkers to assess mental fatigue induced by prolonged memory demands.