High extracellular potassium can induce spreading depression-like depolarizations, elevations of extracellular glutamate and even neuronal death in normal brain. To investigate the contribution of high potassium in vivo, a microelectrode arrays ( MEAs ) probe integrated with recording sites for glutamate concentration (50í150 μm) and local field potential ( LFP) ( diameter=15 μm) was fabricated by Micro-electro-mechanical-systems ( MEMS) technologies. We implanted the MEA probe acutely in the rat brain and exposed the brain to a high potassium solution. During these multi-modal recordings, it was observed that high potassium elevated extracellular glutamate while suppressing the LFP irreversibly. This is one of the first studies in which a dual mode MEA probes is applied in vivo for neuronal death, and it is concluded that our MEA probes are capable of examining specific spatiotemporal relationships between electrical and chemical signaling in the brain.

A wireless electrochemical recording device was designed for in_vivo neurotransmitters real_time detection. Low_power microcontroller MSP430 was chosen as main control unit in hardware system. Other modules were current detection module, waveform generator module and data transceiver module. This device had the merits of small size (2. 3 cm×1. 8 cm×0. 6 cm) and low power consumption. Firmware program design was based on uC/OS operating system. Combined with the PC software, the device could achieve online display and analysis of the recording data. For neurotransmitter detecting needs, the device implemented fast_scan cyclic voltammetry ( FSCV) and fixed_potential amperometry. By using fast_scan cyclic voltammetry method, a linear relationship ( R=0. 99 ) between the concentration of dopamine and response current was acquired in the range of 5. 0×10-7-7. 0×10-5 mol/L. In the in_vivo experiments, the electrically evoked dopamine was recorded in the caudate_putamen area of brain in rats. Experimental results showed that the system had high detection accuracy, which could realize qualitative and quantitative analysis of the brain neurotransmitter. This work would have a broad application prospect in the field of neuroscience research.

The nano-structure TiN was modified on the laboratory self-made planar microelectrode array pMEA by magnetron sputtering method. The performance of modified pMEA was investigated. Research on neuroelectrical and neurochemical recording was studied in vitro. The impedance of the modified pMEA was decreased almost one order of magnitude, and the background noise level was reduced to ±6 μV. In the same testing environment, the signal-to-noise ratio (SNR) of modified electrodes was 1. 7 times of bare electrodes. The SNR of neuroelectrical recording on the brain slice of SD rats reached 10:1 , and the weak signal such as ±12 μV was separated easily. For neuroelectrical recordings, the detection limit of dopamine ( DA) solution reached 50 nmol/L with the 2:1 (S/N). During the concentration range of 0. 05-100 μmol/L, the linearly correlation coefficient of the DA oxidation currents was 0 . 998 . The modification of nano-structure TiN on pMEA reduced pMEA impedance and background noise level, meanwhile the SNR was increased. The weak signals of neuroelectrical and neurochemical recording were successfully recorded.

A dual-mode recording system used for synchronous detection of neuroeletrical and neurochemical signals was developed, and a dual-mode synchronous detection experiment was carried out using the instrument. The device comprised 64-channel neuroelectricity recording module with voltage resolution of 0. 3 μV and 4-channel neurochemistry recording module with current resolution of 1 pA. The software had many basic features, including Spike separation and sort, chronoamperometry, cyclic voltammetry, etc. In particular, the software could observe and analyze the dual-mode neural signals synchronously. The performance of the system was demonstrated in the single mode detection experiments. In neuroeletrical experiments, 64-channel simulate neural signals were detected and the signal to noise ratio ( S/N) of Spike recorded from cortex of Sprague-Dawley ( SD ) rat was 6. In the K3 [ Fe ( CN )6 ] and ascorbic acid measurement experiments, the current response of K3 [ Fe ( CN)6 ] in the range of 0. 1-10 mmol/L was obtained by cyclic voltammetry, with a correlation coefficient of 0. 9889, and the current response of ascorbic acid ( concentration:10-800 μmol/L) by chronoamperometry increased linearly with a correlation coefficient of 0. 9841. Based on the rat model of global cerebral ischemia, a dual-mode detection experiment was carried out. In the experiment, the neuroelectrical and neurochemical signals were synchronously recorded in the SD rat primary visual cortex. According to the experimental results, we got the conclusion that the concentration of ascorbic acid negatively related to the Spike firing in the SD rat primary visual cortex.

Several key problems were analysed for the transdermal noninvasive glucose monitoring. A modified calibration equation was proposed for the high-sensitivity glucose biosensor due to its narrow linear range. The new equation has increased the sensors' linear range by 20 times. A new diffuse model was constructed for the electrode system of glucose sensor,aiming at the unique "finite space" electrochemical problem in trans-dermal technique. In addition,electrode masks were utilized to solve the problem of electrode loss in longtime glucose monitoring. In animal in-vivo experiments,70.1 % of the noninvasive glucose data points were clinically accurate,while the remains were clinically acceptable. All solutions mentioned above were based on both theoretical analysis and experimental validation,promoting the realization and optimization of transdermal noninvasive glucose monitoring techniques.

The magnetic nanoparticle probe was prepared by specifically connecting the streptavidin-conjugated magnetic nanoparticles and the antibody of analyte via the strong streptavidin-biotin interaction. Based on the magnetic nanoparticle probes, the concentration of human chorionicgonadotropin (HCG) was detected and a new CL method for of hormone was further established. The performances of the magnetic nanoparticle probes were characterized by UV-Vis spectrometry, transmission electron microscopy and dynamic light scattering. The experimental conditions that affected the chemiluminescence were optimized. The optimal concentrations of luminal and H_2O_2 were 2×10~(-4) mol/L and 8×10~(-4) mol/L, respectively, and optimal pH was 13. Under the optimized experiment conditions, a linear response of chemiluminescence intensity to HCG concentration was obtained with a correlation coefficients of 0.9924. The linear range was from 0.5 to 250 μg/L and wider than the conventional ELISA method (5-200 μg/L). The relative standard deviation was 3.8%. Correlation analysis showed that there was significant correlation between the method of magnetic nanoparticle probes and ELISA in 34 clinical samples. The proposed method with characters of sensitive, effective, fast response and wide detection range provided good application prospect in analysis of other ultra-micro protein.

A highly sensitive magnetic enzymE-linked chemiluminescent immunoassay method was developed for the detection of human chorionic gonadotropin(HCG). The monoclonal antibody was covalently coupled on the surface of carboxylated magnetic beads to generate magnetic-biotargeting; Alkaline phosphatase(ALP) was utilized as a labeled reagent of another monoclonal antibody, whereas 3-(2-spimadamantane) 4-methoxy-4-(3-phosphoryloxy)phenyl-1,2-dioxetane(AMPPD) was utilized as the chemiluminescent substrate. Based on this concept, a highly sensitive chemiluminescent immunoassay method was established to test HCG. Then, several modifications were made to optimize the method, and the detection sensitivity and procedure were improved accordingly. The detection of the assay could be fulfilled within 60 min and the test result of HCG concentration was linear over the range of 0.15 150 IU/L with good relativity(r=0.960). The relative standard deviation(RSD) were below 5% and the sensitivity of this method was 0.15 IU/L. The proposed method with wide linear range, simple operation and fast detection showed good prospect in practical application on-site.

Subthalamic nucleus (STN) deep brain stimulation (DBS) has become an important surgical treatment of Parkinson disease, but its exact mechanism is still unclear.In this study, a 16-channel implantable microelectrode array (MEA) was prepared by micro-electromechanical system (MEMS) technique and later modified with platinum black/reduced Graphene Oxide/Nafion (Pt/RGO/Nafion) nanocomposites.Extracellular dopamine (DA) content and spike of dorsal striatum neurons were synchronously recorded before and after STN stimulation.The results showed that the dopamine content began to increase within 20 s after electrical stimulation and dropped to normal level after about 50 s, with the highest rising concentration of 1.72 μmol/L.At the same time, there was an increased spike activity of interneurons in the dopamine ascending phase, and the spike firing rate of medium spiny projection neurons (MSNs) was high when the concentration of DA was higher than the normal level.The MEA sensor can simultaneously record dopamine flux and physiological signals in situ, thus providing an ideal tool for neural information detection.

A 8-channel neural signal′s simultaneous transducer detection micro system was developed to research the neural loop located at the brain hippocampus zone. The components of the system contained the neural probe manufactured with the Micro-electro-mechanical-systems (MEMS) technique based on silicon-on-insulator (SOI) substrate, biological low noise chopper-stabilization amplifier, low noise and intermediate speed SAR-ADC converter, reduced and low power ASK/FSK modulation radio transmitter. The micro system was applicable with the characters of small volume, interferences free, neural electrophysiology and neurotransmitter simultaneous detection, high sensitivity, high linearity, etc. The electrode resistance was optimized to 35.0 kΩ after depositing nanometer platinum black on the 4 electrophysiological sites on the Pt electrode. With the modification enzyme technique, nanomaterial enzyme membrane (Pt-mPD-GluOx) was directly fixed on the glutamate detection locus for selectively detecting special neural neurotransmitter matter. In addition, the electrochemistry measurement results indicated that the linear range of glutamate was 6-35 μmol/L with correlation coefficient of 0.97, the sensitivity was 0.0069 pA/(μmol/L). The current response error was less than 3.0 pA, which showed that the neural needle satisfied differential selection. Also, the logic/analog mixed signal 180-nm Application specific integrated circuit (ASIC ) technique (SmicRF180 nm 1Poly6M) was used to manufacture the transducer back-end disposing IC chip, and the test results provided some key parameters such as chopper-stabilization amplifier (equivalent in putting noise voltage ≤0.7 μV rms@1 kHz, gain of 71-82 dB, CMRR/PSRR>100 dB), SAR-ADC (ENOB is 12 bits, power consumption is 1.2 mW when maxmium conversion speed is 1 Msps, signal-noise-ratio is 60.9 dB, etc), and ASK/FSK modulation radio transmitter (the PA′s outputting power of 4-5 dBm, the radiation range of 10 meters). The micro neural transducer integrated system was convenient and wireless wearable for the research of brain hippocampus region.

Objective: To study the mechanism of Heshi-Gejiugao on the nerve endocrine immune network in the treatment of perimenopausal syndrome. Methods: A total of 100 patients with perimenopausal syndrome were randomly divided into treatment group and control group, 50 cases in each group. The control group was only given general treatment, while the treatment group was treated with Heshi-Gejiugao on the basis of general treatment for 30 days. The clinical efficacy, Kupperman score, nerve, endocrine and immune related indexes of the two groups before and after treatment were observed. Results: The total effective rate was 96.0% (48/50) in the treatment group and 50.0% (25/50) in the control group. There was significant difference between the two groups (χ²=37.639, P<0.01). The Kupperman score (17.52 ± 2.73 vs. 24.22 ± 6.87, t=6.409) in the treatment group was significantly lower than that in the control group (P<0.01). After treatment, NE (1 878.08 ± 931.57 ng/m vs. 1 278.43 ± 866.32 ng/ml, t=3.331), DA (1 568.56 ± 597.15 ng/ml vs. 1 183.62 ± 798.72 ng/ml, t=2.729) in the treatment group were significantly higher than those in the control group (P<0.05); E₂ (42.12 ± 9.77 pg/ml vs. 35.91 ± 12.55 pg/ml, t=2.761), FSH (62.70 ± 15.96 mIU/ml vs. 72.67 ± 30.18 mIU/ml, t=2.065), LH (33.88 ± 12.18 mIU/ml vs. 42.93 ± 9.83 mIU/ml, t=4.089) were significantly lower than those of the control group (P<0.05). CD3⁺ (1 087.34/μl ± 432.19/μl vs. 918.27/μl ± 199.72/μl, t=2.511), CD4⁺ (738.16/μl ± 326.75/μl vs. 588.43/μl ± 212.55/μl, t=2.716) and CD4/CD8 (1.87 ± 0.56 vs. 1.16 ± 0.55), t=6.483) were significantly higher than those of the control group (P<0.05); CD8⁺ (788.32/μl ± 214.56/μl vs. 976.37/μl ± 318.62/μl, t=3.462) was significantly lower than that of the control group (P<0.05). Conclusions Heshi-Gejiugao can reduce the symptoms and improve the quality of life by regulating the multi target and multi direction of the neuroendocrine immune network of perimenopausal patients.