A comparative study of microwire electrode array with built-in and external reference electrodes / 中国应用生理学杂志

Objective: To compare the difference between the built-in and external reference electrode of microwire electrode array in the process of recording rat brain neuron firings, optimizing the production and embedding of the microwire electrode array, and providing a more affordable and excellent media tool for multi-channel electrophysiological real-time recording system. Methods: A 16 channel microwire electrode array was made by using nickel chromium alloy wires, circuit board, electrode pin and ground wires (silver wires). The reference electrode of the microwire electrode array was built-in (the reference electrode and electrode array were arranged in parallel) or external (the reference electrode and ground wire were welded at both ends of one side of the electrode), and the difference between the two electrodes was observed and compared in recording neuronal discharges in ACC brain area of rats. Experimental rats were divided into built-in group and external group, n=8-9. The test indicators included signal-to-noise ratio (n=8), discharge amplitude (n=380) and discharge frequency (n=54). Results: The microwire electrode array with both built-in and external reference electrodes successfully recorded the electrical signals of neurons in the ACC brain region of rats. Compared with the external group, the electrical signals of neurons in built-in group had the advantages of a higher signal-to-noise ratio (P＜0.05), a smaller amplitude of background signals and less noise interference, and a larger discharge amplitude(P＜0.05); there was no significant difference in spike discharge frequency recorded by these two types of electrodes (P＞0.05). Conclusion: When recording the electrical activity of neurons in the ACC brain region of rats, the microwire electrode array with built-in reference electrode recorded electrical signals with higher signal-to-noise ratio and larger discharge amplitude, providing a more reliable tool for multi-channel electrophysiology technology.

A spike denoising method combined principal component analysis with wavelet and ensemble empirical mode decomposition / 生物医学工程学杂志

Spike recorded by multi-channel microelectrode array is very weak and susceptible to interference, whose noisy characteristic affects the accuracy of spike detection. Aiming at the independent white noise, correlation noise and colored noise in the process of spike detection, combining principal component analysis (PCA), wavelet analysis and adaptive time-frequency analysis, a new denoising method (PCWE) that combines PCA-wavelet (PCAW) and ensemble empirical mode decomposition is proposed. Firstly, the principal component was extracted and removed as correlation noise using PCA. Then the wavelet-threshold method was used to remove the independent white noise. Finally, EEMD was used to decompose the noise into the intrinsic modal function of each layer and remove the colored noise. The simulation results showed that PCWE can increase the signal-to-noise ratio by about 2.67 dB and decrease the standard deviation by about 0.4 μV, which apparently improved the accuracy of spike detection. The results of measured data showed that PCWE can increase the signal-to-noise ratio by about 1.33 dB and reduce the standard deviation by about 18.33 μV, which showed its good denoising performance. The results of this study suggests that PCWE can improve the reliability of spike signal and provide an accurate and effective spike denoising new method for the encoding and decoding of neural signal.

Design and verification of microelectrode twisting machine / 生物医学工程学杂志

As an interface between external electronic devices and internal neural nuclei, microelectrodes play an important role in many fields, such as animal robots, deep brain stimulation and neural prostheses. Aiming at the problem of high price and complicated fabrication process of microelectrode, a microelectrode twisting machine based on open source electronic prototyping platform (Arduino) and three-dimensional printing technology was proposed, and its microelectrode fabrication performance and neural stimulation performance were verified. The results show that during the fabrication of microelectrodes, the number of positive twisting turns of the electrode wire should generally be set to about 1.8 times of its length, and the number of reverse twisting rings is independent of the length, generally about 5. Moreover, compared with the traditional instrument, the device is not only inexpensive and simple to manufacture, but also has good expandability. It has a positive significance for both the personalization and popularization of microelectrode fabrication and the reduction of experimental cost.

Alzheimer's Disease Diagnosis Using Misfolding Proteins in Blood

Alzheimer's disease (AD) is pathologically characterized by a long progressive phase of neuronal changes, including accumulation of extracellular amyloid-β (Aβ) and intracellular neurofibrillary tangles, before the onset of observable symptoms. Many efforts have been made to develop a blood-based diagnostic method for AD by incorporating Aβ and tau as plasma biomarkers. As blood tests have the advantages of being highly accessible and low cost, clinical implementation of AD blood tests would provide preventative screening to presymptomatic individuals, facilitating early identification of AD patients and, thus, treatment development in clinical research. However, the low concentration of AD biomarkers in the plasma has posed difficulties for accurate detection, hindering the development of a reliable blood test. In this review, we introduce three AD blood test technologies emerging in South Korea, which have distinctive methods of heightening detection sensitivity of specific plasma biomarkers. We discuss in detail the multimer detection system, the self-standard analysis of Aβ biomarkers quantified by interdigitated microelectrodes, and a biomarker ratio analysis comprising Aβ and tau.

Carbon-Fiber Based Microelectrode Array Embedded with a Biodegradable Silk Support for In Vivo Neural Recording

BACKGROUND: Recently, carbon fibers have been utilized to develop a depth-type microelectrode array for chronic neural recording. Since the diameter of carbon fibers is smaller than the conventional electrodes made of metal wires or microfabricated silicon, the carbon fiber electrodes showed an improved capability for chronic neural recording with less tissue damages. However, the carbon fiber based microelectrodes have a limitation of short insertion depth due to a low stiffness. METHODS: We proposed a carbon fiber based microelectrode array embedded with a mechanical support structure to facilitate the penetration into the deeper brain. The support is made of biodegradable silk fibroin to reduce the reactive tissue responses. The 4-channel carbon fiber based microelectrode arrays were fabricated and accessed in terms of electrochemical impedance, recording capability for 1-month implantation in rat hippocampi. The electrodes with tungsten supports were fabricated and tested as a control group. Immunohistochemical analysis was performed to identify the reactive glial responses. RESULTS: The carbon fiber based electrode arrays with silk supports showed about 2-fold impedance increase 2 weeks after implantation while the number of active electrodes decreased simultaneously. However, after 1 month, the electrode impedance decreased back to its initial value and the percentage of active electrodes also increased above 70%. Immunohistochemical staining clearly showed that the electrodes with silk supports induced less reactive glial responses than that with tungsten supports. CONCLUSION: The proposed carbon fiber based microelectrode array is expected to be used for long-term in vivo neural recording from deep brain regions with the minimized reactive tissue response.

Characterization of Tetrodes Coated with Au Nanoparticles (AuNPs) and PEDOT and Their Application to Thalamic Neural Signal Detection in vivo

Tetrodes, consisting of four twisted micro-wires can simultaneously record the number of neurons in the brain. To improve the quality of neuronal activity detection, the tetrode tips should be modified to increase the surface area and lower the impedance properties. In this study, tetrode tips were modified by the electrodeposition of Au nanoparticles (AuNPs) and dextran (Dex) doped poly (3,4-ethylenedioxythiophene) (PEDOT). The electrochemical properties were measured using electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). A decrease in the impedance value from 4.3 MΩ to 13 kΩ at 1 kHz was achieved by the modified tetrodes. The cathodic charge storage capacity (CSC(C)) of AuNPs-PEDOT deposited tetrodes was 4.5 mC/cm², as determined by CV measurements. The tetrodes that were electroplated with AuNPs and PEDOT exhibited an increased surface area, which reduced the tetrode impedance. In vivo recording in the ventral posterior medial (VPM) nucleus of the thalamus was performed to investigate the single-unit activity in normal rats. To evaluate the recording performance of modified tetrodes, spontaneous spike signals were recorded. The values of the L-ratio, isolation distance and signal-to-noise (SNR) confirmed that electroplating the tetrode surface with AuNPs and PEDOT improved the recording performance, and these parameters could be used to effectively quantify the spikes of each cluster.

Terapia electroquímica: relación del patrón espacial del daño tisular con la forma del arreglo de electrodos / Electrochemical therapy: relationship of the tissular damage space pattern with the form of electrodes repair

Se realizó una investigación en la Escuela Superior de Ingeniería Mecánica y Eléctrica del Instituto Politécnico Nacional de Ciudad de México, desde mayo hasta junio de 2016, con el objetivo de determinar cómo cambia el patrón espacial del daño tisular con la forma del arreglo de electrodos en piezas tridimensionales de papa (Solanum tuberosum L) bajo la acción de 10 mA durante 30 min para los arreglos de electrodos con formas colineal, circular, elíptica, parabólica e hiperbólica). Los resultados mostraron la estrecha relación entre el daño tisular y la forma del arreglo de electrodos, así como algunos hallazgos que se observan también en tumores, tales como: necrosis circular alrededor de todos los electrodos, daño tisular extensivo en espacio y en tiempo, burbujeo alrededor del cátodo, zona blanca alrededor del ánodo; igualmente, se observó que las regiones alejadas de los electrodos no se afectaron

An investigation in the Mechanical and Electric Engineering Higher School of the National Polytechnic Institute of Mexico City, was carried out from May to June, 2016, aimed at determining how the tissue damage space pattern changes with the electrodes position form in three-dimensional pieces of potato (Solanum tuberosum L) under the 10 MA action during 30 minutes for electrodes position with cholineal, round, elliptic, parabolic and hyperbolic forms). The results showed a close relationship between the tissue damage and the electrodes position form, as well as some findings that are also observed in tumors, such as: circular necrosis around all the electrodes, extensive tissue damage in space and time, bubbling around the cathode, white area near the anode; likewise, it was observed that the regions far from the electrodes were not affected

Electrical Activity of the Bladder Is Attenuated by Intravesical Inhibition of P2X2/3 Receptors During Micturition in Female Rats / 대한배뇨장애요실금학회지

PURPOSE: To simultaneously monitor electrical discharges in various bladder regions and the external urethral sphincter (EUS) during voiding contractions, and to assess the functional role of myogenic modulation of the lower urinary tract (LUT) by ionotropic purinergic receptors containing the P2X3 subunit. METHODS: Female Sprague-Dawley rats were anesthetized with urethane, and implanted with a suprapubic catheter for open cystometry. Flexible microelectrodes were placed ventrally in the bladder dome, upper bladder, lower bladder, and bladder base, along with the middle section of the exposed EUS. Intravesical P2X3-containing receptors were blocked with AF-323, a specific P2X3-P2X2/3 receptor antagonist. A digital electrophysiology amplifier was used to record electrical and cystometric signals throughout the LUT. RESULTS: Electrical activity in the LUT started before effective voiding contractions. Bladder pressure and electrical waveforms showed consistent out-of-phase activity when compared with the recordings made at the EUS. This pattern was also observed during voiding contractions in the presence of AF-353, supporting the hypothesis that during bladder distension, activation of P2X3-containing receptors is required for voiding contractions. Furthermore, the inhibition of P2X3-containing receptors significantly decreased the amplitude of electrical signals in the urinary bladder, but not the base or EUS. CONCLUSIONS: Our results provide novel information about the regulation of the micturition process by P2X3-containing receptors located in the inner layers of the bladder.

Research progress of visual prosthesis / 生理学报

Vision is one of the most important human sensations about the surrounding world. Visual deprivation not only markedly affects the life of blind people, but also gives a heavy burden to their family and the society. A visual prosthesis is an electronic device that helps the blinds to regain visual perception by directly stimulating the visual pathway using the microelectrodes implanted into the body. In recent years, visual prostheses have been developed rapidly and some devices have already become clinically available. In this paper, we reviewed the history of visual prosthesis, introduced different visual prostheses classified according to the location of the implanted stimulating electrodes. Clinical study results as well as the functional status of the currently available visual prosthesis devices were also summarized.

Effect of acupuncture at different acupoints on electric activities of rat cerebellar fastigial nuclear / 中国中西医结合杂志

<p><b>OJECTIVE</b>To explore whether different acupuncture signals were afferent to the cerebellar fastigial nucleus (FN) neuron and to find out their corresponding effect features through observing the effect of spontaneous discharge of cerebellar FN neuron by needling at different acupoints.</p><p><b>METHODS</b>Totally 120 male SD rats were anesthetized by 20% urethane and their right cerebellar FN were positioned (AP 11. 6 mm, RL 1. 0 mm, H 5. 6 mm). Extracelluar discharge was recorded by glass microelectrode (AP: -11. 6 mm, R: 1. 0 mm, H: 5.7 -7. 0 mm), using extracellular microelectrode recording method, recording the spontaneous discharge of cerebellar FN neurons as a baseline. Random order of needling at zusanli (ST36), quchi (Lil1), weishu (BL21), and zhongwan (CV12) were compared with the baseline before each acupuncture. Their effects on the discharge of cerebellar FN neurons were observed and compared with baselines.</p><p><b>RESULTS</b>The frequency of FN neuronal discharge could be elevated by needling at zusanli (ST36), quchi (LiI), weishu (BL21), and zhongwan (CV12) (P <0. 01, P <0. 05). The response rate of needling at Zhongwan (CV12, 56. 00%) was higher than that of needling at Zusanli (ST36), Quchi (Ll1), and Weishu (BL21) (35. 00%, 34. 62%, 36. 63%, respectively) with statistical difference (P <0. 05). The response rate of needling at zhongwan (CV12) was obviously higher than that of needing at other points (F = 2. 101, P < 0. 05).</p><p><b>CONCLUSIONS</b>Needling at zusanli (ST36 ), quchi (Lil), weishu (BL21), and zhongwan (CV12) could elevate the spontaneous discharge frequency of cerebellar FN neurons. Needling at Zhongwan (CV12) had advantageous roles in regulating cerebellar FN.</p>

Electrophysiological and Mechanical Characteristics in Human Ileal Motility: Recordings of Slow Waves Conductions and Contractions, In vitro

Little human tissue data are available for slow waves and migrating motor complexes, which are the main components of small bowel motility. We investigated the electrophysiological and mechanical characteristics of human ileal motility, in vitro. Ileum was obtained from patients undergoing bowel resection. Electrophysiological microelectrode recordings for membrane potential changes and mechanical tension recordings for contraction from smooth muscle strips and ileal segments were performed. Drugs affecting the enteric nervous system were applied to measure the changes in activity. Slow waves were detected with a frequency of 9~10/min. There were no cross-sectional differences in resting membrane potential (RMP), amplitude or frequency between outer and inner circular muscle (CM), suggesting that electrical activities could be effectively transmitted from outer to inner CM. The presence of the interstitial cell of Cajal (ICC) at the linia septa was verified by immunohistochemistry. Contractions of strips and segments occurred at a frequency of 3~4/min and 1~2/min, respectively. The frequency, amplitude and area under the curve were similar between CM and LM. In segments, contractions of CM were associated with LM, but propagation varied with antegrade and retrograde directions. Atropine, NW-oxide-L-arginine, and sodium nitroprusside exhibited different effects on RMP and contractions. There were no cross-sectional differences with regard to the characteristics of slow waves in CM. The frequency of contractions in smooth muscle strips and ileal segments was lower than slow waves. The directions of propagation were diverse, indicating both mixing and transport functions of the ileum.

Emerging Neural Stimulation Technologies for Bladder Dysfunctions / 대한배뇨장애요실금학회지

In the neural engineering field, physiological dysfunctions are approached by identifying the target nerves and providing artificial stimulation to restore the function. Neural stimulation and recording technologies play a central role in this approach, and various engineering devices and stimulation techniques have become available to the medical community. For bladder control problems, electrical stimulation has been used as one of the treatments, while only a few emerging neurotechnologies have been used to tackle these problems. In this review, we introduce some recent developments in neural stimulation technologies including microelectrode array, closed-loop neural stimulation, optical stimulation, and ultrasound stimulation.

Finite element analysis of temperature field of retina by electrical stimulation with microelectrode array / 生物医学工程学杂志

We studied the influence of electrode array parameters on temperature distribution to the retina during the use of retinal prosthesis in order to avoid thermal damage to retina caused by long-term electrical stimulation. Based on real epiretinal prosthesis, a three-dimensional model of electrical stimulation for retina with 4 X 4 microelectrode array had been established using the finite element software (COMSOL Multiphysics). The steady-state temperature field of electrical stimulation of the retina was calculated, and the effects of the electrode parameters such as the distance between the electrode contacts, the materials and area of the electrode contact on temperature field were considered. The maximum increase in the retina steady temperature was about 0. 004 degrees C with practical stimulation current. When the distance between the electrode contacts was changed from 130 microm to 520 microm, the temperature was reduced by about 0.006 microC. When the contact radius was doubled from 130 microm to 260 microm, the temperature decrease was about 0.005 degrees C. It was shown that there were little temperature changes in the retina with a 4 x 4 epiretinal microelectrode array, reflecting the safety of electrical stimulation. It was also shown that the maximum temperature in the retina decreased with increasing the distance between the electrode contacts, as well as increasing the area of electrode contact. However, the change of the maximum temperature was very small when the distance became larger than the diameter of electrode contact. There was no significant difference in the effects of temperature increase among the different electrode materials. Rational selection of the distance between the electrode contacts and their area in electrode design can reduce the temperature rise induced by electrical stimulation.

Influence of Propofol and Fentanyl on Deep Brain Stimulation of the Subthalamic Nucleus

We investigated the effect of propofol and fentanyl on microelectrode recording (MER) and its clinical applicability during subthalamic nucleus (STN) deep brain stimulation (DBS) surgery. We analyzed 8 patients with Parkinson's disease, underwent bilateral STN DBS with MER. Their left sides were done under awake and then their right sides were done with a continuous infusion of propofol and fentanyl under local anesthesia. The electrode position was evaluated by preoperative MRI and postoperative CT. The clinical outcomes were assessed at six months after surgery. We isolated single unit activities from the left and the right side MERs. There was no significant difference in the mean firing rate between the left side MERs (38.7+/-16.8 spikes/sec, n=78) and the right side MERs (35.5+/-17.2 spikes/sec, n=66). The bursting pattern of spikes was more frequently observed in the right STN than in the left STN. All the electrode positions were within the STNs on both sides and the off-time Unified Parkinson's Disease Rating Scale part III scores at six months after surgery decreased by 67% of the preoperative level. In this study, a continuous infusion of propofol and fentanyl did not significantly interfere with the MER signals from the STN. The results of this study suggest that propofol and fentanyl can be used for STN DBS in patients with advanced Parkinson's disease improving the overall experience of the patients.

Monitoring depth of anesthesia and effect analysis in primary visual cortex of rats based on complexity of local field potential / 生物医学工程学杂志

In the present study carried out in our laboratory, we recorded local field potential (LFP) signals in primary visual cortex (V1 area) of rats during the anesthesia process in the electrophysiological experiments of invasive microelectrode array implant, and obtained time evolutions of complexity measure Lempel-ziv complexity (LZC) by nonlinear dynamic analysis method. Combined with judgment criterion of tail flick latency to thermal stimulus and heart rate, the visual stimulation experiments are carried out to verify the reliability of anesthetized states by complexity analysis. The experimental results demonstrated that the time varying complexity measures LZC of LFP signals of different channels were similar to each other in the anesthesia process. In the same anesthesia state, the difference of complexity measure LZC between neuronal responses before and after visual stimulation was not significant. However, the complexity LZC in different anesthesia depths had statistical significances. Furthermore, complexity threshold value represented the depth of anesthesia was determined using optimization method. The reliability and accuracy of monitoring the depth of anesthesia using complexity measure LZC of LFP were all high. It provided an effective method of realtime monitoring depth of anesthesia for craniotomy patients in clinical operation.

The Effects of Eupatilin (Stillen(R)) on Motility of Human Lower Gastrointestinal Tracts

Gastrointestinal motility consists of phasic slow-wave contractions and the migrating motor complex (MMC). Eupatilin (Stillen(R)) has been widely used to treat gastritis and peptic ulcers, and various cytokines and neuropeptides are thought to be involved, which can affect gastrointestinal motility. We performed a study to identify the effects of eupatilin on lower gastrointestinal motility with electromechanical recordings of smooth muscles in the human ileum and colon. Ileum and colon samples were obtained from patients undergoing bowel resection. The tissues were immediately stored in oxygenated Krebs-Ringer's bicarbonate solution, and conventional microelectrode recordings from muscle cells and tension recordings from muscle strips and ileal or colonic segments were performed. Eupatilin was perfused into the tissue chamber, and changes in membrane potentials and contractions were measured. Hyperpolarization of resting membrane potential (RMP) was observed after administration of eupatilin. The amplitude, AUC, and frequency of tension recordings from circular and longitudinal smooth muscle strips and bowel segments of the ileum and colon were significantly decreased after admission of eupatilin. Eupatilin elicited dose-dependent decreases during segmental tension recordings. In conclusion, eupatilin (Stillen(R)) showed inhibitory effects on the human ileum and colon. We propose that this drug may be useful for treating diseases that increase bowel motility, but further studies are necessary.

GABA-induced inactivation of Cebus apella V2 neurons: effects on orientation tuning and direction selectivity

We investigated the GABA-induced inactivation of V2 neurons and terminals on the receptive field properties of this area in an anesthetized and paralyzed Cebus apella monkey. Extracellular single-unit activity was recorded using tungsten microelectrodes in a monkey before and after pressure-injection of a 0.25 or 0.5 M GABA solution. The visual stimulus consisted of a bar moving in 8 possible directions. In total, 24 V2 neurons were studied before and after blocker injections in 4 experimental sessions following GABA injection into area V2. A group of 10 neurons were studied over a short period. An additional 6 neurons were investigated over a long period after the GABA injection. A third group of 8 neurons were studied over a very long period. Overall, these 24 neurons displayed an early (1-20 min) significant general decrease in excitability with concomitant changes in orientation or direction selectivity. GABA inactivation in area V2 produced robust inhibition in 80% and a significant change in directional selectivity in 60% of the neurons examined. These GABA projections are capable of modulating not only levels of spontaneous and driven activity of V2 neurons but also receptive field properties such as direction selectivity.

The research on high-density flexible microelectrode array of retinal prosthesis based on MEMS technology / 中国医疗器械杂志

The paper proposed a new method to design and fabricate a flexible neural microelectrode arrays (MEA) for retinal prosthesis, the ion-beam technology was introduced to decrease the width of conductive wires and the distances between wires, a high density MEA (120 microelectrodes with a matrix of 10 x 12) was fabricated on a single layer of polymer from this. The MEA was proved to possess a fine electrochemical property. In vitro test, the average impedance of MEA on 1 kHz was 16 k omega +/- 2 k omega and the average phase difference was -85 degrees +/-30 degrees.

In-vitro electrochemical stability evaluation of a flexible MEMS microelectrode / 中国医疗器械杂志

Three-electrode testing method was used to investigate the effect of temperature on electrode impedance, and the pH shifts in saline solution resulting from the electrical stimulation were also determined. Experiments in PBS (phosphate buffered solution) solution showed that the electrode impedance was almost invariable at the human body temperature range (35 degrees C-40 degrees C). And the experiments in unbuffered saline solution showed that pH shifts decreased from 0.03 to 0.005 when the frequency of biphasic charged-balanced pulses increased from 1 Hz to 100 Hz. Even stimulated by monophasic pulses (frequency is 15 Hz, amplitude is 50 microA), the stimulus-induced pH shift of electrode only varies 0.15 (anodic pulse current increased 0.15 and cathodic pulse current decreased 0.15).

Research on human enterovirus 71 infectivity assay based on a real-time cell analysis / 病毒学报

This research aims to evaluate the application of Real - time cell assay (RTCA) based on microelectronics sensor technology in the detection of HEV71 induced cell lesion. Growth indexes of RD cells at different stages were observed dynamically, appropriate cell concentration was selected to test HEV71 infectivity and to determine the HEV71 neutralizing antibody titer in serum. The traditional microplate test was used as methodology comparison and results validation at the same time. Cell impedance was transformed to cell index (CI) value and visual dynamic curve through software, and the result showed that the observation of HEV71 infectivity was more than 5d when the RD cells concentration was 1. 5 X 10(4) hole on the 96 electronic orifice plate. Compared with the traditional cytopathic effect (CPE) through microscope observation method, the end point judgment results were consistent between these two methods at 132h (about 5. 5d) post virus inoculation. In the neutralization tests, three CI values of neutralizing antibody titers against HEV71 in human serum were correspond to those obtained from traditional 96 microplate microscopy. RTCA also suggested that the presentation time of CPE induced by the i virus could be different even the end point judgment was the same with the same neutralization antibody titer. Compared with the traditional microplate monitoring method, RTCA can save labor and eliminate the hands-on error in the monitoring HEV71 infectivity and antibody titer detection in serum. RTCA can be served as one of the supplementary methods of traditional detection method, with the advantages of dynamically observing the occurrence and development of cell pathological changes, and the variation of virus infectivity and serum neutralizing antibodies.