Multi-electrode System Research Articles

Abrupt and gradual onset of synchronized oscillations due to dynamical quorum sensing in the single-cathode multi-anode nickel electrodissolution system.

The nonlinear dynamics of an oscillatory Ni electrodissolution-hydrogen ion reduction system are explored in a multi-electrode anode-single cathode system. A mathematical analysis of the charge balance equations reveals that the coupling scheme is similar to dynamical quorum sensing, where the number of anode wires affects a parameter related to the population density. In a parameter region where the large population exhibits stationary behavior, with sufficiently strong coupling (with small individual resistances attached to the anode wires), synchronized oscillations emerge abruptly with decreasing the number of anodes. Therefore, an "inverse" dynamical quorum sensing takes place. With weak coupling the transition is gradual. The experiments are supported by numerical simulation of a kinetic model of the process. The results thus show that the description of nontrivial cathode-anode interactions in the form of dynamical quorum sensing provides an efficient way of analyzing the dynamical response of complex, interacting electrochemical reactions.

Understanding the Role of Lithium Ions and Electron Transport in a Multi-Electrode System Designed for Lithium-Oxygen Batteries

The formation and decomposition of the discharge products (Li2O2) during the charging and discharging processes in Li-oxygen batteries are the main reactions that drive this technology, initiated at a solid-liquid-gas phase boundary involving Li+, O2 and e- in the cathode compartment. However the mechanistic contribution of each of these component to the electrochemical reactions in a given cell remains unknown. In this study, we seek to understand the role of Li+ and e- at the phase boundary by developing a dual-cathode system containing a lithium conducting electrode(Li3N) and an electron conducting electrode(LiI) separated by nickel mesh. It was observed that, the LiI has the tendency to form reduced oxygens on the electrode surface via I-/I3 - redox couple, while Li-ions migrate to the electrode surface by the Li-ion conductive effect of the Li3N in the reactions leading to the discharge product formation. The discharge products on the Li3N electrode were found to be oxygen-rich, while those on the LiI electrode surface were found to be oxygen-deficient. Electrochemical analyses revealed that the cells could discharge up to a capacity of 3.74mAh/cm2 at a current density of 0.1mA/cm2 with an over potential of 0.59V upon charging. At the same current density the cells were able to discharge-charge up to 184 cycles at a cut-off capacity of 0.2mAh/cm2.

INSIGHT INTO SEISMIC REFRACTION AND ELECTRICAL RESISTIVITY TOMOGRAPHY TECHNIQUES IN SUBSURFACE INVESTIGATIONS

Geophysical subsurface investigations use the principles of physics to unravel intrinsic Earth’s subsurface features and nature of the underlying geology. Over the past two decades, the use of Seismic Refraction Tomography (SRT) and Electrical Resistivity Tomography (ERT) for subsurface investigations has greatly improved the quality of acquired data for two- and three-dimensional (2D and 3D) surveys. SRT employs more shotpoints and receivers than the conventional seismic refraction for its imaging technique. ERT uses automated multi-electrode array systems to improve the confidence of large and dense data collection. SRT and ERT techniques use powerful inversion algorithms to achieve high resolution subsurface inversion models for resolving subsurface characteristics and geological conditions over a complex and larger area that may be difficult with the use of their conventional methods. The 2D and 3D inversion models (tomograms) generated from the field data sets of these techniques efficiently ameliorate inaccurate subsurface boundaries and structural delineation with higher depth resolution, especially the 3D inversion models for areas of complex geology. These state-of-the-art techniques have extensively been used for groundwater, environmental, engineering and mining investigations among others. This study provides insight from theories to data inversion techniques for the known tomography techniques (SRT and ERT) in use for subsurface investigations.

Approximation of a mixed boundary value problem

The mixed boundary value problem for the divergent-type elliptic equation with variable coefficients is considered. It is assumed that the integration domain has a sufficiently smooth boundary that is the union of two disjoint pieces. The Dirichlet boundary condition is given on the first piece, and the Neumann boundary condition is given on the other one. So the problem has discontinuous boundary condition. Such problems with mixed boundary conditions are the most common in practice when modeling processes and are of considerable interest in the development of methods for their solution. In particular, a number of problems in the theory of elasticity, theory of diffusion, filtration, geophysics, a number of problems of optimization in electro-heat and mass transfer in complex multielectrode electrochemical systems are reduced to the boundary value problems of this type. In this paper, we propose an approximation of the original mixed boundary value problem by the third boundary value problem with a parameter. The convergence of the proposed approximations is investigated. Estimates of the approximations’ convergence rate in Sobolev norms are established.

Cellular models of the nervous system diseases

Cellular models are a very important research tool in modern neurobiology. The presented review of Russian and international literature summarizes the main data of experimental studies, conducted over the past 15 years, aimed at modeling in vitro acute and chronic forms of cerebral pathology in order to reveal the mechanisms of their pathogenesis and to develop approaches to their pharmacological correction. The results of modeling of ischemic neurodestructive processes, epilepsy, Parkinson's disease, Alzheimer's disease and Huntington's disease, obtained using modern cellular research methods, such as cell cultivation in a multielectrode system and technology of induced pluripotent stem cells, are presented. A number of key concepts related to this problem are illustrated with the data obtained by the author and his laboratory. In conclusion, the short-term goals and prospects of in vitro studies of pathogenic mechanisms of neurological diseases and of the search for new neuroprotectors are formulated.

Enhanced electrochemical performance of C-NiO/NiCo2O4//AC asymmetric supercapacitor based on material design and device exploration

Asymmetric supercapacitors (ASCs) as a promising candidate to complement batteries, have been studied for decades due to the relatively high power density. The energy storage of ASCs is significantly affected by the well-designed electrode material and delicate charge balance of electrodes. With the hope to design better supercapacitor devices, we firstly synthesize C-NiO/NiCo2O4 nanocomposites with the modified nanowire structure and a small amount of carbon, effectively boosting the specific capacitance and cyclic-stability. In addition, a multi-electrode system is developed to investigate match degrees of C-NiO/NiCo2O4//AC ACSs, and the inter-restricted behavior of positive and negative electrodes. By this real-time electrochemical method, the potential contributions of electrodes in ASCs are further revealed during charge/discharge process. Therefore, ASC device with optimal match degree delivers areal capacitance up to 3482 mF cm−2, and the maximum energy and power density of 42.69 mWh cm−3 and 1.66 W cm−3. Importantly, this work throws light on the fundamental study for supercapacitors in terms of materials design and charge match degrees.

The systemDrive: a Multisite, Multiregion Microdrive with Independent Drive Axis Angling for Chronic Multimodal Systems Neuroscience Recordings in Freely Behaving Animals.

A multielectrode system that can address widely separated targets at multiple sites across multiple brain regions with independent implant angling is needed to investigate neural function and signaling in systems and circuits of small animals. Here, we present the systemDrive, a novel multisite, multiregion microdrive that is capable of moving microwire electrode bundles into targets along independent and nonparallel drive trajectories. Our design decouples the stereotaxic surgical placement of individual guide cannulas for each trajectory from the placement of a flexible drive structure. This separation enables placement of many microwire multitrodes along widely spaced and independent drive axes with user-set electrode trajectories and depths from a single microdrive body, and achieves stereotaxic precision with each. The system leverages tight tube-cannula tolerances and geometric constraints on flexible drive axes to ensure concentric alignment of electrode bundles within guide cannulas. Additionally, the headmount and microdrive both have an open-center design to allow for the placement of additional sensing modalities. This design is the first, in the context of small rodent chronic research, to provide the capability to finely position microwires through multiple widely distributed cell groups, each with stereotaxic precision, along arbitrary and nonparallel trajectories that are not restricted to emanate from a single source. We demonstrate the use of the systemDrive in male Long-Evans rats to observe simultaneous single-unit and multiunit activity from multiple widely separated sleep-wake regulatory brainstem cell groups, along with cortical and hippocampal activity, during free behavior over multiple many-day continuous recording periods.

Detecting Seasonal Flow Pathways in Road Structures Using Tracer Tests and ERT

Roads and traffic can be a source of water-bound pollutants, which can percolate through the unsaturated zone to groundwater. Deicing salt is widely used on roads in northern Europe during winter and is usually applied at a time when the temperature is below zero and the soil is partly frozen. Understanding the mechanism by which water-bound pollutants such as deicing salt are transferred from roads to groundwater is highly important for groundwater protection, environmental sustainability and road maintenance. Electrical resistivity tomography (ERT) can be used for tracing the infiltration of deicing salt in different seasons, including the frozen period, as a step towards identifying pollutant infiltration pathways. In this study, a tracer-ERT monitoring method and analytical process was developed and evaluated for use in investigating and demonstrating deicing salt infiltration pathways in road structures in different seasons and weather conditions. The method involves using dissolved sodium chloride as a tracer and monitoring its infiltration using a multi-electrode array system. The tracer tests were performed at the same location in different seasons over a 1-year period. The results indicated high seasonal variation in percolation pattern and flow velocity, with large decreases in December (winter), most likely due to preferential flow paths within the road shoulder. These findings can be applied to other water-soluble pollutants that move from the road surface to groundwater.

Ablation outcome of irreversible electroporation on potato monitored by impedance spectrum under multi-electrode system

BackgroundIrreversible electroporation (IRE) therapy relies on pulsed electric fields to non-thermally ablate cancerous tissue. Methods for evaluating IRE ablation in situ are critical to assessing treatment outcome. Analyzing changes in tissue impedance caused by electroporation has been proposed as a method for quantifying IRE ablation. In this paper, we assess the hypothesis that irreversible electroporation ablation outcome can be monitored using the impedance change measured by the electrode pairs not in use, getting more information about the ablation size in different directions.MethodsUsing a square four-electrode configuration, the two diagonal electrodes were used to electroporate potato tissue. Next, the impedance changes, before and after treatment, were measured from different electrode pairs and the impedance information was extracted by fitting the data to an equivalent circuit model. Finally, we correlated the change of impedance from various electrode pairs to the ablation geometry through the use of fitted functions; then these functions were used to predict the ablation size and compared to the numerical simulation results.ResultsThe change in impedance from the electrodes used to apply pulses is larger and has higher deviation than the other electrode pairs. The ablation size and the change in resistance in the circuit model correlate with various linear functions. The coefficients of determination for the three functions are 0.8121, 0.8188 and 0.8691, respectively, showing satisfactory agreement. The functions can well predict the ablation size under different pulse numbers, and in some directions it did even better than the numerical simulation method, which used different electric field thresholds for different pulse numbers.ConclusionsThe relative change in tissue impedance measured from the non-energized electrodes can be used to assess ablation size during treatment with IRE according to linear functions.

TCT-30 Renal Denervation Improves Cardiac Function in a Swine Model of Heart Failure

Introduction: Sympathetic nerve overactivity plays a critical role in the pathogenesis of heart failure (HF). Renal denervation (RDN) is currently under evaluation for the treatment of resistant hypertension and reduces blood pressure by disruption of sympathetic pathways that modulate cardiovascular function. We have demonstrated cardioprotective actions of RDN in rodent models of acute myocardial infarction and HF. We sought to determine if RDN treatment could improve cardiac function in a clinically relevant large animal model of HF. Methods: Yucatan miniswine (n=14) underwent 75 min of proximal left anterior descending coronary artery balloon-occlusion followed by 18 wks of reperfusion to generate large transmural infarcts and heart failure. Cardiac function was measured every 3 wks by 2-D echocardiography. HF was defined as left ventricular ejection fraction (LVEF) TM Multi-Electrode System (St. Jude Medical, St. Paul, MN). RDN was performed from distal to proximal in each renal artery, with at total of 24 ablation points separated both longitudinally and rotationally under fluoroscopic guidance. Results: At 3 wks of reperfusion following myocardial ischemia, LVEF was reduced in all pigs (SHAM RDN, 29.92.7%; RDN, 31.41.9%) with no further decline at the 6 wk treatment timepoint. At 6 wks of reperfusion, SHAM RDN and RDN treatments were performed without complication. Three wks after RDN treatment, LVEF was increased compared to SHAM (33.52.5 and 48.04.6%, respectively). LVEF was further increased 6 wks after RDN treatment compared to SHAM (31.51.5 vs. 62.00.6%, respectively). Interestingly, LVEF was higher 6 wks post-RDN compared to 3 wks post-RDN ( p =0.047). Conclusions: Preliminary results demonstrate that RDN significantly improves cardiac function in a clinically relevant swine model of HF.

Loss of Synaptic Tagging in the Anterior Cingulate Cortex after Tail Amputation in Adult Mice.

Anterior cingulate cortex (ACC) is known to play important roles in key brain functions such as pain perception, cognition, and emotion. Different forms of homosynaptic plasticity such as long-term potentiation (LTP) and long-term depression have been studied in ACC synapses. However, heterosynaptic plasticity such as synaptic tagging has not been reported. Here, we demonstrate synaptic tagging in the ACC of adult male mice by using a 64-channel multielectrode array recording system. Weak theta burst stimulation (TBS), normally inducing early-phase LTP or No-LTP in most of the activated channels, produced late phase-LTP (L-LTP) in a majority of channels when a strong TBS was applied earlier to a separate input within a certain time window. Similar to hippocampus, synaptic tagging in the ACC depends on the synthesis of new proteins. Tail amputation-induced peripheral injury caused a loss of this heterosynaptic L-LTP and occluded strong TBS-evoked L-LTP as well. Together, we provide the first report of the synaptic tagging-like phenomenon in the ACC of adult mice, and the loss of synaptic tagging to amputation may contribute to injury-related cognitive changes and phantom limb sensation and pain.SIGNIFICANCE STATEMENT ACC is an important cortical region involved in many brain functions. Previous studies have dissected the molecular mechanism of multiple types of homosynaptic plasticity of ACC synapses. Here, we report a novel form of heterosynaptic plasticity occurring in the ACC. This newly identified, protein synthesis-dependent neocortical synaptic tagging is sensitive to peripheral tail amputation injury and may provide basic mechanisms for synaptic pathophysiology of phantom pain and related cognitive changes.

Procedural and anatomical predictors of renal denervation efficacy using two radiofrequency renal denervation catheters in a porcine model

Introduction:Several renal denervation (RDN) systems are currently under investigation for treatment of hypertension by ablation of renal sympathetic nerves. The procedural efficacy of devices, however, is variable and incompletely understood. This study aimed at investigating procedural and anatomical predictors of RDN efficacy by comparing two radiofrequency catheter systems in a porcine model.Methods:Domestic swine were assigned into two treatment groups (n = 10) and one sham group (n = 3). Bilateral RDN in main and in branch segments of renal arteries was performed using two different multielectrode catheter systems [Symplicity Spyral (SPY) and IberisBloom (IBB)]. After 7 days, measurement of norepinephrine (NEPI) tissue concentrations and histological analyses have been performed.Results:Renal NEPI tissue concentration following RDN was significantly reduced when compared with Sham (SPY: −95 ± 3% vs. Sham, P < 0.001; IBB: −88 ± 11% vs. Sham, P < 0.001). Histological evaluation showed comparable lesion depth and lesion area (lesion depth: SPY-main 6.26 ± 1.62 mm vs. SPY-branch 3.49 ± 1.11 mm; IBB-main 5.93 ± 1.88 mm vs. IBB-branch: 3.26 ± 1.26 mm, P < 0.001; lesion area: SPY-main 43.5 ± 29.5 mm2 vs. SYP-branch 45.0 ± 38.0 mm2; IBB-main 52.3 ± 34.8 mm2 vs. IBB-branch 44.0 ± 42.6 mm2, P = 0.77; intergroup SPY vs. IBB, P = 0.73). Histological investigations documented a significant correlation between number of ablations per millimeter length of renal artery and reduction in NEPI tissue concentration.Conclusion:The two devices under investigation demonstrated similar histopathological lesion characteristics and similar reduction of renal NEPI levels. An increase in number of ablations per millmeter length of renal artery resulted in improved efficacy and reduced variability in treatment effects.

Characterizing Subsurface Archaeological Structures with Full Resolution 3D GPR at the Early Dynastic Foundations of Saqqara Necropolis, Egypt

Currently, Ground Penetrating Radar (GPR) used in archaeological prospection is based on 2-D parallel line methodologies characterized by line spacing from 0.25 to 1 m (common line separation is 0.5 m) with different GPR antennas and extensive interpolation used to fill data gaps. High resolution 3-D GPR images of the subsurface can be obtained by recording data with a quarter wavelength grid spacing in all directions. Recently, we used a new GPR system which is a combination of commercial GPR with a rotary laser positioning system developed at Tohoku University for full-resolution subsurface imaging. In this paper we will show how the high density 3-D GPR data acquired over an area of about 14 m × 28 m can improve the image quality and reveal the subsurface archaeological structure of early dynastic foundations in the Saqqara area. The GPR vertical cross-sections and the horizontal depth slices extracted from the full-resolution 3-D GPR reveal great information about ancient human activities, most likely burial mounds. GPR data at depth greater than 1.3 m were overwhelmed by “ringing features” (repeated horizontal harmonic-like features) most probably caused by the presence of underlying shallow layers of low resistivity shale and claystone. A 2-D electric resistivity tomography (ERT) profile was acquired using a multi-electrode system with 1 m electrode spacing. The ERT section shows high resistivity for the near surface desert sand and gravel deposits. The second geoelectric layer detected by ERT shows a low resistivity value consistent with the presence of a highly conductive layer at a depth of about 1.3 m. Integration of such different geophysical tools (e.g. GPR with ERT) helps to interpret the repeated horizontal features in the 3-D GPR data.

Estimating Localized Bio-impedance with Measures from Multiple Redundant Electrode Configurations.

In most bio-impedance applications, measurements are collected from a single electrode configuration though multi-electrode systems could monitor different tissue sites or serve as a source of redundancy in case of electrode malfunction. However, comparison of impedance data collected from different electrode configurations is difficult. This article proposes an approach to estimate the current tissue impedance collected from a fixed electrode configuration using measurements from different sites of the same localized tissue. Estimated impedance is calculated using the ratio between impedance values from different electrode configurations collected prior to the electrode malfunction event. This approach is validated using measurements of a human forearm collected from 3 kHz to 1 MHz collected with 4 electrode configurations over 3 days. The estimation results using this approach show maximum estimation errors of 2.3% and 16.9% for the resistance and reactance, respectively, compared to the measured impedance.

Neuronal Networks on Multielectrode Arrays as High Sensitive Biosensors of the Functional State of Nerve Cells

The dynamics of changes of spontaneous neuronal activity in primary hippocampal cell cultures developing on a multielectrode array (MEA) was studied using a multielectrode system. The intensification of bioelectrical activity, which depended on the duration of cultivation and stabilized by the second week in vitro, has been revealed. An increase in the concentration of glutamate (up to 2 μM) by addition into the incubation medium during the stabilization period resulted in a rapid and significant reorganization of the neuronal network activity pattern. On the other hand, inhibition and subsequent gradual recovery of the neuronal network activity immediately after the neurotransmitter addition at higher concentrations (50 or 100 μM) have been observed. At the same time, on some electrodes in the presence of high doses of glutamate (100 μM), a complete or partially irreversible suppression of the activity has been recorded. A significant reduction in spontaneous activity of the neuronal network, which was not accompanied by neuronal death, also occurred when copper ions (Cu2+) at a concentration of 10 μM were added into the incubation medium for 48 h. The obtained data demonstrate high biosensor sensitivity of the neuronal network cultured on the multielectrode array, which makes it possible to use it as an effective test system for studies of biologically active compounds.

Feasibility study for a glutamate driven subretinal prosthesis: local subretinal application of glutamate on blind retina evoke network-mediated responses in different types of ganglion cells

Objective. A feasibility study for a transmitter based subretinal prosthesis, generating visual responses in blind mouse retina is presented. Approach. Degenerated rd1 mouse retina were stimulated in subretinal configuration by local glutamate (Glu) or NMDA application via micropipettes (~1.5 μm) and thereby the outer retinal activity was recorded by calcium-imaging or the ganglion cell (GC) activity was recorded by the multi-electrode array system. The network mediated activation of GC via bipolar cells was approved by the administration of Glu receptor blockers. Main results. Data of the degenerated and blind rd1 mouse retina reveals that the outer retina is Glu sensitive and that the subretinal Glu stimulation promotes network mediated GC responses. Analysis of the spatial activity-spread indicates that the Glu induced cell activation radius in the outer retina (~12.5 μm) and postsynaptically activated GC (~40 μm) is focal to the stimulation pipette tip. Moreover, the application of NMDA in subretinal space also evoked network mediated GC responses. The Glu-activated GC were identified as ON–OFF, OFF and two ON cells types. Significance. This study evaluates the prerequisite for the function of a transmitter based implant, that after the loss of the photoreceptors, the remnant blind retinal network is Glu sensitive and functional, positively. The differential activation of ON (hyperpolarisation) and OFF (depolarisation) bipolar cells by transmitter Glu is a unique feature and of high interest for retinal implants. Therefore, the respective bipolar cell types could only be driven by glutamatergic stimulation accurately and not by electrical stimulation. The preserved functionality of the blind retina at the onset of complete blindness is motivating to continue research on a transmitter-based prosthesis. Since the artificial Glu stimulation mimics the natural retinal input, early implantation of a Glu-prosthesis might delay the devastating retinal remodelling positively, due to the neuronal-plasticity.

An Unsupervised Compressed Sensing Algorithm for Multi-Channel Neural Recording and Spike Sorting.

We propose an unsupervised compressed sensing (CS)-based framework to compress, recover, and cluster neural action potentials. This framework can be easily integrated into high-density multi-electrode neural recording VLSI systems. Embedding spectral clustering and group structures in dictionary learning, we extend the proposed framework to unsupervised spike sorting without prior label information. Additionally, we incorporate group sparsity concepts in the dictionary learning to enable the framework for multi-channel neural recordings, as in tetrodes. To further improve spike sorting success rates in the CS framework, we embed template matching in sparse coding to jointly predict clusters of spikes. Our experimental results demonstrate that the proposed CS-based framework can achieve a high compression ratio (8:1 to 20:1), with a high quality reconstruction performance (>8 dB) and a high spike sorting accuracy (>90%).

Atrial Fibrosis Hampers Non-invasive Localization of Atrial Ectopic Foci From Multi-Electrode Signals: A 3D Simulation Study.

Introduction: Focal atrial tachycardia is commonly treated by radio frequency ablation with an acceptable long-term success. Although the location of ectopic foci tends to appear in specific hot-spots, they can be located virtually in any atrial region. Multi-electrode surface ECG systems allow acquiring dense body surface potential maps (BSPM) for non-invasive therapy planning of cardiac arrhythmia. However, the activation of the atria could be affected by fibrosis and therefore biomarkers based on BSPM need to take these effects into account. We aim to analyze the effect of fibrosis on a BSPM derived index, and its potential application to predict the location of ectopic foci in the atria.Methodology: We have developed a 3D atrial model that includes 5 distributions of patchy fibrosis in the left atrium at 5 different stages. Each stage corresponds to a different amount of fibrosis that ranges from 2 to 40%. The 25 resulting 3D models were used for simulation of Focal Atrial Tachycardia (FAT), triggered from 19 different locations described in clinical studies. BSPM were obtained for all simulations, and the body surface potential integral maps (BSPiM) were calculated to describe atrial activations. A machine learning (ML) pipeline using a supervised learning model and support vector machine was developed to learn the BSPM patterns of each of the 475 activation sequences and relate them to the origin of the FAT source.Results: Activation maps for stages with more than 15% of fibrosis were greatly affected, producing conduction blocks and delays in propagation. BSPiMs did not always cluster into non-overlapped groups since BSPiMs were highly altered by the conduction blocks. From stage 3 (15% fibrosis) the BSPiMs showed differences for ectopic beats placed around the area of the pulmonary veins. Classification results were mostly above 84% for all the configurations studied when a large enough number of electrodes were used to map the torso. However, the presence of fibrosis increases the area of the ectopic focus location and therefore decreases the utility for the electrophysiologist.Conclusions: The results indicate that the proposed ML pipeline is a promising methodology for non-invasive ectopic foci localization from BSPM signal even when fibrosis is present.

Establishment of Immunodeficient Retinal Degeneration Model Mice and Functional Maturation of Human ESC-Derived Retinal Sheets after Transplantation.

SummaryIncreasing demand for clinical retinal degeneration therapies featuring human ESC/iPSC-derived retinal tissue and cells warrants proof-of-concept studies. Here, we established two mouse models of end-stage retinal degeneration with immunodeficiency, NOG-rd1-2J and NOG-rd10, and characterized disease progress and immunodeficient status. We also transplanted human ESC-derived retinal sheets into NOG-rd1-2J and confirmed their long-term survival and maturation of the structured graft photoreceptor layer, without rejection or tumorigenesis. We recorded light responses from the host ganglion cells using a multi-electrode array system; this result was consistent with whole-mount immunostaining suggestive of host-graft synapse formation at the responding sites. This study demonstrates an application of our mouse models and provides a proof of concept for the clinical use of human ESC-derived retinal sheets.

Technical feasibility study for production of tailored multielectrode arrays and patterning of arranged neuronal networks.

In this manuscript, we first reveal a simple ultra violet laser lithographic method to design and produce plain tailored multielectrode arrays. Secondly, we use the same lithographic setup for surface patterning to enable controlled attachment of primary neuronal cells and help neurite guidance. For multielectrode array production, we used flat borosilicate glass directly structured with the laser lithography system. The multi layered electrode system consists of a layer of titanium coated with a layer of di-titanium nitride. Finally, these electrodes are covered with silicon nitride for insulation. The quality of the custom made multielectrode arrays was investigated by light microscopy, electron microscopy and X-ray diffraction. The performance was verified by the detection of action potentials of primary neurons. The electrical noise of the custom-made MEA was equal to commercially available multielectrode arrays. Additionally, we demonstrated that structured coating with poly lysine, obtained with the aid of the same lithographic system, could be used to attach and guide neurons to designed structures. The process of neuron attachment and neurite guidance was investigated by light microscopy and charged particle microscopy.Importantly, the utilization of the same lithographic system for MEA fabrication and poly lysine structuring will make it easy to align the architecture of the neuronal network to the arrangement of the MEA electrode.. In future studies, this will lead to multielectrode arrays, which are able to specifically attach neuronal cell bodies to their chemically defined electrodes and guide their neurites, gaining a controlled connectivity in the neuronal network. This type of multielectrode array would be able to precisely assign a signal to a certain neuron resulting in an efficient way for analyzing the maturation of the neuronal connectivity in small neuronal networks.