GABAergic Inhibition Controls Receptive Field Size, Sensitivity, and Contrast Preference of Direction Selective Retinal Ganglion Cells Near the Threshold of Vision.

Information about motion is encoded by direction-selective retinal ganglion cells (DSGCs). These cells reliably transmit this information across a broad range of light levels, spanning moonlight to sunlight. Previous work indicates that adaptation to low light levels causes heterogeneous changes to the direction tuning of ON-OFF (oo)DSGCs and suggests that superior-preferring ON-OFF DSGCs (s-DSGCs) are biased toward detecting stimuli rather than precisely signaling direction. Using a large-scale multielectrode array, we measured the absolute sensitivity of ooDSGCs and found that s-DSGCs are 10-fold more sensitive to dim flashes of light than other ooDSGCs. We measured their receptive field (RF) sizes and found that s-DSGCs also have larger receptive fields than other ooDSGCs; however, the size difference does not fully explain the sensitivity difference. Using a conditional knock-out of gap junctions and pharmacological manipulations, we demonstrate that GABA-mediated inhibition contributes to the difference in absolute sensitivity and receptive field size at low light levels, while the connexin36-mediated gap junction coupling plays a minor role. We further show that under scotopic conditions, ooDSGCs exhibit only an ON response, but pharmacologically removing GABA-mediated inhibition unmasks an OFF response. These results reveal that GABAergic inhibition controls and differentially modulates the responses of ooDSGCs under scotopic conditions.

Effects of chronic insecticide exposure on neuronal network development in vitro in rat cortical cultures.

Developmental exposure to carbamates, organophosphates, and pyrethroids has been associated with impaired neurodevelopmental outcomes. Sex-specific differences following chronic insecticide exposure are rather common in vivo. Therefore, we assessed the chronic effects of in vitro exposure to different carbamates (carbaryl, methomyl and aldicarb), organophosphates [chlorpyrifos (CPF), chlorpyrifos-oxon (CPO), and 3,5,6,trichloropyridinol (TCP)], and pyrethroids [permethrin, alpha-cypermethrin and 3-phenoxy benzoic acid (3-PBA)] on neuronal network development in sex-separated rat primary cortical cultures using micro-electrode array (MEA) recordings. Our results indicate that exposure for 1 week to carbaryl inhibited neurodevelopment in male cultures, while a hyperexcitation was observed in female cultures. Methomyl and aldicarb evoked a hyperexcitation after 2 weeks of exposure, which was more pronounced in female cultures. In contrast to acute MEA results, exposure to ≥ 10 µM CPF caused hyperexcitation in both sexes after 10 days. Interestingly, exposure to 10 µM CPO induced a clear hyperexcitation after 10 days of exposure in male but not female cultures. Exposure to 100 µM CPO strongly inhibited neuronal development. Exposure to the type I pyrethroid permethrin resulted in a hyperexcitation at 10 µM and a decrease in neuronal development at 100 µM. In comparison, exposure to ≥ 10 µM of the type II pyrethroid alpha-cypermethrin decreased neuronal development. In female but not in male cultures, exposure to 1 and 10 µM permethrin changed (network) burst patterns, with female cultures having shorter (network) bursts with fewer spikes per (network) burst. Together, these results show that MEA recordings are suitable for measuring sex-specific developmental neurotoxicity in vitro. Additionally, pyrethroid exposure induced effects on neuronal network development at human-relevant concentrations. Finally, chronic exposure has different effects on neuronal functioning compared to acute exposure, highlighting the value of both exposure paradigms.

Evaluation of insertion quality of a slim perimodiolar electrode array.

OBJECTIVES: The influence of cochlear morphology and electrode array design on scalar position and dislocation rates is of great interest in CI surgery. The aim of this study is to evaluate scalar position and specific points of dislocation in relation to cochlear morphology in patients implanted with a new slim perimodiolar electrode array. MATERIALS AND METHODS: Patients were implanted using the slim modiolar electrode array (= SMA) (= 532/632 electrode array of Cochlear™). Postoperative imaging was performed via cone beam computed tomography (CBCT) and the scans were analyzed regarding cochlear morphology (distances A and B and cochlear height), scalar location of the electrode array, basal insertion depth and apical insertion angle. Furthermore, electrode array design and surgical protocols were evaluated. RESULTS: 81 ears implanted with the SMA were retrospectively included. We evaluated 3 electrode array tip fold over intraoperatively via X-ray imaging and performed revision during the same surgery. The CBCT scans showed 76 initial scala tympani (ST) insertions without dislocation. Two ears showed a dislocated array, one at 77° and the other at 163°. Three arrays were inserted into scala vestibuli (SV) via cochleostomy. These patients showed no signs of obliteration. Cochlear morphology showed no influence on angular insertion depth and scalar position. CONCLUSIONS: The SMA showed a very low rate of scalar dislocations due to its slim electrode array design (2.7%). We could find a learning curve regarding the handling and the risk of dislocation and tip fold over with this electrode array. The rate of intraoperative tip fold over detection via X-ray imaging was 3.7%. Therefore, we highly recommend X-ray imaging and transimpedance matrix measurements within the surgery protocol. Scala vestibuli insertions happened in patients with cochleostomy only. We could identify two specific points of dislocation depending on electrode array design.

Metronome-guided cochlear implantation for slower and smoother insertions of lateral wall electrodes.

INTRODUCTION: Achieving a slow and smooth electrode array insertion is paramount for preserving structural and functional integrity during cochlear implantation. This controlled study evaluates the efficacy of a metronome-guided insertion technique in enhancing the smoothness and speed of electrode array insertions. METHODS: In a prospective cohort study, patients undergoing cochlear implant surgery between 2022 and 2023 with lateral wall electrode arrays were included. Metronome guidance was delivered through an acoustic signal via headphones during electrode array insertion in cochlear implantation and compared to a control group without metronome-guidance. RESULTS: In total, 37 cases were evaluated, including 25 conventional insertions and 12 metronome-guided insertions. The results indicate that metronome-guided insertions were significantly slower (- 0.46 mm/s; p < 0.001) without extending the overall procedure time. This can be attributed to fewer paused sections observed in the metronome-guided technique. Moreover, metronome-guided insertions exhibited superior performance in terms of insertion smoothness and a reduced number of re-gripping events. CONCLUSIONS: The findings support the recommendation for the systematic application of metronome guidance in the manual insertion of cochlear implant electrode arrays, emphasizing its potential to optimize surgical outcomes.

A High-Performance System for Weak ECG Real-Time Detection.

Wearable devices have been widely used for the home monitoring of physical activities and healthcare conditions, among which ambulatory electrocardiogram (ECG) stands out for the diagnostic cardiovascular information it contains. Continuous and unobtrusive sensing often requires the integration of wearable sensors to existing devices such as watches, armband, headphones, etc.; nonetheless, it is difficult to detect high-quality ECG due to the nature of low signal amplitude at these areas. In this paper, a high-performance system with multi-channel signal superposition for weak ECG real-time detection is proposed. Firstly, theoretical analysis and simulation is performed to demonstrate the effectiveness of this system design. The detection system, including electrode array, acquisition board, and the application (APP), is then developed and the electrical characteristics are measured. A common mode rejection ratio (CMRR) of up to 100 dB and input inferred voltage noise below 1 µV are realized. Finally, the technique is implemented in form of ear-worn and armband devices, achieving an SNR over 20 dB. Results are also compared with the simultaneous recording of standard lead I ECG. The correlation between the heart rates derived from experimental and standard signals is higher than 0.99, showing the feasibility of the proposed technique.

Porcine Model of Cerebral Ischemic Stroke Utilizing Intracortical Recordings for the Continuous Monitoring of the Ischemic Area.

PURPOSE: Our aim was to use intracortical recording to enable the tracking of ischemic infarct development over the first few critical hours of ischemia with a high time resolution in pigs. We employed electrophysiological measurements to obtain quick feedback on neural function, which might be useful for screening, e.g., for the optimal dosage and timing of agents prior to further pre-clinical evaluation. METHODS: Micro-electrode arrays containing 16 (animal 1) or 32 electrodes (animal 2-7) were implanted in the primary somatosensory cortex of seven female pigs, and continuous electrical stimulation was applied at 0.2 Hz to a cuff electrode implanted on the ulnar nerve. Ischemic stroke was induced after 30 min of baseline recording by injection of endothelin-1 onto the cortex adjacent to the micro-electrode array. Evoked responses were extracted over a moving window of 180 s and averaged across channels as a measure of cortical excitability. RESULTS: Across the animals, the cortical excitability was significantly reduced in all seven 30 min segments following endothelin-1 injection, as compared to the 30 min preceding this intervention. This difference was not explained by changes in the anesthesia, ventilation, end-tidal CO2, mean blood pressure, heart rate, blood oxygenation, or core temperature, which all remained stable throughout the experiment. CONCLUSIONS: The animal model may assist in maturing neuroprotective approaches by testing them in an accessible model of resemblance to human neural and cardiovascular physiology and body size. This would constitute an intermediate step for translating positive results from rodent studies into human application, by more efficiently enabling effective optimization prior to chronic pre-clinical studies in large animals.

[Insertion of a second electrode array-a rare complication of CI reimplantation. German version]. / Insertion eines zweiten Elektrodenträgers ­ eine seltene Komplikation bei CI-Reimplantation.

Due to a technical defect or a medical indication, it may be necessary to explant a cochlear implant. This case report shows that there is the risk of encountering a nonremovable electrode array-as described here from the scala tympani-during cochlear reimplantation. In the present case, insertion of a second electrode array into the free and nonobstructed scala vestibuli was successful. Nonetheless, the indication for reimplantation must be carefully considered, especially in patients with tolerable limitations with little or no loss of speech understanding. Furthermore, surgery should not be performed solely because an implant upgrade is desired.

Insertion of a second electrode array-a rare complication of CI reimplantation.

Due to a technical defect or a medical indication, it may be necessary to explant a cochlear implant. This case report shows that there is the risk of encountering a nonremovable electrode array-as described here from the scala tympani-during cochlear reimplantation. In the present case, insertion of a second electrode array into the free and nonobstructed scala vestibuli was successful. Nonetheless, the indication for reimplantation must be carefully considered, especially in patients with tolerable limitations with little or no loss of speech understanding. Furthermore, surgery should not be performed solely because an implant upgrade is desired.

Bioimpedance sensor array for monitoring chronic wounds: Validation of method feasibility.

In an ageing society, the incidence of hard-to-heal wounds is rising. Chronic wound healing is a complex process, which requires specialised treatment. Clinical assessment of the wound is essential to establish care approaches but is usually based on visual evaluation and it remains challenging. Therefore, innovative quantitative methods for the assessment of chronic wounds are needed. We conducted a single-centre observational study designed to assess the feasibility of a bioimpedance measurement method conducted with a multielectrode sensor array to monitor the wound healing process in patients with chronic wounds of venous, mixed venous-arterial and diabetic aetiology. In total, 104 measurements of bioimpedance were conducted in 18 ulcers during the study. Across all 7 patients analysed, the bioimpedance of the ulcers was consistently increasing as the wound surface was decreasing. The variables had significant (p < 0.001) and strong negative correlation (r = -0.86). We validated the feasibility of the bioimpedance measurement method for the monitoring of the wound healing process on the lower legs. It may be a promising quantitative method for monitoring the status of the wounds. However, long-term measurements are needed to show the usability of the electrode dressing and bioimpedance measurement in the assessment of chronic wounds.

Characterization of thin film Parylene C device curvature and the formation of helices via thermoforming.

In microfabricated biomedical devices, flexible, polymer substrates are becoming increasingly preferred over rigid, silicon substrates because of their ability to conform to biological tissue. Such devices, however, are fabricated in a planar configuration, which results in planar devices that do not closely match the shape of most tissues. Thermoforming, a process which can reshape thermoplastic polymers, can be used to transform flat, thin film, polymer devices with patterned metal features into complex three-dimensional (3D) geometries. This process extends the use of planar microfabrication to achieve 3D shapes which can more closely interface with the body. Common shapes include spheres, which can conform to the shape of the retina; cones, which can be used as a sheath to interface with an insertion stylet; and helices, which can be wrapped around nerves, blood vessels, muscle fibers, or be used as strain relief feature. This work characterizes the curvature of thin film Parylene C devices with patterned metal features built with varying Parylene thicknesses and processing conditions. Device curvature is caused by film stress in each Parylene and metal layer, which is characterized experimentally and by a mathematical model which estimates the effects of device geometry and processing on curvature. Using this characterization, an optimized process to thermoform thin film Parylene C devices with patterned metal features into 0.25 mm diameter helices while preventing cracking in the polymer and metal was developed.

Full-array channel discrimination in cochlear implants: validation and clinical application.

OBJECTIVE: We sought to validate our proposed tool for estimating channel discrimination of cochlear implant (CI) users along the full electrode array and to assess associations between place-pitch discrimination and speech perception. DESIGN: In two tests, participants identified one stimulus (probe) as the odd-one-out compared with two reference stimuli. Probe stimuli were evoked using dual electrode stimulation characterised by the current steering coefficient α. The first test measured psychometric functions (PFs) on pre-defined contacts, with just a noticeable difference (JNDα) as the outcome variable. The second test estimated channel discrimination on the full electrode array, yielding a discrimination score of Dα. We measured speech perception as free-field consonant-vowel-consonant phoneme recognition scores. STUDY SAMPLE: We included 25 adults with at least 6 months of CI experience. RESULTS: JNDα and Dα scores measured on the same contact correlated significantly (rs = 0.64, p < 0.001). Mean JNDα and speech perception scores showed significant relationships in quiet and in noise. CONCLUSIONS: Dα correlated strongly with JNDα scores obtained with the PFs. For poor performers, the full-array test may underestimate JNDα. The full-array pitch discrimination test could be a helpful clinical tool, such as for fitting regions of lesser pitch discrimination ability.

Conformable Electrode Arrays for Wearable Neuroprostheses.

Wearable electrode arrays can selectively stimulate muscle groups by modulating their shape, size, and position over a targeted region. They can potentially revolutionize personalized rehabilitation by being noninvasive and allowing easy donning and doffing. Nevertheless, users should feel comfortable using such arrays, as they are typically worn for an extended time period. Additionally, to deliver safe and selective stimulation, these arrays must be tailored to a user's physiology. Fabricating customizable electrode arrays needs a rapid and economical technique that accommodates scalability. By leveraging a multilayer screen-printing technique, this study aims to develop personalizable electrode arrays by embedding conductive materials into silicone-based elastomers. Accordingly, the conductivity of a silicone-based elastomer was altered by adding carbonaceous material. The 1:8 and 1:9 weight ratio percentages of carbon black (CB) to elastomer achieved conductivities between 0.0021-0.0030 S cm-1 and were suitable for transcutaneous stimulation. Moreover, these ratios maintained their stimulation performance after several stretching cycles of up to 200%. Thus, a soft, conformable electrode array with a customizable design was demonstrated. Lastly, the efficacy of the proposed electrode arrays to stimulate hand function tasks was evaluated by in vivo experiments. The demonstration of such arrays encourages the realization of cost-effective, wearable stimulation systems for hand function restoration.

Selective Block of Upregulated Kv1.3 Potassium Channels in ON-Bipolar Cells of the Blind Retina Enhances Optogenetically Restored Signaling.

Loss of photoreceptors in retinal degenerative diseases also impacts the inner retina: bipolar cell dendrites retract, neurons rewire, and protein expression changes. ON-bipolar cells (OBCs) represent an attractive target for optogenetic vision restoration. However, the above-described maladaptations may negatively impact the quality of restored vision. To investigate this question, we employed human post-mortem retinas and transgenic rd1_Opto-mGluR6 mice expressing the optogenetic construct Opto-mGluR6 in OBCs and carrying the retinal degeneration rd1 mutation. We found significant changes in delayed rectifier potassium channel expression in OBCs of degenerative retinas. In particular, we found an increase in Kv1.3 expression already in early stages of degeneration. Immunohistochemistry localized Kv1.3 channels specifically to OBC axons. In whole-cell patch-clamp experiments, OBCs in the degenerated murine retina were less responsive, which could be reversed by application of the specific Kv1.3 antagonist Psora-4. Notably, Kv1.3 block significantly increased the amplitude and kinetics of Opto-mGluR6-mediated light responses in OBCs of the blind retina and increased the signal-to-noise ratio of light-triggered responses in retinal ganglion cells. We propose that reduction in Kv1.3 activity in the degenerated retina, either by pharmacological block or by KCNA3 gene silencing, could improve the quality of restored vision.

Epileptiform Events and Kainate Receptor Activity Changes Considerably during Entorhinal Cortex Development: An ex vivo Study.

Epilepsy is a commonly diagnosed neurological disease, which often develops already in childhood. The prominent feature of this dysfunction is the strong, unprovoked hypersynchronous neuronal activity of the brain, especially in the cortex, which appears in recurrent seizures. Previous studies indicated a potential modulatory role of kainate types of glutamate receptors in this mechanism. In our experiments, we used combined hippocampal-entorhinal rat brain slices of different ages. Developing (2-, 3-, and 4-week-old), adolescent (6-week-old), and adult (3-month-old) groups were investigated. During the experiments, first, we provoked convulsions with magnesium-free perfusion solution; then, to investigate the role of kainate receptors, seizure-like events (SLEs) were suppressed by applying a specific GluK1/2 antagonist (UBP-296). Neuronal network activity was recorded by a multi-electrode array chip, and temporal features of field potentials and single-cell activity were analyzed in the different age-groups. The frequency, duration of spontaneous events, the overall seizure characteristics, and spike activities were compared. Spontaneous events were categorized into interictal epileptiform discharges (IEDs) and SLEs on the basis of the temporal structure of activities. In 3- and 4-week-old animals, IEDs were observable, which entirely disappeared after the 4th week. The structure and the length of SLEs varied in the younger animals (3- and 4-week-old animals); however, after the 6th week, these events became more stabilized. In most groups, the count of detected spikes was significantly higher in layer II/III than in layer V. The neuronal networks started to behave like adult ones at 4 weeks of age. The length of events decreased in adult animals due to the maturation of the network, and the inhibition becomes stronger. The IEDs disappeared completely, and the SLEs became stable and stereotypic in 6-week-old animals. UBP-296 administration reduced the number of IEDs; however, this had no substantial effect on the SLEs.

Daily coordination of orexinergic gating in the rat superior colliculus-Implications for intrinsic clock activities in the visual system.

The orexinergic system delivers excitation for multiple brain centers to facilitate behavioral arousal, with its malfunction resulting in narcolepsy, somnolence, and notably, visual hallucinations. Since the circadian clock underlies the daily arousal, a timed coordination is expected between the orexin system and its target subcortical visual system, including the superior colliculus (SC). Here, we use a combination of electrophysiological, immunohistochemical, and molecular approaches across 24 h, together with the neuronal tract-tracing methods to investigate the daily coordination between the orexin system and the rodent SC. Higher orexinergic input was found to occur nocturnally in the superficial layers of the SC, in time for nocturnal silencing of spontaneous firing in this visual brain area. We identify autonomous daily and circadian expression of clock genes in the SC, which may underlie these day-night changes. Additionally, we establish the lateral hypothalamic origin of the orexin innervation to the SC and that the SC neurons robustly respond to orexin A via OX2 receptor in both excitatory and GABAA receptor-dependent inhibitory manners. Together, our evidence elucidates the combination of intrinsic and extrinsic clock mechanisms that shape the daily function of the visual layers of the SC.

Electrophysiological responses to seizurogenic compounds dependent on E/I balance in human iPSC-derived cortical neural networks.

Construction of in vitro functional assay systems using human-induced pluripotent stem cells (iPSCs) as indicators for evaluating seizure liability of compounds has been anticipated. Imbalance of excitation/inhibition (E/I) inputs triggers seizure; however, the appropriate ratio of E/I neurons for evaluating seizure liability of compounds in a human iPSC-derived neural network is unknown. Here, five neural networks with varying E/I ratios (88/12, 84/16, 74/26, 58/42, and 48/52) were constructed by altering the ratios of glutamatergic (E) and GABA (I) neurons. The responsiveness of each network against six seizurogenic compounds and two GABA receptor agonists was then examined by using six representative parameters. The 52% GABA neuron network, which had the highest ratio of GABA neurons, showed the most marked response to seizurogenic compounds, however, it suggested the possibility of producing false positives. Moreover, analytical parameters were found to vary with E/I ratio and to differ for seizurogenic compounds with different mechanism of action (MoA) even at the same E/I ratio. Clustering analysis using six parameters showed the balance of 84/16, which is the closest to the biological balance, was the most suitable for detection of concentration-dependent change and classification of the MoA of seizurogenic compounds. These results suggest the importance of using a human-iPSC-derived neural network similar to the E/I balance of the living body in order to improve the prediction accuracy in the in vitro seizure liability assessment.

Electrode array design determines scalar position, dislocation rate and angle and postoperative speech perception.

PURPOSE: The aim of this study is to examine the scalar dislocation rate in straight and perimodiolar electrode arrays in relation to cochlear morphology. Furthermore, we aim to analyze the specific dislocation point of electrode arrays depending on their design and shape and to correlate these results to postoperative speech perception. METHODS: We conducted a comparative analysis of patients (ears: n = 495) implanted between 2013 and 2018 with inserted perimodiolar or straight electrode arrays from Cochlear™ or MED-EL. CBCT (cone beam computed tomography) was used to determine electrode array position (scalar insertion, intra-cochlear dislocation, point of dislocation and angular insertion depth). Furthermore, cochlear morphology was measured. The postoperative speech discrimination was compared regarding electrode array dislocation, primary scalar insertion and angular insertion depth. RESULTS: The electrode array with the highest rate of primary SV insertions was the CA; the electrode array with the highest rate of dislocations out of ST was the FlexSoft. We did not find significantly higher dislocation rates in cochleostomy-inserted arrays. The angle of dislocation was electrode array design-specific. A multivariate nonparametric analysis revealed that the dislocation of the electrode array has no significant influence on postoperative speech perception. Nevertheless, increasing angular insertion depth significantly reduced postoperative speech perception for monosyllables. CONCLUSION: This study demonstrates the significant influence of electrode array design on scalar location, dislocation and the angle of dislocation itself. Straight and perimodiolar electrode arrays differ from each other regarding both the rate and place of dislocation. Insertion via cochleostomy does not lead to increased dislocation rates in any of the included electrode arrays. Furthermore, speech perception is significantly negatively influenced by angular insertion depth.

Research on a Non-Contact Multi-Electrode Voltage Sensor and Signal Processing Algorithm.

Traditional contact voltage measurement requires a direct electrical connection to the system, which is not easy to install and maintain. The voltage measurement based on the electric field coupling plate capacitance structure does not need to be in contact with the measured object or the ground, which can avoid the above problems. However, most of the existing flat-plate structure voltage measurement sensors are not only expensive to manufacture, but also bulky, and when the relative position between the wire under test and the sensor changes, it will bring great measurement errors, making it difficult to meet actual needs. Aiming to address the above problems, this paper proposes a multi-electrode array structure non-contact voltage sensor and signal processing algorithm. The sensor is manufactured by the PCB process, which effectively reduces the manufacturing cost and process difficulty. The experimental and simulation results show that, when the relative position of the wire and the sensor is offset by 10 mm in the 45° direction, the relative error of the traditional single-electrode voltage sensor is 17.62%, while the relative error of the multi-electrode voltage sensor designed in this paper is only 0.38%. In addition, the ratio error of the sensor under the condition of power frequency of 50 Hz is less than ±1% and the phase difference is less than 4°. The experimental results show that the sensor has good accuracy and linearity.

Sensitive Electrochemical Non-Enzymatic Detection of Glucose Based on Wireless Data Transmission.

Miniaturization and wireless continuous glucose monitoring are key factors for the successful management of diabetes. Electrochemical sensors are very versatile and can be easily miniaturized for wireless glucose monitoring. The authors report a microneedle-based enzyme-free electrochemical wireless sensor for painless and continuous glucose monitoring. The microneedles (MNs) fabricated consist of a 3 × 5 sharp and stainless-steel electrode array configuration. Each MN in the 3 × 5 array has 575 µm × 150 µm in height and width, respectively. A glucose-catalyzing layer, porous platinum black, was electrochemically deposited on the tips of the MNs by applying a fixed cathodic current of 2.5 mA cm-2 for a period of 200 s. For the non-interference glucose sensing, the platinum (Pt)-black-coated MN was carefully packaged into a biocompatible ionomer, nafion. The surface morphologies of the bare and modified MNs were studied using field-emission scanning electron microscopy (FESEM) and energy-dispersive X-ray analysis (EDX). The wireless glucose sensor displayed a broad linear range of glucose (1→30 mM), a good sensitivity and higher detection limit of 145.33 µA mM-1 cm-2 and 480 µM, respectively, with bare AuMN as a counter electrode. However, the wireless device showed an improved sensitivity and enhanced detection limit of 445.75, 165.83 µA mM-1 cm-2 and 268 µM, respectively, with the Pt-black-modified MN as a counter electrode. The sensor also exhibited a very good response time (2 s) and a limited interference effect on the detection of glucose in the presence of other electroactive oxidizing species, indicating a very fast and interference-free chronoamperometric response.

Vertical Nanowire Electrode Array for Enhanced Neurogenesis of Human Neural Stem Cells via Intracellular Electrical Stimulation.

Extracellular electrical stimulation (ES) can provide electrical potential from outside the cell membrane, but it is often ineffective due to interference from external factors such as culture medium resistance and membrane capacitance. To address this, we developed a vertical nanowire electrode array (VNEA) to directly provide intracellular electrical potential and current to cells through nanoelectrodes. Using this approach, the cell membrane resistivity and capacitance could be excluded, allowing effective ES. Human fetal neural stem cells (hfNSCs) were cultured on the VNEA for intracellular ES. Combining the structural properties of VNEA and VNEA-mediated ES, transient nanoscale perforation of the electrode was induced, promoting cell penetration and delivering current to the cell. Intracellular ES using VNEA improved the neuronal differentiation of hfNSCs more effectively than extracellular ES and facilitated electrophysiological functional maturation of hfNSCs because of the enhanced voltage-dependent ion-channel activity. The results demonstrate that VNEA with advanced nanoelectrodes serves as a highly effective culture and stimulation platform for stem-cell neurogenesis.