LTCC Strip Electrode Arrays for Gas Electron Multiplier Detectors

The Low Temperature Cofired Ceramic (LTCC) technology has proven to be highly suitable for 3D microstructures manufacturing in electronic devices due to its excellent electrical and mechanical properties. In this paper, a novel idea of implementing the LTCC structures into high-energy particle detectors technology is proposed. It can be applied in High Energy Physics (HEP) laboratories, where such sophisticated sensors are constantly exposed to particles of the TeV energy range for many years. The most advanced applications of the concept are based on dedicated gas amplifier systems coupled with readout microstructures. Typically, the readout microstructures are made in the Printed Circuit Boards (PCB) technology and processed in a sophisticated and patent-protected way. This article presents the manufacturing process and parameters of the novel microstructures made in the LTCC technology. The structures were implemented into the high-energy particle detector, and the first results are presented.

Comparative study of platinum electroplating to improve micro gold electrode arrays with LCP laminate

Decoding the cellular network interaction of neurons and glial cells are important in the development of new therapies for diseases of the central nervous system (CNS). Electrophysiological in vivo studies in mice will help to understand the highly complex network. In this paper, the optimization of epidural liquid crystal polymer (LCP) electrodes for different platinum electroplating parameters are presented and compared. Constant current and pulsed current electroplating varied in strength and duration was used to decrease the electrode impedance and to increase the charge storage capacity (CSCC). In best cases, both methods generated similar results with an impedance reduction of about 99%. However, electroplating with pulsed currents was less parameter-dependent than the electroplating with constant current. The use of ultrasound was essential to generate platinum coatings without plating defects. Electrode model parameters extracted from the electrode impedance reflected the increase in surface porosity due to the electroplating processes.

Prefrontal cortical plasticity during learning of cognitive tasks

Training in working memory tasks is associated with lasting changes in prefrontal cortical activity. To assess the neural activity changes induced by training, we recorded single units, multi-unit activity (MUA) and local field potentials (LFP) with chronic electrode arrays implanted in the prefrontal cortex of two monkeys, throughout the period they were trained to perform cognitive tasks. Mastering different task phases was associated with distinct changes in neural activity, which included recruitment of larger numbers of neurons, increases or decreases of their firing rate, changes in the correlation structure between neurons, and redistribution of power across LFP frequency bands. In every training phase, changes induced by the actively learned task were also observed in a control task, which remained the same across the training period. Our results reveal how learning to perform cognitive tasks induces plasticity of prefrontal cortical activity, and how activity changes may generalize between tasks.

Inhibition of Neuronal Necroptosis Mediated by RIPK1 Provides Neuroprotective Effects on Hypoxia and Ischemia In Vitro and In Vivo

Ischemic brain injury is a widespread pathological condition, the main components of which are a deficiency of oxygen and energy substrates. In recent years, a number of new forms of cell death, including necroptosis, have been described. In necroptosis, a cascade of interactions between the kinases RIPK1 and RIPK3 and the MLKL protein leads to the formation of a specialized death complex called the necrosome, which triggers MLKL-mediated destruction of the cell membrane and necroptotic cell death. Necroptosis probably plays an important role in the development of ischemia/reperfusion injury and can be considered as a potential target for finding methods to correct the disruption of neural networks in ischemic damage. In the present study, we demonstrated that blockade of RIPK1 kinase by Necrostatin-1 preserved the viability of cells in primary hippocampal cultures in an in vitro model of glucose deprivation. The effect of RIPK1 blockade on the bioelectrical and metabolic calcium activity of neuron-glial networks in vitro using calcium imaging and multi-electrode arrays was assessed for the first time. RIPK1 blockade was shown to partially preserve both calcium and bioelectric activity of neuron-glial networks under ischemic factors. However, it should be noted that RIPK1 blockade does not preserve the network parameters of the collective calcium dynamics of neuron-glial networks, despite the maintenance of network bioelectrical activity (the number of bursts and the number of spikes in the bursts). To confirm the data obtained in vitro, we studied the effect of RIPK1 blockade on the resistance of small laboratory animals to in vivo modeling of hypoxia and cerebral ischemia. The use of Necrostatin-1 increases the survival rate of C57BL mice in modeling both acute hypobaric hypoxia and ischemic brain damage.

Base Editing of Human Pluripotent Stem Cells for Modeling Long QT Syndrome

Human pluripotent stem cells (hPSCs) have great potential for disease modeling, drug discovery, and regenerative medicine as they can differentiate into many different functional cell types via directed differentiation. However, the application of disease modeling is limited due to a time-consuming and labor-intensive process of introducing known pathogenic mutations into hPSCs. Base editing is a newly developed technology that enables the facile introduction of point mutations into specific loci within the genome of living cells without unwanted genome injured. We describe an optimized stepwise protocol to introduce disease-specific mutations of long QT syndrome (LQTs) into hPSCs. We highlight technical issues, especially those associated with introducing a point mutation to obtain isogenic hPSCs without inserting any resistance cassette and reproducible cardiomyocyte differentiation. Based on the protocol, we succeeded in getting hPSCs carrying LQTs pathogenic mutation with excellent efficiency (31.7% of heterozygous clones, 9.1% of homozygous clones) in less than 20 days. In addition, we also provide protocols to analyze electrophysiological of hPSC-derived cardiomyocytes using multi-electrode arrays. This protocol is also applicable to introduce other disease-specific mutations into hPSCs. Graphical abstract

Low-cost and easy-fabrication lightweight drivable electrode array for multiple-regions electrophysiological recording in free-moving mice

Objective. Extracellular electrophysiology has been widely applied to neural circuit dissections. However, long-term multiregional recording in free-moving mice remains a challenge. Low-cost and easy-fabrication of elaborate drivable electrodes is required for their prevalence. Approach. A three-layer nested construct (OD ~1.80 mm, length ~10 mm, <0.1g) was recruited as a drivable component, which consisted of an ethylene-vinyl acetate copolymer (EVA) heat-shrinkable tube, non-closed loop ceramic bushing, and stainless ferrule with a bulge twining silver wire. The supporting and working components were equipped with drivable components to be assembled into a drivable microwire electrode array with a nested structure (drivable MEANS). Two drivable microwire electrode arrays were independently implanted for chronic recording in different brain areas at respective angles. An optic fiber was easily loaded into the drivable MEANS to achieve optogenetic modulation and electrophysiological recording simultaneously. Main results. The drivable MEANS had lightweight (~ 0.37 g), small (~ 15 mm ×15 mm × 4 mm), and low cost (≤ $64.62). Two drivable MEANS were simultaneously implanted in mice, and high-quality electrophysiological recordings could be applied ≥ 5 months after implantation in freely behaving animals. Electrophysiological recordings and analysis of the lateral septum (LS) and lateral hypothalamus (LH) in food-seeking behavior demonstrated that our drivable MEANS can be used to dissect the function of neural circuits. An optical fiber-integrated drivable MEANS (~ 0.47 g) was used to stimulate and record LS neurons, which suggested that changes in working components can achieve more functions than electrophysiological recordings, such as optical stimulation, drug release, and calcium imaging. Significance. Drivable MEANS is an easily fabricated, lightweight drivable microwire electrode array for multiple-region electrophysiological recording in free-moving mice. Our design is likely to be a valuable platform for both current and prospective users, as well as for developers of multifunctional electrodes for free-moving mice.

Neurophysiology of the Developing Cerebral Cortex: What We Have Learned and What We Need to Know

This review article aims to give a brief summary on the novel technologies, the challenges, our current understanding, and the open questions in the field of the neurophysiology of the developing cerebral cortex in rodents. In the past, in vitro electrophysiological and calcium imaging studies on single neurons provided important insights into the function of cellular and subcellular mechanism during early postnatal development. In the past decade, neuronal activity in large cortical networks was recorded in pre- and neonatal rodents in vivo by the use of novel high-density multi-electrode arrays and genetically encoded calcium indicators. These studies demonstrated a surprisingly rich repertoire of spontaneous cortical and subcortical activity patterns, which are currently not completely understood in their functional roles in early development and their impact on cortical maturation. Technological progress in targeted genetic manipulations, optogenetics, and chemogenetics now allow the experimental manipulation of specific neuronal cell types to elucidate the function of early (transient) cortical circuits and their role in the generation of spontaneous and sensory evoked cortical activity patterns. Large-scale interactions between different cortical areas and subcortical regions, characterization of developmental shifts from synchronized to desynchronized activity patterns, identification of transient circuits and hub neurons, role of electrical activity in the control of glial cell differentiation and function are future key tasks to gain further insights into the neurophysiology of the developing cerebral cortex.

The Layer 7 Cortical Interface: A Scalable and Minimally Invasive Brain-Computer Interface Platform

Progress toward the development of brain-computer interfaces has signaled the potential to restore, replace, or augment lost or impaired neurological function in a variety of disease states. Existing brain-computer interfaces rely on invasive surgical procedures or brain-penetrating electrodes, which limit addressable applications of the technology and the number of eligible patients. Here we describe a novel approach to constructing a neural interface, comprising conformable thin-film electrode arrays and a minimally invasive surgical delivery system that together facilitate communication with large portions of the cortical surface in bidirectional fashion (enabling both recording and stimulation). We demonstrate the safety and feasibility of rapidly delivering reversible implants containing over 2,000 microelectrodes to multiple functional regions in both hemispheres of the Gottingen minipig brain simultaneously, without requiring a craniotomy, at an effective insertion rate faster than 40 ms per channel, without damaging the cortical surface. We further demonstrate the performance of this system for high-density neural recording, focal cortical stimulation, and accurate neural decoding. Such a system promises to accelerate efforts to better decode and encode neural signals, and to expand the patient population that could benefit from neural interface technology.

Continuous monitoring of the health status of cement-based structures: electrical impedance measurements and remote monitoring solutions

<p class="Abstract">The continuous monitoring of cement-based structures and infrastructures is fundamental to optimize their service life and reduce maintenance costs. In the framework of the EnDurCrete project (GA no. 760639), a remote monitoring system based on electrical impedance measurements was developed. Electrical impedance is measured according to the Wenner’s method, using 4-electrode arrays embedded in concrete during casting, selecting alternating current as excitation, to avoid the polarization of both electrode/material interface and of material itself. With this measurement, it is possible to promptly identify events related to contaminants ingress or damages (e.g. cracks formation). Conductive additions are included in some elements to enhance signal-to-noise ratio, as well as the self-sensing properties of concrete. Specifically, a distributed sensor network was implemented<span style="text-decoration: line-through;">,</span> consisting of measurement nodes installed in the elements to be monitored, then connected to a central hub (RS-232 protocol). Nodes are realized with an embedded unit for electrical impedance measurements (EVAL-AD5940BIOZ board with AD5940 chip, by Analog Device) and a digital thermometer (DS18B20 by Maxim Integrated), enclosed in cabinets filled with an IP68 gel against moist-related problems. Data are available on a Cloud through Wi-Fi network or LTE modem, hence can be accessed remotely via a use-friendly multi-platform interface.</p>

Impact of High-Dose Irradiation on Human iPSC-Derived Cardiomyocytes Using Multi-Electrode Arrays: Implications for the Antiarrhythmic Effects of Cardiac Radioablation

Cardiac radioablation is emerging as an alternative option for refractory ventricular arrhythmias. However, the immediate acute effect of high-dose irradiation on human cardiomyocytes remains poorly known. We measured the electrical activities of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) upon irradiation with 0, 20, 25, 30, 40, and 50 Gy using a multi-electrode array, and cardiomyocyte function gene levels were evaluated. iPSC-CMs showed to recover their electrophysiological activities (total active electrode, spike amplitude and slope, and corrected field potential duration) within 3–6 h from the acute effects of high-dose irradiation. The beat rate immediately increased until 3 h after irradiation, but it steadily decreased afterward. Conduction velocity slowed in cells irradiated with ≥25 Gy until 6–12 h and recovered within 24 h; notably, 20 and 25 Gy-treated groups showed subsequent continuous increase. At day 7 post-irradiation, except for cTnT, cardiomyocyte function gene levels increased with increasing irradiation dose, but uniquely peaked at 25–30 Gy. Altogether, high-dose irradiation immediately and reversibly modifies the electrical conduction of cardiomyocytes. Thus, compensatory mechanisms at the cellular level may be activated after the high-dose irradiation acute effects, thereby, contributing to the immediate antiarrhythmic outcome of cardiac radioablation for refractory ventricular arrhythmias.