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Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CM) have been intensively used in drug development and disease modeling. Since iPSC-cardiomyocyte (CM) was first generated, their characterization has become a major focus of research. Multi-/micro-electrode array (MEA) systems provide a non-invasive user-friendly platform for detailed electrophysiological analysis of iPSC cardiomyocytes including drug testing to identify potential targets and the assessment of proarrhythmic risk. Here, we provide a systematical overview about the physiological and technical background of micro-electrode array measurements of iPSC-CM. We introduce the similarities and differences between action- and field potential and the advantages and drawbacks of MEA technology. In addition, we present current studies focusing on proarrhythmic side effects of novel and established compounds combining MEA systems and iPSC-CM. MEA technology will help to open a new gateway for novel therapies in cardiovascular diseases while reducing animal experiments at the same time.

In this report, we describe the development of a modified adeno‐associated virus (AAV) capsid and promoter for transduction of retinal ON‐bipolar cells. The bipolar cells, which are post‐synaptic to the photoreceptors, are important retinal targets for both basic and preclinical research. In particular, a therapeutic strategy under investigation for advanced forms of blindness involves using optogenetic molecules to render ON‐bipolar cells light‐sensitive. Currently, delivery of adequate levels of gene expression is a limiting step for this approach. The synthetic AAV capsid and promoter described here achieves high level of optogenetic transgene expression in ON‐bipolar cells. This evokes high‐frequency (~100 Hz) spiking responses in ganglion cells of previously blind, rd1 , mice. Our vector is a promising vehicle for further development toward potential clinical use. Synopsis An engineered genetically modified adeno‐associated virus is shown here to efficiently and specifically drive the optogenetic molecule channelrhodopsin‐2 in ON‐bipolar cells, rendering them light sensitive and restoring retinal function in blind rd1 mice. A synthetic AAV capsid and modified bipolar‐cell specific promoter were developed to enhance transgene expression in retinal bipolar cells. The new virus transduced at least 59% of ON‐bipolar cells in mouse retina. In the blind rd1 mouse the virus was used to drive expression of optogenetic channels at levels high enough to elicit strong and robust spiking responses from the ganglion cells. This new virus‐promoter combination is thus presented as a candidate vector for clinical intervention in advanced forms of retinal degeneration. Graphical Abstract An engineered genetically modified adeno‐associated virus is shown here to efficiently and specifically drive the optogenetic molecule channelrhodopsin‐2 in ON‐bipolar cells, rendering them light sensitive and restoring retinal function in blind rd1 mice.

Surface electromyography (sEMG) signals reflect muscle contraction and hence, can provide information regarding a user’s movement intention. High-density sEMG systems have been proposed to measure muscle activity in small areas and to estimate complex motion using spatial patterns. However, conventional systems based on wet electrodes have several limitations. For example, the electrolyte enclosed in wet electrodes restricts spatial resolution, and these conventional bulky systems limit natural movements. In this paper, a microneedle-based high-density electrode array on a circuit integrated flexible substrate for sEMG is proposed. Microneedles allow for high spatial resolution without requiring conductive substances, and flexible substrates guarantee stable skin–electrode contact. Moreover, a compact signal processing system is integrated with the electrode array. Therefore, sEMG measurements are comfortable to the user and do not interfere with the movement. The system performance was demonstrated by testing its operation and estimating motion using a Gaussian mixture model-based, simplified 2D spatial pattern.

The batch mode electrical discharge machining (EDM) method has been developed to improve the throughput and accuracy in fabricating array structures, but the process suffers from insufficient debris removal caused by the complex electrode geometry. Tool vibration has been used to improve flushing conditions, but to date the underlying mechanism of the tool vibration on the micro EDM of array structures remains unclear. This study aimed to investigate the effect of tool vibration on the machining process by direct observation of the discharge phenomena in the discharge gap by using a high-speed camera. Micro EDM experiments using 9 and 25 array electrodes were performed, and the effect of tool vibration on the discharge uniformity and tool wear was evaluated. It was found that tool vibration improved the uniformity of the discharge distribution, increased the machining efficiency, and suppressed the tool wear. The discharges occurred in periodic intervals, and the intensity increased with the amplitude of tool vibration. The results of this study indicate that the vibration parameters determine the discharge period duration and intensity to achieve optimum stability and efficiency of the machining process.

A mid‐scala cochlear implant electrode array, which was inserted with an atraumatic round window approach, could be replaced with longer lateral wall electrode array. Deeper electrode insertion seems to have beneficial influence on the hearing quality. A mid‐scala cochlear implant electrode array, which was inserted with an atraumatic round window approach, could be replaced with longer lateral wall electrode array. Deeper electrode insertion seems to have beneficial influence on the hearing quality.

Background: Radiological high-resolution computed tomography-based evaluation of cochlear implant candidates’ cochlear duct length (CDL) has become the method of choice for electrode array selection. The aim of the present study was to evaluate if MRI-based data match CT-based data and if this impacts on electrode array choice. Methods: Participants were 39 children. CDL, length at two turns, diameters, and height of the cochlea were determined via CT and MRI by three raters using tablet-based otosurgical planning software. Personalized electrode array length, angular insertion depth (AID), intra- and interrater differences, and reliability were calculated. Results: Mean intrarater difference of CT- versus MRI-based CDL was 0.528 ± 0.483 mm without significant differences. Individual length at two turns differed between 28.0 mm and 36.6 mm. Intrarater reliability between CT versus MRI measurements was high (intra-class correlation coefficient (ICC): 0.929–0.938). Selection of the optimal electrode array based on CT and MRI matched in 90.1% of cases. Mean AID was 629.5° based on the CT and 634.6° based on the MRI; this is not a significant difference. ICC of the mean interrater reliability was 0.887 for the CT-based evaluation and 0.82 for the MRI-based evaluation. Conclusion: MRI-based CDL measurement shows a low intrarater difference and a high interrater reliability and is therefore suitable for personalized electrode array selection.

Bioelectronic medicine is emerging as a powerful approach for restoring lost endogenous functions and addressing life‐altering maladies such as cardiac disorders. Systems that incorporate both modulation of cellular function and recording capabilities can enhance the utility of these approaches and their customization to the needs of each patient. Here we report an integrated optogenetic and bioelectronic platform for stable and long‐term stimulation and monitoring of cardiomyocyte function in vitro. Optical inputs are achieved through the expression of a photoactivatable adenylyl cyclase, that when irradiated with blue light causes a dose‐dependent and time‐limited increase in the secondary messenger cyclic adenosine monophosphate with subsequent rise in autonomous cardiomyocyte beating rate. Bioelectronic readouts are obtained through a multi‐electrode array that measures real‐time electrophysiological responses at 32 spatially‐distinct locations. Irradiation at 27 µW mm−2 results in a 14% elevation of the beating rate within 20–25 min, which remains stable for at least 2 h. The beating rate can be cycled through “on” and “off” light states, and its magnitude is a monotonic function of irradiation intensity. The integrated platform can be extended to stretchable and flexible substrates, and can open new avenues in bioelectronic medicine, including closed‐loop systems for cardiac regulation and intervention, for example, in the context of arrythmias. This study reports an integrated platform for simultaneous modulation and monitoring of cardiomyocyte function in vitro. Optical inputs are achieved through expression of a photoactivatable adenylyl cyclase, that when irradiated causes a reversible increase in beating rate. Bioelectronic outputs are achieved with a multi‐electrode array, which can record the beating rate and wavefront propagation characteristics with high spatiotemporal resolution.

Paired associative stimulation is a relatively new non-invasive brain stimulation technique that combines transcranial magnetic stimulation and peripheral nerve stimulation. The effects of paired associative stimulation on the excitability of the cerebral cortex can vary according to the time interval between the transcranial magnetic stimulation and peripheral nerve stimulation. We established a model of cerebral ischemia in rats via transient middle cerebral artery occlusion. We administered paired associative stimulation with a frequency of 0.05 Hz 90 times over 4 weeks. We then evaluated spatial learning and memory using the Morris water maze. Changes in the cerebral ultra-structure and synaptic plasticity were assessed via transmission electron microscopy and a 64-channel multi-electrode array. We measured mRNA and protein expression levels of brain-derived neurotrophic factor and N-methyl-D-aspartate receptor 1 in the hippocampus using a real-time polymerase chain reaction and western blot assay. Paired associative stimulation treatment significantly improved learning and memory in rats subjected to cerebral ischemia. The ultra-structures of synapses in the CA1 area of the hippocampus in rats subjected to cerebral ischemia were restored by paired associative stimulation. Long-term potentiation at synapses in the CA3 and CA1 regions of the hippocampus was enhanced as well. The protein and mRNA expression of brain-derived neurotrophic factor and N-methyl-D-aspartate receptor 1 increased after paired associative stimulation treatment. These data indicate that paired associative stimulation can protect cognition after cerebral ischemia. The observed effect may be mediated by increases in the mRNA and protein expression of brain-derived neurotrophic factor and N-methyl-D-aspartate receptor 1, and by enhanced synaptic plasticity in the CA1 area of the hippocampus. The animal experiments were approved by the Animal Ethics Committee of Tongji Medical College, Huazhong University of Science & Technology, China (approval No. TJ-A20151102) on July 11, 2015.

This technical report describes a 360-channel flexible multi-electrode array with high spatial resolution, wide coverage area and minimal damage to the recorded neural tissue. Among other descriptions of multiunit in vivo neuronal recording in cats, the authors also use the electrode array to show spiral-patterned spread of epileptic neural activity in the neocortex. Arrays of electrodes for recording and stimulating the brain are used throughout clinical medicine and basic neuroscience research, yet are unable to sample large areas of the brain while maintaining high spatial resolution because of the need to individually wire each passive sensor at the electrode-tissue interface. To overcome this constraint, we developed new devices that integrate ultrathin and flexible silicon nanomembrane transistors into the electrode array, enabling new dense arrays of thousands of amplified and multiplexed sensors that are connected using fewer wires. We used this system to record spatial properties of cat brain activity in vivo , including sleep spindles, single-trial visual evoked responses and electrographic seizures. We found that seizures may manifest as recurrent spiral waves that propagate in the neocortex. The developments reported here herald a new generation of diagnostic and therapeutic brain-machine interface devices.

The Middle East respiratory syndrome corona virus (MERS-CoV) is highly pathogenic. An immunosensor for the determination of MERS-CoV is described here. It is based on a competitive assay carried out on an array of carbon electrodes (DEP) modified with gold nanoparticles. Recombinant spike protein S1 was used as a biomarker for MERS CoV. The electrode array enables multiplexed detection of different CoVs. The biosensor is based on indirect competition between free virus in the sample and immobilized MERS-CoV protein for a fixed concentration of antibody added to the sample. Voltammetric response is detected by monitoring the change in the peak current (typically acquired at a working potential of −0.05 V vs. Ag/AgCl) after addition of different concentrations of antigen against MERS-CoV. Electrochemical measurements using ferrocyanide/ferricyanide as a probe were recorded using square wave voltammetry (SWV). Good linear response between the sensor response and the concentrations from 0.001 to 100 ng.mL −1 and 0.01 to 10,000 ng.mL −1 were observed for MERS-CoV and HCoV, respectively. The assay was performed in 20 min with detection limit as low as 0.4 and 1.0 pg.mL −1 for HCoV and MERS-CoV, respectively. The method is highly selective over non-specific proteins such as Influenza A and B. The method is single-step, sensitive and accurate. It was successfully applied to spiked nasal samples. Graphical abstract An electrochemical immunoassay is described for the Middle East Respiratory Syndrome Corona Virus (MERS-CoV). The method is based on a competitive assay carried out on a carbon array electrodes (DEP) nanostructured with gold nanoparticles. The array electrodes enable the multiplexed detection of different types of Corona Virus.