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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.

The emerging field of neuroprosthetics is focused on the development of therapeutic interventions that restore lost neural function by stimulating sensory or motor pathways, or by harnessing activity recorded from remnant neural pathways to control an external device. As Richard Normann discusses in this Review, penetrating microelectrode arrays are providing unprecedented selective access to the neurons of the CNS and PNS, and are likely to form the basis for new therapies for disorders of the nervous system. Most disorders of the nervous system result from localized sensory or motor pathologies attributable to disease or trauma. The emerging field of neuroprosthetics is focused on the development of therapeutic interventions that will be able to restore some of this lost neural function by selective electrical stimulation of sensory or motor pathways, or by harnessing activity recorded from remnant neural pathways. A key element in this restoration of function has been the development of a new generation of penetrating microelectrode arrays that provide unprecedented selective access to the neurons of the CNS and PNS. The active tips of these microelectrode arrays penetrate the nervous tissues and abut against small populations of neurons or nerve fibers, thereby providing selective access to these cells. These electrode arrays are not only beginning to provide researchers with the ability to better study the spatiotemporal information processing performed by the nervous system, they can also form the basis for new therapies for disorders of the nervous system. In this Review, three examples of this new generation of microelectrode arrays are described, as are potential therapeutic applications in blindness and spinal cord injury, and for the control of prosthetic limbs. Key Points Neuroprosthetic devices are therapeutic interventions that restore lost neural function by electrical stimulation of sensory or motor pathways, or by harnessing activity recorded from remnant neural pathways Research teams at the Universities of Utah and Michigan have developed high-electrode-count, penetrating microelectrode arrays that interface with the CNS and PNS The Utah Electrode Array was originally developed as a means of restoring limited but useful sight to individuals with profound blindness The Utah Slanted Electrode Array can produce a sit-to-stand maneuver in an animal model; similar approaches might eventually be applied to patients with spinal cord injury Another promising application of neuroprosthetic technology is the control of prosthetic limbs via recording and stimulation of severed peripheral nerves In the future, neuroprosthetic technology might also be applied to bladder and bowel control, pacing of the diaphragm, and control of epilepsy and chronic depression

To understand spatiotemporally coordinated activity in neural networks and interaction between different areas or layers in brain tissue, simultaneous multisite recording is a prerequisite. For in vitro studies pursuing these goals, substrate integrated, planar microelectrode arrays (MEAs) have been developed to monitor spikes and local field potentials. Here we report for the first time recordings of single-unit spike activity with MEAs in acute slice preparations of the rat cerebellum. We compare these recordings to results of conventional techniques, and discuss the recording conditions in view of the equivalent circuits commonly used. Simultaneous recordings with tungsten microelectrodes and MEAs verified that recording characteristics and signal-to-noise ratios of MEA electrodes were comparable to those of conventional extracellular electrodes. Spike shapes were identical on both electrodes. We found no detectable overlap between spike signals recorded at neighboring MEA electrodes (200 microm spacing). Neuronal spike activity was detected with MEA electrodes at distances of up to 100 microm from the site of spike generation. We conclude that extracellular recording of independent single-unit spike activity with MEAs is indeed suitable to monitor network activity in acute slices, making MEAs an exceptionally useful tool for the assessment of fast network dynamics in acute slices.

The hormone Neuropeptide Y (NPY) plays critical roles in feeding, satiety, obesity, and weight control. However, its complex peptide structure has hindered the development of fast and biocompatible detection methods. Previous studies utilizing electrochemical techniques with carbon fiber microelectrodes (CFMEs) have targeted the oxidation of amino acid residues like tyrosine to measure peptides. Here, we employ the modified sawhorse waveform (MSW) to enable voltammetric identification of NPY through tyrosine oxidation. Use of MSW improves NPY detection sensitivity and selectivity by reducing interference from catecholamines like dopamine, serotonin, and others compared to the traditional triangle waveform. The technique utilizes a holding potential of −0.2 V and a switching potential of 1.2 V that effectively etches and renews the CFME surface to simultaneously detect NPY and other monoamines with a sensitivity of 5.8 ± 0.94 nA/µM (n = 5). Furthermore, we observed adsorption-controlled, subsecond NPY measurements with CFMEs and MSW. The effective identification of exogenously applied NPY in biological fluids demonstrates the feasibility of this methodology for in vivo and ex vivo studies. These results highlight the potential of MSW voltammetry to enable fast, biocompatible NPY quantification to further elucidate its physiological roles.

While microelectrode arrays (MEAs) offer the promise of elucidating functional neural circuitry and serve as the basis for a cortical neuroprosthesis, the challenge of designing and demonstrating chronically reliable technology remains. Numerous studies report “chronic” data but the actual time spans and performance measures corresponding to the experimental work vary. In this study, we reviewed the experimental durations that constitute chronic studies across a range of MEA types and animal species to gain an understanding of the widespread variability in reported study duration. For rodents, which are the most commonly used animal model in chronic studies, we examined active electrode yield (AEY) for different array types as a means to contextualize the study duration variance, as well as investigate and interpret the performance of custom devices in comparison to conventional MEAs. We observed wide-spread variance within species for the chronic implantation period and an AEY that decayed linearly in rodent models that implanted commercially-available devices. These observations provide a benchmark for comparing the performance of new technologies and highlight the need for consistency in chronic MEA studies. Additionally, to fully derive performance under chronic conditions, the duration of abiotic failure modes, biological processes induced by indwelling probes, and intended application of the device are key determinants.

Bacteria found in diverse ecosystems grow in a community of aggregated cells that favors their survival and colonization. Different extracellular polymeric substances are used to entrap this multispecies community forming a biofilm, which can be associated to biotic and abiotic surfaces. This widespread and successful way of bacterial life, however, can lead to negative effects for human activity since many pathogen and spoiling bacteria form biofilms which are not easy to eradicate. Therefore, the search for novel anti-biofilm bio-active molecules is a very active research area for which simple, reliable, and fast screening methods are demanded. In this work we have successfully validated an impedance-based method, initially developed for the study of adherent eukaryotic cells, to monitor the formation of single-species biofilms of three model bacteria in real time. The xCelligence real time cell analyzer (RTCA) equipment uses specific microtiter E-plates coated with gold-microelectrodes that detect the attachment of adherent cells, thus modifying the impedance signal. In the current study, this technology allowed the distinction between biofilm-producers and non-producers of Staphylococcus aureus and Staphylococcus epidermidis, as well as the formation of Streptococcus mutans biofilms only when sucrose was present in the culture medium. Besides, different impedance values permitted discrimination among the biofilm-producing strains tested regardless of the nature of the polymeric biofilm matrix. Finally, we have continuously monitored the inhibition of staphylococcal biofilm formation by the bacteriophage phi-IPLA7 and the bacteriophage-encoded endolysin LysH5, as well as the removal of a preformed biofilm by this last antimicrobial treatment. Results observed with the impedance-based method showed high correlation with those obtained with standard approaches, such as crystal violet staining and bacteria enumeration, as well as with those obtained upon other abiotic surfaces (polystyrene and stainless steel). Therefore, this RTCA technology opens new opportunities in the biofilm research arena and its application could be further explored for other bacterial genera as well as for different bio-active molecules.

Neurological diseases are a prevalent cause of global mortality and are of growing concern when considering an ageing global population. Traditional treatments are accompanied by serious side effects including repeated treatment sessions, invasive surgeries, or infections. For example, in the case of deep brain stimulation, large, stiff, and battery powered neural probes recruit thousands of neurons with each pulse, and can invoke a vigorous immune response. This paper presents challenges in engineering and neuroscience in developing miniaturized and biointegrated alternatives, in the form of microelectrode probes. Progress in design and topology of neural implants has shifted the goal post toward highly specific recording and stimulation, targeting small groups of neurons and reducing the foreign body response with biomimetic design principles. Implantable device design recommendations, fabrication techniques, and clinical evaluation of the impact flexible, integrated probes will have on the treatment of neurological disorders are provided in this report. The choice of biocompatible material dictates fabrication techniques as novel methods reduce the complexity of manufacture. Wireless power, the final hurdle to truly implantable neural interfaces, is discussed. These aspects are the driving force behind continued research: significant breakthroughs in any one of these areas will revolutionize the treatment of neurological disorders. In this progress report, the evolution of neural stimulation is explored with a view to providing practical design guidelines for innovative, flexible, and fully integrated implantable probes. From the foreign body response, to the material characteristics of the brain, all aspects of the target tissue must be accommodated. Fabrication techniques, as well as wireless power approaches, are also discussed.

This paper describes the use of PolyJet 3D printing to fabricate microchip electrophoresis devices with integrated microwire electrodes for amperometric detection. The fabrication process involves 3D printing of two separate pieces, a channel layer and an electrode layer. The channel layer is created by 3D printing on a pre-fabricated mold with a T-intersection. For the electrode layer, a stencil design is printed directly on the printing tray and covered with a piece of transparent glass. Microwire electrodes are adhered over the glass piece (guided by underlaying stencil) and a CAD design of the electrode layer is then printed on top of the microwire electrode. After delamination from the glass after printing, the microwire is embedded in the printed piece, with the stencil design ensuring that alignment and positioning of the electrode is reproducible for each print. After a thermal bonding step between the channel layer and electrode layer, a complete electrophoresis device with integrated microelectrodes for amperometric detection results. It is shown that this approach enables different microwire electrodes (gold or platinum) and sizes (100 or 50 µm) to be integrated in an end-channel configuration with no gap between the electrode and the separation channel. These devices were used to separate a mixture of catecholamines and the effect of separation voltage on the potential voltage applied on the working electrode was also investigated. In addition, the effect of electrode size on the number of theoretical plates and limit of detection was studied. Finally, a device that contains different channel heights and a detection electrode was 3D-printed to integrate continuous flow sampling with microchip electrophoresis and amperometric detection.

Mapping brain activity has received growing worldwide interest because it is expected to improve disease treatment and allow for the development of important neuromorphic computational methods. MEMS and microsystems are expected to continue to offer new and exciting solutions to meet the need for high-density, high-fidelity neural interfaces. Herein, the state-of-the-art in recording and stimulation tools for brain research is reviewed, and some of the most significant technology trends shaping the field of neurotechnology are discussed. Neuroscience: Cutting-edge microsystems advance brain research Understanding even the most basic brain functions will require considerable advances in the MEMS-based tools that are used in brain research. Sensors that are capable of monitoring single neurons or mapping the complex neural networks responsible for faculties such as memory or learning will be crucial for furthering our knowledge. As the human brain contains around 85 million neurons and 100 trillion synapses, the challenge is enormous. John Seymour and Euisik Yoon and colleagues at the University of Michigan, United States, review the state of the art in microsystem devices that are used to record and stimulate the brain. They highlight innovations in multimodal sensor arrays and illustrate the need for further innovation in packaging and microsystems to match the scale of the neuronal circuits under study. Ultimately the teamwork between neurotechnologists and neuroscientists will lead to critical breakthroughs in brain research over the next decade.

Organic–inorganic hybrid nanocomposites (OIHN), with tailored surface chemistry, offer ultra-sensitive architecture capable of detecting ultra-low concentrations of target analytes with precision. In the present work, a novel nano-biosensor was fabricated, acquainting dynamic synergy of reduced graphene oxide (rGO) decorated hexagonal boron nitride nanosheets (hBNNS) for detection of carcinoembryonic antigen (CEA). Extensive spectroscopic and microscopic analyses confirmed the successful hydrothermal synthesis of cross-linked rGO-hBNNS nanocomposite. Uniform micro-electrodes of rGO-hBNNS onto pre-hydrolyzed ITO were obtained via electrophoretic deposition (EPD) technique at low DC potential (15 V). Optimization of antibody incubation time, pH of supporting electrolyte, and immunoelectrode preparation was thoroughly investigated to enhance nano-biosensing efficacy. rGO-modified hBNNS demonstrated 29% boost in electrochemical performance over bare hBNNS, signifying remarkable electro-catalytic activity of nano-biosensor. The presence of multifunctional groups on the interface facilitated stable crosslinking chemistry, increased immobilization density, and enabled site-specific anchoring of Anti-CEA, resulting in improved binding affinity. The nano-biosensor demonstrated a remarkably low limit of detection of 5.47 pg/mL (R2 = 0.99963), indicating exceptional sensitivity and accuracy in detecting CEA concentrations from 0 to 50 ng/mL. The clinical evaluation confirmed its exceptional shelf life, minimal cross-reactivity, and robust recovery rates in human serum samples, thereby unraveling the potential for early, highly sensitive, and reliable CEA detection.