Search

To cope with the growing needs in research towards the understanding of cellular function and network dynamics, advanced micro-electrode arrays (MEAs) based on integrated complementary metal oxide semiconductor (CMOS) circuits have been increasingly reported. Although such arrays contain a large number of sensors for recording and/or stimulation, the size of the electrodes on these chips are often larger than a typical mammalian cell. Therefore, true single-cell recording and stimulation remains challenging. Single-cell resolution can be obtained by decreasing the size of the electrodes, which inherently increases the characteristic impedance and noise. Here, we present an array of 16,384 active sensors monolithically integrated on chip, realized in 0.18 μm CMOS technology for recording and stimulation of individual cells. Successful recording of electrical activity of cardiac cells with the chip, validated with intracellular whole-cell patch clamp recordings are presented, illustrating single-cell readout capability. Further, by applying a single-electrode stimulation protocol, we could pace individual cardiac cells, demonstrating single-cell addressability. This novel electrode array could help pave the way towards solving complex interactions of mammalian cellular networks., (This journal is © The Royal Society of Chemistry 2012)

APP.V717I and Tau.P301L transgenic mice develop Alzheimer's disease pathology comprising important aspects of human disease including increased levels of amyloid peptides, cognitive and motor impairment, amyloid plaques and neurofibrillary tangles. The combined model, APP.V717I×Tau.P301L bigenic mice (biAT mice) exhibit aggravated amyloid and tau pathology with severe cognitive and behavioral defects. In the present study, we investigated early changes in synaptic function in the CA1 and CA3 regions of acute hippocampal slices of young APP.V717I, Tau.P301L and biAT transgenic animals. We have used planar multi-electrode arrays (MEA) and improved methods for simultaneous multi-site recordings from two hippocampal sub-regions. In the CA1 region, long-term potentiation (LTP) was severely impaired in all transgenic animals when compared with age-matched wild-type controls, while basal synaptic transmission and paired-pulse facilitation were minimally affected. In the CA3 region, LTP was normal in Tau.P301L and APP.V717I but clearly impaired in biAT mice. Surprisingly, frequency facilitation in CA3 was significantly enhanced in Tau.P301L mice, while not affected in APP.V717I mice and depressed in biAT mice. The findings demonstrate important synaptic changes that differ considerably in the hippocampal sub-regions already at young age, well before the typical amyloid or tau pathology is evident., (Copyright © 2011 Elsevier Inc. All rights reserved.)

In drug screening and pharmaceutical research, high-throughput systems that are able to perform single-cell measurements are highly desired. Micro-electrode arrays try to answer this need but still suffer from significant drawbacks such as a small amount of electrodes and the inability to address single cells. Here, we present a novel multi-transistor array chip with 16,384 subcellular-sized electrodes based on 0.18 µm CMOS technology. We show that single-cell stimulation is possible by applying voltage pulses on the electrode to stimulate the cells lying on top. Electroporation of the cell membrane is observed using the whole-cell patch clamp technique and fluorescent dye-based live imaging. This technology could be used for high-throughput, single-cell manipulations for the purpose of large-scale drug screening and the investigation of fundamental cell processes.

Recent advancements in wearable technology have led to a new era of intelligent wound dressings capable of monitoring vital healing biomarkers. While a significant leap from traditional gauze dressings, these innovations still necessitate periodic removal and disposal. Bioresorbable electrochemical sensors have emerged as a promising and sustainable solution, offering continuous monitoring of critical wound healing biomarkers in real‐time and in situ, followed by their full physiological resorption. The current challenge lies in the susceptibility of metallic electrodes to harsh electrolytic biofluids, hindering the development of viable transient electrochemical sensors. This study pioneers a bioresorbable electrochemical material and unique architecture comprising engineered sputtered tungsten (W) plus tungsten oxide (WOx) thin films, taking advantage of their high catalytic activity and uniquely gradual biodissolution. While a bare W film electrode detached from the wafer substrate within 5 hours of soaking, an annealed W‐WOx electrode showcases a notable electrochemical stability at body temperature, for up to several days. The latter reliably senses multiple analytes during 24‐hour room‐temperature tests. These findings underscore the potential of annealed W plus WOx electrodes in future bioresorbable wound management systems. [ABSTRACT FROM AUTHOR]

Neural probes have become the most important tool for enabling neuroscientists to place microelectrode sensors close to individual neurons and to monitor their activity in vivo. With such devices, it is possible to perform acute or chronic extracellular recordings of electrical activity from a single neuron or from groups of neurons. After the many developments in neural implants, it has become clear that large arrays of electrodes are desirable to further investigate the activity performed by complex neural networks. Therefore, in this paper, we propose a CMOS neural probe containing 455 active electrodes in the probe shank (100 \mum wide, 10 mm long, and 50 \mum thick) and 52 simultaneous readout channels in the probe body (2.9\,\times\,3.3 mm^2). In situ amplification under each electrode enables low-impedance interconnection lines, regardless of the electrode impedance, with a residual crosstalk of -44.8 dB. This design has been implemented in a 0.18-\mum standard CMOS technology, with additional CMOS-compatible post-processing performed at wafer level to define the electrodes and the probe outline. In this architecture, the analog front-end achieves an input-referred noise of 3.2 \mu \Vrms and an NEF of 3.08. The power consumption of the core circuit is 949.8 \muW, while the total power consumption is 1.45 mW. The high-density active-electrode array in this neural probe allows for the massive recording of neural activity. In vivo measurements demonstrate successful simultaneous recordings from many individual cells. [ABSTRACT FROM PUBLISHER]

Since a few decades, micro-fabricated neural probes are being used, together with microelectronic interfaces, to get more insight in the activity of neuronal networks. The need for higher temporal and spatial recording resolutions imposes new challenges on the design of integrated neural interfaces with respect to power consumption, data handling and versatility. In this paper, we present an integrated acquisition system for in vitro and in vivo recording of neural activity. The ASIC consists of 16 low-noise, fully-differential input channels with independent programmability of its amplification (from 100 to 6000 V/V) and filtering (1–6000 Hz range) capabilities. Each channel is AC-coupled and implements a fourth-order band-pass filter in order to steeply attenuate out-of-band noise and DC input offsets. The system achieves an input-referred noise density of 37 nV/\sqrt Hz, a NEF of 5.1, a CMRR > 60~dB, a THD < 1\% and a sampling rate of 30 kS/s per channel, while consuming a maximum of 70 \mu A per channel from a single 3.3 V. The ASIC was implemented in a 0.35 \mu m CMOS technology and has a total area of 5.6\,\times \,4.5 mm^2. The recording system was successfully validated in in vitro and in vivo experiments, achieving simultaneous multichannel recordings of cell activity with satisfactory signal-to-noise ratios. [ABSTRACT FROM PUBLISHER]

Abstract: The investigation of single-neuron parameters is of great interest because many aspects in the behavior and communication of neuronal networks still remain unidentified. However, the present available techniques for single-cell measurements are slow and do not allow for a high-throughput approach. We present here a CMOS compatible microelectrode array with 84 electrodes (with diameters ranging from 1.2 to 4.2μm) that are smaller than the size of cell, thereby supporting single-cell addressability. We show controllable electroporation of a single cell by an underlying electrode while monitoring changes in the intracellular membrane potential. Further, by applying a localized electrical field between two electrodes close to a neuron while recording changes in the intracellular calcium concentration, we demonstrate activation of a single cell (∼270%, DF/F0), followed by a network response of the neighboring cells. The technology can be easily scaled up to larger electrode arrays (theoretically up to 137,000electrodes/mm2) with active CMOS electronics integration able to perform high-throughput measurements on single cells. [ABSTRACT FROM AUTHOR]