cmos-based microelectrode arrays (MEAs) enable the recording of electrical activities from biological cells, i.e., neurons or cardiac cells, at multiple sites with single-cell resolution. However, biological and elect...
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ISBN:
(纸本)9798331516185;9798331516178
cmos-based microelectrode arrays (MEAs) enable the recording of electrical activities from biological cells, i.e., neurons or cardiac cells, at multiple sites with single-cell resolution. However, biological and electronic noise sources impair the detection of extracellular voltages. Reliable detection of so-called action potentials (small voltage deflections) would be significantly improved with real-time data processing. Therefore, we present here a Field Programmable Gate array (FPGA) that filters the data stream and extracts the relevant electrophysiological information. In addition to single-cell activity, we analyze the cmos MEA area covered by biological tissue using electrical imaging via adhesion voltage noise spectroscopy. Electrical imaging enables the recording of selected areas at unprecedented spatiotemporal resolution.
A cmos-based microelectrode array (cmosMEA) is presented, where a 10-nm-thick antiferroelectric ZrO2 layer is deposited in the post-cmos process as functional electrode coating for 4225 recording sites and 1024 stimul...
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ISBN:
(纸本)9798350395143;9798350395136
A cmos-based microelectrode array (cmosMEA) is presented, where a 10-nm-thick antiferroelectric ZrO2 layer is deposited in the post-cmos process as functional electrode coating for 4225 recording sites and 1024 stimulation sites. Voltage noise measurements of the ZrO2 recording sites of the cmos-MEA show reduced noise levels as compared to the same cmos-MEA with uncoated TiN electrodes. Moreover, neural recordings of spontaneous activity of retinal ganglion cells reveal full functionality and biocompatibility of the insulating ZrO2 interface material. The stimulation current of the ZrO2 ferroelectric microelectrodes is investigated by applying triangular voltage signals to the stimulation sites of the cmosMEA. Up to voltage amplitudes of 3.2 V, the stimulation current consists of displacement current only, electrochemical (Faradaic) DC currents are suppressed. For voltage amplitudes above similar to 2.2 V, we observe a voltage-dependent increase in the stimulation current which we attribute to the ferroelectric properties of the ZrO2 insulated microelectrodes. However, the enhancement of the charge injection capacity (CIC) of the insulated microelectrodes is below the full potential of antiferroelectric ZrO2 and requires further optimization. Nevertheless, our results demonstrate the potential of ferroelectric cmos-MEAs for safe and efficient neural recording and stimulation.
Objective. Neuromodulation, particularly electrical stimulation, necessitates high spatial resolution to achieve artificial vision with high acuity. In epiretinal implants, this is hindered by the undesired activation...
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Objective. Neuromodulation, particularly electrical stimulation, necessitates high spatial resolution to achieve artificial vision with high acuity. In epiretinal implants, this is hindered by the undesired activation of distal axons. Here, we investigate focal and axonal activation of retinal ganglion cells (RGCs) in epiretinal configuration for different sinusoidal stimulation frequencies. Approach. RGC responses to epiretinal sinusoidal stimulation at frequencies between 40 and 100 Hz were tested in ex-vivo photoreceptor degenerated (rd10) isolated retinae. Experiments were conducted using a high-density cmos-based microelectrode array, which allows to localize RGC cell bodies and axons at high spatial resolution. Main results. We report current and charge density thresholds for focal and distal axon activation at stimulation frequencies of 40, 60, 80, and 100 Hz for an electrode size with an effective area of 0.01 mm2. Activation of distal axons is avoided up to a stimulation amplitude of 0.23 mu A (corresponding to 17.3 mu C cm-2) at 40 Hz and up to a stimulation amplitude of 0.28 mu A (14.8 mu C cm-2) at 60 Hz. The threshold ratio between focal and axonal activation increases from 1.1 for 100 Hz up to 1.6 for 60 Hz, while at 40 Hz stimulation frequency, almost no axonal responses were detected in the tested intensity range. With the use of synaptic blockers, we demonstrate the underlying direct activation mechanism of the ganglion cells. Finally, using high-resolution electrical imaging and label-free electrophysiological axon tracking, we demonstrate the extent of activation in axon bundles. Significance. Our results can be exploited to define a spatially selective stimulation strategy avoiding axonal activation in future retinal implants, thereby solving one of the major limitations of artificial vision. The results may be extended to other fields of neuroprosthetics to achieve selective focal electrical stimulation.
Neuropathic pain is characterized by aberrant activity of specific nociceptor populations, as demonstrated through functional assessments such as microneurography. Current treatments against severe forms of neuropathi...
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Neuropathic pain is characterized by aberrant activity of specific nociceptor populations, as demonstrated through functional assessments such as microneurography. Current treatments against severe forms of neuropathic pain demonstrate insufficient efficacy or lead to unwanted side effects as they fail to specifically target the affected nociceptors. Tools that can recapitulate aspects of microneurography in vitro would enable a more targeted compound screening. Therefore, we developed an in vitro platform combining a cmosbased high-density microelectrodearray with a polydimethylsiloxane (PDMS) guiding microstructure that captures the electrophysiological responses of individual axons. Human induced pluripotent stem cell-derived (hiPSC) sensory neurons were cultured in a way that allowed axons to be distributed through parallel 4 x 10 mu m microchannels exiting the seeding well before converging to a bigger axon-collecting channel. This configuration allowed the measurement of stimulation-induced responses of individual axons. Sensory neurons were found to exhibit a great diversity of electrophysiological response profiles that can be classified into different functional archetypes. Moreover, we show that some responses are affected by applying the TRPV1 agonist capsaicin. Overall, results using our platform demonstrate that we were able to distinguish individual axon responses, making the platform a promising tool for testing therapeutic candidates targeting particular sensory neuron subtypes.
Monitoring cells on substrates time-continuously without relying on optical microscopy imaging is of broad interest in biotechnological applications. We propose an approach to electrically investigate cytotoxic effect...
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ISBN:
(纸本)9798350303872
Monitoring cells on substrates time-continuously without relying on optical microscopy imaging is of broad interest in biotechnological applications. We propose an approach to electrically investigate cytotoxic effects of a chemotherapeutic treatment on cancer cells using cell adhesion noise spectroscopy. Recordings are taken with high-density microelectrodearrays, data are analyzed in terms of spectral power density.
Time-continuous detection of cells on substrates without the need of optical microscopic imaging is of broad interest in biotechnological applications. We present a method how to detect cancer cells using voltage nois...
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ISBN:
(纸本)9798350346046
Time-continuous detection of cells on substrates without the need of optical microscopic imaging is of broad interest in biotechnological applications. We present a method how to detect cancer cells using voltage noise caused by cell adhesion which is recorded by high-density cmos-based microelectrode arrays. We analyze our data in terms of spectral power density for two different types of arrays, each of them being optimized in a different working regime.
Objective. Most neuroprosthetic implants employ pulsatile square-wave electrical stimuli, which are significantly different from physiological inter-neuronal communication. In case of retinal neuroprosthetics, which u...
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Objective. Most neuroprosthetic implants employ pulsatile square-wave electrical stimuli, which are significantly different from physiological inter-neuronal communication. In case of retinal neuroprosthetics, which use a certain type of pulsatile stimuli, reliable object and contrast discrimination by implanted blind patients remained challenging. Here we investigated to what extent simple objects can be discriminated from the output of retinal ganglion cells (RGCs) upon sinusoidal stimulation. Approach. Spatially confined objects were formed by different combinations of 1024 stimulating microelectrodes. The RGC activity in the ex vivo retina of photoreceptor-degenerated mouse, of healthy mouse or of primate was recorded simultaneously using an interleaved recording microelectrodearray implemented in a cmos-based chip. Main results. We report that application of sinusoidal electrical stimuli (40 Hz) in epiretinal configuration instantaneously and reliably modulates the RGC activity in spatially confined areas at low stimulation threshold charge densities (40 nC mm(-2)). Classification of overlapping but spatially displaced objects (1 degrees separation) was achieved by distinct spiking activity of selected RGCs. A classifier (regularized logistic regression) discriminated spatially displaced objects (size: 5.5 degrees or 3.5 degrees) with high accuracy (90% or 62%). Stimulation with low artificial contrast (10%) encoded by different stimulus amplitudes generated RGC activity, which was classified with an accuracy of 80% for large objects (5.5 degrees). Significance. We conclude that time-continuous smooth-wave stimulation provides robust, localized neuronal activation in photoreceptor-degenerated retina, which may enable future artificial vision at high temporal, spatial and contrast resolution.
There is an enduring quest for technologies that provide - temporally and spatially - highly resolved information on electric neuronal or cardiac activity in functional tissues or cell cultures. Here, we present a pla...
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There is an enduring quest for technologies that provide - temporally and spatially - highly resolved information on electric neuronal or cardiac activity in functional tissues or cell cultures. Here, we present a planar high-density, low-noise microelectrode system realized in microelectronics technology that features 11,011 microelectrodes (3,150 electrodes per mm(2)), 126 of which can be arbitrarily selected and can, via a reconfigurable routing scheme, be connected to on-chip recording and stimulation circuits. This device enables long-term extracellular electrical-activity recordings at subcellular spatial resolution and microsecond temporal resolution to capture the entire dynamics of the cellular electrical signals. To illustrate the device performance, extracellular potentials of Purkinje cells (PCs) in acute slices of the cerebellum have been analyzed. A detailed and comprehensive picture of the distribution and dynamics of action potentials (APs) in the somatic and dendritic regions of a single cell was obtained from the recordings by applying spike sorting and spike-triggered averaging methods to the collected data. An analysis of the measured local current densities revealed a reproducible sink/source pattern within a single cell during an AP. The experimental data substantiated compartmental models and can be used to extend those models to better understand extracellular single-cell potential patterns and their contributions to the population activity. The presented devices can be conveniently applied to a broad variety of biological preparations, i.e., neural or cardiac tissues, slices, or cell cultures can be grown or placed directly atop of the chips for fundamental mechanistic or pharmacological studies. (C) 2008 Elsevier B.V. All rights reserved.
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