Dataset Information

High-Density Electrical Recording and Impedance Imaging With a Multi-Modal CMOS Multi-Electrode Array Chip.

ABSTRACT: Multi-electrode arrays, both active or passive, emerged as ideal technologies to unveil intricated electrophysiological dynamics of cells and tissues. Active MEAs, designed using complementary metal oxide semiconductor technology (CMOS), stand over passive devices thanks to the possibility of achieving single-cell resolution, the reduced electrode size, the reduced crosstalk and the higher functionality and portability. Nevertheless, most of the reported CMOS MEA systems mainly rely on a single operational modality, which strongly hampers the applicability range of a single device. This can be a limiting factor considering that most biological and electrophysiological dynamics are often based on the synergy of multiple and complex mechanisms acting from different angles on the same phenomena. Here, we designed a CMOS MEA chip with 16,384 titanium nitride electrodes, 6 independent operational modalities and 1,024 parallel recording channels for neuro-electrophysiological studies. Sixteen independent active areas are patterned on the chip surface forming a 4 × 4 matrix, each one including 1,024 electrodes. Electrodes of four different sizes are present on the chip surface, ranging from 2.5 × 3.5 ?m2 up to 11 × 11.0 ?m2, with 15 ?m pitch. In this paper, we exploited the impedance monitoring and voltage recording modalities not only to monitor the growth and development of primary rat hippocampal neurons, but also to assess their electrophysiological activity over time showing a mean spike amplitude of 144.8 ± 84.6 ?V. Fixed frequency (1 kHz) and high sampling rate (30 kHz) impedance measurements were used to evaluate the cellular adhesion and growth on the chip surface. Thanks to the high-density configuration of the electrodes, as well as their dimension and pitch, the chip can appreciate the evolutions of the cell culture morphology starting from the moment of the seeding up to mature culture conditions. The measurements were confirmed by fluorescent staining. The effect of the different electrode sizes on the spike amplitudes and noise were also discussed. The multi-modality of the presented CMOS MEA allows for the simultaneous assessment of different physiological properties of the cultured neurons. Therefore, it can pave the way both to answer complex fundamental neuroscience questions as well as to aid the current drug-development paradigm.

SUBMITTER: Miccoli B

PROVIDER: S-EPMC6603149 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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High-Density Electrical Recording and Impedance Imaging With a Multi-Modal CMOS Multi-Electrode Array Chip.

Miccoli Beatrice B Lopez Carolina Mora CM Goikoetxea Erkuden E Putzeys Jan J Sekeri Makrina M Krylychkina Olga O Chang Shuo-Wen SW Firrincieli Andrea A Andrei Alexandru A Reumers Veerle V Braeken Dries D

Frontiers in neuroscience 20190625

Multi-electrode arrays, both active or passive, emerged as ideal technologies to unveil intricated electrophysiological dynamics of cells and tissues. Active MEAs, designed using complementary metal oxide semiconductor technology (CMOS), stand over passive devices thanks to the possibility of achieving single-cell resolution, the reduced electrode size, the reduced crosstalk and the higher functionality and portability. Nevertheless, most of the reported CMOS MEA systems mainly rely on a single ...[more]

PMID: 31293372

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Project description:OBJECTIVE:Needle EMG remains the standard clinical test for neuromuscular disease (NMD) assessment, but it only characterizes myofiber membrane depolarization. On the other hand, electrical impedance provides non-electrically active structural and compositional data of tissues. Here, we designed a prototype of needle electrode integrating electrical impedance and EMG measurement capabilities, the so-called I-EMG needle electrode. APPROACH:We use finite element method models to study the impedance recording characteristics of I-EMG needle electrodes. The simulated electrical and mechanical design specifications are then manufactured to create a prototype of an I-EMG needle electrode. We pilot these new needle electrodes by conducting in vivo impedance measurements with muscle at rest on healthy wild-type (wt, n = 5) and muscular dystrophy (mdx, n = 5) mice. Comparisons between wt and mdx mice are performed using Mann-Whitney test, two-tailed, p < 0.05. The electrical characterization of the EMG electrode in the developed I-EMG needles was performed in vitro on saline solution and through EMG detection in wt animal at rest and during voluntary contractions. RESULTS:Muscle impedance demonstrate good repeatability (p < 0.05 and p < 0.005 for resistance and reactance at 50 kHz, respectively) and agreement between different I-EMG needles. Impedance data allows us to discriminate between mdx and wt muscle (p < 0.05 and p < 0.005 for resistance and reactance at 10 kHz, respectively). EMG broadband noise power and peak amplitude using the I-EMG needle were similar to that of a commercial monopolar EMG needle. EMG recordings using the I-EMG needle measured electrical activity similar to a standard monopolar needle with muscle at rest and during voluntary contraction. SIGNIFICANCE:Needle I-EMG technology may offer the opportunity to enhance the diagnostic capability and quantification of NMD beyond that possible with either impedance or EMG techniques separately. Ultimately, needle I-EMG could serve as a new bedside tool to assess NMD without increasing the complexity or duration of the EMG test.

Project description:HighlightsPolyimide-based flexible microneedle array (PI-MNA) electrodes realize high electrical/mechanical performance and are compatible with wearable wireless recording systems. The normalized electrode-skin interface impedance (EII) of the PI-MNA electrodes reaches 0.98 kΩ cm2 at 1 kHz and 1.50 kΩ cm2 at 10 Hz, approximately 1/250 of clinical standard electrodes. This is the first report on the clinical study of microneedle electrodes. The PI-MNA electrodes are applied to clinical long-term continuous monitoring for polysomnography. Microneedle array (MNA) electrodes are an effective solution to achieve high-quality surface biopotential recording without the coordination of conductive gel and are thus very suitable for long-term wearable applications. Existing schemes are limited by flexibility, biosafety, and manufacturing costs, which create large barriers for wider applications. Here, we present a novel flexible MNA electrode that can simultaneously achieve flexibility of the substrate to fit a curved body surface, robustness of microneedles to penetrate the skin without fracture, and a simplified process to allow mass production. The compatibility with wearable wireless systems and the short preparation time of the electrodes significantly improves the comfort and convenience of electrophysiological recording. The normalized electrode-skin contact impedance reaches 0.98 kΩ cm2 at 1 kHz and 1.50 kΩ cm2 at 10 Hz, a record low value compared to previous reports and approximately 1/250 of the standard electrodes. The morphology, biosafety, and electrical/mechanical properties are fully characterized, and wearable recordings with a high signal-to-noise ratio and low motion artifacts are realized. The first reported clinical study of microneedle electrodes for surface electrophysiological monitoring was conducted in tens of healthy and sleep-disordered subjects with 44 nights of recording (over 8 h per night), providing substantial evidence that the electrodes can be leveraged to substitute for clinical standard electrodes.

Dataset Information

High-Density Electrical Recording and Impedance Imaging With a Multi-Modal CMOS Multi-Electrode Array Chip.

Publications

High-Density Electrical Recording and Impedance Imaging With a Multi-Modal CMOS Multi-Electrode Array Chip.

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