A Multimodal CMOS MEA for High-Throughput Intracellular Action Potential Measurements and Impedance Spectroscopy in Drug-Screening Applications

López, Carolina Mora; Chun, Ho Sung; Wang, Shiwei; Berti, L.; Putzeys, Jan; Bulcke, Carl Van Den; Weijers, Jan-Willem; Firrincieli, Andrea; Reumers, Veerle; Braeken, Dries; Helleputte, Nick Van

doi:10.1109/jssc.2018.2863952

Cited by 84 publications

(66 citation statements)

References 30 publications

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“…The full-frame APS readout features a noise level of 10.4 µV rms , while the SM readout achieves a noise level of 3.0 µV rms . The SM performance is comparable to current state-of-the-art devices, while the APS noise performance is significantly improved in comparison to other APS devices with a similarly high spatial resolution [19][20][21][22][23][24][25][26][27] . In addition, we here realized both modes in a single device, which is challenging, as both modes require dedicated circuits and consume area within each pixel.…”

Section: Discussionmentioning

confidence: 67%

“…Today's electrophysiology methods range from classic tools, such as patch-clamping, which can provide the detailed recordings of membrane potentials or even single-ion-channel activity of patched individual cells, to highly parallel network activity recordings with neural probes featuring a multitude of channels. Recently introduced high-density microelectrode arrays (HD-MEAs), based on complementary metaloxide-semiconductor (CMOS) technology, have enabled simultaneous access to the electrical activity of thousands of neurons at high temporal and spatial resolution [19][20][21][22][23][24][25][26][27] , leading to what can be termed "electrical functional imaging". Compared to traditional optical imaging, such as light microscopy, electrical functional imaging by means of HD-MEAs captures the electrical activity of neurons, such as extracellular action potentials (APs) and local-field potentials (LFPs).…”

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confidence: 99%

“…The circuitry architecture used for this approach is called switch-matrix (SM), which includes a flexible switching and addressing scheme within the array. The front-end amplifiers are placed outside of the array area, where there is sufficient area to implement large lownoise amplifiers [24][25][26][27] . The SM approach permits the detection of signals with high sensitivity at dense electrode packing.…”

mentioning

confidence: 99%

“…These low-noise readout channels can be flexibly connected to an arbitrarily selectable subset of the 19,584 electrodes in the array using the SM routing scheme 26 . Compared to previous MEA architectures and systems [20][21][22][23][24][25][26][27] , the DM-MEA system provides large-scale parallel data acquisition from the full array at high electrode density, while offering the option of simultaneous high-SNR readout of areas of interest. Despite the circuit design challenges to integrate two modes into one device, the full-frame read-out circuitry has sufficient SNR to reliably record signals with amplitudes of approximately 50 µV (five times RMS noise).…”

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confidence: 99%

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Versatile live-cell activity analysis platform for characterization of neuronal dynamics at single-cell and network level

et al. 2020

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Chronic imaging of neuronal networks in vitro has provided fundamental insights into mechanisms underlying neuronal function. Current labeling and optical imaging methods, however, cannot be used for continuous and long-term recordings of the dynamics and evolution of neuronal networks, as fluorescent indicators can cause phototoxicity. Here, we introduce a versatile platform for label-free, comprehensive and detailed electrophysiological live-cell imaging of various neurogenic cells and tissues over extended time scales. We report on a dual-mode high-density microelectrode array, which can simultaneously record in (i) full-frame mode with 19,584 recording sites and (ii) high-signal-to-noise mode with 246 channels. We set out to demonstrate the capabilities of this platform with recordings from primary and iPSC-derived neuronal cultures and tissue preparations over several weeks, providing detailed morpho-electrical phenotypic parameters at subcellular, cellular and network level. Moreover, we develop reliable analysis tools, which drastically increase the throughput to infer axonal morphology and conduction speed.

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Section: Discussionmentioning

confidence: 67%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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Versatile live-cell activity analysis platform for characterization of neuronal dynamics at single-cell and network level

et al. 2020

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“…Presently, all these modalities rely on discrete and specialized apparatus. However, complementary metal oxide semiconductor (CMOS) technology presents a new alternative, with integration of many of the sensor and electronic circuits required on a single chip [20]- [24]. This opens a route to bespoke, specific diagnosis and disease management at lowcost and readily deployed outside a specialized laboratory.…”

Section: Introductionmentioning

confidence: 99%

Multimodal Integrated Sensor Platform for Rapid Biomarker Detection

Al-Rawhani

Mitra

Barrett

et al. 2020

IEEE Trans. Biomed. Eng.

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Precision metabolomics and quantification for costeffective, rapid diagnosis of disease are key goals in personalized medicine and point-of-care testing. Presently, patients are subjected to multiple test procedures requiring large laboratory equipment. Microelectronics has already made modern computing and communications possible by integration of complex functions within a single chip. As More than Moore technology increases in importance, integrated circuits for densely patterned sensor chips have grown in significance. Here, we present a versatile single CMOS chip forming a platform to address personalized needs through on-chip multimodal optical and electrochemical detection that will reduce the number of tests that patients must take. The chip integrates interleaved sensing subsystems for quadruplemode colorimetric, chemiluminescent, surface plasmon resonance and hydrogen ion measurements. These subsystems include a photodiode array and a single photon avalanche diode array, with some elements functionalized to introduce a surface plasmon resonance mode. The chip also includes an array of ion sensitive field effect transistors. The sensor arrays are distributed uniformly over an active area on the chip surface in a scalable and modular design. Bio-functionalization of the physical sensors yields a highly selective simultaneous multiple-assay platform in a disposable format. We demonstrate its versatile capabilities through quantified bioassays performed on-chip for glucose, cholesterol, urea and urate, each within their naturally occurring physiological range.

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Large‐Area Field Potential Imaging Having Single Neuron Resolution Using 236 880 Electrodes CMOS‐MEA Technology

et al. 2023

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The electrophysiological technology having a high spatiotemporal resolution at the single‐cell level and noninvasive measurements of large areas provide insights on underlying neuronal function. Here, a complementary metal‐oxide semiconductor (CMOS)‐microelectrode array (MEA) is used that uses 236 880 electrodes each with an electrode size of 11.22 × 11.22 µm and 236 880 covering a wide area of 5.5 × 5.9 mm in presenting a detailed and single‐cell‐level neural activity analysis platform for brain slices, human iPS cell‐derived cortical networks, peripheral neurons, and human brain organoids. Propagation pattern characteristics between brain regions changes the synaptic propagation into compounds based on single‐cell time‐series patterns, classification based on single DRG neuron firing patterns and compound responses, axonal conduction characteristics and changes to anticancer drugs, and network activities and transition to compounds in brain organoids are extracted. This detailed analysis of neural activity at the single‐cell level using the CMOS‐MEA provides a new understanding of the basic mechanisms of brain circuits in vitro and ex vivo, on human neurological diseases for drug discovery, and compound toxicity assessment.

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A Multimodal CMOS MEA for High-Throughput Intracellular Action Potential Measurements and Impedance Spectroscopy in Drug-Screening Applications

Cited by 84 publications

References 30 publications

Versatile live-cell activity analysis platform for characterization of neuronal dynamics at single-cell and network level

Versatile live-cell activity analysis platform for characterization of neuronal dynamics at single-cell and network level

Multimodal Integrated Sensor Platform for Rapid Biomarker Detection

Large‐Area Field Potential Imaging Having Single Neuron Resolution Using 236 880 Electrodes CMOS‐MEA Technology

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