&lt;italic&gt;In Vitro&lt;/italic&gt; Multi-Functional Microelectrode Array Featuring 59 760 Electrodes, 2048 Electrophysiology Channels, Stimulation, Impedance Measurement, and Neurotransmitter Detection Channels

Dragaš, Jelena; Viswam, Vijay; Shadmani, Amir; Chen, Yihui; Bounik, Raziyeh; Stettler, Alexander; Radivojević, Miloš; Geissler, Sydney A.; Obien, Marie Engelene J.; Müller, Jan; Hierlemann, Andreas

doi:10.1109/jssc.2017.2686580

Cited by 168 publications

(148 citation statements)

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“…This approach offers a third alternative, retaining the low tissue damage of small microwires, while enabling rapid application of cutting-edge silicon array technology to neuroscience. Additional advances in CMOS technology, such as low-artifact stimulation (52), higher channel counts (53), and electrochemical monitoring (54,55), can be rapidly deployed using this system. Our design is favorable for recording or stimulation experiments that require large area coverage and high density.…”

Section: Resultsmentioning

confidence: 99%

Massively parallel microwire arrays integrated with CMOS chips for neural recording

et al. 2020

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Section: Resultsmentioning

confidence: 99%

Massively parallel microwire arrays integrated with CMOS chips for neural recording

et al. 2020

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“…This approach offers a third alternative, retaining the low tissue damage of small microwires, while enabling rapid application of cutting-edge silicon array technology to neuroscience. Additional advances in CMOS technology, such as low-artifact stimulation 64 , higher channel counts 21 and electrochemical monitoring 65,66 , can be rapidly deployed using this system. Our design is favorable for recording or stimulation experiments that require large area coverage and high density, such as in the visual cortex.…”

Section: Resultsmentioning

confidence: 99%

Massively Parallel Microwire Arrays Integrated with CMOS chips for Neural Recording

Obaid

Hanna

et al. 2019

Preprint

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Multi-channel electrical recordings of neural activity in the brain is an increasingly powerful method revealing new aspects of neural communication, computation, and prosthetics. However, while planar silicon-based CMOS devices in conventional electronics scale rapidly, neural interface devices have not kept pace. Here, we present a new strategy to interface silicon-based chips with three-dimensional microwire arrays, providing the link between rapidly-developing electronics and high density neural interfaces. The system consists of a bundle of microwires mated to large-scale microelectrode arrays, such as camera chips. This system has excellent recording performance, demonstrated via single unit and local-field potential recordings in isolated retina and in the motor cortex or striatum of awake moving mice. The modular design enables a variety of microwire types and sizes to be integrated with different types of pixel arrays, connecting the rapid progress of commercial multiplexing, digitisation and data acquisition hardware together with a three-dimensional neural interface. Figure 2: Microwire bundle fabrication. a, Fabrication procedure of microwire bundles. (i) Individual microwires are electrically insulated with a robust ceramic or polymeric coating. (ii) A sacrificial layer of parylene-C (PaC) is coated onto the wires to provide spacing. (iii) If desired, the tips of the microwires can be polished to an angular tip, or electrosharpened. (iv) The wires are then bundled together, either by spooling the wire, or mechanical aggregation. The wires naturally pack in a honeycomb array. (v)The bundle is infiltrated with biomedical epoxy to hold the wires together, then the top (proximal) end polished for mating to the CMOS chip. (vi) The proximal end is etched 10-20 µm to mate to the CMOS chip and the distal end of the wires is released by etching with oxygen plasma, allowing each wire to penetrate individually. A threaded collet is added to hold the bundle. b, A backscatter SEM of an individual microwire with a PtIr conductive core and 45 µm PaC coating (a, ii). c, The wires pack into a honeycomb structure, and epoxy is infiltrated in between to fill the gaps (a, v). d, The proximal end of a bundle of 177 20 µm Au wires with 100 µm spacing after etching to expose the conductive wire. e, The predicted volumetric displacement of bundles of microwires as a function of wire-to-wire distance, determined by the wire size and sacrificial coating thickness (t). This assumes a perfect hexagonal packing fraction of ~90.69%. For 15 µm wires with 100 µm spacing, the volume displaced is 2%. f, The distal end of a bundle of 600 7.5µm W wires coated with 1 µm of glass after etching to remove the PaC and embedded epoxy. g,h, The distal end (PtW 20 µm wires, 100 µm spacing) can be shaped with single wire precision to simultaneously access different depths in the tissue.

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“…62,63 The required voltage amplitude of electrical stimulation is typically between 0.1 V and 10 V for successful cell pacing, while the evoked extracellular potential amplitude is only around 100 μV. [17][18][19][20][21] Therefore, simultaneous electrical stimulations and potential recordings require >60 dB realtime broadband stimulation artefact cancellation. In practice, this problem is mitigated by performing extracellular potential recordings at a distant site from the electrical stimulation site, since the stimulation artefact propagating through this spatial distance will be attenuated and delayed, so the artefact can be separated from the evoked extracellular potentials.…”

Section: Resultsmentioning

confidence: 99%

“…Most existing cell-based assays utilize single-modality electronic sensors, each of which only measures one cell physiological property. Examples include microelectrode arrays (MEAs) with extracellular potential amplifiers and stimulators for recording neuron activities and action potential conduction, [17][18][19][20][21] electrical impedance sensors for cell-growth assay, cardiac beating measurements, and myocardial ischemia detection, [22][23][24] ion-sensitive field effect transistor (ISFET) arrays for cell metabolism assay, 25,26 magnetic sensor arrays for capturing cardiac beating or molecular detection, 12,16,[27][28][29] and optical sensors for DNA sensing and sequencing. [30][31][32][33][34] However, cells are highly complex systems with concurrent multi-physical activities, and thereby holistic understanding of such complex cellular physiological responses remains a daunting task.…”

Section: Introductionmentioning

confidence: 99%

Multi-parametric cell profiling with a CMOS quad-modality cellular interfacing array for label-free fully automated drug screening

et al. 2018

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Cells are complex systems with concurrent multi-physical responses, and cell physiological signals are often encoded with spatiotemporal dynamics and further coupled with multiple cellular activities. However, most existing electronic sensors are only single-modality and cannot capture multi-parametric cellular responses. In this paper, a 1024-pixel CMOS quad-modality cellular interfacing array that enables multi-parametric cell profiling for drug development is presented. The quad-modality CMOS array features cellular impedance characterization, optical detection, extracellular potential recording, and biphasic current stimulation. The fibroblast transparency and surface adhesion are jointly monitored by cellular impedance and optical sensing modalities for comprehensive cell growth evaluation. Simultaneous current stimulation and opto-mechanical monitoring based on cardiomyocytes are demonstrated without any stimulation/sensing dead-zone. Furthermore, drug dose-dependent multi-parametric feature extractions in cardiomyocytes from their extracellular potentials and opto-mechanical signals are presented. The CMOS array demonstrates great potential for fully automated drug screening and drug safety assessments, which may substantially reduce the drug screening time and cost in future new drug development.

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<italic>In Vitro</italic> Multi-Functional Microelectrode Array Featuring 59 760 Electrodes, 2048 Electrophysiology Channels, Stimulation, Impedance Measurement, and Neurotransmitter Detection Channels

Cited by 168 publications

References 50 publications

Massively parallel microwire arrays integrated with CMOS chips for neural recording

Massively parallel microwire arrays integrated with CMOS chips for neural recording

Massively Parallel Microwire Arrays Integrated with CMOS chips for Neural Recording

Multi-parametric cell profiling with a CMOS quad-modality cellular interfacing array for label-free fully automated drug screening

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