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On-Chip Cyclic Voltammetry Measurements Using a Compact 1024-Electrode CMOS IC.

ABSTRACT: Complementary metal-oxide-semiconductor (CMOS) microelectrode arrays integrate amplifier arrays with on-chip electrodes, offering high-throughput platforms for electrochemical sensing with high spatial and temporal resolution. Such devices have been developed for highly parallel constant voltage amperometric detection of transmitter release from multiple cells with single-vesicle resolution. Cyclic voltammetry (CV) is an electrochemical method that applies voltage waveforms, which provides additional information about electrode properties and about the nature of analytes. A 16-channel, 64-electrode-per-channel CMOS integrated circuit (IC) fabricated in a 0.5 μm CMOS process for CV is demonstrated. Each detector consists of only 11 transistors and an integration capacitor with a unit dimension of 0.0015 mm². The device was postfabricated using Pt as the working electrode material with a shifted electrode design, which makes it possible to redefine the size and the location of working electrodes. The system incorporating cell-sized (8 μm radius) microelectrodes was validated with dopamine injection tests and CV measurements of potassium ferricyanide at a 1 V/s scanning rate. The cyclic voltammograms were in excellent agreement with theoretical predictions. The technology enables rigorous characterization of electrode performance for the application of CMOS microelectrode arrays in low-noise amperometric measurements of quantal transmitter release as well as other biosensing applications.

SUBMITTER: Huang M

PROVIDER: S-EPMC8650766 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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On-Chip Cyclic Voltammetry Measurements Using a Compact 1024-Electrode CMOS IC.

Huang Meng M Dorta-Quiñones Carlos I CI Minch Bradley A BA Lindau Manfred M

Analytical chemistry 20210526 22

Complementary metal-oxide-semiconductor (CMOS) microelectrode arrays integrate amplifier arrays with on-chip electrodes, offering high-throughput platforms for electrochemical sensing with high spatial and temporal resolution. Such devices have been developed for highly parallel constant voltage amperometric detection of transmitter release from multiple cells with single-vesicle resolution. Cyclic voltammetry (CV) is an electrochemical method that applies voltage waveforms, which provides addit ...[more]

PMID: 34038637

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Project description: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 μm2 up to 11 × 11.0 μm2, with 15 μm 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 μV. 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.

Dataset Information

On-Chip Cyclic Voltammetry Measurements Using a Compact 1024-Electrode CMOS IC.

Publications

On-Chip Cyclic Voltammetry Measurements Using a Compact 1024-Electrode CMOS IC.

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