Twenty-four-micrometer-pitch microelectrode array with 6912-channel readout at 12 kHz via highly scalable implementation for high-spatial-resolution mapping of action potentials

Abstract

A 24-μm-pitch microelectrode array (MEA) with 6912 readout channels at 12 kHz and 23.2-μVrms random noise is presented. The aim is to reduce noise in a “highly scalable” MEA with a complementary metal-oxide-semiconductor integration circuit (CMOS-MEA), in which a large number of readout channels and a high electrode density can be expected. Despite the small dimension and the simplicity of the in-pixel circuit for the high electrode-density and the relatively large number of readout channels of the prototype CMOS-MEA chip developed in this work, the noise within the chip is successfully reduced to less than half that reported in a previous work, for a device with similar in-pixel circuit simplicity and a large number of readout channels. Further, the action potential was clearly observed on cardiomyocytes using the CMOS-MEA. These results indicate the high-scalability of the CMOS-MEA. The highly scalable CMOS-MEA provides high-spatial-resolution mapping of cell action potentials, and the mapping can aid understanding of complex activities in cells, including neuron network activities.

Technologies to Study Action Potential Propagation With a Focus on HD-MEAs

“…However, they do not allow for targeting individual neurons in a network due to the limited number of electrodes (<300), arranged at a comparably large pitch (>30 μm) (Gross et al, 1993; Jimbo and Robinson, 2000; Stett et al, 2003; Rutten et al, 2007). In order to investigate the properties of individual neurons, CMOS (complementary metal oxide semiconductor)-technology-based, planar, HD-MEAs can be used that enable simultaneous recording from a large number of sites at high spatiotemporal resolution (Eversmann et al, 2003; Berdondini et al, 2009; Frey et al, 2009; Huys et al, 2012; Johnson B. et al, 2013; Bertotti et al, 2014; Jackel et al, 2017; Ogi et al, 2017; Tsai et al, 2017). In contrast to a full-frame readout that is also used with CMOS cameras, our lab has developed a flexible readout approach, where a matrix of switches below the electrodes (total number: 26,000–59,000 electrodes) routes arbitrarily selectable subsets of 1024 or 2048 electrodes to a high-end readout circuitry placed outside the electrode array.…”

Extracellular Recording of Entire Neural Networks Using a Dual-Mode Microelectrode Array With 19 584 Electrodes and High SNR

“…The other strategy is to implement as many readout channels as possible and limit the overall number of electrodes so that all electrodes can be read out simultaneously. For this approach, a structure called "active pixel sensor" (APS) has been prevailingly used [10], [16], [18], [19] with readout circuits inside each pixel [see Fig. 1(b)].…”

A 4.8-μVrms-Noise CMOS-Microelectrode Array With Density-Scalable Active Readout Pixels via Disaggregated Differential Amplifier Implementation

“…While readout techniques with Active Pixel Sensors (APS) have been proposed to increase the channel number to over ten thousand, electrode density is limited above electrode pitch of 30 μm, because of the large area of the readout circuits integrated under the each electrode (Huys et al, 2012; Johnson et al, 2013). We present scalability for a higher-density and larger channel number with a 24-um-pitch and 6,912-readout-channels CMOS-MEA (Ogi et al, 2017). However, the noise level was 23 μV rms in this CMOS-MEA, and this was not sufficiently low to observe the neuron APs.…”