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.

Highlights

  • High-resolution imaging of action potentials (APs) in cells can reveal the answers to questions regarding the complexities of neuron network activities, such as the nature of dendritic integration, the electrical functions of dendritic spines, and variations in spontaneous native activity patterns or network oscillations.[1,2] Action potentials have been widely studied through the use of patch clamps or fluorescence imaging methods.[3,4] While the patch clamp method can measure the action potentials directly and with high temporal resolution, the fluorescence method can provide twodimensional (2D) high-spatial resolution imaging of the action potentials.Various implementation methods have been proposed in previous works on the CMOS-microelectrode array (MEA)

  • 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

  • These results indicate the high-scalability of the CMOS-MEA

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Summary

Introduction

High-resolution imaging of action potentials (APs) in cells can reveal the answers to questions regarding the complexities of neuron network activities, such as the nature of dendritic integration, the electrical functions of dendritic spines, and variations in spontaneous native activity patterns or network oscillations.[1,2] Action potentials have been widely studied through the use of patch clamps or fluorescence imaging methods.[3,4] While the patch clamp method can measure the action potentials directly and with high temporal resolution, the fluorescence method can provide twodimensional (2D) high-spatial resolution imaging of the action potentials.Various implementation methods have been proposed in previous works on the CMOS-MEA. High-resolution imaging of action potentials (APs) in cells can reveal the answers to questions regarding the complexities of neuron network activities, such as the nature of dendritic integration, the electrical functions of dendritic spines, and variations in spontaneous native activity patterns or network oscillations.[1,2]. Action potentials have been widely studied through the use of patch clamps or fluorescence imaging methods.[3,4]. While the patch clamp method can measure the action potentials directly and with high temporal resolution, the fluorescence method can provide twodimensional (2D) high-spatial resolution imaging of the action potentials. Scaling of the readout channel number and the electrode density is problematic, as it increases the noise in the readout channels. This trade-off problem mainly arises because of the shrinking of the transistor dimension on the readout channels, and

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