(Invited) Cell Analysis Using Integrated Electrochemical Devices
Authors: Ino Kosuke 
Published: December 2020

For the fields of tissue engineering and organs-on-a-chip, three-dimensional (3D) cultured cells are widely used. These applications require a method that can easily measure cell activities of 3D cultured cells without any cell damages. For the purpose, electrochemical approaches have been proposed [1-3]. By using these electrochemical approaches, several kinds of cell activities such as respiratory activities can be measured.
My group has developed several kinds of integrated electrochemical devices including chip and probe devices. The chip devices contained many electrodes based on complementary metal oxide semiconductor (CMOS)-based devices [3-9]. The detection system is useful for real-time imaging, because it rapidly obtains 2D electrochemical images consisting redox current signals at target positions. By using the CMOS-based electrochemical devices, respiration activity and cell differentiation status were clearly visualized. Also, the device provided electrochemical images of released molecules such as dopamine from 3D cultured cells.
In addition to CMOS-based devices, bipolar electrode (BPE)-based electrode arrays was developed [10]. In BPE system, anodic and cathodic reactions are induced at both ends of the BPE with only a pair of driving electrodes. Therefore, many sensing elements can be incorporated into a small chip without complex wiring. In my BPE device, oxygen reduction currents at the sensor near 3D cultured cells converted electrochemiluminescence (ECL) to detect respiratory activity of 3D cultured cells.
In addition to chip devices, scanning electrochemical microscopy was applied for electrochemical measurement of respiration activity of fibroblast spheroids containing endothelial cell networks [11]. This study reported the effects of endothelial cell networks on cell activity of 3D cultured cells.
Thus, these integrated electrochemical devices were applied for cell analysis. They will be utilized for tissue engineering and organs on a chip. In this presentation, I will summarize these devices.
References
[1] Ino K et al., Bioelectrochemical applications of microelectrode arrays in cell analysis and engineering. Curr. Opin. Electrochem., 5, (2017), 146-151.
[2] Ino K et al., Micro/nanoelectrochemical probe and chip devices for evaluation of three-dimensional cultured cells. Analyst, 142, (2017), 4343-4354.
[3] Ino K et al., Intracellular electrochemical sensing. Electroanalysis, 30 (2018), 2195-2209.
[4] Ino K et al., Electrochemical motion tracking of microorganisms using a large-scale-integration-based amperometric device. Angew. Chem. Int. Edit., 56, (2017), 6818-6822.
[5] Ino K et al., Electrochemicolor imaging of endogenous alkaline phosphatase and respiratory activities of mesenchymal stem cell aggregates in early-stage osteodifferentiation. Electrochim. Acta, 268, (2018), 554-561.
[6] Kanno et al., Electrochemicolor imaging using an LSI-Based device for multiplexed cell assays. Anal. Chem., 89, (2017), 12778-12786.
[7] Ino K et al., Combination of double-mediator system with large-scale integration-based amperometric devices for detecting NAD (P) H: quinone oxidoreductase 1 activity of cancer cell aggregates. ACS Sens., 4, (2019), 1619-1625.
[8] Ino K et al., Differential electrochemicolor imaging using LSI-based device for simultaneous detection of multiple analytes. Sens. Mater., 31, (2019), 13-22.
[9] Ino K et al., Local hydrogel fabrication based on electrodeposition with a large-scale integration (LSI)-based amperometric device. Sens. Actuator B-Chem., 277, (2019), 95-101.
[10] Ino K et al., Closed bipolar electrode array for on-chip analysis of cellular respiration by cell aggregates. ACS Sens. 5, (2020), 740-745.
[11] Hiramoto K et al., Electrochemical measurement of respiratory activity for evaluation of fibroblast spheroids containing endothelial cell networks. Electrochim. Acta, 340, (2020), 135979.