Electrochemical Imaging of Endothelial Permeability Using a Large-Scale Integration-Based Device

Kosuke Ino; Hao-Jen Pai; Kaoru Hiramoto; Yoshinobu Utagawa; Yuji Nashimoto; Hitoshi Shiku

doi:10.1021/acsomega.1c04931

Electrochemical Imaging of Endothelial Permeability Using a Large-Scale Integration-Based Device

ACS Omega. 2021 Dec 1;6(51):35476-35483. doi: 10.1021/acsomega.1c04931. eCollection 2021 Dec 28.

Authors

Kosuke Ino¹, Hao-Jen Pai², Kaoru Hiramoto², Yoshinobu Utagawa², Yuji Nashimoto^{1

3}, Hitoshi Shiku¹

Affiliations

¹ Graduate School of Engineering, Tohoku University, 6-6-11 Aramaki-aza Aoba, Aoba-ku, Sendai 980-8579, Japan.
² Graduate School of Environmental Studies, Tohoku University, 6-6-11 Aramaki-aza Aoba, Aoba-ku, Sendai 980-8579, Japan.
³ Frontier Research Institute for Interdisciplinary Sciences, Tohoku University, 6-3 Aramaki-aza Aoba, Aoba-ku, Sendai 980-8578, Japan.

Abstract

It is important to clarify the transport of biomolecules and chemicals to tissues. Herein, we present an electrochemical imaging method for evaluating the endothelial permeability. In this method, the diffusion of electrochemical tracers, [Fe(CN)₆]^4-, through a monolayer of human umbilical vein endothelial cells (HUVECs) was monitored using a large-scale integration-based device containing 400 electrodes. In conventional tracer-based assays, tracers that diffuse through an HUVEC monolayer into another channel are detected. In contrast, the present method does not employ separated channels. In detail, a HUVEC monolayer is immersed in a solution containing [Fe(CN)₆]^4- on the device. As [Fe(CN)₆]^4- is oxidized and consumed at the packed electrodes, [Fe(CN)₆]^4- begins to diffuse through the monolayer from the bulk solution to the electrodes and the obtained currents depend on the endothelial permeability. As a proof-of-concept, the effects of histamine on the monolayer were monitored. Also, an HUVEC monolayer was cocultured with cancer spheroids, and the endothelial permeability was monitored to evaluate the metastasis of the cancer spheroids. Unlike conventional methods, the device can provide spatial information, allowing the interaction between the monolayer and the spheroids to be monitored. The developed method is a promising tool for organs-on-a-chip and drug screening in vitro.