Assaying Spontaneous Network Activity and Cellular Viability Using Multi-Well Microelectrode Arrays

Seline S Choo; Jackson Y Keever; Jasmine Brown; Jenna D Strickland; Timothy J Shafer

doi:10.1007/978-1-0716-3052-5_9

Assaying Spontaneous Network Activity and Cellular Viability Using Multi-Well Microelectrode Arrays

Methods Mol Biol. 2023:2644:133-154. doi: 10.1007/978-1-0716-3052-5_9.

Authors

Seline S Choo^{1

2}, Jackson Y Keever^{2

3}, Jasmine Brown^{2

4}, Jenna D Strickland^{5

6}, Timothy J Shafer⁷

Affiliations

¹ Oak Ridge Institute for Science and Engineering, Oak Ridge, TN, USA.
² Rapid Assay Development Branch, Biomolecular and Computational Toxicology Division, Center for Computational Toxicology and Exposure, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC, USA.
³ Oak Ridge Associated Universities Student Contractor, Oak Ridge, TN, USA.
⁴ Duke Clinical Research Institute, Durham, NC, USA.
⁵ Axion Biosystems, Atlanta, GA, USA.
⁶ LabCorp Drug Development, Madison, WI, USA.
⁷ Rapid Assay Development Branch, Biomolecular and Computational Toxicology Division, Center for Computational Toxicology and Exposure, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC, USA. shafer.tim@epa.gov.

PMID: 37142920
DOI: 10.1007/978-1-0716-3052-5_9

Abstract

Microelectrode array (MEA) technology is a neurophysiological method that allows for the measurement of spontaneous or evoked neural activity to determine chemical effects thereon. Following assessment of compound effects on multiple endpoints that evaluate network function, a cell viability endpoint in the same well is determined using a multiplexed approach. Recently, it has become possible to measure electrical impedance of cells attached to the electrodes, where greater impedance indicates greater number of cells attached. This would allow rapid and repeated assessments of cell health as the neural network develops in longer exposure assays without impacting cell health. Typically, the lactate dehydrogenase (LDH) assay for cytotoxity and CellTiter-Blue® (CTB) assay for cell viability are only performed at the end of the chemical exposure period because these assays involve lysing of the cells. Procedures describing the multiplexed methods in acute and network formation screening are included in this chapter.

Keywords: Alamar blue; Cytotoxicity; Electrical impedance; Lactate dehydrogenase; Microelectrode array (MEA); Multiplexed assays; Neural network formation; Viability.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Cell Survival
L-Lactate Dehydrogenase*
Microelectrodes
Nerve Net
Neurons*

Substances

L-Lactate Dehydrogenase