Abstract
With the establishment of Modernization 2.0 and the OECD's in vitro battery tests for developmental neurotoxicity, there has been a growing demand for compound evaluation methods using in vitro neuronal cells. Assessment methods utilizing microelectrode array (MEA) are increasingly becoming a primary approach for evaluating the safety and efficacy of compounds, taking the functionality of neural networks as a benchmark. In this presentation, we will introduce compound evaluation methods based on high spatiotemporal resolution measurements using the next-generation MEA, the high-density complementary metal-oxide semiconductor (CMOS)-MEA, and an MEA system capable of simultaneously measuring extracellular potentials and electrochemical measurements. Using the CMOS-MEA, we detected compound responses based on detailed propagation pattern analysis in brain slices and brain organoids, as well as single-cell firing pattern analysis in cultured neurons. We have also developed an enzyme-modified carbon nanotube microelectrode array (CNT-MEA) capable of measuring glutamate at the nM level. By establishing an MEA system that can simultaneously measure extracellular potentials and electrochemical measurements, we successfully achieved real-time measurements of extracellular potentials and glutamate release from acute brain slices. CMOS-MEA and CNT-MEA provides a new understanding of the basic mechanisms of brain circuits in vitro and ex vivo, on human neurological diseases for drug discovery, and compound toxicity assessment.
