Abstract
Abstract
Three-dimensional cell technologies as pre-clinical models are emerging tools for mimicking the structural and functional complexity of the nervous system. The accurate exploration of phenotypes in engineered 3D neuronal cultures, however, demands morphological, molecular and especially functional measurements. Particularly crucial is measurement of electrical activity of individual neurons with millisecond resolution. Current techniques rely on customized electrophysiological recording set-ups, characterized by limited throughput and poor integration with other readout modalities. Here we describe a novel approach, using multiwell glass microfluidic microelectrode arrays, allowing non-invasive electrical recording from engineered 3D neuronal cultures. We demonstrate parallelized studies with reference compounds, calcium imaging and optogenetic stimulation. Additionally, we show how microplate compatibility allows automated handling and high-content analysis of human induced pluripotent stem cell–derived neurons. This microphysiological platform opens up new avenues for high-throughput studies on the functional, morphological and molecular details of neurological diseases and their potential treatment by therapeutic compounds.
Funder
European Union Horizon 2020 Framework Programme for Research and Innovation
Ministry of National Education of Turkey
State Ministry of Baden-Württemberg for Economic Affairs, Labour and Housing Construction
Network of Centres of Excellence in Neurodegeneration
Baden-Württemberg Stiftung GmbH
German Ministry of Education and Research
Subject
Biomedical Engineering,General Medicine,Biomaterials,Biochemistry,Bioengineering,Biotechnology