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Producing a new neural stem cell model requires stages of development, optimization, and validation. For excitable cells, such as neurons, each of these stages requires functional assessment of the cellular electrical activity. Specifically, detection of functional electrical activity defines the development of an iPSC-derived neuronal model and provides a signal on which to optimize the model, ultimately leading to precise electrical phenotypes of human biology. Here, we present a series of case studies demonstrating the use of the Maestro multiwell microelectrode array (MEA) platform as a simple and label-free approach to quantification and optimization of functional electrical activity for human iPSC-derived neuronal models. A planar grid of microelectrodes embedded in the substrate of each well interfaces with cultured networks, such that the electrodes detect the raw electrical activity from the cells. For Neurons, MEA capture unit-level action potentials and quantify comprehensive measures of neural network activity, including synchrony and oscillations. The highlighted case studies will include characterization and optimization of neural network activity, application of iPSC-derived neurons for safety assessment, and validation of neural disease-in-a-dish phenotypes. These results support the continued use of the Maestro multiwell MEA platform for the development, optimization, and validation of iPSC-derived neuronal models to recreate human biology in vitro.
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