Field Application Scientist MaxWell Biosystems AG, Switzerland
Abstract: Three-dimensional neural models derived from human-induced pluripotent stem cells (hiPSCs), including organoids and assembloids, have emerged as indispensable systems for recapitulating fundamental aspects of human brain development. These models have proven critical for studying neurological disorders like Alzheimer's and Parkinson's disease. To fully understand the intricate dynamics of the neural networks within these self-organizing in-vitro cellular models, there is a need for real-time and label-free electrical activity measurement. High-density microelectrode arrays (HD-MEAs) provide a non-invasive approach to high-content electrical imaging by allowing for real-time electrophysiological recordings from a variety of electrogenic materials, such as neural organoids, assembloids, retinal or brain tissue explants. We utilized the MaxOne and MaxTwo HD-MEA platforms, each equipped with 26’400 electrodes per well, to record extracellular action potentials from various 3D neural models at multiple scales, ranging from network-level activity to single-cell and subcellular analyses. We demonstrated the flexible electrode selection for recording neural activity and how it improves the collected data's statistical power and reproducibility. Key parameters like firing rate, spike amplitude, and network burst profile were extrapolated. We used the AxonTracking Assay to trace action potential propagation along axonal branches, enabling a detailed examination of axon morphology and function, including conduction velocity, latency, axonal length, and branching patterns. This breakthrough assay allows for high-resolution investigation of disease models targeting axon initial segments, axonal branching, development, and conduction. The HD-MEA platforms’ capability for targeted electrode selection improves data consistency and enables more comprehensive statistical insights. Furthermore, automated data visualization and metric extraction make these systems a robust and user-friendly choice for in-vitro disease modeling and drug testing in both acute and longitudinal studies.
Funding Source: This work is funded by the HyVIS project, GA 964468, within the H2020 Framework Program of the European Commission.
