EMBO | EMBL Symposium - Organoids: modelling organ development and disease in 3D

Human-induced pluripotent stem cell (hiPSC)-derived three-dimensional neural models, such as organoids and assembloids, have become essential tools for mimicking key aspects of human brain development. These self-organizing in vitro systems significantly contribute to the study of neurodegenerative diseases, including Alzheimer’s and Parkinson’s. Real-time, label-free monitoring of electrical activity is crucial for analyzing the complex behavior of neuronal networks in these models.

High-Density Microelectrode Arrays (HD-MEAs) provide a powerful, non-invasive platform for high-resolution electrical imaging, enabling real-time recordings across a broad spectrum of electrogenic samples, from neural organoids and assembloids to brain and retinal tissue slices. In this study, we used the MaxOne and MaxTwo HD-MEA Systems, each featuring 26,400 electrodes per well, to capture extracellular action potentials from 3D neural models at multiple levels of resolution, ranging from subcellular compartments and single cells to whole networks. Flexible electrode selection capabilities of these platforms contributed to improved data reproducibility and statistical robustness. Key parameters such as firing rates, spike amplitudes, and network burst characteristics were analyzed. To gain deeper insight into subcellular processes, the AxonTracking Assay was employed to map action potential propagation along axonal branches, enabling detailed examination of axonal properties such as conduction velocity, latency, length, and branching patterns.  

The ability of these HD-MEA platforms to selectively target electrodes improves data quality while enhancing reproducibility. Combined with the integrated tools for automated data visualization and metric extraction, the systems presented here offer a robust, user-friendly platform, supporting both acute and long-term electrophysiological studies in disease modelling and drug testing.

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