CSHL Assembloids & Complex Cell-Cell Interactions across Tissues & Organs

Three-dimensional neural systems derived from human-induced pluripotent stem cells (hiPSCs), including organoids and assembloids, have emerged as powerful model systems for mimicking crucial aspects of human brain development. These models are increasingly applied to study neurological disorders such as 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 and assembloids. Here, we utilized the MaxOne and MaxTwo HD-MEA platforms, each equipped with 26,400 electrodes per well, to record extracellular action potentials from a variety of 3D neuronal models across different scales – from entire neuronal networks to individual neurons and even subcellular compartments. 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 development and conduction.  

The capability of targeted electrode selection improves the HD-MEA platforms’ data consistency while supporting more comprehensive statistical analyses. Together with the automated data visualization and parameter extraction, these platforms establish a versatile, accessible and user-friendly technology for in-vitro disease modeling and drug testing in both acute and longitudinal studies.

‍