Inaugural International Conference on Organoid Intelligence (ICOI)

Progress toward organoid intelligence requires interfaces capable of resolving the functional dynamics of complex 3D neural systems across spatial and temporal scales, while supporting longitudinal and scalable experimentation. High-density microelectrode arrays (HD-MEAs) provide a non-invasive interface between neural organoids and quantitative electrophysiology by combining dense spatial sampling with network-level and subcellular functional readouts.

Here, we used the MaxTwo multi-well HD-MEA system to longitudinally characterize human iPSC - derived midbrain organoids as a representative 3D neural model. Organoids were plated at approximately 77 days of age onto 24-well HD-MEA plates containing 26,400 electrodes per well and monitored for approximately one month. High resolution activity scans revealed progressive increases in firing rate, spike amplitude, and active area. Network recordings captured increasingly organized synchronized bursting, with increased burst cadence and neuronal recruitment over time. Acute 4-aminopyridine and tetrodotoxin treatment produced rapid and reproducible bidirectional modulation of activity, demonstrating sensitivity to functional perturbation. At a finer spatial scale, the AxonTracking assay enabled label-free reconstruction of soma-to-axon propagation patterns at the organoid–electrode interface, extending phenotyping from population dynamics to axonal function.

In this study, HD-MEAs were primarily used as high-content recording interfaces. However, the broader technology ecosystem also supports electrical stimulation and programmable control through the MaxLab Live API, enabling more interactive and potentially closed-loop paradigms. In parallel, PDMS application-ready technology enhances compatibility with microphysiological systems (MPS), enabling engineered microenvironments, microfluidics, and more spatially organized tissue architectures. Together, these capabilities position HD-MEA technology as an enabling interface for organoid-based experimentation, resolving maturation and perturbation across functional scales while providing the recording, stimulation, and integration framework needed for future closed-loop investigation of adaptive neural dynamics.

‍