Abstract: The human brain represents the most complex organ of our body and thus modeling a development of functioning human brain-on-dish is an enormous challenge. Recent advances of microphysiological systems are a way to address brain development, homeostasis, functionality and diseases in more physiologically and human-relevant conditions. Microphysiological systems is fast growing field, which implements the modern cell culture technologies in drug development and chemical safety testing as well as basic research to advance our understanding of human biology and diseases. We are implementing a brain MPS (brain organoids) to study developmental neurotoxicity. Specifically, we address the gene environmental interactions in autism by using brain organoids with autism genetic background. Using CRISPR/Cas9 gene-editing technology in iPSC, we have developed multi-fluorescent brain organoids, which allowed to screen environmental chemicals and drugs in a complex brain model. To bring brain organoids closer to in vivo, we introduced iPSC-derived microglia, immune-cells of the brain, which allowed us to study not only the role of microglia in synaptogenesis but also neuroinflammation upon drug/chemical exposure and viral infections. We recently developed a 3D multi-electrode array platform (organoid EEG). We use this EEGs and high-density multi-electrode arrays with the aim to address the ultimate functional readout of the brain – cognitive functions with MPS. Coining the term Organoid Intelligence (OI) to encompass these technical developments, we are showcasing the new multi-disciplinary scientific and engineering field of OI. Here, we describe the scientific and technological basis of OI – bringing to the fore the latest collaborative brain cell culture/bioengineering/AI advances, providing the foundation for the new OI paradigm. This presentation will showcase examples of how we might move towards advanced, cost -effective and human-relevant test systems in a regulatory context and accelerate the screening of the drugs and chemicals with increased predictivity for humans.