Abstract: Human organoids are miniaturized, self-organizing tissues that emulate human physiology and disease. Yet, technical complexity and endpoint measurements limit their use in studying dynamic disease processes. To overcome this, we embedded microsensors within human liver, kidney, cardiac, and brain organoids to continuously track metabolic activity and physiological function. This innovation underlies the DynamiX® platform, a robotic bioanalyzer capable of screening over 20,000 organoids simultaneously during chronic drug exposure or disease progression.
Using DynamiX®, we resolved the idiosyncratic toxicity of troglitazone and created the world’s largest dataset on drug-induced liver injury from 9,600 human liver organoids. The resulting MechaniX® machine-learning model achieved 96% accuracy in predicting FDA-reported hepatotoxicity. The platform also revealed a previously unknown, human-specific mechanism of drug-induced kidney injury, later validated in a clinical study, demonstrating its translational power. Building on this foundation, we developed a vascularized, self-pacing, multi-chambered cardiac organoid containing pacemaker clusters, an endocardial lining, and an epicardial shell. Using our Electro-Metabolic Chip (EM-Chip®), which simultaneously measures metabolic flux, electrical activity, and contractility at >10 Hz, we discovered that cardiac metabolism oscillates with electrical rather than mechanical function. Disruption of this electro-metabolic coupling reproduced cancer treatment–induced arrhythmia (CTIA), which was reversed by mitochondrial modulators such as metformin. Applying the EM-Chip® to human and avian brain organoids revealed similar coupling between neuronal metabolism and electrical activity, suggesting a shared mechanism underlying epileptic hyperexcitability that can likewise be mitigated by metabolic intervention.
Together, these bionic human organoids represent a shift from descriptive biology to quantitative, dynamic physiology. By merging living human tissues with embedded sensing, electro-metabolic tracking, and robotic automation, we can directly observe the mechanisms linking metabolism, electrophysiology, and disease—opening a new frontier in human systems biology.
Biosketch: Prof. Yaakov “Koby” Nahmias is a bioengineer and innovator whose breakthroughs range from the first 3D printing of cells to the first commercial human-on-chip technology. He is a Magna Cum Laude graduate of the Technion, Israel Institute of Technology, and the founding director of the Grass Center for Bioengineering of the Hebrew University of Jerusalem. Nahmias is a recipient of an NIH career award, the Kaye Innovation Award, and the prestigious Rappaport Prize in Biomedical Research. He is the first scientist outside Britain to win the Rosetrees Trust Prize. Nahmias is a fellow of the prestigious American Institute for Medical and Biological Engineering (AIMBE) and the British Royal Society of Medicine (RSM). Nahmias is the co-founding director of BioDesign-Israel. An entrepreneurship program that has educated over 250 fellows since 2013, launching 10 startup companies, including Guide In Medical, CardioVia, and Swiftduct. Nahmias is the founder of two biotechnology startups, including Tissue Dynamics, which is advancing the world’s first autonomous drug development platform, and the world’s leading cultivated meat company, Believer Meats (formerly Future Meat Technologies), focusing on the cost-effective production of cultured meat, ensuring the future of coming generations.