3D-brAIn: 2025 highlights
As 2025 comes to a close, the 3D-BrAIn consortium continues to move closer to its ambitious goal: creating a bio-digital twin of the human brain that is personalised, precise, and predictive. This approach could transform how we understand diseases of the Central Nervous System (CNS) and accelerate the development of more effective treatments.
This year, we continued advancing our three breakthrough technologies that will help turn our vision into reality:
- 3D human cortical organoids that closely mimic real brain tissue
- A unique high-resolution 3D MEA technology that records neural activity in exceptional detail
- Machine-learning algorithms designed to interpret the vast and complex data these models produce
None of this would be possible without the close collaboration between Erasmus MC (Rotterdam), LMU (Munich), 3Brain (Switzerland), and the University of Genoa!
📸 3D-brAin team at their 2025 consortium meeting dinner in Munich, Germany.
What have we achieved in 2025?
A major achievement was refining the protocol for growing hiPSC-derived adherent cortical organoids directly on high-density electrodes. Improvements to coating conditions and confiner design, resulted in a more stable and reliable environment for organoid growth.
“This is a crucial step, because the more consistently we manage to grow these organoids properly, the more clearly we can observe their neural activity – and the more effectively we can use them to study how diseases emerge and to test new potential treatments” – shares Femke de Vrij, 3D-brAIn coordinator.
📸 Adherent cortical organoids from the Erasmus MC department of Psychiatry (picture by Mark van der Kroeg).
At LMU, the protocol was successfully implemented and combined with calcium-imaging techniques, including early work with mutant hiPSC lines.Â
“Being able to adopt the protocol in our lab really shows we’re building something reproducible and scalable. It also brings us much closer to comparing healthy and disease-relevant brain models in a meaningful way,” says Silvia Cappello, Principle Investigator from LMU.
📸 On the left: Live imaging of cells migrating in the 384 well plate at LMU. On the right: First and successful trial of Calcium Imaging at LMU.
The protocol was published in eLife and filed internationally as a patent—an important milestone for both scientific validation and future commercial impact. The consortium also contributed to broader discussions on how advanced human-based models could complement or reduce animal testing in neurotoxicity research.
“I particularly enjoy the scientific exchange we have in this project. Additionally, seeing how the project grows and the first organoids of multiple cell lines is very exciting. It lays the foundation for this project” adds Rebecca Bonrath, PhD student at LMU and 3D-BrAIn researcher.
📸 Rebecca Bonrath, presenting at 2025 NeuroDoWo (Neurobiology Doctoral Students Workshop) in Munich.
Advancing neurotechnology and data analysis
On the engineering side, 3Brain made major progress with the 24-well 3D HD-MEA system, finalising the well format and building the hardware needed to capture high-resolution neural signals. The first systems are now being delivered to Erasmus MC, where they are being integrated into ongoing organoid experiments.
📸 On the left: The HyperCam Delta and CorePlate™ 24W, the first 24-well HD-MEA system capable of simultaneously recording from all 1,024 electrodes per well, across all 24 wells, enabling high-throughput screening of electrogenic cells. 
 On the right: Activity map showing the mean firing rates of 48 rat neuronal spheroids in CorePlate™ 24W (two per well), demonstrating the simultaneous recording capability of all 1,024 electrodes across all 24 wells.Â
“We were thrilled to see the completion of our 24-well HD-MEA system: The HyperCam Delta and CorePlate™ 24W. This system’s ability to capture high-resolution neuronal activity, with simultaneous recording from all electrodes across all wells, marks a significant milestone for neuroscience research and greatly expands the possibilities for functional screening of organoids. We look forward to supporting the research community as they begin to leverage this new technology.” notes Alessandro Maccione, Co-founder and CSO of 3Brain.
At the same time, UNIGE and Erasmus MC continued to strengthen the data-analysis side of the project. Through close collaboration and lab exchanges, they continued refining and developing new machine-learning tools that help improve data quality and begin exploring how patterns of neural activity can be automatically detected and interpreted. These tools will become increasingly important as more data is generated on the new MEA system.
📸 On the left: Spike Sorting on the activity recorded by an electrode. 📸 On the right: Lorenzo Sacchi attending Summer School in Amsterdam.
“The quest for a mathematical model capable of explaining the biological dynamics unfolding within organoids—through the analysis of data in all their scale and complexity—is an exceptionally challenging, yet profoundly inspiring endeavor.” Explains Lorenzo Sacchi, PhD Candidate from UNIGE.
Together, these advances mark a strong year for 3D-BrAIn and lay critical groundwork for what comes next, so…
