Capturing the organoid’s activity
Introducing Alessandro Maccione from 3Brain
The 3D-BrAIn journey begins at Erasmus MC, where the De Vrij Lab is pioneering the development of innovative brain organoids to study neurological diseases. The goal is to investigate how these cells behave and understand how their activity changes when affected by disease. But how is this activity measured, and what technology makes it possible?
The missing piece comes from 3Brain, a Swiss company providing 3D-brAIn with cutting-edge technology to push the boundaries of neurological research and offering new insights into brain function.
With a background in Bioengineering and Bioelectronics, Alessandro Maccione is one of the co-founders and the Chief Scientific Officer (CSO) at 3Brain.
Based in Pfäffikon (CH) with a branch office in Genova (IT), 3Brain is the world’s first company to record cell activity using intelligent cell culture plates. Their CorePlate™ technology integrates cell culture plates with High-Density Multi-Electrode Arrays (HD-MEA), allowing researchers to record the electrophysiological activity of thousands of cells simultaneously. Their mission is simple: to develop microchip-based technology that revolutionises scientific research. They achieve this by providing a sophisticated platform for studying electrogenic cells, such as neurons and cardiac cells.
How does this technology play a role in the 3D-BrAIn project? Alessandro explains: “The 3D-BrAIn project aims to develop personalised precision medicine for central nervous system disorders. To achieve this, three separate technologies are brought together—the iPSC-derived organoids from Erasmus MC, the AI approach for analysing data from the University of Genoa, and the HD-MEAs, which provide the means to record and analyse the data from the grown organoids.”
“A MEA, or in our case a HD-MEA, is a device providing tens to thousands of electrodes with which cells lay in close contact. These electrodes don’t penetrate into the cell, but are capable of measuring the extracellular electrical activity of cells just by being in close contact with them.”
What exactly is an HD-MEA and how does it work?
Cells like neurons communicate by transmitting electrical signals. These cells are “excitable” which means that when active they generate changes in their membrane voltage to send signals. Accurately measuring these electrical signals is crucial for understanding how the brain functions both in health and disease. “The purpose of MEAs is to measure these changes in voltage,” explains Alessandro Maccione.
Traditional methods, like patch clamping—where a tiny electrode is inserted directly into a cell—are invasive and limited in how many cells they can monitor at once. In contrast, High-Density Multi-Electrode Array (HD-MEA) technology provides a non-invasive way to monitor the electrical activity of many cells simultaneously.
“A MEA, or in our case a HD-MEA, is a series of electrodes with which cells lay in close contact,” Maccione adds. “These electrodes don’t penetrate the cell but can still measure the electrical activity by simply being near them.” This approach offers a higher-throughput, less invasive alternative to traditional methods, allowing researchers to gather more data without damaging the cells. Additionally, with this technology scientists can study how well cells are interconnected at a network level and detect changes caused by diseases or drug treatments. This makes HD-MEA technology a powerful tool for understanding brain function and developing more effective treatments.
From collaboration to innovation
Before the 3D-BrAIn project formally began, Alessandro was already collaborating with part of the current 3D-BrAIn team, including with project coordinator and Femke de Vrij and Steven Kushner from Erasmus MC. “They have an amazing top-class approach to organoid development for high-throughput screening, and we were looking at the possibility to combine our technology to exploit their biological capabilities with our engineering skills,” Alessandro mentions.
The European Innovation Council recognised the potential of this collaboration and funded the 3D-BrAIn project, bringing together not only Erasmus MC and 3Brain but also experts like Silvia Cappello from Ludwig Maximilian University of Munich and Michele Piana and Cristina Campi from the University of Genova. The combination of biological and neuro-computational expertise within this team is set to push the boundaries of neurological research.
So, what does a day in the office looks like at 3BrAIn? For Alessandro, a typical day at work at 3Brain starts with the most important ritual – an espresso. After that, the day involves a mix of laboratory work, such as developing and testing new chips, and office-based activities like writing grant proposals and managing scientific collaborations. “Additionally, I dedicate part of my time to coordinating the Customer Success department, which supports our customers in utilizing our systems effectively,” he adds.
“I truly believe this project has the potential to greatly impact the way in which medical treatments are developed.”
Future outlook
Looking to the future, Alessandro is enthusiastic about the potential of the 3D-BrAIn project, seeing it as a groundbreaking concept with significant potential to benefit patients in the future.
Alessandro points out: “The overall aim of the project is to build a platform which can allow reliable, robust, and accurate modelling of the human frontal cortex, to support development of personalised medicine, drug screening and neurotoxicity testing.”
Besides advancing personalized medicine, the 3D-BrAIn project is also seeking to reduce reliance on animal testing. Currently, drug development heavily depends on animal models which often fail to accurately reflect human biology and predict human responses. By creating human-derived organoid models, the 3D-BrAIn project hopes to provide a more ethical and accurate alternative. “I truly believe this project has the potential to greatly impact the way in which medical treatments are developed,” Alessandro says.