Periodic Reporting for period 1 - 3D-BrAIn (Revolutionary high-resolution human 3D brain organoid platform integrating AI-based analytics)
Okres sprawozdawczy: 2023-04-01 do 2024-03-31
The long-term vision of the 3D-BrAIn consortium is to revolutionize personalized precision medicine for central nervous system (CNS) disorders, by developing an innovative bio-digital twin model of the human brain that is personalized, precise, and predictive.
In this project we bring together three breakthrough technologies: 1) a novel, highly reproducible human brain modelling technology using robust adherent iPSC-derived 3D cortical organoid cultures, 2) a unique, state-of-the-art 3D multi-electrode array (MEA) technology for non-invasive high-resolution electrophysiological recordings and 3) a novel approach to analyze and interpret the large quantities of functional data using tailored automated machine learning (ML)-based algorithms.
With this approach we overcome significant hurdles that made it thus far impossible to create a truly representative and functional model of the CNS for personalized medicine, drug screening and neurotoxicity testing. The revolutionary 3D-BrAIn platform will allow robust and accurate modelling of the CNS for a broad range of neuropsychiatric diseases.
In this project a prototype of the 3D-BrAIn platform will be developed by growing functional 3D organoids that faithfully resemble the human cortex on 3D MEA micropillar electrodes, enabling continuous functional monitoring and by developing ML-based algorithms that can process and interpret the large spatiotemporal data sets. Once all individual components are optimized and integrated, proof-of-concept will be obtained by validating the platform using disease-relevant hiPSC cell lines.
In this project we bring together three breakthrough technologies: 1) a novel, highly reproducible human brain modelling technology using robust adherent iPSC-derived 3D cortical organoid cultures, 2) a unique, state-of-the-art 3D multi-electrode array (MEA) technology for non-invasive high-resolution electrophysiological recordings and 3) a novel approach to analyze and interpret the large quantities of functional data using tailored automated machine learning (ML)-based algorithms.
With this approach we overcome significant hurdles that made it thus far impossible to create a truly representative and functional model of the CNS for personalized medicine, drug screening and neurotoxicity testing. The revolutionary 3D-BrAIn platform will allow robust and accurate modelling of the CNS for a broad range of neuropsychiatric diseases.
In this project a prototype of the 3D-BrAIn platform will be developed by growing functional 3D organoids that faithfully resemble the human cortex on 3D MEA micropillar electrodes, enabling continuous functional monitoring and by developing ML-based algorithms that can process and interpret the large spatiotemporal data sets. Once all individual components are optimized and integrated, proof-of-concept will be obtained by validating the platform using disease-relevant hiPSC cell lines.
In this first year of the project, excellent progress has been made in alignment with the original schedule. Five deliverables were successfully executed as planned (D1.1 D2.1 D3.1 D5.1 D5.2). Important scientific progress was made by shipping the BioCAM DupleX system from 3Brain to the lab in Erasmus MC and successfully installing the system there. The first organoids were seeded on planar 2D Accura chips from 3Brain and the first recordings of neuronal activity were performed (D1.1). In parallel, custom biocompatible confiners and PDMS masks were produced by 3Brain to adapt the dimensions of the MEA chips for organoid formation (D2.1). These confiners were successfully mounted onto HD Accura chips and seeded with hiPSC-derived neural progenitor cells for organoid formation. Also in parallel, close communication between the group in UNIGE and Erasmus MC allowed setting up a shared environment for data exchange, pre-processing and quality control of MEA recording data (D3.1). For communication and dissemination a website and logo were created and a concise plan for communication, dissemination and exploitation (CDE) was prepared (Deliverables 5.1 and 5.2).
The previously established Erasmus MC adherent cortical organoid model has been submitted for publication in an open access peer reviewed journal. In parallel, the protocol has been filed for patenting, assuring proper IP protection and commercialization potential in the future . A working prototype of the HD-MEA 24-well system has been implemented; the system offers the capability to record simultaneously from more than 6K electrodes (up to 24k electrodes in one year ) from 24 wells, a result never achieved so far by other systems.