Flexible electronics integrating 3D nanostructured electrodes for cellular-resolution in-depth electrophysiology recordings from developing spheroids and organoids

Project Information

SPHELECTRO

Grant agreement ID: 101028752

DOI

10.3030/101028752

Project closed

EC signature date 24 March 2021

Start date 1 February 2022

End date 24 December 2025

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 295 061,76

EU contribution

€ 295 061,76

Coordinated by

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
France

Periodic Reporting for period 1 - SPHELECTRO (Flexible electronics integrating 3D nanostructured electrodes for cellular-resolution in-depth electrophysiology recordings from developing spheroids and organoids)

Reporting period: 2022-02-01 to 2025-01-31

Summary of the context and overall objectives of the project

Three-dimensional neural models such as spheroids and organoids represent promising platforms for studying human brain development and neurodegenerative disorders, offering advantages for large-scale production and drug screening applications. However, current electrical characterization techniques remain limited to acute, invasive, or superficial recordings that fail to capture the long-term functional dynamics of these 3D structures. The SPHELECTRO project addressed this critical gap by developing a flexible electronics platform capable of seamless integration into 3D brain models for prolonged electrophysiological monitoring.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

The project successfully achieved its core technical objectives through systematic development across multiple work packages. A biocompatible, ultra-thin flexible mesh platform named Neuronet was designed and fabricated using a multilayer SU-8/metal process. Extensive process development resolved critical challenges including mechanical stress management in thin-film structures and unwanted metal-catalyzed polymer crosslinking. Integration protocols were established to incorporate these flexible devices into developing primary cortical spheroids and human iPSC-derived brain organoids at early developmental stages. Leveraging an existing in-house 60-channel acquisition platform developed within the host team, a complete electrophysiology recording system was established through the development of custom packaging solutions compatible with standard cell culture formats and dedicated analysis software (NeuraScope). Proof-of-concept validation demonstrated successful long-term recordings of spontaneous neural activity from both primary spheroids and human organoids, capturing network maturation dynamics over long culture periods.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

This work represents the first demonstration of integrated flexible electronics for chronic, multi-site electrophysiological monitoring throughout 3D neural tissue constructs. The platform's compatibility with standard laboratory culture consumables positions it as a potentially scalable tool for neuroscience research and pharmaceutical applications. By enabling routine functional assessment of organoid models, this technology contributes to European strategic objectives including development of human-relevant alternatives to animal experimentation (3Rs principles) and acceleration of drug discovery for neurological disorders affecting millions of Europeans. Primary end-users include academic laboratories studying brain development and disease, pharmaceutical companies conducting screening assays, and emerging personalized medicine applications. While current technology readiness remains at proof-of-concept stage, the successful demonstration of key functionalities establishes a foundation for future commercial development in the rapidly growing organoid electrophysiology market.

A Neuronet electrophysiology mesh integrated into a primary cortical spheroid