Clinical translation of ultrasoft Fleuron probes for stable, high-density, and tissue-wide bidirectional brain interfaces

Building brain foundation models to capture the underpinning neural dynamics of human behavior requires large functional neural datasets for training, which current implantable Brain-Computer Interfaces (iBCIs) cannot achieve due to the instability of rigid materials in the brain. How can we realize high-density neural recordings with wide brain region access at single-neuron resolution, while maintaining the long-term stability required? In this study, we present a novel approach to overcome these trade-offs, by introducting Fleuron, a family of ultrasoft, ultra-low-k dielectric materials compatible with thin-film scalable microfabrication techniques. We successfully integrate up to 1,024 sites within a single minimally-invasive Fleuron depth electrode. The combination of the novel implant material and geometry enables single-unit level recordings for 18 months in rodent models, and achieves a large number of units detected per electrode across animals. 128-site Fleuron probes, that cover 8x larger tissue volume than state-of-the-art polyimide counterparts, can track over 100 single-units over months. Stability in neural recordings correlates with reduced glial encapsulation compared to polyimide controls up to 9-month post-implantation. Fleuron probes are integrated with a low-power, mixed-signal ASIC to achieve over 1,000 channels electronic interfaces and can be safely implanted in depth using minimally-invasive surgical techniques via a burr hole approach without requiring specialized robotics. Fleuron probes further create a unique contrast in clinical 3T MRI, allowing for post-operative position confirmation. Large-animal and ex vivo human tissue studies confirm safety and functionality in larger brains. Finally, Fleuron probes are used for the first time ever intraoperatively during planned resection surgeries, confirming in-human usability, and demonstrating the potential of the technology for clincical translation in iBCIs.