Clinical translation of ultrasoft Fleuron™ probes for stable, high-density, and 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 obtain due to the instability of rigid materials in the brain. How can we achieve high-density neural recordings with wide brain region access at single-neuron resolution, while maintaining long-term stability? In this study, we present a novel approach to overcome these trade-offs by introducing Fleuron, a family of ultrasoft, ultra-low-k dielectric materials compatible with thin-film scalable microfabrication techniques. We successfully integrate up to 1,024 channels 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-channel Fleuron probes, that cover 8× 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 andex vivohuman 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 clinical translation in iBCIs.