Intraoperative and spatiotemporal mapping of acute inflammation response during neuroelectrode implantation

Intraoperative and spatiotemporal monitoring of neuroinflammatory indices during brain-computer interface (BCI) implantation is essential for ensuring safety and efficacy of the procedure. Current biomolecular detection approaches are unable to obtain spatiotemporally resolved inflammatory profiling, which is important for guiding the placement of microelectrodes intraoperatively. This study presents an intraoperative spatiotemporal acute inflammation detector (ISAID) that harnesses droplet-based sampling and multiplexed titanium oxynitride (TiNO) plasmonic biosensing to assess local inflammation during the insertion of intracortical microelectrodes. Through freestanding sampling droplets and fine-tuned TiNO-based biosensors, the ISAID achieved precise, sensitive, and integrated sampling to biosensing for cytokine detection with a spatial resolution down to 610 μm and a fast equivalent bioassay time of 1.25 min. The proposed system also allows multiple ISAID biosensing modes, enabling both spatial inflammation mapping and multi-cytokine analysis. Quantitative analyses of inflammatory cytokines with in vivo mouse models demonstrate the accuracy and practical advantages of the system.