Intraoperative assessment of microimplantation-induced acute brain inflammation with titanium oxynitride-based plasmonic biosensor

Abstract

Implantable devices for brain-machine interfaces and managing neurological disorders have experienced rapid growth in recent years. Although functional implants offer significant benefits, issues related to transient trauma and long-term biocompatibility and safety are of significant concern. Acute inflammatory reaction in the brain tissue caused by microimplants is known to be an issue but remains poorly studied. This study presents the use of titanium oxynitride (TiNO) nanofilm with defined surface plasmon resonance (SPR) properties for point-of-care characterizing of acute inflammatory responses during robot-controlled micro-neuro-implantation. By leveraging surface-enriched oxynitride, TiNO nanofilms can be biomolecular-functionalized through silanization. This label-free TiNO-SPR biosensor exhibits a high sensitivity toward the inflammatory cytokine interleukin-6 with a detection limit down to 6.3 fg ml−1 and a short assay time of 25 min. Additionally, intraoperative monitoring of acute inflammatory responses during microelectrode implantation in the mice brain has been accomplished using the TiNO-SPR biosensors. Through intraoperative cerebrospinal fluid sampling and point-of-care plasmonic biosensing, the rhythm of acute inflammatory responses induced by the robot-controlled brain microelectrodes implantation has been successfully depicted, offering insights into intraoperative safety assessment of invasive brain-machine interfaces.