Bioelectronic nose for ultratrace odor detection via brain-computer interface with olfactory bulb electrode arrays.

Rapid and accurate detection of hazardous volatile compounds is crucial for public health and environmental safety. While conventional methods, including electronic noses, typically exhibit detection thresholds in the parts-per-million (ppm) range, many harmful substances pose risks at parts-per-billion (ppb) concentrations or lower. To address this challenge, we leverage the exceptional sensitivity of the mammalian olfactory system, specifically that of Rattus norvegicus (lab rat), which has evolved to detect and discriminate a vast array of odors at extremely low concentrations. In this study, we developed a novel bio-hybrid system that integrates behavioral training with in vivo electrophysiological recordings from the olfactory bulb (OB). Rats were operantly conditioned to recognize target odors, namely TNT (2,4,6-trinitrotoluene), TNP (2,4,6-trinitrophenol), and chlorine gas (Cl2), at ppb levels. Concurrent with behavioral testing, we recorded neural activity from both the dorsal and ventral OB using a customdesigned, multi-channel electrode array optimized for the rat OB's cytoarchitecture. Electrophysiological data were decoded using a Support Vector Machine algorithm, achieving a mean accuracy of over 90 % in classifying odor identity at ppb concentrations based on OB activity patterns. These results demonstrate the feasibility of utilizing a brain-computer interface with the olfactory system to achieve ultratrace detection of hazardous substances. This bio-hybrid approach offers significantly enhanced sensitivity compared to existing electronic nose technologies, paving the way for highly effective environmental and biomedical sensing applications.