In Vivo Real-Time Monitoring System Using Probe Electrospray Ionization/Tandem Mass Spectrometry for Metabolites in Mouse Brain

Recent improvements in ambient ionization techniques combined with mass spectrometry has enabled to achieve real-time monitoring of analytes of interest, even for biogenic molecules in living animals. Here, we demonstrate a newly developed system for in vivo real-time monitoring of metabolites in a living mouse brain. It consists of a semi-automated manipulation system and a unique probe electrospray ionization unit, which uses an extremely thin solid needle (tip dia.: 700 nm) for direct sampling and ionization, coupled to a conventional tandem mass spectrometer. The system successfully monitored 8 cerebrum metabolites related to central energy metabolism in an isoflurane-anesthetized mouse in real time with a 20 s interval. Moreover, our system succeeded in capturing dynamics of energy metabolism in a mouse administered with cannabinoid type-1 receptor agonist, which is known to disrupt cerebrum energy metabolism. The present system now opens the door to the next stage of cutting-edge technique in achieving in vivo real-time monitoring.