Operando Monitoring of Metabolic Fluxes In Cholestatic Murine Liver Tissue Slices By Microfluidic Nuclear Magnetic Resonance

Monitoring of the metabolism in living tissues with high temporal resolution and broad metabolite coverage remains a major challenge. We introduce TISuMR, a microfluidic Lab-on-a-Chip platform that enables continuous, non-invasive operando NMR spectroscopy of live tissue slices. The TISuMR platform replaces the conventional NMR sample tube with a fully integrated microfluidic culture system that maintains tissue viability through dynamic nutrient perifusion, gas exchange via a diffusion membrane, and precise temperature control. Coupled with a custom-designed micro-NMR probe, the platform allows detection of nearly two dozens of metabolites from just 2.5 μL of sample. In a proof-of-concept study, we demonstrate the platform's unique ability to resolve dynamic metabolic fluxes and to monitor, in real time, the onset of chlorpromazine-induced cholestasis in murine liver tissue, with a time resolution of just over three minutes. This approach provides a powerful, minimally disruptive tool for studying tissue metabolism in real time.