Microfluidic NMR for Operando Monitoring of Drug-Induced Metabolic Fluxes in Liver Tissue Slices

Abstract

Monitoring metabolism in living tissues with high temporal resolution and broad metabolite coverage remains a major challenge. We introduce the TISuMR platform, 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.