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bioRxiv · 10.1101/2025.10.08.681085

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

Abstract

Monitoring metabolism in living tissues with high temporal resolution and broad metabo-lite 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 {micro}L of sample. In a proof-of-concept study, we demonstrate the platforms 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.

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Barker, S. J., Patra, B., Sharma, M., Karsten, R. E. H., Verpoorte, E., Utz, M.. 2025-10-08. Operando Monitoring of Metabolic Fluxes In Cholestatic Murine Liver Tissue Slices By Microfluidic Nuclear Magnetic Resonance. https://doi.org/10.1101/2025.10.08.681085

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