Combining quantum cascade lasers and plasmonic metasurfaces to monitor <i>de novo</i> lipogenesis with vibrational contrast microscopy

The combination of a tunable quantum cascade laser (QCL) and plasmonic mid-infrared (MIR) metasurface is a powerful tool enabling high-content microscopy of hydrated cells using the vibrational contrast of their constituent biomolecules. While the QCL provides a high-brightness source whose frequency can be rapidly tuned to that of the relevant molecular vibration, the metasurface is used to overcome water absorption of MIR light. Here we employ the resulting metasurface-enabled inverted reflected-light infrared absorption microscopy (MIRIAM) tool for non-destructive monitoring of the vital process of <i>de novo</i> lipogenesis (DNL), by which fat tissue cells (adipocytes) synthesize fatty acids from glucose and store them inside lipid droplets. Using ¹³C-labeled glucose as a metabolic probe, we produce spatially- and temporally-resolved images of ¹³C incorporation into lipids and proteins, observed as red-shifted vibrational peaks in the MIR spectra. These findings demonstrate MIRIAM's capability for studying metabolic pathways with molecular specificity, offering a powerful platform for metabolic imaging.