Combining quantum cascade lasers and plasmonic metasurfaces to monitor de novo 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 label-free 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 de novo 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 MIRIAMs capability for studying metabolic pathways with molecular specificity, offering a powerful platform for label-free imaging of cellular metabolism.