Label-free high-resolution infrared spectroscopy for spatiotemporal analysis of complex living systems

Label-free chemical and structural imaging of complex living tissue and biological systems is the holy grail of biomedical research and clinical diagnostics. The current analysis techniques are time-consuming and/or require extensive sample preparation, often due to the presence of interfering molecules such as water, making them unsuitable for the analysis of such systems. Here, we demonstrate a proof-of-principle study using label-free optical photothermal mid-infrared microspectroscopy (O-PTIR) for fast, direct spatiotemporal chemical analysis of complex living biological systems at submicron resolution. While other analytical methods can provide only static snapshots of molecular structures, our O-PTIR approach enables time-resolved and in situ investigation of chemical and structural changes of diverse biomolecules in their native conditions. This comprises a technological breakthrough in infrared spectroscopy to analyze biomolecules under native conditions over time: in fresh unprocessed biopsies, living brain tissue, and vertebrates without compromising their viability.