Mid-infrared chemical imaging of living cells enabled by plasmonic metasurfaces

Mid-Infrared (MIR) chemical imaging provides rich chemical information of biological samples in a label-free and non-destructive manner. Yet, its adoption to live-cell analysis is limited by the strong attenuation of MIR light in water, often necessitating cell culture geometries that are incompatible with the prolonged viability of cells. Here, we introduce a new approach to MIR microscopy, where cells are imaged through their localized near-field interaction with a plasmonic metasurface. Chemical contrast of distinct molecular groups provided sub-cellular resolution images of the proteins, lipids, and nucleic acids in the cells that were collected using an inverted MIR microscope. Time-lapse imaging of living cells demonstrated that their behaviors, including motility, viability, and substrate adhesion, can be monitored over extended periods of time using low-power MIR light. The presented approach provides a method for the non-perturbative MIR imaging of living cells, which is well-suited for integration with modern high-throughput screening technologies for the label-free, high-content chemical imaging of living cells.