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 and with standard high-throughput workflow. 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.