We developed metasurface-enhanced mid-infrared microscopy for living cells, where cells are cultured on a metasurface-bottomed microwell and are probed from the bottom using a confocal laser scanning microscope with a quantum cascade laser (QCL) as the source. The mid-infrared light interacts with the cells through the near-field of the plasmonic nanoantennas in the metasurface, and the reflected light is detected in the far field. Using this setup, we imaged fixed cells at different vibrational bands for the chemical imaging of different biomolecules, including proteins, lipids, and nucleic acids. Additionally, we have monitored the real-time adhesion and spreading of living cells on the metasurface with protein contrast.
Vertical nanostructures have been studied extensively and been reported to induce unique responses in cells, including the formation of clathrin coating and accumulation of actin filament which leads to cell membrane curvature around the nanostructures. In our previous works, we have demonstrated that arrays of plasmonic nanoantenna can be used as effective label free biosensors to study live cells when combined with IR spectroscopy in the reflection mode, known as metasurface enhanced IR spectroscopy (MEIRS). By fabricating these plasmonic metasurfaces on top of silica nanopillars, we demonstrate that we can expand the potential of MEIRS: increased protein IR absorption in the amide band and increased sensitivity of our biosensor to processes involving cellular interaction with vertical nanostructures.
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