HMNTL Master Calendar

Utilizing Vibrational Contrast: A New Real-time Label-free Imaging Platform for Studying Living Cells

Fluorescent imaging of cells in culture with an inverted epi-illumination microscope is a “work horse” of high-content imaging (HCI) in a multi-well format that can be conveniently integrated with automated pipetting. An important limitation of the fluorescence-based microscopy is the need for potentially photo-toxic labels. I will introduce a new HCI approach to mid-infrared (MIR) high-content imaging that utilizes the vibrational contrast of the endogenous molecular groups in a label-free and non-destructive manner. In our new imaging platform –Metasurface Enabled Epi-illumination Microscopy (MEEM) – cells are cultured atop of plasmonic metasurfaces (arrays of metallic nano-antennas attached to the bottom of multi-well titter plates) and imaged using epi-illumination by a rapidly-tuneable MIR laser. I will describe our recent results demonstrating continuous time-lapse imaging of living fibroblast cells under the influence of actin- and microtubule-disrupting drugs, as they undergo changes in motility, morphology, and adhesion. Since vibrational contrast enables monitoring metabolic processes with stable isotope-labelled precursors (¹³C-glucose), I will also describe how imaging of the molecular composition of the lipid droplets in adipocytes can be used to quantify de novo lipogenesis in a continuous and non-destructive way. Finally, I will describe how large-scale silicon wafers can be used for scaling-up the MEEM imaging platform to large multi-well titter plates.

This work was supported by by the National Cancer Institute of the National Institutes of Health under award number R21CA251052 and by the National Institute of General Medical Sciences of the National Institutes of Health under award number R21GM138947.

References
[1] G. Kelp, N. Arju, A. Lee, E. Esquivel, R. Delgado, Y. Yu, S. Dutta-Gupta, K. Sokolov, and G. Shvets, "Application of metasurface-enhanced infra-red spectroscopy to distinguish between normal and cancerous cell types", Analyst 144, 1115 (2019).|
[2] Steven H. Huang, Jiaruo Li, Zhiyuan Fan, Robert Delgado, and Gennady Shvets, "Monitoring the effects of chemical stimuli on live cells with metasurface-enhanced infrared reflection spectroscopy", Lab on Chip 21, 3991 (2021).
[2] A. Mahalanabish et. al., ACS Sens. 9, 1218 (2024); Nano Lett. 24, 2024, 11607 (2024).
[4] Steven H. Huang, Po-Ting Shen, Aditya Mahalanabish, Giovanni Sartorello, Jenny Li, Xuefeng Liu, and Gennady Shvets, “Mid-infrared chemical imaging of living cells enabled by plasmonic metasurfaces”, Advanced Photonics Nexus 5, 036003 (2026).
[5] Steven H. Huang, Dias Tulegenov and Gennady Shvets, "Combining quantum cascade lasers and plasmonic metasurfaces to monitor de novo lipogenesis with vibrational contrast microscopy", Nanophotonics 14, 4133 (2025).

Bio:
Gennady Shvets is a J. Preston Levis Professor of Applied and Engineering Physics at Cornell University. He received his PhD in Physics from MIT in 1995. Before moving to Cornell in 2016, he was a faculty member of the Physics Department of the University of Texas at Austin for 12 years. Shvets and his group pioneered several key concepts in photonics and metamaterials, including: (a) topological photonics, (b) first experimental demonstrations of active metalenses an metasurfaces controlled by a variety of materials, including graphene, polaritonic materials, and liquid crystals, and (c) first applications of plasmonic metasurfaces to studying biological matter – from protein monolayers to living cells. His most research interests, at the intersection of nanotechnologies, photonics, and nonlinear optics include: bio-nano interface, microscopy with vibrational contrast, high-intensity interactions between light and nanostructures, and topological nanophotonics. Shvets is a Fellow of the American Physical Society, Optical Society of America, and SPIE.