BME7900 Seminar: Gennady Shvets (Cornell AEP)

Description

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 Inverted Reflected-light Infrared Absorption Microscopy (MIRIAM) – 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.

This work was supported 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] C. Wu, A. B. Khanikaev, R. Adato, N. Arju, A. A. Yanik, H. Altug, and G. Shvets, "Fano-resonant asymmetric metamaterials for ultrasensitive spectroscopy and identification of molecular monolayers", Nature Materials 11, 69 (2012).
[2] 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 {\bf 144}, 1115 (2019).
[3] 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).
[4] A. Mahalanabish et. al., ACS Sens. 9, 1218 (2024); Nano Lett. 24, 2024, 11607 (2024).
[5] Steven H. Huang, Po-Ting Shen, Aditya Mahalanabish, Giovanni Sartorello, and Gennady Shvets, “Mid-infrared chemical imaging of living cells enabled by plasmonic metasurfaces”, https://www.biorxiv.org/content/10.1101/2024.09.17.613596v1 (2024).
 

Bio:
Gennady Shvets is a J. Preston Levis Professor of Applied and Engineering Physics at Cornell University. He received his Ph.D. in physics from MIT in 1995. Before moving to Cornell in 2016, he was on the physics faculty of the University of Texas at Austin for 12 years. His research interests at the intersection of nanotechnologies and biophotonics include bio-spectroscopy, chemical imaging of live cells, and microfluidics. He is a Fellow of the American Physical Society, Optical Society of America, and SPIE.

His most recent work deals with the applications of metamaterials and plasmonics to biosensing and molecular fingerprinting of proteins and live cells using metamaterial arrays. He is particularly interested in the integration of plasmonic metasurfaces with various applications-specific platforms such as microfluidics and optical fibers. His group is exploring the nano-bio interface between plasmonic structures and living cells, tissues, and bacterial colonies. Recently, he demonstrated the first metasurface-based tool for studying the effects of pharmaceutical stimuli on living cells in real time, including drug effects on cellular morphology, motility, and metabolism.