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Infrared spectroscopy has found wide applications in the analysis of biological materials. A more recent development is the use of engineered nanostructures – plasmonic metasurfaces – as substrates for metasurface-enhanced infrared reflection spectroscopy (MEIRS). Here, we demonstrate that strong field enhancement from plasmonic metasurfaces enables the use of MEIRS as a highly informative analytic technique for real-time monitoring of cells. By exposing live cells cultured on a plasmonic metasurface to chemical compounds, we show that MEIRS can be used as a label-free phenotypic assay for detecting multiple cellular responses to external stimuli: changes in cell morphology, adhesion, and lipid composition of the cellular membrane, as well as intracellular signaling. Using a focal plane array detection system, we show that MEIRS also enables spectro-chemical imaging at the single-cell level. The described metasurface-based all-optical sensor opens the way to a scalable, high-throughput spectroscopic assay for live cells.
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Probing the Drug Dynamics of Chemotherapeutics Using Metasurface-Enhanced Infrared Reflection Spectroscopy of Live Cells
Infrared spectroscopy has drawn considerable interest in biological applications, but the measurement of live cells is impeded by the attenuation of infrared light in water. Metasurface-enhanced infrared reflection spectroscopy (MEIRS) had been shown to mitigate the problem, enhance the cellular infrared signal through surface-enhanced infrared absorption, and encode the cellular vibrational signatures in the reflectance spectrum at the same time. In this study, we used MEIRS to study the dynamic response of live cancer cells to a newly developed chemotherapeutic metal complex with distinct modes of action (MoAs): tricarbonyl rhenium isonitrile polypyridyl (TRIP). MEIRS measurements demonstrated that administering TRIP resulted in long-term (several hours) reduction in protein, lipid, and overall refractive index signals, and in short-term (tens of minutes) increase in these signals, consistent with the induction of endoplasmic reticulum stress. The unique tricarbonyl IR signature of TRIP in the bioorthogonal spectral window was monitored in real time, and was used as an infrared tag to detect the precise drug delivery time that was shown to be closely correlated with the onset of the phenotypic response. These results demonstrate that MEIRS is an effective label-free real-time cellular assay capable of detecting and interpreting the early phenotypic responses of cells to IR-tagged chemotherapeutics.
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- Award ID(s):
- 1719875
- PAR ID:
- 10411666
- Date Published:
- Journal Name:
- Cells
- Volume:
- 11
- Issue:
- 10
- ISSN:
- 2073-4409
- Page Range / eLocation ID:
- 1600
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Surface-enhanced infrared absorption (SEIRA) based on top-down fabricated nanostructures such as nanoantennas and metasurfaces has attracted much attention in recent years. These plasmonic resonant nanostructures can enhance the IR absorption signal of nearby molecules through its nearfield enhancement and have been shown to be able to detect adsorbed monolayers of proteins and lipids through their IR absorption spectra. Here, we demonstrate the continuous monitoring of cellular responses to stimuli using metasurface-enhanced infrared spectroscopy (MEIRS). A431 cells are seeded on a gold plasmonic metasurface fabricated on CaF2 substrate. Continuous monitoring is made possible by integrating the metasurface with a flow chamber, and the IR absorption spectra of the attached cells are measured in reflectance mode under continuous perfusion of cell culture medium. Scanning electron microscopy (SEM) revealed that the cells preferentially adhere to gold surfaces rather than CaF2 surfaces, suggesting that the IR signal measured through MEIRS is highly sensitive to the cells’ attachment and interaction with the gold metasurface. We have monitored the effect of methyl-beta-cyclodextrin, a cholesterol-depleting compound, on A431 cells. Principal component analysis highlighted the complex and subtle spectral changes of the cells. Keywords: MIR spectroscopy, surface-enhanced infrared absorption, metasurface, metasurface enhanced infrared absorption, MEIRS, cell adhesion, methyl-beta-cyclodextrin, cholesterolmore » « less
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- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.3390/cells11101600
