Observation of Live Cells' Attachment, Spreading, and Drug Interactions Using Metasurface-Enhanced Infrared Reflection Spectroscopy

Optical spectroscopy is a powerful technique that allows for label-free, noninvasive, and real time characterization of biomolecules. Compared with other optical techniques that relies on the shift of a single resonance, such as surface plasmon resonance (SPR) sensors and optical-grating-based cell assays, spectroscopic techniques can discriminate between different chemical species and are suited for analyzing often complex biological samples. Surface-enhanced infrared absorption (SEIRA) based on top-down fabricated substrates such as nanoantennas, nanoslits, and meta-surfaces has been demonstrated as a versatile technique that can enhance the IR signal and characterize small amounts of adsorbed protein and lipid films. Here, we demonstrate the use metasurface-enhanced infrared reflection spectroscopy (MEIRS) to observe live cells cultured on top of the plasmonic metasurface. MEIRS has a penetration depth on the order of tens of nanometers, longer than surface-enhanced Raman spectroscopy (SERS) and yet shorter than attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy. This makes MEIRS uniquely suited for probing the surface of a cell, to observe features such as protein expression in the cell membrane and cellular adhesion. This has important implications in the detection of cancer cells through spectroscopic cytology, as cancer cells differ from regular cells significantly in the expression of membrane proteins and adhesion molecules. In this work, we demonstrate the observation of cancer cell adhesion through IR spectroscopic mapping. Furthermore, we show the effect of different anticancer cocktails (doxorubicin, salinomycin, and their combination) on cancer cells, as observed by MEIRS.