Regioselective Tip-Enhanced Raman Spectroscopy of Lipid Membranes with Sub-Nanometer Axial Resolution

Abstract

Noninvasive and label-free analysis of cell membranes at the nanoscale is essential to comprehend vital cellular processes. However, conventional analytical tools generally fail to meet this challenge due to the lack of required sensitivity and/or spatial resolution. Herein, we demonstrate that tip-enhanced Raman spectroscopy (TERS) is a powerful nanoanalytical tool to analyze dipalmitoylphosphatidylcholine (DPPC) bilayers and human cell membranes with submolecular resolution in the vertical direction. Unlike the far-field Raman measurements, TERS spectra of the DPPC bilayers reproducibly exhibited a uniquely shaped C−H band. These unique spectral features were also reproducibly observed in the TERS spectrum of human pancreatic cancer cells. Spectral deconvolution and DFT simulations confirmed that the TERS signal primarily originated from vibrations of the CH 3 groups in the choline headgroup of the lipids. The reproducible TERS results obtained in this study unequivocally demonstrate the ultrahigh sensitivity of TERS for nanoanalysis of lipid membranes under ambient conditions.

Nanoscale visualization of phase separation in binary supported lipid monolayer using tip-enhanced Raman spectroscopy

“…41 Hyperspectral TERS imaging has been successfully used to probe phospholipid species. 7,42–44 For example, in our previous work, we demonstrated reproducibility of the hyperspectral TERS imaging on supported DPPC monolayers. 42 Furthermore, high-resolution TERS imaging revealed differences in the ordering of DPPC molecules at the nanoscale level.…”

Activity Origin and Catalytic Mechanism of the M–N–C Catalysts for the Oxygen Reduction Reaction

“…Combining SERS and scanning tunneling microscopy (STM) to reveal the origin of ORR activity is essential to address this issue. Ultrahigh vacuum tip enhanced Raman spectroscopy (UHVTERS) is a valuable method to combine the chemical information on SERS with the ultrahigh spatial resolution of STM. − UHVTERS can provide not only chemical information at subnanometer spatial resolution but adsorption-geometry information under controlled environments. , …”

Nanoscale Chemical Analysis of Thin Film Solar Cell Interfaces Using Tip-Enhanced Raman Spectroscopy

“…Over the past two decades, tip-enhanced Raman spectroscopy (TERS) has emerged as a promising analytical tool , for nanoscale molecular characterization across various materials and processes such as two-dimensional (2D) materials, − catalysts, , polymers, , biomaterials, − organic photovoltaic devices, self-assembled monolayers, , surface chemical reactions, etc . TERS employs a metallic scanning probe microscopy tip positioned at the focal point of an excitation laser, which generates an enhanced and confined electromagnetic field (also called near-field) at the tip apex through a combination of the localized surface plasmon resonance and lightning rod effect. − This intense and localized near-field at the TERS tip enables the circumvention of conventional Raman microscopy’s diffraction-limited spatial resolution and enhances sensitivity by several orders of magnitude.…”