Nanoscale Chemical Analysis of Cell Membrane Constituents Using Tip-Enhanced Raman Spectroscopy

The biological membrane plays an important role in numerous cellular processes and is linked to various diseases. Many of its biological functions have been shown to depend on local environments with specific compositions. 1 Self-assembled nanoscale compartments enriched in sphingolipids, cholesterol and proteins called “lipid rafts” are believed to be a locus for biochemical reactions taking place on the cell membrane. 2 Investigation of such domains with nanometer resolution is still a very challenging task, especially when it is done in their natural environment. Tip-enhanced Raman spectroscopy (TERS) is a non-destructive analytical technique capable of yielding vibrational spectra of samples with a lateral resolution below 30 nm. 3 It is essentially an apertureless near-field technique where conventional optics are used to illuminate a metal or metalized scanning probe microscopy (SPM) tip. This tip is brought in close proximity to a sample surface leading to a significant enhancement (several orders of magnitude) of the Raman scattering from the molecules located in the small region under the tip apex. Biological materials are in general very weak Raman scatterers due to their non-resonant character. Therefore, their investigation demands a highly optimized TERS setup, especially with respect to tip fabrication.