Transport of molecules and ions across cellular membranes is a fundamental process in biology. Visualization of such transport is an essential element toward a better understanding of how incoming molecules or ions interact with cellular membranes and diffuse into cytoplasm. However, detection techniques for this purpose have not been explored yet. Here we propose an innovative label-free detection technique that, in principle, permits real-time visualization of molecules across a cellular membrane. Lipid-modified gold nanorods (GNRs) in aqueous solution are exploited as nanoprobes for surface-enhanced Raman scattering (SERS)-based detection of neighboring molecules. For this purpose, the surfaces of as-synthesized GNRs were modified with a variety of phospholipids (DOPC, POPC, and DPPC, respectively) by extraction-based ligand exchange. The lipid-modified GNRs were characterized by transmission electron microscopy (TEM), UV-vis spectroscopy, and zeta potential measurement. As a proof-of-concept, SERS measurement of R6G with the lipid-modified GNRs was carried out. The limit of detection was found to be around 100 nM.
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