Surface Filtration in Mesoporous Au Films Decorated by Ag Nanoparticles for Solving SERS Sensing Small Molecules in Living Cells

For surface-enhanced Raman spectroscopy (SERS) sensing of small molecules in the presence of living cells, biofouling and blocking of plasmonic centers are key challenges. Here, we have developed a mesoporous Au (AuM) film coated with a Ag nanoparticles (NPs) as a plasmonic sensor (AuM@Ag) to analyze aromatic thiols, which is an example of a small molecule, in the presence of a living cell strain (e.g., MDA-MB-231) as a model living system. The resulting AuM@Ag provides 0.1 nM sensitivity and high reproducibility for thiols sensing. Simultaneously, the AuM@Ag film filters large biomolecules, preventing Raman signals from overlapping produced by large biomolecules. After analysis, the AuM@Ag film undergoes recycling by the full dissolution of the Ag-thiol layer and removal of thiols from AuM. Furthermore, fresh AgNPs are formed for further SERS analysis, which circumvents the Ag oxidation issue. The ease of the AgNPs deposition allows up to 12 cycles of on-demand recycling and sensing even after utilization as a sensor in multicomponent media without enhancement and sensitivity loss. The reported mesoporous film with surface filtering ability and prominent recycling procedure promises to offer a new strategy for the detection of various small molecules in the presence of living cells.