SERS in salt wells.

We report herein a simple, inexpensive fabrication methodology of salt microwells, and define the utility of the latter as nanoparticle containers for highly sensitive surface-enhanced Raman scattering (SERS) studies. AFM characterization of Ag and Au loaded salt microwells reveal the ability to contain favorable nanostructures such as nanoparticle dimers, which can significantly enhance the Raman intensity of molecules. By performing diffraction-limited confocal Raman microscopy on salt microwells, we show high sensitivity and fidelity in the detection of dyes, peptides, and proteins, as a proof of our concept. The SERS limit of detection (accumulation time of 1 s) for rhodamine B and TAT contained in salt mircowells is 10 pM and 1 nM, respectively. The Raman characterization measurements of salt microwells with three different laser lines (532 nm, 632.81 nm, 785 nm) reveal low background intensity and high signal-to-noise ratio upon nanoparticle loading, which makes them suitable for enhanced Raman detection. SERS mapping of these sub-femtoliter containers show spatial confinement of the relevant analyte to a few microns, which make them potential candidates for microscale bioreactors.