A digital SERS sensing platform using 3D nanolaminate plasmonic crystals coupled with Au nanoparticles for accurate quantitative detection of dopamine.

We report a digital surface-enhanced Raman spectroscopy (SERS) sensing platform using the arrays of 3D nanolaminate plasmonic crystals (NLPC) coupled with Au nanoparticles and digital (on/off) SERS signal analysis for the accurate quantitative detection of dopamine (DA) at ultralow concentrations. 3D NLPC SERS substrates were fabricated to support the optically dense arrays of vertically-stacked multi-nanogap hotspots and combined with Raman tag-conjugated Au nanoparticles for NLPC-based dual-recognition structures. We demonstrate that the 3D NLPC-based dual-recognition structures including Au nanoparticle-induced additional hotspots can enable more effective SERS enhancement through the molecular recognition of DA. For the accurate quantification of DA at ultralow concentrations, we conducted digital SERS analysis to reduce stochastic signal variation due to various microscopic effects, including molecular orientation/position variation and the spatial distribution of nanoparticle-coupled hotspots. The digital SERS analysis allowed the SERS mapping results from the DA-specific dual-recognition structures to be converted into binary "On/Off" states; the number of "On" events was directly correlated with low-abundance DA molecules down to 1 pM. Therefore, the digital SERS platform using the 3D NLPC-based dual-recognition structures coupled with Au nanoparticles and digital SERS signal analysis can be used not only for the ultrasensitive, accurate, and quantitative determination of DA, but also for the practical and rapid analysis of various molecules on nanostructured surfaces.