Selective, Quantitative, and Multiplexed Surface‐Enhanced Raman Spectroscopy Using Aptamer‐Functionalized Monolithic Plasmonic Nanogrids Derived from Cross‐Point Nano‐Welding

Recent advances in surface-enhanced Raman spectroscopy (SERS) have resulted in multiplexing with unprecedented levels of sensitivity and selectivity in trace-amount detection. However, quantification of multiple trace-amount molecules with ng-level accuracy has yet to be demonstrated due to nonuniform distribution of SERS enhancement and random adsorption of molecules at low concentrations. While Raman reporter-free SERS is favorable for quantification in that the unique fingerprint spectra of molecules enable specific molecular identification, it has yet to be demonstrated due to poor reproducibility and insufficient SERS enhancement. Raman reporter-free multiplex SERS with highly accurate quantification is successfully realized by versatile aptamer-functionalized plasmonic Au nanogrids with uniform SERS enhancement. By cross-point nano-welding, monolithic Au nanogrids with excellent uniformity and high stability in aqueous media are produced. Raman reporter-free multiplex detection and highly accurate quantification of concentration and composition is realized at picomolar levels. As a demonstration, Au nanogrids functionalized with bisphenol A-specific aptamers successfully detect and quantify trace-amounts of bisphenol A (8.49 ng) from thermal receipt paper. Moreover, principal component analysis is applied to multiplex SERS spectra to establish a ternary composition map, which can potentially serve as a practical reference for future Raman reporter-free SERS.