Ag-Coated Au Nanopetals: Dual-Type Single-Nanoparticle Detection of Gap-Enhanced Resonance Raman Tags

Single-molecule (SM) detection in surface-enhanced Raman spectroscopy (SERS) demonstrates ultrahigh sensitivity and boosts wide applications. The bianalyte SERS (BiASERS) technique largely improves the accuracy and reliability of SM SERS detection over the monoanalyte approach by avoiding the use of ultralow-concentration samples and induced inaccuracy and very limited events. Herein, dual-type single-nanoparticle (SNP) SERS detection, an adapted version of the bianalyte SM technique, was developed for the first time with two types of ultrabright gap-enhanced resonance Raman tags (GERRTs) with embedded near-infrared resonant fluorescent molecules, showing concentration- and acquisition time-dependent behaviors and the SNP sensitivity in both aqueous and dry states. Additionally, a correlative Raman imaging and scanning electron (RISE) microscopy confirms the SNP events of GERRTs on the substrate. Therefore, we expand the feasible application scenarios of the BiASERS technique from merely SM to SNP detection and more importantly demonstrate the effectiveness of the pure statistical model of BiASERS with the undoubted experimental examinations. Dual-type SNP detection of GERRTs may open new opportunities for development of ultrasensitive nanotags for reliable localized and quantitative detection in biological environments.