Metal-Mediated Gold Nanospheres Assembled for Dark-Field Microscopy Imaging Scatterometry

Developing rapid, sensitive and intelligent optical probes is important for the growing need of microscope imaging analysis. Herein, we proposed a new strategy to assemble plasmonic nanoprobes in situ for dark-field microscopy imaging scatterometry by making use of the formation, disruption, and re-formation of cytosine-Ag⁺-cytosine (CAg⁺C) bonds. The CAg⁺C bond was formed at first through Ag⁺-mediated base pairing between C-contained aptamer and its C-mismatched complementary DNA. Owing to the subsequent binding of target with the aptamer, the CAg⁺C structure was disrupted, leading Ag⁺ to be quantitatively released. The released Ag⁺ ions can make the CAg⁺C bonds formed again between the C-contained sequence that modified gold nanospheres (AuNSs), and AuNS clusters thus formed in situ, which have strong plasmonic scattering signals owing to the coupling of localized surface plasmon resonance (LSPR). Therefore, the plasmonic scattering signals enhanced following the off-on mode under the dark field microscope from the 'zero' background to on. As a concept of proof, sensitive detections for Aflatoxin B1 (AFB₁) in foods, carcinoembryonic antigen (CEA) in blood serum, and Ricin B in artificial sample, was successfully made by using of the in situ formed AuNS clusters, demonstrating that the newly developed metal-mediated strategy for assembling nanoprobes are universal.