Raspberry-Like Plasmonic Nanoaggregates with Programmable Hierarchical Structures for Reproducible SERS Detection of Wastewater Pollutants and Biomarkers

Conventional solid-based SERS substrates often face challenges with inconsistent sample distribution, while liquid-based SERS substrates are prone to aggregation and precipitation, resulting in irreproducible signals in both cases. In this study, we tackled this dilemma by designing and synthesizing raspberry-like plasmonic nanoaggregates that exhibit a high density of hotspots and are colloidally stable at the same time. In particular, the nanoaggregates consist of a core made of functionalized polystyrene (PS) microspheres, which act as a template for rapid self-assembly of Au@Ag core-shell nanoparticles to form raspberry-like hierarchical nanoaggregates within 5 min of mixing. The optimized nanoaggregates can be used as reproducible and stable SERS substrates for a range of wastewater pollutants (e.g., rhodamine 6G (R6G) and malachite green (MG)) and nucleobases (e.g., adenine and uracil), with the detection limits as low as 1 × 10^-10, 1 × 10^-16, 3 × 10^-8, and 3 × 10^-7 M, respectively. Additionally, the trace detection of adenine in clinical urine samples has been successfully demonstrated. Our modular assembly approach opens up new possibilities in SERS substrate design and advanced trace-chemical detection technologies.