Process optimization for the synthesis of functionalized Au@AgNPs for specific detection of Hg²⁺ based on quality by...

The current study highlights the advantages of using the quality by design (QbD) approach to synthesise and optimize SERS substrates for the detection of Hg²⁺. Considering that the performance of Au@AgNPs is affected by many factors, Plackett-Burman (PB) experimental design was used to determine the critical process parameters (CPPs) for evaluating the performance of Au@AgNPs. The quantitative relationships between the CPPs and the critical quality attributes (CQAs) were assessed by Box-Behnken Design (BBD). The optimal design space for Au@AgNPs was calculated via a Monte Carlo algorithm. Finally, detection of Hg²⁺ in the range of 1 ∼ 100 ng mL^-1 (R ² = 0.9891) was achieved by SERS in combination with 4,4-bipyridine (Dpy) as signal molecules. The recoveries for licorice ranged from 83.53% to 92.96%. Specificity and practicality studies indicated that the method based on the QbD concept and design space not only met the optimal performance of Au@AgNPs but also improved the rapid detection of Hg²⁺ in Chinese medicine samples.