Process optimization for the synthesis of functionalized Au@AgNPs for specific detection of Hg2+ based on quality by design (QbD)

Abstract

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 (R² = 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.