Sensitive SERS assay for L-cysteine based on functionalized silver nanoparticles

L-cysteine, an indispensable amino acid present in natural proteins, plays pivotal roles in various biological processes. Consequently, precise and selective monitoring of its concentrations is imperative. Herein, we propose a Surface -enhanced Raman Scattering (SERS) sensor for detecting L-cysteine based on the anti -aggregation of 4mercaptobenzoic acid (4 -MBA) and histidine (His) functionalized silver nanoparticles (Ag NPs). The presence of Hg 2 + ions can induce the aggregation of Ag NPs@His@4-MBA due to the unique nanostructures of Ag NPs@His@4-MBA, resulting in a robust SERS intensity of 4 -MBA. However, in the presence of L-cysteine, the stronger affinity between L-cysteine and Hg 2 + reduces the concentration of free Hg 2 + , causing the dispersion of the aggregated functionalized Ag NPs and the reduction of the SERS signal intensity of 4 -MBA. The developed SERS platform demonstrates excellent performance with a low detection limit of 5 nM (S/N = 3) and linear detection capabilities within the range of 0.01 -100 mu M for L-cysteine. Additionally, the method was successfully employed for the determination of L-cysteine in spiked serum samples, yielding recoveries ranging from 95.0 % to 108.1 % with relative standard deviations of less than 3.3 %. This study not only presents a novel approach for fabricating highly sensitive and specific SERS biosensors for biomolecule detection but also offers a significant strategy for the development and construction of SERS substrates using anti -aggregation design.