High-Performance SERS Detection of Monoamine Neurotransmitters Using a Nanogap-Engineered Plasmonic Platform with Application to Human Plasma

Norepinephrine (NE) and serotonin (5-hydroxytryptamine, 5-HT) are key neurotransmitters that regulate mood, cognition, and neurochemical balance. Abnormal levels of these molecules are linked with several neuropsychiatric disorders, underscoring the need for highly sensitive and selective detection methods. In this study, a hierarchical plasmonic nanocomposite, denoted as zeolitic imidazolate framework-67 (ZIF-67)@gold nanoparticles (Au)@polydopamine (PDA)@silver nanoparticles (AgNPs) supported on PDA/polyethyleneimine (PEI)-coated glass (glass@PDA/PEI), is reported, which features a metal-organic framework (MOF) template and dual-metal plasmonic coupling between Au (20.6± 5.1 nm) and Ag (5.5 ± 1.8 nm) mediated by a PDA interlayer. This platform demonstrates an excellent surface-enhanced Raman scattering (SERS) performance, achieving detection limits (LOD) of 1.6 × 10^-11 M for NE and 1.3 × 10^-12 M for 5-HT, along with reliable linearity across physiologically relevant concentration ranges. Notably, the SERS system was successfully employed for the first time to detect 5-HT levels in human plasma samples from 25 healthy individuals, yielding an average concentration of 1.9 × 10^-8 M and confirming its feasibility for application in real biological matrices. This work pioneers a SERS-based quantitative platform for detecting 5-HT in human plasma, demonstrating its promise for the early diagnosis and monitoring of neuropsychiatric diseases associated with dysregulated 5-HT levels.