3D hotspot engineering and analytes strategy enabled ultrasensitive SERS platform for biosensing of depression biomarker.

Nowadays, the diagnose of depression mainly relies on clinical examination while impossible to accurately evaluate the occurrence of depression. Chemical approaches are captivating to analyze stress biomarkers for feedbacking body's endocrine response to stress stimuli. However, it remains challenging in exploring accurate, reliable and sensitive approaches. Herein, we rationally design a newly SERS platform with integrated hotspots engineering and analyte strategy to achieve highly sensitive analysis for estrogen, a typical depression biomarker in adolescent female. On the one hand, the 3D micro/nano plasmonic substrate containing Au-Ag Alloy Nanourchins (AAA-NUs) and arrays-based monolayer films of Au nanoparticles (Au NSs) was constructed to achieve high density and availability of hotspots. On the other hand, the analyte strategy was designed via rapid azotizing reaction to further enhance the scattering cross-section of estrogen in the form of azido compounds. With the synergism of them, the proposed SERS platform displayed high sensitivity for estrogen with a limit of detection down to 10-11  mg/mL. More importantly, the blood estrogen levels of depressed patients were evaluated via the proposed SERS platform and presented high consistence with clinical diagnostic results. This integrated SERS platform paves the way for universal and ultrasensitive biosensing and possess great potential for applying in multi-target detection and disease prediction.