Sensitive SERS detection of SARS-CoV‑2 spike protein based on Y‑shaped-aptasensor and AuNPs/COFs composites

Early diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is crucial for timely infection detection and transmission prevention. In this work, we reported a surface-enhanced Raman scattering (SERS)-based aptasensor platform capable of quantifying SARS-CoV-2 spike protein (S protein) with high sensitivity. The aptasensor was produced by coating three specific parts (including thiolated Probe 1, Probe 2-conjugated Au−4-aminothiophenol−silver−gold nanoparticles (Au@4-ATP@Ag@Au NPs), and Aptamer against S protein) to fabricate a ternary "Y-shape" structure onto gold nanoparticles doped covalent organic frameworks (AuNPs/COFs) composite surface. This technique enabled detecting S protein with high sensitivity (LOD = 2.7 ×10−16 g/mL), a wide linear range (10−15 to 10−9 g/mL), and good selectivity. The satisfactory SERS performance was attributed to the stable and high affinity of AuNPs/COFs substrate, as well as its uniform and densely-packed "hotspots" between the Au@4-ATP@Ag@Au NPs and AuNPs/COFs substrates due to the decreased distance caused by "Y-shape" structure. The developed strategy also showed many merits such as easy-operation, good recovery, and excellent stability, which providing new insights into the SERS aptasensor application of population-wide screening of COVID-19 and other epidemics.