Long-Range SERS Detection of the SARS-CoV-2 Antigen on a Well-Ordered Gold Hexagonal Nanoplate Film.

The development of an effective method for identifying severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) via direct viral protein detection is significant but challenging in combatting the COVID-19 epidemic. As a promising approach for direct detection, viral protein detection using surface-enhanced Raman scattering (SERS) is limited by the larger viral protein size compared to the effective electromagnetic field ( E -field) range because only the analyte remaining within the E -field can achieve high detection sensitivity. In this study, we designed and fabricated a novel long-range SERS (LR-SERS) substrate with an Au nanoplate film/MgF 2 /Au mirror/glass configuration to boost the LR-SERS resulting from the extended E -field. On applying the LR-SERS to detect the SARS-CoV-2 spike protein (S protein), reagent-free detection achieved a low detection limit of 9.8 × 10 -11 g mL -1 and clear discrimination from the SARS-CoV S protein. The developed technique also allows testing of the S protein in saliva with 98% sensitivity and 100% specificity.