Addressing the spread of coronavirus disease 2019 (COVID-19) has highlighted the need for rapid, accurate, and low-cost diagnostic methods that detect specific antigens for SARS-CoV-2 infection. Tests for COVID-19 are based on reverse transcription PCR (RT-PCR), which requires laboratory services and is time-consuming. Here, by targeting the SARS-CoV-2 spike protein, we present a point-of-care SERS detection platform that specifically detects SARS-CoV-2 antigen in one step by captureing substrates and detection probes based on aptamer-specific recognition. Using the pseudovirus, without any pretreatment, the SARS-CoV-2 virus and its variants were detected by a handheld Raman spectrometer within 5 min. The limit of detection (LoD) for the pseudovirus was 124 TU μL –1 (18 fM spike protein), with a linear range of 250–10,000 TU μL –1 . Moreover, this assay can specifically recognize the SARS-CoV-2 antigen without cross reacting with specific antigens of other coronaviruses or influenza A. Therefore, the platform has great potential for application in rapid point-of-care diagnostic assays for SARS-CoV-2.

A rapid and accurate diagnostic modality is essential to prevent the wide spread of SARS-CoV-2. In this study, we proposed a SARS-CoV-2 detection sensor based on a Surface-enhanced Raman scattering (SERS) to achieve rapid and ultrasensitive detection. The sensor utilized the spike protein deoxyribonucleic acid (DNA) aptamers with strong affinity as the recognition entity to achieve high specificity. The spherical cocktail aptamers-gold nanoparticles (SCAP) SERS substrate was used as the base and the Au nanoparticle modified with the Raman reporter molecule that resonates with the excitation light and spike protein aptamers were used as the SERS nanoprobes. The SCAP substrate and the SERS nanoprobes were used to target and capture the SARS-CoV-2 S protein to form a sandwich structure on the Au film substrate which can generate ultra-strong 'hot spots' to achieve ultrasensitive detection. Analysis of SARS-CoV-2 S protein was performed by monitoring changes in SERS peak intensity on a SCAP SERS substrate-based detection platform (SCAP RDP). This assay detects S protein with a LOD of less than 0.7 fg mL-1 and pseudovirus (PSV) as low as 0.8 TU mL-1 about 12 min. The results of the simulated oropharyngeal swab system in this study indicated the possibility of it being used for clinical detection, providing a potential option for rapid and accurate diagnosis and more effective control of SARS-CoV-2 transmission.