Rapid and Sensitive Detection of Mutations in SARS-CoV-2 by Surface-Enhanced Raman Spectroscopy

Since the outbreak of the novel coronavirus (SARS-CoV-2), the world has suffered significant losses. At present, the pneumonia disease caused by SARS-CoV-2 virus has not been eliminated, and SARS-CoV-2 has a high mutation rate, and its variant strains also have a high prevalence rate, which has always threatened the health of all mankind. This study aims to develop a rapid and sensitive method to complement existing SARS-CoV-2 diagnostic tools by utilizing surface-enhanced Raman spectroscopy (SERS) for the direct detection of the intrinsic SERS signal from the S proteins of SARS-CoV-2 and its variants (Omicron and Delta) within 5 min using a portable Raman spectrometer. The linear range of S protein detection of Wild-type, Omicron and Delta variants ranged from 1.0 × 10^-7 to 1.0 × 10^-3 g·mL^-1, the limits of detection (LOD) were down to ∼10^-8 g·mL^-1 level. Our proposed method uses portable Raman spectrometer for direct detection, which is characterized by its simplicity, rapidity, portability, and wide applicability. It enables simultaneous detection of diverse mutated targets, thereby playing a pivotal role in the early diagnosis of viral diseases. Moreover, it holds promising prospects in the fields of chemistry, biology, and medicine.