Ratiometric SERS sensing chip for high precision and ultra-sensitive detection of SARS-CoV-2 RNA in human saliva

The rapid and high precision analysis of SARS-CoV-2 RNA in saliva is crucial for the efficient prevention and control of COVID-19. Herein, we developed a novel ratiometric surface-enhanced Raman spectroscopy (SERS) sensing chip based on a two-dimensional core-molecule-shell-molecule nanostructure for quantitative detection of SARS-CoV-2 RNA. Owing to the use of base-complementary pairing mechanism, this SERS sensing chip has better selectivity in discriminating SARS-CoV-2 RNA against other RNA. Besides, an internal standard molecule (4MBN) in the SERS sensing chip can used to calibrate the real-time changing Raman signals of the probe molecule during quantitative assay. Using this cleverly designed SERS sensing chip, the dynamic ranges from 10 –6 M to 10 –12 M with a low of detection limit (LOD = 7.61 ×10 –14 M) can be acquired for detection of SARS-CoV-2 RNA. Meanwhile, this SERS sensing chip was well adapted for point-of-care testing (POCT) in combination with portable Raman spectrometer, which is expected to achieve effective detection of early SARS-CoV-2 infection.