Ultrasensitive Raman spectroscopy-based virus detection using
glycan-coated plasmonic substrates

Hepatitis viral infections are the most common cause of hepatitis liver disease, which eventually leads to cancer and fibrosis if undetected early. Therefore, early detection would allow for pre-ventive and therapeutic actions. Here, a Raman spectroscopy-based biosensor was developed using plasmonic molybdenum trioxide quantum dots-based substrates functionalized with a proteoglycan (Syndecan-1) as a novel bioreceptor for target hepatitis E virus (HEV). The innova-tive bio-detection system achieved a detection limit of 1.05 fg/mL for tested HEV antigen (ORF2), indicating superb clinically relevant sensitivity and performance. The designed biosensing system incorporating a glycan motif as a bioreceptor instead of the conventional antibodies or aptamers, presents new insights for the ultrasensitive detection of HEV and other infectious viruses.