Label-Free Detection of the Receptor-Binding Domain of the SARS-CoV-2 Spike Glycoprotein at Physiologically Relevant...

Area of Science:

• Nanotechnology
• Spectroscopy
• Biophysics

Background:

• Surface-enhanced Raman scattering (SERS) offers high sensitivity for analyte detection.
• The SARS-CoV-2 spike glycoprotein's receptor-binding domain (RBD) is crucial for viral entry.
• Label-free detection methods are desirable for biological sample analysis.

Purpose of the Study:

• To engineer a SERS-active nano-cavity for label-free detection of SARS-CoV-2 RBD.
• To achieve ultrasensitive detection of viral protein antigens.
• To investigate signal enhancement strategies for SERS detection.

Main Methods:

• Fabrication of an ultranarrow metal-dielectric nano-cavity using SARS-CoV-2 RBD and a silver surface.
• Utilizing the light-concentrating properties of the nano-cavity for Raman spectroscopy.
• Applying a silver shell coating to enhance the SERS signal and cavity Q-factor.

Main Results:

• Successfully recorded label-free Raman spectra of protein samples below 1 pg.
• Achieved ultrasensitive detection of viral protein antigens at physiologically relevant levels.
• Demonstrated sub-femtogram sensitivity for viral antigen detection after silver shell coating.

Conclusions:

• The developed SERS nano-cavity enables direct, label-free detection of SARS-CoV-2 RBD.
• This approach significantly lowers detection limits compared to methods requiring whole virus detection.
• The method holds potential for high-performance optical detection and conformational analysis of SARS-CoV-2 and its variants.