Two-Dimensional Material Facilitated Surface-Enhanced Raman Spectroscopy Measurements of SARS CoV-2 Receptor Binding Domain

Surface-enhanced Raman scattering (SERS) offers a powerful method for identifying biomolecules by enhancing Raman signals from molecules adsorbed on or near nanostructured metal surfaces. By exploiting the strong electromagnetic field enhancements generated by plasmonic nanostructures, SERS can amplify weak Raman signals, enabling the sensitive detection and identification of biomolecules in complex biological samples. Hybrid structures combining zero-dimensional (0D) and two-dimensional (2D) materials can provide additional benefits for biological sensing applications. Coupling 2D materials with SERS is particularly useful for detecting the SARS CoV-2 receptor binding domain (RBD) due to its high sensitivity and specificity. In this study, we developed a SERS platform for the ultrasensitive and rapid detection of SARS CoV-2 RBD. We fabricated four types of SERS substrates: one with gold nanoparticles (AuNPs) only, and three based on different 2D material-gold nanoparticle hybrids (AuNPs/graphene, AuNPs/MoS₂, and AuNPs/WSe₂). The SERS spectra collected from these substrates provided spectroscopic signatures and revealed key Raman bands and detection mechanisms for RBD. The AuNPs/graphene substrate demonstrated excellent performance, with a high signal-to-noise (SNR) ratio allowing for the identification of molecular fingerprints and high sensitivity for detection. Here, the AuNP/graphene substrate increases the SNR by reducing noise rather than increasing the signal. A theoretical model explained the observed variations in SNR for different substrates. The AuNPs/graphene hybrid substrate exhibited a low detection limit of 10^-9 M for the RBD. Understanding the mechanisms of light-matter interactions in 0D-2D hybrid structures is crucial for developing highly efficient, label-free biosensors. We envision that our label-free spectroscopic platform will offer a valuable tool for the detection of viruses and their variants.