A nucleic acid-based surface-enhanced Raman scattering of gold nanorods in N-gene integrated principal component analysis for COVID-19 detection

[Display omitted] •Our research highlights a ground-breaking approach where we leverage the N-gene as the main target for COVID-19 detection. In our study, we systematically tested the same gene (N-gene) at different locations, and the results demonstrate a remarkable level of selectivity. Through the application of Surface-Enhanced Raman Spectroscopy (SERS), we enhance the sensitivity and specificity of our detection methodology, making it a powerful tool in the fight against the pandemic.•Unlike many existing studies that primarily focus on the N-protein, our research directly detects the gene encoding the N-protein. This distinction adds a layer of reliability to our findings, as it provides a more direct and accurate representation of the viral presence, contributing to the robustness of our diagnostic approach.•Our findings suggest that the integration of PCA not only refines the data but also unveils hidden patterns crucial for accurate and reliable diagnostics. This signature pattern serves as a hallmark of our approach, showcasing its potential for widespread application in the field of molecular and biomolecular spectroscopy. A rapid, simple, sensitive, and selective point-of-care diagnosis tool kit is vital for detecting the coronavirus disease (COVID-19) based on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain. Currently, the reverse transcriptase-polymerase chain reaction (RT-PCR) is the best technique to detect the disease. Although a good sensitivity has been observed in RT-PCR, the isolation and screening process for high sample volume is limited due to the time-consuming and laborious work. This study introduced a nucleic acid-based surface-enhanced Raman scattering (SERS) sensor to detect the nucleocapsid gene (N-gene) of SARS-CoV-2. The Raman scattering signal was amplified using gold nanoparticles (AuNPs) possessing a rod-like morphology to improve the SERS effect, which was approximately 12–15 nm in diameter and 40–50 nm in length. These nanoparticles were functionalised with the single-stranded deoxyribonucleic acid (ssDNA) complemented with the N-gene. Furthermore, the study demonstrates method selectivity by strategically testing the same virus genome at different locations. This focused approach showcases the method's capability to discern specific genetic variations, ensuring accuracy in viral detection. A multivariate statistical analysis technique was then applied to analyse the raw SERS spectra data using