Rapid Detection of SARS-CoV-2 Nucleocapsid Protein by a Label-Free Biosensor Based on Optical Fiber Cylindrical Micro-Resonator

The current global outbreak of coronavirus (COVID-19) continues to be a severe threat to human health. Rapid, low-cost, and accurate antigen detection methods are very important for disease diagnosis. The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) nucleocapsid protein (N-Protein) is often used as the diagnostic and screening for coronavirus detection. To this end, we propose and experimentally validate a highly sensitive whispering gallery mode (WGM) optical cylindrical micro-resonator (CMR) for bioimmunoassay detection. To study the biokinetic process of immunoassay, the surface of the WGM micro-resonator is functionalized with N-Protein monoclonal antibody (N-Protein-mAb), which led to the specific detection of N-Proteins. The spectral characteristics of the WGM resonance dip were investigated, and it is found that the transmission spectrum of WGM shows a monotonically increasing red-shift as a function of recording time. The WGM red-shift is due to the antibody-antigen reaction and can be used for the analysis of the immunoassay process. The wavelength shift is shown to be proportional to the concentration of N-Protein, which ranges between 0.1 and 100 $\mu \text{g}$ /mL. Finally, different types of samples (concentration of $10~\mu \text{g}$ /mL of N-Protein) were prepared and tested to simulate the specificity of the sensor in the practical application environment. This method has the merits of a rapid assay, lower expense, easy preparation, and miniaturization, which makes the sensor have the potential for broad applications in the field of biochemistry and biomedical detection.