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

Abstract

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 bio-immunoassay 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, 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 μg/mL and 100 μg/mL. Finally, different types of samples (concentration of 10 μg/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 rapid assay, lower expense, easy preparation, and miniaturization, which makes the sensor have potential for broad applications in the field of biochemistry and biomedical detection.