Surface Plasmon Resonance Biosensor with Laser Heterodyne Feedback for Highly-Sensitive and Rapid Detection of COVID-19 Spike Antigen

The ongoing outbreak of the COVID-19 has witnessed the importance of the pandemic prevention and control. A rapid, sensitive antigen assay is a crucial step in diagnosing as well as curbing the pandemic. Here, we report a novel surface plasmon resonance biosensor based on laser heterodyne feedback interferometry to detect the SARS-CoV-2 spike antigen. As far as we know, this is the first time to combine the two techniques. The biosensor converts the refractive index changes at the sensing unit into the intensity changes of the light through surface plasmon resonance, achieving the label-free and real-time detection of the biological samples. Moreover, the gain amplification effect of laser heterodyne feedback interferometry further improves the sensitivity of this biosensor. In this way, tiny difference in the refractive index between various samples can be amplified and easily recognized. The biosensor can rapidly respond to the changes of the refractive index with a high resolution of 3.75×10-8 RIU. Afterwards, the biosensor is immobilized by the anti-SARS-CoV-2 spike monoclonal antibodies, thus increasing the refractive index changes caused by different concentrations of the target SARS-CoV-2 spike antigen and realizing its specific recognition. The biosensor exhibits a high sensitivity towards the SARS-CoV-2 spike antigen with a resolution of 0.08 pg/mL, indicating that this principle can be used as a rapid diagnostic method for COVID-19 antigen without sample labeling.