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 highlighted the importance of the pandemic prevention and control. A rapid and sensitive antigen assay is crucial in diagnosing and curbing pandemic. Here, we report a novel surface plasmon resonance biosensor based on laser heterodyne feedback interferometry for the detection of SARS-CoV-2 spike antigen, which is achieved by detecting the tiny difference in refractive index between different antigen concentrations. The biosensor converts the refractive index changes at the sensing unit into the intensity changes of light through surface plasmon resonance, achieving label-free and real-time detection of biological samples. Moreover, the gain amplification effect of the laser heterodyne feedback interferometry further improved the sensitivity of this biosensor. The biosensor can rapidly respond to continuous and periodic changes in the refractive index with a high resolution of 3.75 × 10-8 RIU, demonstrating the repeatability of the biosensor. Afterwards, the biosensor is immobilized by the anti-SARS-CoV-2 spike monoclonal antibodies, thus realizing the specific recognition of the antigen. The biosensor exhibited a high sensitivity towards the concentration of the antigen with a linear dynamic range of five orders of magnitude and a resolution of 0.08 pg/mL. These results indicate that this principle can be used as a rapid diagnostic method for COVID-19 antigens without sample labelling.