Design and numerical-phase analysis of an SPR system for direct detection of SARS-CoV-2 virus in pharyngeal swab solution

Quick and highly sensitive detection of the SARS-CoV-2 virus can efficiently reduce the possibility of viral spreading. In this study, a differential-phase surface plasmon resonance (SPR) biosensor is constructed to directly detect the SARS-CoV-2 virus. The SARS-CoV-2 spike protein antibodies are applied as bioprobes and functionalized on Au film, forming a sensing surface. A numerical analysis of the phase shifts of the SPR interferogram, termed the index of phase shifts (IoPS), is presented, which does not depend on a reference beam or an s-component beam. The IoPS can sensitively reflect small changes in the refractive index (as low as 3.75 x 10-10 RIU) when NaCl solution is used as an analyte. The limit of detection (LOD) of the proposed SPR biosensor in detecting the SARS-CoV-2 S protein is 1 ag mL-1. In comparison with a SARS-CoV-2 negative control (NC) sample collected from healthy people, which has an IoPS of Delta phi NC = 39 degrees, the SPR biosensor shows a very strong response to the SARS-CoV-2 virus collected from infected people with a phase shift of Delta phi IoPS = 566 degrees. To further improve the detection sensitivity, a sandwich structure is designed by applying SARS-CoV-2 spike protein antibody functionalized gold nanoparticles (anti-S@AuNPs). This reduces the LOD for the detection of the SARS-CoV-2 S protein to 0.1 ag mL-1. An ultrasensitive differential-phase SPR biosensor has been successfully established, capable of direct detection of SARS-CoV-2 virus.