Phase‐sensitive surface plasmon resonance biosensors: methodology, instrumentation and applications

Abstract

Abstract Surface Plasmon Resonance (SPR) has become a central tool for label‐free characterization of biomolecular interactions. Based on monitoring of amplitude characteristics, conventional SPR sensors have been extensively explored, commercialized and applied for studies of many important interactions (antigen‐antibody, protein‐ligand etc), but this technology still lacks of sensitivity for the detection of relatively small and low copy number compounds. Phase‐sensitive SPR has recently emerged as an upgrade of this technology to resolve the sensitivity issue. Profiting from a sharp phase jump under SPR and ultra‐sensitive tools of its control, this technology offers up to 100‐time improvement of the detection limit, giving access to the detection of trace amounts of small molecular weight analytes (drugs etc). This paper intends to provide a tutorial on basic concepts of phase detection in SPR sensing, compare the performance of phase‐ and amplitude‐sensitive sensors, review recent progress in the development and applications of phase‐sensitive SPR sensors, and outline future prospects and trends of this technology.