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

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.