Phase-Sensitive Surface Plasmon Resonance Imaging with Polarization Modulation and Stokes Vector Measurement

Phase-sensitive surface plasmon resonance (P-SPR) techniques offer superior sensitivity compared to conventional intensity-based SPR methods. However, current implementations, such as interference-based and polarization-based phase measurements, often face trade-offs between optical complexity and phase resolution, and typically lack access to full polarization information. Here, we report a compact and versatile Stokes vector-based polarization SPR imaging (Sp-SPRi) system that addresses these limitations through full Stokes vector analysis of imaging light after polarization modulation. This analysis enables the simultaneous acquisition of phase and multiple polarization parameters for enhanced molecular measurement. The Sp-SPRi system achieves a high phase sensitivity of 1.80 × 10^-7 refractive index units (RIU), supporting kinetic, label-free detection and quantification of biomolecular interactions. We demonstrate its performance through kinetic measurements of protein binding, small molecule interactions, and in situ glycoprotein measurement of single cells. With its simplified optical configuration, microfluidic integration, and high-throughput imaging capabilities, Sp-SPRi provides a powerful platform for multidimensional biosensing. This work broadens the analytical scope of P-SPR, offering a robust and accessible approach for applications in point-of-care diagnostics, early disease detection, and drug screening.