Denoising Algorithm for High-Resolution and Large-Range Phase-Sensitive SPR Imaging Based on PFA

Phase-sensitive surface plasmon resonance (SPR) detection is widely employed in molecular dynamics studies and SPR imaging owing to its real-time capability, high sensitivity, and compatibility with imaging systems. A key research objective is to achieve higher measurement resolution of refractive index under optimal dynamic range conditions. We present an enhanced SPR phase imaging system combining a quad-polarization filter array for phase differential detection with a novel polarization pair, block matching, and 4D filtering (PPBM4D) algorithm to extend the dynamic range and enhance resolution. By extending the BM3D framework, PPBM4D leverages inter-polarization correlations to generate virtual measurements for each channel in the quad-polarization filter, enabling more effective noise suppression through collaborative filtering. The algorithm demonstrates 57% instrumental noise reduction and achieves 1.51 × 10^-6 RIU resolution (1.333-1.393 RIU range). The system's algorithm performance is validated through stepwise NaCl solution switching experiments (0.0025-0.08%) and protein interaction assays (0.15625-20 μg/mL). This advancement establishes a robust framework for high-resolution SPR applications across a broad dynamic range, particularly benefiting live-cell imaging and high-throughput screening.