A low-cost, LED-based SPRi platform with adaptive spectral analysis and localized enrichment for ultrasensitive detection of Tau.

Blood-based detection of Tau presents a promising strategy for early screening of Alzheimer's disease (AD). This study introduces a novel surface plasmon resonance imaging (SPRi) platform that employs an array of low-cost monochromatic LEDs as excitation light sources, effectively replacing conventional spectrometer-based systems to achieve cost reduction and enhanced operational stability. We developed an adaptive fitting algorithm that automatically identifies optimal spectral bands for analysis, enabling high-precision SPR measurements across an extended dynamic range. The system demonstrates exceptional performance with a RI resolution of 1.96 × 10-6 RIU and a dynamic range of 0.0136 RIU. To further enhance sensitivity, we implemented a signal amplification strategy based on localized sample heating, which promotes molecular enrichment at both the center and periphery of evaporating droplets. This approach increases local target concentrations and enhances interaction probability with surface-immobilized capture probes. The label-free amplification method eliminates the requirement for secondary signal enhancement, substantially simplifying the detection workflow. Using this integrated approach, we achieved ultrasensitive Tau detection with a limit of detection (LOD) of 437 fg/mL (7.95 fM) and established a linear detection range spanning from 1 pg/mL to 10 ng/mL. This technique provides a robust platform for AD-related Tau quantification and demonstrates significant potential for facilitating early AD diagnosis.