Multimodal Triple-Mode Probe with Colorimetric-Fluorescence-SERS (CFSERS) for Sensitive and Quantitative Detection of C-Reactive Protein in Clinical Diagnostics

Chronic inflammation remains a major global health concern, necessitating the development of advanced tools for continuous, precise monitoring. This study introduces a novel, clinically impactful triple-mode probe that integrates colorimetric, fluorescence, and surface-enhanced Raman scattering (SERS) signals, offering unparalleled multimodal detection capabilities. The probe's design leverages europium chelate-doped polystyrene nanoparticles (ECNPs), ensuring minimal signal cross-interference through a long Stokes shift. A key innovation is the development of a multimodal mapping algorithm that seamlessly integrates these optical signals, providing a sensitive and robust platform for biomarker detection with broad dynamic ranges. The probe's clinical relevance is demonstrated by its application in lateral flow assays (LFAs) for detecting C-reactive protein (CRP) levels, achieving a detection limit of 6.31 ng/mL and dynamic ranges from 23.13 to 2000 ng/mL, significantly outperforming single-mode detection methods. In clinical validation using urine samples from 31 patients, the triple-mode LFA showed excellent correlation (0.9377) and agreement (93.55%) with gold standard enzyme-linked immunosorbent assay (ELISA) results. This demonstrates that the proposed multimodal platform offers a highly sensitive, cost-effective, and versatile tool for monitoring inflammation and other disease biomarkers, with substantial potential for clinical applications in diagnostics and disease management.