Multifunctional SERS substrate of PDMS@UiO-66-NH₂@Ag for direct detection of p-tau217 protein in different biofluids

The sensitive and reliable detection of phosphorylated tau at threonine 217 (p-tau217) in Alzheimer's disease is important for early diagnosis and clinical intervention. However, conventional surface-enhanced Raman scattering (SERS) substrates often suffer from insufficient molecular enrichment and limited electromagnetic enhancement in complex biofluids. Herein, we developed a flexible SERS platform of UiO-66-NH₂@Ag supported by polydimethylsiloxane (PDMS) for the label-free and ultrasensitive detection of p-tau217. Specifically, the porous UiO-66-NH₂ framework enriched target molecules and potentially promoted interfacial charge transfer, whereas the densely packed Ag nanoparticles (NPs) generated abundant electromagnetic "hotspots" through localized surface plasmon resonance. The optimized substrate exhibited a remarkable enhancement factor of 5.4 × 10¹⁰. Benefiting from the superior near-field confinement assisted by charge transfer, the enrichment capability of the UiO-66-NH₂ framework, and the signal uniformity afforded by the PDMS substrate, a quantitative detection of p-tau217 was enabled over a wide concentration range of 10⁻¹¹ - 10⁻⁶ mg/mL. Notably, the platform also achieved reliable and reproducible performance in complex biological matrices, including serum, cerebrospinal fluid, and tear fluid. These results demonstrate that the proposed strategy offers an effective approach to combine molecular enrichment with plasmonic amplification in a flexible sensing system, which is benefit for trace biomarker detection.