Magnetic enrichment and enabled cascade amplification for ultrasensitive SPR analysis of PD-L1⁺ exosomes

Exosomes serve as stable liquid-biopsy biomarkers for early cancer detection due to their molecular resemblance to parent cells. Here, a magnetic enrichment-assisted surface plasmon resonance (SPR) assay is developed based on Zr/Ce-MOF@Fe₃O₄ core-satellite nanocomposites for sensitive exosome analysis. The Zr/Ce-MOF is constructed with Zr as the metal node and doped with Ce, exhibiting intrinsic oxidase-like activity through the Ce³⁺/Ce⁴⁺ redox cycle. It catalyzes the oxidation of 3,3',5,5'-tetramethylbenzidine without exogenous H₂O₂, generating a high-refractive-index precipitate that significantly amplifies the SPR signal. The Zr-O-P coordination enables selective capture of phospholipid membranes on exosomes, while Fe₃O₄ satellites facilitate rapid magnetic enrichment and separation. To further improve specificity and antifouling performance, single-walled carbon nanotube interlayers pre-functionalized with PD-L1 targeting peptides were integrated onto the sensor chip, enabling selective recognition of magnetically enriched PD-L1⁺ exosomes. The combined refractive-index increase from the nanocomposite and the TMB deposition leads to enhanced SPR responses. Under optimized conditions, the assay achieves a detection limit of 2.16 particles mL^-1 (S/N = 3) over a linear range of 10²-10⁷ particles mL^-1. The total analysis time is within 40 min, and the method shows consistent differentiation between serum samples from cancer patients and healthy donors. This approach provides a practical strategy for the analysis of low abundance exosomal biomarkers.