Ni(OH)2/MXene-decorated plasmonic interface with dual signal enhancement for sensitive PSA immunoassay in serum

Prostate-specific antigen (PSA) detection is vital for early prostate cancer diagnosis, yet conventional methods suffer from sensitivity and label-dependent limitations. This study presents a surface plasmon resonance (SPR) biosensor enhanced by Ni(OH) 2 /Ti 3 C 2 T x MXene nanocomposites (NTC) for sensitive detection of total PSA (tPSA) in serum. The NTC architecture synergizes carboxyl-functionalized MXene, amplifying localized electric fields and antibody-binding sites, with Ni(OH) 2 nanoflowers that prevent MXene stacking and enhance refractive index (RI) sensitivity. Optimized via finite element modeling (50-nm Au film, 72.4 ° incident angle), the Au-NTC architecture achieved a 39.34% improvement in RI sensitivity (3064.86 nm/RIU) compared to pristine Au. Through the dual signal amplification mechanism of synergistic enhancement by nanomaterials and sandwich method with gold nanoparticles, enabled detection of tPSA in 20% serum across a wide dynamic range (0.2–160 ng/mL), fully covering the clinical risk threshold (4–10 ng/mL). The platform demonstrated an ultralow limit of detection (LOD) of 0.0361 ng/mL (0.5157 pM) and high specificity against interferons. Kinetic analysis revealed strong antigen-antibody affinity (equilibrium dissociation constant K D = 4 . 26 × 1 0 − 10 M), while batch-producible sensor chips and integrated microfluidics underscored practical applicability. This work advances label-free SPR biosensing for precision prostate cancer diagnostics, offering significant potential in point-of-care testing and early intervention strategies.