Ultrasensitive detection of aquaporin-4 antibodies using ZIF-67@PDA@PtCu nanocomposite-based electrochemical immunosensor for neuromyelitis optica spectrum disorder diagnosis

Neuromyelitis optica spectrum disorder (NMOSD) is a central nervous system demyelinating disease that typically causes severe visual impairment and paralysis, and the aquaporin-4 antibodies (AQP4-IgG) serve as its specific diagnostic marker. In patients presenting with typical NMOSD symptoms, a positive AQP4-IgG result is sufficient to confirm the diagnosis. However, current clinical methods for detecting AQP4-IgG suffer from limited sensitivity, time-consuming procedures, and labor-intensive workflows, underscoring the urgent need for more efficient and reliable diagnostic approaches. To address these limitations, we report a novel electrochemical biosensor leveraging a hierarchical ZIF-67@PDA@PtCu nanozyme for ultrasensitive and rapid AQP4-IgG detection. ZIF-67@PDA@PtCu, a composite material consisting of a ZIF-67 core coated with polydopamine (PDA) and further decorated with PtCu nanoparticles, was utilized as a signal amplification component. The PtCu alloy nanoflowers demonstrated exceptional catalytic activity, which was further amplified by the sturdy ZIF-67 framework that enabled the integration of additional functional materials. In parallel, PDA enhanced the synergy between the unsaturated edge sites of the metal-organic framework and the outstanding catalytic properties of the PtCu alloy, thereby boosting the overall performance of the system. The integration of graphene oxide (GO) and gold nanoparticles (AuNPs) enhanced electrical conductivity. This configuration enabled efficient electrochemical (EC) signal generation, facilitating the detection of AQP4-IgG with high stability, a broad detection range of 0.1–80 U mL −1 , and an impressively low detection limit of 0.05 U mL −1 . Our findings offer a novel approach for the early diagnosis of NMOSD and provide valuable insights into the detection of other antibody-dependent neuroimmune disorders.