Magnetic Large‐Mesoporous Nanoreactors Enable Enzymatically Regulated Background‐Free and Persistently Signalling Diseases Diagnosis

Abstract Diverse diseases and increasing prevalence pose a serious threat to public health. Point‐of‐care testing (POCT) techniques have imposed superior requirements over sensitivity, selectivity, robustness, affordability, and high‐throughput. However, transient signal, complex sample pretreatment, and low signal‐to‐noise ratio make POCT severely limited in detection accuracy, efficiency, and sensitivity. Here, an enzyme‐assisted magnetic large‐mesoporous nanoreactor (FS) is constructed for achieving persistent‐chemiluminescence signal output and eliminating matrix interference in disease diagnosis. The core‐shell structured FS synthesized via an interface coassembly method exhibits uniform size, large and open mesopores (≈22 nm), and intrinsic magnetic separability. Such unique FS acts as efficient nanoreactor for confined cascade reactions enable efficient persistent‐chemiluminescence (pCL) signal transduction and high‐SNR chromogenic analysis of diverse biomarkers. The developed pCL assays facilitate high‐sensitive determination of chronic disease biomarkers glucose and uric acid with detection limits (DL) of 5.4 mg L⁻¹ and 151.2 ng L⁻¹, respectively. The proposed chromogenic immunoassay enables an ultrasensitive and visual determination of alpha‐fetoprotein with a DL of 1.2 ng L⁻¹, which is superior to previously published immunoassays. The feasibility of the developed methods for real‐world applications are demonstrated in 159 clinical serum samples, and the determination results agree well with the clinical data. The proposed technique is expected to promote highly sensitive disease diagnosis in primary medical institutions and resource‐limited areas since not relying on expensive automatic sampling and testing instruments. The good flexibility of the customizable nanoreactor makes it a powerful tool for developing various POCT techniques for rapid, sensitive, and accurate diseases diagnosis.