Intra-Mesopore Immunoassay Based on Core-Shell Structured Magnetic Hierarchically Porous ZIFs

It is crucial yet challenging to sensitively quantify low-abundance biomarkers in blood for early screening and diagnosis of various diseases. Herein, an analytical model of intra-mesopore immunoassay (IMIA) was proposed, which was competent to examine various biomarkers at the femtomolar level. The success is rooted in the design of an innovative superparamagnetic core-shell structure with Fe₃O₄ nanoparticles (NPs) at the core and hierarchically porous zeolitic imidazolate frameworks as a shell (Fe₃O₄@HPZIF-8), achieved through a soft-template directed self-assembly coupled with confinement growth mechanism. Such a unique configuration conceptualized IMIA where the HPZIF-8 shell served as a solid carrier to cover capture antibodies while the Fe₃O₄ core assisted its rapid separation. The large pore channels not only provided a stable microenvironment to maintain the recognition ability of captured antibodies but also enhanced their coating density, thus promoting the probability of capturing and binding target antigens, significantly improving immunoassay (IA) sensitivity. The practical clinic IA for cTnI (Cardiac Troponin I, biomarker of acute myocardial infarction (AMI)) in human serums was exemplified. The developed IMIA could accurately quantify slight fluctuations in cTnI concentrations in the serums of AMI patients at different stages after symptom onset with more than 100-fold enhancement of limit of detection (LOD) in comparison to conventional plate-based enzyme-linked immunosorbent assay (ELISA). Such high sensitivity of IMIA makes it a powerful tool for the accurate diagnosis of different diseases by altering the type of primary capture antibody.