Smartphone-Operated FRET Platform with Aggregation-Induced Emission MOFs and Spiky Carbon Nanospheres for Rapid Quantification of CA125 and HE4.

Ovarian cancer remains the deadliest gynecological malignancy, largely because early screening is inadequate. This work reports a smartphone-based fluorescent homogeneous immunoassay sensor (SFHIS) that combines aggregation-induced emission luminogen-doped metal-organic framework microspheres (AMOFs) as donors and spiky carbon nanospheres (CNPs) as acceptors. Target antigen-antibody sandwich formation brings donor and acceptor into proximity, inducing efficient Förster resonance energy transfer (FRET) and fluorescence quenching, which is linearly related to the natural logarithm of antigen concentration. A dual-correction algorithm removes internal filter effects, enabling accurate quantification. The SFHIS shows linear ranges of 0.8-51.2 U/mL for CA125 and 8-256 pmol/L for HE4, with limits of detection of 0.67 U/mL and 1.03 pmol/L, respectively. The assay is completed within 25 min without washing, exhibits intra- and inter-batch CVs < 10%, no cross-reactivity with CEA, AFP, or PSA, and correlates strongly with chemiluminescence assays (CA125: R2 = 0.970; HE4: R2 = 0.982; P < 0.05). This portable, low-cost platform offers rapid, reliable biomarker detection suitable for clinical laboratories, primary care, community health, and resource-limited settings.