Immunomagnetic‐MXene Bifunctional Probes for Ultrasensitive and Specific Terahertz Metasensing of Tumor‐Derived Exosomes

ABSTRACT

Tumor‐derived exosomes (tExos) are promising biomarkers for early pancreatic cancer (PC) diagnosis, yet current detection methods are limited by cumbersome implementation, high sample consumption, and complex matrix interference. Herein, we developed immunomagnetic‐MXene bifunctional probes coupled with terahertz (THz) metamaterials to synergistically increase the sensitivity and specificity of PC‐derived tExos detection. Antibodies against ZIP4 and glypican‐1 (GPC‐1) were separately conjugated to magnetic beads (MBs) and MXene nanosheets, which yielded two probes that simultaneously targeted PC‐derived tExos, enabling highly specific sandwich‐type capture of target exosomes. Moreover, MXene increased the tExo‐induced THz metamaterial resonance and outperformed AuNPs in signal amplification, endowing the method with a limit of detection (LOD) of 647 particles mL ⁻¹ . The developed THz metasensor achieved accurate detection of early tumor formation and evaluation of therapeutic responses in PC mouse models. In a 60‐subject clinical cohort, it distinguished all‐stage PC patients from healthy controls with an area under the curve (AUC) of 0.997. Compared with that of the conventional CA19‐9 assay, our THz metasensor demonstrated superior diagnostic accuracy in 11 early‐stage PC patients (AUC: 0.991 vs. 0.809), with a simplified workflow, minimal sample requirement (10 µL), and low cost (< $5), highlighting its potential for clinical translation in early PC diagnosis.