All 2D van der Waals junction-FET biosensor with external capacitive sensing for rapid, label-free detection of liver cancer biomarkers.

Accurate, label-free detection of disease-specific biomarkers is essential for early diagnosis and therapeutic monitoring. Here, we present a reusable and ultrasensitive biosensor platform based on van der Waals (vdW) junction field-effect transistor (JFET), integrated with an external metal-insulator-metal (MIM) capacitor. This pseudo-floating gate configuration physically decouples the sensing interface from the transistor's active channel, thereby minimizing charge trapping, eliminating hysteresis, and enabling stable, dynamic step-response measurements and device reusability. This architecture allows for rapid, label-free detection of liver biomarkers-human serum albumin and AFP-L3-with a limit of detection below 0.1 ng mL-1 and a dynamic range from 0.1 ng mL-1 to 1 mg mL-1, addressing the key limitations of conventional ELISA assays. Additionally, we demonstrate its translational potential by evaluating the device with 3D hepatocyte spheroid disease models to detect drug-induced alterations in biomarker secretion in a physiologically relevant context. Notably, the device revealed cell-line-specific biomarker responses to doxorubicin (Dox), highlighting the capability of the device to resolve subtle and physiologically meaningful variations in secretion dynamics. Overall, this work introduces a generalizable sensing strategy for high-performance biosensors, combining electrical robustness, analytical precision, and clinical applicability, paving the way for next-generation technologies in both preclinical research and clinical diagnostics.