Biosensors and Bioelectronics, 8 January, 2026, DOI：https://doi.org/10.1016/j.bios.2026.118382

Engineered bacterial S-layer enhanced high electron mobility transistor sensors for ultrasensitive detection of tumor antigen

Jingya Tang, Chenyang Yang, Jianwen Sun, Zhe Li, Yue Men, Zewen Liu, Guoqi Zhang, Xian-En Zhang, Dian-Bing Wang

Abstract

Ultrasensitive and specific detection of low-abundance tumor biomarkers remains a major challenge for early and minimally invasive cancer diagnosis. Here, we present a high-performance biosensing platform that integrates a genetically engineered bacterial S-layer with an AlGaN/GaN high-electron-mobility transistor (HEMT) sensor for label-free detection of tumor antigens. As a proof-of-concept, the ovarian cancer antigen human epididymis protein 4 (HE4) was selected. Specifically, the S-layer protein rSbpA was fused with HE4-specific nanobody 1G8 to construct a bifunctional membrane capable of self-assembling into an ordered biorecognition layer on the sensor surface. Compared to conventional chemical crosslinking, S-layer-driven assembly increased antibody loading by 50 % and minimized nonspecific adsorption in plasma environments. The resulting HEMT sensor detected HE4 across a dynamic linear range (10^-21 to 10^-14 M), identifying patients with ovarian cancer with 100 % diagnostic accuracy (AUC = 1.0). This study establishes a versatile and modular biosensing strategy for ultra-low-abundance biomarker detection with broad potential applications in the precision diagnostics of cancer and other diseases.

Article link：https://www.sciencedirect.com/science/article/pii/S095656632600014X?via%3Dihub