Biosensors and Bioelectronics, 3 July, 2025, DOI：https://doi.org/10.1016/j.bios.2025.117743

Ultrasensitive detection of miRNA with single-nucleotide resolution using a high-electron-mobility transistor biosensor combined with splint-ligation

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

Abstract

The use of microRNAs as clinical cancer biomarkers is hindered by the absence of accurate, sensitive and rapid assays for their detection in biofluids. Here we report a biosensing approach, SpLig-HEMT, that combines an RNA splint-ligation reaction with an AlGaN/GaN high-electron-mobility transistor biosensor for ultrasensitive miRNA detection. In this system, HEMT functions as a highly effective voltage amplifier to enhance detection sensitivity, while the splint-ligation reaction ensures precise discrimination of single-nucleotide mutations. By detecting miRNA-21, the SpLig-HEMT biosensor achieves an exceptional limit of detection of 10⁻¹⁸ M within 30 min, with a dynamic range from 10⁻¹⁸ M to 10⁻¹³ M. No detectable response is observed for one-mismatch miR-21. Furthermore, the SpLig-HEMT biosensor enables direct analysis of blood serum samples, effectively distinguishing between healthy individuals and patients with ovarian cancer. This study addresses critical challenges in miRNA detection and presents a promising tool for cancer diagnosis and prognosis.

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