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.

The COVID-19 pandemic has highlighted the need for rapid and sensitive detection of SARS-CoV-2. Here, we report an ultrasensitive SARS-CoV-2 immunosensor by integration of an AlGaN/GaN high-electron-mobility transistor (HEMT) and anti-SARS-CoV-2 spike protein antibody. The AlGaN/GaN HEMT immunosensor has demonstrated the capability to detect SARS-CoV-2 spike proteins at an impressively low concentration of 10−22 M. The sensor was also applied to pseudoviruses and SARS-CoV-2 ΔN virions that display the Spike proteins with a single virion particle sensitivity. These features validate the potential of AlGaN/GaN HEMT biosensors for point of care tests targeting SARS-CoV-2. This research not only provides the first HEMT biosensing platform for ultrasensitive and label-free detection of SARS-CoV-2.