Ultrasensitive detection of gastric cancer biomarker using tetrahedral DNA nanostructure-functionalized floating-gate carbon nanotube field-effect transistor biosensor

Early screening is crucial for improving the survival rate of gastric cancer (GC). MiRNA-106a is abnormally overexpressed in GC tissues, making it an ideal biomarker for liquid biopsy. In this study, a floating-gate carbon nanotube field-effect transistor (FG CNTFET) biosensor, functionalized with tetrahedral DNA nanostructure (TDN) probes was developed to enable label-free, highly sensitive detection of miRNA 106a. The FG layer not only physically isolates the CNT channel from the complex biological environment—shielding it against moisture, ions, and impurities—but also amplifies surface potential changes via capacitive coupling, thereby enhancing both device stability and sensitivity. The rigid framework of TDN probes overcomes the issues of aggregation and entanglement issues associated with single-stranded DNA (ssDNA), reducing steric hindrance and improving target accessibility. In static mode, the biosensor exhibited a linear detection range of 1 fM–1 μM with a detection limit (LOD) as low as 7 aM. Under dynamic conditions, it enabled real-time tracking of miRNA-106a binding events with an LOD of 1 pM. Preliminary analysis of 12 pilot clinical serum samples demonstrated the biosensor's capability of distinguishing patients from healthy donors, despite the limited sample size. These findings validate the potential of TDN-functionalized FG CNTFET architecture for aM-level early GC screening, laying a technological foundation for the development of low-cost, portable point-of-care testing (POCT) devices.