Tetrahedral DNA nanostructure based biosensor for high-performance detection of circulating tumor DNA using all-carbon nanotube transistor

Adopting carbon nanotube (CNT) transistors as biosensors has been developed as a promising method for cancer biomarker detection, which has shown superior sensitivity and selectivity. However, the detection of circulating tumor DNA (ctDNA) by the CNT transistor based biosensors is still a challenge and no work has been reported. Here, direct label-free DNA detection of AKT2 gene related to triple-negative breast cancer by all-CNT thin-film transistor (TFT) biosensors incorporated with tetrahedral DNA nanostructures (TDNs) is proposed and achieved for the first time. The adoption of TDNs enables improved biosensor response for at least 35% and even as high as 98% as compared with single-stranded DNA (ssDNA) probes owing to the enhanced DNA hybridization efficiency. Influence of the TDNs’ linker length on the biosensor performance is important and has been investigated. Concentration-dependent DNA detection is achieved by the all-CNT TFT biosensors with a broad linear detection range of six orders of magnitude and a theoretical limit of detection (LOD) of 2 fM. In addition, the all-CNT TFT biosensors exhibit favorable selectivity and repeatability. The platform of all-CNT TFT biosensors incorporated with TDNs has great potential for multiplexed detection of various cancer biomarkers, providing a simple yet high performance universal strategy for low-cost clinical applications.