Ultra-sensitive solid-state nanochannel electrochemical biosensor based on interfacial charge density modulation and signal synergistic amplification for microRNA-155 detection.

Solid-state nanochannel sensors have emerged as a promising platform for next-generation disease marker detection. However, significant challenges remain in detecting low-abundance miRNAs in biological systems. This study presents an ultra-sensitive electrochemical sensing system based on interfacial charge density modulation and signal synergistic amplification within nanochannel for precise detection of microRNA-155 (miR-155). The system triggers a strand displacement reaction (SDA) by miR-155 to release numerous single-stranded DNAs, which assemble into a nanonet structure on the anodic aluminum oxide (AAO) membrane surface, leading to a remarkable increase in negative charge density at the nanochannel interface and nonlinear enhancement of transmembrane ionic current signals. Experimental results demonstrate an excellent linear relationship between the target concentration and current increment within the range of 10 fM to 10 nM with a detection limit as low as 3.1 fM. Hydrophobic modification of the nanochannel inner walls effectively reduces the channel diameter and enhances ion transport sensitivity, forming a synergistic amplification effect with nucleic acid isothermal amplification technology. This sensing strategy exhibits outstanding potential for liver cancer diagnosis in serum samples, providing an innovative technical paradigm for ultra-sensitive detection of miRNA biomarkers and early diagnosis of malignant tumors.