Robust and Sensitive Electrochemical Biosensor Based on Cascade Interface Engineering for piRNA Detection in Breast Cancer Diagnosis

Abstract Point-of-care electrochemical sensors require interfaces that simultaneously deliver high sensitivity, mechanical robustness, and long-term stability. These requirements remain difficult to reconcile at nanostructured electrode interfaces. Here, we report a cascade interfacial engineering strategy that integrates plasma-synthesized polydopamine (PDA), MXene nanosheets, and gold nanoparticles (AuNPs) to construct a high-performance electrochemical sensing interface. A rapid, one-minute plasma process forms a conductive PDA interlayer that serves both as a universal adhesive and as a mediator for the in situ electrodeposition of MXene and pH-regulated AuNPs, yielding a mechanically resilient and highly conductive nanocomposite electrode. This architecture markedly enhances electroactive surface area, electron transport, and interfacial stability under repeated mechanical deformation and prolonged storage. When coupled with catalytic hairpin assembly, the resulting platform enables ultrasensitive nucleic acid detection down to the femtomolar regime (within the linear range of 0–100 nM, the limits of detection are 0.14, 0.44, and 0.06 fM, respectively) and maintains high reproducibility across batches (RSD as low as 2.05%). Integration with a portable printed circuit board further enables reliable analysis of clinical serum samples. Beyond a specific biosensing application, this work establishes a generalizable interface-engineering paradigm for stabilizing nanomaterial-modified electrodes, advancing the design of robust, scalable point-of-care electrochemical systems.