Entropy-driven "two-way signal output" cyclic circuit: An ultra-sensitive electrochemical biosensor for non-invasive ORAOV 1 detection.

The rapid, sensitive and reliable detection of oral cancer overexpressed 1 (ORAOV 1) is crucial for the early, non-invasive diagnosis of oral squamous cell carcinoma (OSCC). Herein, we are the first to construct an ultrasensitive electrochemical (EC) biosensor based on an entropy-driven "two-way signal output" (TWSO) cyclic circuit for salivary ORAOV 1 detection. This innovative TWSO cyclic circuit can skillfully convert by-products into desired signal-generating units, not only reducing the excessive accumulation of by-products but also improving the utilization efficiency of output chains, thereby achieving rapid reaction kinetics and high signal outputs. Furthermore, this novel EC biosensor leverages metal and metal-organic framework nanocomposites, which possess good stability and electrocatalytic activity, to enhance its electrochemical performance. We experimentally demonstrate that this EC biosensor exhibits ultra-high sensitivity (LOD as low as 135 aM), a wide linear range from 1 fM to 1 nM, good reproducibility and stability. Meanwhile, it can determine ORAOV 1 in human saliva samples with good anti-interference and well-pleasing recovery rates. Importantly, this newly developed EC biosensor can accurately discriminate patients with OSCC from clinical samples (AUC = 1), holding immense prospects for the sensitive and non-invasive diagnosis of OSCC.