Sensitive Point-of-Care Salivary miRNA Detection for Oral Squamous Cell Carcinoma: Flexible Electrodes Coupled with a Methylene Blue/G-Quadruplex Biobarcode.

In the era of personalized medicine, the development of affordable, portable biosensors for early, noninvasive diagnosis and screening of oral squamous cell carcinoma (OSCC)-particularly in remote areas-is imperative. Conventional point-of-care (POC) diagnostics are often constrained by insufficient sensitivity, which impedes timely detection. Herein, we present an unprecedented POC electrochemical biosensor that integrates UiO-66@Fe-DNA coordination polymer-functionalized flexible electrodes with a methylene blue (MB)/G-quadruplex biobarcode technology for the detection of OSCC-associated salivary miRNA-31. UiO-66@Fe-DNA coordination polymers were successfully synthesized via a facile self-assembly of Fe-DNA hybrids on UiO-66. These polymers exhibit good electrical conductivity, high stability, and a large active surface area. Meanwhile, leveraging the strong interaction between MB and G-quadruplex, the MB/G-quadruplex biobarcode technology was innovatively deployed as both a signal amplifier and an electrochemical indicator. This novel and label-free electrochemical POC device achieved an ultralow limit of detection (LOD) of 306 aM and good specificity for miRNA-31. Preliminary clinical feasibility assessments revealed good diagnostic performance (AUC = 0.98) in differentiating OSCC patients from healthy controls. These findings underscore its substantial clinical potential for early, noninvasive, and portable OSCC diagnostics.