Biosensors for Circular RNA Profiling in Biological Matrices

Abstract

Early detection of many diseases remains difficult because they often develop silently over the course of years. Circular RNAs are now at the forefront as biomarker candidates with a covalently closed structure, making them highly stable with exonuclease resistance and long half-lives. With their disease-specific expression pattern and their presence in biofluids, they offer easier and noninvasive monitoring of molecular signatures. Conventional detection techniques require centralized laboratories, sophisticated instrumentation, and specialized personnel, which restrict their widespread clinical adoption and limit their applicability in point-of-care diagnostic settings, but recent advances in biosensor technologies enable rapid, sensitive, and highly specific circRNA detection in biological matrices without complex equipment. Integration with nanomaterials, enzymatic amplification, and microfluidic or portable devices further enhances the specificity, signal strength, and clinical applicability. This Tutorial critically evaluates these emerging biosensing strategies, discusses current challenges, and provides practical guidelines for selecting circRNA biomarkers and corresponding detection methods. By bridging circRNA biology with advanced biosensor design, this work aims to accelerate translational research and guide the development of next-generation diagnostics for early disease detection, supporting a shift from reactive treatment to proactive health care.