Biosensors for epigenetic biomarker detection: Recent advances and perspectives

Epigenetics refers to heritable changes in gene function without alterations in the nucleotide sequence, with enzymatic methylation being a central regulatory mechanism. Aberrant methylation of DNA, RNA, and proteins is closely linked to developmental disorders, neurodegenerative diseases, and cancer progression, making these modifications critical biomarkers. However, conventional detection methods such as bisulfite conversion, mass spectrometry, and northern blotting are often hindered by complex procedures, lengthy protocols, and sensitivity limitations. To overcome these challenges, a variety of biosensing platforms—including colorimetric, surface-enhanced Raman spectroscopy (SERS), surface plasmon resonance (SPR), electrochemical (EC), and fluorescent sensors—have been developed. These technologies enable simple, rapid, high-throughput, and highly sensitive detection of epigenetic biomarkers, offering significant potential for clinical diagnosis, drug development, and cancer therapy. This review summarizes recent advances in the field of epigenetic biomarkers, with a focus on the design principles, performance, and applications of various bioanalytical sensors. We compare their working mechanisms, analytical merits, and practical utility in detecting DNA methylation, histone modifications, RNA modifications (e.g., m⁶A), and related non-coding RNAs. Finally, we outline emerging trends and future challenges in this rapidly evolving area of biosensor research.