Emerging electrochemical nanoscale architectures for point-of-care detection of miRNA biomarkers

• Recent advances in electrochemical biosensing technologies for miRNA biomarkers. • Classification of the electrochemical miRNA detection techniques based on their sensing mechanism. • Amplification strategies employed for the detection of low miRNA concentrations. • Evolution of nanomaterials and functionalisation strategies to improve the sensitivity and selectivity of electrochemical miRNA biosensors. • Challenges and potential solutions for implementation of these technologies in point-of-care (POC) scenarios. MicroRNAs (miRNAs) are a class of non-coding ribonucleic acids consisting of approximately 22 nucleotides which can provide a comprehensive insight into various disease mechanisms, facilitating early detection and guiding personalised therapeutic strategies. They become dysregulated in tumorigenesis, metastasis, cell differentiation, cell apoptosis and protein synthesis, providing a promising route for the prognosis, diagnosis, and management of various medical conditions. Despite the availability of established analytical methods for miRNA measurement, such as polymerase chain reaction and hybridisation techniques, there is a growing need for low-cost, miniaturised biosensor technologies for rapid and affordable miRNA detection. Electrochemical biosensors offer ease of integration into portable devices, extremely low limit of detection, and a broad dynamic range, thereby providing a compelling solution for early diagnosis and monitoring of various medical conditions. Here, we provide an overview of emerging electrochemical biosensor approaches for the user-friendly, rapid, and cost-effective detection of a representative subset of clinically relevant miRNA biomarkers. We introduce a broad classification of such technologies based on their overall detection scheme, namely, enzymatic, redox-tagged, and non-tagged. We critically evaluate the strength and weakness of these electrochemical biosensor platforms over commercial laboratory methods, highlighting representative biosensor architectures that are able to maximise sensitivity and selectivity. We conclude by discussing persisting limitations of electrochemical miRNA biosensing technologies, providing directions to direct future research and innovation efforts.