Electrochemical microRNA biosensors for gallbladder cancer: Translational perspectives for clinical chemistry and point-of-care diagnostics

Gallbladder cancer is a biliary malignancy characterized by a high mortality rate, primarily due to the limitations of current serum biomarkers and imaging techniques in detecting the disease at an early stage. Circulating microRNAs (miRNAs) in serum, plasma, and bile are stable, less invasive biomarkers that are indicative of the biology of gallbladder cancer and have the potential for diagnostics through liquid biopsy. This review critically evaluates miRNA-based electrochemical biosensors that have been developed to detect gallbladder cancer, including their analytical performance, sensitivity, specificity, and detection limits in clinically relevant matrices, preanalytical variables, and analytical and clinical validation in clinical laboratories. We provide a brief overview of the relevant miRNA signatures in disease, their specificity to gallbladder cancer over other malignancies and inflammatory responses, comment on the approaches to transduction and nanomaterial-engineered interfaces in the detection of sensitive miRNAs in human biofluids, and critique the performance of biosensors in relation to the conventional molecular procedures, such as RT-qPCR and droplet digital PCR (ddPCR). In routine applications, particular emphasis is placed on specificity, detection limits in clinically relevant matrices, robustness, and sources of both analytical and biological variability. This encompasses the complex composition of bile, which includes bile salts, proteins, and pH changes that can pose challenges such as electrode fouling. We also describe how these biosensors are integrated into central laboratories and point-of-care procedures to diagnose, differentiate between malignant and inflammatory biliary lesions, assess risks, and treat gallbladder cancer. The review provides a conceptual framework of translation that reinforces the purpose and reasoning behind the implementation of electrochemical biosensors in clinical oncology by bridging miRNA pathobiology with miRNA electrochemical biosensors assay engineering and laboratory medicine issues to guide the design and implementation of miRNA electrochemical biosensors as a clinical diagnostic tool.