Translational optical and electrochemical biosensing strategies for liquid biopsy in triple-negative breast Cancer: advances, challenges, and clinical implementation.

Abstract

Triple-negative breast cancer (TNBC) is a highly aggressive subtype with no specific therapeutic targets and a high risk of early metastases. Liquid biopsy has emerged as a promising method for real-time monitoring using biomarkers like microRNAs, circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and Extracellular vesicles. However, current analytical methods face challenges such as low sensitivity, high costs, and a lack of adaptability for point-of-care use, highlighting the need for new biosensing technologies. This review presents a comprehensive and critical examination of recent optical and electrochemical biosensors for TNBC liquid biopsy, focusing on current breakthroughs in detection techniques, signal transduction mechanisms, and clinical applications. Optical platforms such as fluorescence, electrochemiluminescence, surface plasmon resonance, and surface-enhanced Raman scattering offer ultrahigh sensitivity and multiplexing capabilities, enabling attomolar detection limits through nanomaterial integration and nucleic acid amplification methods. Electrochemical biosensors, such as voltammetric (DPV, SWV), electrochemical impedance spectroscopy (EIS), field-effect transistor, and photoelectrochemical systems, provide comparable sensitivity while being more portable, cost-effective, and point-of-care applicable. This review systematically correlates TNBC biomarkers with optimal sensing technologies, emphasizing how biomolecular properties affect sensor selection and performance. It also underscores the translational gap, as most platforms are still limited to proof-of-concept studies validated in TNBC cell line models or spiked samples, with limited clinical cohorts. Key challenges, such as biofouling, lack of standardization, assay complexity, and scalability, are highlighted in regard to real-world deployment. Finally, this review emphasizes future integration of biosensors with CTC-derived organoids, microfluidics, AI, and multiplexed detection to enable portable, clinically deployable systems.