Next-generation electrochemical aptasensors for thrombin detection: the rise of aptamer-MOF architectures

Thrombin is a crucial regulatory enzyme in the blood coagulation cascade that significantly influences cancer metastasis, cardiovascular disease, inflammation, and immunological regulation. Because of its dynamic, concentration-dependent activity, thrombin has emerged as a potential biomarker for the early diagnosis of a wide range of pathological conditions. However, a common drawback of typical thrombin assays is their insufficient specificity, sensitivity, and operational simplicity required for point-of-care or real-time applications. The latest developments in coordination chemistry have resulted in the discovery of metal-organic frameworks (MOFs). These crystalline porous materials have been demonstrated to be robust biosensing platforms due to their extensive surface area, customizable functionality, and biocompatibility. Hence, integrating them with aptamers, synthetic oligonucleotides with remarkable molecular specificity and binding affinity, has led to the emergence of the next generation of electrochemical biosensors called MOF-based aptasensors. The metal-organic framework-based aptasensing strategies outperform current techniques. This review focuses on advancements in MOF-aptamer hybrid platforms and explores their potential to transform from laboratory-scale investigations into clinically viable technologies. Additionally, the study covers a decade of progress from 2015 to 2025, with a focus on innovations in sensor architecture, signal amplification strategies, material synthesis, and clinical applications. Aptamer-MOF complex-based biosensing platforms could revolutionize thrombin diagnosis. This approach leverages molecular diagnostics and supramolecular chemistry to make highly sensitive, portable, and clinically useful devices. This work provides a direct comparative assessment of the clinical performance of MOF-aptamer sensing platforms, classifying them by metal-core chemistry and amplification method. It also outlines commercial and regulatory challenges as well as potential translational prospects. This comprehensive review serves as a design blueprint for developing next-generation biosensors targeting thrombin and other coagulation-related biomarkers.