Electrochemical detection of D-dimer and thrombin for clinical applications: A review

Rapid triage of thrombotic and hemorrhagic disorders requires analytical tools that can deliver quantitative results near clinical decision thresholds using small sample volumes. This review surveys current sensor architectures that translate binding or activity of fibrin degradation and protease targets into electrical readouts, with a focus on D dimer and thrombin as clinically actionable analytes. We summarize how electrochemical impedance spectroscopy, differential pulse voltammetry, chronoamperometry, and related methods are implemented in label free and labeled immunoassay formats, and explain the interfacial mechanisms that govern signal formation, including charge transfer resistance modulation, redox probe blocking, and catalytic turnover. Materials and interface engineering strategies are compared across carbon nanostructures, noble metal nanoparticles, conducting polymers, magnetic bead enrichment, and emerging two dimensional conductors, highlighting how each class increases bioreceptor loading, accelerates electron transfer, or suppresses nonspecific adsorption. Device oriented advances are discussed for disposable screen printed electrodes, interdigitated electrode arrays, and microfluidic cartridges that automate metering, incubation, and washing to improve repeatability in plasma or whole blood. Across reported platforms, we emphasize that clinically relevant dynamic range and precision around the rule out region are often more consequential than record low limits of detection obtained in buffered media. Key translation barriers are critically analyzed, including matrix effects, biofouling, unit standardization, calibration transfer, shelf life, manufacturing variability, and regulatory evidence requirements. Finally, we outline design considerations for multiplex panels and data driven correction of drift to support robust bedside deployment. These principles guide selecting architectures matched to emergency triage, monitoring, and near patient workflows.