Controlling the signal through interfacial design in aptamer-based electrochemical sensors

Abstract

Electrochemical aptamer-based (E-AB) sensors represent a distinct class of biosensing platforms that convert target recognition events into faradaic signals through conformational changes at electrode interfaces. Unlike conventional chemical-or enzyme-dependent systems, E-AB sensors operate via purely physical transduction mechanisms, minimizing susceptibility to pH fluctuations, enzymatic degradation, or interfering side reactions. These attributes enable robust operation in complex physiological environments and have been demonstrated in clinically relevant contexts, including intraoperative cancer diagnostics. Nevertheless, broad implementation has been limited by challenges in interfacial chemistry, aptamer stability, electrode nanostructuring, and signal reproducibility. This review critically examines intrinsic factors governing E-AB performance, with emphasis on interfacial engineering, aptamer selection and modification, and nanostructured electrode architectures. Advances in molecular design and materials integration are highlighted, alongside emerging fabrication strategies that enhance sensitivity, dynamic range, and operational stability. By synthesizing recent progress and identifying persistent bottlenecks, this work outlines pathways toward realizing the clinical and technological potential of E-AB sensors.