Cascade-responsive microsystems with multi-phase electron transfer reactions for precise tumor biomarker profiling and bridging blood-based diagnostics toward interstitial fluid analysis

Aiming to translate the success of blood detection technologies reported in numerous research papers into future development ideas for tumor interstitial fluid (TIF) detection, this review systematically summarizes the latest advancements in electron-transfer and electrochemical signal-readout based sensing of biomarkers from the perspective of multiphase interface reaction flow transfer and control. The review covers electrochemical biosensing with immobilized sensing elements on electrode surfaces, transient or steady-state electrochemical signal readout based on interfacial collision electrochemistry, and homogeneous electrochemical sensors with constrained coupling of electron transfer cascades. We discuss strategies to enhance sensing reliability from three aspects: Avoiding target information loss, signal amplification, and background interference removal. In particular, the readout modes based on accumulated signals after transfer-response-conversion-amplification processes and dynamic feature extraction during the process are discussed and analyzed in detail. Furthermore, this review explores the translation of these blood-based diagnostics to TIF analysis, providing insights into the potential diagnostic and prognostic utility of TIF-based technologies.