Electrochemical Impedimetric Biosensing for Ultrasensitive Glycan and Glycoprotein Detection

Glycans and glycoproteins encode biologically and clinically relevant information that influences molecular stability, immune recognition, disease‐associated signaling, and biotherapeutic quality. Their analysis is therefore important for diagnostics, biomarker discovery, pathogen detection, and biopharmaceutical characterization. Electrochemical impedance spectroscopy (EIS) provides a label‐free, miniaturization‐compatible approach for converting glycan‐mediated recognition events into electrical responses using small sample volumes and simple instrumentation. This review critically examines impedimetric biosensing strategies for targeted detection of glycans, glycoproteins, and disease‐relevant glycoforms, as well as comparative glycoprofiling. We discuss the mechanistic foundations of Faradaic and non‐Faradaic EIS, emphasizing equivalent circuit selection, frequency domain analysis, signal interpretation, and experimental artifacts. Lectin‐ and glycan‐based interfaces, immobilization chemistries, antifouling layers, and nanomaterial‐enabled architectures are evaluated for their effects on charge‐transfer resistance, interfacial capacitance, receptor accessibility, interfacial stability, and reproducibility. Representative platforms are compared according to sample matrix, validation strategy, selectivity, matrix effects, and performance in clinical, biopharmaceutical, and pathogen‐detection settings. EIS is positioned alongside quartz crystal microbalance and surface plasmon resonance as a complementary, fit‐for‐purpose technique rather than a replacement for structural glycomics. Key barriers to translation include lectin cross‐reactivity, uncontrolled multivalent recognition, interfacial instability, inadequate real‐matrix validation, and nonstandardized EIS acquisition and analysis, all of which hinder robust glycoform profiling and targeted glycoanalysis.