Electrochemical Strategies to Evaluate the Glycosylation Status of Biomolecules for Disease Diagnosis

Aberrant glycosylation is linked to several diseases, making glycoproteins and their glycoforms promising biomarkers. Traditional methods like mass spectrometry offer high sensitivity but are costly, time-consuming, and unsuitable for point-of-care testing. Electrochemical biosensors emerge as an attractive alternative due to their simplicity, affordability, portability, and rapid response. This review focuses on electrochemical strategies developed to assess the glycosylation level of a specific glycoprotein or biological structure rather than merely glycoprotein or cell concentration, as in previous reviews. Approaches include the use of aptamers, boronic acid derivatives, antibodies, and lectins, often combined with nanomaterials for enhanced sensitivity. Applications span the diagnosis/prognosis of several illnesses such as diabetes, congenital disorders of glycosylation, cancer, and neurodegenerative diseases. Innovative designs incorporate microfluidic and paper-based platforms for faster, low-cost analysis, while strategies using dual-signal acquisition or competitive assays improve accuracy. Despite promising sensitivity and selectivity, most sensors require multi-step protocols and lack of validation in clinical samples. Future research should focus on simplifying procedures, integrating microfluidics, and exploring novel capture or detection probes such as metal complexes or metal–organic frameworks. Overall, electrochemical sensors hold significant potential for point-of-care testing, enabling rapid and precise evaluation of glycosylation status, which could drive cell-based biomarker discovery and disease diagnostics.