This study presents a proof-of-concept for the development of an impedimetric biosensor for ultra-sensitive glycoprofiling of prostate specific antigen (PSA). The biosensor exhibits three unique characteristics: (1) analysis of PSA with limit of detection (LOD) down to 4 aM; (2) analysis of the glycan part of PSA with LOD down to 4 aM level and; (3) both assays (i.e., PSA quantification and PSA glycoprofiling) can be performed on the same interface due to label-free analysis.

A short description about the importance of glycan biorecognition in physiological (blood cell type) and pathological processes (infections by human and avian influenza viruses) is provided in this review. Glycans are described as much better information storage media, compared to proteins or DNA, due to the extensive variability of glycan structures. Techniques able to detect an exact glycan structure are briefly discussed with the main focus on the application of lectins (glycan-recognising proteins) in the specific analysis of glycans still attached to proteins or cells/viruses. Optical, electrochemical, piezoelectric and micromechanical biosensors with immobilised lectins or glycans able to detect a wide range of analytes including whole cells/viruses are also discussed.

The construction of a sensitive electrochemical lectin-based immunosensor for detection of a prostate specific antigen (PSA) is shown here. Three lectins with different carbohydrate specificities were used in this study to glycoprofile PSA, which is the most common biomarker for prostate cancer (PCa) diagnosis. The biosensor showed presence of α-L-fucose and α-(2,6)-linked terminal sialic acid within PSA´s glycan with high abundance, while only traces of α-(2,3)-linked terminal sialic acid were found. MALDI TOF/TOF mass spectrometry was applied to validate results obtained by the biosensor with a focus on determination of a type of sialic acid linkage by two methods. The first direct comparison of electrochemical immunosensor assay employing lectins for PSA glycoprofiling with mass spectrometric techniques is provided here and both methods show significant agreement. Thus, electrochemical lectin-based immunosensor has potential to be applied for prostate cancer diagnosis.

Glycans are chains of carbohydrates attached to proteins (glycoproteins and proteoglycans) or lipids (glycolipids). Glycosylation is a posttranslational modification and glycans have a wide range of functions in a human body including involvement in oncological diseases. Change in a glycan structure cannot only indicate presence of a pathological process, but more importantly in some cases also its stage. Thus, a glycan analysis has a potential to be an effective and reliable tool in cancer diagnostics. Lectins are proteins responsible for natural biorecognition of glycans, even carbohydrate moieties still attached to proteins or whole cells can be recognized by lectins, what makes them an ideal candidate for designing label-free biosensors for glycan analysis. In this review we would like to summarize evidence that glycoprofiling of biomarkers by lectin-based biosensors can be really helpful in detecting prostate cancer.