The ability to fabricate sensory systems capable of highly selective operation in complex fluid will undoubtedly underpin key future developments in healthcare. However, the abundance of (bio)molecules in these samples can significantly impede performance at the transducing interface where nonspecific adsorption (fouling) can both block specific signal (reducing sensitivity) and greatly reduce assay specificity. Herein, we aim to provide a comprehensive review discussing concepts and recent advances in the construction of antifouling sensors that are, through the use of chemical, physical, or biological engineering, capable of operating in complex sample matrix (e.g., serum). We specifically highlight a range of molecular approaches to the construction of solid sensory interfaces (planar and nanoparticulate) and their characterization and performance in diverse in vitro and in vivo analyte (e.g., proteins, nucleic acids, cells, neuronal transmitters) detection applications via derived selective optical or electrochemical strategies. We specifically highlight those sensors that are capable of detection in complex media or those based on novel architectures/approaches. Finally, we provide perspectives on future developments in this rapidly evolving field.

This review summarizes recent advances in the development of electrochemical sensors and biosensors based on nanomaterial doped conducting polymers.

The rapid, convenient, and selective assaying of clinical targets directly in complex biological media brings with it the potential to revolutionize diagnostics. One major hurdle to impact is retention of selectivity and a tight control of nonspecific surface interactions or biofouling. We report herein, the construction of an antifouling interface through the covalent attachment of designed branched zwitterionic peptides onto electrodeposited polyaniline film. The antifouling capability of the designed branched peptide significantly outperforms that of the commonly used PEG and linear peptides. The interfaces modified with branched peptides are exceptionally effective in reducing a nonspecific protein and cell adsorption, as verified by electrochemical and fluorescent characterization. The derived sensors with mucin1 protein (MUC1) aptamer as the recognition element detect MUC1-positive MCF-7 breast cancer cells in human serum with high sensitivity and selectivity. The linear response range of the cytosensor for the MCF-7 cell is from 50 to 106 cells/mL, with a limit of detection as low as 20 cells/mL. More importantly, the assaying performances remain unchanged in human serum owing to the presence of branched antifouling peptide, indicating feasibility of the cytosensor for practical cancer cell quantification in complex samples.

This minireview summarizes recent trends in the development of low fouling electrochemical biosensors based on different antifouling materials.