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Graphene quantum dots (GQDs) and carbon dots (CDs) are among the latest research frontiers in carbon-based nanomaterials. They provide interesting attributes to current electrochemical biosensing due to their intrinsic low toxicity, high solubility in many solvents, excellent electronic properties, robust chemical inertness, large specific surface area, abundant edge sites for functionalization, great biocompatibility, low cost, and versatility, as well as their ability for modification with attractive surface chemistries and other modifiers/nanomaterials. In this review article, the use of GQDs and CDs as signal tags or electrode surface modifiers to develop electrochemical biosensing strategies is critically discussed through the consideration of representative approaches reported in the last five years. The advantages and disadvantages arising from the use of GQDs and CDs in this context are outlined together with the still required work to fulfil the characteristics needed to achieve suitable electrochemical enzymatic and affinity biosensors with applications in the real world.

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(Bio)fouling processes arising from nonspecific adsorption of biological materials (mainly proteins but also cells and oligonucleotides), reaction products of neurotransmitters oxidation, and precipitation/polymerization of phenolic compounds, have detrimental effects on reliable electrochemical (bio)sensing of relevant analytes and markers either directly or after prolonged incubation in rich-proteins samples or at extreme pH values. Therefore, the design of antifouling (bio)sensing interfaces capable to minimize these undesired processes is a substantial outstanding challenge in electrochemical biosensing. For this purpose, efficient antifouling strategies involving the use of carbon materials, metallic nanoparticles, catalytic redox couples, nanoporous electrodes, electrochemical activation, and (bio)materials have been proposed so far. In this article, biomaterial-based strategies involving polymers, hydrogels, peptides, and thiolated self-assembled monolayers are reviewed and critically discussed. The reported strategies have been shown to be successful to overcome (bio)fouling in a diverse range of relevant practical applications. We highlight recent examples for the reliable sensing of particularly fouling analytes and direct/continuous operation in complex biofluids or harsh environments. Opportunities, unmet challenges, and future prospects in this field are also pointed out.