Recent advances in surface modification and antifouling strategies for electrochemical sensing in complex biofluids

The ability of biosensing systems to act selectively and sensitively in complex biological fluids will play a significant role in future healthcare developments. In this short review, we discuss recent advancements in surface modification strategies, which have seen electrochemical biosensors perform with high ac-curacy in real patient samples (plasma, urine, whole blood, sweat). We discuss novel substrate and interfacial modifications for imparting surfaces with antifouling properties. This has allowed analytical devices to detect cancer biomarkers with a sensitivity of 2 pg/mL in whole blood. We also examine nanobodies (Nbs) for use as robust receptor components, which have recently been shown to have single molecule detection limits of the SARS- CoV-2 S1 spike protein in unprocessed saliva. Although such progress has been made, the review also highlights that current platforms are still limited in their capacity to control biointeractions at the sensing interface and long-term stability continues to be a barrier to many biosensors achieving commercialisation. Finally, future prospects are discussed including the use of stimuli-responsive surfaces for increased control over specific and non-specific biointeractions and on-demand biosensing.