Biomarker-based cancer analysis has great potential to lead to a better understanding of disease at the molecular level and to improve early diagnosis and monitoring. Unlike conventional tissue biopsy, liquid biopsy allows the detection of a large variety of circulating biomarkers, such as microRNA (miRNA), exosomes, circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and proteins, in an easily accessible and minimally invasive way. In this review, we describe and evaluate the relevance and applicability of surface plasmon resonance (SPR) and localized SPR (LSPR)-based platforms for the detection of different classes of cancer biomarkers in liquid biopsy samples. Firstly, we critically discuss unsolved problems and issues in capturing and analyzing biomarkers. Secondly, we highlight current challenges which need to be resolved in applying SPR biosensors into clinical practice. Then, we mainly focus on applications of SPR-based platforms that process a patient sample aiming to detect and quantify biomarkers as a minimally invasive liquid biopsy tool for cancer patients appearing over the last 5 years. Finally, we describe the analytical performances of selected SPR biosensor assays and their significant advantages in terms of high sensitivity and specificity as well as accuracy and workflow simplicity.

Strategies to develop antifouling surface coatings are crucial for surface plasmon resonance (SPR) sensing in many analytical application fields, such as detecting human disease biomarkers for clinical diagnostics and monitoring foodborne pathogens and toxins involved in food quality control. In this review, firstly, we provide a brief discussion with considerations about the importance of adopting appropriate antifouling materials for achieving excellent performances in biosensing for food safety and clinical diagnosis. Secondly, a non-exhaustive landscape of polymeric layers is given in the context of surface modification and the mechanism of fouling resistance. Finally, we present an overview of some selected developments in SPR sensing, emphasizing applications of antifouling materials and progress to overcome the challenges related to the detection of targets in complex matrices relevant for diagnosis and food biosensing.

Biosensors and biomedical devices require antifouling surfaces to prevent the non-specific adhesion of proteins or cells, for example, when aiming to detect circulating cancer biomarkers in complex natural media (e.g., in blood plasma or serum). A mixed-charge polymer was prepared by the coupling of a cationic polyelectrolyte and an anionic oligopeptide through a modified “grafting-to” method. The poly-L-lysine (PLL) backbone was modified with different percentages (y%) of maleimide–NHS ester chains (PLL-mal(y%), from 13% to 26%), to produce cationic polymers with specific grafting densities, obtaining a mixed-charge polymer. The anionic oligopeptide structure (CEEEEE) included one cysteine (C) and five glutamic acid (E) units, which were attached to the PLL-mal(y%) polymers, preadsorbed on gold substrates, through the thiol–maleimide Michael-type addition. Contact angle and PM-IRRAS data confirmed monolayer formation of the modified PLLs. Antifouling properties of peptide–PLL surfaces were assessed in adsorption studies using quartz crystal microbalance with dissipation (QCM-D) and surface plasmon resonance imaging (SPRI) techniques. PLL-mal(26%)-CEEEEE showed the best antifouling performance in single-protein solutions, and the nonspecific adsorption of proteins was 46 ng cm⁻² using diluted human plasma samples. The new PLL-mal(26%)-CEEEEE polymer offers a prominent low-fouling activity in complex media, with rapid and simple procedures for the synthesis and functionalization of the surface compared to conventional non-fouling materials.