Tackling matrix effects in biosensor-based analysis of untreated blood plasma

Human blood plasma is the matrix of choice for clinical diagnostic applications. However, matrix effects associated with its complex composition interfere with the accurate detection of biomarkers that are often present at extremely low concentrations. This study investigates such matrix effects, particularly the nonspecific adsorption of blood plasma to the sensor surface and the interaction of endogenous antibodies with the used receptors, and shows how they can be discriminated using a surface plasmon resonance biosensor. Moreover, we describe a strategy to tackle matrix effects by combining sequential blood plasma/buffer injections, single-surface referencing, and the addition of an antibody against endogenous immunoglobulins to blood plasma. Finally, we apply this strategy to the detection of the cancer biomarker carcinoembryonic antigen in undiluted blood plasma, achieving detection limits of 12 ng/mL using direct detection, and 225 pg/mL using a sandwich assay with functional gold nanoparticles.