A new ultralow fouling surface for the analysis of human plasma samples with surface plasmon resonance

Surface plasmon resonance (SPR) has been widely used to detect a variety of biomolecular systems, but only a small fraction of applications report on the analysis of patients' samples. A critical barrier to the full implementation of SPR technology in molecular diagnostics currently exists for its potential application to analyze blood plasma or serum samples. Such capability is mostly hindered by the non-specific adsorption of interfering species present in the biological sample at the functional interface of the biosensor, often referred to as fouling. Suitable polymeric layers having a thickness ranging from 15 and about 70 nm are usually deposited on the active surface of biosensors to introduce antifouling properties. A similar approach is not fully adequate for SPR detection where the exponential decay of the evanescent plasmonic field limits the thickness of the layer beyond the SPR metallic sensor surface for which a sensitive detection can be obtained. Here, a triethylene glycol (PEG(3))-pentrimer carboxybetaine system is proposed to fabricate a new surface coating bearing excellent antifouling properties with a thickness of less than 2 nm, thus compatible with sensitive SPR detection. The high variability of experimental conditions described in the literature for the quantitative assessment of the antifouling performances of surface layers moved us to compare the superior antifouling capacity of the new pentrimeric system with that of 4-aminophenylphosphorylcholine, PEG-carboxybetaine and sulfobetaine-modified surface layers, respectively, using undiluted and diluted pooled human plasma samples. The use of the new coating for the immunologic SPRI biosensing of human arginase 1 in plasma is also presented.