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Surface plasmon resonance (SPR) biosensors are optical sensors exploiting special electromagnetic waves-surface plasmon-polaritons-to probe interactions between an analyte in solution and a biomolecular recognition element immobilized on the SPR sensor surface. Major application areas include detection of biological analytes and analysis of biomolecular interactions where SPR biosensors provide benefits of label-free real-time analytical technology. This paper reviews fundamentals of SPR affinity biosensors and discusses recent advances in development and applications of SPR biosensors.

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A crucial step in the development of implanted medical devices, in vivo diagnostics, and microarrays is the effective prevention of nonspecific protein adsorption from real-world complex media such as blood plasma or serum. In this work, a zwitterionic poly(carboxybetaine acrylamide) (polyCBAA) biomimetic material was employed to create a unique biorecognition coating with an ultralow fouling background, enabling the sensitive and specific detection of proteins in blood plasma. Conditions for surface activation, protein immobilization, and surface deactivation of the carboxylate groups in the polyCBAA coating were determined. An antibody-functionalized polyCBAA surface platform was used to detect a target protein in blood plasma using a sensitive surface plasmon resonance (SPR) sensor. A selective protein was directly detected from 100% human blood plasma with extraordinary specificity and sensitivity. The total nonspecific protein adsorption on the functionalized polyCBAA surface was very low (<3 ng/cm (2) for undiluted blood plasma). Because of the significant reduction of nonspecific protein adsorption, it was possible to monitor the kinetics of antigen-antibody interactions in undiluted blood plasma. The functionalization effectiveness and detection characteristics using a cancer protein marker candidate of polyCBAA were compared with those of the conventional nonfouling oligo(ethylene glycol)-based surface chemistry.

We report on a unified theoretical model of the resolution of SPR sensors which makes it possible to predict the ultimate performance of all major configurations of SPR sensors. The theory indicates that the performance of SPR sensors is independent of the method of excitation of surface plasmons (prism or grating coupling) or the method of modulation (amplitude, angular or wavelength) and depends dominantly on the noise properties of the light source and detector. Results of the theoretical analysis are compared with the performance reported for several SPR sensors to illustrate that the best state-of-art SPR sensors are approaching their theoretical limits. Possibilities for further advances in the performance of SPR sensor technology are discussed.

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