Here, the research field of nanoplasmonic sensors is placed under scrutiny, with focus on affinity-based detection using refractive index changes. This review describes how nanostructured plasmonic sensors can deliver unique advantages compared to the established surface plasmon resonance technique, where a planar metal surface is used. At the same time, it shows that these features are actually only useful in quite specific situations. Recent trends in the field are also discussed and some devices that claim extraordinary performance are questioned. It is argued that the most important challenges are related to limited receptor affinity and nonspecific binding rather than instrumental performance. Although some nanoplasmonic sensors may be useful in certain situations, it seems likely that conventional surface plasmon resonance will continue to dominate biomolecular interaction analysis. For detection of analytes in complex samples, plasmonics may be an important tool, but probably not in the form of direct refractometric detection.

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