Surface plasmon resonance (SPR) biosensing has become a standard practice in the investigation of biomolecular interaction analysis (BIA), because it is highly sensitive to the resonance condition on the sensing surface caused by environmental changes and do not require any extrinsic labeling. However, the detection limit of the conventional SPR biosensors is insufficient for the monitoring of low concentrations of small biomolecular analytes. In addition, the conventional SPR biosensor only can provide kinetic analysis information in the BIA. A more powerful biorecognition system is required not only to provide the kinetic analysis, but also to have the capability of monitoring biomolecular conformational and structural changes or trends. Therefore, in this study, nanoplasmonic technology was used to overcome three above challenges. First, patternized gold nanoparticle-enhanced plasmonic effects are utilized to manipulate particle plasmons or localized surface plasmons and enhance the biosensor sensitivity. The sensitivity of plasmonic biosensors was enhanced about 10-fold by controlling the size and volume fraction of the embedded Au nanoclusters in dielectric films. Furthermore, a coupled waveguide-surface plasmon resonance biosensor not only retains the same sensing sensitivity as that of a conventional SPR device, but also has the capability of monitoring biomolecular conformational change. Finally, with helps of attenuated total reflection surface-enhanced Raman scattering to detect the structural change of biomolecules, an advanced biomolecular recognition system with the three plasmonic techniques can provide more information in a variety of BIA. Therefore, the nanoplasmonic sensing will be a novel biosensing platform for biomolecular function analysis in fast diagnostics, drug discovery, and proteomics.
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