The highly sensitive shifts of the surface plasmon resonance of metal nanoparticles in response to their environment make these structures very useful as molecular sensors. However, even lower limits of detection are needed for early diagnosis of disease or detection of environmental contamination. To this end, L. Rodrigo-Lorenzo at the University of Vigo, R. de la Rica at Imperial College London and colleagues have recently found a way to invert the conventional sensing paradigm and create plasmonic sensors that actually give a stronger signal at lower molecular concentrations.

Their research, described in the July issue of Nature Materials (DOI: 10.1038/nmat3337; p. 604), uses star-shaped gold nanoparticles, termed “nano-stars” as plasmonic sensors. These were covalently modified with solutions of the enzyme glucose oxidase, resulting in a surface coverage proportional to the concentration of enzyme used. This enzyme oxidizes glucose to generate hydrogen peroxide, which can in turn be used to reduce silver ions to solid silver. For high concentrations of enzyme, more hydrogen peroxide is produced and the rate of silver precipitation is high enough for individual silver nanoparticles to nucleate. At lower concentrations, the silver only grows as a layer on the gold nano-stars. This silver coating has a much larger effect on the absorption spectrum of the nanostars than the precipitated silver nanoparticles, such that the low concentration scenario produces a greater sensor response, allowing down to 10^–20 g ml^–1 of glucose oxidase to be detected.

The researchers were able to adapt this inverse sensing mechanism to detect the cancer biomarker prostate specific antigen, which requires detection at ultralow concentrations for the early diagnosis of cancer recurrence in prostatectomy patients. For this, both the nano-stars and glucose oxidase were modified with antibodies that bind specifically to the antigen, thus directly relating the coverage of surface enzyme to the concentration of antigen. A lower limit of 10^–18 g ml^–1 could be detected, which is an order of magnitude lower than previous methods.

Gold nanostars modified with a low concentration of enzyme become coated with silver and show a large shift in absorption spectrum (top), whereas nanostars with high enzyme concentration cause nucleation of silver nanocrystals and little change to the spectrum (bottom). Reproduced with permission from Nature Mater. 11 (7) (2012), DOI: 10.1038/nmat3337; p. 604. ©2012 Macmillan Publishers Ltd.

The researchers said that the varied chemistry of crystal growth should enable adaptation of this unusual sensing mechanism to incorporate more subtle effects such as crystal size and morphology, and hopefully allow even lower limits to be attained.