Editors' ChoiceNANOSENSORS

Diminishing Returns

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Science Translational Medicine  18 Jul 2012:
Vol. 4, Issue 143, pp. 143ec126
DOI: 10.1126/scitranslmed.3004590

In almost all biomolecule-detection assays, as a target molecule of interest becomes more and more dilute, the assay’s signal becomes smaller and smaller, until it eventually vanishes. To extend the detection range, most biomolecular sensing technologies have mechanisms for enhancing signal strength so that scientists can follow that diminishing tail into lower and lower concentration realms. But what if an assay could be devised in which the signal increases as the analyte becomes more and more diluted? Now, Stevens and co-workers realize this seemingly paradoxical accomplishment, which they term “inverse sensitivity.”

With the new approach, the authors were able to measure prostate-specific antigen at concentrations as low as 4 × 10–20 M in whole serum. How? Their strategy is a clever marriage between nanoparticle plasmonic transducers and enzymatic activity. Using gold nanostars—jagged nanoparticles whose sharp edges produce localized surface plasmon resonance (LSPR) signals in the near-infrared region of the spectrum—Stevens and colleagues devised a way to coat the nanostars with silver under the influence of the enzyme glucose oxidase (GOx). This enzyme oxidizes glucose to generate hydrogen peroxide, which then can reduce silver ions in solution, causing them to precipitate. At very low enzyme concentrations—and herein lies the crux of the technology—the small amounts of hydrogen peroxide produced by GOx were just enough to stimulate the growth of thin layers of silver on the gold nanostars—layers that were capable of shifting the nanostars’ LSPR. At higher GOx concentrations, the silver formed its own nanoparticles in solution rather than being deposited on the gold nanostars’ surfaces. Thus, as GOx concentration increased, the LSPR signal diminished. By linking this GOx-nanoparticle system to standard immunoassays via GOx-antibody conjugates, the authors have developed a highly sensitive assay, which they validated by measuring very low concentrations of prostate-specific antigen in blood.

This versatile modular system may be adapted to detect other low-concentration bioanalytes that to date have eluded measurement. The ability to monitor the appearance—or disappearance—of small amounts of selected biological molecules in physiological solutions has implications for research in systems biology and clinical diagnostics.

L. Rodriguguez-Lorenzo et al., Plasmonic nanosensors with inverse sensitivity by means of enzyme-guided crystal growth. Nat. Mater. 11, 604–607 (2012). [PubMed]

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