Editors' ChoiceNanotechnology

Visible to the Naked Eye

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Science Translational Medicine  07 Nov 2012:
Vol. 4, Issue 159, pp. 159ec205
DOI: 10.1126/scitranslmed.3005261

The human eye can see a single strand of hair held at arm’s distance. Double or triple that distance, and the hair is no longer visible. With these visual limits, it would be impossible to see individual proteins in solution with the naked eye. By cleverly manipulating gold nanoparticles, de la Rica and Stevens make the impossible possible: They allow us to “see” disease-related proteins in solution at extremely low concentrations, thus setting a new stage for point-of-care diagnosis in resource-limited settings.

To create their visual bioassay, de la Rica and Stevens used a traditional sandwich enzyme-linked immunosorbent assay (ELISA) with catalase as the enzyme. Catalase breaks down hydrogen peroxide (H2O2) into water and oxygen. At low concentrations of H2O2, gold nanoparticles aggregate and turn the solution a blue color. In the presence of H2O2, the gold ions are reduced, turning the solution red. Thus, in the presence of a target analyte, such as a disease biomarker, the catalase enzyme would give rise to a blue-tinted readout. The authors applied this “plasmonic ELISA” to the detection of two clinical disease indicators: prostate-specific antigen (PSA) for prostate cancer recurrence, and HIV-1 capsid antigen p24 for human immunodeficiency virus. Initial tests showed detection limits for spiked PSA and p24 at 1 attogram (10-18) per milliliter human serum. In a demonstration using patient samples, the authors were able to see a positive (blue) readout from 10 donors who had viral loads of fewer than 50 copies, which had been undetectable by conventional nucleic acid–based tests. All HIV-negative patient samples produced a red signal, confirming no false positives.

Being able to quickly visualize whether a patient has disease biomarkers in blood sera is an important step toward rapid detection in resource-limited settings. This plasmonic assay avoids expensive or complex imaging setups, allows any end user to “see” the result, and is more sensitive than conventional bench top assays. The only drawback is the inability to quantify the amount of protein in solution—however, that can be done in follow-up assays if the patient tests positively.

R. de la Rica, M. M. Stevens, Plasmonic ELISA for the ultrasensitive detection of disease biomarkers with the naked eye. Nat. Nanotechnol., published online 28 October 2012 (10.1038/nnano.2012.186). [Abstract]

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