Gold usually means extravagance, but now it could be the key to making vital medical tests cheaper.
People in poor countries often do not get timely treatment for cancer or infections, because diagnostic tests that can spot diseases early are too expensive. Now, a team at Imperial College London have figured out that gold could be the solution.
One common type of diagnostic test is the enzyme-linked immunosorbent assay (ELISA). It uses a tiny dish coated with antibodies that bind to a target molecule from a germ or tumour cell present in blood serum. A second lot of antibodies are then added that attach themselves to the bound targets. These antibodies carry an enzyme that can be made to change colour by adding a chemical. The colour change is measured by machine to determine the presence and concentration of the germ or tumour cells. Unfortunately, the machines are expensive.
Molly Stevens and her colleagues have done away with the need for machines by devising a "plasmonic ELISA" ? a test which gives results readable with the naked eye. What's more, it is more sensitive than the best tests for HIV currently available.
Clumps versus spheres
The new test capitalises on the ability of hydrogen peroxide to react with dissolved gold ions, making them come out of solution and form metallic nanoparticles. How fast this reaction takes place, Stevens says, determines what kind of nanoparticles form. Less peroxide means they grow slowly, forming irregular clumps, while more peroxide favours the fast growth of spherical nanoparticles.
Crucially, due to the way that the nanoparticles interact with light, via a cloud of surface electrons called a plasmon, irregular clumps turn the solution blue, while spheres turn it red. And the colour is intense: gold particles were used to colour medieval stained glass.
In the plasmonic ELISA, the second set of antibodies carries an enzyme called catalase, which breaks down hydrogen peroxide. Both sets of antibodies are exposed to blood serum, then the dish is rinsed and peroxide is added, followed by gold ions.
If the target molecule is present, the second set of antibodies binds to it, allowing catalase to destroy peroxide. This in turn means the gold nanoparticles grow slowly, forming clumps that turn the dish visibly blue. If there is no protein, the antibodies do not bind and are rinsed out. Without the bound catalase, peroxide remains abundant, producing a fast reaction that turns the dish red.
This shows whether the protein is present, not how much there is ? but that is enough for most diagnoses. Only a small number of target molecules are needed to turn the dish blue.
Using antibodies that bind to a target molecule from HIV, or to one from prostate cancer, the team could detect attograms ? billionths of a billionth of a gram ? of the protein per millilitre of human serum. The test picked up HIV at levels too low to detect with DNA-based PCR tests ? ironically, considered the gold standard of HIV testing.
Journal reference: Nature Nanotechnology, DOI: 10.1038/nnano.2012.186
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