Detection of substances on the single-molecule level could provide a helpful too for pharmacology, medicine, and product safety. But toxic or otherwise unwanted substances sometimes have a low molecular weight, making them hard to sense. To make a sensor for these molecules, you need materials with special properties, such that their interactions trigger an abrupt change in behavior.

V. G. Kravets and colleagues demonstrated the detection of tiny masses, on the order of a single biomolecule, using nanoscale optics. They fabricated a material that responded resonantly to light. When a tiny amount of mass was added to the surface, it caused a dramatic change in the amount of reflected light. This enabled the researchers to detect the presence of mass accumulation to the level of 10-15 grams over a millimeter patch—equivalent to detecting a single human skin cell landing on a coffee table.

The key to sensitivity in this particular experiment is in the response of a special material in the presence of very few photons. When intensity is high—that is, a large number of photons are present—a small change in the reflectivity of a surface is hard to measure. (Reflectivity is simply the percentage of incoming light that gets reflected back.) However, when intensity is low, the same tiny change in reflectivity can result in no light being reflected at all, an abrupt, qualitative change in behavior.

Achieving sensitivity on the individual photon level required a metamaterial: a carefully fabricated material with distinctive properties not exhibited in nature. In this case, the researchers deposited an array of tiny gold dots ("nanodots") on top of glass in a square lattice structure. Atop that, they set hydrogenated graphene: layers of carbon atoms in a hexagonal lattice, with a few hydrogen atoms attached.

Combined, the gold and graphene throttled acted as a throttle on reflections from the glass, provided the photons had a specific wavelength and arrived at a particular angle (approximately 69°, for those keeping track at home). Additionally, the light that was reflected experienced a change in wavelength—that is, color.

The researchers also measured the dependence of the reflectivity on the amount of hydrogen deposited on the surface. By adjusting the color of the photons to slightly longer wavelengths, they found a relationship between the excess mass on the metamaterial and the reflectivity. In this way, they determined a sensor based on this method could measure mass densities less than 10 femtograms—10-14 g, or roughly the mass of a moderately sized virus—over an area 1 millimeter square.

However, that was detecting the concentration of hydrogen on graphene; the real test is whether the method could be used to detect molecules important for chemical or medical analyses. To check this, the researchers again used the gold nanodots on glass but, instead of graphene, they deposited a molecule called a carboxylate and mixed in some biotin, also known as vitamin B 7 . Biotin has a particularly strong affinity for the streptavidin, a protein found in some bacteria species.

The researchers again measured the reflectance of the surface near the resonant angle and wavelength of light. By comparing with the earlier hydrogen results, they determined they could detect the presence of 1 to 4 streptavidin molecules on a single gold nanodot.

Of course, that's not quite the same as detecting or measuring the mass of a single biomolecule in isolation, but it's still a remarkably sensitive measurement. Even a tiny level of mass produced a sharp, distinct change in reflectivity. Though the researchers tested for a particular biological molecule, this experiment provided a good proof of principle for subsequent sensors.

Nature Materials, 2013. DOI: 10.1038/nmat3537 (About DOIs).