"The small size of an individual nanoparticle brings the possibility of detecting a very low amount of analyte molecules without the need for labelling it with fluorophores," Jochen Feldmann of Ludwig-Maximilians University told nanotechweb.org. "For our sensor we estimate that the sensitivity is high enough to detect less than 50 molecular binding events."

Noble metal nanoparticles that are smaller than the wavelength of light show a pronounced resonance in their scattering spectrum for visible light. This "nanoparticle plasmon (NPP) resonance" depends on factors such as the nanoparticle's material, size, shape and the dielectric properties of its immediate environment. A 40 nm diameter nanoparticle - such as the ones used here - is sensitive to the refractive index 10 to 20 nm above its surface.

A biomolecular binding event close to the surface of a nanoparticle will increase the local refractive index and so shift the NPP resonance. To exploit this phenomenon, Feldmann and colleagues measured the light scattered by the nanoparticles in a dark-field microscope. Under this set-up, any change in the NPP resonance caused the nanoparticles to appear a different colour.

The scientists functionalized their 40 nm gold nanoparticles with biotinylated bovine serum albumin (biotin-BSA) molecules. Adding the protein streptavidin caused binding events to take place, with each streptavidin molecule linking with up to four biotin molecules. As a result, the NPP resonance shifted by 5 meV and the nanoparticles changed colour.

In fact, the technique can detect shifts of just 1 meV, and what's more, the test can monitor the binding of analytes in real-time and operate under physiological conditions. According to Feldmann, the single nanoparticle sensors also have a high potential for miniaturization and massive parallelization.

"Assays based on light scattering from single nanoparticles may be applied in all fields of diagnosis and research where only a small absolute amount of analytes is available or high parallelization is required," he said.

The scientists, who reported their work in Nano Letters, believe they will be able to sharpen the resonance peak, and so improve the limit of detection, by using nanorods instead of nanospheres. Now, they plan to investigate the binding reactions and dynamics of "a relevant antibody-antigen system" as well as simplifying and miniaturizing the experimental set-up. Another goal is to build disposable flow cells containing different species of functionalized nanoparticles.