In a study conducted by two separate teams of researchers, an improved fluorescent microscope allows the researchers to see individual protein molecules on the surface of a living cell. Acquisition of fluorescence images was made by the two teams by dipping a needle-like tip into the focus of the laser used to create the fluorescence. The first team made improvements on how the tip was positioned, while the other team made modifications before letting the light hit the tip. They routed the laser light through a confined aperture.

A good way to view proteins without destroying them is done by optical fluorescence microscopy. The fluorescent microscope stimulates a sample to fluoresce at a different wavelength by using a laser at one wavelength. The major disadvantage of this process is the resolution. An average protein has a resolution of about 1 to 10 nm across while in this process it is 250 up to 300 nm. To enhance the fluorescence signal, researchers used a very sharp tip from an atomic force microscope (AFP) in order to break free from the resolution limit. The tip is placed at the focal point of a laser beam. The beam and the tip move simultaneously across the sample. This technique enhances the electric field and the ensuing fluorescence at the AFM tip since charges are more inclined to be at sharp corners. Images are resolved at close to 10 nanometers but the signal quality is poor since metal tips prevent photon emission by draining off excited electrons away from fluorescent dyes.

The first research team, from the California Institute of Technology in Pasadena, was able to take accurate fluorescence measurements. The team demonstrated that in order to get the best fluorescence and maximum resolution, the metal tip would have to touch the sample instead of just letting the tip stay close a few nanometers above the sample. The fluorescence of the sample increased twenty times beyond the background signal from the laser alone and four times the contrast just by the tip touching the sample. Instead of metal, they used a silicon tip to avoid draining off excited electron away from the fluorescent dyes. The team was successful in observing high quality fluorescence with a resolution of at least 10 nm by scanning the silicon tip over a 5 nm wide semiconductor nanocrystal sitting on a glass surface.

The second team, from the Max Planck Institute for Biochemistry in Martinsried, Germany, used the combination of sensitivity and resolution by placing a metal-coated tip on the rim of a 100 nm wide hole in a glass fiber that is tapered. They first illuminated the tip of a mica surface covered with DNA molecules (whose ends were labeled with fluorescent dye) by having a laser shined down the fiber. They were successful in resolving the separation of individual dye molecules by as little as 10 nm but they had quenching as a result. The research results of both groups are likely to achieve a finer resolution with better methods.