Stefan Hell and co-workers at Gottingen have adapted a technique known as fluorescence microscopy. In this form of microscopy the specimen is irradiated at a wavelength which excites either natural or artificially introduced fluorescent molecules known as fluorochromes. The sample is then studied through a filter that transmits at the fluorescence wavelength, but absorbs light at the excitation wavelength.

In the Gottingen experiments two lasers are shone on the sample: a green laser is used to excite the fluorescence, while a near-infrared laser is then used to "turn off" the fluorescence from the edges of the fluorescent spot. The second laser does this by exciting the fluorochromes to higher-still levels that decay to the ground state without fluorescing. This reduces the size of the spot by a factor of six beyond the diffraction limit length-wise, and by a factor of two in the radial direction. A further advantage is that the resulting fluorescent spot is more spherical than the spots produced with the traditional technique.