Tokunaga, M., Imamoto, N., and Sakata-Sogawa, K.
Highly inclined thin illumination enables clear single-molecule imaging in cells.  Nature Methods 5: 159-161 (2008).

We describe a simple illumination method of fluorescence microscopy for molecular imaging. Illumination by a highly inclined and thin beam increases image intensity and decreases background intensity, yielding a signal/background ratio about eightfold greater than that of epi-illumination. A high ratio yielded clear single-molecule images and three-dimensional images using cultured mammalian cells, enabling one to visualize and quantify molecular dynamics, interactions and kinetics in cells for molecular systems biology.