Problem:
The unambiguous and reliable identification of biological crystals remains a major obstacle in crystallography, particularly in the critical stage of initial screening experiments. Automated imaging at high-resolution in the visible range is often insufficient to identify all conditions that have or may result in crystals.
Trace Florescence Labeling
One possibility to overcome the shortcomings of intrinsic fluorescence, which critically depends on the amount of naturally occurring tryptophan, is Trace Fluorescence Labeling (TFL). There are established protocols that include the rapid labeling of 0.1% of samples with a variety of fluorescent dyes immediately prior to crystallization. In addition to a significantly enhanced signal to noise ratio over intrinsic fluorescence, multiple labeling can be used to verify the presence of multi-subunit complexes in the crystal.