The combination of electron microscopy with transmitted light microscopy (termed correlative light and electron microscopy; CLEM)
has been employed for decades to generate molecular identification that
can be visualized by a dark, electron-dense precipitate. Merging
fluorescence and electron microscopy has proven to be far more
difficult, but recent technological advances have enabled the study of
biological specimens at high resolution through the introduction of
fluorescent probes that are capable of generating contrast for electron
microscopy. Among the new reagents available for these studies are
genetically-encoded fluorescent proteins and hybrid systems that merge
synthetic fluorophores with targeting proteins in living cells. Quantum
dots and plant phototropins are also emerging as candidates for CLEM
assays.