Detecting correlative light and electron microscopic labels by electron spectroscopic imaging

To bridge the gap in resolution and to localize molecules of interest in high-resolution light and electron microscopy a number of correlative approaches have been proposed. One possibility is the use of correlative markers, e.g. fluorescent Quantum Dots (Qdots), which in TEM are imaged and distinguished by their contrast and shape. In 2007 Mhawi et al. demonstrated a more direct possibility, the visualization of electron low energy loss, which represents the TEM equivalent of fluorescence excitation. Such spectral information in the low energy-loss range was used to identify doxorubicin introduced into cells to label nuclei.