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CLEM: Powerful 2 in 1 Technique
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Correlative light and electron microscopy (CLEM) is attractive because it exploits two microscopy techniques that give very different and very complementary information. By combining light microscopy (LM) and electron microscopy (EM), one is able to achieve protein specific localization in the context of a global structure. In regular CLEM, LM resolution is ~200-300 nm, often limiting CLEM to illustration and identification applications, while super-resolution optical microscopy may provide resolution of 10-20 nm - 10x better then wide-field microscopy, much closer match to that of EM (0.1-10 nm) allowing for correlative imaging on comparable resolution scale. With this vision, we develop different correlative optical super-resolution and electron microscopy methods optimized for various types of biological problems and sample configurations, such as culture cells, section, etc. See the following movies of Correlative iPALM and FIB-SEM of mitochondrial DNA and mitochondrial membrane.
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