Using Advanced Correlative Microscopy to Study Complex Biological Samples

Correlation between light, mostly fluorescence, and elec-tron microscopy (EM) is needed to identify biological molecules within their ultrastructural context and/or to relate the ultrastructure to preceding dynamics of biolog-ical molecules. Recent development of labels, sample preparation techniques, and microscopy tools allow researchers to bridge the gap between these two modalities, while dedicated, integrated microscopes merge the two techniques into one. This not only allows broader possi-bilities for implementation of CLEM (correlative light and electron microscopy) in analytical sciences but also enables novel applications crossing boundaries between the traditional microscopes. We provide an overview of the different CLEM approaches, including common labels and sample preparation techniques, and focus attention specifically on the advanced instrumentation and the novel opportunities and challenges these bring for the chemical and biological sciences.