Transmission Electron Microscopy Techniques for the Life Sciences

TEM electron tomography delivers detailed 3D structural information for a sample at the nanometer scale. This technique involves taking a series of 2D images at different tilt angles and then reconstructing them into a 3D model using computational algorithms.

It can provide detailed structural analyses of cellular structures, including organelles, the cytoskeleton, and membranes, as well as organelle morphology. Electron tomography is also used to visualize the spatial arrangement of proteins and large macromolecular complexes.

Combining the high-resolution structural information of electron microscopy with the contextual information of fluorescence light microscopy, correlative light and electron microscopy (CLEM) is a versatile and powerful technique in the life sciences that bridges the gap between the capabilities of both methods. This integrative approach provides a more comprehensive understanding of biological processes and structures.

CLEM with Thermo Scientific TEMs is powered by easy-to-use software, making data collection and correlation both accurate and efficient.

Elemental analysis with EDS (energy-dispersive X-ray spectroscopy) is a technique that can be performed in an electron microscope through the addition of a specialized EDS detector, and is widely used to determine the elemental composition of materials.

For life science researchers, EDS can be leverage to identify the presence of specific elements in cells and tissues, or for mineralization studies of bones and teeth. Pharmaceutical researchers use EDS analysis to investigate the elemental composition of drug formulations, or as a tool for contaminant detection. EDS is widely used in materials science, chemistry, and geology research, making this technique a useful addition to transmission electron microscopes that are shared between multiple departments.

Negative stain imaging is a technique used to enhance the contrast of biological specimens such as viruses, proteins, and other macromolecules, making them more visible under the TEM. The electron dense stain surrounds the sample, creating a high-contrast envelope, or outline, against the background. This rapid and relatively simple method of contrast enhancement allows for the visualization of shape and surface details for a sample, even at relatively low electron doses, which are often needed  to preserve the integrity of delicate biological structures.

Negative stain imaging with TEM can be useful as a standalone technique or to assess the quality of protein samples for subsequent cryo-EM single particle analysis.

Cryo-electron microscopy (cryo-EM) is a collection of techniques that enables direct visualization of biological macromolecules, and the observation of biological systems, in their near-native states without the risk of artifacts from chemical fixation or negative staining. It encompasses single particle analysis for the structural analysis of proteins and complexes, cryo-electron tomography for cellular/subcellular imaging, and microcrystal electron diffraction for the characterization of small molecules and compounds. Cryo-EM techniques can access a broad range of biological samples, including large protein complexes, molecular machines, and virus particles, which have traditionally been challenging for other analytical techniques.

Cryo-EM is available as an additional option for all Thermo Scientific TEMs, or as standard in our line of specialized cryo-TEMs, designed to specifically expand your cryo-EM capabilities.