{"id":1545,"date":"2024-10-30T02:00:28","date_gmt":"2024-10-30T02:00:28","guid":{"rendered":"https:\/\/www.thermofisher.com\/blog\/atomic-resolution\/?p=1545"},"modified":"2026-02-19T21:41:58","modified_gmt":"2026-02-19T21:41:58","slug":"what-is-cryo-em-what-is-cryo-electron-microscopy","status":"publish","type":"post","link":"https:\/\/www.thermofisher.com\/blog\/atomic-resolution\/what-is-cryo-em-what-is-cryo-electron-microscopy\/","title":{"rendered":"What is cryo-EM?"},"content":{"rendered":"<p><a href=\"https:\/\/www.thermofisher.com\/us\/en\/home\/electron-microscopy\/life-sciences\/cryo-em.html\">Cryo-electron microscopy<\/a> (cryo-EM) describes a collection of techniques used to analyze cryogenically frozen samples in specially designed transmission electron microscopes (cryo-TEMs). Recent advancements, including improved sample preparation tools, detectors, and analytical computer algorithms, have even enabled the determination of 3D cryo-EM structures at atomic resolution.<\/p>\n<div id=\"attachment_1546\" style=\"width: 1034px\" class=\"wp-caption aligncenter\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-1546\" class=\"size-full wp-image-1546\" title=\"Single particle analysis cryo-EM workflow.\" src=\"http:\/\/admin.acceleratingscience.com\/atomic-resolution\/wp-content\/uploads\/sites\/22\/2024\/10\/blog-WhatIsCryoEM-SPA-workflow-1024x170-1.jpg\" alt=\"Single particle analysis cryo-EM workflow.\" width=\"1024\" height=\"190\" srcset=\"https:\/\/admin.acceleratingscience.com\/atomic-resolution\/wp-content\/uploads\/sites\/22\/2024\/10\/blog-WhatIsCryoEM-SPA-workflow-1024x170-1.jpg 1024w, https:\/\/admin.acceleratingscience.com\/atomic-resolution\/wp-content\/uploads\/sites\/22\/2024\/10\/blog-WhatIsCryoEM-SPA-workflow-1024x170-1-300x56.jpg 300w, https:\/\/admin.acceleratingscience.com\/atomic-resolution\/wp-content\/uploads\/sites\/22\/2024\/10\/blog-WhatIsCryoEM-SPA-workflow-1024x170-1-768x143.jpg 768w\" sizes=\"auto, (max-width: 1024px) 100vw, 1024px\" \/><p id=\"caption-attachment-1546\" class=\"wp-caption-text\">General workflow used in single particle analysis, a common cryo-EM technique.<\/p><\/div>\n<h2 style=\"font-size: 100%\"><strong>How does cryo-EM work?<\/strong><\/h2>\n<p>When samples are flash frozen (vitrified), the aqueous solution does not form crystalline ice, instead becoming a vitreous solid. This reduces the damage that the freezing process causes to the sensitive biological sample, thereby taking a \u201csnapshot\u201d of the specimen in solution.<\/p>\n<p>Broadly speaking, <a href=\"https:\/\/www.thermofisher.com\/us\/en\/home\/electron-microscopy\/life-sciences\/cryo-em\/techniques.html\">cryo-EM techniques<\/a> then image these samples at a variety of angles at high resolution and then digitally recombine the 2D snapshots into a 3D reconstruction. Cryo-EM can determine structures of challenging proteins and other macromolecules while providing wholly unique insights into how these proteins function. Although once considered a specialty tool used only by a small group of experts, cryo-electron microscopes are now increasingly easier to use, more affordable, and accessible to the wider scientific community.<\/p>\n<h2 style=\"font-size: 100%\"><strong>Benefits of cryo-EM<\/strong><\/h2>\n<p>Cryo-electron microscopy fills a complimentary niche next to other popular structural analysis techniques such as X-ray diffraction and nuclear magnetic resonance. Compared to other techniques, cryo-EM doesn\u2019t require samples to be crystallized, which has been a significant barrier in <a href=\"https:\/\/www.thermofisher.com\/blog\/atomic-resolution\/next-generation-antibiotics-fight-against-antimicrobial-resistance\/\">the analysis of large complexes and membrane protein<\/a>. Typically, all that\u2019s required for cryo-EM is that the samples can be suspended in an aqueous environment.<\/p>\n<p>Additionally, other techniques that require extensive sample preparation always carry the risk of subtly disrupting the biologically accurate structures as they exist in vivo. Through vitrification, this risk is significantly lowered, thereby providing physiologically relevant observations.<\/p>\n<div id=\"attachment_1547\" style=\"width: 710px\" class=\"wp-caption aligncenter\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-1547\" class=\"wp-image-1547\" title=\"Comparison of cryo EM techniques\" src=\"http:\/\/admin.acceleratingscience.com\/atomic-resolution\/wp-content\/uploads\/sites\/22\/2024\/10\/blog-WhatIsCryoEM-comparative-chart-v2.jpg\" alt=\"Comparison of cryo EM techniques\" width=\"700\" height=\"410\" srcset=\"https:\/\/admin.acceleratingscience.com\/atomic-resolution\/wp-content\/uploads\/sites\/22\/2024\/10\/blog-WhatIsCryoEM-comparative-chart-v2.jpg 1024w, https:\/\/admin.acceleratingscience.com\/atomic-resolution\/wp-content\/uploads\/sites\/22\/2024\/10\/blog-WhatIsCryoEM-comparative-chart-v2-300x176.jpg 300w, https:\/\/admin.acceleratingscience.com\/atomic-resolution\/wp-content\/uploads\/sites\/22\/2024\/10\/blog-WhatIsCryoEM-comparative-chart-v2-768x450.jpg 768w\" sizes=\"auto, (max-width: 700px) 100vw, 700px\" \/><p id=\"caption-attachment-1547\" class=\"wp-caption-text\">Comparison of common methods for imaging and structural analysis used in the life sciences, including cryo-electron microscopy techniques.<\/p><\/div>\n<h2 style=\"font-size: 100%\"><strong>Cryo-EM techniques<\/strong><\/h2>\n<p>While cryo-EM is sometimes used synonymously with the most popular technique, single particle analysis, there are a suite of analytical methods that can be performed in a cryo-TEM. We will provide a brief introduction to them here; far more information is available on our website.<\/p>\n<div id=\"attachment_1548\" style=\"width: 710px\" class=\"wp-caption aligncenter\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-1548\" class=\"wp-image-1548\" title=\"Histamine in the binding pocket of human GABA-A determined with single particle analysis.\" src=\"http:\/\/admin.acceleratingscience.com\/atomic-resolution\/wp-content\/uploads\/sites\/22\/2024\/10\/blog-WhatIsCryoEM-SPA-Gabaa-1024x576-1.jpg\" alt=\"Histamine in the binding pocket of human GABA-A determined with single particle analysis.\" width=\"700\" height=\"394\" srcset=\"https:\/\/admin.acceleratingscience.com\/atomic-resolution\/wp-content\/uploads\/sites\/22\/2024\/10\/blog-WhatIsCryoEM-SPA-Gabaa-1024x576-1.jpg 1024w, https:\/\/admin.acceleratingscience.com\/atomic-resolution\/wp-content\/uploads\/sites\/22\/2024\/10\/blog-WhatIsCryoEM-SPA-Gabaa-1024x576-1-300x169.jpg 300w, https:\/\/admin.acceleratingscience.com\/atomic-resolution\/wp-content\/uploads\/sites\/22\/2024\/10\/blog-WhatIsCryoEM-SPA-Gabaa-1024x576-1-768x432.jpg 768w\" sizes=\"auto, (max-width: 700px) 100vw, 700px\" \/><p id=\"caption-attachment-1548\" class=\"wp-caption-text\">Histamine in the binding pocket of human GABA-A (resolved at 1.7 \u00c5 with the Krios Cryo-TEM).<br \/>Data courtesy A. Sente and R. Aricescu, MRC-LMB Cambridge.<\/p><\/div>\n<h2 style=\"font-size: 100%\"><strong>Single particle analysis<\/strong><\/h2>\n<p>In single particle analysis, purified proteins or protein complexes are first vitrified to preserve their native structures. TEM is then used to collect numerous 2D snapshots of the samples. As the proteins are oriented randomly within the ice, these images show the sample at various angles, and can be recombined into a high-resolution 3D reconstruction of the sample.<\/p>\n<div id=\"attachment_1549\" style=\"width: 710px\" class=\"wp-caption aligncenter\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-1549\" class=\"wp-image-1549\" title=\"Cryo-electron tomography of Chlamydomonas reinhardtii Golgi apparatus.\" src=\"http:\/\/admin.acceleratingscience.com\/atomic-resolution\/wp-content\/uploads\/sites\/22\/2024\/10\/blog-WhatIsCryoEM-tomo-golgi-1024x626-1.jpg\" alt=\"Cryo-electron tomography of Chlamydomonas reinhardtii Golgi apparatus.\" width=\"700\" height=\"428\" srcset=\"https:\/\/admin.acceleratingscience.com\/atomic-resolution\/wp-content\/uploads\/sites\/22\/2024\/10\/blog-WhatIsCryoEM-tomo-golgi-1024x626-1.jpg 1024w, https:\/\/admin.acceleratingscience.com\/atomic-resolution\/wp-content\/uploads\/sites\/22\/2024\/10\/blog-WhatIsCryoEM-tomo-golgi-1024x626-1-300x183.jpg 300w, https:\/\/admin.acceleratingscience.com\/atomic-resolution\/wp-content\/uploads\/sites\/22\/2024\/10\/blog-WhatIsCryoEM-tomo-golgi-1024x626-1-768x470.jpg 768w\" sizes=\"auto, (max-width: 700px) 100vw, 700px\" \/><p id=\"caption-attachment-1549\" class=\"wp-caption-text\">Cryo-electron tomography visualization of a Golgi apparatus from the green algae <em>Chlamydomonas reinhardtii<\/em>.<\/p><\/div>\n<h2 style=\"font-size: 100%\"><strong>Cryo-tomography<\/strong><\/h2>\n<p>Cryo-electron tomography (cryo-ET), most commonly applied to whole cells, provides 3D visualization of organelles and protein complexes at nanometer resolution in their physiological environments. This is done by opening windows into the cell with focused ion beam (FIB) milling of a vitrified cell. A series of 2D images are taken of this thinned cellular sample, which are then reconstructed into a 3D dataset. Such high-resolution 3D images of the cell interior can provide new insights into cellular function and sheds light on the arrangement and structure of native protein complexes.<\/p>\n<div id=\"attachment_1550\" style=\"width: 710px\" class=\"wp-caption aligncenter\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-1550\" class=\"wp-image-1550\" title=\"Protein structure determination with microcrystal electron diffraction.\" src=\"http:\/\/admin.acceleratingscience.com\/atomic-resolution\/wp-content\/uploads\/sites\/22\/2024\/10\/blog-WhatIsCryoEM-MicroED-1024x568-1.jpg\" alt=\"Protein structure determination with microcrystal electron diffraction.\" width=\"700\" height=\"388\" srcset=\"https:\/\/admin.acceleratingscience.com\/atomic-resolution\/wp-content\/uploads\/sites\/22\/2024\/10\/blog-WhatIsCryoEM-MicroED-1024x568-1.jpg 1024w, https:\/\/admin.acceleratingscience.com\/atomic-resolution\/wp-content\/uploads\/sites\/22\/2024\/10\/blog-WhatIsCryoEM-MicroED-1024x568-1-300x166.jpg 300w, https:\/\/admin.acceleratingscience.com\/atomic-resolution\/wp-content\/uploads\/sites\/22\/2024\/10\/blog-WhatIsCryoEM-MicroED-1024x568-1-768x426.jpg 768w, https:\/\/admin.acceleratingscience.com\/atomic-resolution\/wp-content\/uploads\/sites\/22\/2024\/10\/blog-WhatIsCryoEM-MicroED-1024x568-1-450x250.jpg 450w\" sizes=\"auto, (max-width: 700px) 100vw, 700px\" \/><p id=\"caption-attachment-1550\" class=\"wp-caption-text\">Protein structure determination with microcrystal electron diffraction.<\/p><\/div>\n<h2 style=\"font-size: 100%\"><strong>Microcrystal electron diffraction<\/strong><\/h2>\n<p>Microcrystal electron diffraction, or MicroED, is a diffraction technique similar to X-ray crystallography (XRD) that utilizes electrons rather than X-rays. Due to electron\u2019s smaller wavelength and stronger interaction with the sample, atomic details can be extracted from individual nanocrystals (&lt;200 nm in size), even in a heterogeneous mixture. This allows for the analysis of crystals that are too small for XRD and other crystallography methods. Data collection is completed in only a few minutes, and 3D structures can be determined at atomic resolution.<\/p>\n<h2 style=\"font-size: 100%\"><strong>Conclusions<\/strong><\/h2>\n<p>We hope this brief introduction has given you a glimpse into the power and possibilities of cryo-electron microscopy. With this revolutionary technology, structural biologists can analyze proteins in all their complex conformations, structures, and modified forms. They can even look at multiple protein conformations or heterogeneous complexes in a single sample.<\/p>\n<p>If you\u2019d like to know more about cryo-electron microscopy and the ways in which it is revolutionizing structural biology, pharmaceutical research, and more, please see some of our other educational posts on our Life in Atomic Resolution blog:<\/p>\n<p>&#8211; <a href=\"https:\/\/www.thermofisher.com\/blog\/atomic-resolution\/seeing-with-electrons-the-anatomy-of-an-electron-microscope\/\">Seeing with Electrons: The Anatomy of an Electron Microscope<\/a><br \/>&#8211; <a href=\"https:\/\/www.thermofisher.com\/blog\/atomic-resolution\/cellular-cryo-electron-tomography-education\/\">Open Access: Cellular Cryo-Electron Tomography Education<\/a><br \/>&#8211; <a href=\"https:\/\/www.thermofisher.com\/blog\/atomic-resolution\/cryo-em-sample-preparation-a-qa-with-university-of-utahs-core-lab-director\/\">Cryo-EM Sample Preparation: A Q&amp;A with University of Utah\u2019s Core Lab Director<\/a><\/p>\n<p>\u00a0<\/p>\n<p><strong>For even more educational resources, visit our <a href=\"https:\/\/www.thermofisher.com\/us\/en\/home\/electron-microscopy\/life-sciences\/learning-center.html?cid=msd_ls_xseg_xmkt_xbl_1879311_gl_oso_blg_ownlar&amp;utm_source=comms-blog&amp;utm_medium=blog&amp;utm_campaign=msd_ls_xseg_xmkt_xbl_1879311_gl_oso_blg_ownlar\">Life Sciences EM Learning Center &gt;&gt;<\/a><\/strong><\/p>\n\n\n<p><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Cryo-electron microscopy (cryo-EM) describes a collection of techniques used to analyze cryogenically frozen samples in specially designed transmission electron microscopes (cryo-TEMs). Recent advancements, including improved sample preparation tools, detectors, and analytical computer algorithms, have even enabled the determination of 3D cryo-EM structures at atomic resolution. How does cryo-EM work? When samples are flash frozen (vitrified),<\/p>\n","protected":false},"author":905,"featured_media":1551,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"_kad_blocks_custom_css":"","_kad_blocks_head_custom_js":"","_kad_blocks_body_custom_js":"","_kad_blocks_footer_custom_js":"","_monsterinsights_skip_tracking":false,"_genesis_hide_title":false,"_genesis_hide_breadcrumbs":false,"_genesis_hide_singular_image":false,"_genesis_hide_footer_widgets":false,"_genesis_custom_body_class":"","_genesis_custom_post_class":"","_genesis_layout":"","_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_feature_clip_id":0,"_jetpack_memberships_contains_paid_content":false,"footnotes":"","jetpack_post_was_ever_published":false},"categories":[330,24,128,14,116,329],"tags":[331,16,134,332,76],"division":[],"class_list":{"0":"post-1545","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-cryo-em-techniques","8":"category-cryo-electron-microscopy-cryo-em","9":"category-cryo-electron-tomography","10":"category-electron-microscopy-101","11":"category-microed","12":"category-single-particle-analysis","13":"tag-cryo-em-techniques","14":"tag-cryo-em","15":"tag-cryo-tomography","16":"tag-microcrystal-electron-diffraction","17":"tag-single-particle-analysis","18":"entry"},"_selected_authors":[1292],"_selected_reviewers":[],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO Premium plugin v27.8 (Yoast SEO v27.8) - https:\/\/yoast.com\/product\/yoast-seo-premium-wordpress\/ -->\n<title>What is Cryo EM? - What is Cryo Electron Microscopy? - Cryo EM - Life in Atomic Resolution<\/title>\n<meta name=\"description\" content=\"What is cryo EM? A collection of techniques for the analysis of cryogenically frozen samples in specialized transmission electron microscopes\" \/>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.thermofisher.com\/blog\/atomic-resolution\/what-is-cryo-em-what-is-cryo-electron-microscopy\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"What is cryo-EM?\" \/>\n<meta property=\"og:description\" content=\"What is cryo EM? A collection of techniques for the analysis of cryogenically frozen samples in specialized transmission electron microscopes\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.thermofisher.com\/blog\/atomic-resolution\/what-is-cryo-em-what-is-cryo-electron-microscopy\/\" \/>\n<meta property=\"og:site_name\" content=\"Life in Atomic Resolution\" \/>\n<meta property=\"article:publisher\" content=\"https:\/\/www.facebook.com\/thermofisher\" \/>\n<meta property=\"article:published_time\" content=\"2024-10-30T02:00:28+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2026-02-19T21:41:58+00:00\" \/>\n<meta property=\"og:image\" content=\"http:\/\/admin.acceleratingscience.com\/atomic-resolution\/wp-content\/uploads\/sites\/22\/2024\/10\/cryoEM-blog-virus-pore4-1920x600_Header.jpg\" \/>\n\t<meta property=\"og:image:width\" content=\"1920\" \/>\n\t<meta property=\"og:image:height\" content=\"600\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/jpeg\" \/>\n<meta name=\"author\" content=\"Alex Ilitchev\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:creator\" content=\"@thermofisher\" \/>\n<meta name=\"twitter:site\" content=\"@thermofisher\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"Alex Ilitchev\" \/>\n\t<meta name=\"twitter:label2\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"5 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"Article\",\"@id\":\"https:\\\/\\\/www.thermofisher.com\\\/blog\\\/atomic-resolution\\\/what-is-cryo-em-what-is-cryo-electron-microscopy\\\/#article\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/www.thermofisher.com\\\/blog\\\/atomic-resolution\\\/what-is-cryo-em-what-is-cryo-electron-microscopy\\\/\"},\"author\":{\"name\":\"Alex Ilitchev\",\"@id\":\"https:\\\/\\\/admin.acceleratingscience.com\\\/atomic-resolution\\\/#\\\/schema\\\/person\\\/7b14b1ad2e6aaf9f989f5fb345363e39\"},\"headline\":\"What is cryo-EM?\",\"datePublished\":\"2024-10-30T02:00:28+00:00\",\"dateModified\":\"2026-02-19T21:41:58+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\\\/\\\/www.thermofisher.com\\\/blog\\\/atomic-resolution\\\/what-is-cryo-em-what-is-cryo-electron-microscopy\\\/\"},\"wordCount\":808,\"commentCount\":0,\"image\":{\"@id\":\"https:\\\/\\\/www.thermofisher.com\\\/blog\\\/atomic-resolution\\\/what-is-cryo-em-what-is-cryo-electron-microscopy\\\/#primaryimage\"},\"thumbnailUrl\":\"https:\\\/\\\/admin.acceleratingscience.com\\\/atomic-resolution\\\/wp-content\\\/uploads\\\/sites\\\/22\\\/2024\\\/10\\\/cryoEM-blog-virus-pore4-1920x600_Header.jpg\",\"keywords\":[\"Cryo EM Techniques\",\"cryo-EM\",\"cryo-tomography\",\"Microcrystal Electron Diffraction\",\"single particle analysis\"],\"articleSection\":[\"Cryo EM Techniques\",\"Cryo-Electron Microscopy (Cryo-EM)\",\"Cryo-Electron Tomography\",\"Electron Microscopy 101\",\"MicroED\",\"Single Particle Analysis\"],\"inLanguage\":\"en-US\",\"potentialAction\":[{\"@type\":\"CommentAction\",\"name\":\"Comment\",\"target\":[\"https:\\\/\\\/www.thermofisher.com\\\/blog\\\/atomic-resolution\\\/what-is-cryo-em-what-is-cryo-electron-microscopy\\\/#respond\"]}]},{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/www.thermofisher.com\\\/blog\\\/atomic-resolution\\\/what-is-cryo-em-what-is-cryo-electron-microscopy\\\/\",\"url\":\"https:\\\/\\\/www.thermofisher.com\\\/blog\\\/atomic-resolution\\\/what-is-cryo-em-what-is-cryo-electron-microscopy\\\/\",\"name\":\"What is Cryo EM? - What is Cryo Electron Microscopy? - Cryo EM - Life in Atomic Resolution\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/admin.acceleratingscience.com\\\/atomic-resolution\\\/#website\"},\"primaryImageOfPage\":{\"@id\":\"https:\\\/\\\/www.thermofisher.com\\\/blog\\\/atomic-resolution\\\/what-is-cryo-em-what-is-cryo-electron-microscopy\\\/#primaryimage\"},\"image\":{\"@id\":\"https:\\\/\\\/www.thermofisher.com\\\/blog\\\/atomic-resolution\\\/what-is-cryo-em-what-is-cryo-electron-microscopy\\\/#primaryimage\"},\"thumbnailUrl\":\"https:\\\/\\\/admin.acceleratingscience.com\\\/atomic-resolution\\\/wp-content\\\/uploads\\\/sites\\\/22\\\/2024\\\/10\\\/cryoEM-blog-virus-pore4-1920x600_Header.jpg\",\"datePublished\":\"2024-10-30T02:00:28+00:00\",\"dateModified\":\"2026-02-19T21:41:58+00:00\",\"author\":{\"@id\":\"https:\\\/\\\/admin.acceleratingscience.com\\\/atomic-resolution\\\/#\\\/schema\\\/person\\\/7b14b1ad2e6aaf9f989f5fb345363e39\"},\"description\":\"What is cryo EM? 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