637:
509:
608:
59:
578:
2935:
613:
612:
609:
2947:
614:
25:
649:
611:
402:, and the highest resolution achieved on record (as of September 30, 2022) is 0.48 Å. As of 2020, the majority of the protein structures determined by cryo-EM are at a lower resolution of 3–4 Å. However, as of 2020, the best cryo-EM resolution has been recorded at 1.22 Å, making it a competitor in resolution in some cases.
382:
Traditionally, X-ray crystallography has been the most popular technique for determining the 3D structures of biological molecules. However, the aforementioned improvements in cryo-EM have increased its popularity as a tool for examining the details of biological molecules. Since 2010, yearly cryo-EM
386:
The resolution of X-ray crystallography is limited by crystal homogeneity, and coaxing biological molecules with unknown ideal crystallization conditions into a crystalline state can be very time-consuming, in extreme cases taking months or even years. To contrast, sample preparation in cryo-EM may
96:. While development of the technique began in the 1970s, recent advances in detector technology and software algorithms have allowed for the determination of biomolecular structures at near-atomic resolution. This has attracted wide attention to the approach as an alternative to
474:. Colloquially, the term "cryogenic electron microscopy" or its shortening "cryo-EM" refers to cryogenic transmission electron microscopy by default, as the vast majority of cryo-EM is done in transmission electron microscopes, rather than scanning electron microscopes.
387:
require several rounds of screening and optimization to overcome issues such as protein aggregation and preferred orientations, but it does not require the sample to form a crystal, rather samples for cryo-EM are flash-frozen and examined in their near-native states.
179:
Thin crystals mounted on carbon film were found to be from 30 to 300 times more beam-resistant at 4 K than at room temperature... Most of our results can be explained by assuming that cryoprotection in the region of 4 K is strongly dependent on the
610:
146:
for structure determination methods was limited because of the radiation damage due to high energy electron beams. Scientists hypothesized that examining specimens at low temperatures would reduce beam-induced radiation damage. Both
383:
structure deposits have outpaced X-ray crystallography. Though X-ray crystallography has drastically more total deposits due to a decades-longer history, total deposits of the two methods are projected to eclipse around 2035.
2254:
Xiao, C., Fischer, M.G., Bolotaulo, D.M., Ulloa-Rondeau, N., Avila, G.A., and Suttle, C.A. (2017) "Cryo-EM reconstruction of the
Cafeteria roenbergensis virus capsid suggests novel assembly pathway for giant viruses".
327:
to be able to resolve protein particles in the image, making 3D reconstruction difficult or impossible. Imaging scaffolds boost the SNR of smaller proteins by binding them to a larger object, the scaffold. The
494:
opened the
Dubochet Center For Imaging (DCI) at the end of November 2021, for the purposes of applying and further developing cryo-EM. Less than a month after the first identification of the
190:
just two years later informing that the beam resistance was less significant than initially anticipated. The protection gained at 4 K was closer to "tenfold for standard samples of L-
636:
498:, researchers at the DCI were able to define its structure, identify the crucial mutations to circumvent individual vaccines and provide insights for new therapeutic approaches.
43:
265:
1903:
528:(cryo-ET), a specialized application where many images are taken of individual samples at various tilt angles, resulting in a 3D reconstruction of a single sample.
505:
was inaugurated on
December 1, 2016. EMBION is a cryo-EM consortium between Danish Universities (Aarhus University host and University of Copenhagen co-host).
291:
to roll out and market the new design. At about the same time, Gatan Inc. of
Pleasanton, California came out with a similar detector designed by Peter Denes (
2579:
249:
198:
648:
315:
More recently, advancements in the use of protein-based imaging scaffolds are helping to solve the problems of sample orientation bias and size limit.
268:
have led to a "resolution revolution" pushing the resolution barrier beneath the crucial ~2-3 Å limit to resolve amino acid position and orientation.
2562:
2557:
483:
577:
2706:
2409:
168:
2696:
2299:
329:
2599:
2572:
808:
2507:
1928:
2567:
2711:
1204:"High-Resolution Crystal Structures of Protein Helices Reconciled with Three-Centered Hydrogen Bonds and Multipole Electrostatics"
2973:
300:
2527:
1795:
Yip KM, Fischer N, Paknia E, Chari A, Stark H (November 2020). "Atomic-resolution protein structure determination by cryo-EM".
2651:
2517:
2464:
417:
411:
333:
292:
202:
2951:
2906:
2634:
2619:
2545:
972:
Knapek E, Dubochet J (August 1980). "Beam damage to organic material is considerably reduced in cryo-electron microscopy".
459:
454:
34:
229:
pattern confirmed the presence of amorphous/vitreous ice. In 1984, Dubochet's group demonstrated the power of cryo-EM in
276:
1445:"Evolution of standardization and dissemination of cryo-EM structures and data jointly by the community, PDB, and EMDB"
1336:"Cryo-EM structure determination of small therapeutic protein targets at 3 Å-resolution using a rigid imaging scaffold"
368:"for developing cryo-electron microscopy for the high-resolution structure determination of biomolecules in solution."
123:"for developing cryo-electron microscopy for the high-resolution structure determination of biomolecules in solution."
2656:
2489:
2342:
2292:
545:
1505:
2644:
2639:
2537:
2512:
2479:
463:
438:
433:
287:
to fund and develop a first prototype. The consortium then joined forces with the electron microscope manufacturer
143:
1846:
Sartori-Rupp A, Cordero
Cervantes D, Pepe A, Gousset K, Delage E, Corroyer-Dulmont S, et al. (January 2019).
2716:
2701:
2681:
2988:
2911:
2484:
2419:
2327:
2149:
Gruene T, Wennmacher JT, Zaubitzer C, Holstein JJ, Heidler J, Fecteau-Lefebvre A, et al. (December 2018).
280:
2901:
2661:
361:
272:
120:
2939:
2499:
2285:
442:
2983:
2686:
2604:
495:
264:
The 2010s were marked with drastic advancements of electron cameras. Notably, the improvements made to
253:
209:
pure water in a thin film by spraying it onto a hydrophilic carbon film that was rapidly plunged into
2051:
Jones CG, Martynowycz MW, Hattne J, Fulton TJ, Stoltz BM, Rodriguez JA, et al. (November 2018).
84:
temperatures. For biological specimens, the structure is preserved by embedding in an environment of
2865:
2691:
1334:
Castells-Graells R, Meador K, Arbing MA, Sawaya MR, Gee M, Cascio D, et al. (September 2023).
676:
567:
531:
512:
365:
108:
2151:"Rapid Structure Determination of Microcrystalline Molecular Compounds Using Electron Diffraction"
854:
2614:
2550:
2424:
2383:
1202:
Kuster, Daniel J.; Liu, Chengyu; Fang, Zheng; Ponder, Jay W.; Marshall, Garland R. (2015-04-20).
525:
642:
Cryo-EM image of an intact ARMAN cell from an Iron
Mountain biofilm. Image width is 576 nm.
2804:
2100:
de la Cruz MJ, Hattne J, Shi D, Seidler P, Rodriguez J, Reyes FE, et al. (February 2017).
1904:"Inauguration of the Dubochet Center for Imaging (DCI) on the campuses of UNIGE, UNIL and EPFL"
487:
2102:"Atomic-resolution structures from fragmented protein crystals with the cryoEM method MicroED"
2978:
2809:
2629:
1640:
Nakane T, Kotecha A, Sente A, McMullan G, Masiulis S, Brown PM, et al. (November 2020).
1271:"High-resolution structure determination of sub-100 kDa complexes using conventional cryo-EM"
377:
324:
97:
2814:
2373:
2211:
2004:"High-resolution structure determination by continuous-rotation data collection in MicroED"
1859:
1804:
1653:
1542:
1347:
1282:
1215:
1152:
1094:
1020:
714:
561:
491:
245:
226:
1443:
Chiu, Wah; Schmid, Michael F.; Pintilie, Grigore D.; Lawson, Catherine L. (January 2021).
8:
2779:
2764:
2671:
2666:
2609:
2474:
2456:
2388:
2378:
2322:
2308:
2053:"The CryoEM Method MicroED as a Powerful Tool for Small Molecule Structure Determination"
681:
508:
63:
2215:
1863:
1808:
1752:
Acta
Crystallographica. Section F, Structural Biology and Crystallization Communications
1657:
1546:
1368:
1351:
1335:
1286:
1219:
1156:
1098:
1082:
1024:
718:
2850:
2429:
2393:
2232:
2199:
2175:
2150:
2126:
2101:
2077:
2052:
2028:
2003:
1880:
1847:
1828:
1772:
1747:
1723:
1698:
1674:
1641:
1614:
1579:
1479:
1444:
1417:
1392:
1311:
1270:
1246:
1203:
1184:
1118:
1066:
1049:
949:
922:
903:
826:
784:
759:
735:
702:
467:
421:
284:
230:
175:
published comments on beam damage at cryogenic temperatures sharing observations that:
1848:"Correlative cryo-electron microscopy reveals the structure of TNTs in neuronal cells"
1140:
570:
cryo-EM, an averaging method to determine protein structure from monodisperse samples.
394:, the median resolution achieved by X-ray crystallography (as of May 19, 2019) on the
2794:
2789:
2237:
2180:
2131:
2082:
2033:
1984:
1976:
1885:
1832:
1820:
1777:
1728:
1679:
1619:
1601:
1560:
1484:
1466:
1422:
1373:
1316:
1298:
1251:
1233:
1176:
1168:
1110:
989:
985:
954:
895:
830:
789:
740:
557:
471:
395:
167:(−195.79 °C or 77 K or −320 °F) were considered as cryogens. In 1980,
39:
2881:
1188:
907:
2744:
2676:
2264:
2227:
2219:
2170:
2162:
2121:
2113:
2072:
2064:
2023:
2015:
1966:
1961:. From Protein Sequence to Structure at Warp Speed: How Alphafold Impacts Biology.
1875:
1867:
1812:
1767:
1759:
1718:
1710:
1669:
1661:
1609:
1591:
1550:
1474:
1456:
1412:
1404:
1363:
1355:
1306:
1290:
1241:
1223:
1160:
1122:
1102:
1061:
1028:
981:
944:
934:
887:
816:
779:
771:
730:
722:
445:
technique with a scanning electron microscope's cold stage in a cryogenic chamber.
353:
304:
241:
186:
172:
112:
101:
88:. An aqueous sample solution is applied to a grid-mesh and plunge-frozen in liquid
58:
2799:
1228:
939:
626:
621:
205:, reported the first successful implementation of cryo-EM. McDowall and Dubochet
164:
104:
for macromolecular structure determination without the need for crystallization.
352:
In recognition of the impact cryo-EM has had on biochemistry, three scientists,
2754:
2368:
2268:
2068:
1871:
1555:
1530:
1340:
Proceedings of the
National Academy of Sciences of the United States of America
1294:
775:
340:(roughly 19 kDa in size) by utilising a rigidified imaging scaffold, and using
125:
77:
1971:
1954:
1816:
1763:
1699:"How cryo-electron microscopy and X-ray crystallography complement each other"
1665:
1596:
1461:
821:
726:
184:
However, these results were not reproducible and amendments were published in
2967:
2830:
2774:
2434:
1980:
1605:
1470:
1302:
1237:
1172:
899:
591:
357:
320:
234:
222:
206:
148:
116:
85:
2223:
1359:
1164:
344:
as modular binding domain between the scaffold and the protein-of-interest.
2891:
2855:
2749:
2739:
2414:
2363:
2241:
2184:
2166:
2135:
2086:
2037:
1988:
1889:
1824:
1781:
1732:
1683:
1623:
1564:
1488:
1426:
1377:
1320:
1255:
1180:
958:
793:
744:
671:
237:
1114:
993:
2835:
2769:
2759:
391:
296:
288:
1845:
2916:
2896:
2337:
2332:
2117:
2019:
891:
210:
160:
2277:
1408:
2784:
2439:
1714:
1106:
1033:
1008:
308:
81:
2886:
2352:
583:
399:
2200:"Single-particle cryo-EM-How did it get here and where will it go"
1580:"Challenges and opportunities in cryo-EM single-particle analysis"
1333:
2840:
2522:
2148:
1748:"Crystal structure of small protein crambin at 0.48 Å resolution"
553:
549:
316:
214:
152:
93:
1929:"Scientists uncover Omicron variant mysteries using microscopes"
2860:
341:
218:
191:
156:
89:
1269:
Herzik, Mark A.; Wu, Mengyu; Lander, Gabriel C. (2019-03-04).
1080:
587:
539:
448:
2050:
2845:
1953:
Bäuerlein, Felix J. B.; Baumeister, Wolfgang (2021-10-01).
1081:
Adrian M, Dubochet J, Lepault J, McDowall AW (March 1984).
655:
535:
337:
279:, Cambridge, UK) formed a consortium with engineers at the
2099:
1745:
1639:
757:
2002:
Nannenga BL, Shi D, Leslie AG, Gonen T (September 2014).
1531:"Revolutionary cryo-EM is taking over structural biology"
405:
336:
were able to create a clearer image of three variants of
1746:
Schmidt A, Teeter M, Weckert E, Lamzin VS (April 2011).
1442:
758:
Cheng Y, Grigorieff N, Penczek PA, Walz T (April 2015).
129:
also named cryo-EM as the "Method of the Year" in 2015.
502:
371:
2001:
760:"A primer to single-particle cryo-electron microscopy"
1794:
1050:"Vitrification of Pure Water for Electron Microscopy"
809:"Structural biology: How proteins got their close-up"
878:
Doerr A (January 2017). "Cryo-electron tomography".
1952:
1201:
501:The Danish National cryo-EM Facility also known as
427:
700:
1635:
1633:
923:"Ups and downs in early electron cryo-microscopy"
2965:
1047:
347:
701:Tivol WF, Briegel A, Jensen GJ (October 2008).
2707:Serial block-face scanning electron microscopy
2410:Detectors for transmission electron microscopy
1955:"Towards Visual Proteomics at High Resolution"
1642:"Single-particle cryo-EM at atomic resolution"
1630:
1268:
971:
920:
849:
847:
16:Form of transmission electron microscopy (TEM)
2293:
1390:
1009:"Cryo-transmission microscopy Fading hopes"
844:
303:). A third type of camera was developed by
2300:
2286:
2044:
1896:
1138:
460:Cryogenic transmission electron microscopy
449:Cryogenic transmission electron microscopy
420:cryo-TEM and cryo-ET were used to observe
2231:
2174:
2125:
2076:
2027:
1970:
1921:
1879:
1771:
1722:
1673:
1613:
1595:
1554:
1478:
1460:
1416:
1367:
1310:
1245:
1227:
1065:
1048:Dubochet J, McDowall AW (December 1981).
1032:
948:
938:
820:
783:
734:
703:"An improved cryogen for plunge freezing"
534:, method to determine the arrangement of
221:cooled to 77 K). The thin layer of
1696:
1528:
806:
507:
201:and Jacques Dubochet, scientists at the
57:
2307:
1577:
1006:
800:
548:, method to determine the structure of
301:University of California, San Francisco
80:technique applied on samples cooled to
2966:
1506:"Resolution - Proteopedia, life in 3D"
406:Correlative light cryo-TEM and cryo-ET
259:
2281:
2197:
1500:
1498:
1438:
1436:
1391:Smyth MS, Martin JH (February 2000).
1134:
1132:
1083:"Cryo-electron microscopy of viruses"
877:
412:Correlative light-electron microscopy
293:Lawrence Berkeley National Laboratory
225:was less than 1 μm thick and an
203:European Molecular Biology Laboratory
2946:
455:Transmission electron cryomicroscopy
372:Comparisons to X-ray crystallography
194:", than what was previously stated.
137:
35:Transmission electron cryomicroscopy
18:
921:Dubochet J, Knapek E (April 2018).
855:"The Nobel Prize in Chemistry 2017"
519:
277:MRC Laboratory of Molecular Biology
13:
1690:
1522:
1495:
1433:
1129:
1067:10.1111/j.1365-2818.1981.tb02483.x
92:or a mixture of liquid ethane and
14:
3000:
2343:Timeline of microscope technology
1697:Wang HW, Wang JW (January 2017).
1139:Kühlbrandt, Werner (2014-03-28).
2945:
2934:
2933:
647:
635:
606:
576:
560:, and inorganic compounds using
464:transmission electron microscopy
439:Scanning electron cryomicroscopy
434:Scanning electron cryomicroscopy
428:Scanning electron cryomicroscopy
307:at the Direct Electron company (
144:transmission electron microscopy
23:
2702:Precession electron diffraction
2248:
2191:
2142:
2093:
1995:
1946:
1839:
1788:
1739:
1584:Journal of Biological Chemistry
1571:
1449:Journal of Biological Chemistry
1384:
1327:
1262:
1195:
1074:
1007:Newmark P (30 September 1982).
484:Federal Institute of Technology
2974:Electron microscopy techniques
1578:Lyumkis, Dmitry (2019-03-29).
1041:
1000:
965:
914:
871:
751:
694:
281:Rutherford Appleton Laboratory
1:
687:
660:(scale bar represents 200 nm)
526:Cryogenic electron tomography
348:2017 Nobel Prize in Chemistry
70:Cryogenic electron microscopy
1959:Journal of Molecular Biology
1529:Callaway E (February 2020).
1229:10.1371/journal.pone.0123146
986:10.1016/0022-2836(80)90382-4
974:Journal of Molecular Biology
940:10.1371/journal.pbio.2005550
707:Microscopy and Microanalysis
443:scanning electron microscopy
323:generally have insufficient
7:
1141:"The Resolution Revolution"
807:Stoddart C (1 March 2022).
665:
32:It has been suggested that
10:
3005:
2687:Immune electron microscopy
2605:Annular dark-field imaging
2420:Everhart–Thornley detector
2269:10.1038/s41598-017-05824-w
2069:10.1021/acscentsci.8b00760
1872:10.1038/s41467-018-08178-7
1556:10.1038/d41586-020-00341-9
1295:10.1038/s41467-019-08991-8
776:10.1016/j.cell.2015.03.050
496:SARS-CoV-2 Omicron variant
477:
466:technique that is used in
452:
431:
424:(TNTs) in neuronal cells.
409:
375:
254:Vesicular-Stomatitis-Virus
132:
2929:
2874:
2841:Hitachi High-Technologies
2823:
2732:
2725:
2592:
2536:
2498:
2455:
2448:
2402:
2351:
2315:
1972:10.1016/j.jmb.2021.167187
1817:10.1038/s41586-020-2833-4
1764:10.1107/S1744309110052607
1666:10.1038/s41586-020-2829-0
1597:10.1074/jbc.rev118.005602
1462:10.1016/j.jbc.2021.100560
822:10.1146/knowable-022822-1
727:10.1017/S1431927608080781
266:direct electron detectors
142:In the 1960s, the use of
49:Proposed since July 2024.
2866:Thermo Fisher Scientific
2692:Geometric phase analysis
2580:Aberration-Corrected TEM
682:Electron tomography (ET)
677:Cryo bio-crystallography
568:Single particle analysis
532:Electron crystallography
513:Single particle analysis
366:Nobel Prize in Chemistry
109:Nobel Prize in Chemistry
2615:Charge contrast imaging
2425:Field electron emission
2224:10.1126/science.aat4346
2198:Cheng Y (August 2018).
1393:"x ray crystallography"
1360:10.1073/pnas.2305494120
1165:10.1126/science.1251652
2805:Thomas Eugene Everhart
2167:10.1002/anie.201811318
516:
488:University of Lausanne
313:
283:and scientists at the
182:
66:
2989:Scientific techniques
2810:Vernon Ellis Cosslett
2630:Dark-field microscopy
1852:Nature Communications
1275:Nature Communications
1054:Journal of Microscopy
654:Cryo-EM image of the
511:
378:X-ray crystallography
309:San Diego, California
270:
177:
98:X-ray crystallography
61:
2815:Vladimir K. Zworykin
2465:Correlative light EM
2374:Electron diffraction
562:electron diffraction
492:University of Geneva
422:tunnelling nanotubes
246:Semliki Forest virus
227:electron diffraction
42:into this article. (
2780:Manfred von Ardenne
2765:Gerasimos Danilatos
2672:Electron tomography
2667:Electron holography
2610:Cathodoluminescence
2389:Secondary electrons
2379:Electron scattering
2323:Electron microscopy
2309:Electron microscopy
2216:2018Sci...361..876C
2161:(50): 16313–16317.
2057:ACS Central Science
1864:2019NatCo..10..342S
1809:2020Natur.587..157Y
1658:2020Natur.587..152N
1547:2020Natur.578..201C
1397:Molecular Pathology
1352:2023PNAS..12005494C
1346:(37): e2305494120.
1287:2019NatCo..10.1032H
1220:2015PLoSO..1023146K
1157:2014Sci...343.1443K
1151:(6178): 1443–1444.
1099:1984Natur.308...32A
1025:1982Natur.299..386N
719:2008MiMic..14..375T
364:, were awarded the
260:Recent advancements
64:University of Leeds
62:Titan Krios at the
2902:Digital Micrograph
2508:Environmental SEM
2430:Field emission gun
2394:X-ray fluorescence
2257:Scientific Reports
2118:10.1038/nmeth.4178
2020:10.1038/nmeth.3043
892:10.1038/nmeth.4115
658:giant marine virus
517:
468:structural biology
285:Max Planck Society
231:structural biology
67:
2984:Protein structure
2961:
2960:
2925:
2924:
2795:Nestor J. Zaluzec
2790:Maximilian Haider
2588:
2587:
2210:(6405): 876–880.
2155:Angewandte Chemie
2063:(11): 1587–1592.
1803:(7832): 157–161.
1758:(Pt 4): 424–428.
1652:(7832): 152–156.
1590:(13): 5181–5197.
1409:10.1136/mp.53.1.8
1019:(5882): 386–387.
813:Knowable Magazine
615:
558:organic molecules
472:materials science
418:correlative light
396:Protein Data Bank
362:Richard Henderson
319:smaller than ~50
250:Bacteriophage CbK
233:with analysis of
199:Alasdair McDowall
138:Early development
121:Richard Henderson
56:
55:
51:
2996:
2949:
2948:
2937:
2936:
2745:Bodo von Borries
2730:
2729:
2490:Photoemission EM
2453:
2452:
2302:
2295:
2288:
2279:
2278:
2272:
2252:
2246:
2245:
2235:
2195:
2189:
2188:
2178:
2146:
2140:
2139:
2129:
2097:
2091:
2090:
2080:
2048:
2042:
2041:
2031:
1999:
1993:
1992:
1974:
1950:
1944:
1943:
1941:
1940:
1925:
1919:
1918:
1916:
1915:
1900:
1894:
1893:
1883:
1843:
1837:
1836:
1792:
1786:
1785:
1775:
1743:
1737:
1736:
1726:
1715:10.1002/pro.3022
1694:
1688:
1687:
1677:
1637:
1628:
1627:
1617:
1599:
1575:
1569:
1568:
1558:
1526:
1520:
1519:
1517:
1516:
1502:
1493:
1492:
1482:
1464:
1440:
1431:
1430:
1420:
1388:
1382:
1381:
1371:
1331:
1325:
1324:
1314:
1266:
1260:
1259:
1249:
1231:
1199:
1193:
1192:
1136:
1127:
1126:
1107:10.1038/308032a0
1078:
1072:
1071:
1069:
1045:
1039:
1038:
1036:
1034:10.1038/299386c0
1004:
998:
997:
969:
963:
962:
952:
942:
918:
912:
911:
875:
869:
868:
866:
865:
851:
842:
841:
839:
837:
824:
804:
798:
797:
787:
755:
749:
748:
738:
698:
651:
639:
617:
616:
600:
599:
580:
564:from 3D crystals
520:Advanced methods
462:(cryo-TEM) is a
354:Jacques Dubochet
305:Nguyen-Huu Xuong
242:T4 bacteriophage
173:Jacques Dubochet
113:Jacques Dubochet
102:NMR spectroscopy
47:
27:
26:
19:
3004:
3003:
2999:
2998:
2997:
2995:
2994:
2993:
2964:
2963:
2962:
2957:
2921:
2870:
2819:
2800:Ondrej Krivanek
2721:
2584:
2532:
2494:
2480:Liquid-Phase EM
2444:
2403:Instrumentation
2398:
2356:
2347:
2311:
2306:
2276:
2275:
2253:
2249:
2196:
2192:
2147:
2143:
2098:
2094:
2049:
2045:
2000:
1996:
1951:
1947:
1938:
1936:
1927:
1926:
1922:
1913:
1911:
1902:
1901:
1897:
1844:
1840:
1793:
1789:
1744:
1740:
1703:Protein Science
1695:
1691:
1638:
1631:
1576:
1572:
1527:
1523:
1514:
1512:
1510:proteopedia.org
1504:
1503:
1496:
1441:
1434:
1389:
1385:
1332:
1328:
1267:
1263:
1214:(4): e0123146.
1200:
1196:
1137:
1130:
1093:(5954): 32–36.
1079:
1075:
1046:
1042:
1005:
1001:
970:
966:
933:(4): e2005550.
919:
915:
876:
872:
863:
861:
853:
852:
845:
835:
833:
805:
801:
756:
752:
699:
695:
690:
668:
661:
659:
652:
643:
640:
631:
627:Pichia pastoris
622:alcohol oxidase
618:
607:
602:
601:× magnification
597:
595:
581:
522:
480:
457:
451:
441:(cryoSEM) is a
436:
430:
414:
408:
380:
374:
350:
262:
165:liquid nitrogen
159:or −452.2
140:
135:
111:was awarded to
52:
28:
24:
17:
12:
11:
5:
3002:
2992:
2991:
2986:
2981:
2976:
2959:
2958:
2956:
2955:
2943:
2930:
2927:
2926:
2923:
2922:
2920:
2919:
2914:
2909:
2907:Direct methods
2904:
2899:
2894:
2889:
2884:
2878:
2876:
2872:
2871:
2869:
2868:
2863:
2858:
2853:
2848:
2843:
2838:
2833:
2827:
2825:
2821:
2820:
2818:
2817:
2812:
2807:
2802:
2797:
2792:
2787:
2782:
2777:
2772:
2767:
2762:
2757:
2755:Ernst G. Bauer
2752:
2747:
2742:
2736:
2734:
2727:
2723:
2722:
2720:
2719:
2714:
2709:
2704:
2699:
2694:
2689:
2684:
2679:
2674:
2669:
2664:
2659:
2654:
2649:
2648:
2647:
2637:
2632:
2627:
2622:
2617:
2612:
2607:
2602:
2596:
2594:
2590:
2589:
2586:
2585:
2583:
2582:
2577:
2576:
2575:
2565:
2560:
2555:
2554:
2553:
2542:
2540:
2534:
2533:
2531:
2530:
2525:
2520:
2515:
2510:
2504:
2502:
2496:
2495:
2493:
2492:
2487:
2482:
2477:
2472:
2467:
2461:
2459:
2450:
2446:
2445:
2443:
2442:
2437:
2432:
2427:
2422:
2417:
2412:
2406:
2404:
2400:
2399:
2397:
2396:
2391:
2386:
2381:
2376:
2371:
2369:Bremsstrahlung
2366:
2360:
2358:
2349:
2348:
2346:
2345:
2340:
2335:
2330:
2325:
2319:
2317:
2313:
2312:
2305:
2304:
2297:
2290:
2282:
2274:
2273:
2247:
2190:
2141:
2112:(4): 399–402.
2106:Nature Methods
2092:
2043:
2014:(9): 927–930.
2008:Nature Methods
1994:
1965:(20): 167187.
1945:
1920:
1895:
1838:
1787:
1738:
1689:
1629:
1570:
1521:
1494:
1432:
1383:
1326:
1261:
1194:
1128:
1073:
1040:
999:
980:(2): 147–161.
964:
913:
880:Nature Methods
870:
859:NobelPrize.org
843:
799:
770:(3): 438–449.
750:
713:(5): 375–379.
692:
691:
689:
686:
685:
684:
679:
674:
667:
664:
663:
662:
653:
646:
644:
641:
634:
632:
619:
605:
603:
582:
575:
572:
571:
565:
543:
529:
521:
518:
479:
476:
453:Main article:
450:
447:
432:Main article:
429:
426:
410:Main article:
407:
404:
376:Main article:
373:
370:
349:
346:
261:
258:
139:
136:
134:
131:
126:Nature Methods
78:cryomicroscopy
54:
53:
31:
29:
22:
15:
9:
6:
4:
3:
2:
3001:
2990:
2987:
2985:
2982:
2980:
2977:
2975:
2972:
2971:
2969:
2954:
2953:
2944:
2942:
2941:
2932:
2931:
2928:
2918:
2915:
2913:
2910:
2908:
2905:
2903:
2900:
2898:
2895:
2893:
2890:
2888:
2885:
2883:
2880:
2879:
2877:
2873:
2867:
2864:
2862:
2859:
2857:
2854:
2852:
2849:
2847:
2844:
2842:
2839:
2837:
2834:
2832:
2831:Carl Zeiss AG
2829:
2828:
2826:
2824:Manufacturers
2822:
2816:
2813:
2811:
2808:
2806:
2803:
2801:
2798:
2796:
2793:
2791:
2788:
2786:
2783:
2781:
2778:
2776:
2775:James Hillier
2773:
2771:
2768:
2766:
2763:
2761:
2758:
2756:
2753:
2751:
2748:
2746:
2743:
2741:
2738:
2737:
2735:
2731:
2728:
2724:
2718:
2715:
2713:
2710:
2708:
2705:
2703:
2700:
2698:
2695:
2693:
2690:
2688:
2685:
2683:
2680:
2678:
2675:
2673:
2670:
2668:
2665:
2663:
2660:
2658:
2655:
2653:
2650:
2646:
2643:
2642:
2641:
2638:
2636:
2633:
2631:
2628:
2626:
2623:
2621:
2618:
2616:
2613:
2611:
2608:
2606:
2603:
2601:
2598:
2597:
2595:
2591:
2581:
2578:
2574:
2571:
2570:
2569:
2566:
2564:
2561:
2559:
2556:
2552:
2549:
2548:
2547:
2544:
2543:
2541:
2539:
2535:
2529:
2528:Ultrafast SEM
2526:
2524:
2521:
2519:
2516:
2514:
2511:
2509:
2506:
2505:
2503:
2501:
2497:
2491:
2488:
2486:
2485:Low-energy EM
2483:
2481:
2478:
2476:
2473:
2471:
2468:
2466:
2463:
2462:
2460:
2458:
2454:
2451:
2447:
2441:
2438:
2436:
2435:Magnetic lens
2433:
2431:
2428:
2426:
2423:
2421:
2418:
2416:
2413:
2411:
2408:
2407:
2405:
2401:
2395:
2392:
2390:
2387:
2385:
2384:Kikuchi lines
2382:
2380:
2377:
2375:
2372:
2370:
2367:
2365:
2362:
2361:
2359:
2354:
2350:
2344:
2341:
2339:
2336:
2334:
2331:
2329:
2326:
2324:
2321:
2320:
2318:
2314:
2310:
2303:
2298:
2296:
2291:
2289:
2284:
2283:
2280:
2270:
2266:
2262:
2258:
2251:
2243:
2239:
2234:
2229:
2225:
2221:
2217:
2213:
2209:
2205:
2201:
2194:
2186:
2182:
2177:
2172:
2168:
2164:
2160:
2156:
2152:
2145:
2137:
2133:
2128:
2123:
2119:
2115:
2111:
2107:
2103:
2096:
2088:
2084:
2079:
2074:
2070:
2066:
2062:
2058:
2054:
2047:
2039:
2035:
2030:
2025:
2021:
2017:
2013:
2009:
2005:
1998:
1990:
1986:
1982:
1978:
1973:
1968:
1964:
1960:
1956:
1949:
1934:
1930:
1924:
1909:
1905:
1899:
1891:
1887:
1882:
1877:
1873:
1869:
1865:
1861:
1857:
1853:
1849:
1842:
1834:
1830:
1826:
1822:
1818:
1814:
1810:
1806:
1802:
1798:
1791:
1783:
1779:
1774:
1769:
1765:
1761:
1757:
1753:
1749:
1742:
1734:
1730:
1725:
1720:
1716:
1712:
1708:
1704:
1700:
1693:
1685:
1681:
1676:
1671:
1667:
1663:
1659:
1655:
1651:
1647:
1643:
1636:
1634:
1625:
1621:
1616:
1611:
1607:
1603:
1598:
1593:
1589:
1585:
1581:
1574:
1566:
1562:
1557:
1552:
1548:
1544:
1541:(7794): 201.
1540:
1536:
1532:
1525:
1511:
1507:
1501:
1499:
1490:
1486:
1481:
1476:
1472:
1468:
1463:
1458:
1454:
1450:
1446:
1439:
1437:
1428:
1424:
1419:
1414:
1410:
1406:
1402:
1398:
1394:
1387:
1379:
1375:
1370:
1365:
1361:
1357:
1353:
1349:
1345:
1341:
1337:
1330:
1322:
1318:
1313:
1308:
1304:
1300:
1296:
1292:
1288:
1284:
1280:
1276:
1272:
1265:
1257:
1253:
1248:
1243:
1239:
1235:
1230:
1225:
1221:
1217:
1213:
1209:
1205:
1198:
1190:
1186:
1182:
1178:
1174:
1170:
1166:
1162:
1158:
1154:
1150:
1146:
1142:
1135:
1133:
1124:
1120:
1116:
1112:
1108:
1104:
1100:
1096:
1092:
1088:
1084:
1077:
1068:
1063:
1059:
1055:
1051:
1044:
1035:
1030:
1026:
1022:
1018:
1014:
1010:
1003:
995:
991:
987:
983:
979:
975:
968:
960:
956:
951:
946:
941:
936:
932:
928:
924:
917:
909:
905:
901:
897:
893:
889:
885:
881:
874:
860:
856:
850:
848:
832:
828:
823:
818:
814:
810:
803:
795:
791:
786:
781:
777:
773:
769:
765:
761:
754:
746:
742:
737:
732:
728:
724:
720:
716:
712:
708:
704:
697:
693:
683:
680:
678:
675:
673:
670:
669:
657:
650:
645:
638:
633:
629:
628:
623:
620:Structure of
604:
593:
592:amorphous ice
590:suspended in
589:
585:
579:
574:
573:
569:
566:
563:
559:
555:
551:
547:
544:
541:
537:
533:
530:
527:
524:
523:
514:
510:
506:
504:
499:
497:
493:
489:
485:
475:
473:
469:
465:
461:
456:
446:
444:
440:
435:
425:
423:
419:
413:
403:
401:
397:
393:
390:According to
388:
384:
379:
369:
367:
363:
359:
358:Joachim Frank
355:
345:
343:
339:
335:
331:
326:
322:
318:
312:
310:
306:
302:
298:
294:
290:
286:
282:
278:
274:
269:
267:
257:
255:
251:
247:
243:
239:
236:
232:
228:
224:
223:amorphous ice
220:
216:
212:
208:
204:
200:
195:
193:
189:
188:
181:
176:
174:
170:
166:
162:
158:
154:
150:
149:liquid helium
145:
130:
128:
127:
122:
118:
117:Joachim Frank
114:
110:
107:In 2017, the
105:
103:
99:
95:
91:
87:
83:
79:
75:
71:
65:
60:
50:
45:
41:
37:
36:
30:
21:
20:
2979:Cell biology
2950:
2938:
2892:EM Data Bank
2856:Nion Company
2750:Dennis Gabor
2740:Albert Crewe
2624:
2518:Confocal SEM
2469:
2415:Electron gun
2364:Auger effect
2260:
2256:
2250:
2207:
2203:
2193:
2158:
2154:
2144:
2109:
2105:
2095:
2060:
2056:
2046:
2011:
2007:
1997:
1962:
1958:
1948:
1937:. Retrieved
1935:. 2021-12-30
1933:swissinfo.ch
1932:
1923:
1912:. Retrieved
1910:. 2021-11-30
1907:
1898:
1855:
1851:
1841:
1800:
1796:
1790:
1755:
1751:
1741:
1709:(1): 32–39.
1706:
1702:
1692:
1649:
1645:
1587:
1583:
1573:
1538:
1534:
1524:
1513:. Retrieved
1509:
1452:
1448:
1400:
1396:
1386:
1343:
1339:
1329:
1278:
1274:
1264:
1211:
1207:
1197:
1148:
1144:
1090:
1086:
1076:
1057:
1053:
1043:
1016:
1012:
1002:
977:
973:
967:
930:
927:PLOS Biology
926:
916:
883:
879:
873:
862:. Retrieved
858:
834:. Retrieved
812:
802:
767:
763:
753:
710:
706:
696:
672:Cryofixation
625:
500:
481:
458:
437:
415:
389:
385:
381:
351:
314:
271:
263:
196:
185:
183:
180:temperature.
178:
169:Erwin Knapek
141:
124:
106:
86:vitreous ice
73:
69:
68:
48:
33:
2836:FEI Company
2770:Harald Rose
2760:Ernst Ruska
2449:Microscopes
2357:with matter
2355:interaction
1403:(1): 8–14.
1281:(1): 1032.
542:using a TEM
392:Proteopedia
297:David Agard
151:(−269
2968:Categories
2917:Multislice
2733:Developers
2593:Techniques
2338:Microscope
2333:Micrograph
1939:2022-04-30
1914:2022-04-30
1858:(1): 342.
1515:2020-10-27
1455:: 100560.
1060:(3): 3–4.
864:2022-09-30
688:References
630:by Cryo-EM
238:adenovirus
217:or liquid
155:or 4
2785:Max Knoll
2440:Stigmator
1981:0022-2836
1833:224823207
1606:0021-9258
1471:0021-9258
1303:2041-1723
1238:1932-6203
1173:0036-8075
900:1548-7091
886:(1): 34.
831:247206999
586:image of
416:In 2019,
332:group at
273:Henderson
235:vitrified
207:vitrified
197:In 1981,
82:cryogenic
2940:Category
2887:CrysTBox
2875:Software
2546:Cryo-TEM
2353:Electron
2263:: 5484.
2242:30166484
2185:30325568
2136:28192420
2087:30555912
2038:25086503
1989:34384780
1908:unige.ch
1890:30664666
1825:33087927
1782:21505232
1733:27543495
1684:33087931
1624:30804214
1565:32047310
1489:33744287
1427:10884915
1378:37669364
1369:10500258
1321:30833564
1256:25894612
1208:PLOS ONE
1189:35524447
1181:24675944
959:29672565
908:27162203
836:25 March
794:25910204
745:18793481
666:See also
554:peptides
550:proteins
515:workflow
490:and the
398:is 2.05
317:Proteins
240:type 2,
213:(liquid
2952:Commons
2600:4D STEM
2573:4D STEM
2551:Cryo-ET
2523:SEM-XRF
2513:CryoSEM
2470:Cryo-EM
2328:History
2233:6460916
2212:Bibcode
2204:Science
2176:6468266
2127:5376236
2078:6276044
2029:4149488
1881:6341166
1860:Bibcode
1805:Bibcode
1773:3080141
1724:5192981
1675:7611073
1654:Bibcode
1615:6442032
1543:Bibcode
1480:8050867
1418:1186895
1348:Bibcode
1312:6399227
1283:Bibcode
1247:4403875
1216:Bibcode
1153:Bibcode
1145:Science
1123:4319199
1115:6322001
1095:Bibcode
1021:Bibcode
994:7441748
950:5929567
785:4409659
736:3058946
715:Bibcode
584:Cryo-EM
546:MicroED
478:Centers
342:DARPins
215:propane
211:cryogen
133:History
94:propane
76:) is a
74:cryo-EM
44:Discuss
2897:EMsoft
2882:CASINO
2861:TESCAN
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