Skip to main content
    • Aa
    • Aa
  • Get access
    Check if you have access via personal or institutional login
  • Cited by 22
  • Cited by
    This article has been cited by the following publications. This list is generated based on data provided by CrossRef.

    Russo, Christopher J and Passmore, Lori A 2016. Progress towards an optimal specimen support for electron cryomicroscopy. Current Opinion in Structural Biology, Vol. 37, p. 81.

    Russo, Christopher J. and Passmore, Lori A. 2016. Ultrastable gold substrates: Properties of a support for high-resolution electron cryomicroscopy of biological specimens. Journal of Structural Biology, Vol. 193, Issue. 1, p. 33.

    Thompson, Rebecca F. Walker, Matt Siebert, C. Alistair Muench, Stephen P. and Ranson, Neil A. 2016. An introduction to sample preparation and imaging by cryo-electron microscopy for structural biology. Methods, Vol. 100, p. 3.

    Belnap, David M. 2015. Current Protocols in Protein Science.

    Cheng, Yifan Grigorieff, Nikolaus Penczek, Pawel A. and Walz, Thomas 2015. A Primer to Single-Particle Cryo-Electron Microscopy. Cell, Vol. 161, Issue. 3, p. 438.

    Kelly, Deborah F. 2015. Improving Our Vision of Nanobiology. Microscopy and Microanalysis, Vol. 21, Issue. S3, p. 1383.

    Meyerson, Joel R. Rao, Prashant Kumar, Janesh Chittori, Sagar Banerjee, Soojay Pierson, Jason Mayer, Mark L. and Subramaniam, Sriram 2014. Self-assembled monolayers improve protein distribution on holey carbon cryo-EM supports. Scientific Reports, Vol. 4, p. 7084.

    Russo, C. J. and Passmore, L. A. 2014. Ultrastable gold substrates for electron cryomicroscopy. Science, Vol. 346, Issue. 6215, p. 1377.

    Gilmore, Brian Tanner, Justin McKell, Allison Boudreaux, Crystal Dukes, Madeline McDonald, Sarah and Kelly, Deborah 2013. Molecular Surveillance of Viral Processes Using Silicon Nitride Membranes. Micromachines, Vol. 4, Issue. 1, p. 90.

    Karimi Nejadasl, Fatemeh Karuppasamy, Manikandan Newman, Emily R. McGeehan, John E. and Ravelli, Raimond B. G. 2013. Non-rigid image registration to reduce beam-induced blurring of cryo-electron microscopy images. Journal of Synchrotron Radiation, Vol. 20, Issue. 1, p. 58.

    Liu, Ying Meng, Xing and Liu, Zheng 2013. Deformed grids for single-particle cryo-electron microscopy of specimens exhibiting a preferred orientation. Journal of Structural Biology, Vol. 182, Issue. 3, p. 255.

    Sader, Kasim Stopps, Martyn Calder, Lesley J. and Rosenthal, Peter B. 2013. Cryomicroscopy of radiation sensitive specimens on unmodified graphene sheets: Reduction of electron-optical effects of charging. Journal of Structural Biology, Vol. 183, Issue. 3, p. 531.

    Berriman, John A. and Rosenthal, Peter B. 2012. Paraxial charge compensator for electron cryomicroscopy. Ultramicroscopy, Vol. 116, p. 106.

    Brilot, Axel F. Chen, James Z. Cheng, Anchi Pan, Junhua Harrison, Stephen C. Potter, Clinton S. Carragher, Bridget Henderson, Richard and Grigorieff, Nikolaus 2012. Beam-induced motion of vitrified specimen on holey carbon film. Journal of Structural Biology, Vol. 177, Issue. 3, p. 630.

    Gallyamov, Marat O. 2011. Scanning Force Microscopy as Applied to Conformational Studies in Macromolecular Research. Macromolecular Rapid Communications, Vol. 32, Issue. 16, p. 1210.

    Glaeser, R.M. McMullan, G. Faruqi, A.R. and Henderson, R. 2011. Images of paraffin monolayer crystals with perfect contrast: Minimization of beam-induced specimen motion. Ultramicroscopy, Vol. 111, Issue. 2, p. 90.

    Glaeser, Robert M. and Hall, Richard J. 2011. Reaching the Information Limit in Cryo-EM of Biological Macromolecules: Experimental Aspects. Biophysical Journal, Vol. 100, Issue. 10, p. 2331.

    Grigorieff, Nikolaus and Harrison, Stephen C 2011. Near-atomic resolution reconstructions of icosahedral viruses from electron cryo-microscopy. Current Opinion in Structural Biology, Vol. 21, Issue. 2, p. 265.

    Massover, William H. 2011. New and unconventional approaches for advancing resolution in biological transmission electron microscopy by improving macromolecular specimen preparation and preservation. Micron, Vol. 42, Issue. 2, p. 141.

    Orlova, E. V. and Saibil, H. R. 2011. Structural Analysis of Macromolecular Assemblies by Electron Microscopy. Chemical Reviews, Vol. 111, Issue. 12, p. 7710.


Cryomesh™: A New Substrate for Cryo-Electron Microscopy

  • Craig Yoshioka (a1), Bridget Carragher (a1) and Clinton S. Potter (a1)
  • DOI:
  • Published online: 01 January 2010

Here we evaluate a new grid substrate developed by ProtoChips Inc. (Raleigh, NC) for cryo-transmission electron microscopy. The new grids are fabricated from doped silicon carbide using processes adapted from the semiconductor industry. A major motivating purpose in the development of these grids was to increase the low-temperature conductivity of the substrate, a characteristic that is thought to affect the appearance of beam-induced movement (BIM) in transmission electron microscope (TEM) images of biological specimens. BIM degrades the quality of data and is especially severe when frozen biological specimens are tilted in the microscope. Our results show that this new substrate does indeed have a significant impact on reducing the appearance and severity of beam-induced movement in TEM images of tilted cryo-preserved samples. Furthermore, while we have not been able to ascertain the exact causes underlying the BIM phenomenon, we have evidence that the rigidity and flatness of these grids may play a major role in its reduction. This improvement in the reliability of imaging at tilt has a significant impact on using data collection methods such as random conical tilt or orthogonal tilt reconstruction with cryo-preserved samples. Reduction in BIM also has the potential for improving the resolution of three-dimensional cryo-reconstructions in general.

Corresponding author
Corresponding author. E-mail:
Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

F.P. Booy & J.B. Pawley (1993). Cryo-crinkling: What happens to carbon films on copper grids at low temperature. Ultramicroscopy 48, 273280.

B. Bottcher (1995). Electron cryo-microscopy of graphite in amorphous ice. Ultramicroscopy 58, 417424.

J. Brink , M.B. Sherman , J. Berriman & W. Chiu (1998). Evaluation of charging on macromolecules in electron cryomicroscopy. Ultramicroscopy 72, 4152.

J.Z. Chen , C. Sachse , C. Xu , T. Mielke , C.M. Spahn & N. Grigorieff (2008). A dose-rate effect in single-particle electron microscopy. J Struct Biol 161, 92100.

K. Downing , H. Sui & M. Auer (2007). Electron tomography: A 3D view of the subcellular world. Anal Chem 79, 79497957.

J. Dubochet & J. Lepault (1984). Cryo-electron microscopy of vitrified water. J Phys Colloques 45, 8494.

R.M. Glaeser (1985). Electron crystallography of biological macromolecules. Ann Rev Phys Chem 36, 243275.

R.M. Glaeser (2008). Retrospective: Radiation damage and its associated information limitations. J Struct Biol 163, 271276.

N. Gyobu , K. Tani , Y. Hiroaki , A. Kamegawa , K. Mitsuoka & Y. Fujiyoshi (2004). Improved specimen preparation for cryo-electron microscopy using a symmetric carbon sandwich technique. J Struct Biol 146, 325333.

R. Henderson (1992). Image contrast in high-resolution electron microscopy of biological macromolecules: TMV in ice. Ultramicroscopy 46, 118.

R. Henderson & R.M. Glaeser (1985). Quantitative analysis of image contrast in electron micrographs of beam-sensitive crystals. Ultramicroscopy 16, 139150.

G.C. Lander , R. Khayat , R. Li , P.E. Prevelige , C.S. Potter , B. Carragher & J.E. Johnson (2009). The P22 tail machine at subnanometer resolution reveals the architecture of an infection conduit. Structure 17, 789799.

A.E. Leschziner & E. Nogales (2006). The orthogonal tilt reconstruction method: An approach to generating single-class volumes with no missing cone for ab initio reconstruction of asymmetric particles. J Struct Biol 153, 284299.

M. Radermacher (1988). Three-dimensional reconstruction of single particles from random and nonrandom tilt series. J Elec Microsc Tech 9, 359394.

D. Rhinow & W. Kühlbrandt (2008). Electron cryo-microscopy of biological specimens on conductive titanium-silicon metal glass films. Ultramicroscopy 108, 698705.

S.M. Stagg , G.C. Lander , J. Quispe , N.R. Voss , A. Cheng , H. Bradlow , S. Bradlow , B. Carragher & C.S. Potter (2008). A test-bed for optimizing high-resolution single particle reconstructions. J Struct Biol 163, 2939.

C. Suloway , J. Pulokas , D. Fellmann , A. Cheng , F. Guerra , J. Quispe , S. Stagg , C.S. Potter & B. Carragher (2005). Automated molecular microscopy: The new Leginon system. J Struct Biol 151, 4160.

J. Vonck (2000). Parameters affecting specimen flatness of two-dimensional crystals for electron crystallography. Ultramicroscopy 85, 123129.

C. Yoshioka , J. Pulokas , D. Fellmann , C.S. Potter , R.A. Milligan & B. Carragher (2007). Automation of random conical tilt and orthogonal tilt data collection using feature-based correlation. J Struct Biol 159, 335346.

Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Microscopy and Microanalysis
  • ISSN: 1431-9276
  • EISSN: 1435-8115
  • URL: /core/journals/microscopy-and-microanalysis
Please enter your name
Please enter a valid email address
Who would you like to send this to? *