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Direct Observation of Wet Biological Samples by Graphene Liquid Cell Transmission Electron Microscopy

Journal Article · · Nano Letters
 [1];  [2];  [3];  [1];  [4];  [5];  [6];  [1]
  1. Harvard Univ., Cambridge, MA (United States)
  2. Ulsan National Institute of Science and Technology, Ulsan (Korea, Republic of)
  3. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
  4. Brandeis Univ., Waltham, MA (United States)
  5. Hanyang Univ., Seoul (Korea, Republic of)
  6. Amore-Pacific Co. R&D Center, Yongin (Korea, Republic of)
Recent development of liquid phase transmission electron microscopy (TEM) enables the study of specimens in wet ambient conditions within a liquid cell; however, direct structural observation of biological samples in their native solution using TEM is challenging since low-mass biomaterials embedded in a thick liquid layer of the host cell demonstrate low contrast. Furthermore, the integrity of delicate wet samples is easily compromised during typical sample preparation and TEM imaging. To overcome these limitations, we introduce a graphene liquid cell (GLC) using multilayer graphene sheets to reliably encapsulate and preserve biological samples in a liquid for TEM observation. We achieve nanometer scale spatial resolution with high contrast using low-dose TEM at room temperature, and we use the GLC to directly observe the structure of influenza viruses in their native buffer solution at room temperature. The GLC is further extended to investigate whole cells in wet conditions using TEM. We also demonstrate the potential of the GLC for correlative studies by TEM and fluorescence light microscopy imaging.
Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22), Scientific User Facilities Division (SC-22.3)
Grant/Contract Number:
AC02-05CH11231
OSTI ID:
1670114
Journal Information:
Nano Letters, Journal Name: Nano Letters Journal Issue: 7 Vol. 15; ISSN 1530-6984
Publisher:
American Chemical SocietyCopyright Statement
Country of Publication:
United States
Language:
English

References (31)

High-Resolution Electron Microscopy and Spectroscopy of Ferritin in Biocompatible Graphene Liquid Cells and Graphene Sandwiches journal February 2014
Chemical Imaging at Atomic Resolution as a Technique To Refine the Local Structure of Nanocrystals journal January 2011
Imaging Protein Structure in Water at 2.7 nm Resolution by Transmission Electron Microscopy journal February 2012
Breaking the Diffraction Barrier: Super-Resolution Imaging of Cells journal December 2010
Total internal reflection fluorescence microscopy: technical innovations and novel applications journal February 2005
Towards atomic resolution structural determination by single-particle cryo-electron microscopy journal April 2008
Visualizing cells at the nanoscale journal February 2009
Single-particle electron cryo-microscopy: towards atomic resolution journal November 2000
Three-Dimensional Scanning Transmission Electron Microscopy of Biological Specimens journal January 2010
In Situ Electron Energy-Loss Spectroscopy in Liquids journal May 2013
Dynamics of Soft Nanomaterials Captured by Transmission Electron Microscopy in Liquid Water journal January 2014
3D Motion of DNA-Au Nanoconjugates in Graphene Liquid Cell Electron Microscopy journal August 2013
Electrons, Photons, and Force: Quantitative Single-Molecule Measurements from Physics to Biology journal January 2011
Two microscopes are better than one journal December 2012
Sub-ångstrom resolution using aberration corrected electron optics journal August 2002
Collective cell guidance by cooperative intercellular forces journal May 2011
Fast, three-dimensional super-resolution imaging of live cells journal May 2011
Electron counting and beam-induced motion correction enable near-atomic-resolution single-particle cryo-EM journal May 2013
Fluorescence microscopy journal November 2005
Electron microscopy of specimens in liquid journal October 2011
Fluorescent probes for super-resolution imaging in living cells journal November 2008
Advances in tomography: probing the molecular architecture of cells journal October 2012
Visualizing viral assemblies in a nanoscale biosphere journal January 2013
Fluorescence micro(spectro)scopy as a tool to study catalytic materials in action journal January 2010
A direct transfer of layer-area graphene journal March 2010
Electron microscopy of whole cells in liquid with nanometer resolution journal January 2009
Direct observation of stick-slip movements of water nanodroplets induced by an electron beam journal April 2012
Cryo-EM-the first thirty years: CRYO-ELECTRON MICROSCOPY journal November 2011
High-Resolution EM of Colloidal Nanocrystal Growth Using Graphene Liquid Cells journal April 2012
Electron Tomography in the (S)TEM: From Nanoscale Morphological Analysis to 3D Atomic Imaging journal August 2012
Aberration-corrected scanning transmission electron microscopy for atomic-resolution studies of functional oxides journal March 2014

Cited By (27)

Quantitative Analysis of Calcium Phosphate Nanocluster Growth Using Time-of-Flight Medium-Energy-Ion-Scattering Spectroscopy journal August 2018
Self-assembling peptides imaged by correlated liquid cell transmission electron microscopy and MALDI-imaging mass spectrometry journal October 2019
X-ray ptychographic and fluorescence microscopy of frozen-hydrated cells using continuous scanning journal March 2017
Correlative cellular ptychography with functionalized nanoparticles at the Fe L-edge journal July 2017
High-resolution imaging of living mammalian cells bound by nanobeads-connected antibodies in a medium using scanning electron-assisted dielectric microscopy journal February 2017
Graphene Liquid Cells Assembled through Loop‐Assisted Transfer Method and Located with Correlated Light‐Electron Microscopy journal February 2020
Liquid-Phase Transmission Electron Microscopy for Studying Colloidal Inorganic Nanoparticles journal November 2017
State-of-the-Art and Future Prospects for Atomically Thin Membranes from 2D Materials journal August 2018
In Situ Electron Microscopy of Poly(ethylene glycol) Crystals Grown in Thin Ionic Liquids Films journal January 2020
Advances in Graphene‐Based Liquid Cell Electron Microscopy: Working Principles, Opportunities, and Challenges journal January 2019
Initial growth dynamics of 10 nm nanobubbles in the graphene liquid cell journal December 2018
An Open-Cell Environmental Transmission Electron Microscopy Technique for In Situ Characterization of Samples in Aqueous Liquid Solutions journal January 2020
Universal shape and pressure inside bubbles appearing in van der Waals heterostructures journal August 2016
Resolution and aberration correction in liquid cell transmission electron microscopy journal December 2018
Ultra-large suspended graphene as a highly elastic membrane for capacitive pressure sensors journal January 2016
Bio-camouflage of anatase nanoparticles explored by in situ high-resolution electron microscopy journal January 2017
Spectromicroscopic observation of a live single cell in a biocompatible liquid-enclosing graphene system journal January 2018
Monitoring the dynamics of cell-derived extracellular vesicles at the nanoscale by liquid-cell transmission electron microscopy journal January 2018
Linking nanomaterial properties to biological outcomes: analytical chemistry challenges in nanotoxicology for the next decade journal January 2018
Rational design and observation of the tight interface between graphene and ligand protected nanocrystals journal January 2019
Investigation of the magnetosome biomineralization in magnetotactic bacteria using graphene liquid cell – transmission electron microscopy journal January 2019
Electrocoiling-guided printing of multiscale architectures at single-wavelength resolution journal January 2019
On the structure and chemistry of iron oxide cores in human heart and human spleen ferritins using graphene liquid cell electron microscopy journal January 2019
Opportunities and challenges in liquid cell electron microscopy journal December 2015
Particle analogs of electrons in colloidal crystals journal June 2019
Water without windows: Evaluating the performance of open cell transmission electron microscopy under saturated water vapor conditions, and assessing its potential for microscopy of hydrated biological specimens journal November 2017
Resolution and aberration correction in liquid cell transmission electron microscopy collection January 2018

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