skip to main content
DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: A novel low energy electron microscope for DNA sequencing and surface analysis

Abstract

Monochromatic, aberration-corrected, dual-beam low energy electron microscopy (MAD-LEEM) is a novel technique that is directed towards imaging nanostructures and surfaces with sub-nanometer resolution. The technique combines a monochromator, a mirror aberration corrector, an energy filter, and dual beam illumination in a single instrument. The monochromator reduces the energy spread of the illuminating electron beam, which significantly improves spectroscopic and spatial resolution. Simulation results predict that the novel aberration corrector design will eliminate the second rank chromatic and third and fifth order spherical aberrations, thereby improving the resolution into the sub-nanometer regime at landing energies as low as one hundred electron-Volts. The energy filter produces a beam that can extract detailed information about the chemical composition and local electronic states of non-periodic objects such as nanoparticles, interfaces, defects, and macromolecules. The dual flood illumination eliminates charging effects that are generated when a conventional LEEM is used to image insulating specimens. A potential application for MAD-LEEM is in DNA sequencing, which requires high resolution to distinguish the individual bases and high speed to reduce the cost. The MAD-LEEM approach images the DNA with low electron impact energies, which provides nucleobase contrast mechanisms without organometallic labels. Furthermore, the micron-size field of view whenmore » combined with imaging on the fly provides long read lengths, thereby reducing the demand on assembling the sequence. Finally, experimental results from bulk specimens with immobilized single-base oligonucleotides demonstrate that base specific contrast is available with reflected, photo-emitted, and Auger electrons. Image contrast simulations of model rectangular features mimicking the individual nucleotides in a DNA strand have been developed to translate measurements of contrast on bulk DNA to the detectability of individual DNA bases in a sequence.« less

Authors:
 [1];  [1];  [2];  [3];  [4];  [2]
  1. Electron Optica Inc., Palo Alto, CA (United States)
  2. Stanford Univ. School of Medicine, Palo Alto, CA (United States)
  3. Electron Optica Inc., Palo Alto, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
  4. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES)
OSTI Identifier:
1257846
Grant/Contract Number:  
AC02-05CH11231; R43HG006303
Resource Type:
Accepted Manuscript
Journal Name:
Ultramicroscopy
Additional Journal Information:
Journal Volume: 145; Journal ID: ISSN 0304-3991
Publisher:
Elsevier
Country of Publication:
United States
Language:
English
Subject:
47 OTHER INSTRUMENTATION; Low energy electron microscopy; Monochromator; Aberration correction; Dual beam illumination; Energy filtering; DNA Sequencing; Contrast

Citation Formats

Mankos, M., Shadman, K., Persson, H. H. J., N’Diaye, A. T., Schmid, A. K., and Davis, R. W.. A novel low energy electron microscope for DNA sequencing and surface analysis. United States: N. p., 2014. Web. https://doi.org/10.1016/j.ultramic.2014.01.007.
Mankos, M., Shadman, K., Persson, H. H. J., N’Diaye, A. T., Schmid, A. K., & Davis, R. W.. A novel low energy electron microscope for DNA sequencing and surface analysis. United States. https://doi.org/10.1016/j.ultramic.2014.01.007
Mankos, M., Shadman, K., Persson, H. H. J., N’Diaye, A. T., Schmid, A. K., and Davis, R. W.. Fri . "A novel low energy electron microscope for DNA sequencing and surface analysis". United States. https://doi.org/10.1016/j.ultramic.2014.01.007. https://www.osti.gov/servlets/purl/1257846.
@article{osti_1257846,
title = {A novel low energy electron microscope for DNA sequencing and surface analysis},
author = {Mankos, M. and Shadman, K. and Persson, H. H. J. and N’Diaye, A. T. and Schmid, A. K. and Davis, R. W.},
abstractNote = {Monochromatic, aberration-corrected, dual-beam low energy electron microscopy (MAD-LEEM) is a novel technique that is directed towards imaging nanostructures and surfaces with sub-nanometer resolution. The technique combines a monochromator, a mirror aberration corrector, an energy filter, and dual beam illumination in a single instrument. The monochromator reduces the energy spread of the illuminating electron beam, which significantly improves spectroscopic and spatial resolution. Simulation results predict that the novel aberration corrector design will eliminate the second rank chromatic and third and fifth order spherical aberrations, thereby improving the resolution into the sub-nanometer regime at landing energies as low as one hundred electron-Volts. The energy filter produces a beam that can extract detailed information about the chemical composition and local electronic states of non-periodic objects such as nanoparticles, interfaces, defects, and macromolecules. The dual flood illumination eliminates charging effects that are generated when a conventional LEEM is used to image insulating specimens. A potential application for MAD-LEEM is in DNA sequencing, which requires high resolution to distinguish the individual bases and high speed to reduce the cost. The MAD-LEEM approach images the DNA with low electron impact energies, which provides nucleobase contrast mechanisms without organometallic labels. Furthermore, the micron-size field of view when combined with imaging on the fly provides long read lengths, thereby reducing the demand on assembling the sequence. Finally, experimental results from bulk specimens with immobilized single-base oligonucleotides demonstrate that base specific contrast is available with reflected, photo-emitted, and Auger electrons. Image contrast simulations of model rectangular features mimicking the individual nucleotides in a DNA strand have been developed to translate measurements of contrast on bulk DNA to the detectability of individual DNA bases in a sequence.},
doi = {10.1016/j.ultramic.2014.01.007},
journal = {Ultramicroscopy},
number = ,
volume = 145,
place = {United States},
year = {2014},
month = {1}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record

Citation Metrics:
Cited by: 5 works
Citation information provided by
Web of Science

Save / Share:

Works referenced in this record:

High-energy-resolution monochromator for aberration-corrected scanning transmission electron microscopy/electron energy-loss spectroscopy
journal, September 2009

  • Krivanek, Ondrej L.; Ursin, Jonathan P.; Bacon, Neil J.
  • Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences, Vol. 367, Issue 1903
  • DOI: 10.1098/rsta.2009.0087

Transmission electron microscopy at 20kV for imaging and spectroscopy
journal, July 2011


Principles of scanning electron microscopy at high specimen chamber pressures: SEM at High Specimen Chamber Pressures
journal, January 1979


An analytical reflection and emission UHV surface electron microscope
journal, January 1985


Thickness Determination of Graphene Layers Formed on SiC Using Low-Energy Electron Microscopy
journal, January 2008

  • Hibino, H.; Kageshima, H.; Maeda, F.
  • e-Journal of Surface Science and Nanotechnology, Vol. 6
  • DOI: 10.1380/ejssnt.2008.107

Optics of high-performance electron microscopes
journal, March 2008


A monochromatic, aberration-corrected, dual-beam low energy electron microscope
journal, July 2013


Double aberration correction in a low-energy electron microscope
journal, October 2010


A new aberration-corrected, energy-filtered LEEM/PEEM instrument. I. Principles and design
journal, June 2010


Correction properties of electron mirrors
journal, January 1997


Aberration correction for electron beam inspection, metrology, and lithography
journal, November 2008

  • Munro, Eric; Rouse, John; Liu, Haoning
  • Journal of Vacuum Science & Technology B: Microelectronics and Nanometer Structures, Vol. 26, Issue 6
  • DOI: 10.1116/1.2991515

Progress toward an aberration-corrected low energy electron microscope for DNA sequencing and surface analysis
journal, November 2012

  • Mankos, Marian; Shadman, Khashayar; N'Diaye, Alpha T.
  • Journal of Vacuum Science & Technology B, Nanotechnology and Microelectronics: Materials, Processing, Measurement, and Phenomena, Vol. 30, Issue 6
  • DOI: 10.1116/1.4764095

Simulation of a mirror corrector for PEEM3
journal, February 2004

  • Wan, W.; Feng, J.; Padmore, H. A.
  • Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, Vol. 519, Issue 1-2
  • DOI: 10.1016/j.nima.2003.11.159

Nondestructive Imaging of Individual Biomolecules
journal, March 2010


Colloquium : The quest for high-conductance DNA
journal, January 2004


Conductivity of a single DNA duplex bridging a carbon nanotube gap
journal, February 2008

  • Guo, Xuefeng; Gorodetsky, Alon A.; Hone, James
  • Nature Nanotechnology, Vol. 3, Issue 3
  • DOI: 10.1038/nnano.2008.4

Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid
journal, April 1953

  • Watson, J. D.; Crick, F. H. C.
  • Nature, Vol. 171, Issue 4356
  • DOI: 10.1038/171737a0

Quantitative Analysis and Characterization of DNA Immobilized on Gold
journal, April 2003

  • Petrovykh, Dmitri Y.; Kimura-Suda, Hiromi; Whitman, Lloyd J.
  • Journal of the American Chemical Society, Vol. 125, Issue 17
  • DOI: 10.1021/ja029450c

Geometrical characterization of pyrimidine base molecules adsorbed on Cu() surfaces: XPS and NEXAFS studies
journal, June 2003


Force-Induced Melting of the DNA Double Helix 1. Thermodynamic Analysis
journal, February 2001


Stretching DNA with a Receding Meniscus: Experiments and Models
journal, June 1995


    Works referencing / citing this record:

    Coming of age: ten years of next-generation sequencing technologies
    journal, May 2016

    • Goodwin, Sara; McPherson, John D.; McCombie, W. Richard
    • Nature Reviews Genetics, Vol. 17, Issue 6
    • DOI: 10.1038/nrg.2016.49

    Human genomics projects and precision medicine
    journal, August 2017

    • Carrasco-Ramiro, F.; Peiró-Pastor, R.; Aguado, B.
    • Gene Therapy, Vol. 24, Issue 9
    • DOI: 10.1038/gt.2017.77