Nucleotide-Specific Contrast for DNA Sequencing by Electron Spectroscopy
Abstract
DNA sequencing by imaging in an electron microscope is an approach that holds promise to deliver long reads with low error rates and without the need for amplification. Earlier work using transmission electron microscopes, which use high electron energies on the order of 100 keV, has shown that low contrast and radiation damage necessitates the use of heavy atom labeling of individual nucleotides, which increases the read error rates. Other prior work using scattering electrons with much lower energy has shown to suppress beam damage on DNA. Here we explore possibilities to increase contrast by employing two methods, X-ray photoelectron and Auger electron spectroscopy. Using bulk DNA samples with monomers of each base, both methods are shown to provide contrast mechanisms that can distinguish individual nucleotides without labels. In conclusion, both spectroscopic techniques can be readily implemented in a low energy electron microscope, which may enable label-free DNA sequencing by direct imaging.
- Authors:
- Publication Date:
- Research Org.:
- Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Basic Energy Sciences (BES)
- OSTI Identifier:
- 1337763
- Alternate Identifier(s):
- OSTI ID: 1378725
- Grant/Contract Number:
- AC02-05CH11231
- Resource Type:
- Published Article
- Journal Name:
- PLoS ONE
- Additional Journal Information:
- Journal Name: PLoS ONE Journal Volume: 11 Journal Issue: 5; Journal ID: ISSN 1932-6203
- Publisher:
- Public Library of Science (PLoS)
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 60 APPLIED LIFE SCIENCES; 59 BASIC BIOLOGICAL SCIENCES; X-ray photoelectron spectroscopy; Nitrogen; Oxygen; DNA sequencing; Nucleotide sequencing; Purines; Chemical elements; Electron microscopes
Citation Formats
Mankos, Marian, Persson, Henrik H. J., N’Diaye, Alpha T., Shadman, Khashayar, Schmid, Andreas K., Davis, Ronald W., and Dedkov, ed., Yuriy. Nucleotide-Specific Contrast for DNA Sequencing by Electron Spectroscopy. United States: N. p., 2016.
Web. doi:10.1371/journal.pone.0154707.
Mankos, Marian, Persson, Henrik H. J., N’Diaye, Alpha T., Shadman, Khashayar, Schmid, Andreas K., Davis, Ronald W., & Dedkov, ed., Yuriy. Nucleotide-Specific Contrast for DNA Sequencing by Electron Spectroscopy. United States. https://doi.org/10.1371/journal.pone.0154707
Mankos, Marian, Persson, Henrik H. J., N’Diaye, Alpha T., Shadman, Khashayar, Schmid, Andreas K., Davis, Ronald W., and Dedkov, ed., Yuriy. Thu .
"Nucleotide-Specific Contrast for DNA Sequencing by Electron Spectroscopy". United States. https://doi.org/10.1371/journal.pone.0154707.
@article{osti_1337763,
title = {Nucleotide-Specific Contrast for DNA Sequencing by Electron Spectroscopy},
author = {Mankos, Marian and Persson, Henrik H. J. and N’Diaye, Alpha T. and Shadman, Khashayar and Schmid, Andreas K. and Davis, Ronald W. and Dedkov, ed., Yuriy},
abstractNote = {DNA sequencing by imaging in an electron microscope is an approach that holds promise to deliver long reads with low error rates and without the need for amplification. Earlier work using transmission electron microscopes, which use high electron energies on the order of 100 keV, has shown that low contrast and radiation damage necessitates the use of heavy atom labeling of individual nucleotides, which increases the read error rates. Other prior work using scattering electrons with much lower energy has shown to suppress beam damage on DNA. Here we explore possibilities to increase contrast by employing two methods, X-ray photoelectron and Auger electron spectroscopy. Using bulk DNA samples with monomers of each base, both methods are shown to provide contrast mechanisms that can distinguish individual nucleotides without labels. In conclusion, both spectroscopic techniques can be readily implemented in a low energy electron microscope, which may enable label-free DNA sequencing by direct imaging.},
doi = {10.1371/journal.pone.0154707},
journal = {PLoS ONE},
number = 5,
volume = 11,
place = {United States},
year = {Thu May 05 00:00:00 EDT 2016},
month = {Thu May 05 00:00:00 EDT 2016}
}
Free Publicly Available Full Text
Publisher's Version of Record
https://doi.org/10.1371/journal.pone.0154707
https://doi.org/10.1371/journal.pone.0154707
Other availability
Search WorldCat to find libraries that may hold this journal
Cited by: 9 works
Citation information provided by
Web of Science
Web of Science
Save to My Library
You must Sign In or Create an Account in order to save documents to your library.
Works referenced in this record:
Alignment and sensitive detection of DNA by a moving interface
journal, September 1994
- Bensimon, A.; Simon, A.; Chiffaudel, A.
- Science, Vol. 265, Issue 5181
Stretching DNA with a Receding Meniscus: Experiments and Models
journal, June 1995
- Bensimon, D.; Simon, A. J.; Croquette, V.
- Physical Review Letters, Vol. 74, Issue 23
Overstretching B-DNA: The Elastic Response of Individual Double-Stranded and Single-Stranded DNA Molecules
journal, February 1996
- Smith, S. B.; Cui, Y.; Bustamante, C.
- Science, Vol. 271, Issue 5250
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
Electron holography of individual DNA molecules
journal, January 1997
- Fink, Hans-Werner; Schmid, Heinz; Ermantraut, Eugen
- Journal of the Optical Society of America A, Vol. 14, Issue 9
X-ray induced damage in DNA monitored by X-ray photoelectron spectroscopy
journal, August 2008
- Ptasińska, Sylwia; Stypczyńska, Agnieszka; Nixon, Tony
- The Journal of Chemical Physics, Vol. 129, Issue 6
A comparison of weak molecular adsorption of organic molecules on clean copper and platinum surfaces
journal, May 1984
- Sexton, B. A.; Hughes, A. E.
- Surface Science, Vol. 140, Issue 1
Nondestructive Imaging of Individual Biomolecules
journal, March 2010
- Germann, Matthias; Latychevskaia, Tatiana; Escher, Conrad
- Physical Review Letters, Vol. 104, Issue 9
DNA: An Extensible Molecule
journal, February 1996
- Cluzel, P.; Lebrun, A.; Heller, C.
- Science, Vol. 271, Issue 5250
DNA-modified electrodes Part 3.: spectroscopic characterization of DNA-modified gold electrodes
journal, May 1999
- Zhao, Yuan-Di; Pang, Dai-Wen; Hu, Shen
- Analytica Chimica Acta, Vol. 388, Issue 1-2
Quantitative X-ray Photoelectron Spectroscopy and Time-of-Flight Secondary Ion Mass Spectrometry Characterization of the Components in DNA
journal, February 2004
- May, Collin J.; Canavan, Heather E.; Castner, David G.
- Analytical Chemistry, Vol. 76, Issue 4
Theoretical models for single-molecule DNA and RNA experiments: from elasticity to unzipping
journal, January 2002
- Cocco, Simona; Marko, John F.; Monasson, Rémi
- Comptes Rendus Physique, Vol. 3, Issue 5
First Nucleotide Sequence Data from an Electron Microscopy Based DNA Sequencer
journal, August 2013
- Own, C.; Bleloch, A.; Lerach, W.
- Microscopy and Microanalysis, Vol. 19, Issue S2
Spectroscopic quantification of covalently immobilized oligonucleotides
journal, January 2005
- Saprigin, Alexey V.; Thomas, Chris W.; Dulcey, Charles S.
- Surface and Interface Analysis, Vol. 37, Issue 1
Structural Transitions of a Twisted and Stretched DNA Molecule
journal, August 1999
- Léger, J. F.; Romano, G.; Sarkar, A.
- Physical Review Letters, Vol. 83, Issue 5
Force-Induced Melting of the DNA Double Helix 1. Thermodynamic Analysis
journal, February 2001
- Rouzina, Ioulia; Bloomfield, Victor A.
- Biophysical Journal, Vol. 80, Issue 2
DNA Base Identification by Electron Microscopy
journal, October 2012
- Bell, David C.; Thomas, W. Kelley; Murtagh, Katelyn M.
- Microscopy and Microanalysis, Vol. 18, Issue 5
Theory of high-force DNA stretching and overstretching
journal, May 2003
- Storm, C.; Nelson, P. C.
- Physical Review E, Vol. 67, Issue 5
A novel low energy electron microscope for DNA sequencing and surface analysis
journal, October 2014
- Mankos, M.; Shadman, K.; Persson, H. H. J.
- Ultramicroscopy, Vol. 145
Versatile Method for Chemical Reactions with Self-Assembled Monolayers of Alkanethiols on Gold
journal, June 2001
- Persson, Henrik H. J.; Caseri, Walter R.; Suter, Ulrich W.
- Langmuir, Vol. 17, Issue 12