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Title: DNA Methylation Detection Using Resonance and Nanobowtie-Antenna-Enhanced Raman Spectroscopy

Abstract

In this paper, we show that DNA carrying 5-methylcytosine modifications or methylated DNA (m-DNA) can be distinguished from DNA with unmodified cytosine by Raman spectroscopy enhanced by both a bowtie nanoantenna and excitation resonance. In particular, m-DNA can be identified by a peak near 1000 cm-1 and changes in the Raman peaks in the 1200–1700 cm-1 band that are enhanced by the ring-absorption resonance. The identification is robust to the use of resonance Raman and nanoantenna excitation used to obtain significant signal improvement. The primary differences are three additional Raman peaks with methylation at 1014, 1239, and 1639 cm-1 and spectral intensity inversion at 1324 (C5=C6) and 1473 cm-1 (C4=N3) in m-DNA compared to that of DNA with unmodified cytosine. We attribute this to the proximity of the methyl group to the antenna, which brings the (C5=C6) mode closer to experiencing a stronger near-field enhancement. We also show distinct Raman spectral features attributed to the transition of DNA from a hydrated state, when dissolved, to a dried/denatured state. We observe a general broadening of the larger lines and a transfer of spectral weight from the ~1470 cm-1 vibration to the two higher-energy lines of the dried m-DNA solution. We attributemore » the new spectral characteristics to DNA softening under high salt conditions and find that the m-DNA is still distinguishable via the ~1000 cm-1 peak and distribution of the signal in the 1200–1700 cm-1 band. The nanoantenna gain exceeds 20,000, whereas the real signal ratio is much less because of a low average enhanced region occupancy even with these relatively high DNA concentrations. It is improved when fixed DNA in a salt crystal lies near the nanoantenna. Finally, the Raman resonance gain profile is consistent with A-term expectations, and the resonance is found at ~259 nm excitation wavelength.« less

Authors:
 [1];  [1];  [2];  [1];  [1]
+ Show Author Affiliations
  1. North Carolina State Univ., Raleigh, NC (United States). Dept. of Physics
  2. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Center for Nanophase Materials Sciences
Publication Date:
Research Org.:
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); North Carolina State University, Raleigh, NC (United States)
Sponsoring Org.:
USDOE Office of Science (SC); National Inst. of Health (NIH) (United States); National Science Foundation (NSF)
OSTI Identifier:
1468193
Grant/Contract Number:  
AC05-00OR22725; R21CA13207; CBET 1067508
Resource Type:
Accepted Manuscript
Journal Name:
Biophysical Journal
Additional Journal Information:
Journal Volume: 114; Journal Issue: 11; Journal ID: ISSN 0006-3495
Publisher:
Elsevier
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Li, Ling, Lim, Shuang Fang, Puretzky, Alexander, Riehn, Robert, and Hallen, Hans D. DNA Methylation Detection Using Resonance and Nanobowtie-Antenna-Enhanced Raman Spectroscopy. United States: N. p., 2018. Web. doi:10.1016/j.bpj.2018.04.021.
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Li, Ling, Lim, Shuang Fang, Puretzky, Alexander, Riehn, Robert, & Hallen, Hans D. DNA Methylation Detection Using Resonance and Nanobowtie-Antenna-Enhanced Raman Spectroscopy. United States. https://doi.org/10.1016/j.bpj.2018.04.021
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Li, Ling, Lim, Shuang Fang, Puretzky, Alexander, Riehn, Robert, and Hallen, Hans D. Thu . "DNA Methylation Detection Using Resonance and Nanobowtie-Antenna-Enhanced Raman Spectroscopy". United States. https://doi.org/10.1016/j.bpj.2018.04.021. https://www.osti.gov/servlets/purl/1468193.
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@article{osti_1468193,
title = {DNA Methylation Detection Using Resonance and Nanobowtie-Antenna-Enhanced Raman Spectroscopy},
author = {Li, Ling and Lim, Shuang Fang and Puretzky, Alexander and Riehn, Robert and Hallen, Hans D.},
abstractNote = {In this paper, we show that DNA carrying 5-methylcytosine modifications or methylated DNA (m-DNA) can be distinguished from DNA with unmodified cytosine by Raman spectroscopy enhanced by both a bowtie nanoantenna and excitation resonance. In particular, m-DNA can be identified by a peak near 1000 cm-1 and changes in the Raman peaks in the 1200–1700 cm-1 band that are enhanced by the ring-absorption resonance. The identification is robust to the use of resonance Raman and nanoantenna excitation used to obtain significant signal improvement. The primary differences are three additional Raman peaks with methylation at 1014, 1239, and 1639 cm-1 and spectral intensity inversion at 1324 (C5=C6) and 1473 cm-1 (C4=N3) in m-DNA compared to that of DNA with unmodified cytosine. We attribute this to the proximity of the methyl group to the antenna, which brings the (C5=C6) mode closer to experiencing a stronger near-field enhancement. We also show distinct Raman spectral features attributed to the transition of DNA from a hydrated state, when dissolved, to a dried/denatured state. We observe a general broadening of the larger lines and a transfer of spectral weight from the ~1470 cm-1 vibration to the two higher-energy lines of the dried m-DNA solution. We attribute the new spectral characteristics to DNA softening under high salt conditions and find that the m-DNA is still distinguishable via the ~1000 cm-1 peak and distribution of the signal in the 1200–1700 cm-1 band. The nanoantenna gain exceeds 20,000, whereas the real signal ratio is much less because of a low average enhanced region occupancy even with these relatively high DNA concentrations. It is improved when fixed DNA in a salt crystal lies near the nanoantenna. Finally, the Raman resonance gain profile is consistent with A-term expectations, and the resonance is found at ~259 nm excitation wavelength.},
doi = {10.1016/j.bpj.2018.04.021},
journal = {Biophysical Journal},
number = 11,
volume = 114,
place = {United States},
year = {2018},
month = {6}
}
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Journal Article:
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Publisher's Version of Record
https://doi.org/10.1016/j.bpj.2018.04.021
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Cited by: 15 works
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Figures / Tables:

Figure 1 Figure 1: Background spectrum used in the spectra analysis routine. It was collected by averaging and normalizing spectra of buffer solution on top of aluminum bowtie antenna coverslip.
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    • Advanced Optical Materials, Vol. 7, Issue 5
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