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Plasmonic Nanopores for Trapping, Controlling Displacement, and Sequencing of DNA.

Belkin M, Chao SH, Jonsson MP, Dekker C, Aksimentiev A - ACS Nano (2015)

Bottom Line: Using molecular dynamics simulations, we show that high-intensity optical hot spots produced by a metallic nanostructure can arrest DNA translocation through a solid-state nanopore, thus providing a physical knob for controlling the DNA speed.Switching the plasmonic field on and off can displace the DNA molecule in discrete steps, sequentially exposing neighboring fragments of a DNA molecule to the pore as well as to the plasmonic hot spot.Surface-enhanced Raman scattering from the exposed DNA fragments contains information about their nucleotide composition, possibly allowing the identification of the nucleotide sequence of a DNA molecule transported through the hot spot.

View Article: PubMed Central - PubMed

Affiliation: Department of Physics, University of Illinois at Urbana-Champaign , Urbana, Illinois 61801, United States.

ABSTRACT
With the aim of developing a DNA sequencing methodology, we theoretically examine the feasibility of using nanoplasmonics to control the translocation of a DNA molecule through a solid-state nanopore and to read off sequence information using surface-enhanced Raman spectroscopy. Using molecular dynamics simulations, we show that high-intensity optical hot spots produced by a metallic nanostructure can arrest DNA translocation through a solid-state nanopore, thus providing a physical knob for controlling the DNA speed. Switching the plasmonic field on and off can displace the DNA molecule in discrete steps, sequentially exposing neighboring fragments of a DNA molecule to the pore as well as to the plasmonic hot spot. Surface-enhanced Raman scattering from the exposed DNA fragments contains information about their nucleotide composition, possibly allowing the identification of the nucleotide sequence of a DNA molecule transported through the hot spot. The principles of plasmonic nanopore sequencing can be extended to detection of DNA modifications and RNA characterization.

No MeSH data available.


Related in: MedlinePlus

SERS detection of DNA sequence. (a) Typical conformation of dsDNA trapped between two hot spots. The base pairs are numbered in ascending order from the trailing to the leading end of the molecule. (b–d) SERS signals from a poly(AT) block in the poly(CG) background. The calculated SERS intensity in the four frequency channels is shown for different locations of the poly(AT) block. The intensities are plotted in the units of peak intensities that would have been measured in each channel under the same illumination in the absence of the plasmonic enhancement. For each substitution, the DNA molecule is assumed to have the same conformation (shown in panel a). The base pair index specifies the location of the first base pair of the poly(AT) block from the trailing end of the molecule using the base pair numbering defined in panel a. Data in panels b–d correspond to poly(AT) blocks containing 12, 5, and 1 base pairs. Dashed lines in panel d indicate the signal from a TA base pair. The TA and AT base pairs differ from one another by the strands the A and T nucleotides located in the helix. (e) SERS detection of a single nucleotide substitution. The calculated SERS signals from the GATTACA and TATTACA blocks inserted at a specified location in the poly(CG) molecule. (f) Difference between the signals from the GATTACA and TATTACA blocks. (g) Effect of thermal fluctuations on SERS signal. The SERS intensity of a thymine nucleotide is plotted for a sequence of DNA conformations obtained from the all-atom MD trajectory of dsDNA trapping (at 3.7 mW laser power). The first frame of the trajectory is shown in panel a. The DNA is assumed to be made entirely from CG base pairs with the exception of a single AT base pair inserted 19, 20, 21, 22, or 23 base pairs away from the trailing end of the molecule. The color of the lines indicates the location of the thymine nucleotide in the DNA molecule (panel h). (h) Averaged over the MD trajectory SERS signals from the thymine nucleotide at the specified location in the DNA molecule. The error bars show the standard deviation of the signal.
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fig5: SERS detection of DNA sequence. (a) Typical conformation of dsDNA trapped between two hot spots. The base pairs are numbered in ascending order from the trailing to the leading end of the molecule. (b–d) SERS signals from a poly(AT) block in the poly(CG) background. The calculated SERS intensity in the four frequency channels is shown for different locations of the poly(AT) block. The intensities are plotted in the units of peak intensities that would have been measured in each channel under the same illumination in the absence of the plasmonic enhancement. For each substitution, the DNA molecule is assumed to have the same conformation (shown in panel a). The base pair index specifies the location of the first base pair of the poly(AT) block from the trailing end of the molecule using the base pair numbering defined in panel a. Data in panels b–d correspond to poly(AT) blocks containing 12, 5, and 1 base pairs. Dashed lines in panel d indicate the signal from a TA base pair. The TA and AT base pairs differ from one another by the strands the A and T nucleotides located in the helix. (e) SERS detection of a single nucleotide substitution. The calculated SERS signals from the GATTACA and TATTACA blocks inserted at a specified location in the poly(CG) molecule. (f) Difference between the signals from the GATTACA and TATTACA blocks. (g) Effect of thermal fluctuations on SERS signal. The SERS intensity of a thymine nucleotide is plotted for a sequence of DNA conformations obtained from the all-atom MD trajectory of dsDNA trapping (at 3.7 mW laser power). The first frame of the trajectory is shown in panel a. The DNA is assumed to be made entirely from CG base pairs with the exception of a single AT base pair inserted 19, 20, 21, 22, or 23 base pairs away from the trailing end of the molecule. The color of the lines indicates the location of the thymine nucleotide in the DNA molecule (panel h). (h) Averaged over the MD trajectory SERS signals from the thymine nucleotide at the specified location in the DNA molecule. The error bars show the standard deviation of the signal.

Mentions: The SERS signal from a DNA molecule passing through a plasmonic nanopore is determined by both the sequence and the trapping conformation of the DNA molecule. To evaluate the potential utility of SERS for nanopore sequencing of DNA, we first consider a situation where the conformational fluctuations of the molecule are negligible, which, in practice, would correspond to trapping the DNA molecule in the same conformation for each of the translocation steps. Starting from a typical conformation of the trapped dsDNA molecule observed in our all-atom MD simulations (Figure 5a), we examine the effect of the nucleotide sequence on the SERS signal by assigning custom sequences to the trapped DNA fragment. To compute the Raman signal, we approximate the Raman spectrum of each type of DNA nucleotides by a Gaussian, centered at 800 (cytosine), 780 (thymine), 735 (adenine), and 660 (guanine) cm–1.43 The contribution of an individual nucleotide to the overall spectrum depends on the nucleotide’s location within the hot spot. Assuming that the probability of SERS emission is proportional to the square of the local field intensity43 and knowing the position of all DNA bases, we can compute the spectrum of the entire DNA molecule as a superposition of the individual nucleotide’s Gaussians scaled by the local field enhancement factor I2(r)/I02. Thus, our calculations account for the variation of the field enhancement between the triangles. Figure 1 shows a superposition of the A, C, G, and T Gaussians scaled by the same field enhancement factor. In the subsequent analyses, we characterize the spectra by plotting the intensity at the peak frequencies of the four Gaussians, referred hereafter as the four (A, C, G, and T) frequency channels.


Plasmonic Nanopores for Trapping, Controlling Displacement, and Sequencing of DNA.

Belkin M, Chao SH, Jonsson MP, Dekker C, Aksimentiev A - ACS Nano (2015)

SERS detection of DNA sequence. (a) Typical conformation of dsDNA trapped between two hot spots. The base pairs are numbered in ascending order from the trailing to the leading end of the molecule. (b–d) SERS signals from a poly(AT) block in the poly(CG) background. The calculated SERS intensity in the four frequency channels is shown for different locations of the poly(AT) block. The intensities are plotted in the units of peak intensities that would have been measured in each channel under the same illumination in the absence of the plasmonic enhancement. For each substitution, the DNA molecule is assumed to have the same conformation (shown in panel a). The base pair index specifies the location of the first base pair of the poly(AT) block from the trailing end of the molecule using the base pair numbering defined in panel a. Data in panels b–d correspond to poly(AT) blocks containing 12, 5, and 1 base pairs. Dashed lines in panel d indicate the signal from a TA base pair. The TA and AT base pairs differ from one another by the strands the A and T nucleotides located in the helix. (e) SERS detection of a single nucleotide substitution. The calculated SERS signals from the GATTACA and TATTACA blocks inserted at a specified location in the poly(CG) molecule. (f) Difference between the signals from the GATTACA and TATTACA blocks. (g) Effect of thermal fluctuations on SERS signal. The SERS intensity of a thymine nucleotide is plotted for a sequence of DNA conformations obtained from the all-atom MD trajectory of dsDNA trapping (at 3.7 mW laser power). The first frame of the trajectory is shown in panel a. The DNA is assumed to be made entirely from CG base pairs with the exception of a single AT base pair inserted 19, 20, 21, 22, or 23 base pairs away from the trailing end of the molecule. The color of the lines indicates the location of the thymine nucleotide in the DNA molecule (panel h). (h) Averaged over the MD trajectory SERS signals from the thymine nucleotide at the specified location in the DNA molecule. The error bars show the standard deviation of the signal.
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fig5: SERS detection of DNA sequence. (a) Typical conformation of dsDNA trapped between two hot spots. The base pairs are numbered in ascending order from the trailing to the leading end of the molecule. (b–d) SERS signals from a poly(AT) block in the poly(CG) background. The calculated SERS intensity in the four frequency channels is shown for different locations of the poly(AT) block. The intensities are plotted in the units of peak intensities that would have been measured in each channel under the same illumination in the absence of the plasmonic enhancement. For each substitution, the DNA molecule is assumed to have the same conformation (shown in panel a). The base pair index specifies the location of the first base pair of the poly(AT) block from the trailing end of the molecule using the base pair numbering defined in panel a. Data in panels b–d correspond to poly(AT) blocks containing 12, 5, and 1 base pairs. Dashed lines in panel d indicate the signal from a TA base pair. The TA and AT base pairs differ from one another by the strands the A and T nucleotides located in the helix. (e) SERS detection of a single nucleotide substitution. The calculated SERS signals from the GATTACA and TATTACA blocks inserted at a specified location in the poly(CG) molecule. (f) Difference between the signals from the GATTACA and TATTACA blocks. (g) Effect of thermal fluctuations on SERS signal. The SERS intensity of a thymine nucleotide is plotted for a sequence of DNA conformations obtained from the all-atom MD trajectory of dsDNA trapping (at 3.7 mW laser power). The first frame of the trajectory is shown in panel a. The DNA is assumed to be made entirely from CG base pairs with the exception of a single AT base pair inserted 19, 20, 21, 22, or 23 base pairs away from the trailing end of the molecule. The color of the lines indicates the location of the thymine nucleotide in the DNA molecule (panel h). (h) Averaged over the MD trajectory SERS signals from the thymine nucleotide at the specified location in the DNA molecule. The error bars show the standard deviation of the signal.
Mentions: The SERS signal from a DNA molecule passing through a plasmonic nanopore is determined by both the sequence and the trapping conformation of the DNA molecule. To evaluate the potential utility of SERS for nanopore sequencing of DNA, we first consider a situation where the conformational fluctuations of the molecule are negligible, which, in practice, would correspond to trapping the DNA molecule in the same conformation for each of the translocation steps. Starting from a typical conformation of the trapped dsDNA molecule observed in our all-atom MD simulations (Figure 5a), we examine the effect of the nucleotide sequence on the SERS signal by assigning custom sequences to the trapped DNA fragment. To compute the Raman signal, we approximate the Raman spectrum of each type of DNA nucleotides by a Gaussian, centered at 800 (cytosine), 780 (thymine), 735 (adenine), and 660 (guanine) cm–1.43 The contribution of an individual nucleotide to the overall spectrum depends on the nucleotide’s location within the hot spot. Assuming that the probability of SERS emission is proportional to the square of the local field intensity43 and knowing the position of all DNA bases, we can compute the spectrum of the entire DNA molecule as a superposition of the individual nucleotide’s Gaussians scaled by the local field enhancement factor I2(r)/I02. Thus, our calculations account for the variation of the field enhancement between the triangles. Figure 1 shows a superposition of the A, C, G, and T Gaussians scaled by the same field enhancement factor. In the subsequent analyses, we characterize the spectra by plotting the intensity at the peak frequencies of the four Gaussians, referred hereafter as the four (A, C, G, and T) frequency channels.

Bottom Line: Using molecular dynamics simulations, we show that high-intensity optical hot spots produced by a metallic nanostructure can arrest DNA translocation through a solid-state nanopore, thus providing a physical knob for controlling the DNA speed.Switching the plasmonic field on and off can displace the DNA molecule in discrete steps, sequentially exposing neighboring fragments of a DNA molecule to the pore as well as to the plasmonic hot spot.Surface-enhanced Raman scattering from the exposed DNA fragments contains information about their nucleotide composition, possibly allowing the identification of the nucleotide sequence of a DNA molecule transported through the hot spot.

View Article: PubMed Central - PubMed

Affiliation: Department of Physics, University of Illinois at Urbana-Champaign , Urbana, Illinois 61801, United States.

ABSTRACT
With the aim of developing a DNA sequencing methodology, we theoretically examine the feasibility of using nanoplasmonics to control the translocation of a DNA molecule through a solid-state nanopore and to read off sequence information using surface-enhanced Raman spectroscopy. Using molecular dynamics simulations, we show that high-intensity optical hot spots produced by a metallic nanostructure can arrest DNA translocation through a solid-state nanopore, thus providing a physical knob for controlling the DNA speed. Switching the plasmonic field on and off can displace the DNA molecule in discrete steps, sequentially exposing neighboring fragments of a DNA molecule to the pore as well as to the plasmonic hot spot. Surface-enhanced Raman scattering from the exposed DNA fragments contains information about their nucleotide composition, possibly allowing the identification of the nucleotide sequence of a DNA molecule transported through the hot spot. The principles of plasmonic nanopore sequencing can be extended to detection of DNA modifications and RNA characterization.

No MeSH data available.


Related in: MedlinePlus