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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 signal from DNA block copolymer translocation. (a) Stepwise displacement of dsDNA simulated using the coarse-grained MD approach. The simulation was performed at a constant transmembrane bias of 50 mV; the plasmonic field was periodically switched on and off for 2.0 and 0.4 μs, respectively. (b) SERS signal from the trajectory featured in panel a. The SERS intensity in the adenine (green) and cytosine (blue) channels is plotted as a function of the simulation time. To compute the SERS intensity, the DNA molecule was assumed to comprise blocks of 25 AT and 25 CG base pairs. Solid squares indicate the SERS intensity in the adenine (green) and cytosine (blue) channels averaged over each trapping phase of the plasmonic field pulse. Lines are guides for the eyes. The temporal changes of the SERS intensity in the guanine and thymine channels follow the dependences in the cytosine and adenine channels, respectively. (c) Same as in panel b but for a DNA molecule comprising alternating blocks of 2 AT and 48 CG base pairs. SERS intensities in the cytosine and adenine channels are shown on the left and right axes, respectively. Green dashed lines indicate the average intensity of the odd (top) and even (bottom) cycles. The difference between the average intensities in the odd and even cycles is defined as ΔIAT. (d) Dependence of ΔIAT on the length of the AT block, NAT. The length of the CG block is NCG = 50 – NAT. The dashed line illustrates a linear fit to the data in the NAT < 8 regime.
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fig6: SERS signal from DNA block copolymer translocation. (a) Stepwise displacement of dsDNA simulated using the coarse-grained MD approach. The simulation was performed at a constant transmembrane bias of 50 mV; the plasmonic field was periodically switched on and off for 2.0 and 0.4 μs, respectively. (b) SERS signal from the trajectory featured in panel a. The SERS intensity in the adenine (green) and cytosine (blue) channels is plotted as a function of the simulation time. To compute the SERS intensity, the DNA molecule was assumed to comprise blocks of 25 AT and 25 CG base pairs. Solid squares indicate the SERS intensity in the adenine (green) and cytosine (blue) channels averaged over each trapping phase of the plasmonic field pulse. Lines are guides for the eyes. The temporal changes of the SERS intensity in the guanine and thymine channels follow the dependences in the cytosine and adenine channels, respectively. (c) Same as in panel b but for a DNA molecule comprising alternating blocks of 2 AT and 48 CG base pairs. SERS intensities in the cytosine and adenine channels are shown on the left and right axes, respectively. Green dashed lines indicate the average intensity of the odd (top) and even (bottom) cycles. The difference between the average intensities in the odd and even cycles is defined as ΔIAT. (d) Dependence of ΔIAT on the length of the AT block, NAT. The length of the CG block is NCG = 50 – NAT. The dashed line illustrates a linear fit to the data in the NAT < 8 regime.

Mentions: Next, we used one of our coarse-grained MD trajectories of stepwise dsDNA translocation to evaluate the type of signals that could be recorded by a SERS detector in the presence of conformation disorder. Figure 6a shows a displacement trace of dsDNA obtained from coarse-grained simulations under a 50 mV transmembrane bias and a 2 μs on / 0.4 μs off pulse of the plasmonic field. In this trajectory, the DNA moves through the nanopores in 25 base pair steps (Movie S4). Figure 6b–d shows the SERS signals evaluated from the coarse-grained MD trajectory assuming that the nucleotide sequence of the DNA is made of blocks of AT and CG nucleotides (our coarse-grained model does not have explicit information about DNA sequence). In the case of the equal-length 25 base pair blocks, the presence of either AT and CG block in the plasmonic hot spots could be clearly identified from the SERS signal. The stepwise displacement was reproducible enough to distinguish the presence of two neighboring AT base pairs placed every 48 base pairs in the poly(CG) DNA (Figure 6c). For small AT blocks, the strength of the AT-specific signal linearly increases with the length of the block (Figure 6d), saturating for blocks greater than 10 base pairs. The relatively small variation of the signal within and between the trapping phases and the highly nonlinear dependence of the Raman emission probability on the local field enhancement factor suggests that DNA sequence detection at base pair resolution may be possible for small-amplitude stepwise displacement of dsDNA.


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

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

SERS signal from DNA block copolymer translocation. (a) Stepwise displacement of dsDNA simulated using the coarse-grained MD approach. The simulation was performed at a constant transmembrane bias of 50 mV; the plasmonic field was periodically switched on and off for 2.0 and 0.4 μs, respectively. (b) SERS signal from the trajectory featured in panel a. The SERS intensity in the adenine (green) and cytosine (blue) channels is plotted as a function of the simulation time. To compute the SERS intensity, the DNA molecule was assumed to comprise blocks of 25 AT and 25 CG base pairs. Solid squares indicate the SERS intensity in the adenine (green) and cytosine (blue) channels averaged over each trapping phase of the plasmonic field pulse. Lines are guides for the eyes. The temporal changes of the SERS intensity in the guanine and thymine channels follow the dependences in the cytosine and adenine channels, respectively. (c) Same as in panel b but for a DNA molecule comprising alternating blocks of 2 AT and 48 CG base pairs. SERS intensities in the cytosine and adenine channels are shown on the left and right axes, respectively. Green dashed lines indicate the average intensity of the odd (top) and even (bottom) cycles. The difference between the average intensities in the odd and even cycles is defined as ΔIAT. (d) Dependence of ΔIAT on the length of the AT block, NAT. The length of the CG block is NCG = 50 – NAT. The dashed line illustrates a linear fit to the data in the NAT < 8 regime.
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Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4660389&req=5

fig6: SERS signal from DNA block copolymer translocation. (a) Stepwise displacement of dsDNA simulated using the coarse-grained MD approach. The simulation was performed at a constant transmembrane bias of 50 mV; the plasmonic field was periodically switched on and off for 2.0 and 0.4 μs, respectively. (b) SERS signal from the trajectory featured in panel a. The SERS intensity in the adenine (green) and cytosine (blue) channels is plotted as a function of the simulation time. To compute the SERS intensity, the DNA molecule was assumed to comprise blocks of 25 AT and 25 CG base pairs. Solid squares indicate the SERS intensity in the adenine (green) and cytosine (blue) channels averaged over each trapping phase of the plasmonic field pulse. Lines are guides for the eyes. The temporal changes of the SERS intensity in the guanine and thymine channels follow the dependences in the cytosine and adenine channels, respectively. (c) Same as in panel b but for a DNA molecule comprising alternating blocks of 2 AT and 48 CG base pairs. SERS intensities in the cytosine and adenine channels are shown on the left and right axes, respectively. Green dashed lines indicate the average intensity of the odd (top) and even (bottom) cycles. The difference between the average intensities in the odd and even cycles is defined as ΔIAT. (d) Dependence of ΔIAT on the length of the AT block, NAT. The length of the CG block is NCG = 50 – NAT. The dashed line illustrates a linear fit to the data in the NAT < 8 regime.
Mentions: Next, we used one of our coarse-grained MD trajectories of stepwise dsDNA translocation to evaluate the type of signals that could be recorded by a SERS detector in the presence of conformation disorder. Figure 6a shows a displacement trace of dsDNA obtained from coarse-grained simulations under a 50 mV transmembrane bias and a 2 μs on / 0.4 μs off pulse of the plasmonic field. In this trajectory, the DNA moves through the nanopores in 25 base pair steps (Movie S4). Figure 6b–d shows the SERS signals evaluated from the coarse-grained MD trajectory assuming that the nucleotide sequence of the DNA is made of blocks of AT and CG nucleotides (our coarse-grained model does not have explicit information about DNA sequence). In the case of the equal-length 25 base pair blocks, the presence of either AT and CG block in the plasmonic hot spots could be clearly identified from the SERS signal. The stepwise displacement was reproducible enough to distinguish the presence of two neighboring AT base pairs placed every 48 base pairs in the poly(CG) DNA (Figure 6c). For small AT blocks, the strength of the AT-specific signal linearly increases with the length of the block (Figure 6d), saturating for blocks greater than 10 base pairs. The relatively small variation of the signal within and between the trapping phases and the highly nonlinear dependence of the Raman emission probability on the local field enhancement factor suggests that DNA sequence detection at base pair resolution may be possible for small-amplitude stepwise displacement of dsDNA.

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