Pressure-Controlled Motion of Single Polymers through Solid-State Nanopores

Lu, Bo; Hoogerheide, David P.; Zhao, Qing; Zhang, Hengbin; Tang, Zhaofeng; Yu, Dapeng; Golovchenko, Jene Andrew

doi:10.1021/nl402052v

Cited by 103 publications

(126 citation statements)

References 30 publications

(53 reference statements)

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“…Specifically, reducing solvent temperature [29,30] and increasing viscosity [31][32][33] both showed a reduction in translocation speed when passing DNA molecules. Additionally, solid-state researchers have explored the use of alternate salts [14,34] and the introduction of a salt concentration gradient [35,36] or counter pressure [37,38], achieving close to 10-fold translocation rate reductions by each of these means [38].…”

Section: The Environmentmentioning

confidence: 99%

Interfacing solid‐state nanopores with gel media to slow DNA translocations

et al. 2015

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We demonstrate the ability to slow DNA translocations through solid‐state nanopores by interfacing the trans side of the membrane with gel media. In this work, we focus on two reptation regimes: when the DNA molecule is flexible on the length scale of a gel pore, and when the DNA behaves as persistent segments in tight gel pores. The first regime is investigated using agarose gels, which produce a very wide distribution of translocation times for 5 kbp dsDNA fragments, spanning over three orders of magnitude. The second regime is attained with polyacrylamide gels, which can maintain a tight spread and produce a shift in the distribution of the translocation times by an order of magnitude for 100 bp dsDNA fragments, if intermolecular crowding on the trans side is avoided. While previous approaches have proven successful at slowing DNA passage, they have generally been detrimental to the S/N, capture rate, or experimental simplicity. These results establish that by controlling the regime of DNA movement exiting a nanopore interfaced with a gel medium, it is possible to address the issue of rapid biomolecule translocations through nanopores—presently one of the largest hurdles facing nanopore‐based analysis—without affecting the signal quality or capture efficiency.

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Section: The Environmentmentioning

confidence: 99%

Interfacing solid‐state nanopores with gel media to slow DNA translocations

et al. 2015

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“…Proteins such as RecA from Escherichia coli form filaments around the DNA that slows DNA transport and prevents its folding (26,34,35), although this approach inherently masks chemical information contained within the DNA, such as the presence of DNA chemical modifications (7,36) or small bound drug/reporter molecules (37)(38)(39)(40). Explorations of the effects of parameters such as the electrolyte viscosity (41,42), salt type (43,44), membrane material (45,46), applied pressure (47,48), and chemical composition inside (49)(50)(51)(52) and outside (53) the pore have yielded only moderate DNA retardation factors.…”

Section: Introductionmentioning

confidence: 99%

Smooth DNA Transport through a Narrowed Pore Geometry

Carson

Wilson

Aksimentiev

et al. 2014

Biophysical Journal

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Voltage-driven transport of double-stranded DNA through nanoscale pores holds much potential for applications in quantitative molecular biology and biotechnology, yet the microscopic details of translocation have proven to be challenging to decipher. Earlier experiments showed strong dependence of transport kinetics on pore size: fast regular transport in large pores (> 5 nm diameter), and slower yet heterogeneous transport time distributions in sub-5 nm pores, which imply a large positional uncertainty of the DNA in the pore as a function of the translocation time. In this work, we show that this anomalous transport is a result of DNA self-interaction, a phenomenon that is strictly pore-diameter dependent. We identify a regime in which DNA transport is regular, producing narrow and well-behaved dwell-time distributions that fit a simple drift-diffusion theory. Furthermore, a systematic study of the dependence of dwell time on DNA length reveals a single power-law scaling of 1.37 in the range of 35-20,000 bp. We highlight the resolution of our nanopore device by discriminating via single pulses 100 and 500 bp fragments in a mixture with >98% accuracy. When coupled to an appropriate sequence labeling method, our observation of smooth DNA translocation can pave the way for high-resolution DNA mapping and sizing applications in genomics.

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“…Using this method, an eight-fold reduction in the translocation speed was obtained. 127 The fluid dynamics of single molecules within nanopores has not yet been fully clarified, and research studies designed to provide greater understanding of the influence of the ion concentration, temperature, electrophoresis, electroosmotic flow, and water pressure will be important in the future. Specifically, understanding the dynamics of single molecules passing through nanopores will provide important insights for improving the precision of single molecule identification using nanopores.…”

Section: Controlling Single Molecule Fluid Dynamicsmentioning

confidence: 99%

Selective Multidetection Using Nanopores

Taniguchi

2014

Anal. Chem.

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Pressure-Controlled Motion of Single Polymers through Solid-State Nanopores

Cited by 103 publications

References 30 publications

Interfacing solid‐state nanopores with gel media to slow DNA translocations

Interfacing solid‐state nanopores with gel media to slow DNA translocations

Smooth DNA Transport through a Narrowed Pore Geometry

Selective Multidetection Using Nanopores

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