Precise control of the size and noise of solid-state nanopores using high electric fields

Beamish, Eric; Kwok, Harold; Tabard‐Cossa, Vincent; Godin, Michel

doi:10.1088/0957-4484/23/40/405301

Cited by 91 publications

(123 citation statements)

References 34 publications

(42 reference statements)

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“…Typically this is achieved by performing a piranha clean on the chip, which employs a sulfuric acid and hydrogen peroxide solution [20]. Unfortunately, this harsh treatment frequently leads to enlargement of the nanopore and thus negates the benefits of being able to visually inspect the nanopore with the TEM to confirm nanopore size and geometry [17,19].…”

Section: Temmentioning

confidence: 99%

“…Conveniently, a computer program can be used to interrupt the voltage immediately after the current reaches a certain threshold. This immediate voltage shutoff is important to maintain a small pore size, as a large voltage applied to an existing nanopore tends to grow the pore, and it can easily reach sizes that are too large to be useful [20]. decayed (which can take ~1-2 s), a stable leakage current is measured, which slowly decays.…”

Section: Controlled Dielectric Breakdownmentioning

confidence: 99%

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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: Temmentioning

confidence: 99%

Section: Controlled Dielectric Breakdownmentioning

confidence: 99%

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

et al. 2015

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“…While the protocol described can be applied to solid-state nanopores of various material fabricated using any method, they are commonly drilled by TEM using previously established protocols 11,14 . Nanopores drilled by TEM are typically between 4-8 nm in diameter (Figure 2).…”

Section: Representative Resultsmentioning

confidence: 99%

“…The ionic current through solid-state nanopores can also suffer from high noise, the sources of which are an intensely investigated topic in nanopore literature 2,3,10,11 . While various methods have been proposed to reduce electrical noise, the yield of reliable, stable low-noise nanopores is typically low.…”

Section: Introductionmentioning

confidence: 99%

Fine-tuning the Size and Minimizing the Noise of Solid-state Nanopores

Beamish

Kwok

Tabard‐Cossa

et al. 2013

JoVE

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Solid-state nanopores have emerged as a versatile tool for the characterization of single biomolecules such as nucleic acids and proteins 1 . However, the creation of a nanopore in a thin insulating membrane remains challenging. Fabrication methods involving specialized focused electron beam systems can produce well-defined nanopores, but yield of reliable and low-noise nanopores in commercially available membranes remains low 2,3 and size control is nontrivial 4,5 . Here, the application of high electric fields to fine-tune the size of the nanopore while ensuring optimal low-noise performance is demonstrated. These short pulses of high electric field are used to produce a pristine electrical signal and allow for enlarging of nanopores with subnanometer precision upon prolonged exposure. This method is performed in situ in an aqueous environment using standard laboratory equipment, improving the yield and reproducibility of solid-state nanopore fabrication.

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“…Recently, increase in conductance during experiment has been attributed to changes in pore radius [12, 20], however, both the diameter and pore thickness are expected to play a role in pore conductance. Plan-view TEM images similar to those in Figure 1A that give the pore diameter and thin film measurements of the membrane thickness supporting the pore are typically the only information used to estimate pore conductance.…”

Section: Introductionmentioning

confidence: 99%

The effects of geometry and stability of solid-state nanopores on detecting single DNA molecules

et al. 2015

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In this work we use a combination of 3D-TEM tomography, energy filtered TEM, single molecule DNA translocation experiments, and numerical modeling to show a more precise relationship between nanopore shape and ionic conductance and show that changes in geometry while in solution can account for most deviations between predicted and measured conductance. We compare the structural stability of Ion Beam Sculpted (IBS), IBS-annealed, and TEM drilled nanopores. We demonstrate that annealing can significantly improve the stability of IBS made pores. Furthermore, the methods developed in this work can be used to predict pore conductance and current drop amplitudes of DNA translocation events for a wide variety of pore geometries. We discuss that chemical dissolution is one mechanism of the geometry change for SiNx nanopores and show that small modification in fabrication procedure can significantly increase the stability of IBS nanopores.

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Precise control of the size and noise of solid-state nanopores using high electric fields

Cited by 91 publications

References 34 publications

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

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

Fine-tuning the Size and Minimizing the Noise of Solid-state Nanopores

The effects of geometry and stability of solid-state nanopores on detecting single DNA molecules

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