Improving Signal-to-Noise Performance for DNA Translocation in Solid-State Nanopores at MHz Bandwidths

Balan, Adrian; Machielse, Bartholomeus; Niedzwiecki, David J.; Lin, Jianxun; Ong, Peijie; Engelke, Rebecca; Shepard, Kenneth L.; Drndić, Marija

doi:10.1021/nl504345y

Cited by 98 publications

(132 citation statements)

References 19 publications

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“…dielectric and capacitive, are mainly related to the capacitance of the system. 27,39,40 According to the geometry and material of our nanopore chip, the parasitic capacitance is estimated to be 30 pF. As the amplitude of the 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 7 where, α H the Hooge parameter and N c is the total number of conducting carriers.…”

Section: Acs Sensorsmentioning

confidence: 99%

Generalized Noise Study of Solid-State Nanopores at Low Frequencies

et al. 2017

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Nanopore technology has been extensively investigated for analysis of biomolecules, and a success story in this field concerns DNA sequencing using a nanopore chip featuring an array of hundreds of biological nanopores (BioNs). Solid-state nanopores (SSNs) have been explored to attain longer lifetime and higher integration density than what BioNs can offer, but SSNs are generally considered to generate higher noise whose origin remains to be confirmed. Here, we systematically study low-frequency (including thermal and flicker) noise characteristics of SSNs measuring 7 to 200 nm in diameter drilled through a 20-nm-thick SiN x membrane by focused ion milling. Both bulk and surface ionic currents in the nanopore are found to contribute to the flicker noise, with their respective contributions determined by salt concentration and pH in electrolytes as well as bias conditions. Increasing salt concentration at constant pH and voltage bias leads to increase in the bulk ionic current and noise therefrom. Changing pH at constant salt concentration and current bias results in variation of surface charge density, and hence alteration of surface ionic current and noise. In addition, the noise from Ag/AgCl electrodes can become predominant when the pore size is large and/or the salt concentration is high. Analysis of our comprehensive experimental results leads to the establishment of a generalized nanopore noise model. The model not only gives an excellent account of the experimental observations, but can also be used for evaluation of various noise components in much smaller nanopores currently not experimentally available.

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Section: Acs Sensorsmentioning

confidence: 99%

Generalized Noise Study of Solid-State Nanopores at Low Frequencies

et al. 2017

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“…Ideally, a voltage could be applied that would overcome the issue of Brownian motion while simultaneously reducing the velocity to a level where each nucleotide on a ssDNA molecule would be sampled for ≥20 μs. Importantly, advances have been made in increasing the bandwidth of detection instruments to the 1 to 5 MHz range [27,28] which reduce the necessary dwell time of each individual nucleotide, however molecules are still translocating over an order of magnitude too quickly for complete nanopore-based DNA sequencing to become a reality [27]. In order to address this issue, researchers have turned their attention to three basic components of the nanopore system -the environment, the molecule of interest, and the nanopore itself.…”

Section: Rapidity Of Dna Translocationmentioning

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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“…Future experiments should therefore make use of recent developments in lower noise nanopore chips to attempt detection of proteins at lower voltages with sufficiently high signal-to-noise ratios. 13,49 METHODS Nanopore Fabrication. Nanopores were formed in ultrathin, freestanding films of low-stress silicon nitride (SiN x ) using a 2010F JEOL Transmission Electron Microscope (TEM), as described previously.…”

Section: Discussionmentioning

confidence: 99%

Observing Changes in the Structure and Oligomerization State of a Helical Protein Dimer Using Solid-State Nanopores

et al. 2015

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Protein analysis using solid-state nanopores is challenging due to limitations in bandwidth and signal-to-noise ratio. Recent improvements of those two aspects have made feasible the study of small peptides using solid-state nanopores, which have an advantage over biological counterparts in tunability of the pore diameter. Here, we report on the detection and characterization of peptides as small as 33 amino acids. Silicon nitride nanopores with thicknesses less than 10 nm are used to provide signal-to-noise (S/N) levels up to S/N ∼ 10 at 100 kHz. We demonstrate differentiation of monomer and dimer forms of the GCN4-p1 leucine zipper, a coiled-coil structure well studied in molecular biology, and compare with the unstructured 33-residue monomer. GCN4-p1 is sequence segment associated with homodimerization of the transcription factor General Control Nonderepressible 4 (GCN4), which is involved in the control of amino acid synthesis in yeast. The differentiation between two oligomeric forms demonstrates the capabilities of improved solid-state nanopore platforms to extract structural information involving short peptide structures.

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Improving Signal-to-Noise Performance for DNA Translocation in Solid-State Nanopores at MHz Bandwidths

Cited by 98 publications

References 19 publications

Generalized Noise Study of Solid-State Nanopores at Low Frequencies

Generalized Noise Study of Solid-State Nanopores at Low Frequencies

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

Observing Changes in the Structure and Oligomerization State of a Helical Protein Dimer Using Solid-State Nanopores

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