Single-molecule sensing with nanopores

Muthukumar, Murugappan; Plesa, Calin; Dekker, Cees

doi:10.1063/pt.3.2881

Cited by 71 publications

(83 citation statements)

References 20 publications

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“…11 However, shrinking the pore diameter directly leads to the predominance of the surface current contribution and a decrease in number of carriers thereby increase in fluctuation of ionic current. This signal-noise dilemma may find remedies by examining the root causes of noise and the relationship between noise and operational conditions.…”

Section: E Strategies For Signal Enhancement and Noise Controlmentioning

confidence: 99%

“…10 A success example is the use of biological or synthetic nanopores (BioNs), such as α-Hymolysin, immobilized onto a biological membrane to sequence DNA, [11][12][13] a pursuit that already began in the 1990's and has led to a portable DNA sequencing system MinION being commercialized by Oxford Nanopore Technologies. 14 However, nanopore sensors based on the BioN-membrane combination usually suffer from mechanical fragility with short lifetime and sensitivity to working environments.…”

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confidence: 99%

“…14 However, nanopore sensors based on the BioN-membrane combination usually suffer from mechanical fragility with short lifetime and sensitivity to working environments. 11 Compatibility with the well-developed silicon process technology is also highly desired in order to achieve massively parallelized sequencing at low costs. 11,15 Solid-state nanopores (SSNs) have, therefore, been intensively explored in recent years as a competitive alternative to the biological ones for high-throughput sequencing of single DNA strands.…”

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confidence: 99%

“…One of the major challenges with SSNs is its high background noise level, 11,16 which can severely distort the very weak signal carrying critical information of the detected molecules.…”

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confidence: 99%

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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: E Strategies For Signal Enhancement and Noise Controlmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

“…One of the major challenges with SSNs is its high background noise level, 11,16 which can severely distort the very weak signal carrying critical information of the detected molecules.…”

mentioning

confidence: 99%

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Generalized Noise Study of Solid-State Nanopores at Low Frequencies

et al. 2017

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“…A fairly good understanding of the mechanism pertaining to variations in ionic current caused by DNA translocation has been established and it gives valuable insights for general nanopore design and operation. [29] But much remains to be confirmed with respect to the influence on ionic current of pore size, size of nts, translocation speed and manner, sampling rate and bandwidth, noise, morphology (position and orientation) of nts inside and nearby the pore, ionic strength and nature of ions in the two electrolyte reservoirs, membrane properties, etc. The nanopore sequencing builds on the assumption that the variations in ionic current are predominantly, if not solely, determined by the differences in nts.…”

Section: Introductionmentioning

confidence: 99%

On nanopore DNA sequencing by signal and noise analysis of ionic current

et al. 2016

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Scheicher, R. et al. (2016) On nanopore DNA sequencing by signal and noise analysis of ionic current. Our focus is placed on signal-boosting and noise-suppressing strategies in order to attain the single-nucleotide resolution. Apart from decreasing pore diameter and thickness, it is crucial to also reduce the translocation speed and facilitate a stepwise translocation. Our best-case scenario analysis points to severe challenges with employing plain nanopore technology, i.e., without recourse to any signal amplification strategy, in achieving sequencing with the desired single-nucleotide resolution. A conceptual approach based on strand synthesis in the nanopore of the translocating DNA from single-stranded to double-stranded is shown to yield a 10-fold signal amplification. Although it involves no advanced physics and is very simple in mathematics, this simple model captures the essence of nanopore sequencing and is useful in guiding the design and operation of nanopore sequencing. Nanotechnology

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Recent Advances in Nanopore Sensing†

Cui

Zhuge

et al. 2021

Chin. J. Chem.

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Nanopore sensing is developing into a powerful label‐free approach to investigate the features of biomolecules at the single‐molecule level. When a charged molecule is captured within a nanopore, it modulates the ionic current, which can be recorded in real time to reveal the properties of the target molecule. To date, nanopores have been used to sense a variety of analytes, including DNA, RNA, proteins, enzymes, small molecules, cancer cells, and metal ions, and can also provide information on biomolecular structures. In this review, we highlight the progress made in nanopore sensing over the past five years (2016—2020), and provide an outlook on future developments and directions in the field

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Single-molecule sensing with nanopores

Abstract: A 70-year-old idea for measuring blood cells has evolved into a powerful, versatile tool for studying DNA, proteins, and other biomolecules.

Cited by 71 publications

References 20 publications

Generalized Noise Study of Solid-State Nanopores at Low Frequencies

Generalized Noise Study of Solid-State Nanopores at Low Frequencies

On nanopore DNA sequencing by signal and noise analysis of ionic current

Recent Advances in Nanopore Sensing†

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