Chemically Modified Solid-State Nanopores

Wanunu, Meni; Meller, A.

doi:10.1021/nl070462b

Cited by 351 publications

(335 citation statements)

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“…By analogy, engineered pores might be used to increase the capture efficiency of individual bases during exonuclease sequencing (9), which would be vital for accurate reads. Finally, these results with protein nanopores might be translated to solid-state nanopores by using chemical surface modification (55).…”

Section: Discussionmentioning

confidence: 93%

Enhanced translocation of single DNA molecules through α-hemolysin nanopores by manipulation of internal charge

Maglia

Rincón-Restrepo²,

Mikhailova³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

266

303

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Both protein and solid-state nanopores are under intense investigation for the analysis of nucleic acids. A crucial advantage of protein nanopores is that site-directed mutagenesis permits precise tuning of their properties. Here, by augmenting the internal positive charge within the ␣-hemolysin pore and varying its distribution, we increase the frequency of translocation of a 92-nt single-stranded DNA through the pore at ؉120 mV by Ϸ10-fold over the wild-type protein and dramatically lower the voltage threshold at which translocation occurs, e.g., by 50 mV for 1 event⅐s ؊1 ⅐ M ؊1 . Further, events in which DNA enters the pore, but is not immediately translocated, are almost eliminated. These experiments provide a basis for improved nucleic acid analysis with protein nanopores, which might be translated to solid-state nanopores by using chemical surface modification.DNA sequencing ͉ electroosmosis ͉ nanopore ͉ protein engineering ͉ single-molecule detection P ores with diameters of a few to hundreds of nanometers, ''nanopores,'' are being developed for a wide variety of analytical applications (1-5). Nanopores can be fabricated by using particle beams and etchants to treat various substrates, including silicon nitride (3, 6) and plastics, for instance poly(ethylene terephthalate) (4). Alternatively, protein pores such as ␣-hemolysin (␣HL) can be used (1, 5). In both cases, to be detected, an analyte must travel into the pore by electrodiffusion, but few systematic attempts have been made to optimize this process. In the present work, we show how the manipulation of charge on the internal surface of the ␣HL pore can be used to improve the rate of capture of an important analyte, DNA.The ␣HL protein nanopore is advantageous in sensing applications because it can be engineered with subnanometer precision with reference to the high resolution crystal structure (7). Further, the ␣HL pore is far more stable than commonly held, operating as normal at temperatures approaching 100°C (8). In stochastic sensing, a binding site for a family of analytes is formed within the pore by site-directed mutagenesis or targeted chemical modification (1). The concentration of an analyte is estimated from the number of binding events per unit time to a single pore. An analyte is identified through the signature provided by the amplitude and mean duration of the individual binding events. In this way, a great variety of analytes have been examined including: cations, anions, organic molecules, and various polymers (1). For example, all 4 DNA bases can be detected as nucleoside monophosphates by an ␣HL pore equipped with an aminocyclodextrin adapter (9). In addition, individual covalent chemical reactions occurring within the lumen of the pore can be observed (5), offering a basis for the detection of reactive molecules (10).Polymers can also be analyzed from the characteristics of transit events through the ␣HL pore (11-15). Studies of nucleic acids have been especially intensive, following the demonstration of the transit of single str...

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Section: Discussionmentioning

confidence: 93%

Enhanced translocation of single DNA molecules through α-hemolysin nanopores by manipulation of internal charge

Maglia

Rincón-Restrepo²,

Mikhailova³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

266

303

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“…† Due to highly confined nanostructure (radius in the order of 10 nm), ion-ion correlations were expected to be strong. To capture the strong correlation, the effective diameter of an ion, a, is fixed to be 7.5 nm, 30 so that ν is proportional to the bulk electrolyte concentration from eqn (9) of which values are summarized in ESI Table 2. †…”

Section: Counter-ion Condensationmentioning

confidence: 99%

Sub-10 nm transparent all-around-gated ambipolar ionic field effect transistor

Lee

Jin

et al. 2015

Nanoscale

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“…Figure 2 summarizes the three main new concepts that can be employed in these systems. One of the easiest and most obvious control mechanisms is surface modification [69]. The binding of polymers to the nanopore is a particularly successful and thus promising example (figure 2a).…”

Section: Solid-state Nanoporesmentioning

confidence: 99%

Controlling molecular transport through nanopores

Keyser

2011

J. R. Soc. Interface.

174

191

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Nanopores are emerging as powerful tools for the detection and identification of macromolecules in aqueous solution. In this review, we discuss the recent development of active and passive controls over molecular transport through nanopores with emphasis on biosensing applications. We give an overview of the solutions developed to enhance the sensitivity and specificity of the resistive-pulse technique based on biological and solid-state nanopores.

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Chemically Modified Solid-State Nanopores

Cited by 351 publications

References 53 publications

Enhanced translocation of single DNA molecules through α-hemolysin nanopores by manipulation of internal charge

Enhanced translocation of single DNA molecules through α-hemolysin nanopores by manipulation of internal charge

Sub-10 nm transparent all-around-gated ambipolar ionic field effect transistor

Controlling molecular transport through nanopores

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