Method of Creating a Nanopore-Terminated Probe for Single-Molecule Enantiomer Discrimination

Gao, Changlu; Ding, Shu Li; Tan, Qiulin; Gu, Li-Qun

doi:10.1021/ac802348r

Cited by 91 publications

(119 citation statements)

References 56 publications

(115 reference statements)

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“…Reliably diameters of 30 nm can be reached using laser pullers; however to increase the sensitivity for smaller molecules smaller diameters would be essential. 9 Hence, a technique would be needed to further decrease the diameter of the laser-pulled glass nanocapillaries.…”

Section: T He Resistive Pulse Technique (Also Called Coulter Countermentioning

confidence: 99%

“…22 A similar technique is used by Gao et al who corrode a nanopore into a sealed capillary pipette using an HF solution. 9 Again the pore opening is controlled nonoptically by measuring the conductance. A novel technique were the pore diameter can even be changed in situ was presented by Platt, Willmott, and Lee who use a tunable pore made out of thermoplastic polyurethane membrane.…”

Section: T He Resistive Pulse Technique (Also Called Coulter Countermentioning

confidence: 99%

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Controllable Shrinking and Shaping of Glass Nanocapillaries under Electron Irradiation

Steinbock

Radenović

2013

Nano Lett.

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The ability to reshape nanopores and observe their shrinkage under an electron microscope is a powerful and novel technique. It increases the sensitivity of the resistive pulse sensing and enables to detect very short and small molecules. However, this has not yet been shown for glass nanocapillaries. In contrast to their solid-state nanopore counterparts, nanocapillaries are cheap, easily fabricated and in the production do not necessitate clean room facilities. We show for the first time that quartz nanocapillaries can be shrunken under a scanning electron microscope beam. Since the shrinking is caused by the thermal heating of the electrons, increasing the beam current increases the shrink rate. Higher acceleration voltage on the contrary increases the electron penetration depth and reduces the electron density causing slower shrinkage. This allows us to fine control the shrink rate and to stop the shrinking process at any desired diameter. We show that a shrunken nanocapillary detects DNA translocation with six times higher signal amplitudes than an unmodified nanocapillary. This will open a new path to detect small and short molecules such as proteins or RNA with nanocapillaries.

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Section: T He Resistive Pulse Technique (Also Called Coulter Countermentioning

confidence: 99%

Section: T He Resistive Pulse Technique (Also Called Coulter Countermentioning

confidence: 99%

Controllable Shrinking and Shaping of Glass Nanocapillaries under Electron Irradiation

Steinbock

Radenović

2013

Nano Lett.

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“…[12b, 14,15] We recently showed the possibility of using nanopipettes for resistive-pulse sensing of Au nanoparticles (AuNP), nanoparticles coated with an allergen epitope peptide layer, AuNP with bound antipeanut antibodies [16a] and protein biomarker. [16b] Similarly to a nanopore, a nanopipette can sense the analyte species entering and partially blocking its nanometer-sized orifice.…”

mentioning

confidence: 99%

Delivery of Single Nanoparticles from Nanopipettes under Resistive‐Pulse Control

2014

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“…In addition CDs bind to a variety of other pores, including porins (20,21) and connexins (22), and are being tested in vivo as blockers of the anthrax protective antigen pore (23,24). The CD adapter concept has also been incorporated into other formats, e.g., with glass nanopores (25), and artificial pores based on CDs have been made by several groups (26)(27)(28). Our work is pertinent to these studies.…”

mentioning

confidence: 99%

Molecular bases of cyclodextrin adapter interactions with engineered protein nanopores

Banerjee

Mikhailova

Cheley

et al. 2010

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

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108

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Engineered protein pores have several potential applications in biotechnology: as sensor elements in stochastic detection and ultrarapid DNA sequencing, as nanoreactors to observe singlemolecule chemistry, and in the construction of nano-and microdevices. One important class of pores contains molecular adapters, which provide internal binding sites for small molecules. Mutants of the α-hemolysin (αHL) pore that bind the adapter β-cyclodextrin (βCD) ∼10 4 times more tightly than the wild type have been obtained. We now use single-channel electrical recording, protein engineering including unnatural amino acid mutagenesis, and highresolution x-ray crystallography to provide definitive structural information on these engineered protein nanopores in unparalleled detail.alpha-hemolysin | single molecule | stochastic sensing | structure | unnatural amino acid M any research groups have used protein engineering to obtain enzymes and antibodies with new properties suited for specific tasks (1-6). Fewer groups have taken on the difficult problem of engineering membrane proteins (7). We have engineered the α-hemolysin protein pore, mindful of several potential applications in biotechnology, including its ability to act as a detector in stochastic sensing (8) and ultrarapid DNA sequencing (9), to serve as a nanoreactor for the observation of singlemolecule chemistry (10) and to act as a component for the construction of nano-and microdevices (11).An important breakthrough in this area, which enabled the stochastic sensing of organic molecules including the detection of DNA bases in the form of nucleoside monophosphates (12, 13), was the discovery of internal molecular adapters, a form of noncovalent protein modification (14). Most useful have been cyclodextrin (CD) adapters, which have until now been used in the absence of detailed structural information about how they work. The present paper is a definitive investigation, which provides such information through the application of a wide variety of technical approaches: single-channel electrical recording, protein engineering including unnatural amino acid mutagenesis, and x-ray crystallography. The studies employing mutagenesis show that the striking interactions seen in the crystal structures also occur in individual pores in lipid bilayers.We reveal that the tight-binding αHL mutants (15) M113N 7 and M113F 7 bind βCD in different orientations within the heptameric pore. In the case of M113N 7 , the top (primary hydroxyls) of the CD ring faces the trans entrance of the pore. In the case of M113F 7 , the bottom (secondary hydroxyls) of the CD ring faces the trans entrance, while the top of the ring is bonded to the pore through remarkable CH-π interactions. Another tight-binding mutant, M113V 7 , can bind the CD in both orientations. These results illustrate the exquisite level of engineering that can be achieved with protein nanopores, which is, for example, far beyond what is possible with solid-state pores. The work also provides information valuable for the design of ...

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Method of Creating a Nanopore-Terminated Probe for Single-Molecule Enantiomer Discrimination

Cited by 91 publications

References 56 publications

Controllable Shrinking and Shaping of Glass Nanocapillaries under Electron Irradiation

Controllable Shrinking and Shaping of Glass Nanocapillaries under Electron Irradiation

Delivery of Single Nanoparticles from Nanopipettes under Resistive‐Pulse Control

Molecular bases of cyclodextrin adapter interactions with engineered protein nanopores

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