Protein detection using tunable pores: resistive pulses and current rectification

Blundell, Emma L. C. J.; Mayne, Laura J.; Lickorish, Michael; Christie, S.; Platt, Mark

doi:10.1039/c6fd00072j

Cited by 31 publications

(56 citation statements)

References 60 publications

(155 reference statements)

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“…Whilst some current rectification is observed here, it is likely to be a small contributing factor in the experiment and on a much smaller scale then seen in other TRPS systems. 40 …”

Section: Resultsmentioning

confidence: 99%

“…38,39 Conical nanopores, as used within TRPS, exhibit ionic rectification properties. [40][41][42][43] The charge on the pore wall creates areas of ion accumulation and depletion within the pore depending on the applied polarity. 42,[44][45][46] This leads to the current being higher at one voltage compared to the voltage of opposite polarity, often expressed as the rectification ratio.…”

Section: Introductionmentioning

confidence: 99%

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A tunable nanopore sensor for the detection of metal ions using translocation velocity and biphasic pulses

2016

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Citation: MAYNE, L.J., CHRISTIE, S.D.R. and PLATT, M., 2016. A tunable nanopore sensor for the detection of metal ions using translocation velocity and biphasic pulses. Nanoscale, 8, 19139-19147. Additional Information:• This paper was accepted for publication in the journal ) from solution. By tuning the pH and ionic strength of the solution, a biphasic pulse, a conductive followed by a resistive pulse is recorded. Biphasic pulses are becoming a powerful way to characterise materials, and provide an insight into the translocation mechanism, and here we present their first use to detect the presence of metal ions in solution. We demonstrate how combinations of translocation speed and/ or biphasic pulse behaviour are used to detect Cu

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“…Whilst some current rectification is observed here, it is likely to be a small contributing factor in the experiment and on a much smaller scale then seen in other TRPS systems. 40 …”

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A tunable nanopore sensor for the detection of metal ions using translocation velocity and biphasic pulses

2016

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“…Only in recent years, nanopore technology has been extended to protein sequencing as nanopores could sequence full‐length proteins with high temporal and spatial resolution while traditional sequencing methods such as mass spectrometry and Edman degradation only rely on digestion of proteins into short peptides. Many experiments have shown that protein molecules can be electrophoretically driven through nanopores . Some experiments showed that proteins can be unfolded using nanopores by adjusting pH values of the solution, adding denaturing agents into the solution, increasing the applied bias voltage, elevating system temperature, using tiny nanopores smaller than the protein or by a molecular motor .…”

Section: Introductionmentioning

confidence: 99%

Discrimination of Protein Amino Acid or Its Protonated State at Single‐Residue Resolution by Graphene Nanopores

Zhang

et al. 2019

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cellular processes at a single-molecule level by taking advantage of the electrochemical nanoconfinement of a nanopore. Thus nanopore is a powerful sensor for investigation of fundamental physical, chemical or biological issues, such as molecule gating [5] and cation-induced current changing, [6] at single-molecule resolution [8] compared to other traditional technologies. To date, nanopores have been exploited for expanded applications, including detection of nanoparticles, [9][10][11] biopolymers, [1,12] proteins, [13][14][15] DNA-origami, [16] DNA-protein complexes, [17][18][19][20] and so on. One of the most potential applications of nanopore technology is nucleic acid sequencing, which is characterized as low cost and high throughput. Most recently, a lot of works have shown that each type of DNA nucleotide can induce correlated modulation of ionic current as they translocate through a nanopore. [12,[21][22][23] With the help of enzyme [24] or polymerase, [25] some biological nanopores [26,27] have shown the ability to determine the nucleotide sequence of a singlestranded DNA at single-base resolution.Different from DNA molecules, proteins consist of more than 20 amino acids (AAs) and are irregularly and slightly charged. Besides, proteins usually keep in folded state in natural environment. Thus, investigation of proteins is much more challenging than DNA. Unraveling the mechanisms of protein folding and unfolding and even realizing protein sequencing are essential for cellular behaviors and diseases. [28] Measurement of tunneling current [29,30] was reported to recognize single amino acids, however to make the tunneling device be a protein sequencing tool it should be coupled with a means that can thread the peptide chain through the gap in a controllable way, which could be possibly realized if the tunneling device is coupled to a nanopore. In the past two decades, most interests in nanopores have focused on DNA sequencing. Only in recent years, nanopore technology has been extended to protein sequencing as nanopores could sequence full-length proteins with high temporal and spatial resolution while traditional sequencing methods such as mass spectrometry [31] and Edman degradation [32] only rely on digestion of proteins into short peptides. Many experiments have shown that protein molecules can be electrophoretically driven through nanopores. [33,34] Some experiments showed that proteins can be unfolded using nanopores by adjusting pH values of the solution, [35] The function of a protein is determined by the composition of amino acids and is essential to proteomics. However, protein sequencing remains challenging due to the protein's irregular charge state and its high-order structure. Here, a proof of principle study on the capability of protein sequencing by graphene nanopores integrated with atomic force microscopy is performed using molecular dynamics simulations. It is found that nanopores can discriminate a protein sequence and even its protonation state at single-residue resolution. Both the pull...

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“…24,25 This is measured through a change in translocation velocity and can provide quantitative information. [26][27][28] However RPS signals can be affected by the experimental setup. Studies have shown that ionic strength, off-axial translocation, the pore wall charge density and applied potential can affect the pulse size and width.…”

Section: Introductionmentioning

confidence: 99%

The Design and Characterization of Multifunctional Aptamer Nanopore Sensors

et al. 2018

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Aptamer-modified nanomaterials provide a simple, yet powerful sensing platform when combined with resistive pulse sensing technologies. Aptamers adopt a more stable tertiary structure in the presence of a target analyte, which results in a change in charge density and velocity of the carrier particle. In practice the tertiary structure is specific for each aptamer and target, and the strength of the signal varies with different applications and experimental conditions. Resistive pulse sensors (RPS) have single particle resolution, allowing for the detailed characterization of the sample. Measuring the velocity of aptamer-modified nanomaterials as they traverse the RPS provides information on their charge state and densities. To help understand how the aptamer structure and charge density effects the sensitivity of aptamer-RPS assays, here we study two metal binding aptamers. This creates a sensor for mercury and lead ions that is capable of being run in a range of electrolyte concentrations, equivalent to river to seawater conditions. The observed results are in excellent agreement with our proposed model. Building on this we combine two aptamers together in an attempt to form a dual sensing strand of DNA for the simultaneous detection of two metal ions. We show experimental and theoretical responses for the aptamer which creates layers of differing charge densities around the nanomaterial. The density and diameter of these zones effects both the viability and sensitivity of the assay. While this approach allows the interrogation of the DNA structure, the data also highlight the limitations and considerations for future assays.

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Protein detection using tunable pores: resistive pulses and current rectification

Cited by 31 publications

References 60 publications

A tunable nanopore sensor for the detection of metal ions using translocation velocity and biphasic pulses

A tunable nanopore sensor for the detection of metal ions using translocation velocity and biphasic pulses

Discrimination of Protein Amino Acid or Its Protonated State at Single‐Residue Resolution by Graphene Nanopores

The Design and Characterization of Multifunctional Aptamer Nanopore Sensors

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