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SCIENCE CHINA Chemistry, Volume 62 , Issue 12 : 1576-1587(2019) https://doi.org/10.1007/s11426-019-9509-6

Nanopore-based sensing interface for single molecule electrochemistry

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  • ReceivedApr 19, 2019
  • AcceptedMay 30, 2019
  • PublishedJul 19, 2019

Abstract


Funded by

the National Natural Science Foundation of China(61871183,21834001)

Yi-Lun Ying is sponsored by National Ten Thousand Talent Program for young top-notch talent and Shanghai Rising-Star Program(19QA1402300)

Yao Lin is sponsored by the China Scholarship Council(201806740044)


Acknowledgment

This work was supported by the National Natural Science Foundation of China (61871183, 21834001), Yi-Lun Ying is sponsored by National Ten Thousand Talent Program for young top-notch talent and Shanghai Rising-Star Program (19QA1402300), Yao Lin is sponsored by the China Scholarship Council (201806740044). We acknowledge Professor Dong-Ping Zhan’s valuable suggestions and great help to this review.


Interest statement

The authors declare that they have no conflict of interest.


Contributions statement

These authors contributed equally to this work.


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  • Figure 1

    (a) Structure of aerolysin heptamer (PDB ID: 5JZT). (b) Illustration of Poly(dA)4 translocating through wild-type and mutant aerolysin nanopores. Positively charged amino acids (R220 and K238) produce distinguishable current blockage. R220E mutant generates a high entropic energy barrier for the negatively charged oligonucleotide molecules. K238E mutant negatively charged glutamic acid at the lumen leads to a prolonged duration for the analyte. Reproduced with permission from Ref. [28], copyright 2018, American Chemical Society. (c) A plasmonic assisted controlled dielectric breakdown for self-aligned formation of nanopores. The nanopore is generated at the optical field hotspot of the plasmonic nanostructure. Reproduced with permission from Ref. [47], copyright 2015, American Chemical Society. (d) Detection mechanism of wireless nanopore electrode. The nanopore with a metal layer inside where the bipolar electrochemical reactions can occur at the two terminals when a sufficient potential applied. (e) A hybrid nanopore comprising a hydrophilic portal protein derived from the thermostable virus G20c embedded into a silicon nitride nanopore. Reprinted with permission from Ref. [65], open access copyright under a Creative Commons Attribution 4.0 International (CC BY 4.0) License. (f) DNA origami-solid state nanopore for single molecule detection. Reproduced with permission from Ref. [67], copyright 2012, John Wiley and Sons (color online).

  • Figure 2

    (a) Detection schematic of the uracil-DNA glycosylase reaction by the latch sensitive zone of a wide-type α-HL. Reproduced with permission from Ref. [78], copyright 2013, American Chemical Society. (b) Scheme of a dsDNA captured by the α-HL and typical current oscillations of the backbone demage in a DNA duplex. Reproduced with permission from Ref. [79], copyright 2016, American Chemical Society. (c) Discrimination of oligonucleotides of different lengths with a wild-type aerolysin nanopore. Left: illustration of an aerolysin nanopore-based detection for a short oligonucleotide; right: current trace and histogram for the detection of mixed dA2, dA3, dA4, dA5, and dA10. Reproduced with permission from Ref. [27], copyright 2016, Springer Nature. (d) The detection of a 102 nt ssDNA by an aerolysin nanopore in LiCl (left) and KCl (right) solution. Reprinted with permission from Ref [81], open access copyright under a Creative Commons Attribution-NonCommercial 3.0 Unported (CC BY-NC 3.0) Licence. (e) Detection of single oligonucleotide photoisomers by an aerolysin nanopore. Top: reversible conversion of Azo-ODN molecule under UV-Vis irradiation; bottom: the structural variation detection of the Azo-ODN molecule by an aerolysin nanopore and the corresponding current distribution controlled by light. Reproduced with permission from Ref. [82], copyright 2018, American Chemical Society (color online).

  • Figure 3

    (a) The current trace and two typical blockages of DNA duplexes traversing the solid-state nanopore under a 400 mV bias voltage. Type I: a DNA duplex translocation event with unzipping in the pore; type II: the resident of a DNA duplex inside the pore. Reproduced with permission from Ref. [86], copyright 2017, Royal Society of Chemistry. (b) The schematic and current trace of a streptavidin-ssDNA complex capture, docking, and release process by the solid-state nanopore. Under a positive bias voltage, the DNA complex is attracted in the pore inducing a current fluctuation in the current trace and it is released at a negative potential. Reproduced with permission from Ref. [87], copyright 2018, American Chemical Society. (c) Experiment representation of the nanopore detection of DNA molecule manipulated by optical tweezers. Top: the setup schematic, the SEM image of the nanopore, and the image of optically trapped DNA-coated bead with nanopore tip. The schematic is not to scale, the scale bar in SEM image is 2 μm and in the optical image is 3 μm. Bottom: current trace from a single molecule translocation process driven by optical tweezers. Reproduced with permission from Ref. [89], copyright 2014, American Chemical Society. (d) Schematic and time-dependent signals on plasmonic nanopore-based single DNA molecule detection. Top left: schematic of DNA translocation through a plasmonic nanopore detected by ionic current oscillation and optical backscattering readout. Top right: comparison of ionic current and scattering intensity of all data points; bottom: ionic current (blue) readout and backscattering (orange) trace of the single molecule detection. Reprinted with permission from Ref. [95], open access copyright under a Creative Commons Attribution Non-Commercial No Derivative Works (CC-BY-NC-ND) 4.0 license (color online).

  • Figure 4

    (a) Illustration of Aβ35–25 and Aβ25–35 translocating through α-HL nanopore. Aβ35–25 adopts random coil (red) while Aβ25–35 β-sheet (blue) as their initial structures. Their initial structures could be distinguished in real-time by the characteristic blockades. Reproduced with permission from Ref. [102], copyright 2016, Royal Society of Chemistry. (b) Detection of a mixture of arginine peptides of different lengths (5, 6, 7, 8, 9, and 10 amino acids). Peptides of single amino acid differences can be well discriminated with the current signals. Reprinted with permission from Ref. [118], open access copyright under a Creative Commons Attribution 4.0 International (CC BY 4.0) License (color online).

  • Figure 5

    (a) Schematic of the detection of H2 and Ag+ at the single-molecule level and the corresponding typical current signal by a silver-coated WNE. Reproduced with permission from Ref. [62], copyright 2017, American Chemical Society. (b) The gold-coated WNE for nicotinamide adenine dinucleotide (NADH) detection in the single cell and the redox reaction induced transient responses. Reproduced with permission from Ref. [130], copyright 2018, American Chemical Society. (c) Schematic of a nanoparticle collision experiment by the close-type WNE and the corresponding current signals from mixed nanoparticle sample. The red spikes represent collision events caused by 60 nm gold nanoparticles and the spikes in blue are from the 13 nm gold nanoparticles collision process. Reproduced with permission from Ref. [131], copyright 2017, John Wiley and Sons. (d) Schematic of the fabrication of a gold scanning probe for electrochemical imaging. Left: schematic of experiment setup and the conical gold nanowire deposited inside the nanopore by a bipolar electrodeposition; right: the SECM imaging of one single gold nanoparticle produced by the deposited nanopore. The scale bar is 50 nm. Reproduced with permission from Ref. [132], copyright 2017, Springer Nature (color online).

  • Figure 6

    (a) Intelligent identification of multi-level current blockage recognition for accurate detection of cancer biomarkers. Left: the translocation process of microRNA 21 Probe21 molecule. Middle: the computational procedure of the HMM based algorithm; right: the original blockage of the target molecule (black) and the algorithm identified current (red). Reproduced with permission from Ref. [138], copyright 2017, Royal Society of Chemistry. (b) Schematic of the DBC method-based data process and the blockage recognition procedure. Reproduced with permission from Ref. [143], copyright 2015, American Chemical Society. (c) Nanopore sensing for DNA molecules and the data analysis process by convolutional neural networks. Reprinted with permission from Ref. [144], open access copyright under a Creative Commons Attribution Non-Commercial No Derivative Works (CC-BY-NC-ND) 4.0 license. (d) The HHT analysis for the ionic responses from wild type (K238) and mutant K238E aerolysin. Left: schematic of a DNA molecule detection; middle: the empirical mode decomposition results derived from intrinsic mode functions; right: the energy-frequency-time Hilbert spectra of a DNA translocation event. Reproduced with permission from Ref. [145], copyright 2018, Royal Society of Chemistry (color online).

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