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SCIENCE CHINA Chemistry, Volume 60 , Issue 9 : 1187-1190(2017) https://doi.org/10.1007/s11426-017-9082-5

Single-molecule analysis in an electrochemical confined space

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  • ReceivedApr 20, 2017
  • AcceptedMay 18, 2017
  • PublishedJul 17, 2017

Abstract

Electrochemical analysis of single molecules is a method with the strong ability of the enhanced efficiency and ultra-sensitivity. Here, we demonstrate that the electrochemical confined space could efficiently convert single molecule characteristics into measurable electrochemical signatures with high temporal resolution. The human telomere repeat sequence T8 was used as a probe to determine the electrochemical confined effect in a nanopore. Our results show that the nanopore with comparable confined space of the telomere repeat sequence exhibits the most distinguishable single-molecule signals which suggest the folded conformation of T8. This method will greatly extend the lifetime of a metastable conformation for a single biomolecule by strong analyte-nanopore interactions, which brings the new insight into the understanding of the biomolecule’s function at single-molecule level.


Funded by

National Natural Science Foundation of China(21421004,21505043,21327807)

Fundamental Research Funds for the Central Universities(222201718001,222201717003,222201714012)


Acknowledgment

This work was supported by the National Natural Science Foundation of China (21421004, 21505043, 21327807), and the Fundamental Research Funds for the Central Universities (222201718001, 222201717003, 222201714012).


Interest statement

The authors declare that they have no conflict of interest.


Supplement

The supporting information is available online at http://chem.scichina.com and http://link.springer.com/journal/11426. The supporting materials are published as submitted, without typesetting or editing. The responsibility for scientific accuracy and content remains entirely with the authors.


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  • Figure 1

    (a) Schematic illustration of human telomeric DNA T8 detection using a solid-state nanopore. During the experiment, the nanopore chip is placed to divide two chambers of 50 mM KCl with 950 mM LiCl (pH 8) solution. A pair of Ag/AgCl electrodes was immersed into two chambers and connected to the amplifier. A SiNx membrane separates the cis and trans compartments. Initially the T8 molecules was added to the cis side with only buffer in the trans side. A voltage is applied across the membrane to drive the human telomeric DNA T8 into the pore. (b) The diagram of electric circuit for integrating the nanopore fabrication with the electrical detection device. (c) A leakage current at 8 V on a 10 nm SiNx membrane in 1 M KCl, 10 mM Tris, and 1 mM EDTA (pH 10) solution. The nanopore is allowed to grow until a predetermined threshold of 120 nA current is reached, at which point the voltage is cut off (color online).

  • Figure 2

    (a) I-V curves of seven fabricated SiNx nanopores by CDB measured in 1 M KCl (pH 8). The diameters of the five pores are 1.7, 3.8, 6.2, 7.3, 8.4, 9.8 and 12.1 nm corresponding to its conductance of 5.0, 17.5, 37.4, 46.6, 56.3, 69.8 and 91.2 nS, respectively. All pores are equilibrated for several hours in 4 M LiCl (pH 8) until the pores are stable and not rectifying. The I-V characterization details are shown in Supporting Information online. (b) Three TEM images of nanopores fabricated by CDB (color online).

  • Figure 3

    (a) Current traces of T8 using a 1.7 nm solid-state nanopore at an applied voltage of 300 mV. (b) The corresponding histograms of current blockade (Δi/i0) and duration time for T8. The histogram of Δi/i0 and duration time is fitted to a Gaussian function. (c) Current trace of T8 using a 6.2 nm solid-state nanopore at applied voltage of 300 mV. (d) The corresponding histograms of current blockade (Δi/i0) and duration time for T8. The histogram of Δi/i0 is fitted to a Gaussian function, and the histogram of duration time is fitted to an exponential function (color online).

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