SCIENCE CHINA Chemistry, Volume 60, Issue 10: 1277-1284(2017) https://doi.org/10.1007/s11426-017-9109-7

Nanoelectrochemical architectures for high-spatial-resolution single cell analysis

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  • ReceivedApr 20, 2017
  • AcceptedJul 7, 2017
  • PublishedAug 11, 2017


The analysis of single cells instead of cell populations is important for characterizing cellular heterogeneity and elucidating the cellular signalling pathways. Nanoelectrodes have emerged as an increasingly important tool for biomolecule analyses at the single-cell level with high spatial or temporal resolution. Various electrochemical methods, such as amperometry and scanning electrochemical microscopy (SECM), have been applied. Research to date has focused on the development of new nanoelectrochemical architectures, such as arrays, to achieve higher spatial resolution and faster analysis rates for single-cell analysis. In this review, the fabrication of these new nanoelectrochemical architectures and their applications in high spatial resolution single-cell analyses are discussed. The recent progress of Chinese researchers is highlighted.


This work was supported by the National Natural Science Foundation of China (21327902).

Interest statement

The authors declare that they have no conflict of interest.


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  • Figure 1

    Schematic diagrams of the (a) modified laser-assisted pulling process to prepare Pt nanoelectrodes. Reprinted with permission from Ref. [28], copyright 2009 American Chemical Society. (b) The preparation of the capillary with a Pt ring at the nanotip. Reprinted with permission from Ref [29], copyright 2016 National Academy of Sciences (color online).

  • Figure 2

    Simultaneous monitoring of vesicular exocytosis under “semi-artificial synapse” and “inside synapse” configurations with two CFNEs. (a,b) Schematic diagram (a) and photomicrograph (b) of two CFNEs (black arrows; the left one is inside the synapse, and the right one is on top of the synapse) to simultaneously detect vesicular exocytosis from the basal and apical pole of a single varicosity (white arrow). (c) Quantal amperometric spikes (the upper and bottom traces represent current spikes recorded on the electrodes inside the synapse and at the apical pole). Reprinted with permission from Ref. [47], copyright 2014 John Wiley and Sons (color online).

  • Figure 3

    (A) Optical microscopic micrograph of a nanoelectrode (a=75 nm; 800 nm O.D.) inside a macrophage and two typical amperometric current traces of the ROS/RNS release inside a macrophage, which is induced by the insertion of a platinized nanoelectrode. Reprinted with permission from Ref. [50], copyright 2012 National Academy of Sciences. (B) Bright-field photomicrograph of a nanotip conical carbon-fiber microelectrode, which is placed in the cytoplasm of a single PC12 cell (scale bar: 20 μm), and amperometric trace for a nanotip conical carbon-fibre microelectrode placed inside a PC12 cell. Reprinted with permission from Ref. [51], copyright 2015 John Wiley and Sons. (C) Bright-field image of a nanocapillary inserted into the cell and the difference in charges after the extraction of the nonfaradic charge collected outside the cell using capillaries, which include glucose oxidase (trace a) or PBS alone. Reprinted with permission from Ref. [29], copyright 2016 National Academy of Sciences (color online).

  • Figure 4

    (A) Nanopillar electrode devices and their interactions with HL-1 cardiomyocytes. (a) An optical image of a nanopillar electrode device with 4-by-4 Pt pads and leads connected to the recording amplifiers; (b) an scanning electron microscope (SEM) image of an array of five 150 nm-diameter, 1.5 μm-long vertical nanopillar electrodes on the Pt pad as shown in (a). (B) Parallel intracellular recording of multiple HL-1 cells in the same culture and monitoring of the action potential evolution of single cells in consecutive days. (a) Simultaneous intracellular recording with five different electrodes in the same culture before confluence; (b) extracellular (left) and intracellular (right) recording of a mature HL-1 cell in 3 consecutive days. The action potential shape and amplitude exhibit minimal changes. Reprinted with permission from Ref. [68], copyright 2012 Nature Publishing Group. (C) Optical image of an aligned axon crossing an array of 50 NW devices with a 10-μm interdevice spacing. (D) Electrical data from the 50-device array. The yield of the functional devices is 86%. The peak latency from NW1 (top arrow) to NW49 (bottom arrow) is 1060 μs. Reprinted with permission from Ref. [71], copyright 2006 American Association for the Advancement of Science (color online).

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