Asymmetric Nanopore Electrode-Based Amplification for Electron Transfer Imaging in Live Cells

Yi Lun Ying, Yong Xu Hu, Rui Gao, Ru Jia Yu, Zhen Gu, Luke P. Lee, Yi Tao Long

Research output: Contribution to journalArticlepeer-review

205 Scopus citations


Capturing real-time electron transfer, enzyme activity, molecular dynamics, and biochemical messengers in living cells is essential for understanding the signaling pathways and cellular communications. However, there is no generalizable method for characterizing a broad range of redox-active species in a single living cell at the resolution of cellular compartments. Although nanoelectrodes have been applied in the intracellular detection of redox-active species, the fabrication of nanoelectrodes to maximize the signal-to-noise ratio of the probe remains challenging because of the stringent requirements of 3D fabrication. Here, we report an asymmetric nanopore electrode-based amplification mechanism for the real-time monitoring of NADH in a living cell. We used a two-step 3D fabrication process to develop a modified asymmetric nanopore electrode with a diameter down to 90 nm, which allowed for the detection of redox metabolism in living cells. Taking advantage of the asymmetric geometry, the above 90% potential drop at the two terminals of the nanopore electrode converts the faradaic current response into an easily distinguishable bubble-induced transient ionic current pattern. Therefore, the current signal was amplified by at least 3 orders of magnitude, which was dynamically linked to the presence of trace redox-active species. Compared to traditional wire electrodes, this wireless asymmetric nanopore electrode exhibits a high signal-to-noise ratio by increasing the current resolution from nanoamperes to picoamperes. The asymmetric nanopore electrode achieves the highly sensitive and selective probing of NADH concentrations as low as 1 pM. Moreover, it enables the real-time nanopore monitoring of the respiration chain (i.e., NADH) in a living cell and the evaluation of the effects of anticancer drugs in an MCF-7 cell. We believe that this integrated wireless asymmetric nanopore electrode provides promising building blocks for the future imaging of electron transfer dynamics in live cells.

Original languageEnglish
Pages (from-to)5385-5392
Number of pages8
JournalJournal of the American Chemical Society
Issue number16
StatePublished - 25 Apr 2018

Bibliographical note

Funding Information:
This research was supported by the National Natural Science Foundation of China (21421004 and 21505043), Innovation Program of Shanghai Municipal Education Commission (2017-01-07-00-02-E00023), the Program of Introducing Talents of Discipline to Universities (B16017), the “Chen Guang” project supported by Shanghai Municipal Education Commission and Shanghai Education Development Foundation (17CG27), and the Fundamental Research Funds for the Central Universities (222201718001, 222201717003, and 222201714012).

Publisher Copyright:
© 2018 American Chemical Society.


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