Letter | Published:

Free-standing kinked nanowire transistor probes for targeted intracellular recording in three dimensions

Nature Nanotechnology volume 9, pages 142147 (2014) | Download Citation

Abstract

Recording intracellular (IC) bioelectrical signals is central to understanding the fundamental behaviour of cells and cell networks in, for example, neural and cardiac systems1,2,3,4. The standard tool for IC recording, the patch-clamp micropipette5 is applied widely, yet remains limited in terms of reducing the tip size, the ability to reuse the pipette5 and ion exchange with the cytoplasm6. Recent efforts have been directed towards developing new chip-based tools1,2,3,4,7,8,9,10,11,12,13, including micro-to-nanoscale metal pillars7,8,9, transistor-based kinked nanowires10,11 and nanotube devices12,13. These nanoscale tools are interesting with respect to chip-based multiplexing, but, so far, preclude targeted recording from specific cell regions and/or subcellular structures. Here we overcome this limitation in a general manner by fabricating free-standing probes in which a kinked silicon nanowire with an encoded field-effect transistor detector serves as the tip end. These probes can be manipulated in three dimensions within a standard microscope to target specific cells or cell regions, and record stable full-amplitude IC action potentials from different targeted cells without the need to clean or change the tip. Simultaneous measurements from the same cell made with free-standing nanowire and patch-clamp probes show that the same action potential amplitude and temporal properties are recorded without corrections to the raw nanowire signal. In addition, we demonstrate real-time monitoring of changes in the action potential as different ion-channel blockers are applied to cells, and multiplexed recording from cells by independent manipulation of two free-standing nanowire probes.

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Acknowledgements

C.M.L. acknowledges support of this work by a National Institutes of Health Director's Pioneer Award (5DP1OD003900), National Basic Research Program of China (2013CB934103), and International Science & Technology Corporation Program of China (2013DFA50840).

Author information

Author notes

    • Quan Qing
    •  & Zhe Jiang

    These authors contributed equally to this work

Affiliations

  1. Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA

    • Quan Qing
    • , Zhe Jiang
    • , Lin Xu
    • , Ruixuan Gao
    •  & Charles M. Lieber
  2. State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, WUT-Harvard Joint Nano Key Laboratory, Wuhan University of Technology, Wuhan 430070, China

    • Lin Xu
    • , Liqiang Mai
    •  & Charles M. Lieber
  3. School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, USA

    • Charles M. Lieber

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Contributions

Q.Q., Z.J. and C.M.L. designed the experiments, Q.Q., Z.J., and L.X. performed the experiments, R.G. helped in cardiomyocyte culture experiments, Q.Q., Z.J., L.X. and C.M.L. analysed data and Q.Q., Z.J. and C.M.L. wrote the paper. All authors discussed the results and commented on the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Charles M. Lieber.

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DOI

https://doi.org/10.1038/nnano.2013.273

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