Much of the functionality of multicellular systems arises from the spatial organization and dynamic behaviours within and between cells. Current single-cell genomic methods only provide a transcriptional ‘snapshot’ of individual cells. The real-time analysis and perturbation of living cells would generate a step change in single-cell analysis. Here we describe minimally invasive nanotweezers that can be spatially controlled to extract samples from living cells with single-molecule precision. They consist of two closely spaced electrodes with gaps as small as 10–20 nm, which can be used for the dielectrophoretic trapping of DNA and proteins. Aside from trapping single molecules, we also extract nucleic acids for gene expression analysis from living cells without affecting their viability. Finally, we report on the trapping and extraction of a single mitochondrion. This work bridges the gap between single-molecule/organelle manipulation and cell biology and can ultimately enable a better understanding of living cells.

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The data that support the plots within this paper and other findings of this study are available from the corresponding author upon reasonable request.

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J.B.E. has been funded in part by an ERC starting (NanoP) and consolidator (NanoPD) investigator grant. A.P.I. and J.B.E. acknowledge support from EPSRC grant EP/P011985/1 and BBSRC grant BB/R022429/1. A.P.I. acknowledges IC Research Fellowship funding. We thank B. Akpinar for helping with TEM and EDX spectroscopy and S. Rothery for helping with the cell viability studies. A.B. and S.-H.O. acknowledge support from the US National Science Foundation (NSF ECCS no. 1610333). M.J.D. is supported by a Wellcome Trust Clinical Postdoctoral Fellowship (106713/Z/14/Z) and J.T.K. received funding from an ERC starting grant (282430).

Author information

Author notes

  1. These authors contributed equally: Binoy Paulose Nadappuram, Paolo Cadinu.


  1. Department of Chemistry, Imperial College London, London, UK

    • Binoy Paulose Nadappuram
    • , Paolo Cadinu
    • , Alexander J. Ainscough
    • , Minkyung Kang
    • , Jorge Gonzalez-Garcia
    • , Keith R. Willison
    • , Ramon Vilar
    • , Aleksandar P. Ivanov
    •  & Joshua B. Edel
  2. Department of Electrical and Computer Engineering, University of Minnesota, Minneapolis, MN, USA

    • Avijit Barik
    •  & Sang-Hyun Oh
  3. Department of Experimental Medicine and Toxicology, Imperial College London, London, UK

    • Alexander J. Ainscough
    •  & Beata Wojciak-Stothard
  4. Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK

    • Michael J. Devine
    •  & Josef T. Kittler
  5. School of Electronic and Electrical Engineering, Pollard Institute, University of Leeds, Leeds, UK

    • Paolo Actis


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J.B.E. and A.P.I. designed and supervised the research. B.P.N. and P.C. performed the experiments and contributed equally to this work. B.P.N., P.C., J.B.E. and A.P.I. analysed the data and prepared the manuscript. A.B. and S.-H.O. developed the finite element model and performed the theoretical calculations. A.J.A., M.J.D., J.G.-G. and B.W.-S. prepared the cell samples and contributed to the cell biopsy experiments. M.K. recorded the electron micrographs. J.T.K., K.R.W., R.V. and P.A. helped with the experiments. All the authors discussed the results and commented on the manuscript.

Competing interests

The authors declare no competing interests.

Corresponding authors

Correspondence to Aleksandar P. Ivanov or Joshua B. Edel.

Supplementary information

  1. Supplementary Information

    Supplementary Results, Supplementary Figures 1–15, Supplementary Table 1, Supplementary References

  2. Reporting Summary

  3. Single-molecule trapping and writing (SI section 10b)

    Video showing the pick and release of single 10 kbp DNA molecule using the DEP nanotweezers. The DNA molecule was captured at the nanotweezer tip by turning on the a.c. field (DEP on). Transfer of the captured single molecule from one position to another was achieved by moving the nanotweezer using a micromanipulator while the DEP was on. Turning off the DEP resulted in the release of the captured molecule from the nanotweezers tip into the solution

  4. Protein trapping (SI section 7)

    Trapping of α-synuclein (SI section 7). Video showing the fluorescence profile at the nanotweezers tip during trapping and releasing of the α-Synuclein molecule. No fluoresce change was observed when DEP was off. Upon application of an a.c. field (DEP on) a sharp increase in fluorescence around the nanotweezer tip was observed. (n = 4.)

  5. Single Molecule trapping and writing (SI section 10a)

    Video showing the Pick and release of single 10 kbp DNA molecule using the DEP nanotweezers. The DNA molecule was captured at the nanotweezer tip by turning on the a.c. field (DEP on). Transfer of the captured single molecule from one position to another was achieved by moving the nanotweezer using a micromanipulator while the DEP was on. Turning off the DEP resulted in the release of the captured molecule from the nanotweezers tip into the solution

  6. Single organelle extraction (Figure 6)

    Video showing the trapping an extraction of a single mitochondrion inside a neuron. The nanotweezers (dark spot) was positioned close to a labelled mitochondrion (bright spot). Upon application of an a.c. field (DEP on), the mitochondrion gets trapped at the nanotweezer tip. Extraction of the mitochondrion from the neuron was achived by withdrawing the nanotweezer from the neuron while keeping the a.c. field turned on (DEP on). (n = 4.)

  7. Single Molecule trapping and writing (Figure 3)

    Video showing the Pick and release of single 10 kbp DNA molecule using the DEP nanotweezers. The DNA molecule was captured at the nanotweezer tip by turning on the a.c. field (DEP on). Transfer of the captured single molecule from one position to another was achieved by moving the nanotweezer using a micromanipulator while the DEP was on. Turning off the DEP resulted in the release of the captured molecule from the nanotweezers tip into the solution. (n = 5.)

  8. DNA trapping(Figure2)

    Video showing the trapping and release of 10 kbp DNA. When DEP is turned on, the force generated around the tip is sufficiently strong to capture freely diffusing DNA molecules in solution resulting in the accumulation of fluorescently tagged DNA molecule at the nanotweezers (bright spot). This operation is fully reversible; as soon as the DEP is turned off the trapped molecules are immediately released back into the solution. (n = 4.)

  9. DNA trapping in cells (Figure4)

    Video showing the trapping of DNA inside the cell nucleus. The tip was approached and then inserted into the cell nucleus. Application of an a.c. bias (DEP on) traps the DNA fragments at the nanotweezers tip as can be seen by an increase in fluorescence signal around the tip (bright spot) (n = 4).

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