Nanoscale tweezers for single-cell biopsies

Binoy Paulose Nadappuram, Paolo Cadinu, Avijit Barik, Alexander J. Ainscough, Michael J. Devine, Minkyung Kang, Jorge Gonzalez-Garcia, Josef T. Kittler, Keith R. Willison, Ramon Vilar, Paolo Actis, Beata Wojciak-Stothard, Sang Hyun Oh, Aleksandar P. Ivanov, Joshua B. Edel

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)80-88
Number of pages9
JournalNature Nanotechnology
Volume14
Issue number1
DOIs
StatePublished - Jan 1 2019

Bibliographical note

Funding Information:
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).

Publisher Copyright:
© 2018, The Author(s), under exclusive licence to Springer Nature Limited.

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