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Multifunctional carbon-nanotube cellular endoscopes

Abstract

Glass micropipettes, atomic force microscope tips and nanoneedles can be used to interrogate cells, but these devices either have conical geometries that can damage cells during penetration or are incapable of continuous fluid handling. Here, we report a carbon-nanotube-based endoscope for interrogating cells, transporting fluids and performing optical and electrochemical diagnostics at the single organelle level. The endoscope, which is made by placing a multiwalled carbon nanotube (length, 50–60 µm) at the tip of a glass pipette, can probe the intracellular environment with a spatial resolution of 100 nm and can also access organelles without disrupting the cell. When the nanotube is filled with magnetic nanoparticles, the endoscope can be remotely manoeuvered to transport nanoparticles and attolitre volumes of fluids to and from precise locations. Because they are mounted on conventional glass micropipettes, the endoscopes readily fit standard instruments, creating a broad range of opportunities for minimally invasive intracellular probing, drug delivery and single-cell surgery.

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Figure 1: Comparison between cellular endoscopes and glass pipettes.
Figure 2: Mechanical robustness, flexibility and remote manipulation of the nanotube endoscope.
Figure 3: Fluid and particulate flow through the nanotube endoscope.
Figure 4: Application of nanotube endoscopes for SERS and electrochemistry.
Figure 5: Intracellular Ca2+ response to mechanical stimulation.
Figure 6: Effect of probe insertion on the cytoskeleton.

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Acknowledgements

This work was supported by a grant from the W.M. Keck Foundation to establish the Keck Institute for Attofluidic Nanotube-based Probes at Drexel University. S.B., Y.G. and G.F. were also supported by the National Science Foundation Nanoscale Interdisciplinary Research Teams (grant CTS-0609062). The authors are grateful to J. Azizkhan-Clifford, M. Bouchard, B. Layton and A. Fatatis for many useful suggestions. Thanks also go to W.-H. Shih for providing CdSe quantum dots, M. Herbert for assistance with pipette assembly, C. Johnson for TEM assistance, and G. Gallo for providing EYFP-β-actin plasmid.

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Y.G., G.F., E.P. and M.G.S. conceived the project and planned experiments. R.S. designed and fabricated the cellular endoscopes for all studies. Z.O. performed cell studies. R.S. and R.V.K.S. performed fluid and particulate flow studies. R.V.K.S. and M.G.S. carried out electrochemical studies. J.N., M.G.S. and E.V. performed SERS studies using the endoscopes. S.B. performed fluorescent labelling of the nanotubes. R.S., M.G.S., G.F. and Y.G. organized the manuscript, and all authors contributed to writing the manuscript.

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Correspondence to Gary Friedman or Yury Gogotsi.

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The authors declare no competing financial interests.

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Singhal, R., Orynbayeva, Z., Kalyana Sundaram, R. et al. Multifunctional carbon-nanotube cellular endoscopes. Nature Nanotech 6, 57–64 (2011). https://doi.org/10.1038/nnano.2010.241

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