Volume 233, 2022

Development of multifunctional nanopipettes for controlled intracellular delivery and single-entity detection

Abstract

The intracellular delivery of biomolecules and nanoscale materials to individual cells has gained remarkable attention in recent years owing to its wide applications in drug delivery, clinical diagnostics, bio-imaging and single-cell analysis. It remains a challenge to control and measure the delivered amount in one cell. In this work, we developed a multifunctional nanopipette – containing both a nanopore and nanoelectrode (pyrolytic carbon) at the apex – as a facile, minimally invasive and effective platform for both controllable single-cell intracellular delivery and single-entity counting. While controlled by a micromanipulator, the baseline changes of the nanopore ionic current (I) and nanoelectrode open circuit potential (V) help to guide the nanopipette tip insertion and positioning processes. The delivery from the nanopore barrel can be facilely controlled by the applied nanopore bias. To optimize the intracellular single-entity detection during delivery, we studied the effects of the nanopipette tip geometry and solution salt concentration in controlled experiments. We have successfully delivered gold nanoparticles and biomolecules into the cell, as confirmed by the increased scattering and fluorescence signals, respectively. The delivered entities have also been detected at the single-entity level using either one or both transient I and V signals. We found that the sensitivity of the single-entity electrochemical measurement was greatly affected by the local environment of the cell and varied between cell lines.

Graphical abstract: Development of multifunctional nanopipettes for controlled intracellular delivery and single-entity detection

Associated articles

Article information

Article type
Paper
Submitted
20 aug 2021
Accepted
04 okt 2021
First published
04 okt 2021

Faraday Discuss., 2022,233, 315-335

Author version available

Development of multifunctional nanopipettes for controlled intracellular delivery and single-entity detection

P. Pandey, A. Sesena-Rubfiaro, S. Khatri and J. He, Faraday Discuss., 2022, 233, 315 DOI: 10.1039/D1FD00057H

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