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Issue 7, 2021
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Monitoring the heterogeneity in single cell responses to drugs using electrochemical impedance and electrochemical noise

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Abstract

Impedance spectroscopy is a widely used technique for monitoring cell–surface interactions and morphological changes, typically based on averaged signals from thousands of cells. However, acquiring impedance data at the single cell level, can potentially reveal cell-to-cell heterogeneity for example in response to chemotherapeutic agents such as doxorubicin. Here, we present a generic platform where light is used to define and localize the electroactive area, thus enabling the impedance measurements for selected single cells. We firstly tested the platform to assess phenotypic changes in breast cancer cells, at the single cell level, using the change in the cell impedance. We next show that changes in electrochemical noise reflects instantaneous responses of the cells to drugs, prior to any phenotypical changes. We used doxorubicin and monensin as model drugs and found that both drug influx and efflux events affect the impedance noise signals. Finally, we show how the electrochemical noise signal can be combined with fluorescence microscopy, to show that the noise provides information on cell susceptibility and resistance to drugs at the single cell level. Together the combination of electrochemical impedance and electrochemical noise with fluorescence microscopy provides a unique approach to understanding the heterogeneity in the response of single cells to stimuli where there is not phenotypic change.

Graphical abstract: Monitoring the heterogeneity in single cell responses to drugs using electrochemical impedance and electrochemical noise

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Supplementary files

Article information


Submitted
04 Oct 2020
Accepted
28 Dec 2020
First published
28 Dec 2020

This article is Open Access
All publication charges for this article have been paid for by the Royal Society of Chemistry

Chem. Sci., 2021,12, 2558-2566
Article type
Edge Article

Monitoring the heterogeneity in single cell responses to drugs using electrochemical impedance and electrochemical noise

Y. Yang, F. M. Mansfeld, M. Kavallaris, K. Gaus, R. D. Tilley and J. J. Gooding, Chem. Sci., 2021, 12, 2558
DOI: 10.1039/D0SC05489E

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