Evaluation of Impedance-Based Label-Free Technology as a Tool for Pharmacology and Toxicology Investigations

The use of label-free technologies based on electrical impedance is becoming more and more popular in drug discovery. Indeed, such a methodology allows the continuous monitoring of diverse cellular processes, including proliferation, migration, cytotoxicity and receptor-mediated signaling. The objec...

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Main Authors: Stéphane Dhalluin, Gaëlle Toussaint, Karen Tilmant, Franck André Atienzar, Helga Gerets
Format: Article
Language:English
Published: MDPI AG 2013-03-01
Series:Biosensors
Subjects:
Online Access:http://www.mdpi.com/2079-6374/3/1/132
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author Stéphane Dhalluin
Gaëlle Toussaint
Karen Tilmant
Franck André Atienzar
Helga Gerets
author_facet Stéphane Dhalluin
Gaëlle Toussaint
Karen Tilmant
Franck André Atienzar
Helga Gerets
author_sort Stéphane Dhalluin
collection DOAJ
description The use of label-free technologies based on electrical impedance is becoming more and more popular in drug discovery. Indeed, such a methodology allows the continuous monitoring of diverse cellular processes, including proliferation, migration, cytotoxicity and receptor-mediated signaling. The objective of the present study was to further assess the usefulness of the real-time cell analyzer (RTCA) and, in particular, the xCELLigence platform, in the context of early drug development for pharmacology and toxicology investigations. In the present manuscript, four cellular models were exposed to 50 compounds to compare the cell index generated by RTCA and cell viability measured with a traditional viability assay. The data revealed an acceptable correlation (ca. 80%) for both cell lines (i.e., HepG2 and HepaRG), but a lack of correlation (ca. 55%) for the primary human and rat hepatocytes. In addition, specific RTCA profiles (signatures) were generated when HepG2 and HepaRG cells were exposed to calcium modulators, antimitotics, DNA damaging and nuclear receptor agents, with a percentage of prediction close to 80% for both cellular models. In a subsequent experiment, HepG2 cells were exposed to 81 proprietary UCB compounds known to be genotoxic or not. Based on the DNA damaging signatures, the RTCA technology allowed the detection of ca. 50% of the genotoxic compounds (n = 29) and nearly 100% of the non-genotoxic compounds (n = 52). Overall, despite some limitations, the xCELLigence platform is a powerful and reliable tool that can be used in drug discovery for toxicity and pharmacology studies.
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spelling doaj.art-3cac9229d50043ebb715adc91b65d80c2022-12-22T01:12:54ZengMDPI AGBiosensors2079-63742013-03-013113215610.3390/bios3010132Evaluation of Impedance-Based Label-Free Technology as a Tool for Pharmacology and Toxicology InvestigationsStéphane DhalluinGaëlle ToussaintKaren TilmantFranck André AtienzarHelga GeretsThe use of label-free technologies based on electrical impedance is becoming more and more popular in drug discovery. Indeed, such a methodology allows the continuous monitoring of diverse cellular processes, including proliferation, migration, cytotoxicity and receptor-mediated signaling. The objective of the present study was to further assess the usefulness of the real-time cell analyzer (RTCA) and, in particular, the xCELLigence platform, in the context of early drug development for pharmacology and toxicology investigations. In the present manuscript, four cellular models were exposed to 50 compounds to compare the cell index generated by RTCA and cell viability measured with a traditional viability assay. The data revealed an acceptable correlation (ca. 80%) for both cell lines (i.e., HepG2 and HepaRG), but a lack of correlation (ca. 55%) for the primary human and rat hepatocytes. In addition, specific RTCA profiles (signatures) were generated when HepG2 and HepaRG cells were exposed to calcium modulators, antimitotics, DNA damaging and nuclear receptor agents, with a percentage of prediction close to 80% for both cellular models. In a subsequent experiment, HepG2 cells were exposed to 81 proprietary UCB compounds known to be genotoxic or not. Based on the DNA damaging signatures, the RTCA technology allowed the detection of ca. 50% of the genotoxic compounds (n = 29) and nearly 100% of the non-genotoxic compounds (n = 52). Overall, despite some limitations, the xCELLigence platform is a powerful and reliable tool that can be used in drug discovery for toxicity and pharmacology studies.http://www.mdpi.com/2079-6374/3/1/132real-time cell analyzer (RTCA)impedancedrug discoveryinvestigative pharmacologypredictive toxicologyscreening
spellingShingle Stéphane Dhalluin
Gaëlle Toussaint
Karen Tilmant
Franck André Atienzar
Helga Gerets
Evaluation of Impedance-Based Label-Free Technology as a Tool for Pharmacology and Toxicology Investigations
Biosensors
real-time cell analyzer (RTCA)
impedance
drug discovery
investigative pharmacology
predictive toxicology
screening
title Evaluation of Impedance-Based Label-Free Technology as a Tool for Pharmacology and Toxicology Investigations
title_full Evaluation of Impedance-Based Label-Free Technology as a Tool for Pharmacology and Toxicology Investigations
title_fullStr Evaluation of Impedance-Based Label-Free Technology as a Tool for Pharmacology and Toxicology Investigations
title_full_unstemmed Evaluation of Impedance-Based Label-Free Technology as a Tool for Pharmacology and Toxicology Investigations
title_short Evaluation of Impedance-Based Label-Free Technology as a Tool for Pharmacology and Toxicology Investigations
title_sort evaluation of impedance based label free technology as a tool for pharmacology and toxicology investigations
topic real-time cell analyzer (RTCA)
impedance
drug discovery
investigative pharmacology
predictive toxicology
screening
url http://www.mdpi.com/2079-6374/3/1/132
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