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Application of xCELLigence RTCA Biosensor Technology for Revealing the Profile and Window of Drug Responsiveness in Real Time.

Kho D, MacDonald C, Johnson R, Unsworth CP, O'Carroll SJ, du Mez E, Angel CE, Graham ES - Biosensors (Basel) (2015)

Bottom Line: In this manuscript, we demonstrate how xCELLigence technology has been invaluable in the identification of (1) not only if cells respond to a particular drug, but (2) the window of drug responsiveness.The latter aspect is often left to educated guess work in classical end-point assays, whereas biosensor technology reveals the temporal profile of the response in real time, which enables both acute responses and longer term responses to be profiled within the same assay.In our experience, the xCELLigence biosensor technology is suitable for highly targeted drug assessment and also low to medium throughput drug screening, which produces high content temporal data in real time.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, University of Auckland, Auckland 1023, New Zealand. s.ocarroll@auckland.ac.nz.

ABSTRACT
The xCELLigence technology is a real-time cellular biosensor, which measures the net adhesion of cells to high-density gold electrode arrays printed on custom-designed E-plates. The strength of cellular adhesion is influenced by a myriad of factors that include cell type, cell viability, growth, migration, spreading and proliferation. We therefore hypothesised that xCELLigence biosensor technology would provide a valuable platform for the measurement of drug responses in a multitude of different experimental, clinical or pharmacological contexts. In this manuscript, we demonstrate how xCELLigence technology has been invaluable in the identification of (1) not only if cells respond to a particular drug, but (2) the window of drug responsiveness. The latter aspect is often left to educated guess work in classical end-point assays, whereas biosensor technology reveals the temporal profile of the response in real time, which enables both acute responses and longer term responses to be profiled within the same assay. In our experience, the xCELLigence biosensor technology is suitable for highly targeted drug assessment and also low to medium throughput drug screening, which produces high content temporal data in real time.

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Related in: MedlinePlus

xCELLigence SP “Well Graph” view for drug discovery. An additional component of the ACEA software is the Well Graph view, which provides an overview of the entire time course for each well. This is useful for drug discovery applications or for experimental quality control. This snap-shot allows easy identification of specific or unusual responses, as highlighted by the encircled responses. These have been enlarged with the time of drug addition marked with the asterisk (24 h post seeding). The response in these highlighted wells is immediate and reveals substantial loss of adhesion, which would be consistent with a cytotoxic drug effect.
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biosensors-05-00199-f009: xCELLigence SP “Well Graph” view for drug discovery. An additional component of the ACEA software is the Well Graph view, which provides an overview of the entire time course for each well. This is useful for drug discovery applications or for experimental quality control. This snap-shot allows easy identification of specific or unusual responses, as highlighted by the encircled responses. These have been enlarged with the time of drug addition marked with the asterisk (24 h post seeding). The response in these highlighted wells is immediate and reveals substantial loss of adhesion, which would be consistent with a cytotoxic drug effect.

Mentions: In our experience, xCELLigence provides a valuable platform to screen small compound libraries for either global responses (e.g., any change in cell adhesion) or identification of specific drug responses (e.g., cytotoxic effects). We have done this for a range of inflammatory cytokines, chemokines and various novel compounds using brain endothelial cells (hCMVECs) and NT2-derived astrocytes [22]. Figure 9 shows data where several compounds of interests induced marked death of hCMVEC endothelial cells. These responses are circled red in the Well Graph view plot (a) and enlarged in (b), whereas the control treated cells are in Column 1. The asterisk indicates the addition of compounds at 24 h post seeding. The time course of this experiment was 192 h (8 days). Several of the compounds induced immediate and substantial cell death, indicated by the rapid loss in the Cell Index. The data also suggest that the death/compromise was partial, as the initial substantial loss of adhesion is followed by a slow gradual increase in the Cell Index, consistent with proliferation of the surviving endothelial cells.


Application of xCELLigence RTCA Biosensor Technology for Revealing the Profile and Window of Drug Responsiveness in Real Time.

Kho D, MacDonald C, Johnson R, Unsworth CP, O'Carroll SJ, du Mez E, Angel CE, Graham ES - Biosensors (Basel) (2015)

xCELLigence SP “Well Graph” view for drug discovery. An additional component of the ACEA software is the Well Graph view, which provides an overview of the entire time course for each well. This is useful for drug discovery applications or for experimental quality control. This snap-shot allows easy identification of specific or unusual responses, as highlighted by the encircled responses. These have been enlarged with the time of drug addition marked with the asterisk (24 h post seeding). The response in these highlighted wells is immediate and reveals substantial loss of adhesion, which would be consistent with a cytotoxic drug effect.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493546&req=5

biosensors-05-00199-f009: xCELLigence SP “Well Graph” view for drug discovery. An additional component of the ACEA software is the Well Graph view, which provides an overview of the entire time course for each well. This is useful for drug discovery applications or for experimental quality control. This snap-shot allows easy identification of specific or unusual responses, as highlighted by the encircled responses. These have been enlarged with the time of drug addition marked with the asterisk (24 h post seeding). The response in these highlighted wells is immediate and reveals substantial loss of adhesion, which would be consistent with a cytotoxic drug effect.
Mentions: In our experience, xCELLigence provides a valuable platform to screen small compound libraries for either global responses (e.g., any change in cell adhesion) or identification of specific drug responses (e.g., cytotoxic effects). We have done this for a range of inflammatory cytokines, chemokines and various novel compounds using brain endothelial cells (hCMVECs) and NT2-derived astrocytes [22]. Figure 9 shows data where several compounds of interests induced marked death of hCMVEC endothelial cells. These responses are circled red in the Well Graph view plot (a) and enlarged in (b), whereas the control treated cells are in Column 1. The asterisk indicates the addition of compounds at 24 h post seeding. The time course of this experiment was 192 h (8 days). Several of the compounds induced immediate and substantial cell death, indicated by the rapid loss in the Cell Index. The data also suggest that the death/compromise was partial, as the initial substantial loss of adhesion is followed by a slow gradual increase in the Cell Index, consistent with proliferation of the surviving endothelial cells.

Bottom Line: In this manuscript, we demonstrate how xCELLigence technology has been invaluable in the identification of (1) not only if cells respond to a particular drug, but (2) the window of drug responsiveness.The latter aspect is often left to educated guess work in classical end-point assays, whereas biosensor technology reveals the temporal profile of the response in real time, which enables both acute responses and longer term responses to be profiled within the same assay.In our experience, the xCELLigence biosensor technology is suitable for highly targeted drug assessment and also low to medium throughput drug screening, which produces high content temporal data in real time.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, University of Auckland, Auckland 1023, New Zealand. s.ocarroll@auckland.ac.nz.

ABSTRACT
The xCELLigence technology is a real-time cellular biosensor, which measures the net adhesion of cells to high-density gold electrode arrays printed on custom-designed E-plates. The strength of cellular adhesion is influenced by a myriad of factors that include cell type, cell viability, growth, migration, spreading and proliferation. We therefore hypothesised that xCELLigence biosensor technology would provide a valuable platform for the measurement of drug responses in a multitude of different experimental, clinical or pharmacological contexts. In this manuscript, we demonstrate how xCELLigence technology has been invaluable in the identification of (1) not only if cells respond to a particular drug, but (2) the window of drug responsiveness. The latter aspect is often left to educated guess work in classical end-point assays, whereas biosensor technology reveals the temporal profile of the response in real time, which enables both acute responses and longer term responses to be profiled within the same assay. In our experience, the xCELLigence biosensor technology is suitable for highly targeted drug assessment and also low to medium throughput drug screening, which produces high content temporal data in real time.

Show MeSH
Related in: MedlinePlus