Researchers have devised a live-cell morphological profiling approach to monitor small-molecule compounds.
The approach is based on impedance measurement of cells and uses Roche's Xcelligence RTCA system.
The approach was tested by screening a library containing FDA-approved drugs, experimental compounds and natural compounds.
Compounds with similar activity produced similar impedance-based time-dependent Cell Response Profiles (TCRPs) and then clustered based on TCRP similarity.
The researchers identified mechanisms for existing drugs, confirmed previously-reported calcium modulating activity for COX-2 inhibitor celecoxib, and discovered an additional mechanism for the experimental compound - monastrol.
They also recognised and characterised a new antimitotic agent.
This approach is also designed to detect the off-target effect of a given compound.
In combination with measurement of cell number, morphology and adhesion, the TCR technique allows greater expansion of the 'biological space' at which compounds are screened.
It provides ample opportunity to detect and identify biological activity associated with small molecules.
The findings indicate that the time-dependent resolution, provided by the TCRP approach, can be used in conjunction with phenotypic profiling approaches to obtain additional data associated with small molecule compounds.
The approach also provides predictive mechanistic information for small molecule compounds.
The non-invasive and label-free Xcelligence analysis method is based on measuring the impedance of cells and uses an electronic readout of impedance to non-invasively quantify cellular status in real time.
Cells are seeded in E-Plate microtiter plates, which are integrated with microelectronic sensor arrays.
The interaction of cells with the microelectrode surface generates a cell-electrode impedance response, which not only indicates cell viability but also correlates with the number of the cells seeded in the well.
