xCELLigence™, a cell-based assay system codeveloped by ACEA Biosciences and Roche Applied Science, combines microelectronics and cell biology to provide a label-free process to monitor live cells under physiological conditions. A disposable 96-well E plate contains a microelectronic biosensor in each well. “The cells interact with the gold microelectrodes, leading to changes in impedance,” explains Yama Abassi, Ph.D., senior director, cell biology, ACEA. Each change in the cells’ status, i.e., adhesion, cytotoxicity, cell proliferation, cell-cell interactions, or morphological changes, alters the impedance measurements, and therefore, can be quickly detected in real-time.
Eliminating labels brings the cells closer to physiological conditions and avoids costs associated with radioactive dyes. The microelectronic readout is noninvasive, so cells are not destroyed and can be continuously monitored. This, says Dr. Abassi, allows the user to build a kinetic profile of the experiment. “It gives us a quality-control picture of how the cells are behaving inside the wells and then when we treat the cells with a particular compound, we can observe if the response is immediate. This could not be accomplished by standard endpoint assays.”
Recent research efforts have been focused on two areas: morphological profiling and safety pharmacology. “We’ve noticed that, when we grow cells and add compounds, we get specific genetic signature patterns. These are dependent on the mechanism of action of the compound,” Dr. Abassi states.
Safety pharmacology efforts are focused on cardiotoxicity effects. His group uses embryonic stem cells differentiated into cardiomyocytes and monitors the effects of pro-arrhythmic compounds on these cells. This is significant because, according to Dr. Abassi, “almost 30 percent of lead compounds being developed ultimately fail because of some type of cardiotoxicity. It’s a huge problem and people are looking for ways to predict it much earlier in the drug discovery pipeline.”