To test the tool, the researchers analyzed drugs that make cells either contract or relax, using human smooth muscle cells that line airways in the body—in effect, simulating an asthma attack in the lab. The researchers compared the results of those tests to what was already known about how lung tissue reacts to the drugs and found that FLECS captured the same types of reactions—only more precisely because it could analyze the reactions in cell-by-cell detail.
The researchers conducted additional testing to further demonstrate the device’s versatility and effectiveness. For example, they tested the force of macrophages, cells in the immune system that rid the body of potentially harmful particles, bacteria and dead cells. They found that when a typical macrophage receives a signal that an infection is present, it can exert force approximately 200,000 times its own weight in water. But some macrophages were more than three times stronger than that.
The researchers also used FLECS to analyze cell force and then compared the results of that test to a current standard test, which judges cell force by analyzing the amount of calcium in the cells. They were surprised that the results of the calcium test did not correlate well with how much cells contracted. The finding suggests that the calcium test may be limited, because—unlike that test—FLECS looks at a level of detail down to an individual cell.
“This finding has strong implications for safety evaluations of current drugs where unintended contraction of cells may lead to adverse reactions in patients,” said Damoiseaux, who is also director of CNSI’s Drug Discovery Technology Center.
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Ivan Pushkarsky et al. Elastomeric sensor surfaces for high-throughput single-cell force cytometry, Nature Biomedical Engineering (2018). DOI: 10.1038/s41551-018-0193-2