Droplet-based microfluidic
devices are used to investigate monocytic
THP-1 cells in response to drug administration. Consistent and reproducible
droplets are created, each of which acts as a bioreactor to carry
out single cell experiments with minimized contamination and live
cell tracking under an inverted fluorescence microscope for more than
2 days. Here, the effects of three different drugs (temsirolimus,
rifabutin, and BAY 11-7082) on THP-1 are examined and the results
are analyzed in the context of the inflammasome and apoptosis relationship.
The ASC adaptor gene tagged with GFP is monitored as the inflammasome
reporter. Thus, a systematic way is presented for deciphering cell-to-cell
heterogeneity, which is an important issue in cancer treatment. The
drug temsirolimus, which has effects of disrupting the mTOR pathway
and triggering apoptosis in tumor cells, causes THP-1 cells to express
ASC and to be involved in apoptosis. Treatment with rifabutin, which
inhibits proliferation and initiates apoptosis in cells, affects ASC
expression by first increasing and then decreasing it. CASP-3, which
has a role in apoptosis and is directly related to ASC, has an increasing
level in inflammasome conditioning. Thus, the cell under the effect
of rifabutin might be faced with programmed cell death faster. The
drug BAY 11-7082, which is responsible for NFκB inhibition,
shows similar results to temsirolimus with more than 60% of cells
having high fluorescence intensity (ASC expression). The microfluidic
platform presented here offers strong potential for studying newly
developed small-molecule inhibitors for personalized/precision medicine.