An advanced microfluidic platform for assessment of DOX uptake by MCF-7 cells inside microenvironment mimicking blood capillary networks

Estimating drug uptake by cells in vitro is widely determined in a static environment or centrifuge. Such an uptake study cannot give a correct estimation of drug uptake on cells as drug uptake by cells happens when both drug and cells are in movement. Considering these two aspects, microchannels with two different configurations were fabricated to replicate the confinement of the blood capillary network. Channel A was designed to replicate the bifurcations of blood capillaries, while Channel B was designed to replicate its curves. The microchannels were fabricated to decipher the drug uptake on breast cancer cells (MCF-7 cells) when they flow through conditions similar to the blood capillary network. The drug uptake in Channel A and Channel B was observed to be 1.17 and 1.78 times higher than the conventional method. The inflection region where channel curvature changed caused MCF-7 cells to deform, resulting in an alteration of cytoskeleton morphology, thus allowing a better drug uptake by cells. Furthermore, the hydrodynamic effect on cell movement inside the microchannel was also investigated. It was observed that the MCF-7 cells showed noticeable deformation at the entry of the bifurcations and the inflection region. The MCF-7 cells also exhibited faster stress relaxation in the region of higher stresses. The cells’ fore tip and tail end were observed to move at different speeds during stress relaxation. The novel microfluidic channel discussed in the study provided a new and efficient platform for the complete assessment of cellular uptake of drugs.