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Perspective: Flicking with flow: Can microfluidics revolutionize the cancer research?
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Image of FIG. 1.
FIG. 1.

Tumor microenvironment and confinement. (a) Typical architecture of normal and transformed epithelial tissue. Other than the cancer cells, the tumor microenvironment is composed of several non-cancer cell types including cancer associated fibroblasts (CAFs) and tumor associated macrophages (TAMs). These help the cancer cells to become invasive and move towards the blood vessel. Also the interstitial flow, which originates because of the pressure gradient (ΔP) between arterial and venous flow, could facilitate the directional migration of cancer cells. Lastly, either the cancer themselves or the other tumor associated cells can align and bundle the matrix fiber to make a track for the migrating cancer cells. (b) Concentration distribution of secreted growth factor in a confined environment, and (c) the same in the presence of a flow, directed right to left. Even a small magnitude flow can bias the growth factor in one direction, which could lead to autologous cell migration. (d) Migrating cancer cell in a confined tissue environment. (e) Cancer cell within confined environment of circulatory system.

Image of FIG. 2.
FIG. 2.

Microfluidic devices in cancer research. (a) Microfluidic Model of Tumor-Vascular interface. I. A 3-D extracellular matrix (ECM) channel (dark grey) separates the tumor channel (red) and the endothelial channel (green). Scale bar is 2 mm. II. A 3-D confocal image showing ECM invasion of the tumor cells and their adherence to the endothelium. Scale bar is 30 μm. Images reproduced with permission from K. Zervantonakis, S. K. Hughes-Alford, J. L. Charest, J. S. Condeelis, F. B. Gertler, and R. D. Kamm, Proc. Natl. Acad. Sci. U.S.A. 109(34), 13515-13520 (2012). Copyright 2012 National Academy of Sciences, USA. (b) Microfluidic Device for Spheroid Entrapment and Drug Screening. Overlapped differential interference contrast and fluorescence confocal image showing the entrapment of an ovarian cancer spheroid and the distribution of live (green) and dead (red) cells within the spheroid. Cell death occurs mostly at the center. Trap width is 500 μm, while the width of the subsequent narrow neck region is 200 μm. (c) Microfluidic platform to study independent regulation of tumor cell migration by matrix stiffness and confinement. (Top) Phase contrast image of device fabricated from 120 kPa polyacrylamide hydrogel and containing consecutive wide (width = 40 μm) and narrow (width = 10 μm) sections. Scale bar 40 μm. Variation of cell morphology with the changes in matrix stiffness in narrow (middle row) and wide (bottom row) sections. Scale bar is 20 μm. Images reproduced with permission from A. Pathak and S. Kumar, Proc. Natl. Acad. Sci. U.S.A. 109(26), 10334-10339 (2012). Copyright 2012 National Academy of Sciences, USA. (d). Confinement increases the stress response speed of cancer cells. I. Fluorescence image of a HeLa cell, cultured inside a microchannel, and labeled for membrane lipid rafts. II. Cell-substrate Traction force landscape before the application of shear stress, and III, the same after the application of shear stress. Flow direction is right to left. Cell loses adhesion in upstream section. Scale bar is 10 μm. IV. Confinement, represented by channel height to cell height ratio, decreases the time taken by the cells to respond to shear stress. This decrease is more prominent in cancer cells (top four in the legend) than in normal cells (bottom four). Images reproduced with permission from T. Das, T. K. Maiti, and S. Chakraborty, Integr. Biol. (Camb) 3(6), 684–695 (2011). Copyright 2011 The Royal Society of Chemistry.


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752b84549af89a08dbdd7fdb8b9568b5 journal.articlezxybnytfddd
Scitation: Perspective: Flicking with flow: Can microfluidics revolutionize the cancer research?