Microfluidic platform for tumor microenvironments through the formation of an oxygen tension gradient

The simplified design of a tumor microenvironment using microfluidic devices enables the investigation of cancer cell responses to varying oxygen tensions and cancer drugs in a hypoxic tumor microenvironment.

Article | Special Issue

Cancer metastasis, which is prevalent in malignant tumors, is present in a variety of cases depending on the primary tumor and metastatic site. The cancer metastasis is affected by various factors that surround and constitute a tumor microenvironment. One of the several factors, oxygen tension, can affect cancer cells and induce changes in many ways, including motility, directionality, and viability.

A research team of Prof. Jessie S. Jeon in the Department of Mechanical Engineering at KAIST and Prof. Kenichi Funamoto in the Institute of Fluid Science at Tohoku University employed a microfluidic device composed of oxygen-permeable poly(dimethylsiloxane) to mimic the oxygen tension gradient in the tumor microenvironment and confirmed its feasibility through the cell response and various applications according to different oxygen levels.

Under an oxygen tension gradient, the average speed increased with decreasing oxygen tension. Also, the directional persistence in the right gradient and left gradient increased by 2.27-fold and 9.7-fold compared to the absolute mean value of directional persistence in normoxic condition, showing a significant increase in the left gradient condition compared to normoxic condition (Figure 1). As a result, the cancer cells tended to migrate in the direction of higher oxygen tension, which was enhanced in lower oxygen tension ranges, suggesting that oxygen plays an important role in cancer metastasis.

More importantly, when the anticancer drug was treated for 48 hours, the viability of the cancer cells varied significantly as the oxygen tension decreased. When the concentration of Tirapazamine was 500 ㎛, the viability decreased by 88.38% in hypoxia to 0.093 ∓ 0.029 compared to 10 ㎛, whereas in normoxia, the viability was 0.51 ∓ 0.097, which was 40% decrease compared to 10 ㎛ (Figure 2).

The microfluidic device, which is designed to consider the oxygen gradient in tumor microenvironment, makes it possible to more clearly observe the causal relationship between the changes in the oxygen tension and the responses of the cancer cells that were difficult to observe previously. This research was published in Biomicrofluidics under the title of “Cancer cell migration and cancer drug screening in oxygen tension gradient chip” (DOI: 10.1063/5.0011216). All figures are reproduced from [Biomicrofluidics 14 (4), 044107 (2020)], with the permission of AIP Publishing.