A Novel Microfluidic Bypass as a Tumor-on-a-chip: Design, Development and Experimentation with Confined-3D Cell Culture

Microelectromechanical Systems (MEMS) have led to an important revolution in technology and science, and their implementations in life sciences provide interesting advantages. It is hoped that during the current century, this will revolutionize the medical field. On the other hand, 2D standard preclinical in vitro models do not represent the in vivo condition of humans; hence, it is required to have more reliable models for anticancer drugs. In this context, a microfluidic bypass as a Tumor-on-chip (TOC) prototype was developed, aiming to combine the advantages of microfluidics and 3D perfused cell culture. Parameters like Flow Velocity (FV), Shear Stress (ShS), oxygen diffusion, pressure, and geometry were studied with Finite Element Method simulations. The prototype was fabricated and tested in the laboratory with two types of tumoroids. The proposed bypass design can capture the inoculated tumoroids allowing a continuous supply of nutrients and oxygen, removal of waste material, as well as in situ characterization. Taking advantage of the superior benefits of perfused 3D cell culture and the use of non-toxic materials like PDMS and glass, a dramatic increase in cell culture growth was observed. It was found that the most effective way to change the FV and the ShS inside the cell culture chamber relative to the Perfusion-microchannel is to change the distance between micropillars that surround the tumoroid. A method to tune the FV and ShS in the cell culture chamber with analytic equations was proposed. Cell culture growth is found to be higher when FV is between 1.2E-5 and 2.9E-5 m/s, while the ShS at the bottom of the TOC was in the range from 3.3E-4 to 7.9E-4 Pa. The TOC was also tested with two different types of drugs, and it showed to have a clear potential to be used in drug screening experiments in 3D cell culture, as well as the potential to be implemented as a research or therapeutic tool in the field of personalized medicine.