Spatially controlled diffusion range of tumor-associated angiogenic factors to develop a tumor model using a microfluidic resistive circuit

• Published in: Lab on a chip 2024-05, Vol.24 (1), p.2644-2657
• Main Authors: Hsu, Yu-Hsiang, Yang, Wen-Chih, Chen, Yi-Ting, Lin, Che-Yu, Yang, Chiou-Fong, Liu, Wei-Wen, Shivani, Subhashree, Li, Pai-Chi
• Format: Article
• Language: English
• Subjects: Angiogenesis; Angiogenesis Inducing Agents - metabolism; Angiogenesis Inducing Agents - pharmacology; Blood vessels; Cell Line, Tumor; Chambers; Concentration gradient; Diffusion; Equipment Design; Human Umbilical Vein Endothelial Cells; Humans; Lab-On-A-Chip Devices; Microchannels; Microfluidic Analytical Techniques - instrumentation; Microfluidics; Neoplasms - metabolism; Neoplasms - pathology; Neovascularization, Pathologic; Tumors
• ISSN: 1473-0197; 1473-0189; 1473-0189
• DOI: 10.1039/d3lc00891f

Developing a tumor model with vessels has been a challenge in microfluidics. This difficulty is because cancer cells can overgrow in a co-culture system. The up-regulation of anti-angiogenic factors during the initial tumor development can hinder neovascularization. The standard method is to develop a quiescent vessel network before loading a tumor construct in an adjacent chamber, which simulates the interaction between a tumor and its surrounding vessels. Here, we present a new method that allows a vessel network and a tumor to develop simultaneously in two linked chambers. The physiological environment of these two chambers is controlled by a microfluidic resistive circuit using two symmetric long microchannels. Applying the resistive circuit, a diffusion-dominated environment with a small 2-D pressure gradient is created across the two chambers with velocity