3D Multicellular Tumor Spheroids in a Microfluidic Droplet System for Investigation of Drug Resistance
Sang Ik Lee, Yoon Young Choi, Seong Goo Kang, Tae Hyeon Kim, Ji Wook Choi, Young Jae Kim, Tae‐Hyung Kim, Taewook Kang, Bong Geun Chung
Abstract
A three-dimensional (3D) tumor spheroid model plays a critical role in mimicking tumor microenvironments in vivo. However, the conventional culture methods lack the ability to manipulate the 3D tumor spheroids in a homogeneous manner. To address this limitation, we developed a microfluidic-based droplet system for drug screening applications. We used a tree-shaped gradient generator to control the cell density and encapsulate the cells within uniform-sized droplets to generate a 3D gradient-sized tumor spheroid. Using this microfluidic-based droplet system, we demonstrated the high-throughput generation of uniform 3D tumor spheroids containing various cellular ratios for the analysis of the anti-cancer drug cytotoxicity. Consequently, this microfluidic-based gradient droplet generator could be a potentially powerful tool for anti-cancer drug screening applications.