Heterotypic 3D tumor culture in a reusable platform using pneumatic microfluidics

Abstract

The construction of a micro-platform capable of microscale control for continuous, dynamic, and high-throughput biomimetic tumor manipulation and analysis plays a significant role in biological and clinical research. Here, we introduce a pneumatic microstructure-based microfluidic platform for versatile three-dimensional (3D) tumor cultures. The manipulative potential of pneumatic microstructures in a fabrication-optimized microfluidic device can be stimulated to achieve ultra-repetitive (tens of thousands of times) and persistent (over several months) microfluidic control. We demonstrated that the microfluidic platform is reusable (dozens of times) for stable, reproducible, and high-throughput generation of tumors with uniform size. Various heterotypic and homotypic 3D tumor arrays can be produced successfully in the device based on robust pneumatic control. On-chip monitoring and analysis of tumor phenotypes and responses to different culture conditions and chemotherapies were also achieved in real-time in the microfluidic platform. The results indicate that fibroblasts cocultured with tumor cells positively promote the phenotypical appearance of heterotypic tumors. This microfluidic advancement offers a new methodological approach for the development of high-performance and non-disposable 3D culture systems and for tissue-mimicking cancer research. We believe that it could be valuable for various tumor-related research fields such as oncology, pharmacology, tissue engineering, and bioimaging.