title: 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.
authors.affiliation: College of Science, Northwest A&F University, Yangling, Shaanxi 712100, China. liuwenming0229@nwsuaf.edu.cn jywang@nwsuaf.edu.cn.
authors.forename: Wenming
authors.initials: W
authors.lastname: Liu
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Tian
authors.affiliation: College of Science, Northwest A&F University, Yangling, Shaanxi 712100, China. liuwenming0229@nwsuaf.edu.cn jywang@nwsuaf.edu.cn.
authors.forename: Mingming
authors.initials: M
authors.lastname: Yan
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Ma
authors.affiliation: College of Science, Northwest A&F University, Yangling, Shaanxi 712100, China. liuwenming0229@nwsuaf.edu.cn jywang@nwsuaf.edu.cn.
authors.forename: Tianbao
authors.initials: T
authors.lastname: Li
authors.affiliation: College of Science, Northwest A&F University, Yangling, Shaanxi 712100, China. liuwenming0229@nwsuaf.edu.cn jywang@nwsuaf.edu.cn.
authors.forename: Juan
authors.initials: J
authors.lastname: Xu
authors.affiliation: College of Science, Northwest A&F University, Yangling, Shaanxi 712100, China. liuwenming0229@nwsuaf.edu.cn jywang@nwsuaf.edu.cn and College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, China.
authors.forename: Jinyi
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D018929:Cell Culture Techniques / Q000295:instrumentation*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D004789:Enzyme Activation; D004867:Equipment Design; D056656:Lab-On-A-Chip Devices; D051379:Mice; D041681:NIH 3T3 Cells
chemical_list: D053148:Caspase 3