Large-Scale Antitumor Screening Based on Heterotypic 3D Tumors Using an Integrated Microfluidic Platform.

ABSTRACT

Chemotherapy screening plays a crucial role in cancer drug discovery and clinical medicine. Although conventional methods have contributed greatly to macromanipulation of cell populations, profounder insights related to the tumor microenvironment require approaches for completing integrated cell-3D tumor micromanipulation, massive tumor simulation and production, and dynamic and high-throughput tumor analysis. In this study, we introduced an integrated microfluidic platform with multiparallel components for heterotypic 3D tumor reconstruction and antitumor screening. Sequential microfluidic manipulations including sample loading, precise localization, 3D tumor formation, chemical stimulation, on-chip analysis, and tumor recovery for off-chip assessment were permitted and experimentally confirmed in the device on the basis of facile and efficient pneumatic control. Heterotypic 3D tumors with tissue-biomimetic phenotypes can be produced in massive and size-uniform manners. Notably, we accomplished a screening-like chemotherapy assessment involving different heterotypic 3D tumors and antitumor drugs and demonstrated the versatility of the platform in large-scale tumor manipulation and analysis. This advancement in microfluidics has potential applications in the fields of oncology, pharmacology, and tissue engineering and provides insight into the construction of high-performance microsystems for drug development and cancer research.