Polydimethylsiloxane micropatterning-aided multi-size biomimetic tumor spheroid-on-a-chip for investigating chemotherapy and photodynamic therapy

Three-dimensional (3D) tumor spheroids are increasingly recognized as promising and prospective models for in vitro cancer research and preclinical screening. However, it remains an unmet need for facile construction of a micro-platform to synchronously produce spheroids with controlled multi-sizes and diverse pathophysiological characteristics for downstream applications. Here, a user-friendly tumor spheroid-on-a-chip system for multi-size biomimetic tumor model fabrication for supporting different antitumor investigations is developed based on the usage of polydimethylsiloxane-micropatterned chip with high fidelity. Simultaneous and massive production of multi-size tumor spheroids with the respective geometric uniformity is achieved on the simple-to-operate chips. The fabricated multi-size spheroids possess multiple native tumor-like features including complicated multilayer arrangement, multiple phenotypical/biochemical gradients, and various microenvironmental molecule and stroma compositions. The applicability of the system in throughput and multi-parallel investigation of multi-size tumor responses to both chemotherapy and photodynamic therapy is experimentally validated too. The size control of tumor models and their biomimetic degree are proved to be important for identifying drug susceptibility and resistance during the antitumor therapy evaluation. This microengineering advancement has potential applications in oncology, drug development, and tissue engineering and provides an insight into the development of the accessible and generalizable microplatform for cancer research.