A Microfluidic 3D-Tumor-Spheroid Model for the Evaluation of Targeted Therapies from Angiogenesis-Related Cytokines at the Single Spheroid Level

Angiogenesis is a key player in drug resistance to targeted therapies for breast cancer. The average expression of angiogenesis-related cytokines is widely associated with the treatments of target therapies for a population of cells or spheroids, overlooking the distinct responses for individuals. In this work, a highly integrated microfluidic platform is developed for the generation of monodisperse multicellular tumor spheroids (MTSs), drug treatments, and the measurement of cytokines for individual MTSs in a single chip. The platform allows the correlation evaluation between cytokine secretion and drug treatment at the level of individual spheroids. For validation, quantities of six representative proangiogenic cytokines are tested against treatments with four model drugs at varying times and concentrations. By applying a linear regression model, significant correlations are established between cytokine secretion and the treated drug concentration for individual spheroids. The proposed platform provides a high-throughput method for the investigation of the molecular mechanism of the cytokine response to targeted therapies and paves the way for future drug screening using predictive regression models at the single-spheroid level. In this work, a microfluidic platform is provided that allows for the integration of multiple functions within a single microfluidic chip. These include monodisperse multicellular tumor spheroids (MTS) generation, drug treatment, and cytokine detection. From this platform, the correlation between angiogenesis-related cytokines and the treated drug concentration can be established at the single spheroid level. image