Three-dimensional (3D) cell culture technologies, such as organoids, are physiologically relevant models for basic and clinical applications. Automated microfluidics offers advantages in high-throughput and precision analysis of cells but is not yet compatible with organoids. Here, we present an automated, high-throughput, microfluidic 3D organoid culture and analysis system to facilitate preclinical research and personalized therapies. Our system provides combinatorial and dynamic drug treatments to hundreds of cultures and enables real-time analysis of organoids. We validate our system by performing individual, combinatorial, and sequential drug screens on human-derived pancreatic tumor organoids. We observe significant differences in the response of individual patient-based organoids to drug treatments and find that temporally-modified drug treatments can be more effective than constant-dose monotherapy or combination therapy in vitro. This integrated platform advances organoids models to screen and mirror real patient treatment courses with potential to facilitate treatment decisions for personalized therapy.

三维（3D）细胞培养技术（例如类器官）是用于基本和临床应用的生理相关模型。自动化的微流体技术在细胞的高通量和精密分析方面具有优势，但尚未与类器官相容。在这里，我们介绍了一种自动化的高通量微流体3D类器官培养和分析系统，以促进临床前研究和个性化治疗。我们的系统为数百种文化提供组合和动态药物治疗，并能够对类器官进行实时分析。我们通过对源自人类的胰腺肿瘤类器官进行单独，组合和顺序的药物筛选来验证我们的系统。我们观察到个体患者类器官对药物治疗的反应存在显着差异，并且发现临时修饰的药物治疗比恒剂量单一疗法或体外联合疗法更有效。该集成平台提高了类器官模型，以筛选和镜像实际的患者治疗过程，并有可能促进针对个性化治疗的治疗决策。