Pathology

Nanotechnology

Bioinformatics

Cell culture

Microfluidics

Biology

3D cell culture

Precision medicine

Materials science

Drug

Organoid

Personalized medicine

Computer science

Computational biology

Drug discovery

Cell biology

Drug response

Genetics

Medicine

Pharmacology

Nature Communications

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.

Automated microfluidic platform for dynamic and combinatorial drug screening of tumor organoids