Microencapsulated tumor organoids maintain drug sensitivity stratification

Drug sensitivity profiling on patient-derived organoids mirrors patient response for gastrointestinal cancers and is currently being evaluated in clinical trials to guide treatment decisions. However, long expansion times are typically required to achieve adequate cell numbers. Accordingly, miniaturization of organoid cultures can be leveraged to reduce assay time and increase the number of compounds tested. Microencapsulation by droplet microfluidics has been applied to produce miniaturized organoid cultures, but the predictive accuracy has yet to be fully established. Here, we show that drug response can be preserved while reducing pancreatic cancer organoid culture volume by 100-fold. Testing five standard-of-care chemotherapeutics in miniaturized 0.5 μL cultures versus standard 50 μL cultures, we find that rank-ordering by drug sensitivity produced near identical stratification. Overall, these data demonstrate the potential for platforms based on this strategy to accurately pharmacotype tumor biopsies while reducing the time needed to inform treatment.