Microfluidic Platform for Generating and Releasing Patient‐Derived Cancer Organoids with Diverse Shapes: Insight into Shape‐Dependent Tumor Growth

Multicellular spheroids and patient-derived organoids find many applications in fundamental research, drug discovery, and regenerative medicine. Advances in the understanding and recapitulation of organ functionality and disease development require the generation of complex organoid models, including organoids with diverse morphologies. Microfluidics-based cell culture platforms enable time-efficient confined organoid generation. However, the ability to form organoids with different shapes with a subsequent transfer from microfluidic devices to unconstrained environments for studies of morphology-dependent organoid growth is yet to be demonstrated. Here, a microfluidic platform is introduced that enables high-fidelity formation and addressable release of breast cancer organoids with diverse shapes. Using this platform, the impact of organoid morphology on their growth in unconstrained biomimetic hydrogel is explored. It is shown that proliferative cancer cells tend to localize in high positive curvature organoid regions, causing their faster growth, while the overall growth pattern of organoids with diverse shapes tends to reduce interfacial tension at the organoid-hydrogel interface. In addition to the formation of organoids with diverse morphologies, this platform can be integrated into multi-tissue micro-physiological systems.