Patient-derived micro-organospheres (MOS) enable clinical precision oncology

Patient-derived xenografts (PDX) and organoids (PDO) have been shown to model clinical response to cancer therapy. However, it remains challenging to use these models to guide timely clinical decisions for the treatment of cancer patients. Here we used droplet emulsion microfluidics with temperature control and dead-volume minimization to rapidly generate thousands of Micro-Organospheres (MOS) from low-volume patient tissues, which serve as an ideal patient-derived model for clinical precision oncology. A clinical study of newly diagnosed metastatic colorectal cancer (CRC) patients using a MOS-based precision oncology pipeline reliably predicted patient treatment outcome within 14 days, a timeline suitable for guiding treatment decisions in clinic. Furthermore, MOS capture stromal cells in the original tumor microenvironment as well as maintain functional immune cells that can be activated by immunotherapy to target tumor cells, providing a clinical assay for testing immuno-oncology therapy on patient tumors.