Patient-derived xenografts (PDXs) and patient-derived organoids (PDOs) have been shown to model clinical response to cancer therapy. However, it remains challenging to use these models to guide timely clinical decisions for cancer patients. Here, we used droplet emulsion microfluidics with temperature control and dead-volume minimization to rapidly generate thousands of micro-organospheres (MOSs) from low-volume patient tissues, which serve as an ideal patient-derived model for clinical precision oncology. A clinical study of recently diagnosed metastatic colorectal cancer (CRC) patients using an MOS-based precision oncology pipeline reliably assessed tumor drug response within 14 days, a timeline suitable for guiding treatment decisions in the clinic. Furthermore, MOSs capture original stromal cells and allow T cell penetration, providing a clinical assay for testing immuno-oncology (IO) therapies such as PD-1 blockade, bispecific antibodies, and T cell therapies on patient tumors.

患者来源的异种移植物（PDX）和患者来源的类器官（PDO）已被证明可以模拟癌症治疗的临床反应。然而，使用这些模型来指导癌症患者及时的临床决策仍然具有挑战性。在这里，我们使用具有温度控制和死体积最小化的液滴乳液微流体，从低体积的患者组织中快速生成数千个微有机球（MOS），这是临床精准肿瘤学的理想患者衍生模型。一项针对最近诊断的转移性结直肠癌 (CRC) 患者的临床研究使用基于 MOS 的精准肿瘤学流程，在 14 天内可靠地评估了肿瘤药物反应，该时间线适合指导临床治疗决策。此外，MOS 捕获原始基质细胞并允许 T 细胞渗透，为测试免疫肿瘤 (IO) 疗法（例如 PD-1 阻断、双特异性抗体和针对患者肿瘤的 T 细胞疗法）提供临床测定。