Tsinghua-Berkeley Shenzhen Institute (TBSI), Shenzhen International Graduate School (SIGS), Shenzhen Key Laboratory of Gene and Antibody Therapy, State Key Laboratory of Chemical Oncogenomics, Tsinghua University, Shenzhen 518055, China.
Department of Oncology, The First Affiliated Hospital of Zhengzhou University, No1 Jianshe East Road, Zhengzhou 450052, China.
Cell Rep Med. 2020 Dec 22;1(9):100161. doi: 10.1016/j.xcrm.2020.100161.
Current organoid technologies require intensive manual manipulation and lack uniformity in organoid size and cell composition. We present here an automated organoid platform that generates uniform organoid precursors in high-throughput. This is achieved by templating from monodisperse Matrigel droplets and sequentially delivering them into wells using a synchronized microfluidic droplet printer. Each droplet encapsulates a certain number of cells (e.g., 1,500 cells), which statistically represent the heterogeneous cell population in a tumor section. The system produces >400-μm organoids within 1 week with both inter-organoid homogeneity and inter-patient heterogeneity. This enables automated organoid printing to obtain one organoid per well. The organoids recapitulate 97% gene mutations in the parental tumor and reflect the patient-to-patient variation in drug response and sensitivity, from which we obtained more than 80% accuracy among the 21 patients investigated. This organoid platform is anticipated to fulfill the personalized medicine goal of 1-week high-throughput screening for cancer patients.
当前的类器官技术需要密集的手动操作，并且类器官的大小和细胞组成缺乏一致性。我们在这里提出了一种自动化的类器官平台，可以高通量生成均匀的类器官前体。这是通过从单分散的基质胶液滴中进行模板化，并使用同步微流控液滴打印机将其顺序递送到孔中来实现的。每个液滴封装一定数量的细胞（例如 1500 个细胞），这些细胞在统计学上代表肿瘤切片中异质细胞群体。该系统在 1 周内产生 >400-μm 的类器官，具有类器官间的同质性和患者间的异质性。这使得自动化类器官打印能够在每个孔中获得一个类器官。类器官重现了亲本肿瘤中 97%的基因突变，并反映了患者对药物反应和敏感性的个体间差异，我们从 21 名接受调查的患者中获得了超过 80%的准确性。预计该类器官平台将满足癌症患者 1 周高通量筛选的个性化医疗目标。
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