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  3. An Automated Organoid Platform with Inter-organoid Homogeneity and Inter-patient Heterogeneity

An Automated Organoid Platform with Inter-organoid Homogeneity and Inter-patient Heterogeneity

  • Cell Rep Med. 2020 Dec 22;1(9):100161. doi: 10.1016/j.xcrm.2020.100161.
Shengwei Jiang 1,  Haoran Zhao 1,  Weijie Zhang 2,  Jiaqi Wang 1,  Yuhong Liu 3,  Yuanxiong Cao 1,  Honghui Zheng 1,  Zhiwei Hu 1,  Shubin Wang 4,  Yu Zhu 4,  Wei Wang 5,  Shuzhong Cui 6,  Peter E Lobie 1,  Laiqiang Huang 1 3,  Shaohua Ma 1
Affiliations

Affiliations

  • 1 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.
  • 2 Department of Oncology, The First Affiliated Hospital of Zhengzhou University, No1 Jianshe East Road, Zhengzhou 450052, China.
  • 3 Department of Chemistry, Tsinghua University, Beijing 100084, China.
  • 4 Department of Oncology, Peking University Shenzhen Hospital, Shenzhen Key Laboratory of Gastrointestinal Cancer Translational Research, Cancer Institute of Shenzhen PKU-HKUST Medical Center, 1120 Lianhua Road, Shenzhen 518036, China.
  • 5 Department of Pathology, Shenzhen University General Hospital, Shenzhen 518055, China.
  • 6 Department of Abdominal Surgery, Affiliated Cancer Hospital of Guangzhou Medical University, Guangzhou 510095, China.
PMID: 33377132 DOI: 10.1016/j.xcrm.2020.100161
Abstract

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.

Keywords

droplet; microfluidics; organoid; printing; tumor.

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