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On-line Access: 2022-03-03

Received: 2021-10-04

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Bio-Design and Manufacturing  2022 Vol.5 No.3 P.437-450

http://doi.org/10.1007/s42242-022-00188-1


Development of digital organ‑on‑a‑chip to assess hepatotoxicity and extracellular vesicle‑based anti‑liver cancer immunotherapy


Author(s):  Guohua Wu, Jianguo Wu, Zihan Li, Shengyu Shi, Di Wu, Xuanbo Wang, Han Xu, Hui Liu, Yixiao Huang, Rending Wang, Jia Shen, Zhihong Dong & Shuqi Wang

Affiliation(s):  The First Afliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310029, China ; more

Corresponding email(s):   jiashen@zju.edu.cn, zhdong@cdu.edu.cn, shuqi@scu.edu.cn

Key Words:  Digital, Organ-on-a-chip, Microwell array, Microspheres, Extracellular vesicles


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Guohua Wu, Jianguo Wu, Zihan Li, Shengyu Shi, Di Wu, Xuanbo Wang, Han Xu, Hui Liu, Yixiao Huang, Rending Wang, Jia Shen, Zhihong Dong & Shuqi Wang. Development of digital organ‑on‑a‑chip to assess hepatotoxicity and extracellular vesicle‑based anti‑liver cancer immunotherapy[J]. Journal of Zhejiang University Science D, 2022, 5(3): 437-450.

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Abstract: 
organ-on-a-chip systems have been increasingly recognized as attractive platforms to assess toxicity and to develop new therapeutic agents. However, current organ-on-a-chip platforms are limited by a “single pot” design, which inevitably requires holistic analysis and limits parallel processing. Here, we developed a digital organ-on-a-chip by combining a microwell array with cellular microspheres, which significantly increased the parallelism over traditional organ-on-a-chip for drug development. Up to 127 uniform liver cancer microspheres in this digital organ-on-a-chip format served as individual analytical units, allowing for analysis with high consistency and quick response. Our platform displayed evident anti-cancer efficacy at a concentration of 10 μM for sorafenib, and had greater alignment than the “single pot” organ-on-a-chip with a previous in vivo study. In addition, this digital organ-on-a-chip demonstrated the treatment efficacy of natural killer cell-derived extracellular vesicles for liver cancer at 50 μg/mL. The successful development of this digital organ-on-a-chip platform provides high-parallelism and a low-variability analytical tool for toxicity assessment and the exploration of new anticancer modalities, thereby accelerating the joint endeavor to combat cancer.

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