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

作　　者：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 

机构地区：[1]The First Affiliated Hospital,School of Medicine,Zhejiang University,Hangzhou 310029,China [2]Institute for Translational Medicine,Zhejiang University,Hangzhou 310029,China [3]Department of Chemical Engineering,University of Waterloo,200 University Avenue West,Waterloo,ON N2L 3G1,Canada [4]Department of Building Environment and Energy Engineering,Xi’an Jiaotong University,Xi’an 710049,China [5]National Engineering Research Center for Biomaterials,Sichuan University,Chengdu 610065,China [6]Clinical Research Center for Respiratory Disease,West China Hospital,Sichuan University,Chengdu 610065,China [7]Kidney Disease Center,The First Affiliated Hospital,School of Medicine,Zhejiang University,Hangzhou 310029,China [8]School of Mechanical Engineering,Chengdu University,Chengdu 610106,China [9]Institute for Advanced Study,Chengdu University,Chengdu 610106,China

出　　处：《Bio-Design and Manufacturing》2022年第3期437-450,共14页生物设计与制造（英文）

基　　金：supports from the General Program (No. 31871016);the National Key Scientific Instrument and Equipment Development Projects (No. 61827806) from the National Natural Science Foundation of China;the National Major Science and Technology Projects (No. 2018ZX10732401-003-007);the National Key Research and Development Program (No. 2016YFC1101302) from the Ministry of Science and Technology of China;the National Natural Science Foundation of China (No. 81770719);Science and Technology Department of Zhejiang Province (No. 2019C03029)

摘　　要：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 10μM 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 50μg/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.

关 键 词：DIGITAL Organ-on-a-chip Microwell array Microspheres Extracellular vesicles 

分 类 号：TN492[电子电信—微电子学与固体电子学] R735.7[医药卫生—肿瘤]