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High-throughput"read-on-ski"automated imaging and label-free detection system for toxicity screening of compounds usingpersonalised human kidney organoids

摘要Organoid models are used to study kidney physiology, such as the assessment of nephrotoxicity and underlying disease processes. Personalized human pluripotent stem cell-derived kidney organoids are ideal models for compound toxicity studies, but there is a need to accelerate basic and translational research in the field. Here, we developed an automated continuous imaging setup with the"read-on-ski"law of control to maximize temporal resolution with minimum culture plate vibration. High-accuracy performance was achieved: organoid screening and imaging were performed at a spatial resolution of 1.1μm for the entire multi-well plate under 3 min. We used the in-house developed multi-well spinning device and cisplatin-induced nephrotoxicity model to evaluate the toxicity in kidney organoids using this system. The acquired images were processed via machine learning-based classification and segmentation algorithms, and the toxicity in kidney organoids was determined with 95%accuracy. The results obtained by the automated"read-on-ski"imaging device, combined with label-free and non-invasive algorithms for detection, were verified using conventional biological procedures. Taking advantage of the close-to-in vivo-kidney organoid model, this new development opens the door for further application of scaled-up screening using organoids in basic research and drug discovery.

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作者 Qizheng WANG [1] Jun LU [2] Ke FAN [3] Yiwei XU [3] Yucui XIONG [3] Zhiyong SUN [2] Man ZHAI [3] Zhizhong ZHANG [2] Sheng ZHANG [3] Yan SONG [3] Jianzhong LUO [3] Mingliang YOU [4] Meijin GUO [1] Xiao ZHANG [2] 学术成果认领
作者单位 State Key Laboratory of Bioreactor Engineering,East China University of Science and Technology,Shanghai 200237,China [1] Guangzhou Institutes of Biomedicine and Health,Chinese Academy of Sciences,Guangzhou 510530,China;Bioland Laboratory(Guangzhou Regenerative Medicine and Health Guangdong Laboratory),Guangzhou 510320,China [2] Guangzhou Institutes of Biomedicine and Health,Chinese Academy of Sciences,Guangzhou 510530,China [3] Hangzhou Cancer Institute,Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province,Affiliated Hangzhou Cancer Hospital,Zhejiang University School of Medicine,Hangzhou 310002,China [4]
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发布时间 2022-07-14(万方平台首次上网日期,不代表论文的发表时间)
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浙江大学学报(英文版)(B辑:生物医学和生物技术)

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