High-throughput "read-on-ski" automated imaging and label-free detection system for toxicity screening of compounds using personalised human kidney organoids.
- Author:
Qizheng WANG
1
;
Jun LU
2
;
Ke FAN
2
;
Yiwei XU
2
;
Yucui XIONG
2
;
Zhiyong SUN
2
;
Man ZHAI
2
;
Zhizhong ZHANG
2
;
Sheng ZHANG
2
;
Yan SONG
2
;
Jianzhong LUO
2
;
Mingliang YOU
3
;
Meijin GUO
4
;
Xiao ZHANG
5
Author Information
- Publication Type:Journal Article
- Keywords: High-throughput microscopy; Kidney organoid; Machine learning; Nephrotoxicity
- MeSH: Humans; Kidney; Organoids; Pluripotent Stem Cells
- From: Journal of Zhejiang University. Science. B 2022;23(7):564-577
- CountryChina
- Language:English
- Abstract: 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 1.1 μm 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.
