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High-throughput "read-on-ski" automated imaging and label-free detection system for toxicity screening of compounds
Qizheng Wang1, Jun Lu2,3, Ke Fan2
1State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China.
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.
Insights
Researchers developed an automated imaging system for rapid, high-accuracy kidney organoid screening. This innovation accelerates toxicity studies and drug discovery using personalized stem cell models.
Area of Science:
- Biotechnology
- Regenerative Medicine
- Toxicology
Background:
- Organoid models, particularly human pluripotent stem cell-derived kidney organoids, are crucial for studying kidney physiology and disease.
- Current methods for assessing nephrotoxicity and compound effects in organoids are often slow, hindering research acceleration.
Purpose of the Study:
- To develop an automated, high-throughput imaging system for kidney organoids.
- To enhance the speed and accuracy of toxicity assessments in organoid models for drug discovery and translational research.
Main Methods:
- An automated continuous imaging setup utilizing the "read-on-ski" control law was developed to minimize vibration and maximize temporal resolution.
- High-resolution (1.1 μm) imaging of entire multi-well plates was achieved in under 3 minutes.
- Machine learning-based classification and segmentation algorithms processed acquired images for toxicity determination.
Main Results:
- The system achieved high-accuracy performance in screening and imaging kidney organoids.
- Cisplatin-induced nephrotoxicity was evaluated in kidney organoids with 95% accuracy using the automated system.
- Label-free, non-invasive algorithms combined with the imaging device provided results verified by conventional biological methods.
Conclusions:
- The developed automated "read-on-ski" imaging system significantly accelerates kidney organoid screening and toxicity assessment.
- This technology facilitates scaled-up screening for basic research and drug discovery, leveraging the in vivo-like nature of organoid models.
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