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High Content Screening in Neurodegenerative Diseases
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HCS-3DX, a next-generation AI-driven automated 3D-oid high-content screening system.
Akos Diosdi1,2,3, Timea Toth1, Maria Harmati1
1Synthetic and Systems Biology Unit, HUN-REN Biological Research Centre (HUN-REN BRC), Szeged, Hungary.
Nature Communications
|October 7, 2025
Summary
A new system, HCS-3DX, enhances high-content screening (HCS) for 3D cell cultures (3D-oids). It enables precise, single-cell analysis in 3D tumor models, improving drug screening and personalized medicine.
Area of Science:
- Biotechnology
- Cell Biology
- Medical Imaging
Background:
- Three-dimensional (3D) cell cultures (3D-oids) like spheroids and organoids are vital for drug analysis and cancer research.
- Standardizing high-content screening (HCS) for 3D-oids remains a significant challenge.
- Current HCS systems lack the resolution and efficiency for detailed single-cell analysis in 3D models.
Purpose of the Study:
- To develop and validate HCS-3DX, a next-generation system for 3D imaging and image evaluation of 3D-oids.
- To address the limitations of current HCS systems in analyzing complex 3D cell cultures.
- To enhance the accuracy and efficiency of drug screening and personalized medicine using 3D models.
Main Methods:
- Development of HCS-3DX, incorporating an AI-driven micromanipulator for 3D-oid selection.
- Utilization of an HCS foil multiwell plate optimized for 3D imaging.
- Implementation of AI-based software for single-cell data analysis in 3D.
Main Results:
- HCS-3DX demonstrated high-resolution 3D HCS at the single-cell level.
- The system was successfully validated on 3D tumor models, including tumor-stroma co-cultures.
- HCS-3DX overcomes the resolution limitations of existing HCS systems.
Conclusions:
- HCS-3DX provides a reliable and effective solution for 3D HCS analysis.
- The system significantly enhances the accuracy and efficiency of drug screening processes.
- HCS-3DX facilitates personalized medicine and detailed cellular behavior studies in 3D structures.
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