A versatile, automated and high-throughput drug screening platform for zebrafish embryos

Area of Science:

• * Developmental biology
• * Pharmacology
• * High-content imaging

Background:

• * Zebrafish embryos are valuable for drug screening due to their transparency and rapid development.
• * Limitations in imaging and analysis platforms have hindered high-throughput zebrafish drug screening.
• * Need for automated, flexible, and user-friendly screening procedures.

Purpose of the Study:

• * To develop a customizable, automated platform for high-throughput, phenotype-based screening of live zebrafish.
• * To leverage artificial intelligence for efficient image analysis and data acquisition.
• * To validate the platform's utility in drug discovery and genetic studies.

Main Methods:

• * Utilized the WiScan® Hermes High Content Imaging System for rapid image acquisition (brightfield and fluorescence).
• * Employed the WiSoft® Athena Zebrafish Application with an AI-driven algorithm for automated fish detection, anatomical identification, and region partitioning.
• * Validated using GFP-tagged cells, genetic mutations, X-ray irradiation, and dual fluorophores for simultaneous multi-cell type analysis.

Main Results:

• * Demonstrated successful automated detection and analysis of zebrafish embryos.
• * Validated accuracy in enumerating GFP-tagged hematopoietic stem and progenitor cells, correlating with manual counts.
• * Showcased the system's capability for high-content assessment of genetic mutations and irradiation effects.
• * Achieved simultaneous high-throughput analysis of multiple cell types using dual fluorophores.

Conclusions:

• * Presented a broadly applicable and rapidly customizable platform for high-content screening in zebrafish.
• * The developed system significantly enhances the efficiency and throughput of zebrafish-based drug discovery and research.
• * The AI-driven approach offers a robust solution for complex biological analyses in live animal models.