A compatible gravity-driven organoid perfusion (GDOP) platform for drug screening with sensitivity and toxicity...

Area of Science:

• Biotechnology
• Oncology
• Drug Discovery

Background:

• Existing tumor organoid chips struggle with high-throughput experiments, unidirectional fluid control, real-time monitoring, and simultaneous drug testing.
• Developing advanced organoid platforms is crucial for efficient drug screening and personalized cancer therapy.

Purpose of the Study:

• To develop a novel gravity-driven organoid perfusion (GDOP) platform for scalable, high-throughput drug sensitivity and toxicity assessments.
• To validate the platform's capabilities using triple-negative breast cancer (TNBC) organoids and brain organoids.

Main Methods:

• Fluid dynamics simulations were used to validate the unidirectional perfusion and operational parameters of the GDOP chip.
• Uniform on-chip triple-negative breast cancer (TNBC) organoids were established and monitored for morphological and grayscale changes during drug treatment.
• Drug sensitivity and toxicity tests were performed on the TNBC organoids to determine optimal chemotherapeutic drug concentrations.

Main Results:

• The GDOP platform successfully facilitated scalable throughput and supported drug sensitivity and toxicity assessments.
• On-chip TNBC organoids exhibited endpoint detection results consistent with clinical diagnosis.
• Morphological and grayscale analyses provided insights into organoid responses to chemotherapeutic drugs, revealing optimal concentration ranges.
• Feasible establishment of on-chip brain organoids was demonstrated, paving the way for complex organoid toxicity testing.

Conclusions:

• The GDOP platform offers a powerful and reliable method for organoid-based research, enhancing drug discovery and development.
• The integrated evaluation method complements the GDOP platform, providing a comprehensive approach for organoid analysis.
• This technology has the potential to significantly advance personalized medicine through more accurate and efficient drug screening.