Haoran Tang outlines the efforts within AstraZeneca R&D to enhance the efficiency and cost-effectiveness of drug discovery processes. The primary focus is on the DMTA cycle, which involves screening numerous compounds to identify potential drugs for patients. The workflow incorporates patient-derived organoids into cellular screening and mechanism of action studies, aiming to simplify, reduce costs, and standardise protocols.
Key requirements for the workflow include high throughput, low cost, simple standardised protocols, and standardised readouts. The approach involves using floating organoid cultures with BME2 gels in cost-effective plastic well plates, significantly reducing expenses compared to traditional methods. The process is designed to be as simple as possible, with protocols similar to suspension cell culture, allowing for easy adoption by scientists.
The workflow includes the use of multi-drop dispensers for rapid and efficient plate preparation, enabling the scaling up of organoid production. The integration of existing lab instruments within AstraZeneca R&D allows for multiplex cell loading and viability readouts without compromising the integrity of the cultures. The use of tools like CellTiter-Glo 3D and PhenoSpace AI enhances the accuracy and reliability of data, providing comprehensive phenotypical analysis.
Automation plays a crucial role in the workflow, with protocols for washing, staining, fixation, and imaging being automated to minimise user input while maintaining high data quality. The workflow supports large-scale drug synergy screens and compound profiling, enabling the assessment of therapeutic indices and drug responses. The AI-driven image analysis software further refines the data, ensuring consistent and high-quality results over time.
In summary, this presentation represents a significant advancement in drug discovery, combining cost-effective methods, automation, and AI-driven analysis to streamline the screening process and improve the accuracy of results.
