Assay Establishment and Validation of a High Throughput Screening Platform for Three Dimensional Patient Derived Colon Cancer Organoid Cultures
The application of patient derived three dimensional culture systems as disease specific drug sensitivity models has enormous potential to connect compound screening and clinical trials. However, the implementation of complex cell based assay systems in drug discovery requires reliable and robust screening platforms. Here we describe the establishment of an automated platform in 384 well format for three dimensional organoid cultures derived from colon cancer patients. Single cells were embedded in an extracellular matrix by an automated workflow and subsequently self organized into organoid structures within 4 days of culture before being exposed to compound treatment. We performed validation of assay robustness and reproducibility via plate uniformity and replicate experiment studies. After assay optimization, the patient derived organoid platform passed all relevant validation criteria. In addition, we introduced a streamlined plate uniformity study to evaluate patient derived colon cancer samples from different donors. Our results demonstrate the feasibility of using patient derived tumor samples for high throughput assays and their integration as disease specific models in drug discovery.
Journal of biomolecular screening