Development of an Extracellular Matrix Plate for Drug Screening Using Patient-Derived Tumor Organoids

Abstract

With the advances in organoid culture, patient-derived organoids are utilized in diverse fields to broaden our understanding of conventional 2-dimensional (2D) culture methods and animal models. Patient-derived organoids have found new applications, such as screening for patient-matching drugs, immune checkpoint drugs, and mutation-target drugs, in the field of drug screening. However, conventional dome-shaped Matrigel drop-based screening methods using 24-, 48-, and 96-well plates are not effective for carrying out large-scale drug screening using organoids. Here, we present a newly developed 96-well plate-based method for the effective screening of patient-derived tumor organoids embedded in Matrigel. The new screening plate has a central hole with a diameter of 3 or 5 mm to provide a definite space for placing Matrigel in a cylindrical shape. Compared to the conventional dome-shaped Matrigel where the Matrigel drop is located arbitrarily, a cylinder-shaped Matrigel position in confined central wells allowed for faster and cost-effective tumor organoid screening. Importantly, the cylinder-shaped Matrigel ensures better consistency in high-throughput image-based analysis, which is used worldwide. Our results demonstrate the possibility of replacing the conventional 24-, 48-, and 96-well plates with the newly developed plates for effective tumor organoid screening.