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High-throughput screening with organoids is an emerging technology and scientists are looking for efficient ways to address it. Corning® Matrigel® matrix is the matrix of choice for organoid workflows and lends itself well to the growth of various types of organoids. There are two commonly used methods to dispense organoids in HTS formats; a “sandwich method” wherein the matrix is dispensed into the plate-format of choice and allowed to polymerize. Next, the organoid cell suspension is mixed with a dilution of matrix and dispensed on top of the polymerized layer and allowed to incubate for an additional duration (Cell 2015 161, 933–945). The other option is to mix the organoid cells with Matrigel® matrix and dispense it into HTS-format of interest using a robotic platform while the plates are kept on a cool rack (Journal of Biomolecular Screening 2016 Vol. 21(9) 931–941). They were then pre-cultured for a few days before challenged with drug compounds. We have also had success with utilizing Corning 96-well spheroid microplates to differentiate iPSC spheroids and then overlay with Corning Matrigel matrix. This method allows for a single organoid to form in each well. An imaging-compatible plate format is ideal if the end-point is microscopy; Corning offers a variety of imaging-compatible plate formats that are either round-bottomed, flat bottom or spheroid bottom. Often, researchers also use viability assays also to assess drug toxicity in these 3D cultures.