This article explores the automation of patient-derived organoid high-content assays.
Sponsored Content by Molecular Devices UK LtdJun 5 2024Reviewed by Aimee Molineux Patient-derived organoids , including those from tumors, are implemented as predictive models of patient responses to drugs and therapies. Incorporation of the BioAssembly™ platform has been demonstrated to optimize the complex and indispensable three-dimensional tissue models for drug screening.
In the study discussed in this article, an automated PDO drug screen involving automated imaging and High Content Analysis with the BAB platform was performed. On the second day of culture, the BAB changed culture media and introduced a serial dilution series of trametinib or adavosertib to the wells.
Considerable practice is required for a scientist to achieve a high success rate of dome formation. Incorporation of the BAB is shown to improve the dome formation rate by 10 %, as well as reduce dome dispensing time by 50 %, compared with no automation, as shown in Figure 2. Figure 3. ATP production of PDOs, as measured by CellTiter-Glo 3D, performed at the end of the assay. Image Credit: Molecular Devices UK Ltd
Figure 5. Heat maps and principal component analysis . For Donor 1 , 2 components are shown, which show limited clustering within or between drug concentrations. Donor 2, however, had clear clustering in components 1, 2, and 3, within each drug compared to controls. Image Credit: Molecular Devices UK Ltd
Conclusions This study demonstrates the effectiveness of a fully integrated automation platform for screening the effects of therapeutic compounds on patient-derived tumor organoids. The automated PDO assay was able to identify patient-specific differences in PDO responses to selected signaling inhibitors via high-content image analyses.
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