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Abstract :
To test the safety and efficacy of drugs via a high does drug heat map, a multi-spheroids
array chip was developed by adopting a micropillar and microwell structure. In the chip,
patient-derived cells were encapsulated in alginate and grown to maturity for more than 7
days to form cancer multi-spheroids. Multi-spheroids grown in conventional well plates
require many cells and are easily damaged as a result of multiple pipetting during maintenance culture or experimental procedures. To address these issues, we applied a micropillar and microwell structure to the multi-spheroids array. Patient-derived cells from patients
with Glioblastoma (GBM), the most common and lethal form of central nervous system cancer, were used to validate the array chip performance. After forming multi-spheroids with a
diameter greater than 100μm in a 12×36 pillar array chip (25mm × 75mm), we tested 70
drug compounds (6 replicates) using a high-dose to determine safety and efficacy for drug
candidates. Comparing the drug response of multi-spheroids derived from normal cells and
cancer cells, we found that four compounds (Dacomitinib, Cediranib, LY2835219, BGJ398)
did not show toxicity to astrocyte cell and were efficacious to patient-derived GBM cells.