Abstract
Simple SummaryPersonalized drug cocktails have been widely implemented in cancer treatment, due to their merits of using a drug synergistic combination rather than a single effector. Through the incorporation of a cell microarray chip, the usage of both cell amount and reagent can be optimized and effectively reduced in cost. Herein, we present a laser direct writing strategy to fabricate a microcrater-arrayed (µCA) chip incorporated with an automatic liquid handling platform. Each cell droplet with a critical volume of 200 nL containing 100 SK-N-DZ or MCF-7 cells was utilized. The drug synergy screening took less than 30 s for a total of 81 tests. The results show that the potent drug prediction of the µCA chip is more accurate than the conventional 96-well plate assay, which are all compared using zebrafish DiI-labelled tumor xenograft models. Taken together, these findings may impact high-throughput drug screening and personalized drug medicine.Purpose: The aim of this study was to develop a rapid and automatic drug screening platform using microcrater-arrayed (µCA) cell chips. Methods: The µCA chip was fabricated using a laser direct writing technique. The fabrication time required for one 9 × 9 microarray wax chip was as quick as 1 min. On a nanodroplet handling platform, the chip was pre-coated with anti-cancer drugs, including cyclophosphamide, cisplatin, doxorubicin, oncovin, etoposide, and 5-fluorouracil, and their associated mixtures. Cell droplets containing 100 SK-N-DZ or MCF-7 cells were then loaded onto the chip. Cell viability was examined directly through a chemiluminescence assay on the chip using the CellTiter-Glo assay. Results: The time needed for the drug screening assay was demonstrated to be less than 30 s for a total of 81 tests. The prediction of optimal drug synergy from the µCA chip was found by matching it to that of the zebrafish MCF-7 tumor xenograft model, instead of the conventional 96-well plate assay. In addition, the critical reagent volume and cell number for each µCA chip test were 200 nL and 100 cells, respectively, which were significantly lower than 100 µL and 4000 cells, which were achieved using the 96-well assay. Conclusion: Our study for the µCA chip platform could improve the high-throughput drug synergy screening targeting the applications of tumor cell biology.
Highlights
Cell-based microarray chips have been widely utilized to explain the gaps in limited cell sources, critical reagent volumes, and high-throughput and high-content drug screening [1,2,3,4,5,6]
To address the technology gaps described above, we present a microcraterarrayed cell chip for facilitating the high-throughput screening of optimal drug combinations
The results show that the screened optimal drug combination #36 from the μCA chip presented significant tumor inhibition, as compared with the control (Figure 5b)
Summary
Cell-based microarray chips have been widely utilized to explain the gaps in limited cell sources, critical reagent volumes, and high-throughput and high-content drug screening [1,2,3,4,5,6]. Based on these merits, cells cultured in microscales would possess drug responses resembling those in vivo microenvironments. Large-scale cell simulations could contribute more efficacy to in vivo drug prediction than conventional approaches [13,14] All of these approaches were accomplished using multi-well plates. The multilayered 3D cell culture has been revealed with a respective efficacy targeting tumor microenvironments, both the cell numbers and the testing period are still of concern [16]
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