Miniaturized Drug Sensitivity and Resistance Test on Patient-Derived Cells Using Droplet-Microarray

被引:16
|
作者
Popova, Anna A. [1 ]
Dietrich, Sascha [2 ,3 ,4 ,5 ]
Huber, Wolfgang [4 ,5 ]
Reischl, Markus [6 ]
Peravali, Ravindra [1 ]
Levkin, Pavel A. [1 ,7 ]
机构
[1] Karlsruhe Inst Technol, Inst Chem & Biol Syst, Hermann von Helmholtz Pl 1, D-76344 Eggenstein Leopoldshafen, Germany
[2] Natl Ctr Tumor Dis, Heidelberg, Germany
[3] Univ Hosp Heidelberg, Med Klin 5, Heidelberg, Germany
[4] European Mol Biol Labs EMBL, Heidelberg, Germany
[5] Mol Med Partnership Unit MMPU, Heidelberg, Germany
[6] Karlsruhe Inst Technol, Inst Automat & Appl Informat, Eggenstein Leopoldshafen, Germany
[7] Karlsruhe Inst Technol, Inst Organ Chem, Karlsruhe, Germany
来源
SLAS TECHNOLOGY | 2021年 / 26卷 / 03期
关键词
drug sensitivity and resistance test (DSRT); Droplet-Microarray; drug screening; primary cells; superhydrophobicity; personalized medicine; LEUKEMIA; COMBINATIONS; CHEMOTHERAPY; MUTATIONS; PATTERNS; MEDICINE; PLATFORM; THERAPY; SYSTEMS;
D O I
10.1177/2472630320934432
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Testing the sensitivity of patient-derived tumor cells ex vivo can potentially help determining the appropriate treatment for each patient and spot the development of resistance to a given therapy. The number of cells obtainable from a biopsy is, however, often insufficient for performing ex vivo tests in conventional microtiter plates. Here, we introduce a novel Droplet-Microarray platform based on a hydrophilic-superhydrophobic patterned surface that enables screenings using only 100 cells and 30 picomoles of a drug per individual nanoliter-sized droplet. We demonstrate that the dose-response of as few as 100 primary patient-derived chronic lymphocytic leukemia (CLL) cells to anticancer compounds on the Droplet-Microarray platform resembles the dose-response obtained in 384-well plates requiring 20,000 tumor cells per experiment. The extremely miniaturized Droplet-Microarray platform thus carries great potential for ex vivo drug sensitivity and resistance tests on patient-derived tumor cells and potentially for implementing such tests in medical practice of precision medicine.
引用
收藏
页码:274 / 286
页数:13
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