A microfluidics platform for combinatorial drug screening on cancer biopsies

被引:169
|
作者
Eduati, Federica [1 ,2 ,9 ]
Utharala, Ramesh [2 ]
Madhavan, Dharanija [2 ]
Neumann, Ulf Peter [3 ,4 ,5 ]
Longerich, Thomas [6 ,10 ]
Cramer, Thorsten [4 ,5 ,7 ]
Saez-Rodriguez, Julio [1 ,8 ,11 ]
Merten, Christoph A. [2 ]
机构
[1] European Bioinformat Inst EMBL EBI, European Mol Biol Lab, Wellcome Trust Genome Campus, Cambridge CB10 1SD, England
[2] European Mol Biol Lab, Genome Biol Unit, Meyerhofstr 1, D-69117 Heidelberg, Germany
[3] RWTH Univ Hosp, Dept Surg, D-52057 Aachen, Germany
[4] European Surg Ctr Aachen Maastricht, Aachen, Germany
[5] European Surg Ctr Aachen Maastricht, Maastricht, Netherlands
[6] RWTH Univ Hosp, Inst Pathol, D-52057 Aachen, Germany
[7] RWTH Univ Hosp, Dept Surg, Mol Tumor Biol, D-52057 Aachen, Germany
[8] Rhein Westfal TH Aachen, Fac Med, Joint Res Ctr Computat Biomed JRC COMBINE, D-52057 Aachen, Germany
[9] Eindhoven Univ Technol, Dept Biomed Engn, NL-5600 MB Eindhoven, Netherlands
[10] Univ Hosp Heidelberg, Inst Pathol, D-69120 Heidelberg, Germany
[11] Heidelberg Univ, Fac Med, Inst Computat Biomed, BIOQUANT Ctr, D-69120 Heidelberg, Germany
来源
NATURE COMMUNICATIONS | 2018年 / 9卷
关键词
DROPLET-BASED MICROFLUIDICS; DUCTAL PANCREATIC-CANCER; EMBRYONIC STEM-CELLS; LUNG-CANCER; THERAPY; SENSITIVITY; MEDICINE; GROWTH; GENERATION; RESISTANCE;
D O I
10.1038/s41467-018-04919-w
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Screening drugs on patient biopsies from solid tumours has immense potential, but is challenging due to the small amount of available material. To address this, we present here a plug-based microfluidics platform for functional screening of drug combinations. Integrated Braille valves allow changing the plug composition on demand and enable collecting >1200 data points (56 different conditions with at least 20 replicates each) per biopsy. After deriving and validating efficient and specific drug combinations for two genetically different pancreatic cancer cell lines and xenograft mouse models, we additionally screen live cells from human solid tumours with no need for ex vivo culturing steps, and obtain highly specific sensitivity profiles. The entire workflow can be completed within 48 h at assay costs of less than US$ 150 per patient. We believe this can pave the way for rapid determination of optimal personalized cancer therapies.
引用
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页数:13
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