Reconfigurable microfluidic hanging drop network for multi-tissue interaction and analysis

被引:326
作者
Frey, Olivier [1 ]
Misun, Patrick M. [1 ]
Fluri, David A. [2 ]
Hengstler, Jan G. [3 ]
Hierlemann, Andreas [1 ]
机构
[1] Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, Bio Engn Lab, CH-4058 Basel, Switzerland
[2] InSphero AG, CH-8952 Schlieren, Switzerland
[3] TU Dortmund Univ, Leibniz Res Ctr Working Environm & Human Factors, D-44139 Dortmund, Germany
基金
瑞士国家科学基金会;
关键词
CELL-CULTURE; TUMOR SPHEROIDS; DRUG DISCOVERY; HUMAN LIVER; 3D; CHIP; HEPATOCYTES; COCULTURE; BIOLOGY; SYSTEMS;
D O I
10.1038/ncomms5250
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
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
Integration of multiple three-dimensional microtissues into microfluidic networks enables new insights in how different organs or tissues of an organism interact. Here, we present a platform that extends the hanging-drop technology, used for multi-cellular spheroid formation, to multifunctional complex microfluidic networks. Engineered as completely open, 'hanging' microfluidic system at the bottom of a substrate, the platform features high flexibility in microtissue arrangements and interconnections, while fabrication is simple and operation robust. Multiple spheroids of different cell types are formed in parallel on the same platform; the different tissues are then connected in physiological order for multi-tissue experiments through reconfiguration of the fluidic network. Liquid flow is precisely controlled through the hanging drops, which enable nutrient supply, substance dosage and inter-organ metabolic communication. The possibility to perform parallelized microtissue formation on the same chip that is subsequently used for complex multi-tissue experiments renders the developed platform a promising technology for 'body-on-a-chip'-related research.
引用
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页数:11
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