Microfluidic tissue model for live cell screening

被引:19
作者
Lee, Philip J. [1 ]
Gaige, Terry A. [1 ]
Ghorashian, Navid [1 ]
Hung, Paul J. [1 ]
机构
[1] CellASIC Corp, San Leandro, CA 94577 USA
关键词
D O I
10.1021/bp070053l
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
We have developed a microfluidic platform modeled after the physiologic microcirculation for multiplexed tissue-like culture and high-throughput analysis. Each microfabricated culture unit consisted of three functional components: a 50 mu m wide cell culture pocket, an artificial endothelial barrier with 2,mu m pores, and a nutrient transport channel. This configuration enabled a high density of cancer cells to be maintained for over I week in a solid tumor-like morphology when fed with continuous flow. The microfluidic chip contained 16 parallel units for "flow cell" based experiments where live cells were exposed to a soluble factor and analyzed via fluorescence microscopy or flow-through biochemistry. Each fluidically independent tissue unit contained similar to 500 cells fed with a continuous flow of 10 nL/min. As a demonstration, the toxicity profile of the anti-cancer drug paclitaxel was collected on HeLa cells cultured in the microfluidic format and compared with a 384-well dish for up to 5 days of continuous drug exposure.
引用
收藏
页码:946 / 951
页数:6
相关论文
共 36 条
[1]   Probing the role of multicellular organization in three-dimensional microenvironments [J].
Albrecht, DR ;
Underhill, GH ;
Wassermann, TB ;
Sah, RL ;
Bhatia, SN .
NATURE METHODS, 2006, 3 (05) :369-375
[2]   Long-term monitoring of bacteria undergoing programmed population control in a microchemostat [J].
Balagaddé, FK ;
You, LC ;
Hansen, CL ;
Arnold, FH ;
Quake, SR .
SCIENCE, 2005, 309 (5731) :137-140
[3]   Tissue architecture: the ultimate regulator of breast epithelial function - Commentary [J].
Bissell, MJ ;
Rizki, A ;
Mian, IS .
CURRENT OPINION IN CELL BIOLOGY, 2003, 15 (06) :753-762
[4]   Context, tissue plasticity, and cancer: Are tumor stem cells also regulated by the microenvironment? [J].
Bissell, MJ ;
LaBarge, MA .
CANCER CELL, 2005, 7 (01) :17-23
[5]   Microfluidics-based systems biology [J].
Breslauer, DN ;
Lee, PJ ;
Lee, LP .
MOLECULAR BIOSYSTEMS, 2006, 2 (02) :97-112
[6]   Multicellular resistance: a paradigm for clinical resistance? [J].
Desoize, B ;
Jardillier, JC .
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY, 2000, 36 (2-3) :193-207
[7]   Contribution of three-dimensional culture to cancer research [J].
Desoize, B .
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY, 2000, 36 (2-3) :59-60
[8]   Cells on chips [J].
El-Ali, Jamil ;
Sorger, Peter K. ;
Jensen, Klavs F. .
NATURE, 2006, 442 (7101) :403-411
[9]   Capturing complex 3D tissue physiology in vitro [J].
Griffith, LG ;
Swartz, MA .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2006, 7 (03) :211-224
[10]   Tissue engineering - Current challenges and expanding opportunities [J].
Griffith, LG ;
Naughton, G .
SCIENCE, 2002, 295 (5557) :1009-+