Micro-bioreactor arrays for controlling cellular environments: Design principles for human embryonic stem cell applications

被引:73
作者
Cimetta, Elisa [2 ]
Figallo, Elisa [2 ]
Cannizzaro, Christopher [3 ]
Elvassore, Nicola [2 ]
Vunjak-Novakovic, Gordana [1 ]
机构
[1] Columbia Univ, Dept Biomed Engn, New York, NY 10032 USA
[2] Univ Padua, Dept Chem Engn, Padua, Italy
[3] Tufts Univ, Dept Biomed Engn, Medford, MA 02155 USA
关键词
Bioreactor; Human embryonic stem cells; Hydrogel; Microfluidics; Steady-state; Dynamic conditions; Time scale; Transport phenomena; ON-A-CHIP; CULTURE ARRAY; MICROFLUIDICS; DIFFERENTIATION; BIOLOGY; SCALE;
D O I
10.1016/j.ymeth.2008.10.015
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
We discuss the utilization of micro-bioreactor arrays for controlling cellular environments in studies of factors that regulate the differentiation of human embryonic stem cells. To this end, we have designed a simple and practical system that couples a microfluidic platform with an array of micro-bioreactors, and has the size of a microscope slide [E. Figallo, C. Cannizzaro, S. Gerecht, J.A. Burdick, R. Langer, N. Elvassore, G. Vunjak-Novakovic, Lab Chip 7 (2007) 710-719]. The system allows quantitative studies of cells cultured in monolayers or encapsulated in three-dimensional hydrogels. We review the operating requirements for studies of human embryonic stem cells (hESCs) under steady-state and dynamic conditions, and the related control of the mass transport and hydrodynamic shear. We describe the design and fabrication of the individual bioreactor components, and the criteria for selecting the bioreactor configuration and operating parameters, based on the analysis of the characteristic times and scales of reaction, convection and diffusion. To illustrate the utility of the bioreactor, we present a "case study" of hESC cultivation with detailed experimental methods and representative biological readouts. (C) 2008 Elsevier Inc. All rights reserved.
引用
收藏
页码:81 / 89
页数:9
相关论文
共 17 条
[11]   Microfluidic large-scale integration: The evolution of design rules for biological automation [J].
Melin, Jessica ;
Quake, Stephen R. .
ANNUAL REVIEW OF BIOPHYSICS AND BIOMOLECULAR STRUCTURE, 2007, 36 :213-231
[12]   Niche-mediated control of human embryonic stem cell self-renewal and differentiation [J].
Peerani, Raheem ;
Rao, Balaji M. ;
Bauwens, Celine ;
Yin, Ting ;
Wood, Geoffrey A. ;
Nagy, Andras ;
Kumacheva, Eugenia ;
Zandstra, Peter W. .
EMBO JOURNAL, 2007, 26 (22) :4744-4755
[13]   It's the ecology, stupid! [J].
Powell, K .
NATURE, 2005, 435 (7040) :268-270
[14]   Microfluidic devices fabricated in poly(dimethylsiloxane) for biological studies [J].
Sia, SK ;
Whitesides, GM .
ELECTROPHORESIS, 2003, 24 (21) :3563-3576
[15]   Microfluidics: Fluid physics at the nanoliter scale [J].
Squires, TM ;
Quake, SR .
REVIEWS OF MODERN PHYSICS, 2005, 77 (03) :977-1026
[16]   Blood-on-a-chip [J].
Toner, M ;
Irimia, D .
ANNUAL REVIEW OF BIOMEDICAL ENGINEERING, 2005, 7 :77-103
[17]   Shear stress induces endothelial differentiation from a murine embryonic mesenchymal progenitor cell line [J].
Wang, H ;
Riha, GM ;
Yan, SY ;
Li, M ;
Chai, H ;
Yang, H ;
Yao, QZ ;
Chen, CY .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2005, 25 (09) :1817-1823