Microfluidic organs-on-chips

被引:2236
作者
Bhatia, Sangeeta N. [1 ,2 ,3 ,4 ]
Ingber, Donald E. [5 ,6 ,7 ,8 ,9 ]
机构
[1] MIT, Koch Inst, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA
[2] MIT, Inst Med Engn & Sci, Cambridge, MA 02139 USA
[3] Broad Inst, Cambridge, MA USA
[4] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA
[5] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA
[6] Boston Childrens Hosp, Dept Pathol, Vasc Biol Program, Boston, MA USA
[7] Boston Childrens Hosp, Dept Surg, Boston, MA USA
[8] Harvard Univ, Sch Med, Boston, MA USA
[9] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA
基金
美国国家卫生研究院;
关键词
PRIMARY HUMAN HEPATOCYTES; PLURIPOTENT STEM-CELL; IN-VITRO MODEL; A-CHIP; BREAST-CANCER; HUMAN LIVER; EXTRACELLULAR-MATRIX; HEPATIC-CLEARANCE; ENDOTHELIAL-CELLS; GENE-EXPRESSION;
D O I
10.1038/nbt.2989
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
An organ-on-a-chip is a microfluidic cell culture device created with microchip manufacturing methods that contains continuously perfused chambers inhabited by living cells arranged to simulate tissue-and organ-level physiology. By recapitulating the multicellular architectures, tissue-tissue interfaces, physicochemical microenvironments and vascular perfusion of the body, these devices produce levels of tissue and organ functionality not possible with conventional 2D or 3D culture systems. They also enable high-resolution, real-time imaging and in vitro analysis of biochemical, genetic and metabolic activities of living cells in a functional tissue and organ context. This technology has great potential to advance the study of tissue development, organ physiology and disease etiology. In the context of drug discovery and development, it should be especially valuable for the study of molecular mechanisms of action, prioritization of lead candidates, toxicity testing and biomarker identification.
引用
收藏
页码:760 / 772
页数:13
相关论文
共 156 条
[51]   The outgrowth of the nerve fiber as a mode of protoplasmic movement [J].
Harrison, RG .
JOURNAL OF EXPERIMENTAL ZOOLOGY, 1910, 9 (04) :787-U27
[52]   A microfluidic platform for generating large-scale nearly identical human microphysiological vascularized tissue arrays [J].
Hsu, Yu-Hsiang ;
Moya, Monica L. ;
Hughes, Christopher C. W. ;
George, Steven C. ;
Lee, Abraham P. .
LAB ON A CHIP, 2013, 13 (15) :2990-2998
[53]   Acoustically detectable cellular-level lung injury induced by fluid mechanical stresses in microfluidic airway systems [J].
Huh, Dongeun ;
Fujioka, Hideki ;
Tung, Yi-Chung ;
Futai, Nobuyuki ;
Paine, Robert ;
Grotberg, James B., III ;
Takayama, Shuichi .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (48) :18886-18891
[54]   A Human Disease Model of Drug Toxicity-Induced Pulmonary Edema in a Lung-on-a-Chip Microdevice [J].
Huh, Dongeun ;
Leslie, Daniel C. ;
Matthews, Benjamin D. ;
Fraser, Jacob P. ;
Jurek, Samuel ;
Hamilton, Geraldine A. ;
Thorneloe, Kevin S. ;
McAlexander, Michael Allen ;
Ingber, Donald E. .
SCIENCE TRANSLATIONAL MEDICINE, 2012, 4 (159)
[55]   Reconstituting Organ-Level Lung Functions on a Chip [J].
Huh, Dongeun ;
Matthews, Benjamin D. ;
Mammoto, Akiko ;
Montoya-Zavala, Martin ;
Hsin, Hong Yuan ;
Ingber, Donald E. .
SCIENCE, 2010, 328 (5986) :1662-1668
[56]   Mechanobiology and diseases of mechanotransduction [J].
Ingber, DE .
ANNALS OF MEDICINE, 2003, 35 (08) :564-577
[57]   Human kidney proximal tubule-on-a-chip for drug transport and nephrotoxicity assessment [J].
Jang, Kyung-Jin ;
Mehr, Ali Poyan ;
Hamilton, Geraldine A. ;
McPartlin, Lori A. ;
Chung, Seyoon ;
Suh, Kahp-Yang ;
Ingber, Donald E. .
INTEGRATIVE BIOLOGY, 2013, 5 (09) :1119-1129
[58]   A multi-layer microfluidic device for efficient culture and analysis of renal tubular cells [J].
Jang, Kyung-Jin ;
Suh, Kahp-Yang .
LAB ON A CHIP, 2010, 10 (01) :36-42
[59]   In Vitro Model of Tumor Cell Extravasation [J].
Jeon, Jessie S. ;
Zervantonakis, Ioannis K. ;
Chung, Seok ;
Kamm, Roger D. ;
Charest, Joseph L. .
PLOS ONE, 2013, 8 (02)
[60]   Neutrophil chemotaxis in linear and complex gradients of interleukin-8 formed in a microfabricated device [J].
Jeon, NL ;
Baskaran, H ;
Dertinger, SKW ;
Whitesides, GM ;
Van de Water, L ;
Toner, M .
NATURE BIOTECHNOLOGY, 2002, 20 (08) :826-830