Drop-based microfluidic devices for encapsulation of single cells

被引:430
作者
Koester, Sarah [1 ]
Angile, Francesco E. [1 ,2 ]
Duan, Honey [1 ]
Agresti, Jeremy J. [1 ]
Wintner, Anton [1 ]
Schmitz, Christian [1 ]
Rowat, Amy C. [1 ]
Merten, Christoph A. [3 ]
Pisignano, Dario [2 ,4 ]
Griffiths, Andrew D. [3 ]
Weitz, David A. [1 ]
机构
[1] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA
[2] Univ Salento, CNR INFM, Natl Nanotechnol Lab, Lecce, Italy
[3] Univ Strasbourg 1, ISIS, CNRS, UMR 7006, F-7006 Strasbourg, France
[4] Univ Salento, Scuola Super ISUFI, Lecce, Italy
关键词
D O I
10.1039/b802941e
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
We use microfluidic devices to encapsulate, incubate, and manipulate individual cells in picoliter aqueous drops in a carrier fluid at rates of up to several hundred Hz. We use a modular approach with individual devices for each function, thereby significantly increasing the robustness of our system and making it highly flexible and adaptable to a variety of cell-based assays. The small volumes of the drops enables the concentrations of secreted molecules to rapidly attain detectable levels. We show that single hybridoma cells in 33 pL drops secrete detectable concentrations of antibodies in only 6 h and remain fully viable. These devices hold the promise of developing microfluidic cell cytometers and cell sorters with much greater functionality, allowing assays to be performed on individual cells in their own microenvironment prior to analysis and sorting.
引用
收藏
页码:1110 / 1115
页数:6
相关论文
共 23 条
[1]   Dielectrophoretic manipulation of drops for high-speed microfluidic sorting devices [J].
Ahn, K ;
Kerbage, C ;
Hunt, TP ;
Westervelt, RM ;
Link, DR ;
Weitz, DA .
APPLIED PHYSICS LETTERS, 2006, 88 (02) :1-3
[2]   Electrocoalescence of drops synchronized by size-dependent flow in microfluidic channels [J].
Ahn, Keunho ;
Agresti, Jeremy ;
Chong, Henry ;
Marquez, Manuel ;
Weitz, D. A. .
APPLIED PHYSICS LETTERS, 2006, 88 (26)
[3]   Formation of dispersions using "flow focusing" in microchannels [J].
Anna, SL ;
Bontoux, N ;
Stone, HA .
APPLIED PHYSICS LETTERS, 2003, 82 (03) :364-366
[4]   Microfluidic high-throughput encapsulation and hydrodynamic self-sorting of single cells [J].
Chabert, Max ;
Viovy, Jean-Louis .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (09) :3191-3196
[5]   Droplet-based microfluidic platforms for the encapsulation and screening of mammalian cells and multicellular organisms [J].
Clausell-Tormos, Jenifer ;
Lieber, Diana ;
Baret, Jean-Christophe ;
El-Harrak, Abdeslam ;
Miller, Oliver J. ;
Frenz, Lucas ;
Blouwolff, Joshua ;
Humphry, Katherine J. ;
Koster, Sarah ;
Duan, Honey ;
Holtze, Christian ;
Weitz, David A. ;
Griffiths, Andrew D. ;
Merten, Christoph A. .
CHEMISTRY & BIOLOGY, 2008, 15 (05) :427-437
[6]   Selective encapsulation of single cells and subcellular organelles into picoliter- and femtoliter-volume droplets [J].
He, MY ;
Edgar, JS ;
Jeffries, GDM ;
Lorenz, RM ;
Shelby, JP ;
Chiu, DT .
ANALYTICAL CHEMISTRY, 2005, 77 (06) :1539-1544
[7]  
Hendershot L. M. S., 2003, MOL BIOL B CELLS
[8]  
HOLTZE C, 2008, UNPUB
[9]   Quantitative detection of protein expression in single cells using droplet microfluidics [J].
Huebner, A. ;
Srisa-Art, M. ;
Holt, D. ;
Abell, C. ;
Hollfelder, F. ;
deMello, A. J. ;
Edel, J. B. .
CHEMICAL COMMUNICATIONS, 2007, (12) :1218-1220
[10]   Geometrically mediated breakup of drops in microfluidic devices [J].
Link, DR ;
Anna, SL ;
Weitz, DA ;
Stone, HA .
PHYSICAL REVIEW LETTERS, 2004, 92 (05) :4-545034