High-throughput measurement of single-cell growth rates using serial microfluidic mass sensor arrays

被引:174
作者
Cermak, Nathan [1 ]
Olcum, Selim [2 ]
Delgado, Francisco Feijo [2 ,3 ]
Wasserman, Steven C. [3 ]
Payer, Kristofor R. [4 ]
Murakami, Mark A. [5 ]
Knudsen, Scott M. [3 ]
Kimmerling, Robert J. [3 ]
Stevens, Mark M. [6 ]
Kikuchi, Yuki [4 ,11 ]
Sandikci, Arzu [2 ]
Ogawa, Masaaki [7 ]
Agache, Vincent [8 ]
Baleras, Francois [8 ]
Weinstock, David M. [5 ,9 ]
Manalis, Scott R. [1 ,2 ,3 ,4 ,10 ]
机构
[1] MIT, Program Computat & Syst Biol, 77 Massachusetts Ave, Cambridge, MA 02139 USA
[2] MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA
[3] MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA
[4] MIT, Microsyst Technol Labs, Cambridge, MA 02139 USA
[5] Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA
[6] MIT, Dept Biol, 77 Massachusetts Ave, Cambridge, MA 02139 USA
[7] Innovat Micro Technol, Goleta, CA USA
[8] CEA LETI, Minatec Campus, Grenoble, France
[9] Broad Inst, Cambridge, MA USA
[10] MIT, Dept Mech Engn, Cambridge, MA 02139 USA
[11] Hitachi High Technol Corp, Hitachinaka, Ibaraki, Japan
基金
美国国家科学基金会;
关键词
SIZE CONTROL; IN-VITRO; BACTERIAL; VARIABILITY; HOMEOSTASIS; TOLERANCE; TIME;
D O I
10.1038/nbt.3666
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
Methods to rapidly assess cell growth would be useful for many applications, including drug susceptibility testing, but current technologies have limited sensitivity or throughput. Here we present an approach to precisely and rapidly measure growth rates of many individual cells simultaneously. We flow cells in suspension through a microfluidic channel with 10-12 resonant mass sensors distributed along its length, weighing each cell repeatedly over the 4-20 min it spends in the channel. Because multiple cells traverse the channel at the same time, we obtain growth rates for >60 cells/h with a resolution of 0.2 pg/h for mammalian cells and 0.02 pg/h for bacteria. We measure the growth of single lymphocytic cells,. mouse and human T cells, primary human leukemia cells, yeast, Escherichia coli and Enterococcus faecalis. Our system reveals subpopulations of cells with divergent growth kinetics and enables assessment of cellular responses to antibiotics and antimicrobial peptides within minutes.
引用
收藏
页码:1052 / 1059
页数:8
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