High-throughput measurement of single-cell growth rates using serial microfluidic mass sensor arrays.
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.
Program in Computational and Systems Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Nathan
N
Cermak
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Selim
http://orcid.org/0000-0002-6417-1007
S
Olcum
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Francisco Feijó
FF
Delgado
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Steven C
SC
Wasserman
Microsystems Technology Laboratories, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Kristofor R
KR
Payer
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
Mark
M
A Murakami
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Scott M
SM
Knudsen
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Robert J
RJ
Kimmerling
Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Mark M
MM
Stevens
Microsystems Technology Laboratories, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Yuki
Y
Kikuchi
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Arzu
A
Sandikci
Innovative Micro Technology, Goleta, California, USA.
Masaaki
M
Ogawa
CEA-LETI, Minatec Campus, Grenoble, France.
Vincent
V
Agache
CEA-LETI, Minatec Campus, Grenoble, France.
François
F
Baléras
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.|Broad Institute, Cambridge, Massachusetts, USA.
David M
DM
Weinstock
Program in Computational and Systems Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Microsystems Technology Laboratories, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Scott R
SR
Manalis
D049109:Cell Proliferation / Q000187:drug effects* / Q000502:physiology*; D004353:Drug Evaluation, Preclinical / Q000295:instrumentation* / Q000379:methods; D004867:Equipment Design; D019544:Equipment Failure Analysis; D057166:High-Throughput Screening Assays / Q000295:instrumentation* / Q000379:methods; D056656:Lab-On-A-Chip Devices; D055617:Micro-Electrical-Mechanical Systems / Q000295:instrumentation* / Q000379:methods; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014159:Transducers