TY - JOUR
T1 - Multiparametric Biomechanical and Biochemical Phenotypic Profiling of Single Cancer Cells Using an Elasticity Microcytometer
AU - Hu, Shuhuan
AU - Liu, Guangyu
AU - Chen, Weiqiang
AU - Li, Xiang
AU - Lu, Wei
AU - Lam, Raymond H.W.
AU - Fu, Jianping
N1 - Funding Information:
The authors acknowledge fi nancial support from the National Science Foundation (ECCS 1231826, CBET 1263889, and CMMI 1536087; JF), the National Institutes of Health (R01 HL119542; JF), the UM Comprehensive Cancer Center Prostate SPORE Pilot Project (NIH/NCI P50 CA069568; JF), the Michigan Center for Integrative Research in Critical Care (M-CIRCC; JF), the Michigan Translational Research and Commercialization for Life Sciences Program (MTRAC; JF), the National Natural Science Foundation of China (NSFC 31500758; RL), and the City University of Hong Kong (SRG-Fd 7004540; RL). The Lurie Nanofabrication Facility at the University of Michigan, a member of the National Nanotechnology Infrastructure Network (NNIN) funded by the National Science Foundation, is acknowledged for support in microfabrication.
Publisher Copyright:
© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
PY - 2016/5/4
Y1 - 2016/5/4
N2 - Deep phenotyping of single cancer cells is of critical importance in the era of precision medicine to advance understanding of relationships between gene mutation and cell phenotype and to elucidate the biological nature of tumor heterogeneity. Existing microfluidic single-cell phenotyping tools, however, are limited to phenotypic measurements of 1-2 selected morphological and physiological features of single cells. Herein a microfluidic elasticity microcytometer is reported for multiparametric biomechanical and biochemical phenotypic profiling of free-floating, live single cancer cells for quantitative, simultaneous characterizations of cell size, cell deformability/stiffness, and surface receptors. The elasticity microcytometer is implemented for measurements and comparisons of four human cell lines with distinct metastatic potentials and derived from different human tissues. An analytical model is developed from first principles for the first time to convert cell deformation and adhesion information of single cancer cells encapsulated inside the elasticity microcytometer to cell deformability/stiffness and surface protein expression. Together, the elasticity microcytometer holds great promise for comprehensive molecular, cellular, and biomechanical phenotypic profiling of live cancer cells at the single cell level, critical for studying intratumor cellular and molecular heterogeneity using low-abundance, clinically relevant human cancer cells. A microfluidic elasticity microcytometer is developed for multiparametric biochemical and biomechanical phenotypic profiling of single live cancer cells in terms of cell size, deformability/stiffness, and surface receptors, promising for studying intratumor cellular and molecular heterogeneity using low-abundance, clinically relevant human cancer cells..
AB - Deep phenotyping of single cancer cells is of critical importance in the era of precision medicine to advance understanding of relationships between gene mutation and cell phenotype and to elucidate the biological nature of tumor heterogeneity. Existing microfluidic single-cell phenotyping tools, however, are limited to phenotypic measurements of 1-2 selected morphological and physiological features of single cells. Herein a microfluidic elasticity microcytometer is reported for multiparametric biomechanical and biochemical phenotypic profiling of free-floating, live single cancer cells for quantitative, simultaneous characterizations of cell size, cell deformability/stiffness, and surface receptors. The elasticity microcytometer is implemented for measurements and comparisons of four human cell lines with distinct metastatic potentials and derived from different human tissues. An analytical model is developed from first principles for the first time to convert cell deformation and adhesion information of single cancer cells encapsulated inside the elasticity microcytometer to cell deformability/stiffness and surface protein expression. Together, the elasticity microcytometer holds great promise for comprehensive molecular, cellular, and biomechanical phenotypic profiling of live cancer cells at the single cell level, critical for studying intratumor cellular and molecular heterogeneity using low-abundance, clinically relevant human cancer cells. A microfluidic elasticity microcytometer is developed for multiparametric biochemical and biomechanical phenotypic profiling of single live cancer cells in terms of cell size, deformability/stiffness, and surface receptors, promising for studying intratumor cellular and molecular heterogeneity using low-abundance, clinically relevant human cancer cells..
KW - cell deformability
KW - cell phenotyping
KW - elasticity microcytometers
KW - microfluidics
KW - surface proteins
UR - http://www.scopus.com/inward/record.url?scp=84977868448&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84977868448&partnerID=8YFLogxK
U2 - 10.1002/smll.201503620
DO - 10.1002/smll.201503620
M3 - Article
C2 - 26929029
AN - SCOPUS:84977868448
VL - 12
SP - 2300
EP - 2311
JO - Small
JF - Small
SN - 1613-6810
IS - 17
ER -