title: Multiparametric Biomechanical and Biochemical Phenotypic Profiling of Single Cancer Cells Using an Elasticity Microcytometer.
abstract: 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.
authors.affiliation: Department of Mechanical and Biomedical Engineering, City University of Hong Kong, 852, Hong Kong.
authors.forename: Shuhuan
authors.initials: S
authors.lastname: Hu
authors.affiliation: Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI, 48109, USA.
authors.forename: Guangyu
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI, 48109, USA.|Department of Mechanical and Aerospace Engineering, New York University, NY, 11201, USA.
authors.forename: Weiqiang
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI, 48109, USA.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI, 48109, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.affiliation: Department of Mechanical and Biomedical Engineering, City University of Hong Kong, 852, Hong Kong.|Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI, 48109, USA.|City University of Hong Kong Shenzhen Research Institute, Shenzhen, 518057, China.
authors.forename: Raymond H W
authors.initials: RH
authors.lastname: Lam
authors.affiliation: Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI, 48109, USA.|Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, 48109, USA.|Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI, 48109, USA.|Michigan Center for Integrative Research in Critical Care, University of Michigan, Ann Arbor, MI, 48109, USA.
authors.forename: Jianping
authors.initials: J
authors.lastname: Fu
mesh_terms: D001696:Biomechanical Phenomena; D002469:Cell Separation / Q000295:instrumentation*; D000071858:Epithelial Cell Adhesion Molecule / Q000378:metabolism; D006801:Humans; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation*; D014407:Tumor Cells, Cultured
chemical_list: D000071858:Epithelial Cell Adhesion Molecule
keywords: cell deformability; cell phenotyping; elasticity microcytometers; microfluidics; surface proteins