title: Extracting Cell Stiffness from Real-Time Deformability Cytometry: Theory and Experiment.
abstract: Cell stiffness is a sensitive indicator of physiological and pathological changes in cells, with many potential applications in biology and medicine. A new method, real-time deformability cytometry, probes cell stiffness at high throughput by exposing cells to a shear flow in a microfluidic channel, allowing for mechanical phenotyping based on single-cell deformability. However, observed deformations of cells in the channel not only are determined by cell stiffness, but also depend on cell size relative to channel size. Here, we disentangle mutual contributions of cell size and cell stiffness to cell deformation by a theoretical analysis in terms of hydrodynamics and linear elasticity theory. Performing real-time deformability cytometry experiments on both model spheres of known elasticity and biological cells, we demonstrate that our analytical model not only predicts deformed shapes inside the channel but also allows for quantification of cell mechanical parameters. Thereby, fast and quantitative mechanical sampling of large cell populations becomes feasible.
authors.affiliation: Biotechnology Center, Technische Universität Dresden, Dresden, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Mietke
authors.affiliation: Biotechnology Center, Technische Universität Dresden, Dresden, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Otto
authors.affiliation: Biotechnology Center, Technische Universität Dresden, Dresden, Germany.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Girardo
authors.affiliation: Biotechnology Center, Technische Universität Dresden, Dresden, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Rosendahl
authors.affiliation: Biotechnology Center, Technische Universität Dresden, Dresden, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Taubenberger
authors.affiliation: Biotechnology Center, Technische Universität Dresden, Dresden, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Golfier
authors.affiliation: Biotechnology Center, Technische Universität Dresden, Dresden, Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Ulbricht
authors.affiliation: Institute of Scientific Computing, Technische Universität Dresden, Dresden, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Aland
authors.affiliation: Biotechnology Center, Technische Universität Dresden, Dresden, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Guck
authors.affiliation: Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany; Max Planck Institute for the Physics of Complex Systems, Dresden, Germany. Electronic address: efischer@pks.mpg.de.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Fischer-Friedrich
mesh_terms: D045744:Cell Line, Tumor; D002469:Cell Separation / Q000379:methods*; D048430:Cell Shape; D004548:Elasticity; D006801:Humans; D044085:Microfluidics / Q000379:methods*; D008962:Models, Theoretical; D013314:Stress, Mechanical