title: Multiparameter mechanical and morphometric screening of cells.
abstract: We introduce a label-free method to rapidly phenotype and classify cells purely based on physical properties. We extract 15 biophysical parameters from cells as they deform in a microfluidic stretching flow field via high-speed microscopy and apply machine-learning approaches to discriminate different cell types and states. When employing the full 15 dimensional dataset, the technique robustly classifies individual cells based on their pluripotency, with accuracy above 95%. Rheological and morphological properties of cells while deforming were critical for this classification. We also show the application of this method in accurate classifying cells based on their viability, drug screening and detecting populations of malignant cells in mixed samples. We show that some of the extracted parameters are not linearly independent, and in fact we reach maximum classification accuracy by using only a subset of parameters. However, the informative subsets could vary depending on cell types in the sample. This work shows the utility of an assay purely based on intrinsic biophysical properties of cells to identify changes in cell state. In addition to a label-free alternative to flow cytometry in certain applications, this work, also can provide novel intracellular metrics that would not be feasible with labeled approaches (i.e. flow cytometry).
authors.affiliation: Department of Bioengineering, University of California, Los Angeles, CA, USA.|California NanoSystems Institute, Los Angeles, CA, USA.|Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Mahdokht
authors.initials: M
authors.lastname: Masaeli
authors.affiliation: Department of Bioengineering, University of California, Los Angeles, CA, USA.
authors.forename: Dewal
authors.initials: D
authors.lastname: Gupta
authors.affiliation: Department of Bioengineering, University of California, Los Angeles, CA, USA.|California NanoSystems Institute, Los Angeles, CA, USA.
authors.forename: Sean
authors.initials: S
authors.lastname: O'Byrne
authors.affiliation: Department of Bioengineering, University of California, Los Angeles, CA, USA.|California NanoSystems Institute, Los Angeles, CA, USA.|CytoVale Inc, South San Francisco, CA, USA.
authors.forename: Henry T K
authors.initials: HT
authors.lastname: Tse
authors.affiliation: Department of Bioengineering, University of California, Los Angeles, CA, USA.|California NanoSystems Institute, Los Angeles, CA, USA.|CytoVale Inc, South San Francisco, CA, USA.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Gossett
authors.affiliation: Department of Bioengineering, University of California, Los Angeles, CA, USA.|California NanoSystems Institute, Los Angeles, CA, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Tseng
authors.affiliation: Department of Bioengineering, University of California, Los Angeles, CA, USA.|California NanoSystems Institute, Los Angeles, CA, USA.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Utada
authors.affiliation: Molecular Biology Institute, University of California, Los Angeles, CA, USA.
authors.forename: Hea-Jin
authors.initials: HJ
authors.lastname: Jung
authors.affiliation: Molecular Biology Institute, University of California, Los Angeles, CA, USA.|Department of Medicine, University of California, Los Angeles, USA.|Department of Human Genetics, University of California, Los Angeles, CA, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Young
authors.affiliation: Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, CA, USA.|The Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, CA, USA.
authors.forename: Amander T
authors.initials: AT
authors.lastname: Clark
authors.affiliation: Department of Bioengineering, University of California, Los Angeles, CA, USA.|California NanoSystems Institute, Los Angeles, CA, USA.
authors.forename: Dino
authors.initials: D
authors.lastname: Di Carlo
mesh_terms: D000818:Animals; D001703:Biophysics; D002452:Cell Count; D053595:Embryonic Stem Cells / Q000166:cytology*; D005347:Fibroblasts / Q000166:cytology; D005434:Flow Cytometry; D006801:Humans; D057446:Hydrodynamics; D000069550:Machine Learning; D051379:Mice; D046210:Microfluidic Analytical Techniques; D044085:Microfluidics; D010641:Phenotype; D012212:Rheology