title: Brillouin flow cytometry for label-free mechanical phenotyping of the nucleus.
abstract: The mechanical properties of the nucleus are closely related to many cellular functions; thus, measuring nuclear mechanical properties is crucial to our understanding of cell biomechanics and could lead to intrinsic biophysical contrast mechanisms to classify cells. Although many technologies have been developed to characterize cell stiffness, they generally require contact with the cell and thus cannot provide direct information on nuclear mechanical properties. In this work, we developed a flow cytometry technique based on an all-optical measurement to measure nuclear mechanical properties by integrating Brillouin spectroscopy with microfluidics. Brillouin spectroscopy probes the mechanical properties of material via light scattering, so it is inherently label-free, non-contact, and non-invasive. Using a measuring beam spot of submicron size, we can measure several regions within each cell as they flow, which enables us to classify cell populations based on their nuclear mechanical signatures at a throughput of ∼200 cells per hour. We show that Brillouin cytometry has sufficient sensitivity to detect physiologically-relevant changes in nuclear stiffness by probing the effect of drug-induced chromatin decondensation.
authors.affiliation: Fischell Department of Bioengineering, University of Maryland, College Park, Maryland 20742, USA. scarc@umd.edu.
authors.forename: Jitao
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Fischell Department of Bioengineering, University of Maryland, College Park, Maryland 20742, USA. scarc@umd.edu.
authors.forename: Xuefei A
authors.initials: XA
authors.lastname: Nou
authors.affiliation: Canon U.S. Life Sciences, Inc., 9800 Medical Center Drive, Suite C-120, Rockville, MD 20850, USA.
authors.forename: Hanyoup
authors.initials: H
authors.lastname: Kim
authors.affiliation: Fischell Department of Bioengineering, University of Maryland, College Park, Maryland 20742, USA. scarc@umd.edu.
authors.forename: Giuliano
authors.identifier: 0000-0002-1736-077X
authors.initials: G
authors.lastname: Scarcelli
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000145:classification* / Q000648:ultrastructure*; D002843:Chromatin; D005434:Flow Cytometry / Q000295:instrumentation / Q000379:methods*; D007091:Image Processing, Computer-Assisted; D051379:Mice; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation*; D008856:Microscopy, Fluorescence / Q000295:instrumentation*; D041681:NIH 3T3 Cells; D010641:Phenotype
chemical_list: D002843:Chromatin