title: Iso-acoustic focusing of cells for size-insensitive acousto-mechanical phenotyping.
abstract: Mechanical phenotyping of single cells is an emerging tool for cell classification, enabling assessment of effective parameters relating to cells' interior molecular content and structure. Here, we present iso-acoustic focusing, an equilibrium method to analyze the effective acoustic impedance of single cells in continuous flow. While flowing through a microchannel, cells migrate sideways, influenced by an acoustic field, into streams of increasing acoustic impedance, until reaching their cell-type specific point of zero acoustic contrast. We establish an experimental procedure and provide theoretical justifications and models for iso-acoustic focusing. We describe a method for providing a suitable acoustic contrast gradient in a cell-friendly medium, and use acoustic forces to maintain that gradient in the presence of destabilizing forces. Applying this method we demonstrate iso-acoustic focusing of cell lines and leukocytes, showing that acoustic properties provide phenotypic information independent of size.
authors.affiliation: Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.|Department of Biomedical Engineering, Lund University, Ole Römers väg 3, 22363, Lund, Sweden.
authors.forename: Per
authors.identifier: 0000-0001-8542-7924
authors.initials: P
authors.lastname: Augustsson
authors.affiliation: Department of Physics, Technical University of Denmark, DTU Physics Bldg 309, DK-2800 Kongens Lyngby, Denmark.
authors.forename: Jonas T
authors.initials: JT
authors.lastname: Karlsen
authors.affiliation: Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
authors.forename: Hao-Wei
authors.initials: HW
authors.lastname: Su
authors.affiliation: Department of Physics, Technical University of Denmark, DTU Physics Bldg 309, DK-2800 Kongens Lyngby, Denmark.
authors.forename: Henrik
authors.initials: H
authors.lastname: Bruus
authors.affiliation: Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
authors.forename: Joel
authors.initials: J
authors.lastname: Voldman
mesh_terms: D000162:Acoustics; D000818:Animals; D001773:Blood Cells / Q000166:cytology / Q000187:drug effects; D002460:Cell Line; D048429:Cell Size / Q000187:drug effects; D017097:Electric Impedance; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D046210:Microfluidic Analytical Techniques / Q000379:methods*; D010641:Phenotype; D014283:Triiodobenzoic Acids / Q000494:pharmacology
chemical_list: D014283:Triiodobenzoic Acids; C044834:iodixanol