title: Cell separation using tilted-angle standing surface acoustic waves.
abstract: Separation of cells is a critical process for studying cell properties, disease diagnostics, and therapeutics. Cell sorting by acoustic waves offers a means to separate cells on the basis of their size and physical properties in a label-free, contactless, and biocompatible manner. The separation sensitivity and efficiency of currently available acoustic-based approaches, however, are limited, thereby restricting their widespread application in research and health diagnostics. In this work, we introduce a unique configuration of tilted-angle standing surface acoustic waves (taSSAW), which are oriented at an optimally designed inclination to the flow direction in the microfluidic channel. We demonstrate that this design significantly improves the efficiency and sensitivity of acoustic separation techniques. To optimize our device design, we carried out systematic simulations of cell trajectories, matching closely with experimental results. Using numerically optimized design of taSSAW, we successfully separated 2- and 10-µm-diameter polystyrene beads with a separation efficiency of ∼ 99%, and separated 7.3- and 9.9-µm-polystyrene beads with an efficiency of ∼ 97%. We illustrate that taSSAW is capable of effectively separating particles-cells of approximately the same size and density but different compressibility. Finally, we demonstrate the effectiveness of the present technique for biological-biomedical applications by sorting MCF-7 human breast cancer cells from nonmalignant leukocytes, while preserving the integrity of the separated cells. The method introduced here thus offers a unique route for separating circulating tumor cells, and for label-free cell separation with potential applications in biological research, disease diagnostics, and clinical practice.
authors.affiliation: Department of Engineering Science and Mechanics, The Pennsylvania State University, University Park, PA 16802;
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Ding
authors.affiliation: Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139; Department of Aerospace and Mechanical Engineering, University of Notre Dame, Notre Dame, IN 46556;
authors.forename: Zhangli
authors.initials: Z
authors.lastname: Peng
authors.affiliation: Department of Engineering Science and Mechanics, The Pennsylvania State University, University Park, PA 16802;
authors.forename: Sz-Chin Steven
authors.initials: SC
authors.lastname: Lin
authors.affiliation: Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139;
authors.forename: Michela
authors.initials: M
authors.lastname: Geri
authors.affiliation: Cell and Developmental Biology Program, The Pennsylvania State University, University Park, PA 16802; and.
authors.forename: Sixing
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Engineering Science and Mechanics, The Pennsylvania State University, University Park, PA 16802;
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Engineering Science and Mechanics, The Pennsylvania State University, University Park, PA 16802;
authors.forename: Yuchao
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139; mingdao@mit.edu suresh@cmu.edu junhuang@psu.edu.
authors.forename: Ming
authors.initials: M
authors.lastname: Dao
authors.affiliation: Department of Biomedical Engineering and Department of Materials Science and Engineering, Carnegie Mellon University, Pittsburgh, PA 15213 mingdao@mit.edu suresh@cmu.edu junhuang@psu.edu.
authors.forename: Subra
authors.initials: S
authors.lastname: Suresh
authors.affiliation: Department of Engineering Science and Mechanics, The Pennsylvania State University, University Park, PA 16802; mingdao@mit.edu suresh@cmu.edu junhuang@psu.edu.
authors.forename: Tony Jun
authors.initials: TJ
authors.lastname: Huang
mesh_terms: D049109:Cell Proliferation; D002469:Cell Separation / Q000379:methods*; D002470:Cell Survival; D003198:Computer Simulation; D005453:Fluorescence; D006801:Humans; D007962:Leukocytes / Q000166:cytology; D061986:MCF-7 Cells; D008863:Microspheres; D009716:Numerical Analysis, Computer-Assisted; D011137:Polystyrenes; D013016:Sound; D013499:Surface Properties
chemical_list: D011137:Polystyrenes
keywords: acoustofluidics; cancer cell separation; microfluidics; particle separation; tilt-angle optimization