Cell separation using tilted-angle standing surface acoustic waves
- Proc Natl Acad Sci U S A. 2014 Sep 9;111(36):12992-7. doi: 10.1073/pnas.1413325111.
- 1. Department of Engineering Science and Mechanics, The Pennsylvania State University, University Park, PA 16802;
- 2. 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;
- 3. Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139;
- 4. Cell and Developmental Biology Program, The Pennsylvania State University, University Park, PA 16802; and.
- 5. Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139; [email protected] [email protected] [email protected].
- 6. Department of Biomedical Engineering and Department of Materials Science and Engineering, Carnegie Mellon University, Pittsburgh, PA 15213 [email protected] [email protected] [email protected].
- 7. Department of Engineering Science and Mechanics, The Pennsylvania State University, University Park, PA 16802; [email protected] [email protected] [email protected].
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.