title: Acoustic separation of circulating tumor cells.
abstract: Circulating tumor cells (CTCs) are important targets for cancer biology studies. To further elucidate the role of CTCs in cancer metastasis and prognosis, effective methods for isolating extremely rare tumor cells from peripheral blood must be developed. Acoustic-based methods, which are known to preserve the integrity, functionality, and viability of biological cells using label-free and contact-free sorting, have thus far not been successfully developed to isolate rare CTCs using clinical samples from cancer patients owing to technical constraints, insufficient throughput, and lack of long-term device stability. In this work, we demonstrate the development of an acoustic-based microfluidic device that is capable of high-throughput separation of CTCs from peripheral blood samples obtained from cancer patients. Our method uses tilted-angle standing surface acoustic waves. Parametric numerical simulations were performed to design optimum device geometry, tilt angle, and cell throughput that is more than 20 times higher than previously possible for such devices. We first validated the capability of this device by successfully separating low concentrations (∼100 cells/mL) of a variety of cancer cells from cell culture lines from WBCs with a recovery rate better than 83%. We then demonstrated the isolation of CTCs in blood samples obtained from patients with breast cancer. Our acoustic-based separation method thus offers the potential to serve as an invaluable supplemental tool in cancer research, diagnostics, drug efficacy assessment, and therapeutics owing to its excellent biocompatibility, simple design, and label-free automated operation while offering the capability to isolate rare CTCs in a viable state.
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: Zhangming
authors.initials: Z
authors.lastname: Mao
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: Division of Hematology/Oncology, Penn State Hershey Cancer Institute, Hershey, PA 17033; and.
authors.forename: Lanlan
authors.initials: L
authors.lastname: Zhou
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 Engineering Science and Mechanics, The Pennsylvania State University, University Park, PA 16802;
authors.forename: Po-Hsun
authors.initials: PH
authors.lastname: Huang
authors.affiliation: Division of Hematology/Oncology, Penn State Hershey Cancer Institute, Hershey, PA 17033; and.
authors.forename: Cristina I
authors.initials: CI
authors.lastname: Truica
authors.affiliation: Division of Hematology/Oncology, Penn State Hershey Cancer Institute, Hershey, PA 17033; and.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Drabick
authors.affiliation: Division of Hematology/Oncology, Penn State Hershey Cancer Institute, Hershey, PA 17033; and.
authors.forename: Wafik S
authors.initials: WS
authors.lastname: El-Deiry
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: D000162:Acoustics; D001943:Breast Neoplasms / Q000097:blood / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002469:Cell Separation / Q000379:methods*; D002470:Cell Survival; D004560:Electricity; D005260:Female; D005455:Fluorescent Antibody Technique; D057166:High-Throughput Screening Assays; D006801:Humans; D009360:Neoplastic Cells, Circulating / Q000473:pathology*
keywords: acoustic tweezers; cell separation; circulating cancer cells; microfluidics; rare-cell sorting
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