title: Highly efficient and selective isolation of rare tumor cells using a microfluidic chip with wavy-herringbone micro-patterned surfaces.
abstract: Circulating tumor cells (CTCs) in peripheral blood have been recognized as a general biomarker for diagnosing cancer and providing guidance for personalized treatments. Yet due to their rarity, the challenge for their clinical utility lies in the efficient isolation while avoiding the capture of other non-targeted white blood cells (WBCs). In this paper, a wavy-herringbone (HB) microfluidic chip coated with antibody directly against epithelial cell adhesion molecule (anti-EpCAM) was developed for highly efficient and selective isolation of tumor cells from tumor cell-spiked whole blood samples. By extending the concept of the hallmark HB-Chip in the literature, the wavy-HB chip not only achieves high capture efficiency (up to 85.0%) by micro-vortexes induced by HB structures, but also achieves high purity (up to 39.4%) due to the smooth wavy microstructures. These smooth wavy-HB structures eliminate the ultra-low shear rate regions in the traditional grooved-HB structures that lead to non-specific trapping of cells. Compared with the grooved-HB chip with sharp corners, the wavy-HB chip shows significantly higher purity while maintaining similarly high capture efficiency. Furthermore, the wavy-HB chip has up to 11% higher captured cell viability over the grooved-HB chip. The distributions of tumor cells and WBCs along the grooves and waves are investigated to help understand the mechanisms behind the better performance of the wavy-HB chip. The wavy-HB chip may serve as a promising platform for CTC capture and cancer diagnosis.
authors.affiliation: Department of Mechanical Engineering and Mechanics, Lehigh University, Bethlehem, PA 18015, USA. yal310@lehigh.edu.
authors.forename: Shunqiang
authors.initials: S
authors.lastname: Wang
authors.affiliation: Bioengineering Program, Lehigh University, Bethlehem, PA 18015, USA.
authors.forename: Antony
authors.initials: A
authors.lastname: Thomas
authors.affiliation: Lawrence Livermore National Laboratory, Livermore, California 94550, USA and Department of Materials Science and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Elaine
authors.initials: E
authors.lastname: Lee
authors.affiliation: Department of Materials Science and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Shu
authors.initials: S
authors.lastname: Yang
authors.affiliation: Bioengineering Program, Lehigh University, Bethlehem, PA 18015, USA and Department of Materials Science and Engineering, Lehigh University, Bethlehem, PA 18015, USA.
authors.forename: Xuanhong
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Department of Mechanical Engineering and Mechanics, Lehigh University, Bethlehem, PA 18015, USA. yal310@lehigh.edu and Bioengineering Program, Lehigh University, Bethlehem, PA 18015, USA.
authors.forename: Yaling
authors.initials: Y
authors.lastname: Liu
mesh_terms: D002469:Cell Separation / Q000295:instrumentation*; D004867:Equipment Design; D045325:HCT116 Cells; D006801:Humans; D056656:Lab-On-A-Chip Devices; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D033081:Shear Strength; D013499:Surface Properties