title: Screening and Molecular Analysis of Single Circulating Tumor Cells Using Micromagnet Array.
abstract: Immunomagnetic assay has been developed to detect rare circulating tumor cells (CTCs), which shows clinical significance in cancer diagnosis and prognosis. The generation and fine-tuning of the magnetic field play essential roles in such assay toward effective single-cell-based analyses of target cells. However, the current assay has a limited range of field gradient, potentially leading to aggregation of cells and nanoparticles. Consequently, quenching of the fluorescence signal and mechanical damage to the cells may occur, which lower the system sensitivity and specificity. We develop a micromagnet-integrated microfluidic system for enhanced CTC detection. The ferromagnetic micromagnets, after being magnetized, generate localized magnetic field up to 8-fold stronger than that without the micromagnets, and strengthen the interactions between CTCs and the magnetic field. The system is demonstrated with four cancer cell lines with over 97% capture rate, as well as with clinical samples from breast, prostate, lung, and colorectal cancer patients. The system captures target CTCs from patient blood samples on a standard glass slide that can be examined using the fluorescence in-situ hybridization method for the single-cell profiling. All cells showed clear hybridization signals, indicating the efficacy of the compact system in providing retrievable cells for molecular studies.
authors.affiliation: Thayer School of Engineering, Dartmouth College, Hanover, NH 03755.
authors.forename: Yu-Yen
authors.initials: YY
authors.lastname: Huang
authors.affiliation: Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712-0238.
authors.forename: Peng
authors.initials: P
authors.lastname: Chen
authors.affiliation: Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712-0238.
authors.forename: Chun-Hsien
authors.initials: CH
authors.lastname: Wu
authors.affiliation: Department of Biomedical Engineering, University of Connecticut, Storrs, CT 06269-3247.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Hoshino
authors.affiliation: Department of Imaging Physics, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Sokolov
authors.affiliation: Harold C. Simons Comprehensive Center of the University of Texas Southwestern Medical Center, Dallas TX 75390.
authors.forename: Nancy
authors.initials: N
authors.lastname: Lane
authors.affiliation: Harold C. Simons Comprehensive Center of the University of Texas Southwestern Medical Center, Dallas TX 75390.
authors.forename: Huaying
authors.initials: H
authors.lastname: Liu
authors.affiliation: Harold C. Simons Comprehensive Center of the University of Texas Southwestern Medical Center, Dallas TX 75390.
authors.forename: Michael
authors.initials: M
authors.lastname: Huebschman
authors.affiliation: Harold C. Simons Comprehensive Center of the University of Texas Southwestern Medical Center, Dallas TX 75390.
authors.forename: Eugene
authors.initials: E
authors.lastname: Frenkel
authors.affiliation: Thayer School of Engineering, Dartmouth College, Hanover, NH 03755.
authors.forename: John X J
authors.initials: JX
authors.lastname: Zhang
mesh_terms: D002452:Cell Count / Q000379:methods; D045744:Cell Line, Tumor; D002469:Cell Separation / Q000379:methods; D006801:Humans; D061986:MCF-7 Cells; D060526:Magnetic Fields; D059346:Magnets; D044085:Microfluidics / Q000379:methods; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D011379:Prognosis; D012680:Sensitivity and Specificity; D059010:Single-Cell Analysis / Q000379:methods