title: Quantitative Magnetic Separation of Particles and Cells Using Gradient Magnetic Ratcheting.
abstract: Extraction of rare target cells from biosamples is enabling for life science research. Traditional rare cell separation techniques, such as magnetic activated cell sorting, are robust but perform coarse, qualitative separations based on surface antigen expression. A quantitative magnetic separation technology is reported using high-force magnetic ratcheting over arrays of magnetically soft micropillars with gradient spacing, and the system is used to separate and concentrate magnetic beads based on iron oxide content (IOC) and cells based on surface expression. The system consists of a microchip of permalloy micropillar arrays with increasing lateral pitch and a mechatronic device to generate a cycling magnetic field. Particles with higher IOC separate and equilibrate along the miropillar array at larger pitches. A semi-analytical model is developed that predicts behavior for particles and cells. Using the system, LNCaP cells are separated based on the bound quantity of 1 μm anti-epithelial cell adhesion molecule (EpCAM) particles as a metric for expression. The ratcheting cytometry system is able to resolve a ±13 bound particle differential, successfully distinguishing LNCaP from PC3 populations based on EpCAM expression, correlating with flow cytometry analysis. As a proof-of-concept, EpCAM-labeled cells from patient blood are isolated with 74% purity, demonstrating potential toward a quantitative magnetic separation instrument.
authors.affiliation: Department of Bioengineering, University of California, 420 Westwood Plaza, 5121 Engineering V, P.O. Box 951600, Los Angeles, CA, 90095-1600, USA.|California NanoSystems Institute, University of California, Los Angeles, 570 Westwood Plaza, Building 114, Los Angeles, CA, 90095, USA.
authors.forename: Coleman
authors.initials: C
authors.lastname: Murray
authors.affiliation: Department of Bioengineering, University of California, 420 Westwood Plaza, 5121 Engineering V, P.O. Box 951600, Los Angeles, CA, 90095-1600, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Pao
authors.affiliation: Department of Bioengineering, University of California, 420 Westwood Plaza, 5121 Engineering V, P.O. Box 951600, Los Angeles, CA, 90095-1600, USA.|California NanoSystems Institute, University of California, Los Angeles, 570 Westwood Plaza, Building 114, Los Angeles, CA, 90095, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Tseng
authors.affiliation: Department of Bioengineering, University of California, 420 Westwood Plaza, 5121 Engineering V, P.O. Box 951600, Los Angeles, CA, 90095-1600, USA.
authors.forename: Shayan
authors.initials: S
authors.lastname: Aftab
authors.affiliation: UCLA Jonsson Comprehensive Cancer Center, 10833 Le Conte Avenue, Los Angeles, CA, 90024, USA.|Departments of Medicine and Urology, UCLA David Geffen School of Medicine, 10833 Le Conte Avenue, Los Angeles, CA, 90095-1738, USA.
authors.forename: Rajan
authors.initials: R
authors.lastname: Kulkarni
authors.affiliation: UCLA Jonsson Comprehensive Cancer Center, 10833 Le Conte Avenue, Los Angeles, CA, 90024, USA.|Departments of Medicine and Urology, UCLA David Geffen School of Medicine, 10833 Le Conte Avenue, Los Angeles, CA, 90095-1738, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Rettig
authors.affiliation: Department of Bioengineering, University of California, 420 Westwood Plaza, 5121 Engineering V, P.O. Box 951600, Los Angeles, CA, 90095-1600, USA.|California NanoSystems Institute, University of California, Los Angeles, 570 Westwood Plaza, Building 114, Los Angeles, CA, 90095, USA.|UCLA Jonsson Comprehensive Cancer Center, 10833 Le Conte Avenue, Los Angeles, CA, 90024, USA.
authors.forename: Dino
authors.initials: D
authors.lastname: Di Carlo
mesh_terms: D045744:Cell Line, Tumor; D002469:Cell Separation / Q000379:methods*; D000071858:Epithelial Cell Adhesion Molecule / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D008280:Magnetics; D008297:Male
chemical_list: C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule
keywords: cell manipulation; circulating tumor cells; equilibrium separation; magnetic separation