title: Velocity valleys enable efficient capture and spatial sorting of nanoparticle-bound cancer cells.
abstract: The development of strategies for isolating rare cells from complex matrices like blood is important for a wide variety of applications including the analysis of bloodborne cancer cells, infectious pathogens, and prenatal testing. Due to their high colloidal stability and surface-to-volume ratio, antibody-coated magnetic nanoparticles are excellent labels for cellular surface markers. Unfortunately, capture of nanoparticle-bound cells at practical flow rates is challenging due to the small volume, and thus low magnetic susceptibility, of magnetic nanoparticles. We have developed a means to capture nanoparticle-labeled cells using microstructures which create pockets of locally low linear velocity, termed velocity valleys. Cells that enter a velocity valley slow down momentarily, allowing the magnetic force to overcome the reduced drag force and trap the cells. Here, we describe a model for this mechanism of cell capture and use this model to guide the rational design of a device that efficiently captures rare cells and sorts them according to surface expression in complex matrices with greater than 10,000-fold specificity. By analysing the magnetic and drag forces on a cell, we calculate a threshold linear velocity for capture and relate this to the capture efficiency. We find that the addition of X-shaped microstructures enhances capture efficiency 5-fold compared to circular posts. By tuning the linear velocity, we capture cells with a 100-fold range of surface marker expression with near 100% efficiency and sort these cells into spatially distinct zones. By tuning the flow channel geometry, we reduce non-specific cell adhesion by 5-fold.
authors.affiliation: Institute for Biomaterials and Biomedical Engineering, University of Toronto, Toronto, M5S 3M2, Canada. shana.kelley@utoronto.ca.
authors.forename: Justin D
authors.initials: JD
authors.lastname: Besant
authors.forename: Reza M
authors.initials: RM
authors.lastname: Mohamadi
authors.forename: Peter M
authors.initials: PM
authors.lastname: Aldridge
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Edward H
authors.initials: EH
authors.lastname: Sargent
authors.forename: Shana O
authors.initials: SO
authors.lastname: Kelley
mesh_terms: D000912:Antibodies, Neoplasm / Q000737:chemistry*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002469:Cell Separation; D006801:Humans; D060526:Magnetic Fields; D053758:Nanoparticles / Q000737:chemistry*; D009360:Neoplastic Cells, Circulating
chemical_list: D000912:Antibodies, Neoplasm