Issue 14, 2015

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.

Graphical abstract: Velocity valleys enable efficient capture and spatial sorting of nanoparticle-bound cancer cells

Supplementary files

Article information

Article type
Paper
Submitted
03 Feb 2015
Accepted
05 Mar 2015
First published
18 Mar 2015

Nanoscale, 2015,7, 6278-6285

Author version available

Velocity valleys enable efficient capture and spatial sorting of nanoparticle-bound cancer cells

J. D. Besant, R. M. Mohamadi, P. M. Aldridge, Y. Li, E. H. Sargent and S. O. Kelley, Nanoscale, 2015, 7, 6278 DOI: 10.1039/C5NR00797F

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