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Next Generation: Separation Two Ways

Researchers designed a microfluidics chip to separate cells using gravity and a force field.

By | June 26, 2012

image: Next Generation: Separation Two Ways An artist's rendering of tumor cells flowing over an array of physical barriers. Martin Rietveld/Johns Hopkins University

An artist's rendering of tumor cells flowing over an array of physical barriers. MARTIN RIETVELD/JOHNS HOPKINS UNIVERSITY

The Device: Researchers at Johns Hopkins University have developed a simple microfluidics chip to separate biological particles, like cells or proteins, by speed and location. Developed by graduate student Jorge Bernate with professor German Drazer, the strategy is a twist on chromatography, wherein separation of particles, like cells or peptides, occurs over time, with fast-moving particles being collected first and slow-moving particles being picked up later. Instead of relying on the single dimension of time, however, Bernate uses a strategy termed vector chromatography, which also uses space to separate biological entities.

The device relies a very simple and cheap force—gravity—to flow particles over an array of micron-sized bumps arranged “like rumble strips on a highway,” said David Inglis, who also researches microfluidics for biological applications at Macquarie University in Sydney, Australia. If the particles can’t jump the strip (due to large size or density), they’ll move along it laterally, while the lighter particles continue downward. Because it takes some energy to hop the barriers, most particles will not continue in a straight line, but move sideways slightly as each barrier is cleared—again with size and density determining their trajectory. A periodic force field, like that generated by magnetic strips, can also be applied to separate cell types, such as cells with and without magnetic bead labels.

What’s New: Previous strategies for separating particles by flowing them through a set of arrayed barriers, like the chip’s grooves, only relied on one type of separation. Some used physical barriers, like “rumble strips,” while others used force fields like those produced by magnetic strips. Bernate and Drazer’s strategy of applying a force field perpendicular to the physical grooves allows particles or cells to be separated based on more than just the size or magnetism. Furthermore, the duo was able to apply a unified set of principles that enable researchers to predict better how particles will respond to either type of periodic barrier, said Bernate.

Importance: Using both space and time to separate entities theoretically allows for higher-throughput applications, said Kevin Dorfman, who studies DNA dynamics (like movement through nanochannels) at the University of Minnesota.

Physical barriers and force field barriers like magnetic strips also separate particles differently. A magnetic strip works well to separate particles into two pools— magnetic and not magnetic, explained Inglis. Using size or density as the separation parameter could allow the particles to separate into several parameters, including size and density, simultaneously.

Needs Improvement: Although Bernate and Drazer have only published experiments separating silica and polystyrene beads based on size and density, they’re currently working on using this strategy to separate red blood cells. Inglis fears that gravity, though cheap, is not a strong enough force to efficiently separate very small or light objects. In their experiments, Bernate and Drazer successfully “separated 4-micron beads, but for [particles] less than a micron, you’d have to wait a week,” Inglis predicted. And while their strategy will allow cells to be separated into a variety of categories, the tradeoff is that the separation may not be as clean as binary separation using only a single parameter, said Dorfman.

J. Bernate, G. Drazer, “Stochastic and deterministic vector chromatography of suspended particles in one-dimensional periodic potentials,” Physical Review Letters, 108:214501-5, 2012.

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