Researchers from MIT and Harvard’s Brigham and Women’s Hospital have developed a microchip that deterministically sorts cells using a naturally occurring rolling mechanism. Cell rolling is known to occur, for example, in inflammation, where carbohydrate ligands on the circulating leukocytes bind to selectin molecules on the endothelium, causing the leukocytes to slow down, and then be pulled toward areas of inflammation.
Here’s how MIT press statement describes this new cell sorting microchip:
The device takes in mixtures of cells, which flow through tiny channels coated with sticky molecules. Cells with specific receptors bind weakly to these molecules, rolling away from the rest of the flow, and out into a separate receptacle.
The cell sorters, about the size of postage stamps, may be fabricated and stacked one on top of another to sift out many cells at once — an advantage for scientists who want to isolate large quantities of cells quickly. The device doesn’t necessarily require an external pump to push cells through the chip, which makes it a portable, affordable option for use in laboratories or clinics, where cell samples may be taken and sorted without specialized equipment.
“We’re working on a disposable device where you wouldn’t even need a syringe pump to drive the separation,” says Rohit Karnik, the d’Arbeloff Assistant Professor of Mechanical Engineering at MIT. “You could potentially buy a $5 or $10 kit and get the cells sorted without needing any kind of [additional] instrument.”
The initial proof-of-principle design was relatively simple: Cells were injected into a single inlet, which gave way to a large chamber coated on one side with sticky, roll-inducing molecules. The incoming cells flowed through the chamber; the cells that bound to the molecules rolled to one side, then out to a collection chamber.
However, the researchers found that in order to allow target cells to first settle on the chamber’s surface, long channels were required, which would make the device too large. Instead, Choi came up with a surface pattern that causes cells to circulate within the chamber. The pattern comprises 10 parallel channels with 50 ridges and trenches, each ridge about 40 microns high. The researchers coated the ridges with P-selectin, a well-known molecule that promotes cell rolling. They then injected two kinds of leukemia cells: one with receptors for P-selectin, the other without.
They found that once injected, the cells entered the chamber and bounced across the top of the ridges, exiting the chip through an outlet. The cells with P-selectin receptors were “caught” by the sticky molecule and flipped into trenches that led to a separate receptacle. Through their experiments, the team successfully recovered the cells they intended to sift out with 96 percent purity.
Press release: Rolling in the chip
Abstract in Lab on a Chip: Cell sorting by deterministic cell rolling