Researchers at Massachusetts Institute of Technology (MIT) and Brigham and Women’s Hospital have designed a cell-sorting microchip that takes advantage of a cell-rolling mechanism used to navigate through the body.
The device takes in mixtures of cells, which flow through tiny channels coated with sticky molecules. Cells with specific receptors bind weakly to the molecules, rolling away from the rest of the flow, and out into a separate receptacle.
The cell sorters 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 require an external pump to push cells through the chip, allowing it 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.
While current cell-sorting technologies separate large batches of cells quickly and efficiently, they have several limitations. Fluorescence-activated cell sorting, requires lasers and voltage to sort cells based on their electric charge. Researchers have also used fluorescent markers and magnetic beads that bind to desired cells, making them easy to spot and sift out. Once collected, the cells need to be separated from the beads and markers—an added step that risks modifying the samples.
Karnik’s team designed a compact cell sorter that requires no additional parts or steps. The team built upon previous work, in which they first came up with the sorting-by-rolling principle. Since then the group has been turning principle into practice, designing a working device to sort cells. 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.
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, Sung Young Choi, an MIT postdoc, 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 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% purity.
Karnik says the device may be replicated and stacked to sort large batches of cells. He and his colleagues are hoping to apply the device to sort other blood cells, as well as certain types of cancer cells for diagnostic applications and stem cells for therapeutic applications. To do that, the team is investigating molecules similar to P-selectin that bind weakly to such cells.
The team reported their findings online in Lab on a Chip.
Release Date: Feb. 24, 2012
Source: Massachusetts Institute of Technology