The number of CTCs found in a milliliter of a particular patient's blood can range from just a few to several thousand. To isolate those rare cells, researchers have tried building microfluidic channels dotted with antibodies specific to a protein found on the target cells. However, because the antibodies only extend tens of nanometers from the bottom of the channel, the capture of cells by the antibodies is slow.
To extend the reach of the capture molecules, Karp and Karnik's team mimicked the tentacles of jellyfish, creating long strands of repeating DNA sequences. Those sequences, known as aptamers, target a protein found in large numbers on leukemia cells.
The DNA strands are attached to a microchannel with a herringbone pattern on its floor. Those patterned ridges cause the blood to swirl as it flows through the channel, improving the chances that individual cells will come into contact with the tentacles, which extend hundreds of microns into the channel. This allows the researchers to increase the rate of blood flow.
"Normally what happens at high flow rates is the cells don't really come close to the surface, and it's very challenging to capture the target cells," Karnik says. "But this combination of these herringbone grooves to mix the solution and bring the cells into contact with surfaces, plus having aptamers that are sticking out into the solution, enables very high capture rates at very high flow rates."
Flow rates in the new device are 10 times higher than those reported for previous devices, and the system can capture 60 to 80 percent of the target cells. In the current model, which measur
|Contact: Kimberly Allen|
Massachusetts Institute of Technology