Circulating tumor cells (CTC) promise a good way to spot early signs of cancer as well as help track the progression of the disease throughout treatment. Because of their extreme rarity in blood, filtering them out quickly and being able to perform tests on them has proven difficult.
Researchers at MIT and Harvard’s Brigham and Women’s Hospital have developed a microfluidic device that features long jellyfish-like tentacles of DNA that attract proteins associated with specific cancers. Because these strands have a much higher surface area than previous methods used, the researchers were able to get a ten fold increase in captured cells over similar devices.
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This type of device could also enable personalized treatments: Once cells are isolated from a patient, doctors could test different drugs on them to determine which are most effective
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.
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 measures 1 square centimeter, the flow rate is 1 milliliter per hour. By making the device larger, the researchers say they could boost the flow rate to 100 milliliters of blood per hour — fast enough to rapidly process the 10- to 20-milliliter samples that would be needed to get an accurate CTC count from an individual patient.
“In the first part of this video, a particle covered with DNA strands that can bind to a protein found on cancer cells approaches a cell. Though the particle does not directly contact the cell, the DNA strands entangle the cell, as demonstrated when the particle is pulled away and the cell is pulled towards the particle.
In the second part, a particle covered with small molecules that target the same cancer protein does not achieve the same strong binding, even though it comes in direct contact with the cell.”
Press release: On the hunt for rare cancer cells
Study in Proceedings of the National Academy of Sciences: Bioinspired multivalent DNA network for capture and release of cells