(left) Emre Ozkumur; (right) Berkin Cilingiroglu/Courtesy of Emre Ozkumur

Needle in a haystack. A cancer cell (left) can cause havoc if it enters the bloodstream. Researchers use micro-scale instruments (right) to hunt for cancer cells in blood samples.

Miniature Chip Detects Rogue Cancer Cells

For cancer patients, things go from bad to worse when tumor cells escape into the bloodstream. The marauding cells—sometimes just one among a billion blood cells—can lodge anywhere in the body, spreading cancer in a process called metastasis. Now, researchers have developed a device that can detect even a single cell of any type of cancer circulating in blood, allowing early treatment of metastasis and new insights into cancer genetics.

Cancer cells that migrate into the bloodstream are called circulating tumor cells (CTCs). In 2007, a team led by biomedical engineer Mehmet Toner of Massachusetts General Hospital in Boston devised a method to trap and detect CTCs on a silicon chip the size of a microscope slide etched with microchannels each no wider than a hair. Toner pumped samples of whole blood through the channels, which were coated with an antibody designed to trap any cancer cell that carries a common surface protein, much as flypaper snags pesky insects. But cancer cells without that protein, such as melanoma (a type of skin cancer), slid past undetected.

The new device gets around that limitation. Called the CTC-iChip system (the "i" is for "inertial focusing"), it targets blood cells instead of cancer cells. Sorting by cell size, the first chip skims off small red blood cells and platelets, letting only CTCs and white blood cells flow past. Then, a second chip winds the cells through curving channels, channeling the remaining cells into a single-file line. Magnetic beads the size of a bacterium attach to specific surface proteins on white blood cells, and a magnetic field nudges these cells out of the stream of CTCs. That leaves just the CTCs, which can be collected in a vial and individually analyzed by conventional lab methods.

The clinical application of this technology is clear, says lead author Emre Ozkumur, a biomedical engineer also at Massachusetts General Hospital who developed the system with Toner. Early CTC detection allows doctors to begin antimetastatic treatments, he says, potentially slowing or stopping cancer's final, fatal onslaught.

Not all CTCs develop into metastatic tumors, however, and cancer researchers are still discovering why. Because CTCs show such large amounts of genetic variation, analyzing cells in bulk won't reveal the reason, Ozkumur says. "You have to analyze one by one."

The team, which reports its findings online today in Science Translational Medicine, is already pondering its next improvements to bring manufacturing costs down and prepare the CTC-iChip for clinical use. The researchers' to-do list includes integrating the current two-chip system into one, Ozkumur says.

The group's work is "a solid advance," says engineer Robert Langer of the Massachusetts Institute of Technology in Cambridge. Langer, who holds more than 800 biomedical patents, applauds the improvements in this device compared with previous models. Other diseases, such as the rare lung disease LAM, also involve circulating abnormal cells, Langer says. This technology may advance research in those diseases as well.

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