needle in a haystack. a cancer cell ( left ) can cause havoc if it enters the bloodstream. Researchers use micro-scale instruments ( right ) to remove the cancer cells in blood samples.
(left) Emre Ozkumur; (Right) Berkin Cilingiroglu / Courtesy of Emre Ozkumur
For cancer patients, things go from bad to worse when tumor cells escape into the blood stream. Cells sometimes marauding just one among a billion blood cells can lodge anywhere in the body, the spread of cancer in a process called metastasis. Now researchers have developed a device that can detect even a single cell of any type of cancer in the blood, allowing early treatment of metastasis and new knowledge of cancer genetics.
The cancer cells that migrate into the bloodstream are called circulating tumor cells (CTC). In 07, a team led by Mehmet Toner biomedical engineer at Massachusetts General Hospital in Boston has developed a method to trap and detect CTCs on a silicon chip the size of a microscope slide etched with microchannels each no wider that 'a strand of hair. Toner pumped from whole blood samples through the channels, which have been coated with an antibody designed to trap any cancerous cell that carries a common surface protein, as far as flypaper snags annoying insects. But cancer cells without the protein, such as melanoma (a type of skin cancer), slipped unnoticed.
The new system gets around this limitation. CTC-called iChip system (the "i" is for "inertial focusing"), it targets the blood cells instead of cancer cells. Sorting by size of the cell, the first chip creams out of small cells and red blood platelets, leaving only CTCs and white blood cells flow past. Then, a second chip winds cells through curving channels, channeling the remaining cells in a single file line. Magnetic beads of the size of bacteria attach to specific surface proteins on white blood cells, and a magnetic field nudges these cells out of the flow of CTC. That leaves just the CTCs, which can be collected in a vial and analyzed individually by conventional laboratory methods.
The clinical application of this technology is clear, said lead author Emre Ozkumur, a biomedical engineer also at Massachusetts General Hospital who developed the system with toner. Early detection of CTC allows doctors to begin anti-metastatic therapies, he said, which could slow or stop final fatal attack cancer.
all CTCs not develop into metastatic tumors, however, and cancer researchers are still discovering why. Because the CTC show such large amounts of genetic variation, bulk analysis of cells will not reveal the reason, said Ozkumur. "You have to analyze one by one."
The team reports its findings online today in Science Translational Medicine is already pondering its next improvements to reduce manufacturing costs down and prepare CTC-iChip for clinical use. The researchers' task list includes the integration of the system with two current chips into one, said Ozkumur.
The group's work is "a solid lead," said the engineer Robert Langer of the Massachusetts Institute of Technology in Cambridge. Langer, who owns more than 800 biomedical patents, welcomes the improvements in this device relative previous models. other diseases, like rare LAM lung disease, also involve circulating abnormal cells, says Langer. This technology can advance research in these diseases.
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