For more than 200 years, doctors have known that tumor cells can circulate in the bloodstream. Yet circulating tumor cells (CTCs) are a problematic diagnostic marker: in eight milliliters of blood there are about 60 to 80 billion cells, but only a handful of CTCs.
Now, using a silicon microchip the size of a business card, HMS researchers have created a technology that can sift through two milliliters of blood per hour and catch roaming CTCs. The study appears in the Dec. 20 issue of Nature.
“It is our hope that the CTC chip will one day become part of the routine checkup for early detection and screening,” said Mehmet Toner, senior author and HMS professor of surgery at Massachusetts General Hospital.
The microchip is equipped with 78,000 posts that are each 50 microns in diameter and coated with antibodies that recognize epithelial tumor cells.
“Out of 60 billion cells, all of them end up touching the posts,” said Toner. He explained that 85 to 90 percent of all cancers originate in epithelial cells, which normally do not circulate in the blood. Once the fragile epithelial tumor cells bind to the posts, the researchers can enumerate them as well as analyze their nucleic acids.
Using the CTC chip, the researchers tested blood samples from 68 patients with five different types of tumor. Of the 116 samples collected, only one microchip did not identify CTC cells, giving the chip a 99 percent sensitivity reading. In the control group of samples from 20 cancer-free subjects, no CTC cells were found.
Toner and his colleagues set two essential parameters when designing the microchip. The first, flow velocity, influences the duration of cell–micropost contact. The second, shear force, ensures maximum cell–micropost attachment. Accordingly, the researchers designed the microchip so that peripheral blood would run through it at one tenth the speed it travels in humans.
The researchers hope that the microchip will help them understand the process of blood-borne metastasis, which is the path most cancers use in spreading to other parts of the body and the ultimate cause of most cancer deaths.
In addition, the microchip may help doctors tailor treatment to patients.
“It turns out that when a patient responds to a treatment, you can see a decline in the number of circulating tumor cells relatively quickly,” said co-author Daniel Haber, the Laurel Schwartz professor of medicine at HMS and MGH and director of the hospital’s cancer center. “The ability to follow these cells, test them for genetic abnormalities and for evidence that drugs are effectively suppressing their targets may revolutionize the way we test the effectiveness of new cancer treatments.”
