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April 7, 2013

Cancer Chip

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Researchers have found a new way to identify loose cancer cells in patients' blood. As this ScienCentral News video explains, use of a high tech chip could give doctors a quicker and less invasive way to tell if treatments are working.

Capturing Cancer Cells

Thanks to new microfluidics and nanotechnology, cancer doctors may be able to design custom therapies for patients by analyzing just a teaspoon of their blood. Researchers from Massachusetts General Hospital's Center for Engineering Medicine and its Cancer Center have reported that their new high-tech chip--the size of a credit card--can capture the rare cancer cells that tumors shed into the bloodstream. Counting and analyzing these wandering tumor cells could mean better early cancer detection and an improved method for monitoring whether treatments are working.

"When a treatment works, we can see a decline, a reduction in the number of cells that we can pull out in the blood," says Daniel Haber, director of the Cancer Center and a leader of the research team. "And when these patients have tumors that do recur, we see a rise or an increase in the number of these cells."

Certain tumors shed cells into the bloodstream, but the stray cells have proved difficult to trap. "These cells in the blood are incredibly rare," says Haber. "They may be about one cell per billion blood cells. So it's a tremendous challenge of technology to be able to find these cells. But if you can find them, and if you can identify them, then it opens a whole world in terms of measuring them, picking them up, and doing particular analyses on them and tests on them."

The new chip uses microfluidics technology to gently flow blood cells around 80,000 nanoscale pillars. Each of these pillars is coated with a protein that acts like flypaper for tumor cells. Over several hours, researchers slowly pass a sample of blood through the machine. While tumor cells cling to the columns, normal blood cells flow by undisturbed. "By the time we're done…we can pull out about 100 cells out of the billions of normal cells in a teaspoon of blood," says Haber. "This is the first time, I think, that we can really get a handle on tumor cells in the blood."

Haber hopes that cancer doctors will be able to use the new device to track genetic markers on their patients' tumors. That way, they can use this genetic information to determine the best therapy for their patients. Until now, such tumor tracking has been difficult.

Biopsies are invasive, so they aren't repeated enough to keep up with a patient's evolving cancer. "Generally, with patients who have cancer, we do an initial biopsy to make sure that it is a tumor, but we don't put them through repeat biopsies over and over." Haber says. "What we're discovering now is that cancers actually change over time, and they respond to treatments in different ways. So this would open up the possibility of following a cancer as it evolves during a patient's care to make sure that the treatment that we give is always the best one for a cancer at a particular time."

Another problem with biopsies is that they often don't provide enough details. To make biopsies less invasive, doctors try to take very small amounts of tissue. The downside of this biopsy downsizing is that tiny samples do not allow for detailed genetic testing. The new microchip technique requires an even less invasive procedure than a biopsy, but as Haber points out, "It gives even more information than is usually available for some of these fine needle aspirate biopsies."

To test their technology, the researchers first tried an experiment with donated blood from healthy volunteers. The researchers spiked the donated blood samples with specific numbers of tumor cells, so they could evaluate their machine's sensitivity: how many tumor cells it found and how many it missed. In all the trials, the machine found over 60 percent of the added tumor cells.

The researchers also tested 116 blood samples from patients with different forms of advanced cancer. "That's where we knew the cells should be," says Haber, "and in fact we could find about one hundred cells in about one teaspoon of blood." In this trial, the device detected tumor cells in every blood sample except one.

"What we're starting to study now is how far can we push the detection," says Haber. He says his group is working to refine the microchip device so that it can detect cancer in its earliest stages. "We want to try to apply this to patients who, for example, might be smokers or have genetic risks for cancers. Can we pick these up earlier and earlier?" he says. The technology may also allow researchers to learn more about why cancers spread.

CellPoint Diagnostics, a young biotechnology company based in Mountain View, California, is working to develop this technology for commercial use. Mehmet Toner and Ronald Tompkins, co-leaders of the study, serve as scientific advisors for CellPoint.

The machine still needs to be developed from a lab apparatus into a device that would be easy for hospitals and clinics to use. Haber explains, "The hope would be that this could be a machine with an on switch, an off switch, basically an easy machine to operate that could be put at the point of care, so in a clinic or any place that handles patients."

"We're not there yet," says Haber. "But our hope would be that within a year or two, we'll be there."

This research was published in Nature on December 27, 2007 and was funded by the National Institutes of Health and the Doris Duke Distinguished Clinical Scientist Award.

       email to a friend by Jessica Tanenbaum

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