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Using a plastic chip, doctors may soon be able to detect a much wider range of cancer cells in their patients' blood, according to a study published yesterday in Science Transitional Medicine. Their work focuses on a new version of the CTC-Chip, a technology first developed in 2007 to detect circulating tumor cells, the cells that leave a tumor and travel through the bloodstream to metastasize in other parts of the body.

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The original lab-on-a-chip, no bigger than a microscope slide, works by passing blood samples through a set of nearly 80,000 posts, each barely the size of a human hair and coated with antibodies that attract circulating tumor cells, or CTCs. Once the sample has passed through, researchers can examine the chip and count CTCs to see how far the cancer has progressed. The problem until now has been that chips rely on the presence of the cell-surface protein EpCAM to capture CTCs. But some cancer cells—including those found in melanoma and certain types of breast cancer—have a reduced number of EpCAMs or lack them completely, making them hard to catch.

The new device, made of multiple chips, gets around this problem by targeting the blood cells in a patient's sample rather than the cancer cells. The first chip in the system skims off the tiny red blood cells and platelets so that only the CTCs and white blood cells flow into the second. This second chip draws the remaining cells into a single-file line, where tiny magnetic beads, each about the size of a bacterium, grab surface proteins specific to white blood cells. Finally, a magnetic field attracts the pairs of white blood cells and magnetic beads, leaving just the CTCs to be collected.

Mehmet Toner, a biomedical engineer and professor of surgery at Harvard Medical School who worked on both models of the chip, says the new generation makes three major improvements.

First, he tells PM, the chip has a much higher throughput. For early cancer detection, when cancer cells are scarce, a chip needs to be able to process about 10 to 20 milliliters of blood. The first chip could process only 1 to 2 milliliters per hour, meaning hours of processing for a single test. The new chip can process 10 milliliters of blood per hour.

The new chip can also find CTCs that lack the EpCAM protein, which escaped the earlier model. "Our original vision was that most cancers are epithelial and had EpCAMs," Toner says, "but it turns out that you need different flavors of antibody for different stages of cancer—cells can change their phenotype," or composition, "with time and treatment. So looking for a specific antibody on the surface of the cancer cell was a little bit naïve." Now the antigen-independent chip can detect cells from virtually any kind of cancer.

Finally, the new chip preserves CTCs in an "unaltered and pristine state" instead of letting them get stuck to tiny posts on the microchip. With these cells, Toner says, doctors can do precise pathological and genetic studies, telling them much more about the progression of their patients' cancers. These three improvements, Toner says, could make the chips much better at detecting cancer early.

"AIDS is a good analogy for cancer treatment," Toner says. "In this country, it's a chronic disease. We have a test, we can diagnosis it and treat it and monitor the patient. You have a very individual level of monitoring and diagnosis. We can't do this with cancer. In underdeveloped countries, they detect AIDS too late and bombard the patient with toxic drugs, and still barely anyone survives. We are treating cancer in the West like they treat AIDS in Third World countries. We wait too long to find it, and treatment is expensive, and survival rates are low."

Toner also hopes the chip's relative ease of production—it is plastic instead of glass and uses commercially available magnetic beads—will make its transition to the mass market a quick one. The developers are working with Johnson & Johnson to distribute the product, which will soon undergo clinical trials. "We are hopeful and excited," he says, "that this will become a reality in the very-near term."

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