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Rewriting Life

Cheaper Cancer Gene Tests, by the Drop

A single-molecule gene test requires much less DNA to identify cancer-causing mutations.

Many tumor biopsy samples haven’t been good candidates for the increasingly popular genetic tests that can expose a cancer’s progression and its susceptibility to drugs and other treatments.

A cost-effective new testing method could make it easier for scientists to identify the assortment of cancer-causing genetic mutations in tumor cells. Developed by RainDance Technologies, a maker of genomic tools in Billerica, Massachusetts, the technology could enable researchers to analyze tiny samples collected by needles, a less invasive option than the surgical biopsies required for many molecular diagnostic tests.

Medical researchers and physicians are increasingly testing tumor DNA to follow the progression of a cancer, identify molecular targets for new drugs, and determine which existing treatments will work best for specific patients. But many tumor samples aren’t suitable for sequencing, the most comprehensive way to identify genetic mutations, because they don’t contain enough DNA or because the DNA they do contain is damaged by standard processing methods. Although RainDance’s technology is currently offered only to researchers, it may one day enable doctors to perform a variety of molecular tests on small numbers of cells harvested from solid tumors or even found floating in blood samples.

RainDance’s test uses microscopic droplets of liquid in place of the small plastic tubes where DNA-manipulating reactions normally occur. Each droplet is around eight picoliters in volume—about one millionth of teaspoon. When the droplets are generated on a RainDance machine, they contain the components needed to amplify a known cancer gene. Researchers can then add a patient’s DNA to the droplets, and reactions that duplicate the DNA occur inside them.

Because the droplets are so tiny, only very small amounts of reagent are required, which helps make the process much cheaper than other methods. After amplifying the DNA in a sample, researchers can either sequence the genes using standard equipment or look for the presence of cancer genes using a machine made by RainDance itself.

The company was founded in 2004 to commercialize a system that chief technology officer Darren Link developed as a postdoctoral researcher at Harvard University. He originally developed the technology as a way to study the physics of materials, but he says that as word of the tiny reaction chambers spread, biologists became interested in them for studying single biomolecules.

What makes RainDance’s test unique is that only a tiny amount of tumor DNA is needed. That could make it possible to sequence the DNA from many more tumor samples. Besides requiring less DNA, the technology makes it possible to sequence samples that have been treated with chemical fixatives for preservation—a standard practice, says Roopom Banerjee, RainDance’s CEO and a former clinical scientist at the Dana Farber Cancer institute in Boston. The challenge has been that the fixative breaks down DNA, so most DNA-sequencing methods can’t be used on these samples. RainDance’s technology, however, can make use of even a single intact copy of a gene, so now the more than 100 million preserved cancer samples currently stored in biobanks around the world could be used in cancer research, says Banerjee.

For now, RainDance does not sell the test to doctors for use on patients, but Banerjee says it’s possible that the company’s research customers could use it to develop in-house tests.

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