Safer Prenatal Testing

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A similar technology developed by Biocept, also based in San Diego, has likewise been clinically validated, and it will launch in early May. It expands upon Sequenom's approach by scanning for a large number of SNPs that distinguish between maternal and fetal DNA. That way, a negative result can be confidently attributed to an Rh-negative fetus rather than to a failure to detect the Rh-encoding gene.

A complementary approach to noninvasive prenatal testing involves isolating fetal cells, rather than nucleic acids, from the maternal bloodstream. This strategy is especially amenable to testing for Down syndrome and other chromosome copy number defects. With fetal cells on hand, diagnosing Down syndrome is straightforward: all it takes is a probe to fluorescently stain chromosome 21 and a microscope to count how many copies are present.

"If you can get an intact fetal cell, you have access to the entire fetal genome noninvasively," says Bianchi. "So that's what's enchanted people for a long period of time." But because a milliliter of maternal blood contains fewer than five fetal cells, this tactic presents enormous technical hurdles."You're on the hunt for extremely rare cells," says Bianchi.

Biocept deals with this challenge by targeting immature, nucleated red blood cells (NRBCs), which are much more likely to come from the fetus than from the mother. NRBCs can be sorted from other cell types using antibodies that latch on to proteins unique to their surfaces, and their unusual morphology makes them easy to spot under a microscope.

"When you find an NRBC, chances are it's going to be fetal," says Farideh Bischoff, Biocept's vice president of translational research and development.

The Biocept cell-based testing platform uses a microfluidic system, in which the mother's blood is channeled across a surface studded with antibodies that capture immature red blood cells. The surface is microscopically engineered to maximize the blood's exposure to the antibodies, dramatically upping the chances of pulling out any immature red blood cells that may be present.

Biocept will begin clinical evaluation of this platform next month as a noninvasive Down syndrome test, and it may become commercially available before the end of 2008.

Another company tackling the fetal-cell-based approach to noninvasive prenatal testing is Ikonisys, based in New Haven, CT. Instead of physically sorting NRBCs from other cell types, Ikonisys takes a brute-force computational approach. The company has developed an automated microscope that scans slide after slide of maternal blood, using cell shape to distinguish fetal cells from other nucleated cell types. The microscope includes software that compiles the locations of potentially relevant cells, obviating the need for a more subjective manual scan and thus reducing human error. A technician can then inspect those cells and make a final ruling on their status.

"Rather than mechanically filtering, we're using a combination of visualization and artificial intelligence," says Paul White, CFO and president of Ikonisys. "The microscope does the hard part."

Ikonisys plans to launch its Down syndrome test in late 2008. The company is also adapting its technology for use in oncology, where the ability to identify rare cancerous cells in a sea of healthy cells could help diagnose certain cancers and monitor their response to treatment.