Magnetic beads first pull out white blood cells, which are burst open using sonic energy, releasing fragments of DNA. Everything but the DNA is then washed away, and a solution of these DNA fragments flows over the glass slide. Target DNA binds to spots on the slide that have been printed with DNA sequences complementary to those of the target sequence. Gold nanoparticles, about 13 nanometers in diameter, then attach to the other end of captured DNA fragments, sandwiching the target. Each gold nanoparticle is coated with silver, expanding the diameter to half a micron, thus allowing it to be easily detected when hit with light.
“If it works, this could be a convenient way for physicians and coagulation clinics to incorporate pharmacogenomic information into warfarin dosing,” says Weck. However, she adds, “the accuracy of the test should be carefully compared to more traditional molecular tests before it is widely used.” Nanosphere already has FDA approval for a warfarin test used in an older version of its system and plans to file for regulatory approval for its new test next year.
The company is also developing a pharmacogenomics test for use with the anticlotting drug Plavix, which is prescribed to people given heart stents. The drug must be metabolized into its active form, and scientists recently discovered that about 30 percent of Caucasians have a poorly functioning variant of the enzyme that metabolizes the drug and are thus less likely to benefit from it. While it’s currently possible to identify these patients through mail-order testing, “we want to know the answer before the patient goes home,” says Marc Sabatine, a cardiologist at Brigham and Women’s Hospital in Boston.
Nanosphere’s device is one of a number of microfluidics technologies in development for so-called “point of care” genetic testing–diagnostics that can be performed in the hospital or doctor’s office while the patient is there. Verigene, which was approved by the FDA in October, can come with different modules, ranging from $40,000 to $80,000, designed for different types of testing.
“You could have a version of our system in a molecular diagnostics lab running genetic assays, like those for cystic fibrosis and warfarin, or in a microbiology lab running virus assays, or in a stat lab for ER running tests, like the cardiac troponin test, a biomarker to diagnose heart attack, and pharmacogenomic testing for [Plavix metabolism],” says Moffitt. The Verigene system can also detect respiratory viruses, such as the H1N1 flu. Over the past month, the company has been installing the systems in medical centers ranging from typical community hospitals to large academic research hospitals.
Researchers hope the availability of this type of testing will enable the discovery of new applications in pharmacogenomic testing. “There are also drugs we use in [intensive care units] that would benefit from genetic-guided therapy, but because of the absence of technology [for quick pharmacogenomic] testing, no one is really trying,” says McLeod.