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Stanford Scientist to Commercialize New MagArray Detection Chip


A team led by Stanford University's Shan Wang has used a blend of silicon engineering, nanotechnology, and magnetism to create a prototype biomarker detection chip that can identify blood serum biomarkers and is more sensitive than current tests involving fluorescence-based detection. "This is essentially a special type of protein chip," says Wang, director of the Stanford Center for Magnetic Nanotechnology. "Instead of optics we replace the readout with magnetic nanotechnology."

These MagArray biodetection chips can find tumor antigens in blood in less than an hour and with much greater sensitivity then existing commercial devices, researchers say. In a paper published in PNAS in December, Wang noted that his chip was tens to hundreds of times more sensitive and estimated that it could detect levels of human chorionic gonadotropin, widely known as a pregnancy hormone but also an important tumor marker, at a level about 400 times lower than that required for ELISA detection. "The main breakthrough in that article is that we were able to detect seven candidate cancer markers at one pico-gram per milliliter," Wang adds.

The -technology behind the chip combines a sandwich antibody -assay with magnetic nanoparticles. The technology starts with a chip that has been embedded with 64 magnetic sensors to detect changes in nearby magnetic fields. Antibodies sensitive for the tumor antigens of interest are attached to the sensors, so that when a patient's blood sample is flowed over the chip, the tumor antigen will be captured. A biotinylated detection antibody is then flowed over the chip to find and attach to that same tumor antigen. Then, magnetic nanotags coated in streptavidin are floated over the chip and will seek out the detection antibodies. As a result of this setup, the number of nanoparticles on each sensor will be proportional to the number of antigens in the bloodstream, Wang says. "We read out the signal by magnetizing these nanoparticles. The resistance of the sensor changes [and] the more nanoparticles [there] are above each sensor, the more [the] resistance will change," he says.

The main advantage to using magnetic detection is that it has very low background compared to fluorescence-based approaches. Autofluorescence due to impurities in the blood can also tweak fluorescent readout. With magnetic transduction, "the sensing part is very, very specific [with] low noise," Wang says. However, the fact remains that no antibody is perfect, so affinity is critical to making the chip work. "The specificity is still limited by the antibody pairs," Wang says. "If the antibodies we use are not good, this technology will not be good either. We're still limited by biology, essentially."

In an effort to commercialize the technology, Wang has created a company to continue its development. MagArray is based at the Panorama Institute for Molecular Medicine in Sunnyvale, Calif., and currently employs two people. While the overarching goal is to bring the test to the clinic, Wang would specifically like to develop some "panel-based protein assay for personalized medicine." Two major clinical areas where Wang sees the chip having the best application are in cancer therapy monitoring and cardiovascular disease diagnosis. He and his colleagues have begun pilot studies for both, and Wang has clinical collaborations in lung and prostate cancer. As for cardiovascular diagnostics, he says, "We're very interested in acute coronary syndrome detection as a stratification [technique] in emergency rooms."

Wang would like to use the Mag-Array chips not only for disease diagnosis, but also for biomarker validation. While he thinks the questionable nature of what is a biomarker has been resolved when it comes to cardiovascular proteins, cancer markers are still a controversial topic. "The consensus is that there is probably no single biomarker which will be specific enough for any cancer, but there very likely will be some kind of biomarker panels which have 10 to 20 biomarkers — most of them proteins, they can be DNA also — [that] together will make cancer diagnostics very specific," he says.

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