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Shan Wang: How magnetic nanoparticles can be used as medical sensors

A team of researchers tracks disease the way naturalists track animals in the wild.

A time-lapse image shows the trajectories of tumor cells (green) after being stained with fluorescent dyes and labeled with magnetic nanoparticles. | Image courtesy of R. J. Wilson, C.M. Earhart and S. X. Wang

 

Shan Wang’s lab has what sounds like a quirky motto: “Make magnetics work for humankind, not vice versa!

Wang, a professor of materials science and engineering and of electrical engineering, explains with his ever-ready chuckle that his students coined the phrase both as a rebellion against their graduate student workload and as a pledge to focus on practical applications of magnetic nanotechnologies, not just pure research.

“I really like that slogan,” says Wang. “What we do is for the greater good of humankind.”

Wang, who already holds 46 issued or pending patents, is an expert in the application of magnetism on the nanoscale – that is, to particles that measure just a few tens of billionths of a meter. Magnetic nanoparticles turn out to be very useful in diagnosing disease. A nanoparticle’s magnetic moment, the same physical property that makes the needle of a compass align to Earth’s north, offers a conspicuous beacon for precisely tuned sensors. And nanoparticles are so tiny that they can attach to or even get inside a target as tiny as a single cancer protein molecule or tumor cell – marking it as it moves through the body just as an ear tag helps naturalists track an animal moving through its environs.

Finally, the rules of physics are different at the nanoscale than they are in our macro world, and researchers like Wang are learning how to exploit these differences to cause nanoparticles to perform feats such as adhering to a cancer cell and then letting go.

Working with the students in his lab and a variety of key academic collaborators, Wang is exploring several projects involving the use magnetic nanoparticles in health applications:

  • Teamed up with Cloud DX in Canada, they’re competing for a slice of the $10 million Qualcomm Tricorder XPRIZE by helping create a Star Trek-style device that would diagnose or check 18 diseases and vital signs through minimally invasive methods. The Wang Group’s part of the project, which could net them just over a million dollars in prize money, is to use giant magnetoresistance (GMR) biosensors to screen for HIV, mononucleosis and anemia. Wang’s lab has already shown that GMR, which involves using nanoparticles to mark a protein, antibody or even a bit of DNA, can be used to create diagnostics that are more sensitive and faster than existing tests for cancer and other conditions.
  • Along with Dr. Sam So, the director of Asian Liver Center at Stanford School of Medicine, they’re refining a mobile hepatitis B test that, using a smartphone as a processor, could help battle this major public health threat in East Asia and Africa. The lab’s original mobile hepatitis B test, which won the Nokia Sensing XCHALLENGE in 2014, used GMR to find hepatitis B antibodies in the blood. A new test, funded by a grant from the Center for Innovation in Global Health, where Wang is a senior fellow, will screen for four hepatitis-B-related proteins, resulting in a test that Wang says is “more powerful, more accurate,” and gives doctors more actionable information.
  • Wang is collaborating with Stanford University School of Medicine to search for biomarkers in the bloodstreams of cancer patients in order to create new tests that would detect tumors earlier, monitor how cancer patients respond to treatment and distinguish between indolent and aggressive tumors.

Separately, Wang and his students are pushing for advances in spintronics (a nano-based form of data storage), power management for computing and creating a sensor network for drones.

Although Wang says he is equally passionate about all of his research projects, he understands that using nanosensors to detect cancer and other dire diseases stirs a much greater public response than creating more efficient data storage. In 2009, for instance, after the publication of his first paper on the potential use of nanosensors in cancer detection, members of the general public started calling his office, something that had never happened before.

“One person called me and said, ‘My relative is going to have a colonoscopy. He wants to avoid this invasive procedure. Can we send a blood sample to your lab to do this test?’”

Wang of course had to explain that, without approval from the Food and Drug Administration, he couldn’t throw open his lab doors and offer nanoparticle cancer screenings to the public. However, in the years since, that notion has come closer to reality: MagArray Inc., a company co-founded by Wang, is in the validation stage of commercializing a cancer assay using magneto-nanosensor technology developed in his lab.

Wang has also noticed that the medical aspects of his work, including cancer detection, are a hit with his family.

“It is very easy to explain to my kids and my relatives,” he says, adding, “My motivation on working in biosensor arena is really inspired by their societal impact.”

In a recent presentation to members of Stanford’s SystemX Alliance, bringing together industrial and academic researchers, Wang underlined that motivation with two grim facts: “In the United States, 224,390 are diagnosed with lung cancer each year. The majority of them will die” from the disease.

Speaking at the same conference, Dr. Sam Gambhir, a professor of radiology at Stanford School of Medicine, said earlier detection could prevent many cancer deaths.

“The healthcare system mainly fails because we catch cancer way too late,” Gambhir said.

That’s why Wang and Gambhir are collaborating on multiple projects funded by the National Institutes of Health to use magnetic nanoparticles to sift through the blood, searching for minute amounts of cancer-associated proteins and individual tumor cells.

In addition to helping doctors diagnose cancer earlier, Wang hopes to develop more sophisticated techniques that provide more information about what form of treatment to use. Nanosensors could help doctors avoid over-diagnosis, a problem in which aggressive screening leads to unnecessary invasive treatments.

“With new technology and new biomarkers, we can tell if a prostate cancer is indolent or aggressive. For an aggressive cancer, you recommend treatment, and for indolent, you recommend observation,” Wang says, adding, “No test in the market can do that now. That’s potentially the Holy Grail in cancer diagnostics.”

But Wang doesn’t want to stop with cancer. One day he hopes to develop magnetic-based diagnostics for ailments like Alzheimer’s disease, epilepsy or depression that attack the nervous system and brain.

“I’m very interested in developing these sensors for detecting neural signals,” Wang says.

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