Nanotechnology At NASA Could Play Medical Role On Earth

Nanotechnology At NASA Could Play Medical Role On Earth

By Katie Leitch
Posted: 29-July-2008

WASHINGTON—Startling changes can come over a material when it is manipulated at the atomic or molecular level—the only difference between graphite and diamond, for instance, is the arrangement of carbon atoms.

Those carbon atoms can also be arranged to form tiny, rolled-up cylinders called carbon nanotubes. Extremely sturdy and flexible, these nanotubes are 50,000 times thinner than a human hair but are much, much longer than they are wide. They have been used to create lighter, stronger materials, and they could have applications in electronics and plastics.

The National Aeronautics and Space Administration (NASA) is interested in their adaptability to the extreme environment of spaceflight, but NASA's carbon nanotubes could very soon be playing biomedical roles on Earth, as well.

Sensing Pathogens In Water
Nanotechnology research began at NASA's Ames Research Center in Moffett Field, Calif., in 1996. Nanotechnology-driven development could affect many areas of space exploration: it could create new materials that are stronger and self-healing, for example, or develop tiny rovers capable of driving, flying and taking measurements.

It could also help scientists identify life on Mars. This was the motivation behind a project to develop a carbon nanotube-based biosensor, which began at Ames about seven years ago.

The carbon nanotubes are made by vaporizing graphite in a reactor during a process called chemical vapor deposition, which can also make silicon and artificial diamonds. The result—tiny carbon nanotubes that stand upright—is an extremely conductive material, capable of transmitting the faint electrical signals that result when two strands of a nucleic acid make contact.

The carbon nanotubes are arranged by the millions on a small chip, and a probe molecule is placed on the end of each nanotube. When the probe molecule comes into contact with a biomolecule of the targeted substance, this creates an electrical impulse, which is transmitted to the chip. By arranging the carbon nanotubes in different patterns and attaching different probe molecules to them, a single biosensor can be designed to detect many kinds of matter. The biosensors are also small, light, and energy-efficient—perfect for spaceflight.

"We were interested in it because when you're looking for life on other planets, you need something compact that doesn't take up much power," said Dr. Meyya Meyyappan, chief scientist for exploration technology at the Center for Nanotechnology at Ames. "And if scientists want to look for life on Mars, then you could design a biosensor that would look for a particular life signature—like a particular amino acid, for example.

"So that was the motivation for us to go into that. But we always knew, just like a lot of other things at NASA, that there would be other applications for society."

Other applications in security, for example—the sensor could be useful in detecting nerve gas or anthrax. It could also be used in environmental monitoring, which is why a partnership formed between Dr. Meyyappan's team and Early Warning, a company based in New York that develops systems to detect biohazards.

When scientists at Ames were starting their biosensor project seven years ago, Neil Gordon, Early Warning's president, was also trying to develop a portable device that could detect biological hazards in the field instead of in a laboratory. Most biotesting is done in a lab, and it can take up to 72 hours to determine if a sample—water, for instance—has pathogens in it.

"A lot of chemistry has to take place, and you need to have many copies of the target microorganism," Gordon said. "To do that, you have to incubate them in an oven or use other techniques, and then make copies. So this is a very laboratory-intensive and time-intensive process."

Instead, Gordon wanted a biosensor that could work quickly under harsh conditions and be able to detect small amounts of multiple pathogens. NASA's biosensor, which can deliver results in as little as a half hour, met all those needs.

Early Warning plans to adapt the biosensor to test for pathogens in multiple situations: in food, air, surfaces, insects, animals and humans. The first application for the sensor, however, will be water.

According to the Centers for Disease Control and Prevention, public drinking water is responsible for anywhere from 4 million to 33 million cases of gastrointestinal illness every year in the United States.

According to Gordon, aging infrastructure in old cities, especially on the east coast, can often be the culprit behind contaminated water.

"There are a lot of openings, and a lot of problems. The pipes for the sewage water are often located right next to the pipes for the clean drinking water," Gordon said. "And it's possible for microorganisms to enter the water system through broken pipes. When a cemetery or a sanitation tank is located near a point of entry or a broken water main, or if there happens to be construction work, there are a lot of issues that no one is really testing for."

The biosensors will each be able to test for more than 30 specific strains of waterborne microorganisms, including the extremely pathogenic E. coli 0157:H7. Water will interact with the carbon nanotubes through a microfluidic chamber, which is a series of tiny pipes, pumps and filters that sit on top of the biosensor.

"Essentially, it's a laboratory on a chip," Gordon said.

Early Warning will be doing field tests with the biosensors in August, and will also be evaluating manufacturing techniques. The biosensors can only be used once, and right now Early Warning can produce tens of thousands of carbon nanotubes per day, according to Gordon. He aims to have a sellable product by the end of the year, and for clients to have systems of the biosensors installed at water treatment plants and at other points in the water distribution system, to continuously test for microorganisms.

"That would be in hospitals, in schools or in homes for the elderly, because healthy people are not necessarily going to be the people affected," Gordon said. "There are a lot of vulnerable people in our society—they could be cancer patients, HIV patients, the elderly, pregnant women, children—and they're most likely to pick up an infection by drinking or consuming a pathogen."

As part of its five-year cooperative agreement with Early Warning, NASA will continue to work with the company to adapt the biosensor, at no cost to the taxpayer—Early Warning reimburses NASA for the data and services it provides.

But NASA might also look into its own biomedical application for the sensor, as well.

"We're playing around with some ideas—for example, for astronaut health monitoring," Dr. Meyyappan said. "Basically, instead of having a whole lab in the space station or the shuttle, which would take up so much space, some of these miniature biosensors with multiple probe molecules could test for routine things, like blood analysis. That's a possible goal."

Fighting Brain Tumors
Carbon nanotubes made by NASA may someday be used for the medical treatment of people on Earth, as well.

Dr. Behnam Badie, a neurosurgeon at the City of Hope National Medical Center in Duarte, Calif., is a brain tumor specialist who focuses his research on immunotherapy. Specifically, he studies macrophages, or white blood cells, which tend to be the first line of defense against any parasites, bacteria or germs in the body.

In the brain, macrophages play a role in defending against head injuries, stroke and Alzheimer's, among other things. They are also present inside brain tumors, although their role there is less certain.

"There are some people who think these macrophages are active and actually work in the brain tumors, that they're there to flight the tumor," Dr. Badie said. "But our thinking is that, perhaps, they're there to do that but they're suppressed; they're not active."

It is also possible that in their struggle with the tumors, the macrophages are helping them by releasing growth factors and proteins.

Dr. Badie and his team would like to genetically modify the macrophages inside brain tumors to make them more active. Pieces of RNA, called inhibitory RNA or siRNA, could enter the cells, block the expression of a targeted gene, and make the macrophages stronger.

But this is difficult, since macrophages are designed to scavenge for damaged cells and tissues in the body, and their nature is to destroy anything introduced to them.

"So if you give them a virus, for example, or a piece of DNA to modify them genetically, they are very resistant, as compared to other cells," Dr. Badie said.

When he came to City of Hope in 2005, Dr. Badie learned about research at NASA's Jet Propulsion Laboratory (JPL) in Pasadena, Calif. JPL's Nano and Micro Systems Group is capable of growing carbon nanotubes, which are used to develop electronics and miniaturize spectroscopic instruments.

It was the nanotubes' material that interested Dr Badie, however.

"I thought, ‘Wow, that could be a great collaboration, because the macrophages like to take up debris, and these nanotubes are really carbon,’" he said.

The macrophages could essentially be tricked into consuming siRNA, if the siRNA were attached to the carbon nanotubes.

Now, JPL supplies City of Hope with the carbon nanotubes they need to run experiments. The nanotubes come on small wafers, from which they have to be stripped off. Because the nanotubes are so small and their weight is so negligible, Dr. Badie and his team can only estimate exactly how many come on each wafer, based on the dimensions of the wafer and the length and molecular weight of the nanotubes. But a one-centimeter by one-centimeter square provides enough nanotubes for a number of experiments, Dr. Badie said.

First, the City of Hope team showed that macrophages do consume the carbon nanotubes, just like any other waste particles they might find.

In a second study, mice with brain tumors were injected with the nanotubes. The City of Hope team found that 70 to 90 per cent of the macrophages inside the animals' brain tumors ended up engulfing the carbon.

More recently, the team has modified the surface of the nanotubes and attached siRNA to them. Macrophages engulfed these nanotubes, too, and the siRNA blocked the expression of a gene in the macrophages.

"We've actually made some important progress," Dr. Badie said. "We've shown that we can knock out a gene with this technology—we're confirming that."

One gene, called STAT3, is the next target for the nanotubes—macrophages have been shown to become more active when STAT3 is knocked out, using different methods. Other questions remain to be answered, like whether creating a cocktail of several different kinds of siRNA on the nanotubes could stimulate the microphages even more, and how long the macrophages would remain stimulated in the brain after the treatment.

Eventually, the nanotubes could be delivered to cancer patients in the same way as existing therapies. During other immunology protocols, City of Hope doctors have removed brain tumors, left tubes in the cavities where the tumors used to be, and attached the tubes to reservoirs that remain under the skin. Then, engineered T-cells are injected through the patient's scalp and into the reservoir. Ideally, siRNA-enhanced nanotubes could be injected into cancer patients' brains in the same way, to prevent new tumors from forming after surgery, or to fight tumors that cannot be surgically removed.

The treatment could also be applicable to not only brain tumors that come from the brain—called gliomas—but also to metastatic tumors in the brain, which are more common and come from other cancers like breast cancer, or lung cancer.

"If we could come up with a way of activating these macrophages in one area—again, this needs to be proven—potentially, they could migrate throughout the brain and attack other tumors," Dr. Badie said.

"So that's the whole vision," he added. "But it's very futuristic right now."

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