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Other applications could benefit from same dynamic

By David Forman

If a Chinese nanotechnology firm and its American partner are successful, they could have a profound effect on the next summer Olympics. The two companies could improve the air quality, reduce the noise pollution, and increase the – well, overall energy – of the 29th edition of the modern Olympic Games.

The companies are working on nanostructured batteries that aim to be the holy grail of electric transportation: batteries that charge up rapidly, hold a lot of energy, and can expend their energy at the varying rates required by an automobile, all the while being lightweight, safe and rugged.

It’s a tall order for any technology. It also happens to be an area where Chinese nanotech research has firmly connected with a commercial energy application. Much has been made of both China’s impending energy crisis and its position as an up-and-coming leader in nano and other areas of emerging technology. Experts say the country is beginning to connect the dots between nano-enabled energy research and its applications.

Batteries are at the forefront of those efforts toward real commercialization. “Our materials can run right down the manufacturing line without changes,” said Alan Gotcher, president and chief executive officer of Altair Nanotechnologies Inc., a U.S. firm that is providing its nanostructured electrode material to Advanced Battery Technologies Inc. of Harbin, China.

Advanced Battery, in turn, is integrating the material into batteries for a variety of applications. It recently announced two milestones. Late last year, tests showed that its batteries met the U.S. Council for Automotive Research FreedomCAR specifications for energy storage in hybrid electric vehicles. And in early 2006 the company announced it had started shipments of its rechargeable polymer lithium-ion (li-ion) batteries to Aiyingsi Co. Ltd., a Taiwanese maker of electric bicycles and motorcycles.

Gotcher said his company’s crystalline material has a high energy density but at the same time can move energy rapidly, both of which are desirable attributes for battery applications but which are often mutually exclusive. “The more surface area, the more the ions are moving faster and faster,” he explained. Historically, he added, the problem with using crystalline material was that the very nanoscale crystals that made the performance possible would fracture under the stress. However, “Our crystals aren’t breaking,” he said.

Advanced Battery is building prototype buses for completion by the end of the second quarter to compete for selection for the 2008 Olympics. The Chinese government has said it wants to use at least a thousand electric buses as part of a fleet for ferrying people around the Games.

Advanced Battery is hardly the only Chinese firm commercializing nano-related battery innovations. China BAK Battery Inc., a Shenzhen, China, manufacturer of li-ion battery cells, announced earlier this year that it had signed agreements with Lenovo Group of Hong Kong and A123 Systems of Watertown, Mass.

Lenovo is the Chinese company that bought IBM’s computer division in late 2004, making it the third largest personal computer manufacturer in the world. China BAK has been supplying Lenovo with batteries for cellular phones since last August. The intent now is to supply batteries for laptop computers.

A123 is developing nanophosphate li-ion batteries using technology licensed from Massachusetts Institute of Technology. It and China BAK have been working together since early 2005 and recently announced starting volume production to make batteries for power tools, medical devices and hybrid electric vehicles.

Such academic collaborations are not surprising. Advanced Battery contracted with Harbin University of Science and Technology in China to make the electrical controls and other systems for an electric car project using Altair’s nanomaterials. It also has a cooperative agreement with the Beijing Institute of Technology in China to develop and test the four buses it is building as prototypes for the Olympic electric bus program.

On the other hand, what may be surprising is that there is not more of such commercial collaboration between nanotech research and energy applications.

There is no doubt that Chinese nanotech research is ramping up, according to Mike Roco, the senior adviser to the U.S. National Science Foundation who tracks international nanotech development closely. By Roco’s count, China has moved up impressively, ranking second behind the United States as measured by the number of academic papers published on nanotechnology in a year.

However, warned Roco, prolific papers do not necessarily equal superiority in research. “If you look at the citations index they are not in the top-five cited,” he said. He argues that successive researchers citing previous works is a stronger indicator of the quality of research than the sheer number of papers produced.

“I like to get people to be more realistic,” Roco said. There is a perception of “China going from nothing a few years ago to a superpower (in nanotech research) …but it’s not the same level of quality.” Give it at least another decade, he said.

But perhaps more importantly, a community of corporate executives, engineers, entrepreneurs and academic researchers committed to connecting nanotech innovation to energy solutions has not yet congealed.

“Hydrogen storage, solar, fuel cells, thermoelectrics. These are all using nanotechnology,” said Gang Chen, a mechanical engineering professor at Massachusetts Institute of Technology who retains close ties with researchers in his native China.

“But generally speaking, nano for energy is still a ways off,” said Chen, whose research focuses on energy transfer and conversion and who recently organized a conference on energy and nanotechnology. “It’s not making a big wave when people are thinking about nanotechnology.”

Chen points out that China’s national research program includes projects for both energy and nanotech research, such as high energy battery development and solar power for hydrogen generation. But there is no Chinese version of the U.S. National Nanotechnology Initiative explicitly linking the two developments. And, he said, “Chinese corporate research is not at a scale of a GE or IBM.”

However, a facet of Chinese academic funding could help make up the difference. Chen said that in China, when the government funds a science project – even a basic science project – there is generally an application focus and a physical result.

“Every project they have,” he said, “they ask you to deliver some hardware after one to two years.”

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“Sometimes there are rumors about China which are exaggerated,” says Mike Roco, the senior adviser to the U.S. National Science Foundation. He says China is coming on strong but is still far from competing head-to-head with the U.S. in nanotech research. Photo courtesy of Peter West/National Science Foundation

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“Our materials can help them make a distinctive product,” says Alan Gotcher, CEO of Altair Nanotechnologies, which supplies nanostructured materials to Advanced Battery Technologies Inc. for use in batteries fabricated in Harbin, China. Photo courtesy of Altair Nanotechnologies Inc.

By Kyle James

BASF, the world’s largest chemical company, is devoting $221 million to nano-technology research and development between 2006 and 2008. The German corporation is opening up a new nanotech center in Singapore this year as well. The investments are part of an expansion of its global R&D activities, with nanotech one of five “growth clusters” that BASF will build over the next two years to ensure it stays competitive.

“Nanotechnology gives us the possibi-lity to innovate, especially in a hard market like chemicals,” said Elmar Kessenich, manager of nanotechnology coordination at BASF. “Most of the chemical market is commodities, so if you really want to be competitive, you have to add value. You can do that with nanotechnology.”

Besides nanotechnology, BASF is concentrating on energy management, raw material change, plant biotechnology and white biotechnology. (White biotechnology uses biological systems and techniques to make cleaner or more energy efficient industrial processes.) All together, the five areas will receive $982 million.


Ultradur High Speed, a nanoparticle-based engineering plastic developed at BASF, flows twice as far as conventional Ultradur. Better flow saves manufacturers time and money. Photo courtesy of BASF
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The list of nanotech areas BASF plans to support with the cash infusion is long. It includes new products for the automotive and construction markets, cosmetics, printed electronics, electronic components and energy management systems such as fuel cells, OLED displays, and a variety of surfaces, such as scratch-resistant coatings and dirt-repellent paint.

BASF says its R&D strategy will enable it to stay at the forefront of materials innovation. While nanotechnology is still in its early stages regarding widespread application, even conservative estimates put growth rates at 10 percent a year and an end-user market size at $614 billion in 2010. BASF expects the market for its nanosystems and components to be between $61 billion and $74 billion in four years.

“It’s a key technology for us, since it helps us meet challenges of the global market not only with new products but also with old ones,” Kessenich said.

As an example, he cited the company’s Ultradur High Speed product, an engineered plastic for electronic components. While a previous version of the product had been on the market for several years, BASF added nanoparticles to the mix, which brought down manufacturing costs and increased performance.

Part of BASF’s more intensive focus on nanotechnology is a new research center in Singapore, the company’s first nanotech facility to be opened in Asia. Set up to open at the end of the first quarter of 2006, the center will concentrate on nanostructured surface modifications, such as controlling the hydrophobic or hydrophilic characteristics of a surface. Hydrophobic molecules shun water; hydrophilic molecules have an affinity for water.


Nanocubes’ three-dimensional lattice structure has numerous pores and channels, making nanocubes an ideal storage medium for hydrogen. Hydrogen is one energy source being proposed for miniaturized fuel cells for portable devices. Photo courtesy of BASF
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The facility will employ about 20 people, including six researchers, technicians and post-docs, with most of them coming from the region. BASF chose Singapore because of the city-state’s good infrastructure, its location and the fact that intellectual property protection is better there than in China. That’s “a prerequisite for any R&D project,” said Harald Lauke, president of the company’s Asia-Pacific division.

According to Kessenich, Asia is focusing more of its attention on nanotech. “There are a lot of interesting nano startups there,” he said. “At international conferences we see increasing numbers of good researchers from Asia presenting their results.”

Asia in general is also becoming a more important market for BASF, which is interested in getting a firm foothold there. BASF is not completely new to Asia; the company opened a chemical production facility in Nanjing, China in 2005. A presence in the region will also help BASF recruit Asian chemists, since the company could offer them a position closer to home instead of asking them to move to another continent.

BASF’s strategy appears to be on target, since Asia as a recruiting ground is looking more fertile all the time. A Georgia Institute of Technology study found that as more Asians earn doctorates, they increasingly apply them to Asian – not U.S.-based – careers. In the meantime, the number of U.S. citizens earning advanced degrees continues to decline.

The investment advisory group Innovest gave BASF good marks in the nanotechnology index it published in the fall. It highlighted the company as having high growth potential relative to its competitors, especially regarding transparency and addressing potential concerns like product safety.

“It’s not all sunshine. Some of their products are still in the commodity range and they do have a lot of risk,” said Heather Langsner, author of the report. “But they have paid attention to nanotech risk factors and will most likely succeed in sensitive markets.”

Mar. 1, 2006 — Stanford University School of Medicine was named one of the National Cancer Institute’s Centers for Cancer Nanotechnology Excellence, according to a news release.

The institute has allotted approximately $20 million over five years to the Stanford-based center, which will be led by professor of radiology and bioengineering Sanjiv Sam Gambhir, who also directs the molecular imaging program at Stanford.

The Stanford center is slated to receive $3.83 million in its first year. It will aim its efforts at imaging diseases in vivo and determining what is going on within patients’ bodies through blood or tissue sample analysis.

Participants at Stanford will include faculty from a variety of disciplines with the intention of combining their expertise to develop new ways to detect cancer and evaluate therapies. UCLA, Cedars-Sinai Medical Center, Fred Hutchinson Cancer Research Center, the University of Texas-Austin, General Electric Global Research and Intel Corp will also participate.

Seven other Centers for Cancer Nanotechnology Excellence were announced last October. Each of the eight centers has its own focus in seeking to eliminate suffering and death due to cancer.

– David Forman

By Richard Acello

This July, delegates to an international conference will meet in Geneva, Switzerland, to consider recommendations aimed at improving the risk governance of nanotechnology. The conference, sponsored by the International Risk Governance Council (IRGC), is designed to improve the understanding and assessment of risk issues and design innovative, efficient, and balanced governance strategies.

In advance of the conference, scientists have been working on a comprehensive survey designed to provide a portrait of nanotechnology governance across 27 economies from around the globe. Experts from industry, academia, government and non-governmental organizations gathered in Geneva in January for a workshop to develop strategies and to review the IRGC’s “Survey on Nanotechnology Governance.”

The report was authored by Mike Roco, a senior adviser for the National Science Foundation, a federal agency that funds research in the United States, and Emily Litten, nanotechnology project manager for IRGC, an independent foundation in Switzerland. The Swiss Federal Agency for Development and Cooperation, the U.S. Department of State and Swiss Reinsurance Co. (Swiss Re) funded the survey.

“Societal relationships and the governance of science may either accelerate or dampen the development of emerging technologies, in particular nanotechnology,” Roco said. “Nanotechnology operates at the first level of organization of atoms and molecules, so the implications of its development will be broader than in other emerging technologies, both positive and with potentially unexpected consequences. For this reason, nanotechnology has to be addressed in the cultural, economic and societal context.”

Governance of nanotechnology is in a race with development that has accelerated as applications such as nanocoatings become more sophisticated. Those applications may soon be leapfrogged by second-generation “active nanostructures,” such as nanobiotech assemblies, according to Roco.

“In the last two or three years, industry has entered nanotechnology in a significant way,” Roco said. “It has become a subject of international competition and the public is a lot more aware of its development.”

The Roco-Litten report targets deficits in nanotechnology governance. Its recommendations fall into four categories of risk research, stakeholder engagement, risk communication, and governance approaches.

Should a “supranational” governance policy for nanotech products – one that involves a number of nations – be adopted by the IRGC, it would have to overcome traditional cultural differences to R&D in the U.S. and Europe. The U.S. operates on a “risk assessment” model that assumes all risks cannot be known in advance; Europe is more likely to embrace a “principle of precaution” approach that seeks to discover all the consequences of nanotechnology prior to its widespread use.

Prior to the IRGC’s July meeting, Roco said, the group hopes to arrive at a consensus on the types of governance applicable to each stakeholder group and issue final recommendations by the fall of 2006. Though an international scheme of governance is destined to encounter nationalist, competitive appetites for nanotech development, a U.S.-based environmentalist said she believes it’s worth the effort. “Markets respond to demand, but they also respond to rejection,” said Jennifer Sass, senior scientist in health and environmental programs with Natural Resources Defense Council in Washington, D.C. “Good governance approaches are consistent with good marketing and business strategies. It’s essential they go hand in hand.”


Four focus areas for recommendations

  • Risk research recommendations include advancing studies of hazard, exposure and risk of nanoproducts; requiring input on the environmental, health and safety impacts to research and development projects; developing specific plans for environmental impact, chemical toxicity and pollution control; and “green” design and manufacturing, among others.
  • Recommended stakeholder engagements include regular workshops; social scientist participation at the R&D level; and international dialogue between ethical advisory committees.
  • Communication of risk recommendations seek a balanced disclosure of positive and negative evidence; encouragement of independent sources of information; communication of secondary unanticipated consequences; and periodical re-evaluation of risk to be disseminated to the public.
  • Governance approaches include a “supranational body” to supervise international rules; a role for the United Nations in resolving conflicting national policies; self-regulation through voluntary peer review of decision making processes; government labeling of nano-related products; and national, international and supranational cohesiveness on regulatory schemes, definitions and nomenclatures, best practices, common assessment policies and testing periods.

Startup expects to sign deals for Loop, navigation system

By David Raths

As MEMS-based products make their way into the consumer electronics market, one promising application is a device a reviewer dubbed the “remote control bagel.”

Hillcrest Labs, a startup from Rockville, Md., generated considerable buzz at the January Consumer Electronics Show in Las Vegas with its “Loop” air mouse for televisions. It holds out the promise of replacing clunky 50-button remote controls with a device that has just two buttons and a scroll bar.

But the MEMS-based free-space pointing device is only part of Hillcrest’s offering. The company also has created an on-screen navigation system that abandons the TV Guide-style grid for zoomable visual directories. For instance, users can choose videos from a full-screen mosaic of movie covers. This system, “Spontaneous Navigation,” is key to handling the growing number of media offerings, according to Andy Addis, Hillcrest’s executive vice president and a former Comcast executive.

“People translate visual information 60 times faster than textual information. As the number of offerings grows, presenting things visually offers greater scalability,” he said. “With a grid-based guide, if you have 20,000 media choices, that’s 4,000 page-down pushes on your remote. It just doesn’t work.”

Addis stressed that the Loop and navigation system go hand in hand. “When the mouse was invented, there wasn’t really any application until Apple developed the graphical user interface,” he noted. “It was a pointing device with nothing to point at.” The Loop itself would be the same today without the navigation system, he said. “We think we’ve developed the mouse and Windows for your TV.”


The Loop, a pointer-based remote control, uses two buttons and a scroll bar for navigating TV options. Photo courtesy of Hillcrest Labs
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Founded in 2001 and backed by more than $30 million in venture capital, Hillcrest at first focused on the pointing device. Founder and Chief Executive Dan Simpkins had previously led SALIX Technologies, a developer of voice switches that was acquired by Tellabs in 2000. In developing ideas for the Loop, Simpkins and a team of Hillcrest engineers “studied every input device known to man,” Addis said.

He said one-third of the company’s patent filings are related to the Loop itself, which has sophisticated digital signal processing technology built in. Unlike the Gyration Air Mouse, he stressed, the pointer technology is not based on a gyroscope. Addis was reluctant to talk about the inner workings of the Loop or the MEMS component. “Suffice it to say that we leverage multiple low-cost sensors,” he said.

Hillcrest has succeeded at generating a wow factor among consumers and industry analysts, but getting its innovation deployed in a challenging market for startups will be more difficult. As Forrester Research analyst Josh Bernoff wrote last May, although the system looks promising, it has yet to be used anywhere. “It’s still enabling technology that must be built into set-top boxes or consumer electronics devices.”

Hillcrest is talking to companies in the consumer electronics, PC, telecommunications, satellite and cable markets. Addis said its first deals, to be announced later this year, would likely be with consumer electronics companies because that market moves the fastest. The technology may appear first in products such as digital video recorders and game consoles. The cable and telecom companies will be the toughest sell, he admitted.

“The trick is they are trying to sell into companies that do not do revolutions,” said Danny Briere, CEO of telecommunications consulting firm TeleChoice, in Mansfield Center, Conn. “The cable companies are protecting a bunch of paradigms that Hillcrest is blowing away. With Hillcrest’s product, you pick it up and instantly know how to use it. You don’t have to learn how to use it or remember how to use it.”

It’s just a matter of time before the cable companies come around to graphical menus and pointing devices, Briere said. “The cable companies realize that to generate more revenue, they have to become a portal to other media, gaming, and e-commerce, and they run up against a wall really fast in the two-dimensional environment.”

Briere, whose clients include large phone companies, said all the major players are interested in Hillcrest. “It’s a huge competitive advantage for whoever partners with them first. The migration path to this will be insane.”

Forrester’s Bernoff predicted that new navigation products like Hillcrest’s are likely to change the face of TV by 2008.

R&D UPDATES


March 1, 2006

Toshiba unveils MEMS tool for biotech use

TOKYO – Toshiba Corp. has developed a MEMS-based technology for injecting nanoparticles in cells. The technology is said to have advantages over conventional techniques that use laser beams, including the ability to simultaneously manipulate numerous cells.

The MEMS component produces subtle vibrations that cause nanoparticles in a liquid to adhere to cell surfaces. Continuous vibration gets converted to thermal energy that affects cell surfaces, resulting in injection of nanoparticles into the cells.


Toshiba has fabricated a nanoparticle manipulator with a water-repellent MEMS-based diaphragm. It tested the technology by placing a water droplet containing yeast cells and nanoparticles on a vibrating diaphragm. Vibrations caused the nanoparticles to adhere to cells, and once immobile, heat up, affecting the cell surface.
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Toshiba said it expected applications to include medical analytical tools for studying and manipulating cells. The company unveiled the technology at the 2005 IEEE International Electron Devices Meeting in December in Washington, D.C.

300 volunteers in Pacific Northwest to test energy-monitoring technology

RICHLAND, Wash. – About 300 volunteers on Washington’s Olympic Peninsula, in Yakima, Wash., and in Gresham, Ore., will test equipment that is expected to make the electrical grid more reliable while offsetting huge investments in new transmission and distribution equipment.

Pacific Northwest National Laboratory said that it launched a regional initiative in January to test and speed adoption of GridWise, its collection of smart technologies designed to make the power grid more resilient and efficient. GridWise uses miniaturized sensors, software and advanced analytical tools to monitor energy use in home appliances. The technology can sense when the grid is being strained, and shut down appliances to avoid outages.

The year-long study is funded primarily by the Department of Energy. Utilities, appliance manufacturers and technology companies also are supporting the effort to demonstrate the devices and assess the resulting consumer response.

Gold nanoparticles show potential for Alzheimer’s treatment

SANTIAGO, Chile and BARCELONA, Spain – Chemists at the University of Chile in Santiago and the University of Barcelona in Spain have identified a new approach for the possible treatment of Alzheimer’s disease that they say has the potential to destroy beta-amyloid fibrils and plaque, which are hypothesized to contribute to the mental decline of Alzheimer’s patients. The researchers say the new technique could halt or slow the disease’s progress without harming healthy brain cells.

Using test tube studies, the scientists attached gold nanoparticles to a group of beta-amyloid fibrils, incubated the resulting mixture for several days and then exposed it to weak microwave fields for several hours. The energy levels of the fields were six times smaller than that of conventional cell phones and unlikely to harm healthy cells, the researchers said.

The fibrils dissolved and remained dissolved for at least one week after being irradiated, indicating that the treatment was not only effective at breaking up the fibrils but also resulted in a lower tendency of the proteins to re-aggregate, according to the researchers. The research appeared in the Jan. 11 issue of Nano Letters.

UCLA-Bologna team’s nanomotor relies on sunlight for power

LOS ANGELES and BOLOGNA, Italy – Chemists at Italy’s University of Bologna, University of California, Los Angeles, and the California NanoSystems Institute have designed and constructed a nanomotor that does not consume fuels. Instead, their nanomotor is powered only by sunlight.

The nanomotor is a multi-component molecular-scale system called rotaxane, a mechanically interlocked molecule consisting of one or more rings trapped on a rod by bulky stoppers at either end. It was designed, assembled and run by the research groups at UCLA and the University of Bologna.


The nanomotor system operates in a fashion that is analogous to a four-stroke engine: light excitation and subsequent transfers of an electron (“combustion”); displacement of the ring along the rod (“piston displacement”); removal of the electron (“exhaust removal”); and relocation of the piston. A full cycle is carried out in less than one-thousandth of a second. Image courtesy of UCLA
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It works continuously without any external interference, and operates without consuming or generating chemical fuels or waste, said Fraser Stoddart, UCLA’s Fred Kavli Professor of NanoSystems Sciences and the director of the institute. The research was published Jan. 31 in Proceedings of the National Academy of Sciences.

Nanomix, Pitt use detectors to spot gene mutations linked to diseases

PITTSBURGH and EMERYVILLE, Calif. – Researchers at the University of Pittsburgh and at sensor maker Nanomix have developed devices made of carbon nanotubes that can find mutations in genes causing hereditary diseases. The researchers used nanotubes’ electrical properties to find a particular mutation in the gene that causes hereditary hemochromatosis, a disease in which too much iron accumulates in body tissues.

“The size compatibility between the detector and the detected species – DNA molecules in this case – makes this approach very attractive for further development of label-free electronic methods,” said Alexander Star, an assistant professor of chemistry at Pitt.

Label-free electronic detection of DNA has several advantages over state-of-the-art optical techniques, including cost, time, and simplicity, they said. They reported their findings in the Jan. 16 issue of Proceedings of the National Academy of Science.

DNA self-assembling properties used to mass-produce nanostructures

DURHAM, N.C. – Duke University scientists have used the self-assembling properties of DNA to mass-produce nanometer-scale structures in the shape of grids on which patterns of molecules can be specified. They said the achievement represents a step toward mass-producing electronic or optical circuits at a scale 10 times smaller than the smallest circuits now being manufactured.

Instead of using silicon as the platform for tiny circuits, Duke researchers used DNA strands to create grids. The smallest features on these square DNA lattices are approximately 5 to 10 nanometers, according to the scientists, compared with about 65 nanometers in silicon circuits created using photolithography.


Duke University scientists demonstrated that they could mass-produce grids with infinitesimal patterns by making batches of trillions of separate grids showing the letters “D,” “N” and “A.” Image courtesy of Duke University
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To demonstrate their ability to mass-produce grids, the scientists created batches of trillions of separate grids with the letters “D,” “N” and “A” written with a protein that can be seen through atomic force microscopy. They were able to create the grids by using the binding properties of DNA to ensure that large numbers of DNA strands would assemble themselves in specified patterns. Their work appeared in the Jan. 23 issue of Angewandte Chemie.

Nanoparticle catalyst offers cleaner manufacturing method

BETHLEHEM, Pa. and CARDIFF, Wales – Materials scientists in the United States and chemists in Wales have uncovered secrets of the “nanoworld” that promise to lead to cleaner methods of producing, among other things, flavorings and perfumes. The researchers reported their results Jan. 20 in the journal Science.

Christopher Kiely of Lehigh University in Pennsylvania determined the structure of a type of gold-palladium nanoparticle, which is the active component of a new environmentally friendly catalyst that promotes the oxidation of primary alcohols to aldehydes. The catalyst system was developed by a group headed by Graham Hutchings at Cardiff University in Wales.

The chemical, pharmaceutical and perfume industries rely on expensive and environmentally harsh oxidation reactions to manufacture products such as vanilla. The new catalyst, consisting of gold-palladium nanoparticles dispersed on a titanium oxide support, allows this reaction to take place using oxygen under mild solvent-free conditions.

Particle size matters


March 1, 2006

Studies fail to include basics for assessing toxicity

By Candace Stuart

Vicki Colvin has a question for colleagues who study nanoparticles and how they may affect people and the environment. “Exactly what do you mean by size?”

When chemists, toxicologists or other researchers report the dimensions of an engineered nanoparticle, are they measuring the core, the core plus a coating, or perhaps the core, a coating and attachments that help nanoparticles adhere to cells? What happens after exposure to water, or to blood?

“We want to know how particle size changes as it marches through the body,” Colvin said at a workshop designed to identify roadblocks to nanobiotech commercialization. Size, composition, shape and other characteristics help distinguish the scores of different engineered nanoparticles that exist today. They also help determine their wanted – and unwanted – properties. “Can I take a material that is active (potentially harmful) and make it safe?” she asked. “How can I engineer a safe nanoparticle?”

Colvin, a chemistry and chemical engineering professor and director of the Center for Biological and Environmental Nanotechnology at Rice University, is not alone in her quest. The federal agencies that may decide to impose environmental, health and workplace regulations on industry face a mishmash of toxicological data that often lacks basic information about nanoparticle size, surface area and other characteristics.


Rice University researchers Vicki Colvin and Mark Wiesner explore the two sides of nanotechnology: its use for remediation as well as its possible toxic effects. Photo by George Craig
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Toxicologists and other scientists studying nanomaterials say these gaps make it difficult if not impossible to compare studies and get an accurate picture of how nanoparticles interact with the body.

Reporting basics like size will go a long way toward ensuring that regulations are based on sound rather than spotty science, they say. Scientists will be able to see the relationships between a nanoparticle’s size or surface area or charge, for instance, and how it behaves in the body to predict which traits could be harmful. That knowledge may help them design benign nanoparticles.

“It was kind of where dioxins and PCBs were in the ’60s,” said Nigel Walker, a staff scientist with the National Toxicology Program (NTP) of his initiation into nanotechnology about three years ago. NTP, part of the National Institutes of Health’s environmental sciences division, has launched a program to evaluate potential health hazards of nanomaterials. Dioxins, a byproduct of combustion processes, and polychlorinated biphenyls, an industrial chemical, were found to be cancer-causing pollutants that required costly cleanups once their toxicity was discovered.

“We introduced a technology without understanding the implications and then spent 30 years trying to eliminate or reduce the risk,” Walker said. He recognized that with nanotechnology he and other scientists had an opportunity to spot troublesome nanoparticles early in the commercial process, before they cause damage. “Now we can make sure we can prevent that. We can choose the kinds of experiments that reduce the risk. We can be at the forefront.”

Their size makes nanoparticles promising candidates for medical applications. They are small enough to fit within cells and also can roam undetected by biological sentries such as the blood-brain barrier or the liver, according to Scott McNeil, director of the National Cancer Institute’s Nanotechnology Characterization Laboratory. As coordinator of pre-clinical characterization of nanomaterials, McNeil is helping the NCI in its goal of developing nano-based therapies and diagnostics for cancer.

His team has already begun tests on gold nanoparticles, liposomes, dendrimers and buckyballs. Each nanoparticle offers benefits: Branch-shaped dendrimers and spherical liposomes can transport drugs into cells. Contrast agents can be put in the hollow centers of buckyballs for tumor imaging. Gold particles known as nanoshells can attach to cancer cells, and when exposed to harmless near ultraviolet light, heat up and kill the cells.


Preliminary research on gold nanoparticles suggests that nanoparticles grow larger in the presence of plasma. Researchers consider the results a trend until their studies undergo further review. Image courtesy of the Nanotechnology Characterization Laboratory
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“These can leach into tumors because they are smaller than the pores of the blood vessel wall,” McNeil said. Nanoparticles are also smaller than the filter mechanisms in the spleen and liver that capture and eliminate other foreign matter. That leaves nanoparticles free to circulate until they find their cancer target.

Nanoparticles pose a risk, though, if they are or become toxic and the body’s defense systems can’t detect and eliminate them, McNeil and Walker pointed out. For medical applications – where tissue is deliberately exposed to nanoparticles – it is critical to understand how cells react to the presence of various types and forms of nanoparticles during various stages of exposure. Unintended exposure through the skin, lungs and other pathways also needs to be considered.

“Size will be a critical component for toxicology,” Walker said. Studies on ultrafine particles, which are typically a byproduct of combustion, suggest a link between particle size and toxicity, for instance. “But size is contextual. How do you report size? What kind of methodology do you use? What is the tool?”

The Nanotechnology Characterization Laboratory is collaborating with the Food and Drug Administration and the National Institute of Standards and Technology to find methods for analyzing nanomaterials in various stages: before exposure to any biological environment, exposure in test tubes and other in vitro environments, and exposure within living organisms, or in vivo environments. They accept applications for materials from manufacturers on a quarterly basis, but will only take materials that can be produced in sufficient quantities.

“We don’t accept material for characterization unless they can produce a gram of material. We don’t want to have multiple industrial batches,” McNeil said. Batches can vary in purity, for instance. “We want to make sure we have the same stuff in the lab as in the animal.”

McNeil’s team follows a methodical system to plot the physical attributes of each type of nanoparticle. But nanoparticles rarely are used in their natural, or “naked,” form. Many nanomaterials that function in the dry world of chemistry need to be “dressed” to work in the wet world of biology. They also often have antibodies or other biomolecules attached to their surface that complement molecules on a cancer cell’s surface. The attachments help the nanoparticles latch onto target tumor cells.

“We attempt to have a baseline characterization so we can have some familiarity with that category of nanoparticle,” McNeil said. Each time it is dressed, or functionalized, it is studied again. “Each one would be unique in its behavior. Functionalizing it changes its properties.”

Designers can use the ability to alter properties in their favor. A nanoparticle’s surface charge can make it less biocompatible, for instance. Adding a coating that neutralizes charge may solve the problem, though. In what McNeil characterizes as a possible trend, his team noticed naked gold nanoparticles get larger when placed in plasma. To better understand gold nanoparticles’ blood-contact properties, they plan to add molecules that could stop proteins from absorbing on the surface. That also may be a way to keep the gold nanoparticles from growing larger.

The National Toxicology Program is studying buckyballs and carbon nanotubes, semiconductor nanocrystals called quantum dots and metal oxides such as the sunscreen ingredient titanium dioxide. It is developing a program based on dendrimers, too. NTP, which agreed to take on the initiative at Colvin’s request, allocated between $1.5 million and $2 million in the past year for the program, Walker said.


Veeco’s BioScope II allows scientists to image molecular features within living systems. Photo courtesy of Veeco Instruments
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Walker said the NTP is more or less starting from scratch after scouring the toxicology literature and finding it lacking. But accurately measuring nanoparticles in their various states may prove difficult. Microscopy tools for measuring an electron-dense nanoparticle may not be as suitable for gauging less electron-dense coatings or attachments. Tools using probes may compress flexible structures.

Craig Prater, a fellow at Veeco Instruments who has been integral in the commercialization of several of its microscopy products, said today’s tools can adequately measure nanoparticle size, even in the wet world of biology. Prater helped launch Veeco’s nanobio atomic force microscope, the BioScope. The BioScope II, introduced in December, can be used to image molecules within living cells.

He’s also involved in a project with Dow Chemical Co. to develop ways to better understand nanoparticles’ structure-function relationships. The goal of the Veeco-Dow partnership is to provide a predictive mechanism that will allow manufacturers to efficiently design nanoparticles that perform exactly as desired.

“If we can understand the structure-function and surface chemistry connection to toxicity, that will help us accelerate the design of consistently safe nanoparticles,” Prater said. “All of the chemical companies and scientists take that responsibility seriously.”

But reliable predictions depend on sound data, and scientists like Walker, McNeil and Colvin warn that, for the most part, good fundamental information is not available now. The haphazard reporting of basic characteristics like size threatens to hamper commercialization. “We need to do a better job of describing material,” Walker said. “This will be a roadblock.”

In an effort to get consistency in nanoparticle reporting, Walker contacted funding agencies and editors of key scientific journals and asked that grants or acceptance of a paper be contingent on reporting basic information such as size and methodology. Colvin has been prodding the academic research community to agree to some accepted norms. McNeil hopes to develop voluntary standards for industries and toxicologists based on a consensus process.

It’s the chance to avoid another dioxin or PCB incident.

“If we could provide the structure-activity tools,” Walker said, “then we could say (to nanoparticle designers), ‘You really don’t want to go there with this one.’ They could make an informed decision. The further we can get to providing that assessment upfront, the better it will be for everybody.”


Online sources of information

everal organizations offer searchable databases and inventories on nanoparticles and their health and environmental implications. Here are a few:

International Council on Nanotechnology
http://icon.rice.edu/research.cfm

U.S. National Institute for Occupational Health and Safety
http://www2a.cdc.gov/niosh-nil/index.asp

European Union’s NanoSafe project
http://www.nanosafe.org/

Wilson Center’s Project on Emerging Nanotechnologies
http://www.nanotechproject.com/index.php?id=18

On Jan. 19, a mix of industrial, government and academic researchers and officials gathered on the campus of Rice University in Houston to discuss one of the stumbling blocks facing nanobiotechnology. The participants joined forces at the one-day workshop to identify gaps in the nation’s measurement system that impede innovation, and to suggest potential solutions.

The National Institute for Standards and Technology organized the workshop as part of a nationwide assessment. NIST was on a mission to address unmet or emerging needs for new or better tools and services that could give the United States a competitive edge. As part of the Department of Commerce, NIST is expected to drive technological innovation and economic growth in the nation.

“We hope this will serve as a catalyst for action,” said James Whetstone, chief of NIST’s Process Measurement Division, as he encouraged participants to help the agency prioritize key innovations and pinpoint barriers.

NIST has overseen about a dozen workshops focusing on topics like nanotechnology, photonics and biotechnology – all broad-based technologies that could create significant economic gains and contribute to national needs. Fact-gathering workshops will continue into at least March. NIST will compile its findings and produce a report by mid-June.
– Candace Stuart

Dear Small Times:

After reading Patti Glaza’s column, “Oh Canada! Sing your praises for your nanotech successes” (Small Times Magazine, January/February 2006) I came away disappointed. I met with Ms. Glaza on her recent tour of Canadian nanotech companies. In fact, we spent an hour and half together over a private lunch arranged a month in advance by a Canadian trade organization.

I arranged my air travel for this meeting, representing our company, the province, and to ensure that Small Times would have a clear understanding of what Canada’s “rising nano stars are doing to promote their success.” Indeed, to gain this understanding is why Small Times attended this event in the first place. So, you can imagine my surprise when I read the assertion that Canada is doing nothing to promote its nanotech success, especially when Small Times just attended an event to promote that very subject!

So what’s happening here? After reviewing the Small Times Web site, I discovered that since 2001, Small Times posted, or reported on, a total of three press releases issued by Micromem Technologies. But since 2004, Micromem has issued over 25 press releases – all sent to Small Times as well as other media outlets.

I believe that the press has a responsibility to report the news. My conclusion is that Small Times is either ignoring that responsibility, or doing a very poor job of it.

Sincerely,
Cynthia Kuper
Micromem Technologies
Toronto, Ontario

PCAST gets 14 new members


February 28, 2006

Feb. 28, 2006 – President Bush has appointed 14 new members to his Council of Advisors on Science and Technology (PCAST), including several supporters of micro and nanotechnology. The appointments bring the total PCAST membership to 38.

These appointments follow the president’s Sept. 29, 2005 amendment to PCAST’s executive order to increase its membership and to designate PCAST to serve as his information technology advisory panel.

New members are: F. Duane Ackerman, chairman, president and chief executive of Bellsouth Corp.; Paul Anderson, chairman and CEO of Duke Energy; Robert Brown, president of Boston University; Nance Dicciani, president and CEO of Honeywell Specialty Materials; Richard Herman, chancellor of the University of Illinois; Fred Kavli, founder and chairman of the Kavli Foundation; Daniel Reed, director of Renaissance Computing Institute; Hector de Jesus Ruiz, chairman and president of Advanced Micro Devices; Stratton Sclavos, chairman and CEO of VeriSign; John Brooks Slaughter, president and CEO of the National Action Council for Minorities in Engineering; Joseph Tucci, president and CEO of EMC Corp.; Robert Witt, president of the University of Alabama, and Tadataka Yamada, chairman for research and development at GlaxoSmithKline.

Many of the advisers champion micro and nanotechnology. For instance, Kavli has funded several nanoscience centers at universities and launched awards for nanotech research. Jischke has been an advocate for the Birck Nanotechnology Center at Purdue. Honeywell and AMD are involved in micro and nanotech R&D.