Nanotechnology: Small science not without big challenges


Over the next decade, nanotechnology will revolutionize multiple industries-but first it will have to overcome a few obstacles with construction, handling, and sterility of nanomaterials

The nanotech industry, while still in its infancy, is poised on the brink of a significant growth spurt that could have implications in industries across the economy. Between 1997 and 2003, world-wide government investment in the field rose from $432 million a year to nearly $3 billion a year. Sales of products incorporating emerging nanotechnology are predicted to rise from less than .1 percent of global manufacturing output today to 15 percent in 2014, totaling $3.6 trillion, according to a new report from Lux Research (New York), a research and advisory firm focusing on nanotechnology and related technologies. The report, “Sizing Nanotechnology’s Value Chain,” also predicts that the value of this industry will approach the size of the information technology and telecom industries combined and its revenues will be ten times larger than that of biotechnology. “We project that 4 percent of general manufactured goods, 50 percent of electronics and IT products, and 16 percent of goods in healthcare and life sciences by revenue will incorporate emerging nanotechnology,” says Matthew Nordan, vice president of research for Lux Research. “Initially, electronics and IT applications will dominate as microprocessors and memory chips built using new nanoscale processes come to market.”

From sharper LCD screens and denser computer chips, to advances in cancer research and treatment, within a decade nanotechnology could change the way we think about technological and medical limitations-if these industries can find ways to control the production processes and sterility of atomic-sized products.

Manufacturing at the atomic level

Nanotechnology covers devices and systems that have a length scale of 1 to 100 nanometers. It is the creation of materials, devices and systems through control of matter on the nanometer length scale and the exploitation of novel properties and phenomena.

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Nanotech research uses contamination control techniques similar to that of larger scale production, including HEPA filters, UV lights to kill microorganisms and standard operating procedures common to cleanroom production facilities. But unlike shrinking technologies, which take larger materials and grind them down, nanotech materials are developed from the bottom up. According to Michael LoCascio, chief technology officer at Evident Technologies, a nanomaterials and technology applications company in Troy, N.Y., this offers some benefits for contamination control because the development is done entirely in enclosed environments.

Evident Technologies primarily produces quantum dots, which are nanoscale crystalline structures made from cadmium selenide and other II-VI, III-V, IV-VI semiconductors that absorb shorter wavelength light and then re­emit it in a specific longer wavelength color (see Fig. 1). When illuminated, they act as molecule-sized LEDs that can be linked to antibodies, proteins, or DNA, and used to detect viruses and bacteria in diagnostic tests within the human body. The quantum dots can also be combined with plastics, electrical conducting organic materials, silicones, epoxies, and sol-gels, and used in numerous applications including LEDs, solar cells, photodetectors, flat panel displays, and military night vision equipment.

To create quantum dots, scientists begin with organo-metallic reagents that are carefully prepared in oxygen- and moisture-controlling glove boxes with inert atmosphere fed by nitrogen environments that can be sterile to Class 1 levels with fine particle HEPA filters, or to Class 100 levels with standard filters (see Fig. 2). The precursors are injected into inert environments, such as surfactant chemical vats where the nanocrystals grow. For biological applications, the finished quantum dots are post-processed and attached to proteins, antibodies or single-stranded DNA in sterile water with accompanying UV lights to kill microbes. The nanomaterials remain in these enclosed sterile environments, never coming in contact with human elements or environmental conditions, enabling many nanoproducts to be produced in Class 100 to Class 1000 cleanrooms.

Once in the vats, high temperatures are used to cook the crystals, causing a chemical reaction that results in the creation of core quantum dots. Once the dots reach a desired size or shape-measured by a light spectrum-the process is halted and the dots are separated from the remaining nanodebris. At this stage the dots are fragile, LoCascio admits. The surface of the core tends to be reactive. Solvent molecules, air molecules, or other impurities can easily pollute the dots, compromising their emission capabilities. Even more problematic, many cores are prone to spontaneous dissolution. Simple dilution of core samples often leads to irreversible decomposition of the nanocrystals.

To protect the cores, the dots are put through another chemical process that creates a protective shell composed of a non-emissive, transparent, but structurally related material to insulate them from potential harm. Then, a coating of organic ligands, which attach to the surface of the shell, is added. Once the process is complete, the dots are suspended in sterile water or an organic polymer, or dispersed in a cured or uncured polymer, which further protects them from outside contaminants or damage. “By the time the dots are in the polymer they are robust,” LoCascio says. Because the vats are cooked at such high temperatures, and because the dots at this stage are used for research purposes only, sterility is not yet a concern. However, he says, that could soon change.

Control issues could hinder progress

One of the primary application goals for quantum dots is human imagery and diagnosis (see Fig. 3). Before that can happen, FDA regulations will need to be written for the construction and handling of the materials to ensure their integrity and safety for human consumption. “But that’s several years out,” LoCascio says. At this stage, there are no regulations being developed and it could be five years before researchers are ready to use quantum dots in humans. In the meantime, work is still focused on tapping the commercial viability of nanomaterials. “Right now, contamination is not the priority-determining usefulness is.”

Mihail Roco, senior advisor for nanotechnology at the National Science Foundation (NSF; Arlington, Va.) and chair of the NSF Engineering and Technology Council’s Subcommittee on Nanoscale Science, Engineering and Technology (NSET), agrees. “The emerging fields of nanoscale science, engineering, and technology-the ability to work at the molecular level, atom by atom, to create large structures with fundamentally new properties and functions-are leading to unprecedented understanding and control over the basic building blocks and properties of all natural and man-made things,” he says. “The trend now is to move from fundamental discovery to technological innovations.”

The transition from nanotechnology research to manufactured products is still limited, however, by control and production issues. Managing the impact of the environment at the atomic level presents unique challenges, says Eric Steel, deputy director of the National Institute of Standards and Technology (Gaithersburg, Md.). In growing nano-sized materials, manufacturers and researchers face tremendous control issues that will impact manufacturers’ abilities to work with them. Just as with technology components today, there will be defects in the materials and manufacturing process, and particle contamination will always be a concern. “No matter how perfect you think your nanoscale process is, you are going to have defects that cause failures,” Steel says. “You can’t do perfect manufacturing at an atomic scale.”

Figure 1. Quantum dots are nanoscale crystalline structures that absorb shorter wavelength light and then reemit it in a specific longer wavelength color. Source: Evident Technologies (Troy, N.Y.)
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Handling and environmental interference could also affect the usefulness of nanomaterials, especially as they come in contact with products that are not nano-made, suggests LoCascio. For example, even if certain elements of an electronic system could be made from nanomaterials, the challenge that remains is how to effectively bring them together with traditional materials. “There could be a meshing of the two manufacturing processes, where certain parts are grown from the bottom up and others are produced conventionally, but there are still a lot of challenges.”

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Managing nanoscale defects

In non-medical industries that could benefit from nanomaterials, experts agree that the same level of contamination control as is in place for larger materials will be required for nanomaterial use. Particulate contamination and airflow pressure will continue to be concerns, and the ongoing struggle to control environmental conditions in cleanrooms is only likely to increase.

Scientists are struggling to find ways to manage and manipulate nanoproduction to reduce errors and defects and to maximize its potential, Steel says. He predicts that years from now, as nanotech elements become commonplace in the semiconductor and hard drive industries, the way manufacturers will deal with the potential increase in defects is to build massive redundancies into the production systems. “We have to find new ways to handle atomic scale errors,” he says. Likening it to biological production processes today, he believes that the most cost-effective approach may be to produce in excess with the expectation that a certain percentage of product will fail.

It’s also possible that earlier and more sensitive reliability testing systems will be developed to ensure that sufficient redundancies are built into processes and that mechanical and electrical elements may have repair or rerouting systems built into the product. Because the circuitry will be so small, it’s reasonable to imagine that redundancies could be built directly into products, enabling the system to route power away from a failed circuit to a back-up circuit.

Figure 2. The creation of quantum dots begins with organo-metallic reagents that are carefully prepared in oxygen- and moisture-controlling glove boxes with inert atmosphere fed by nitrogen environments. Source: MBraun (Stratham, N.H.)
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Controlling the growth process to reduce defects and improve efficiencies of other nanomaterials, such as carbon nanotubes, is also a continuing struggle for researchers. The carbon nanotube was discovered in 1991 as an excellent source of field-emitted electrons. Nanotubes are extraordinarily strong, conduct electricity, vibrate at high frequencies, emit light, and are sensitive to the presence of minute amounts of substances. They can be up to 100 times stronger than steel, yet a fraction of the weight.

Next-generation computer chips, integrated circuits, and the micro electro-mechanical (MEMS) devices that power them depend upon carbon nanotubes that can be grown in specific lengths and directions. However, controlling the growth of nanotubes is fraught with problems. “Researchers would love to be able to grow [a] single-walled carbon nanotube that is miles long that they could spin on a spool like a thread and use it to weave circuitry,” says Steel, but the growth process is messy, resulting in graphite contamination and environmental factors that impede the length and direction of the tube’s development. The smallest changes in pressure, temperature, or levels of gases affect the nanotube growth process, causing kinks and limiting length. “We are used to controlling these issues [on] a large scale, but not at nanoscales,” Steel adds, pointing out the need for more sensitive cleanroom equipment that measures at nanoscales. “Things like vacuum systems are still measured by the cubic foot.”

Finding ways to control and purify the nanotube development process is now a hot research area in nanotech. Scientists are exploring ways to better control the environment and to purify the tubes post-production to remove contaminating elements. For example, researchers at Motorola Labs have developed a high accuracy carbon nanotube substrate placement method that could pave the way for the development of smaller, faster nanotube-based transistors and product improvements, such as high brightness flat panel displays. The Motorola Labs team has developed a technique using chemical vapor deposition (CVD) which can position individual single-walled carbon nanotubes at pre-determined locations in a uniformly parallel manner that is compatible with conventional semiconductor processing techniques. Around 90 percent of the nanotubes produced in this way were semiconducting in nature.

NSF funds the next wave of research

These types of solutions may now be easier to find, thanks to the recent significant investments into nanotech research across the economy. Companies and investors are beginning to see the viable commercial potential of nanotech objects, and are allocating substantial attention and funding to its development, LoCascio says. “Until recently, nanomaterial was not available to people outside of research. Now that it is, people can see the possibilities. There is a higher level of understanding of what we can do.”

Figure 3. Human epithelial cell components visualized with QDOT protein conjugates. Source: Quantum Dot Corporation (Hayward, Calif.)
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To support those fields of research, in September 2004 the NSF awarded $69 million over five years to fund six major centers in nanoscale science and engineering through the National Nanotechnology Initiative (NNI). The NNI is a federal R&D program established to coordinate the multi-agency efforts in nanoscale science, engineering, and technology. These awards complement eight existing nanoscale centers established since 2001. The awards are part of a series of NSF grants totaling $250 million for nanoscale research in multiple disciplines in fiscal year 2004.

“The first four years we focused on research into new phenomena in nanotechnology, such as building quantum dots, nanotubes and particles,” Roco says. “Over the next five years, the focus will shift toward creating systems from these nanocomponents that will be relevant in the fields of energy conversion, nanomedicine, agricultural systems, and molecular architecture for manufacturing.” The large capital investment is due to the fact that nanotechnology has broad implications across all sectors of the economy and the NSF is committed to supporting nanoresearch wherever its applications show promise. “The nanoscale initiative supports high-risk, high-reward, priority research themes aligned with societal needs,” Roco says.

Research at the Center on Molecular Function at the Nano/Bio Interface at the University of Pennsylvania is aimed at the interface of nanotechnology and biology at the molecular level which will have applications for nanoscale device manufacturing, drug delivery and

Each new center has a bold vision for researchand education at the frontiers of science and technology,” says Roco. “With the existing centers, they provide a coherent approach to U.S. nanotechnology research and education.”

Standards needed for common language, tools

In order to achieve this expected growth, however, standards need to be developed to define and characterize nano-technology. “One of the most pressing issues facing nanoscientists and technologists today is that of communicating with the non-scientific community and with each other,” Nordan says. “People don’t agree on what a nanoparticle is, or what its properties are, or how to measure it.”

In the beginning, when there were only a few scientists working together, standards were unnecessary because they were all working together, but as involvement and investment expands, it is becoming increasingly difficult to share research or have relevant conversations, Steel says. “Everyone agrees the terminology for nanotech is a little loose, and it has reached [such] a level of maturity that it now requires standards.” Steel is the NIST Representative to the American National Standards Institute Nanotechnology Standards Panel (ANSI-NSP), a new coordinating body for the development of standards in the area of nanotechnology. The panel will focus its initial work on nomenclature and terminology and later on materials properties and measurement procedures to facilitate commercialization of the applications and uses of nanotechnology. “Our first goal,” Steel says, “is to figure out exactly what nanotechnology is and to establish a suite of terms that define technical standards and characteristics so we know what each other is talking about.”

Defining the language of nanotech is critical on many fronts. Without standards, two people may be discussing the same materials using different terms, or different materials using the same terms, making it difficult to verify or compare research, validate tests, or commercialize products. “A standard language is necessary to interpret discoveries. It drives what you can describe,” Steel explains.

The ANSI panel convened for the first time in September, with representatives from academia, the legal profession, industry, government, standards developing organizations and other subject matter experts to define the scope and strategy of the group. Steel expects it will take a year or more before the first real set of standards for nomenclature are completed. “Because standards development is a consensus process, it’s hard to say when something will be available,” he explains. “We are really just getting started.”

Along with establishing a common language, more advanced measuring and handling tools must also be developed for any nanotech industries to continue to move forward, says Kathryn Moler, head of the Center for Probing the Nanoscale. Research conducted at the center will allow researchers to measure, image and control nanoscale phenomena. “There’s a huge effort in this country to advance nanoscale research, but we don’t have the tools,” Moler says. “If we want to engineer what’s at the nanoscale, we need to be able to see it and handle it. That’s what our center’s all about.” Work conducted at the center will enhance the nanotechnology community’s ability to observe, manipulate, measure, image and control nanoscale phenomena. Researchers at the center hope to develop probes with revolutionary capabilities, such as mapping a single electron’s behavior in a semiconductor and controlling a single electron’s magnetic orientation, or spin.

Nanoparticles and health risks

Nanomaterials can behave unpredictably when handled and they may interact with the human body in different ways than more conventional materials, due to their extremely small size. For example, studies have established that the comparatively large surface area of inhaled nanoparticles can increase their toxicity. Such small particles can penetrate deep into the lungs and may move to other parts of the body, including the liver and brain.

Many nanomaterials and devices are formed from nanometer-scale particles that are initially produced as aerosols or colloidal suspensions. Exposure to these materials during manufacturing and use may occur through inhalation, dermal contact and ingestion. According to the National Institute for Occupational Safety and Health (NIOSH), minimal information is currently available on dominant exposure routes, potential exposure levels and material toxicity. What information does exist comes primarily from studying ultra-fine particles, typically defined as smaller than 100 nanometers.

Studies have also indicated that low solubility ultra-fine particles are more toxic than larger particles and there are indications that particle surface area and surface chemistry are primarily responsible for observed responses in cell cultures and animals. There are indications that ultra-fine particles can penetrate through the skin, or translocate from the respiratory system to other organs. Research is being conducted to understand how these unique modes of biological interaction may lead to specific health effects.

Meanwhile, NIOSH is participating in an international effort comprised of research groups, government agencies and industries seeking to understand the health impact of nanotechnology and how to control potential risks. The group is pursuing a number of initiatives, including studying the mechanisms leading to nanoparticle toxicity; developing and testing methods to characterize and monitor the health related properties of nanomaterials; and investigating nanoparticle exposure and ways to control exposure in the workplace.

Nanotechnology may hold the key to the future of technological innovations, but there are still many questions to be answered before researchers fully understand how to work safely with nanomaterials. The new standard for nanotech nomenclature will aid the research on health effects because it will help to clarify the materials and techniques being tested and avoid dangerous generalizations. “Any new technology scares people,” Steel says. “I think every­one in the nanotech industry wants to be sure no person or business is hurt.