NOTES FROM UNDERGROUND: Manoharan's lab features extreme controls to guard the delicate scanning tunneling microscope from vibration, heat and dust.

more than 350 years ago, the Dutch scientist Anton van Leeuwenhoek focused his single-lens microscope on a bee’s mouth. His recorded observations so stirred imaginations that scientists ever since have worked to develop tools that let them see farther and farther beyond the limits of human vision. Today, cutting-edge microscopy has brought the subatomic world into view. Researchers in the fledgling fields of nanoscience and nanotechnology seek not only to observe and understand the infinitesimal, but also to manipulate it, building new structures and devices that seem worthy of science fiction.

Most scientists use the prefix nano when referring to materials measuring less than 100 nanometers. Thomas Kenny, associate professor of mechanical engineering, offers some comparisons. A nanometer—one-billionth of a meter—is almost as wide as a DNA molecule, or roughly 10 times the diameter of a hydrogen atom. If one were to spread a drop of water over a square meter, it would form a thin film of roughly one nanometer. Or think of the metal film layered onto tinted sunglasses: a nanometer is one-tenth that thickness. In the world of microprocessors and semiconductors, the smallest lithographic feature on a Pentium computer chip is about 100 nanometers.

Nanotechnology is often hailed as the engine that will generate waves of innovation across all industries. That prediction is based on the discovery that nanosized particles of any given substance exhibit different properties and behave differently from larger particles of the same substance. In effect, these tiny building blocks can be used to create new materials with unprecedented capabilities.

FIRST THINGS FIRST: Moler's center works on tools for probing the nanoscale.

Three nanostructures in particular have gained a lot of attention: fullerenes, nanotubes and quantum dots. Fullerenes, also called buckyballs for their similarity to the geodesic domes of architect Buckminster Fuller, are soccer ball-shaped molecules made of 60 carbon atoms. While these nifty little objects are expensive to produce, their remarkable properties could make them suitable for use as insulators or for delivering drugs into humans. Cylindrical fullerenes, or nanotubes, are roughly 100 times stronger than steel and able to withstand temperatures of 6,500 degrees Fahrenheit. A quantum dot can be visualized as a minuscule box used by researchers to trap individual electrons and monitor their movements. Scientists suggest they could one day be used to make solid-state lasers that emit light at wavelengths never achieved before, with welcome implications for high-speed data transmission.

Although much of the basic investigation into how the nanoworld works will take years or decades, researchers are making dramatic headway, and Stanford physicists, biologists, chemists and engineers are in the thick of developments.

• Hari Manoharan, assistant professor of physics, is a pioneer in manipulating single atoms and molecules to create experimental structures. He also is reportedly the first scientist to record the sound of an atom moving. (It starts with a soft hum, followed by a rhythmic popping sound, like a ball bearing rumbling down a hollow tube.)

• Associate professor of chemistry Hongjie Dai synthesizes carbon nanotubes. His experiments include incorporating them into memory chips that might hold exponentially more data than silicon chips, and employing them as sensors capable of detecting single molecules. Eventual applications might range from more efficient medical diagnoses at the earliest stages of disease to effective sleuthing of trace amounts of chemical agents.

• Using nanotech instruments devised in his lab, biological sciences and applied physics professor Steven Block and colleagues made history by isolating single molecules of RNAP, the enzyme that copies genes from DNA onto strands of RNA, and watching that basic life process unfold. This led Block’s team to hypothesize that RNAP “proofreads” and corrects its mistakes as it goes along to avoid creating defective proteins. Their achievement stands to advance the understanding of genetic factors in disease.

• Last fall, the National Science Foundation awarded the University $7.5 million over five years to establish the Center for Probing the Nanoscale, one of six NSF-funded centers to support nanoscale science and engineering. Through advances in manufacturing, biotechnology, electronics, medicine and more, nanotechnology may account for a $1 trillion annual market and employ 2 million people within 10 to 15 years, according to an NSF report.

Buried two stories beneath the Varian Physics building is a dark, quiet chamber that houses a scanning tunneling microscope. The STM is a big step up from conventional notions of lab table microscopes—starting with its vacuum column, which must remain chilled to absolute zero. The surrounding environment must be kept absolutely still, so even the inaudible buzz of fluorescent lights in the chamber must be silenced (and lights turned off) when the STM is being used, says Manoharan. To eliminate vibration in his lab, shock absorbers are built in under the special concrete pad that supports the chamber, thus dampening Planet Earth’s movements. For further cushioning, the STM sits atop stacked tables whose hollow legs are filled with compressed air. The entire lab is encased in 4-inch-thick steel walls, shielding the high-powered microscope from heat and air movements.

SMART MOVES: Experiments manipulating cobalt atoms hint at an electronics revolution. Courtesy IBM Almaden Research Center

Such extreme precautions are crucial when the object under investigation is an atom being magnified 100 million times. Think how difficult it is to steady a home telescope on one of the moon’s small craters. Then consider trying to focus on an object beyond the edge of the solar system. That’s the magnitude of the challenge nanoscientists face.

Only this kind of telescope isn’t used for mere gazing. The STM and similar instruments offer the means to control as well as observe the invisible. They are the frontline tools in nanotechnology.

Scientists and engineers take two approaches to the nanoworld. Working “top down,” effort is focused on stretching the limits of existing technologies and machines by introducing ever smaller design features, such as nano-sized optical switching systems. In contrast, the “bottom-up” approach aims to build new devices from scratch, one molecule at a time.

“It is a new way of doing things,” says Malcolm Beasley, professor of applied physics and electrical engineering. “We have to think differently because we’re measuring differently. In the past, the methodology was to measure [larger] things and try to determine what is going on at the nanoscale. Now, in some sense we have inverted the process and you measure at the nanoscale and work out from there.”

The idea of unraveling the inner workings of the nanoworld was outlined in 1959 by the Nobel physicist Richard Feynman in a speech at Caltech titled “There’s Plenty of Room at the Bottom.” He talked about “the importance of improving the electron microscope by a hundred times. It is not impossible; it is not against the laws of diffraction of the electron.” Feynman’s musings on the possibilities set the ball in motion. But not until the invention of the scanning tunneling microscope in 1981 by IBM’s Gerd Binnig and Heinrich Rohrer did the potential of observing molecules and atoms start to be realized.

Electron microscopes in the STM family feature a needle-like tip, or probe. As the electron-beaming tip scans a sample, moving up and down across its contours like a record-player needle, electrons from the surface of the sample are set loose, creating a “tunnel current.” To keep the current flowing steadily, the tip is continually adjusted to maintain a distance of about one nanometer from the sample. Measurements of the tip’s fluctuations are recorded and represented on a computer screen as a three-dimensional image of the sample.

A carbon nanotube is 5 million times smaller than a one-centimeter silicon wafer. In the space required to place a million transistors today, you could place 2.5 billion. A motherboard the size of a baby's fingernail would have enough processing power to run a network server.

There are about two dozen types of scanning-probe microscopes capable of producing amazing multicolor images of atomic-level interactions. In 1985, applied physics professor Calvin Quate co-invented the atomic force microscope to overcome the STM ’s basic drawback: it could only be used to image conducting or semiconducting surfaces. The AFM can generate images of almost any type of surface, including polymers, ceramics, composites, glass and biological samples.

But these microscopes can do much more: their tips can form a strong enough electron bond with the atoms under examination to move them, as scientists at IBM’s Almaden Research Center in San Jose demonstrated in 1990. Using an atomic force microscope, they positioned 35 xenon atoms on the surface of a nickel crystal to form the letters IBM.

Before coming to Stanford in 2001, Manoharan worked for three years as a research scientist at IBM Almaden, where he used a miniature probe and an AFM to nudge 36 individual cobalt atoms into a circle on a surface of copper. The stunning image of blue dots on a surface became the cover photo for Nature magazine five years ago. (He captured the sound of the atoms by amplifying the current created by their movement.)

MIGHTY MITES: Computer renditions of the molecular structure of a nanotube trapping an ion (top) and a futuristic nanorobot that might sail through the bloodstream and deliver drugs to targeted cells. Photo Credit

Lining up cobalt atoms like marbles isn’t just an academic exercise. It paves the way for the next waves of nanotech innovation, including the development of nanoscopic machines called assemblers, programmed to manipulate atoms and molecules at will. It would take thousands of years for a single assembler to produce a material one atom at a time, but trillions of assemblers could conceivably be used to develop products in a commercial time frame.

The basis for much of the excitement over nanotechnology is its potential for overcoming physical barriers that will soon limit improvements in electronic devices. The integrated circuitry that runs everything from iPods to NASA computers relies on millions of transistors integrated on silicon wafers. The more transistors crammed into a device, the faster and more capable it becomes. And the smaller the transistors, the smaller the housing needed to accommodate it. Thus, advancements in semiconductor manufacturing over the past 40 years that have steadily shrunk the size of the circuitry have enabled superfast processing in ever-smaller devices. But this trend is about to hit a wall.

In the next seven to 10 years, scientists estimate, the transistors will need to be so small they will jump into an entirely different realm. Silicon can only be sliced so thin. At that point, the only place to go is down to the molecular level, using matter a few atoms across. “We will need a new material to use for conduction to continue advancements in performance,” says Yoshio Nishi, professor of electrical engineering, director of research at the Center for Integrated Systems and director of Stanford’s Nanofabrication Facility. “Nanotechnology is the tunnel we can take to get past that barrier.”

If scientists can coax, say, a few carbon atoms to behave like silicon, it will unlock a world of possibilities that seem almost unimaginable. A carbon nanotube is 5 million times smaller than a one-centimeter silicon wafer. In the space required to place a million transistors today, you could place 2.5 billion. A motherboard the size of a baby’s fingeRNAil would have enough processing power to run a network server. “You could have a high-resolution digital camera three millimeters square,” says Nishi.

Stanford engineers have successfully provoked electrical signals from carbon nanotubes. The next hurdle is getting those signals to connect with others, an important step toward an integrated circuit. Getting there will take time, but Nishi says it will happen. “There will be many engineering challenges but the path is there and we just need to keep following it. This is not science fiction.”

REACHING OUT: Goldhaber-Gordon hopes Stanford's new center will inspire middle school kids through their teachers.

Indeed, in late 2003, Stanford chemists led by Dai teamed with UC-Berkeley engineers and assembled the most advanced nanoelectronic product to date, incorporating newly synthesized carbon nanotubes into a working integrated silicon circuit. This work was reported in the January 2004 issue of Nano Letters, a publication of the American Chemical Society.

However, Nishi is careful to differentiate the promise of this nanotechnology, which he refers to as “evolutionary,” from “revolutionary” nanotech touted by some futurists. Theoretically, molecular “machines” could be made small enough to have extraordinary uses in medicine, for example. A robot smaller than a grain of rice with onboard computer and navigation could be injected into the bloodstream of a patient, travel to targeted cells and administer treatment. But even as he describes it, Nishi is backpedaling. “That’s a long way off,” he says.

Part of the problem is achieving the same reliability in a nanotechnology device that silicon provides for existing products. Current technologies are nowhere near delivering it. The purity of the base material is essential to quality performance, and silicon-based circuitry has a purity factor of 99.99999999999999999999999999999 percent. “At this moment, carbon nanotubes have a purity factor of 95 percent. We need another 22 nines,” jokes Nishi.

Much of the speed and efficiency of research depends on training a new generation of nanoscientists, and on merging biology, physics and chemistry. “It is challenging in that we speak different languages,” says Tim Harper, founder and president of CMP-Cinetifica, a UK-based nanotechnology consultancy. But, he adds, “A lot of the new nanoscience facilities are interdisciplinary.”

Certainly Stanford’s are. Campus lab members at the Stanford Nanofabrication Facility come from the departments of physics, aeronautics and astronautics, chemistry, electrical engineering, geological and environmental sciences, materials science and engineering and mechanical engineering. In addition, outsiders from industry, government and other universities use its 10,500-square-foot state-of-the-art semiconductor clean room. While most clean rooms are devoted to a single purpose, work here ranges from microelectrical-mechanical systems to biological and chemical applications. “This multidisciplinary focus creates an environment that stimulates intellectual discovery,” director Nishi says.

At the Stanford Nanocharacterization Laboratory—in simple terms, researchers analyze the composition and properties of materials here, whereas at the SNF they use those materials to fabricate structures and devices—members also come from multiple academic fields, government and industry.

Like most emerging fields of technology, nanotechnology has had its fair share of start-up companies aiming to capitalize on these innovations. Those with limited funding cannot afford expensive equipment like the AFM and the STM. Shared-use facilities such as those at Stanford provide a needed boost for pushing the boundaries of science as van Leeuwenhoek did nearly four centuries ago.

The new Center for Probing the Nanoscale began with a casual conversation two years ago between Kathryn Moler, associate professor of applied physics and of physics, and assistant physics professor David Goldhaber-Gordon, now the center’s co-directors. They envisioned a lab where investigators from different fields could collaborate. But the center has an unusual twofold mission.

On the scientific side, the goal is to look for ways to shrink various manufacturing, computer and medical technologies and to develop the novel tools—nanoprobes—necessary to investigate materials and learn more about their form and function. Manoharan, Dai, Quate and others will lend their expertise. “We are building these tools to do the science we want to do,” Beasley adds. “We are not building them and asking who will come. And we have a lot of support for that notion from our industrial friends who sell nanoprobes.”

The center is also a teaching lab founded as a partnership between Stanford and researchers at IBM and other companies. Some of the NSF grant money will be used for educational outreach to middle schools through a summer institute modeled after programs at Cornell and Rice universities. During a two-week period each year, the summer school trains 40 teachers in the concepts of nanotechnology so that they may convey them to a younger audience.

Among the outside scientists working with the center is Don Eigler from IBM Almaden, a pioneer of low-temperature scanning tunneling microscopy, spectroscopy and atom manipulation. He will participate in the middle-school educational outreach program.

“The idea is to inspire teachers and have students learn from them, and with that there is potential for reaching many more students,” says Goldhaber-Gordon. “A well-educated populace is better able to make informed decisions when deciding on technologies.” The hope, too, is that by the time the students reach high school, they will be more motivated to continue studying science than has been the case in the past—and provide the brainpower for this new frontier.

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