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November 2001
Vol. 10, No. 11,
pp 36–38, 40.
Today's Chemist at Work
Focus: Nanotechnology


Manipulating molecules

From sci-fi to sci-fact, nanotechnology accomplishes “very little” with ever increasing flair.

    opening art“He wished to manipulate living nerve tissue. . . . So, he used tiny waldoes which . . . could manipulate things much too small for the eye to see.”

—Robert A. Heinlein [Waldo & Magic, Inc., 1942]

Recently, an episode of Star Trek: Voyager showed crew members performing genetic engineering simply by touching pictures of genes on the screen of a computer. Yes, it’s only television, and science fiction at that, but life is beginning to imitate art at the University of North Carolina at Chapel Hill (UNC-CH). Scientists there have combined virtual reality and an atomic force microscope to create a nanoManipulator.

The nanoManipulator project is developing a three-dimensional, tactile user interface to scanning probe microscopes such as scanning tunneling microscopes (STM) and atomic force microscopes (AFM). An STM probes by tunneling electrons to and from the sample, while the AFM measures forces between the surface and the tip. Tunneling is the quantum mechanical phenomenon that describes the ability of lower energy subatomic particles to penetrate higher energy barriers.

Specifically, an STM measures subatomic distances by maintaining a constant height and recording current flows between the flow and the sample based on quantum mechanical tunneling effects. An AFM measures atomic forces between a sharp probe and the sample surface to provide an image of atomic and molecular features of the sample.

The nanoManipulator uses virtual reality (VR) goggles and a force feedback probe as an interface to a scanning probe microscope, providing researchers with a new way to interact with the atomic world. Researchers can travel over genes, tickle viruses, push bacteria around, and tap on molecules. Of course, most chemists are already familiar with the famous picture of “IBM” written in 1989 by Don Eigler using 35 Xenon atoms on a nickel surface, but the nanoManipulator simplifies the process and allows researchers to play with their atoms. It seems like something out of Robert Heinlein’s 1942 book, Waldo & Magic, Inc., in which the hero of the story learns to manipulate tiny forces with his remote control machines. “From a pure coolness point of view, it’s phenomenal!”, proclaimed Eric Henderson of Iowa State University after he had visited the UNC-CH campus.

An Amazing Experience
The VR goggles allow researchers to view and traverse molecules as if they were walking down a neighborhood street. The force feedback allows researchers to roll nanotubes and feel the bumps on a crystal surface or the resilience of a virus molecule. Although the individual capabilities are not new, the package, taken in totality, makes for an amazing experience. It takes the tedium out of molecular manipulation and puts the fun back into fundamental research. By playing with the molecules, researchers gain greater insight into properties, such as strength, flexibility, durability, and even shape. Researchers will likely find ways to decrease the costs of this tool and create devices that can also be used for development applications.

The nanoManipulator is the result of the convergence of physics and computer science. Experts from both fields worked together to combine the technologies to achieve this amazing device. Many chemists and biologists are familiar with tunnel-effect microscopy. The scanning tunneling microscope has been an important tool in physics, chemistry, and materials science since the late 1980s. It uses quantum mechanical tunneling to link the macro and micro worlds, allowing researchers to examine material at the atomic level.

Just as ultrasound can be used to read surfaces within the body via changes in sound, changes to current flow can be monitored via tunnel-effect microscopy to read atom-sized bumps, ridges, and valleys on a molecule, material, or other surface. The changes in current can be transformed into graphical representations. This ability to turn “tunneling” into topology has been around for about a decade. What is new is the interface, which facilitates natural-feeling interaction and manipulation.

The nanoManipulator multiplies the visualization and control nearly one million fold, so that researchers can interact with a system as if they were playing a video game. Improved multicolor, three-dimensional graphics provide a real-world perspective to the interaction. Surfaces are represented as bumpy or hilly landscapes and are refreshed in real-time as researchers relocate the probes and view the results on a monitor or with VR goggles.

The most amazing part of the system is force feedback. Scientists have been able to see pictures and even manipulate atoms and molecules for a few years, but with force feedback, they can gain a sense of interaction. Researchers use the goggles and an elongated joystick to follow the contours of the atomic-level landscape. As the probe comes across resistance, the feeling of resistance is passed through the joystick back to the user. Movement across valleys results in a falloff of resistance, movement into a bump or a wall results in an increase in resistance, and pushing on a virus provides a feeling of resilience. An apparently smooth crystal feels bumpy because of its component atoms, and proteins may have edges and holes. Molecules that bend or twist with some elasticity provide a rubbery sensation.

Manipulating the nanoManipulator
Looking at the low-level landscape may not seem so spectacular, but actually interacting with it and moving components—atoms and molecules—is a completely new experience with the nanoManipulator. As mentioned, pressing on a virus provides a bouncy feeling. If the probe pushes a virus, it will bend and then finally move. When crushed, a virus behaves like a Nerf ball: it deforms and then recovers. The researcher can see all of these phenomena with the goggles while feeling them with the force feedback of the probe.

Another nice feature of the nanoManipulator is that researchers can see and feel the results of their theories and models. They can stretch, twist, push, pull, and in general, play with their molecules. Just as Microsoft Excel lets certified public accountants run financial “what-if” calculations, the nanoManipulator lets chemists, physicists, and biologists run low-level, hands-on, what-if experiments with their favorite molecules. In addition to seeing the shapes and flexibility of complex proteins, researchers can explore the different degrees of molecular and atomic attraction of real molecules, comparing the predictions of models with the results in their “bare hands”. Rather than the abstract modeled molecular force, researchers can feel differences and describe them in more subjective terms of friction and flexibility.

Researchers can manipulate nanotubes as if they were molecular toothpicks. The researchers can pick them up, stack them, roll them around, and bend them just like a child playing with Lincoln Logs. One day, descendants of the nanoManipulator may be used to build nanotube-based machines and electronics. It would not be too far-fetched to imagine a researcher using a special genetic nanoManipulator to string a thread of DNA around or through a set of nanotubes.

Since the early 1990s, researchers have explored a wide variety of different applications using different versions of the nanoManipulator. For example, microscopic items have been manipulated, bent, pressed, and pushed—somewhat like exploring a piece of wet spaghetti with a toothpick.

Much work has been done with the mechanical and electrical properties of nanotubes. Researchers have experimented with friction and adhesion, bending and buckling of nanotubes and mechanical nanodevices. It is one thing to calculate the stress tensor of a nanotube. It is a much more intuitive and exciting experience to manipulate a nanotube to observe its properties firsthand. The force feedback enables the user to position nanotubes next to each other to make a bridge or electric circuit. One study has revealed that the relative orientation of very small contacts, such as a couple of nanotubes, has a significant effect on the electron flow. This finding will help in the design of microscopic electromagnetic switches.

In fact, researchers have looked at several molecular samples under the nanoManipulator. Researchers have stretched DNA molecules to observe rupture limits. Scientists have also investigated viruses to correlate form and function and explore effects of mechanical stresses on integrity. Some of these applications are described at www.3rdtech.com.

Medical researchers have used the nanoManipulator to study fibrin fibers, the major components of blood clots. The researchers hope to gain insight into the healing process by observing the strength and mechanical properties of blood clots under a variety of parameters and conditions. Documentation of the results may further the understanding of the biochemical mechanisms behind heart attacks and strokes and provide insights into wound healing. The nanoManipulator allows researchers to directly observe the rupture force and other properties of fibrin under a variety of controlled conditions.

Students in North Carolina and Iowa are gaining concrete experience with the nanoManipulator, exploring and manipulating objects at the atomic and molecular levels. The students will use the Web and Internet2 for more realistic interactions, such as force feedback of the three-dimensional aspects of a DNA molecule or a virus. Initially, students explore the parameters of the device, but later they design and perform their own experiments with DNA molecules and viruses. For example, students can push around a cold virus with a probe to observe its physical characteristics at the molecular level.

Both scientists and students develop a renewed respect for the reality of proteins when they can experience the real-life properties such as adhesion, friction, strength, and resistance as felt through the force feedback probe and observed on the graphic screen.

Accessing the Atoms
All of this activity and fun comes at a price. A scanning probe microscope can cost from $100,000 up to $1 million, depending on the features, quality, and resolution. The nanoManipulator’s functions—both hardware and software—will double the cost. At that price, there are only about four or five systems available throughout the world. However, UNC-CH is trying to tie the Internet2 to its nanoManipulator to provide wider access to the experience. According to researchers, although the graphics work reasonably well, the tactile features are not in sync, due to latency and data transmission time delays. Although delays of a fraction of a second are acceptable for some graphics and sound, tactile feedback suffers with too much delay between user action and probe reaction. The feeling is somewhat reminiscent of the old dubbed-over movies where the actor’s lips move, and then a fraction of a second later, the words come out. The effect is so uncomfortable that it is funny. But with the nanoManipulator, the effect is frustrating, not funny.

Join the Fun
The nanoManipulator has been online since the 1990s. Serious researchers who have a valid research project can contact the labs at UNC-CH to schedule time with the device. The nanoManipulator system is a National Institutes of Health National Research Resource, so there is no cost to use the device other than for probes and other consumables, although time may be at a premium. For researchers who are interested in using the facility, simply submit a brief statement describing and outlining the investigation as well as how the nanoManipulator will benefit the research. For more details or to contact the labs at UNC-CH, visit www.cs.unc.edu/Research/nano/index.html. For those lucky folks who already have a scanning tunneling microscope, the electronics for a nanoManipulator system can be purchased from 3rdTech (http://3rdtech.com).

Tools like the nanoManipulator allow scientists, students, and researchers to experience the molecular world and gain a better intuitive feel for its interactions. When they can manipulate their environment, people tend to stick around and explore it more persistently than when they have to guesstimate with arcane calculations and models. In this way, a scientist might be more inclined to explore pure “what-if” scenarios, developed during his intuitive experience, rather than focus only on the point of the calculation. This experience can provide the opportunity that favors the prepared mind. Indeed, many inventors are kinesthetic types of people who prefer a hands-on approach to feel how things can be changed and improved. The nanoManipulator is a phenomenal tool toward this end.

The nanoManipulator is out of the price range of most laboratories. From a cost viewpoint, it is like the MRI of molecular modeling. It is very powerful but also very expensive. When the cost of tools like the nanoManipulator drops below $10,000, labs will beat a path to buy and modify them for innovative technical advancement. There is a good chance that a simplification of the technology and a reduction in cost will create a cycle with an increasing spiral of functionality and a decreasing spiral of costs. At least, let’s hope that will happen. With a technology like this one, it should.

Further Reading
Falvo, M. R.; Taylor II, R. M.; Helser, A.; Chi, V.; Brooks Jr., F. P.; Washburn, S.; Superfine, R. Rolling and sliding of carbon nanotubes Nature 1999, 397, 236–238.

Guthold, M.; Matthews, G.; Negishi, A.; Taylor, R. M.; Erie, D.; Brooks, F. P.; Superfine, R. Quantitative Manipulation of DNA and Viruses with the nanoManipulator Scanning Force Microscope. Surf. Interf. Analys. 1999, 27, 437–443.

Guthold, M.; Falvo, M. R.; Matthews, W. G.; Paulson, S.; Washburn, S.; Erie, D.; Superfine, R.; Brooks, F. P.; Taylor, R. M. Controlled Manipulation of Molecular Samples with the nanoManipulator. IEEE/ASME Trans. Mechatron. 2000, 5, 189–198.

Hank Simon has worked with information technology, IT architectures, and XML technologies for 25 years. He received an M.S. and Ph.D. in nuclear chemistry research and a focus in Information Technology, respectively. Send your comments or questions regarding this article to tcaw@acs.org or the Editorial Office 1155 16th St N.W., Washington, DC 20036.

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