This article presents research work of various groups that are working on using nanotechnology in medical treatments. The researchers at Cornell University’s nanofabrication lab needed to make the propellers on the chip and harvest them, rather than rinse them off. After trial and error, the Cornell engineers came upon a workable combination of biochemical methods and fabrication. Mounting a 2-micrometer polystyrene sphere to the motor, the Cornell researchers made a mechanical amplifier to evaluate the motion of the FI-ATPase enzyme. The group made a small photosynthetic cell by installing the protein, bacteriorhodopsin, into liposomes. The protein converts light energy into chemical energy by synthesizing ATP. The ATP runs the motor and then gets recycled back to adenosine diphosphate in a closed chemical system. A nanotube bearing could provide frictionless rotation without wear.
Molecular motors and Nano Bearings and Engines: That's the way the agenda listed two speeches at ASME's recent nanotechnology workshop in Washington. For engineers in the audience inclined toward the pragmatic, surely these two talks, by Carlo Montemagno and Alex Zettl, would warrant attention. They did.
Montemagno heads the nanoscale biological engineering and transport research group at Cornell University's nanofabrication lab. Recently, his group powered a nanometer-scale device using a biological motor.
During the December 2000 nanotechnology conference, Montemagno was quick to caution that the device, although it imitated the whirling blade of a helicopter, should in no way conjure up images of microscopic rotorcraft being injected into the bloodstream to seek and destroy cancer cells. That's still science fiction. But the science fact is fantastic enough.
The prime mover in Montemagno's experiments was one of nature's own, the biomolecular motor F1-ATPase-anenzyme that uses adenosine triphosphate, or ATP, for its energy source. The Cornell group, in a series of experiments lasting more than a year, was able to mount biomolecular motors to nickel-capped posts, attach propellers to the motors, and then, after immersing the bitty machines in ATP solutions, videograph a propeller turning.
Montemagno ran the video for conference attendees. As the audience watched the propeller spin counterclockwise, a dust particle entered the image. The vortex from the propeller sucked the particle in, then spat it out near the bottom of the frame.
"The motor ran for a little over two and a half hours," he said, "and our efficiency was about 82 percent. If you consider that the motor is running at room temperature, and it's a purely chemical reaction, that's quite extraordinary."
The group made the propellers large-750 nm long by 106 nm wide-specifically so they would show up on video, Montemagno said. The motors themselves were diminutive by comparison, a mere 11 nm in diameter. The mounting posts were slightly fatter at 50 nm across.
The video's bouncing dust particle helped put a frame of reference around this nano world. According to Michael Roukes, a physics professor at California Institute of Technology, where MEMS can take structural features down to a single micrometer, nano-scaled structures can similarly take features down to a single nanometer. That's a world where dust is the wrecker's ball
Indeed, one of the biggest problems with the Cornell nanomotor is its sensitivity to dust. "Every time they fail, dust has always been the culprit," Montemagno said. Cleanliness also played a role in making the propellers. That time, though, it was more a problem of the chemicals used to make nanostructures being incompatible with biological materials.
"We had to try and make the fabrication process ultraclean," he said, "because we found that having one or two molecules of KOH (potassium hydroxide) or whatever would kill your protein."
In microelectromechanical work, "Everything we make is on the chip, and everything that comes off the chip is washed away," Montemagno said. But making the nanoscale propellers turned that idea back on itself. The researchers needed to make the propellers on the chip and harvest them, rather than rinse them off. After trial and error, the Cornell engineers came upon a workable combination of biochemical methods and fabrication techniques.
Drag force of a biological medium was another concern of the group as it engineered its device, Montemagno said. Drag force in the solution increased by the power of six as the tiny propellers neared the substrate, he explained.
"The drag forces right comes a sensor, and that allows you to have some engineering utility," he added. Mounting a 2-micrometer polystyrene sphere to the motor, the Cornell researchers made a mechanical amplifier to evaluate the motion of the F1-ATPase enzyme. The group was seeking additional information that mechanical engineers might need when they begin coupling such motors at the surface become so high that anything this small couldn't move," he said. To get around this block, the group built motor mounts using silicon dioxide deposition to raise the motors up off the substrate. To these posts, the experimenters applied electron-beam lithography and metallic deposition, tipping each one with nickel.
Then, using a technique that produced ordered, sequential addition of components, the researchers began assembling F1-ATPase motors to posts and propellers to motors.
As Montemagmo addressed an ASME audience made up, as a show of hands would later attest, almost entirely of mechanical engineers, he had already anticipated the question many in the room were no doubt thinking. How do you turn this scientific achievement into a device with practical value?
"We've repeated this a number of times," he said. "The basic premise seems to bear out. Now we want to move to the next step, making a practical device, a device that does real work."
Montemagno ticked off a list of tasks his group was tackling: understand better the force characteristics of the motor, find a fueling scheme more in scale with the motor, and figure out a way to actively control it. "When that happens, all of a sudden it be-comes a sensor, and that allows you to have some engineering utility," he added.
Mounting a 2-micrometer polystyrene sphere to the motor, the Cornell researchers made a mechanical amplifier to evaluate the motion of the F1-ATPase enzyme. The group was seeking additional information that mechanical engineers might need when they begin coupling such motors to devices, Montemagno said. For instance, the researchers discovered that the little motor actually wobbles, or steps, through three distinct 120-degree increments in one revolution. To learn this, Montemagno's team used a differential inferometer coupled to a laser spot tracker.
As for fueling its biological motors, the Cornell team opted to "take advantage of what biology gives us," Montemagno said. The group made a small photosynthetic cell by installing the protein, bacteriorhodopsin, into liposomes. The protein converts light energy into chemical energy by synthesizing ATP. The ATP runs the motor, he said, then gets recycled back to adenosine diphosphate in a "closed chemical system." The group has been able to run one motor continuously with such a cell by exposing a 350 by 350 11111 collecting area to 12- hour cycles of light and dark, he said.
Eye On The Future: Nanotechnology
"Biological motors do not work properly in all environments," said Alex Zettl, a physics professor at the University of California, Berkeley. Zettl, whose talk at the conference followed Montemagno's, suggested that biological motors would be impractical in areas of high temperatures or ultrahigh vacuums, for instance.
"Think of the Space Shuttle," Zettl said. "You don't have it covered in horsehide and fueled by wood. Synthetic materials work a lot better." For him, the benefit of exploring the biological side of the very small was what it could show engineers about the assembly of nanodevices. Ultimately, he thought nanodevices would be fabricated from synthetic materials able to withstand high frequencies, high temperatures, and high vacuums.
Zettl began by addressing the considerations necessary for working with nanotubes. It is their predicted properties that are most astonishing, he said.
"Nanotubes themselves come in different forms," Zettl said. The single wall tube, for instance, might typically be a nanometer in diameter and many micrometers long. Those that are very pure and moderately dispersed tend to crystallize into "ropes-sort of a spaghetti package of tubes," he said. Depending on the growth conditions, the tubes can nest concentrically to form multiwalled cylinders capped on the ends.
Researchers have predicted a set of impressive properties for nanotubes, Zettl said, such as "a record Young's modulus on the order of a terapascal, record strength, high thermal conductivity, and high electrical conductivity." But, Zettl cautioned, before building nanodevices from nano tubes, it would be a good idea to test the tubes to see how well the predictions match reality.
Zettl then pointed to a picture of a long nanotube suspended over a hole in the grid of a transmission electron microscope. The tube, about 10 walls thick, vibrated in response to thermal excitation, he said. The vibration, he added, was useful for analyzing the properties of the nanotube itself.
But analysis proved difficult. "I went to the best mechanical engineers I could find, and they said it's an impossible problem they've been working on for 20 years and they still haven't come close to solving the complex differential equations," Zettl said.
Zettl reached a compromise solution for finding Young's modulus by using an equation for the normal vibration mode of a cantilevered beam and taking temperature into account. Zettl said he found "exceptionally high values," on the order of 1.2 terapascals for a single wall nanotube. By contrast, carbon steel has a Young's modulus of 207 gigapascals.
Thermal conductivity turned out to be remarkable as well. "Down here you get into an interesting quantum regime where thermal conductivity becomes linear." At room temperature, for example, the thermal conductivity for diamond is on its way down, while the thermal conductivity of a nanotube is still going up, he said.
It was some of Zettl's "wild thoughts," however, that must have captivated at least some imaginations in the audience. "How do you manipulate things on the nanoscale?" Zettl asked. By brute force, he answered. You can build structures with a scanning tunneling microscope by moving individual atoms around. Or, you can use an atomic force microscope to push nanostructures around. The latter method has the advantage of working on insulators, he added.
Zettl's first wild thought was how a nanotube could make the "ultimate" tip for an atomic force microscope. He suggested growing a single-wall tube on the end of a standard tip. Make it too long, however, and it would flop around. Make it too short, and it wouldn't go deep. Instead, the ideal AFM tip should be made from a multiwall bundle, he said, one that is stepped down and held together by van der Waals forces. Such a tip could "take advantage of incredible stiffness," he said
For his second wild thought, Zettl's conjured up a nanobearing. Van der Waals forces permit sheets of carbon to slide past one another, he explained. Graphite makes an excellent lubricant. Two concentric shells would yield a bearing; multiwall tubes would create a multisleeve bearing
Another thought: the ultimate constant force nanospring. "Not a Hooke's law spring, where you pull on it and the restoring force is proportionate to the displacement," Zettl said. ''I'm talking constant force independent of displacement: a mass on a string over a pulley.
"What about just calculating the force, the energetics, of a nanotube core interacting with its shell?" Zettl asked. "This is van der Waals forces," he explained. The force, it turns out, remains the same regardless of the overlap between core and shell. "If you calculate the force in nanonewtons, it's sort of equivalent to the radius of the nanotube in nanometers," Zettl said.
"So, a typical 10-nanometer tube gives you 10 nanonewtons force."
Stronger than Dirt
As for nano-engines, Zettl said, "Operating with your favorite thermodynamic cycle-a Stirling cycle, say-fill a nanotube with gas, heat it with a match, expand the gas. That pushes the core out. You could have a nano steam engine."
Such an engine would benefit from two major nanotube strengths. Low friction is one ("It may be zero," Zettl said.) No seals needed is another.
No seals? "We tried to jam the bearing to test a multisleeve bearing. None of the crud even went inside," Zettl said. "Zero clearance," he proclaimed. "Perfection." No dirt molecule could get in; no gas molecule would get out.
That perfection relates to wear as well. Normally, he said, you look for wear in a part by cycling the thing a million times and then examining it for scratches beneath a powerful microscope. For a nanotube, you cycle it a few times, then see if any atoms have dislodged. "No matter how many times you move it up and down not a single atom is displaced.
Zero wear. A wear-free bearing," he said.
It is difficult to talk about nanotechnology without glancing occasionally at the future. For example, Zettl measured a carbon nanotube for its time of flight-the time it takes a core, drawn partly back from the shell, to retract. He measured 4.6 nanoseconds. This duration is comparable to a good computer that has electronic switching, he said.
"These are electromechanical switches that are switching at very, very fast times," he added.
"The nice thing about nanotubes is they seem relatively compatible with silicon electronic technology," Zettl said. That may mean that one day computers could use electromechanical switches.
Nanotechnology, many at the conference said, could present a way around what is looking like the end of electronic memory that expands according to the tenets of Moore's law.
To get there, though, devices will have to be engineered, Zettl said. Physicists are good at discussing great new technologies and new ideas, he said, but bringing ideas into existence demands engineering. "If you had physicists building a car, you'd say that there's a car that has incredible potential, but I'm not sure you'd want to drive it. You have to engineer it."
Zettl's words echoed an earlier statement Montemagno had made: "People who want to work in nanotechnology have to be willing to work in areas that they're not fully comfortable in," he said. The work requires practitioners who can draw from different specialties, who often find themselves many times removed from their original training. "They have to speak the language of many disciplines," Montemagno said.
It's a bright future, though. Montemagno expects to see the development of a single molecule sorter in the next three or four years. Beyond that time frame, he envisions applications such as "smart dust," which could be dispatched to monitor crops for stress, or sent off to Mars to extend the reach of scientific investigation.
He sees the possibility of a "pharmacy on a cell," where nanoscale machines might coerce cells into producing chemicals on demand, which could then be transported and released somewhere else within the body. Helicopter flights through arterial space, however, remain a far ways off .