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Unbounding the Future:

the Nanotechnology Revolution

Chapter 5

The Threshold of Nanotechnology

In the last chapter, we looked at the state of current research, but from there to the nanotechnology of even the Pocket Library scenario is a leap. How will this gap be crossed?

In this chapter, we outline how emerging technologies can lead to nanotechnology. The actual path to nanotechnology—the one that history books will record—could emerge from any one of the research directions in physics, biochemistry, and chemistry recounted in the last chapter, or (more likely) from a combination of them. The availability of so many good options builds confidence that the goal can be reached, even while it decreases confidence that some particular path will be fastest. To see how advances might cross the gap from present technology to early nanotechnology, let's follow one path out of the many possible.

Bridging the Gap

One way to bridge the gap would through the development of an AFM-based molecular manipulator capable of doing primitive molecular manufacturing. This device would combine a simple molecular device—a molecular gripper—with an AFM positioning mechanism. An AFM can move its tip with precision; a molecular manipulator would add a gripper to the tip to hold a molecular tool. A molecular manipulator of this kind would guide chemical reactions by positioning molecules, like a slow, simple, but enormous assembler. (In our standard simulation view, where a molecular assembler arm fits in a room, the AFM apparatus of a molecular manipulator would be the size of a moon.) Despite its limits, an AFM molecular manipulator will be a striking advance.

How might this advance occur? Since we're choosing one path out of many possible, we may as well include more details and tell a story. (A more technical description of a device like the following can be found in Nature; see the technical bibliography).

Scenario: Developing a Molecular Manipulator

Several years ago, researchers at the University of Brobdingnag began work on developing a molecular manipulator. To reach this goal, a team of a dozen physicists, chemists, and protein researchers banded together (some working full time, some part time) and began the creative teamwork needed to solve the basic problems.

First they needed to attach a gripper to an AFM tip. As grippers, they chose fragments of antibody molecules, the selectively sticky proteins that the immune system uses to bind and identify germs. If they could get the "back" of the molecule stuck onto a tip, then the "front" could bind and hold molecular tools. (The advantage of antibody fragments was this: freedom of tool choice. Since the late 1980s, researchers had been able to generate antibodies able to bind almost any preselected molecule-or molecular tool.) They tried half a dozen methods before finding one that worked reliably, with results like those shown in Figure 6. A graduate student got her Ph.D., and the AFM tip got its gripper.


A molecular manipulator (AFM tip and tool holder, above) would bind and position reactive molecular tools to build up a workpiece, molecule by molecule.

In parallel, the U. Brob AFM researchers worked on placing tips in a precise location and then holding them there with atomic accuracy for seconds at a time. This proved straightforward. They used techniques developed elsewhere during the early 1990s, adding only modest refinements.

They now had their gripper and a way of putting it where they wanted it, but they needed a set of tools. The gripper was like the chuck of a drill, waiting to have different bits fitted into its tool-holder slot. So as the final step, the synthetic chemists on the team made a dozen different molecular tools, all identical at one end but different at the other. The similar parts all bound to the same antibody tool-holder, slotting neatly into position. The different parts were all chemically reactive in different ways. Like the molecular tools in the hall of assembler arms in Chapter 3, each of these tools could use a chemical reaction to transfer some atoms to a molecular object under construction.

Developing the molecular tool kit was the toughest part of the project; it took about as much work as had gone into duplicating the palytoxin molecule back in the 1980s. None of the tasks in the project demanded the solution of a deep scientific puzzle, and none demanded the solution of a notoriously difficult engineering problem. Each task had many possible solutions, the problem was to find a compatible set of solutions and apply them. After a few years, the solutions came together and the U. Brob research team began building new molecules by molecular manipulation. Now many teams are doing likewise.

Building with Molecular Grippers and Tools

To build something with the U. Brob team's AFM-based molecular manipulator system, you use it as follows: First, choose a surface to build on and place it under the tip in a pool of liquid. Then dunk the AFM tip into the liquid, bringing it down to the surface, and back it off a little. Construction can now begin as soon as a tool is loaded into the gripper.

Tubes and pumps can flow different liquids over the surface and past the gripper, carrying different tool molecules. If you want to do something with a tool of Type A, you wash in the proper liquid, and a Type A molecule promptly sticks the to the gripper as shown in Figure 6. Once it is in the gripper, you can use the AFM mechanism to move it around and put it where you want it. Move it up to the surface at a convenient spot, wait a few seconds, and it reacts, forming a bond and leaving a molecular fragment attached to the spot you chose. To add a different fragment, you can use a tool of Type B: you back up the tip, flow in a fresh liquid carrying the new tools, and in a moment a tool of the new type is bound in place and ready to apply, either on or alongside the first spot. Step by step, you build up a precise molecular structure.

Each step takes only seconds. Molecular tools pop into the gripper in a fraction of a second, and used tools pop off at the same rate. Once the tip has positioned a molecule, it reacts quickly, about a million times faster than unwanted reactions at other sites. In this way, the molecular manipulator gives good control of where reactions will occur (though it is not as reliable as an advanced assembler would be). It is fairly fast by a chemist's standards—per cycle—but still a million times slower than an advanced assembler. It can perform a variety of steps, but isn't as flexible and capable as an advanced assembler. In short, it is hardly the last word in nanotechnology, yet is a great advance over what has gone before.


With its ability to accelerate desired reactions by a factor of a million or so, the U. Brob team's molecular manipulator can perform 10,000 to 100,000 steps with good reliability. Back in the 1980s, chemists making protein molecules struggled to perform just one hundred steps. The U. Brob research team (and its many imitators) can now build structures that are stronger and easier to design than proteins: not floppy, folded chains, but rugged objects held together by a sturdy network of bonds. Though not as strong and dense as diamond, these structures are like bits of a tough engineering plastic. A specially adapted computer-aided design system makes it easy to design molecular objects made from these materials.

Yet the AFM-based molecular manipulator has one grave disadvantage: It does chemistry one molecule at a time, and it ties up a machine as expensive as a car for hours or days to produce that one large molecule. Some molecules, though, are valuable enough to be worth building even one at a time. These draw prompt attention.

A single molecule isn't much use as a dye, a drug, or a floor wax, but it can have substantial value if it provides useful information. The U. Brob team quickly publishes a pile of scientific papers based on experiments with single molecules: they build a molecule, probe it, report the results, and build another. Some of these results show chemists elsewhere in the multibillion-dollar chemical industry how to design new catalysts, molecules that can help make other molecules more cheaply, cleanly, and efficiently. This information is worth a lot.

Three new products of special interest are among the first to be made. The first—molecular electronics—begins with experiments conducted by a research group at a computer chip company. They use their molecular manipulator to build single molecules and probe them, gradually learning how to build the parts needed for molecular electronic computers. These new computers don't immediately become practical, because the costs are too high for making such large molecules with AFM-based technology. Yet some companies begin to produce simpler molecular electronic devices for use in sensors and specialized high-speed signal processing. A specialty industry is born and begins to expand.

The second product is a gene reader, a complex molecular device built on the surface of a chip. The biologists who built the reader combined proteins borrowed from cells with special-purpose molecular machines designed from scratch. The result was a molecular system that binds DNA molecules and pulls them past a read-head-like tape through a tape recorder. The device works as fast as some naturally occurring molecular machines that read DNA, with one key advantage: it outputs its data electronically. At that speed, a single device can read a human genome in about a year. Though still too expensive for a doctor's office, these readers are promptly in great demand from research laboratories. Another small industry is born.

The third product is far more important, in the long run: replacement tips for molecular manipulators, grippers, and tools that are better than the originals. With these new, more versatile devices, researchers are now building more ambitious products and tools.

More Scenario: The Next Step to Nanotechnology

While the physicist-led team at U. Brob was finishing its work on the AFM-based molecular manipulator, a chemist-led team at the University of Lilliput was working furiously. They saw the U. Brob desktop machine as too large and its expected products as too expensive. Even back in the 1980s, David Biegelsen of the Xerox Palo Alto Research Center had noted, "The main drawback I see to using a hybrid protoassembler [AFM-based molecular manipulator] is that it would take a long time to build just one unit. Building requires a series of atom-by-atom construction steps. It would be better to build in parallel from the very beginning, making many trillions of these molecules all at the same time. I think there is tremendous power in parallel assembly. Maybe another field, chemistry or biology, offers a better way to do it." The chemists at U. Lill aimed to develop that better way, building first simple and then more and more complex molecular machines. The eventual result was a primitive molecular assembler able to build molecular objects by the trillions.

Chemist's Tools

How did the chemists achieve this? During the years when the U. Brob team was developing the molecular manipulator, researchers working in protein science and synthetic chemistry had made better and better systems of molecular building blocks. Chemists were well prepared for doing this: by the late 1980s, it had become possible to build stable structures the size of medium-sized protein molecules, and work had begun to focus on making these molecules perform useful work by binding and modifying other molecules. Chemists learned to use these sophisticated catalysts-early molecular devices-to make their own work easier by helping in the manufacture of still more large molecules.

Another traditional chemist's tool was software for doing computer-aided design. The early software designed by Jay Ponder and Frederic Richards of Yale University ultimately led to semi-automatic tools for designing molecules of a particular shape and function. Chemists then could easily design molecules that would self-assemble into larger structures, several tens of nanometers across.

Molecular Construction Machines

These advances in software and chemical synthesis let the U. Lill team tackle the task of building a primitive version of a molecular assembler. Although they couldn't build anything as complex as a nanocomputer or as stiff as diamond, they didn't need to. Their design used sliding molecular rods to position a molecular gripper much like the gripper used at U. Brob, again using the surrounding liquid to control which tool the gripper held. Instead of an AFM's electronic controls, they used the surrounding liquid to control the position of the rods as well. In a neutral solution, the rods would withdraw; in an acid solution, they would extend. How far they moved depended on what other molecules were around to lodge in special pockets and block the motion.

Their primitive assemblers built much the same sorts of products that the U. Brob molecular manipulator did; the tools were similar, and speed and accuracy were about the same. Yet there was one dramatic advantage: About 1,000,000,000,000,000,000,000 U. Lill assemblers could fit in the space occupied by one U. Brob manipulator, and it was easy to produce a mere 1,000,000,000,000,000 times as much product at the same cost.

With the first, primitive assemblers, construction was slow because each step required new liquid baths and several seconds of soaking and waiting, and a typical product might take thousands of steps. Nonetheless, the U. Lill team made a lot of money licensing their technology to researchers trying to commercialize products they had first researched with the U. Brob machine. After starting an independent company (Nanofabricators, Inc.), they poured their research efforts into building better machines. Within a few years, they had assemblers with multiple grippers, each loaded with a different kind of tool; flashes of colored light would flip molecules from state to state (they copied these molecules from the pigments of the retina of the eye); flipping molecules would change tools and change rod positions. Soaking and waiting become a thing of the past, and soon they were pouring out parts that, when mixed with liquid and added to dishes with special blank chips would build up the dense memory layers that made possible the Pocket Library.

That was when things started moving fast. The semiconductor industry went the way of the vacuum tube industry. Money and talent poured into the new technology. Molecular CAD tools got better, assemblers made it easy to build what was designed, and fast production and testing made molecular engineering as easy as playing with software. Assemblers got better, faster, and cheaper. Researchers used assemblers to build nanocomputers, and nanocomputers to control better, faster assemblers. Using tools to build better tools is an ancient story. Within a decade, almost anything could be made by molecular manufacturing, and was.


Nanotechnology development flow chart

Will developments in the late pre-breakthrough days be as just described? Certainly not: the technical approaches will differ, and the U.S. academic research setting implied by the scenario could easily be replaced by academic, commercial, governmental, or military research settings in any of the advanced nations. What do seem realistic are the implied requirements for effort, technology, and time, as well as the basic capabilities of different devices. We are approaching a threshold of capability beyond which further advances will become easy and fast.

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