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Many Options for Molecular Manufacturing


Molecular manufacturing is the use of programmable chemistry to build exponential manufacturing systems and high-performance products. There are several ways this can be achieved, each with its own benefits and drawbacks. This essay analyzes the definition of molecular manufacturing and describes several ways to achieve the requirements.

Exponential Manufacturing Systems

An exponential manufacturing system is one that can, within broad limits, build additional equivalent manufacturing systems. To achieve that, the products of the system must be as intricate and precise as the original. Although there are ways to make components more precise after initial manufacture, such as milling, lapping, and other forms of machining, these are wasteful and add complications. So the approach of molecular manufacturing is to build components out of extremely precise building blocks--molecules and atoms, which have completely deterministic structures. Although thermal noise will cause temporary variations in shape, the average shape of two components with identical chemical structures will also be identical, and products can be made with no loss of precision relative to the factories.

The intricacy of a product is limited by its inputs. Self-assembled nanotechnology is limited by this: the intricacy of the product has to be built into the components ahead of time. There are some molecular components such as DNA that can hold quite a lot of information. But if those are not used--and even if they are--the manufacturing system will be much more flexible if it includes a programmable manipulation function to move or guide parts into the right place.

Programmable Chemistry: Mechanosynthesis

Chemistry is extremely flexible, and extremely common; every waft of smoke contains hundreds or thousands of carbon compounds. But a lot of chemistry happens randomly and produces intricate but uncontrolled mixtures of compounds. Other chemistry, including crystal growth, is self-templating and can be very precise, but produces only simple results. It takes special techniques to make structures using chemistry that are both intricate and well-planned.

There are several different ways, at least in theory, that atoms can be joined together in precise chemical structures. Individual reactive groups can be fastened to a growing part. Small molecules can be strung together like beads in a necklace. It's been proposed that small molecules can be placed like bricks, building 3D shapes with the building blocks fastened together at the edges or corners. Finally, weak parts can be built by self-assembly--subparts can be designed to match up and fall into the correct position. It may be possible to strengthen these parts chemically after they are assembled.

Mechanosynthesis is the term for building large parts by fastening a few atoms at a time, using simple reactions repeated many times in programmable positions. So far, this has been demonstrated for only a few chemical reactions, and no large parts have been built yet. But it may not take many reactions to complete a general-purpose toolbox that can be used in the proper sequence and position to build arbitrary shapes with fairly small feature sizes. See http://foresight.org/stage2/project1A.html.

The advantage of a mechanosynthetic approach is that it allows direct fabrication of engineered shapes, and very high bond densities (for strength). There are two disadvantages. First, the range of molecular patterns that can be built may be small, at least initially--the shapes may be quite programmable, but lack the molecular subtlety of biochemistry. This may be alleviated as more reactions are developed.
Second, mechanosynthesis will require rather intricate and precise machinery--of a level that will be hard to build without mechanosynthesis. This creates a “bootstrapping” problem--how to build the first fabrication machine. Scanning probe microscopes have the required precision, or one of the lower-performance machine-building alternatives described in this essay may be used to build the first mechanosynthesis machine.

Programmable Chemistry: Polymers and Possibilities

Biopolymers are long heterogeneous molecules borrowed from biology. They are formed from a menu of small molecules called monomers stuck end-to-end in a sequence that can be programmed. Different monomers have different parts sticking out the sides, and some of these parts are attracted to the side parts of other monomers. Because the monomer joining is flexible, these attractive parts can pull the whole polymer molecule into a “folded” configuration that is more or less stable. Thus the folded shape can be indirectly programmed by choosing the sequence of monomers. Nucleic acid shapes (DNA and RNA) are a lot easier to program than protein shapes.

Biopolymers have been studied extensively, and have a very flexible
chemistry: it's possible to build lots of different features into one molecule. However, protein folding is complex (not just complicated, but inherently hard to predict), so it's only recently become possible to design a sequence that will produce a desired shape. Also, because there's only one chemical bond between the monomers, biopolymers can't be much stronger than plastic. And because the folded configurations hold their shapes by surface forces rather than strong bonds, the structures are not very stiff at all, which makes engineering more difficult. Biopolymers are constructed (at least to date) with bulk chemical processes, meaning that it's possible to build lots of copies of one intricate shape, but harder to build several different engineered versions. (Copying by bacteria, and construction of multiple random variations, don't bypass this limitation.) Also, reactants have to be flushed past the reaction site for each monomer addition, which takes significant time and leads to a substantial error rate.

A new kind of polymer has just been developed (see http://www.foresight.org/Conferences/AdvNano2004/Abstracts/Schafmeister/index.html).
It's based on amino acids, but the bonds between them are stiff rather than floppy. This means the folded shape can be directly engineered rather than emerging from a complex process. It also means the feature size should be smaller than in proteins, and the resulting shapes should be stiffer. This appears to be a good candidate for designing near-term molecular machine systems, since relatively long molecules can be built with standard solution chemistry. At the moment, it takes about an hour to attach each monomer to the chain, so a machine with many thousands of features would not be buildable.

There's a theorized approach that's halfway between mechanosynthesis and polymer synthesis. The idea is to use small homogeneous molecules that can be guided into place and then fastened together. Because this requires lower precision, and may use a variety of molecules and fastening techniques, this may be a useful bootstrapping approach. Ralph Merkle wrote a paper on it a few years ago (http://www.zyvex.com/nanotech/mbb/mbb.html).

A system that uses solution chemistry to build parts can probably benefit from mechanical control of that chemistry. Whether by deprotecting only selected sites to make them reactive, or mechanically protecting some sites while leaving others exposed, or moving catalysts and reactants into position to promote reactions at chosen sites, a fairly simple actuator system may be able to turn bulk chemistry into programmable chemistry.

Living organisms provide one possible way to use biopolymers. If a well-designed stretch of DNA is inserted into bacteria, then the bacteria will make the corresponding protein; this can either be the final product, or can work with other bacterial systems or transplanted proteins. (The bacteria also duplicate the DNA, which may be the final
product.) However, this is only semi-controlled due to complex interactions within the bacterial system. Living organisms dedicate a lot of structure and energy to dealing with issues that engineered systems won't have to deal with, such as metabolism, maintaining an immune system, food-seeking, reproduction, and adapting to environmental perturbations. The use of bacteria as protein factories has already been accomplished, but the use of bacteria-produced biopolymers for engineered-shape products has only been done in a very small number of cases (e.g. Shih's recent octahedra, see http://www.nature.com/nature/journal/v427/n6975/pdf/nature02307.pdf; in this case it was DNA, not protein), and only for relatively simple shapes.

Manufacturing Systems, Again

Now that we have some idea of the range of chemical manipulations, we can look at how those chemical shapes can be joined into machines.
Machines are important because some kind of machine will be necessary to translate programmed information into mechanical operations. Also, the more functions that can be implemented by nano-fabricated machines, the fewer will have to be implemented by expensive, conventionally manufactured hardware.

A system with the ability to build intricate parts by mechanosynthesis or small building blocks probably will be able to use the same equipment to move those shapes around to assemble machines, since the latter function is probably simpler and doesn't require much greater range of motion. A system based on biopolymers could in theory rely on self-assembly to bring the molecules together. However, this process may be slow and error-prone if the molecules are large and many different ones have to come together to make the product. A bit of mechanical assistance, grabbing molecules from solution and putting them in their proper places while protecting other places from incorrect molecules dropping in, would introduce another level of programmability.

Any of these operations will need actuators. For simple systems, binary actuators working ratchets should be sufficient. Several kinds of electrochemical actuators have been developed in recent months. Some of these may be adaptable for electrical control. For initial bootstrapping, actuators controlled by flushing through special chemicals (e.g. DNA strands) may work, although quite slowly. Magnetic and electromagnetic fields can be used for quite precise steering, though these have to be produced by larger external equipment and so are probably only useful for initial bootstrapping. Mechanical control by varying pressure has also been proposed for intermediate systems.

In order to scale up to handle large volumes of material and make large products, computational elements and eventually whole computers will have to be built. The nice thing about computers is that they can be built using anything that makes a decent switch. Molecular electronics, buckytube transistors, and interlocking mechanical systems are all candidates for computer logic.

High Performance Products

The point of molecular manufacturing is to make valuable products.
Several things can make a product valuable. If it's a computer circuit, then smaller component size leads to faster and more efficient operation and high circuit density. Any kind of molecular manufacturing should produce very small feature sizes; thus, almost any flavor of molecular manufacturing can be expected to make valuable computers. A molecular manufacturing system that can make all the expensive components of its own machinery should also drive down manufacturing cost, increasing profit margins for manufacturers and/or allowing customers to budget for more powerful computers.

Strong materials and compact motors can be useful in applications where weight is important, such as aerospace hardware. If a kilowatt or even just a hundred watt motor can fit into a cubic millimeter, this will be worth quite a lot of money for its weight savings in airplanes and space ships. Even if raw materials cost $10,000 a kilogram, as some biopolymer ingredients do, a cubic millimeter weighs about a milligram and would cost about a penny. Of course this calculation is specious since the mounting hardware for such a motor would surely weigh more than the motor itself. Also, it's not clear whether biopolymer or building-block styles of molecular manufacturing can produce motors with anywhere near this power density; and although the scaling laws are pretty straightforward, nothing like this has been built or even simulated in detail in carbon lattice.

Once a process is developed that can make strong programmable shapes out of simple cheap chemicals, then product costs may drop precipitously.
Mechanosynthesis is expected to achieve this, as shown by the preliminary work on closed-cycle mechanosynthesis starting with acetylene. No reaction cycle of comparable cost has been proposed for solution chemistry, but it seems likely that one can be found, given that some polymerizable molecules such as sugar are quite cheap.

Future Directions

This essay has surveyed numerous options for molecular manufacturing.
Molecular manufacturing requires the ability to inject programmability for engineering, but this can be done at any of several stages. For scalability, it also requires the ability to build nanoscale machines capable of building their duplicates. There are several options for machines of various compositions and in various environments.

At the present time, no self-duplicating chemical-building molecular machine has been designed in detail. However, given the range of options, it seems likely that a single research group could tackle this problem and build at least a partial proof of concept device--perhaps one that can do only limited chemistry, or a limited range of shapes, but is demonstrably programmable.

Subsequent milestones would include:
1) Not relying on flushing sequences of chemicals past the machine
2) Machines capable of general-purpose manufacturing
3) Structures that allow several machines to cooperate in building large products
4) Building and incorporating control circuits

Once these are achieved, general-purpose molecular manufacturing will not be far away. And that will allow the pursuit of more ambitious goals, such as machines that can work in gas (instead of solution) or vacuum for greater mechanical efficiency. Working in inert gas or vacuum also provides a possible pathway (one of several) to what may be the ultimate performer: products built by mechanosynthesis out of carbon lattice.

The Center for Responsible Nanotechnology(TM) (CRN) is an affiliate of World Care(R), an international, non-profit, 501(c)3 organization. All donations to CRN are handled through World Care. The opinions expressed by CRN do not necessarily reflect those of World Care


Chris has studied nanotechnology and molecular manufacturing for more than a decade. After successful careers in software engineering and dyslexia correction, Chris co-founded the Center for Responsible Nanotechnology in 2002, where he is Director of Research. Chris holds an MS in Computer Science from Stanford University.

Copyright © 2004 Chris Phoenix


Chris Phoenix

CRN Director of Research