Nanoparticle

A nanoparticle is a microscopic particle with at least one dimension less than 100 nm.

Nanoparticle research is currently an area of intense scientific research, due to a wide variety of potential applications in biomedical, optical, and electronic fields. Nanoparticles are of great scientific interest as they are effectively a bridge between bulk materials and atomic or molecular structures.

A bulk material should have constant physical properties regardless of its size, but at the nano-scale this is often not the case.

Size-dependent properties are observed such as quantum confinement in semiconductor particles, surface plasmon resonance in some metal particles and superparamagnetism in magnetic materials. The properties of materials change as their size approaches the nanoscale and as the percentage of atoms at the surface of a material becomes significant.

For bulk materials larger than one micrometre the percentage of atoms at the surface is minuscule relative to the total number of atoms of the material.

The interesting and sometimes unexpected properties of nanoparticles are not partly due to the aspects of the surface of the material dominating the properties in lieu of the bulk properties. Nanoparticles exhibit a number of special properties relative to bulk material.

For example, the bending of bulk copper (wire, ribbon, etc.) occurs with movement of copper atoms/clusters at about the 50 nm scale.

Copper nanoparticles smaller than 50 nm are considered super hard materials that do not exhibit the same malleability and ductility as bulk copper.

The change in properties is not always desirable.

Ferroelectric materials smaller than 10 nm can switch their magnetisation direction using room temperature thermal energy, thus making them useless for memory storage.

Suspensions of nanoparticles are possible because the interaction of the particle surface with the solvent is strong enough to overcome differences in density, which usually result in a material either sinking or floating in a liquid.

Nanoparticles often have unexpected visible properties because they are small enough to confine their electrons and produce quantum effects.

For example gold nanoparticles appear deep red to black in solution. Nanoparticles have a very high surface area to volume ratio.

This provides a tremendous driving force for diffusion, especially at elevated temperatures.

Sintering can take place at lower temperatures, over shorter time scales than for larger particles.

This theoretically does not affect the density of the final product, though flow difficulties and the tendency of nanoparticles to agglomerate complicates matters.

Nanomaterials

Nanomaterials is a field which takes a materials science-based approach to nanotechnology. It studies materials with morphological features on the nanoscale, and especially those which have special properties stemming from their nanoscale dimensions. Nanoscale is usually defined as smaller than a one tenth of a micrometer in at least one dimension, though this term is sometimes also used for materials smaller than one micrometer.


An aspect of nanotechnology is the vastly increased ratio of surface area to volume present in many nanoscale materials which makes possible new quantum mechanical effects, for example the “quantum size effect” where the electronic properties of solids are altered with great reductions in particle size. This effect does not come into play by going from macro to micro dimensions. However, it becomes pronounced when the nanometer size range is reached. A certain number of physical properties also alter with the change from macroscopic systems. Novel mechanical properties of nanomaterials is a subject of nanomechanics research. Catalytic activities also reveal new behaviour in the interaction with biomaterials.
Nanotechnology can be thought of as extensions of traditional disciplines towards the explicit consideration of these properties. Additionally, traditional disciplines can be re-interpreted as specific applications of nanotechnology. This dynamic reciprocation of ideas and concepts contributes to the modern understanding of the field. Broadly speaking, nanotechnology is the synthesis and application of ideas from science and engineering towards the understanding and production of novel materials and devices. These products generally make copious use of physical properties associated with small scales.


As mentioned above, materials reduced to the nanoscale can suddenly show very different properties compared to what they exhibit on a macroscale, enabling unique applications. For instance, opaque substances become transparent (copper); inert materials attain catalytic properties (platinum); stable materials turn combustible (aluminum); solids turn into liquids at room temperature (gold); insulators become conductors (silicon). Materials such as gold, which is chemically inert at normal scales, can serve as a potent chemical catalyst at nanoscales. Much of the fascination with nanotechnology stems from these unique quantum and surface phenomena that matter exhibits at the nanoscale.


Uniformity

The chemical processing and synthesis of high performance technological components for the private, industrial and military sectors requires the use of high purity ceramics, polymers, glass-ceramics and material composites. In condensed bodies formed from fine powders, the irregular sizes and shapes of nanoparticlesin a typical powder often lead to non-uniform packing morphologies that result in packing density variations in the powder compact.
Uncontrolled agglomeration of powders due to attractive van der Waals forces can also give rise to in microstructural inhomogeneities. Differential stresses that develop as a result of non-uniform drying shrinkage are directly related to the rate at which the solvent can be removed, and thus highly dependent upon the distribution of porosity. Such stresses have been associated with a plastic-to-brittle transition in consolidated bodies, and can yield to crack propagation in the unfired body if not relieved.


In addition, any fluctuations in packing density in the compact as it is prepared for the kiln are often amplified during the sintering process, yielding inhomogeneous densification. Some pores and other structural defects associated with density variations have been shown to play a detrimental role in the sintering process by growing and thus limiting end-point densities. Differential stresses arising from inhomogeneous densification have also been shown to result in the propagation of internal cracks, thus becoming the strength-controlling flaws.
It would therefore appear desirable to process a material in such a way that it is physically uniform with regard to the distribution of components and porosity, rather than using particle size distributions which will maximize the green density. The containment of a uniformly dispersed assembly of strongly interacting particles in suspension requires total control over particle-particle interactions. It should benoted here that a number of dispersants such as ammonium citrate (aqueous) and imidazoline or oleyl alcohol (nonaqueous) are promising solutions as possible additives for enhanced dispersion and deagglomeration. Monodisperse nanoparticles and colloids provide this potential.


Monodisperse powders of colloidal silica, for example, may therefore be stabilized sufficiently to ensure a high degree of order in the colloidal crystal or polycrystalline colloidal solid which results from aggregation. The degree of order appears to be limited by the time and space allowed for longer-range correlations to be established. Such defective polycrystalline colloidal structures would appear to be the basic elements of submicrometer colloidal materials science, and, therefore, provide the first step in developing a more rigorous understanding of the mechanisms involved in microstructural evolution in high performance materials and components.

What are Nanorobots

Nanorobots are theoretical microscopic devices measured on the scale of nanometers (1nm equals one millionth of 1 millimeter). When fully realized from the hypothetical stage, they would work at the atomic, molecular and cellular level to perform tasks in both the medical and industrial fields that have heretofore been the stuff of science fiction.

A few generations from now someone diagnosed with cancer might be offered a new alternative to chemotherapy, the traditional treatment of radiation that kills not just cancer cells but healthy human cells as well, causing hair loss, fatigue, nausea, depression, and a host of other symptoms. A doctor practicing nanomedicine would offer the patient an injection of a special type of nanorobot that would seek out cancer cells and destroy them, dispelling the disease at the source, leaving healthy cells untouched. The extent of the hardship to the patient would essentially be a prick to the arm. A person undergoing a nanorobotic treatment could expect to have no awareness of the molecular devices working inside them, other than rapid betterment of their health.

Nanomedicine's nanorobots are so tiny that they can easily traverse the human body. Scientists report the exterior of a nanorobot will likely be constructed of carbon atoms in a diamondoid structure because of its inert properties and strength. Super-smooth surfaces will lessen the likelihood of triggering the body's immune system, allowing the nanorobots to go about their business unimpeded. Glucose or natural body sugars and oxygen might be a source for propulsion, and the nanorobot will have other biochemical or molecular parts depending on its task.

According to current theories, nanorobots will possess at least rudimentary two-way communication; will respond to acoustic signals; and will be able to receive power or even re-programming instructions from an external source via sound waves. A network of special stationary nanorobots might be strategically positioned throughout the body, logging each active nanorobot as it passes, then reporting those results, allowing an interface to keep track of all of the devices in the body. A doctor could not only monitor a patient's progress but change the instructions of the nanorobots in vivo to progress to another stage of healing. When the task is completed, the nanorobots would be flushed from the body.

Molecular nanotechnology (MNT), the umbrella science of nanomedicine, envisions nanorobots manufactured in nanofactories no larger than the average desktop printer. The nanofactories would use nano-scale tools capable of constructing nanorobots to exacting specifications. Design, shape, size and type of atoms, molecules, and computerized components included would be task-specific. Raw material for making the nanorobots would be nearly cost-free, and the process virtually pollution-free, making nanorobots an extremely affordable and highly attractive technology.

The first generation of nanorobots will likely fulfill very simple tasks, becoming more sophisticated as the science progresses. They will be controlled not only through limited design functionality but also through programming and the aforementioned acoustic signaling, which can be used, notably, to turn the nanorobots off.

Robert A. Freitas Jr., author of Nanomedicine, gives us an example of one type of medical nanorobot he has designed that would act as a red blood cell. It consists of carbon atoms in a diamond pattern to create what is basically a tiny, spherical pressurized tank, with "molecular sorting rotors" covering just over one-third of the surface. To make a rough analogy, these molecules would act like the paddles on a riverboat grabbing oxygen (O2) and carbon dioxide (CO2) molecules, which they would then pass into the inner structure of the nanorobot.

The entire nanorobot which Freitas dubbed a respirocyte, consists of 18-billion atoms and can hold up to 9-billion O2 and CO2 molecules, or just over 235 times the capacity of a human red blood cell. This increased capacity is made possible because of the diamond structure supports greater pressures than a human cell. Sensors on the nanorobot would trigger the molecular rotors to either release gasses, or collect them, depending on the needs of the surrounding tissues. A healthy dose of these nanorobots injected into a patient in solution, Freitas explains, would allow someone to comfortably sit underwater near the drain of the backyard pool for nearly four hours, or run at full speed for 15 minutes before taking a breath.

While potential medical and even military applications seem obvious for this one simple type of nanorobot, implications for every-day life are also intriguing. Imagine scuba diving without tank or regulator, but a swarm of respirocytes in your bloodstream; or the 2030 Olympics when, perhaps, super-athletes will not be scanned for drugs, but for nanorobotic augmentation.

Although nanorobots applied to medicine hold a wealth of promise from eradicating disease to reversing the aging process (wrinkles, loss of bone mass and age-related conditions are all treatable at the cellular level), nanorobots are also candidates for industrial applications. In great swarms they might clean the air of carbon dioxide, repair the hole in the ozone, scrub the water of pollutants, and restore our ecosystems.

Early theories in The Engines Of Creation (1986), by "the father of nanotechnology," Eric Drexler, envisioned nanorobots as self-replicating. This idea is now obsolete but at the time the author offered a worst-case scenario as a cautionary note. Runaway microscopic nanobugs exponentially disassembling matter at the cellular level in order to make more copies of themselves - a situation that could rapidly wipe out all life on Earth by changing it into "gray goo." This unlikely but theoretically feasible ecophage triggered a backlash and blockade to funding. The idea of self-replicating nanobugs rapidly became rooted in many popular science fiction themes including Star Trek's nanoalien, the Borg.

Over the years MNT theory continued to evolve eliminating self-replicating nanorobots. This is reflected in Drexler's later work, Nanosystems (1992). The need for more control over the process and position of nanomachines has led to a more mechanical approach, leaving little chance for runaway biological processes to occur.


Nanorobots are poised to bring the next revolution in technology and medicine, replacing the cumbersome and toxic Industrial Age and opening humankind up to incredible possibilities. But while gray goo is no longer a central concern, more potential dangers and abuses of nanotechnology remain under serious consideration by scientists and watchdog groups alike.

Nanorobotics

Nanorobotics is the technology of creating machines or robots at or close to the microscopic scale of a nanometer (10−9 meters). More specifically, nanorobotics refers to the still largely hypothetical nanotechnology engineering discipline of designing and building nanorobots, devices ranging in size from 0.1-10 micrometers and constructed of nanoscale or molecular components. As no artificial non-biological nanorobots have yet been created, they remain a hypothetical concept. The names nanobots, nanoids, nanites or nanomites have also been used to describe these hypothetical devices.

Another definition sometimes used is a robot which allows precision interactions with nanoscale objects, or can manipulate with nanoscale resolution. Following this definition even a large apparatus such as an atomic force microscope can be considered a nanorobotic instrument when configured to perform nanomanipulation. Also macroscale robots or microrobots which can move with nanoscale precision can also be considered nanorobots.

Nanomachines are largely in the research-and-development phase[1], but some primitive molecular machines have been tested. An example is a sensor having a switch approximately 1.5 nanometers across, capable of counting specific molecules in a chemical sample. The first useful applications of nanomachines, if such are ever built, might be in medical technology, where they might be used to identify cancer cells and destroy them. Another potential application is the detection of toxic chemicals, and the measurement of their concentrations, in the environment. Recently, Rice University has demonstrated a single-molecule car which is developed by a chemical process and includes buckyballs for wheels. It is actuated by controlling the environmental temperature and by positioning a scanning tunneling microscope tip.

More specifically, nanorobotics refers to the still largely theoretical nanotechnology engineering discipline of designing and building nanorobots.

Nanorobots (nanobots or nanoids) are typically devices ranging in size from 0.1-10 micrometres and constructed of nanoscale or molecular components.

As no artificial non-biological nanorobots have so far been created, they remain a hypothetical concept at this time.

Another definition sometimes used is a robot which allows precision interactions with nanoscale objects, or can manipulate with nanoscale resolution.

Following this definition even a large apparatus such as an atomic force microscope can be considered a nanorobotic instrument when configured to perform nanomanipulation.

Also, macroscale robots or microrobots which can move with nanoscale precision can also be considered nanorobots.

Molecular Manufacturing

Molecular manufacturing is the hypothetical future use of reprogrammable nanoscale "assemblers" to build products atom by atom. A molecular assembler would be a nanoscale robotic manipulator capable of placing single atoms, for example carbon, onto a surface with atomic precision. An everyday person would experience this technology in the form of a "nanofactory," a self-contained desktop molecular manufacturing unit that uses a purified feedstock material, such as propane gas.

For a molecular assembler to be useful to humans, it would have to be able to make copies of itself. Otherwise, it would take too long for a single assembler to build anything of significant size or value. If a large array of assemblers could be made to cooperate, they could construct macroscale products with atomic precision, using a fully automated process with high throughput. This is significant enough that, if the technical obstacles are overcome, the technology would launch another Industrial Revolution, probably more transformative than the first two put together.

Molecular assemblers and molecular manufacturing are nothing new. We have trillions of them in our bodies: organelles called ribosomes. Working in large numbers, ribosomes synthesize every protein in every organism in nature, from extremophile microbes to the blue whale. Their basic design is all the same, because every living thing evolved from a common ancestor that already had the basic protein synthesis machinery in place. Of course, ribosomes are also self-replicating.

If an inorganic molecular assembler were created capable of making copies of itself, it could create a new form of "life," albeit a type controlled directly by programming. This idea has been called molecular manufacturing, and some of the technical details for it have actually been worked out. Theorists have designed physically-viable nanoscale gears, motors, batteries, wires, moving rods, sorters, shafts, and more. Some of these nanoscale devices have already been fabricated, others are being actively worked on.


Molecular manufacturing has the potential to turn society upside-down, but barely anyone has heard of it. Often, the ideas of molecular manufacturing are combined or conflated with other possible applications of the wider field of nanotechology in general, which makes it difficult to come up with regulation policies for the latter. One study found that public opinions on nanotechnology could easily be manipulated by changing just a few sentences in the way the topic is introduced. These gaps in knowledge are worrisome to some futurists and policymakers, who would like to see more discussion on the futuristic possibilities of molecular manufacturing, and the way it might be regulated.

Molecular Nanotechnology

Molecular nanotechnology is an anticipated manufacturing technology that would allow precise control and positional assembly of molecule-sized building blocks through the use of nano-scale manipulator arms. Molecular nanotechnology is usually considered distinct from the more inclusive term "nanotechnology", which is now used to refer to a wide range of scientific or technological projects that focus on phenomena or properties of the nanometer scale (around 0.1-100nm). Nanotechnology is already a blossoming field, but molecular nanotechnology — the goal of productive, molecular-scale machine systems — is still in the preliminary research stage.


Nanotechnology was first introduced in 1959, in a talk by the Nobel Prize-winning physicist Richard Feynman, entitled "There's Plenty of Room at the Bottom". Feynman proposed using a set of conventional-sized robot arms to construct a replica of themselves, but one-tenth the original size, then using that new set of arms to manufacture an even smaller set, and so on, until the molecular scale is reached. If we had many millions or billions of such molecular-scale arms, we could program them to work together to create macro-scale products built from individual molecules — a "bottom-up manufacturing" technique, as opposed to the usual technique of cutting away material until you have a completed component or product — "top-down manufacturing".

Feynman's idea remained largely undiscussed until the mid-80s, when the MIT-educated engineer K. Eric Drexler published "Engines of Creation", a book to popularize the potential of molecular nanotechnology. Because MNT would allow manufacturers to fabricate products from the bottom up with precise molecular control, a very wide range of chemically possible structures could be created. Since MNT systems could put every molecule in its specific place, molecular manufacturing processes could be very clean and efficient. Also, because every little bit of matter in an molecular nanotechnology system would be part of a nano-scale manipulator, nanotechnological systems could be far more productive and maintain much higher throughputs than modern manufacturing techniques, which use macro-scale manipulators to fabricate products.


To initiate an MNT revolution would require an "assembler" — a reprogrammable nano-scale manipulator capable of creating a wide range of molecular structures, including a complete copy of itself. The first assemblers will only function effectively in lab-controlled environments, such as a vacuum. The advent of self-replicating molecular nanomachines could quickly lead to "desktop nanofactories", tabletop appliances that consume modest amounts of power and contain the software required to manufacture an interesting range of useful products. The arrival of MNT would revolutionize wide sectors of human activity, including manufacturing, medicine, scientific research, communication, computing, and warfare. When full-blown molecular nanotechnology will arrive is currently unknown, but some experts foresee its arrival sometime between 2010 and 2030.

Biotechnology as a route to nanotechnology

Introduction
Nanotechnology is creating a growing sense of excitement because we see an opportunity of unprecedented magnitude looming on the horizon: the ability to arrange and rearrange molecular structures in most of the ways consistent with physical law. This will have a pervasive impact on how we manufacture almost everything -- what is manufacturing but a way to arrange atoms? If we can arrange atoms with greater precision, at lower cost, and with greater flexibility then almost all the familiar products in our world will be revolutionized. To name just three: we'll pack more computational power into a sugar cube than exists in the world today, we'll make inexpensive structural materials that are as light and strong as diamond (which will have a major impact on the aerospace industry), and we'll make surgical tools and instruments that are molecular in their size and precision, able to intervene directly at the fundamental level where most sickness and disease are caused.

Underlying the excitement is a very simple fact: while atoms can be arranged in almost infinite permutations, today we can make only an infinitesimal fraction of what is possible. Very roughly, if we can pack 100 atoms into a cubic nanometer, and each atom can be any of the approximately 100 elements, then there are something like 100100 different ways we can arrange the atoms in just a single cubic nanometer. A cubic micron expands this to 100100000000000, while an object the size of you or me makes even this number seem vanishingly small. The goal that now seems possible: to take a healthy bite out of this enormous range of possibilities; to make most of the things that are possible, rather than an infinitesimally small fraction.

In 1959 Feynman said: "The principles of physics, as far as I can see, do not speak against the possibility of maneuvering things atom by atom. It is not an attempt to violate any laws; it is something, in principle, that can be done; but in practice, it has not been done because we are too big." More recently, Smalley said "Most interesting structures that are at least substantial local minima on a potential energy surface can probably be made one way or another."
The breathtaking magnitude of this opportunity is attracting interest. Neal Lane, the Director of NSF, said: "The possibilities of nanotechnology are endless. Entirely new classes of incredibly strong, extremely light and environmentally benign materials could be created" and went on to discuss inexpensive superconductors and medical applications. NSF is backing up this rhetoric with grants. NASA has a computational molecular nanotechnology research group examining the ways in which this technology can be used to advance the exploration and human habitation of space. IBM is doing pathbreaking research to revolutionize computing. Storing one bit in a few atoms no longer seems outlandish, and molecular switches will someday replace the bulky devices made today using optical lithography.

As we move beyond the vision and start asking how we are going to do this and how long it will take, opinions begin to diverge. Should we make ever better scanning probe microscopes (SPM's)? These remarkable instruments have already demonstrated an ability to move atoms and molecules on a surface in a controlled way (often spelling out names of interest to the researchers or their sponsors), but have so far been confined to two dimensions. Stacking molecules one on top of another is the next obvious goal, which will no doubt be accomplished in the next few years. Could these versatile instruments go on to make molecular machines?
Or perhaps the design and modification of proteins and their self assembly will provide the key to progress? Living systems already use many molecular machines, such as molecular motors. Could we adapt them to our own uses, perhaps using them to power tiny pumps or open and close tiny valves?1

There are many novel uses of existing biopolymers that could provide us with new tools. DNA, for example, is known primarily for its ability to encode information. But it can also produce structures as complex as a truncated octahedron2 and even provide power when it's chemical conformation changes in response to changes in its environment3.
The great diversity of proposals, ideas, and experimental capabilities makes it very difficult to predict exactly how we will proceed towards the more general goals of nanotechnology. Yet there are a few principles that seem both powerful enough and clear enough that they can provide some sort of framework for orienting ourselves. The first principle we consider is that of positional assembly.
Positional assemblyThere are two main ways to assemble parts. In self assembly, the parts move randomly under the influence of thermal noise and explore the space of possible mutual orientations. If some particular arrangement is more stable, then it will be preferred. Given sufficient time, this preferred arrangement will be adopted. For example, two complementary strands of DNA in solution will eventually find each other and stick together in a double-helical configuration.

In positional assembly, some restoring force keeps the part positioned at or near a particular location, and two parts are assembled when they are deliberately moved into close proximity and linked together. While common at the scale of humans (we commonly hold, position and assemble parts with our hands) this ability is still quite novel at the molecular scale. Thermal noise still plays a significant role, as "holding" a molecular part does not provide absolute certainty about its position but instead imposes a bias on the range of positions it can adopt. Using a linear approximation, an object might be subjected to a restoring force F which is proportional to its distance from the desired location, i.e., F = ks x, where x is the distance between the part and its desired location, and ks is the restoring force.
Restoring forces on the order of 10 N/m (Newtons/meter) or better can be achieved with scanning probe microscopes, which can position an object quite accurately. The fundamental equation relating positional uncertainty, temperature and stiffness is4:
s2 = kbT/ks

Where s is the mean error in position, kb is Boltzmann's constant, T is the temperature in Kelvins, and ks is the "spring constant" of the restoring force. If ks is 10 N/m, the positional uncertainty s at room temperature is ~0.02 nm (nanometers). This is accurate enough to permit alignment of molecular parts to within a fraction of an atomic diameter. It is important to remember, however, that the actual error could be many times s. The probability that the actual error is xerr is exp[-ks xerr2/(2s2)] / (s sqrt(2p)). Errors of a few times s are common, but errors of 20 times s would be extremely unlikely.

The distinction between self assembly and positional assembly is not binary, but moves continuously along a scale depending on the positional uncertainty (which is a function of the restoring force and the temperature). When the positional uncertainty s is large, we are near the self assembly end of the spectrum. When s is small, we are at the positional assembly end of the spectrum. Intermediate points along this spectrum are occupied by, for example, a molecule "tethered" to an SPM tip by a polymer; or an object held by optical tweezers (a restoring force of 10-4 N/m implies a positional uncertainty s at room temperature of ~6 nm).

While the SPM provides programmable positional control (you can adjust x, y and z to essentially any values), a simple form of positional assembly can also be seen in enzymes which bind two substrate molecules. The two bound molecules are positioned with respect to each other, thus facilitating their assembly. A limited form of positional assembly is also used in the ribosome, which can position the end of a growing protein adjacent to the next amino acid to be incorporated into that protein5.

This combination of positional assembly and self assembly can also be seen at the macroscopic scale. The vibratory bowl feeder6 is commonly used in manufacturing to position parts with sizes on the order of a centimeter. The bowl is shaken by a motor, causing parts in the bowl to bounce onto and along a spiral track leading out of the bowl. By careful design of the track, parts in the right orientation continue to move along it, out of the bowl and into further assembly steps. Parts in the wrong orientation are bounced back into the bowl, where they can try again to move up the spiral path leading out of the bowl.

While the power of self assembly has been amply demonstrated by the wide range of complex molecular structures it has made (including a remarkable range of biological structures), we have barely begun to explore the power of positional assembly at the molecular scale. Despite this, it seems clear that this new capability will play a major role in our future ability to synthesize molecular structures. The power of positional assembly has been amply demonstrated at the macroscopic scale in today's factories and by our own ability to make things with our hands. While its application at the molecular scale will differ in many details, it will provide a new and remarkably powerful tool for extending the range of structures that we can make.

Biotechnology and programmable positional control

Schematic illustration of a Stewart platform. The lower (blue) triangle forms the base, while the upper (green) triangle froms the platform.
The position and orientation of the platform with respect to the base can be controlled in six degrees of freedom (X, Y, Z, rool, pitch, and yaw) by adjusting the lengths of the six gray struts.

Today's SPMs are large, relatively slow, and will never make mole quantities of product. If we really want positional assembly to make products in the volume that ribosomes make proteins, we must have small, fast positional devices7. Yet it seems unlikely that biotechnology will directly give us a molecular robotic arm.

Which brings us to the Stewart platform8,9,10. This device, basically an octahedron six of whose struts can be lengthened or shortened under programmatic control (see illustration), provides six degree of freedom positional control for the "platform," (the green triangle at the top of the octahedron) with respect to its base (the blue triangle at the bottom of the octahedron). The ability to make an octahedron does not seem beyond the capabilities of biotechnology (in the broad sense of the term), particularly when the ability to self assemble a truncated octahedron has already been demonstrated by Seeman2.

All we need are twelve stiff struts, some way to make their ends stick together, and some way to lengthen or shorten six of those struts. As the latter seems the harder problem, we discuss one possible approach to solving it.

Consider a single strut: how can we change its length? One way would be to use two struts that overlap, and then make them slide past each other in a controlled fashion. Suppose that the first strut is made of three repeat units, ABCABCABCABCABC...., while the second strut is also made of three repeat units, XYZXYZXYZXYZ.... If we want to combine these two struts into one long strut, then we have to join them together. Suppose we use "joiners" that have two ends: one end binds to the A units of the first strut, while the other end binds to the X units of the second strut. Then, as illustrated above, the two struts would be held together by this a-x joiner to form a single longer strut.

But how can we change the position of the ABC strut with respect to the XYZ strut? First, we add a c-y joiner. These new joiners will bridge between the C and Y units of the ABC and XYZ struts. They will at first be strained, but as we add more and more c-y joiners they will start to balance out the a-x joiners. If we now wash the a-x joiners out of solution (the simplest arrangement would be to anchor the octahedron in place by a tether, and flow a solution with an appropriate concentration of joiners past them), then the c-y joiners will dominate the linkage between the two struts leading to the results in the final illustration, below. At this point, the ABC and XYZ struts have moved past each other by one monomer.

If we repeat the whole process again, this time washing in a b-z joiner and washing out the c-y joiner, we can again move the two struts over by one monomer. Finally, if we wash in an a-x joiner and wash out the b-z joiner, we are back where we started. By repeating the whole cycle, we can move the ABC strut past the XYZ strut as much as we want. By running the cycle in reverse, we can reverse the motion. In essence, we have a three-phase linear motor. While this is slow (it's limited by the speed at which we can wash the joiners into and out of position) it does provide a flexible means of controlling the length of the strut, and does not seem hopelessly difficult.

The essential point here is not that this particular approach is the right one or even necessarily a good one, but that biotechnology and self assembly can be used to make positional devices. This is just one possible way: there are a great many more.
Building blocksIf we are to use positional assembly, we must have something to assemble. In biotechnology and self assembly, the most common building blocks are monomers that are built into polymers. Each monomer has two linkage groups which let it become part of a chain. The best known polymers are proteins, DNA, and RNA5. Proteins and RNA form complex three dimensional structures because the monomers from which they are made have strong preferences in how they bind to each other. By appropriately arranging the linear sequence of monomeric units, it is possible to indirectly control the three dimensional structure of the resulting polymer.

While the demonstrated capabilities of this approach are remarkable, if we could hold and position building blocks in three dimensions we should be able to assemble complex three dimensional structures much more directly from building blocks. To this end, we require building blocks that have more than two linking groups (as two linking groups would give us polymers, which provide only indirect control over three dimensional structure). Three points define a plain, and so three groups are frequently found in two-dimensional structures. In graphite, for example, each carbon atom is joined to three neighbors. Four points define a three-space, so four linking groups in tetrahedral symmetry are well suited to the formation of three dimensional structures, much as the carbon atoms in diamond are each bonded to four neighbors.

In the near term, building blocks that are relatively large (many atoms) and which can be readily manipulated in solution are more likely to be experimentally accessible. While synthetic methodologies and reactions for arranging carbon atoms in desired patterns have been proposed4,11,12,13, these approaches require very controlled conditions, extremely good absolute positioning capbabilities, and very clean ultra-high vacuum environments. While these conditions should be achievable in the future, at present they present formidable experimental challenges. Molecular building blocks made from many atoms can be designed that are easier to manipulate, easier to link, less susceptible to contaminants, and more easily positioned. We need to start with large, easy to use building blocks.

If we are to build large, stiff structures then the building blocks themselves should be stiff. Drexler has proposed the use of artificially designed proteins in which simultaneous use of many stabilization techniques produces a protein that is much more stable than naturally occuring proteins14. The recent explosion of interest in fullerenes has produced not only functionalized C60, which is both large and stiff, but also long fullerene tubes which can be functionalized at the ends. Adamantane, essentially a small fragment of diamond, is a tetrahedrally symmetric molecule with a 10-carbon framework which is very stiff. Over 20,000 substituted or functionalized variants of adamantane are known, and even more are possible.

The linking groups between building blocks should also be strong and stiff. Krummenacker15 proposed the use of dienes and dieneophiles as linking groups which would combine in a Diels-Alder cycloaddition. Because the diene and dienophile are selectively reactive, molecular building blocks with these groups would be relatively immune to contaminants and the reaction could take place in any of a wide range of solvents.

The requirements for building blocks designed for positional assembly are not the same as the requirements for building blocks that self assemble. For example, positionally assembled building blocks must not only link with each other, they must also bind and release from the positional device. Drexler proposed the use of antibody-derived proteins bound to an SPM tip to provide a flexible method of binding to and positioning a wide range of building blocks4.
A second difference is that the linkage groups between positionally assembled building blocks can be much stronger. In self assembly, the use of many weak bonds (such as hydrogen bonds) provides a high degree of specificity in the inter-building-block reactions5. More reactive moieties (radicals, for example) would tend to combine promiscously, and so cause the self assembled building blocks to "clump" in random patterns rather than forming the desired structures. By contrast, positionally controlled building blocks can be more reactive, provided that encounters between building blocks are controlled. Rather than stirring positionally controlled building blocks together in solution, they could be introduced while bound to a surface. The positional device would pick them up from the surface and then move them to a work area where they would be joined to other building blocks which had already been formed into a partial structure. At no point would the positionally assembled building blocks be allowed to encounter each other in uncontrolled or random orientations, thus eliminating undesired side reactions.