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NANOTECHNOLOGY - Building up from atoms

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In 1959, the Nobel Prize winning physicist Richard Feynman said "There's plenty of room at the bottom." In this speech, he envisioned a discipline devoted to manipulating smaller and smaller units of matter. Feynman continued, "Ultimately-in the great future-we can arrange the atoms the way we want; the very atoms, all the way down!"

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In 1974 the term nanotechnology itself was coined by Norio Taniguchi at the University of Tokyo . Taniguchi, perceived engineering at the micrometer scale-so-called micro-technology-from a new, sub-micrometer level, which he dubbed "nano-technology."

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In 1986, MIT researcher Eric Drexler wrote "Engines of Creation", the book widely credited with bringing nanotechnology into the public's consciousness. He envisaged a nanoworld where nanomachines called assemblers and replicators would operate at the molecular level. The replicators would make trillions of copies of the assemblers to do useful work. He also postulated a ‘grey goo’ theory where replicators at the top of the food change would reproduce indefinitely and cover the Earth in ‘grey goo’.

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At the same time, researchers at the American Rice University in Houston Texas , were studying a bizarre molecule. By vaporizing carbon and allowing it to condense in an inert gas, Richard Smalley's research team observed that the carbon formed highly stable crystals of sixty atoms apiece. They suspected the crystals shared the familiar soccer-ball structure used in architect Buckminster Fuller's geodesic domes, and named their discovery "buckminsterfullerene," which was quickly shortened to "fullerene," or "buckyball."

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The buckyball remains nanotechnology's most famous discovery. It earned Smalley and his colleagues the 1996 Nobel Prize in Chemistry, and cemented nanotechnology's reputation as a cutting-edge research field. Having explained the prefix, it wouldn't do to overlook the workaday root. Nanotechnology is not just the study of the very small -- it is also very much a technology.

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New techniques, including laser tweezers and the atomic force microscope, have been developed to a point where they allow researchers to handle nanoscale objects (such as protein molecules) individually, to position them and to examine their response to experimentally induced changes of conditions

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Looks like a neon sign but this is 35 atoms of Xenon manipulated individually to form the sponsor’s logo.

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Scientists in the United States say they have made a motor that is more than 250 times smaller than the human hair, a breakthrough in the new frontier of nanotechnology. The gadget comprises a gold blade attached to an axle made from a carbon nanotube whose ends are anchored to two silicon dioxide electrodes. Voltage flows through the electrodes and down the conductive nanotube to rotate the blade. Three other electrodes — two placed either side of the axle, one underneath — provide additional voltage control, so that the speed of the blade, its direction and position can be governed precisely.

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The arrangement, so tiny that it has been imbedded in a silicon chip, is not the smallest nanoscale device in the world; that title belongs to experimental "bio-switches" made from molecular DNA and driven by chemicals. But, said the inventors, it offers several advantages. As an electrical-mechanical device, it can tolerate wider temperature ranges, operate in a vacuum and cope with harsher chemical environments than its "bio" equivalents.

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Nanotechnology is now moving from exploration to application. For instance, nanoscale electronics has seen rapid progress in the past couple of years thanks to competing approaches based on carbon nanotubes (championed by Cees Dekker at Delft, in the Netherlands) and nanowires (taken up by Charles Lieber at Harvard) in developing the first electronic components (transistors, simple circuits) made from nanoscale elements. The nanotube and nanowire may hold the key to the electronics of the future when the silicon chip reaches the limits of miniaturisation. As the smallest structures in computer chips are now well below the one micrometre size, one could count every new computer and mobile phone as a nanotechnology product. On the other hand, these products result from the steady progress of miniaturisation that has followed Moore 's Law (the doubling of computer performance every 18 months) over the past three decades. They arise from gradual improvements more than from new thinking.

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The first nanotechnology breakthrough outside the information technology market is the micro fabricated impact sensor to trigger airbags in cars. The new kind of sensor is based on a Mems (micro-electromechanical system) device, which means that it is fabricated by the same kind of technology as a computer chip, only that its function is mainly mechanical rather than electronic. When it was introduced in 1995, it turned out to be not only smaller and more efficient than the sensors previously available, but also 100 times cheaper. Understandably, it took over the world market in a matter of months.

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But how about products designed from molecules upwards? There is at least one that you can buy already. It is the self-cleaning window. It uses a combination of two clever molecular tricks. First, it contains a catalyst that uses the energy of light to oxidise common kinds of dirt, to convert them into smaller, more soluble molecules that wash away with rain water. At this point, the second trick comes in. Ordinary glass is fairly water-repellent (hydrophobic), which means that water does not cover it smoothly, but tends to form droplets. The surface of self-cleaning glass, however, is coated in molecules that attract water and encourage it to spread out. So, instead of sitting around as drops which leave drying spots when they evaporate, the rain will cover the surface evenly, dissolve what the photo catalyst made of the dirt, and run off. Simple.

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Yet it would not be possible without molecular design on the nanometre scale

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Further miniaturisation will mean that equipment can increasingly shrink out of sight, so a mobile phone might be no bigger than a shirt button (or be built into a hollow tooth). And after 25 years in which computers have become ubiquitous in our lives, they will now spend the next 25 years becoming invisible.

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At this scale, individual atoms have become visible. This image represents the packed nucleic acids (either DNA or RNA, but not both) that form the reproductive core of viruses. The double helix structure of the DNA is clearly visible. When the virus invades a living cell, the virus's DNA takes over the cellular mechanisms of the host to make more copies of itself.

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This is a representation of a portion of deoxyribonucleic acid, or DNA. The atom in the centre square is carbon, an essential building block for all life on Earth. Carbon bonds to other atoms in a number of different ways allowing for the formation of a multitude of molecules. DNA is a carbon-based molecule that forms a double helix -- a spiral ladder. The rungs of the ladder are composed of pairs of complimentary bases. Each base is attached to a sugar. The sugars are connected to each other along the rail of the ladder by phosphates. This image shows a very small piece of DNA -- about a third of one complete spiral. The length of a single coil of DNA is about 3 nm.

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One good reason to believe that this nanotech revolution will happen in medicine is everywhere around us: nature. Look in the mirror and you will see an incredibly complex structure, which has assembled itself from the genetic instructions encoded in the molecules of a single cell (the fertilised egg). Life has many layers of complexity, but all of them ultimately arise from what happens on the nanometre scale. Molecules interact with each other to form cells, cells form tissues, and tissues make animals.

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The living cell can do many things that are way beyond our technical abilities. It can read out the information of a single strand of DNA (we would have to "amplify" it to millions of copies before we could read it); it can produce complex molecular machines which self-assemble from many different parts; it can recognise faults on the molecular scale and fix them efficiently; and it can produce structures on the nanoscale that eventually combine to make amazing macro scale structures, such as a tree, an elephant or a human.

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Over the past five decades, scientists have learnt to understand the basic principles and details of how the nanotechnology of nature works. Mechanistic understanding of biological systems has progressed rapidly from the structure of DNA through to the genome sequences of Homo sapiens and a dozen other higher organisms. Some of the most important molecular machines of the cell have become open books. Scientists can download their structures and work out how they would interact, for instance, with a new drug. Even highly complex systems, like the photosynthesis machinery and the protein factory of the cell, can now be studied this way.

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While there are still many blank spaces on the map, the principles of the molecular machinery of life are now clear. They differ from the way we make small structures (such as computer chips) in a number of ways:

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Nature builds complex architecture from the bottom up, while computer engineers work from the large scale downwards.

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To achieve complexity, nature starts from simple building blocks, which can be lined up to chain molecules (such as DNA), then fold up to three-dimensional structures, then assemble to molecular machines.

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While chemists have been building molecular structures by making or breaking solid bonds between atoms (known as covalent bonds), nature does so by making use of so-called weak interactions, which can be formed and broken much more readily.

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Finally, when it comes to assembling a complex piece of equipment from a number of parts, there is no mechanic in the cell to put the parts together. The molecular parts are designed in such a clever way that they snap together by themselves.

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Chemists and biochemists working in the nanotechnology field typically use the bottom-up approach, borrowing one or several of these principles from nature.

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Further miniaturisation will mean that equipment can increasingly shrink out of sight, so a mobile phone might be no bigger than a shirt button (or be built into a hollow tooth). And after 25 years in which computers have become ubiquitous in our lives, they will now spend the next 25 years becoming invisible.

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But the biggest impact of forthcoming nanotechnology applications will probably be in medicine. Disease typically arises from malfunctioning at the cellular scale. Treating cells with a scalpel is like fixing a computer chip with an axe, and treating them with drugs that invade the whole body is like immersing a computer in a bath to clean up one chip. Nanomachines may perform surgery at the tissue and cell level. While many drugs work on the principle of addressing a property that is specific to the targeted cell type, unwanted side effects are still common in most drug treatments. Efficient therapy would address the right group of cells at the right time with the right doses. Ideally, a nanoscale device that could be implanted or worn on the skin near the organ in question should contain: sensors that assess the physiological state of the malfunctioning organ; a primitive computer that assesses the correct response; and compartments that release the drug molecules at the right time in the right place. The world’s smallest biological computer has already been built at the Weizman Institute in Israel and is just 100nm in size. Details were published in the journal Nature in April of this year. There are at least two areas in which we might see such developments in the near future. One is post-surgery pain treatment, used for example after hip replacements. It should soon become possible to implant a Mems-style drug release chip together with the artificial joint, which could take care of the patient's drug needs in a localised way and over a time scale of months. Secondly, diabetics could soon benefit from devices that combine insulin sensors and dispensers. As this disease is common, and the insulin supply from injections is never optimal, there would bea huge demand for such a device.

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A further important trend that will affect both the information technology and the biomedical applications of nanotechnology is the disappearance of the distinction we now make between biological and electronic systems. With the advent of molecular scale technology, electronic components will begin to resemble living cells more than silicon chips. On the other hand, faulty body parts will more and more easily be fixed by implants that might be on the micro or the nano scale. With very similar molecules being used on both sides, there will be a continuum of molecular devices linking the (as yet) distinct domains of biology and technology.

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While many drugs work on the principle of addressing a property that is specific to the targeted cell type, unwanted side effects are still common in most drug treatments. Efficient therapy would address the right group of cells at the right time with the right doses. Ideally, a nanoscale device that could be implanted or worn on the skin near the organ in question should contain: sensors that assess the physiological state of the malfunctioning organ; a primitive computer that assesses the correct response; and compartments that release the drug molecules at the right time in the right place. The world’s smallest biological computer has already been built at the Weizman Institute in Israel and is just 100nm in size. Details were published in the journal Nature in May of this year.

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Such computers, using biological molecules as input data and biologically active molecules as outputs, could produce a system for 'logical' control of biological processes. This is an autonomous bio molecular computer that, at least in vitro, logically analyses the levels of messenger RNA species, and in response produces a molecule capable of affecting levels of gene expression. The computer operates at a concentration of close to a trillion computers per micro litre and consists of three programmable modules: a computation module, an input module, by which specific mRNA levels regulate molecule concentrations; and an output module, capable of controlled release of a short single-stranded DNA molecule. This approach might be applied in vivo to biochemical sensing, genetic engineering and even medical diagnosis and treatment. As a proof of principle the computer was programmed to identify and analyse mRNA of disease-related genes associated with models of small-cell lung cancer and prostate cancer, and to produce a single-stranded DNA molecule modelled after an anticancer drug. The Weizmann Institute-developed nanotubes will extend the use of the recently developed nanomicroscope, now in use from Beijing to Stanford. In this microscope, laser light is passed through a hole only nanometers in size, allowing us to examine single genes and even single proteins, and how they attach themselves on the cell surface. Punching glass to make a hole only 10 nanometers wide for the microscope demanded the creation of new technology. This knowledge led, in turn, to the development of tiny glass tubes into which Lewis slid an even tinier metal wire, creating an instrument that functions like a surgical laser at a fraction of the cost of a variety of surgical lasers, it is now in clinical trials in Israel . Another tool that evolved from the new technology is what Prof. Lewis calls a nano-fountain pen. It is, in fact, a hollow nanotube, which can deposit chemicals at nanodimensions. Its uses may include chemically altering faulty genes. Nanoshells – Hazle and a team of researchers in his department are working with scientists at Rice University in Houston Texas to perfect microscopic silicone spheres coated in gold that can “find” a cluster of cancer cells and attach to them. Shining laser light on the devices heats up their gold shells and destroys the cancer cells they cling to.

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Nanoparticles – These particles link together to form a biological homing device. Rosenblum is working with Rice scientists to test types of nanoparticles called “nanotubes” and “buckyballs.” Rosenblum likens these devices to a kind of miniscule robot “because they are programmed to perform a certain task and report back to us. We can track exactly where they are in the body.”

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Nanoshuttles – These substances can refer to destinations within the organ and blood system in the same way that the post office refers to street addresses, says Renata Pasqualini, Ph.D., associate professor in the Department of Genitourinary Medical Oncology and Cancer Biology at M. D. Anderson, who is part of a team designing the mechanisms. The shuttles will deliver diagnostic and therapeutic agents to specific organs and tumors.

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