Philip Ball sizes up the latest developments in nanotechnology.

Philip Ball sizes up the latest developments in nanotechnology.


International Sematech

One day in the not-so-distant future, the current interest in nanotechnology will seem quaint. Not because nanotechnology will have failed and vanished, but because it will be so ubiquitous and so diverse that people will consider it curious, if not perverse, that it was once all lumped together under a single umbrella. In engineering terms, there seems so far to be nothing we can do on the macroscale that we can’t do at the nanoscale. We can make nanoelectronic circuits, nano light emitters, nanomechanical devices with moving parts, nanohydraulic turbines, sensors, medical devices, composite materials, energy-generating units. We can even write nano-books and create nano-art.

That’s not to say that nanotechnology is no more than macrotechnology writ small. Some things are very different down at the scale of molecules and cells. Fluids start to look grainy and highly viscous. Surface tension becomes a dominant force. Quantum effects come into play, and everything is buffeted by Brownian motion. But with a bit of ingenuity, all of these things can be used to advantage.

In this fecund field, new research is always likely to take unexpected directions. The current smattering of commercial applications of nanoscience seems at face value to present a romanticised contrast to the field’s futuristic image. If there are nanoparticles in tennis balls, stain-resistant trousers, sun creams and dirt-repellent paint, it’s not because that’s the best use anyone could find for them. Such relatively low-tech applications merely face the lowest barriers to commercialisation and so will be the first to spin off. The zinc oxide nanoparticles supplied by the tonne to BASF and Schering-Plough for their sun creams and other cosmetics can be more or less poured into the mix straight from the sack.

That’s why, for some researchers, nanotechnology (as opposed to exploratory nanoscience) is at present very much an extrapolation of the familiar, an evolutionary rather than revolutionary affair. Semiconductor manufacturing for computers can already claim to have entered the nano regime (it currently works at scales of about 100-200 nm) without a substantial change in methodology.

Silicon chips are made using photolithography: photochemical patterning of a ’resist’ through a mask, followed by chemical etching of exposed areas. The minimum feature size accessible by such a process is determined by the wavelength of the illumination - to extend to the nanoscale, optical wavelengths are being replaced by extreme ultraviolet. But although the principles remain the same, changing the wavelength to this degree demands new kinds of optics, and the technology is challenging.

So this traditionally competitive arena is being forced to become collaborative, as big companies share the cost of the technical innovations. A consortium of key semiconductor manufacturers called Sematech, which includes IBM, Intel, Motorola and Hewlett-Packard, is currently funding the development of a $125 million ’nanotechnology centre’ at the State University of New York at Albany, US, which looks set to develop the next-generation methods of manufacturing. To these people, nanotechnology is about taking current practice and making it smaller. ’For very good reasons, it’s quite a conservative world technically,’ says George Whitesides of Harvard University, US.

The successor to Intel’s Pentium 4 microprocessor chip, called the Prescott and due to be launched on 2 February 2004, contains transistors just 50 nm in size, made lithographically with ultraviolet light of 193 nm wavelength. But that won’t be enough to keep pace for long with the seemingly inexorable trend in miniaturisation dictated by Moore’s Law, and Intel has its sights set on wavelengths of 157 nm by 2007.

And even if the industry succeeds in developing new kinds of photolithography, it will not be long before it encounters a more fundamental limit. In less than 10 years’ time, Moore’s Law would take us to the point where conventional semiconductor transistors have some features only a few nm thick. At this point the traditional materials and circuits no longer fulfil their tasks: silicon dioxide, the usual insulator, becomes leaky for example, and electrons in adjacent wires begin to interact strongly. So that is when an entirely new materials basis for electronic devices will be needed.

Small wonder that companies such as IBM are starting to look seriously at nascent technologies, including molecular self-assembly, carbon nanotubes and other nanowires, and scanning-probe devices. One such approach being explored at IBM’s research laboratories in Zurich, Switzerland, is the Millipede. This is a device not for data processing but for data storage. The information revolution has relied not only on ever smaller transistors but on ever more capacious memories, which has entailed a steady increase in data storage densities. (Magnetic storage densities doubled every year in the late 1990s.) This demands that the bit size gets smaller.

In state-of-the-art hard drives, the magnetic domains used to store a single bit are just 10 nm or so across. But there are fundamental limits on how small conventional magnetic storage can go, largely because the energy required to ’flip’ the magnetisation of nanoscale domains begins to fall towards the energy of room-temperature thermal fluctuations.

The Millipede stores data not magnetically but mechanically, rather like an old-fashioned punch card. It uses the needle tip of an atomic force microscope (AFM), attached to a flexible cantilever arm, to impress indentations into a plastic film. This kind of surface modification has been possible with the AFM for several years now, and indeed this device and its sibling the scanning tunnelling microscope (STM) have been used to manipulate individual atoms and molecules. The potential of these tools for nanotechnological data storage was literally spelled out in 1990 when researchers at IBM’s Almaden lab in California, US, wrote their company name with xenon atoms moved over a nickel surface by an STM tip.

The drawback for any practical technology, however, is that this is a very slow way to write and read data. The Millipede seeks to address this limitation by a fantastic proliferation of tips: hence the name. The latest version of the device deploys over 4000 AFM tips, each of them individually controllable, vastly speeding up the operating rate. To write a bit, a tip is brought into contact with the plastic film and heated electrically, which softens the plastic locally. This allows the tip to sink into the film, creating an indentation 10 nm across. At that size, 200 billion bits can be stored in one square inch of material. The marks are erasable by using the tip to press around the pit and fill it in. To read data, the tip is heated to a lower temperature than for writing. When the tip dips into a depression, it experiences greater heat loss, and the electrical resistance through the cantilever arm drops measurably.

The Millipede has low power consumption, well below that of magnetic recording. It is still rather slow, being able to write at a rate of a few megabits per second. But IBM researchers think that it should be possible to achieve that rate for each tip separately, in which case the entire tip array would be several thousand times faster because of its parallel operation. Thanks to micromachining technology, the array is just a few mm across, and the IBM team hopes that it will find its way into the memories used for personal organisers, mobile phones, video cameras and watches.

Such natural nanotechnology is strictly of the ’bottom-up’ variety, being manufactured from atoms or molecules in ’factories’ that are often far smaller than their products. Biology shows that self-assembly and hierarchical organisation of programmed components might ultimately be the most efficient way to do nanotechnology.

But some of the near-term applications of bio-nanotechnology don’t involve direct intervention with living systems. They are instead diagnostics to be used for in vitro analysis of biomolecules (Box 2, p36). For example, techniques for depositing nanoscale domains of DNA or proteins onto solid substrates could be used to create ’gene chips’ and protein arrays that will enable molecular biologists to obtain instantaneous genetic or proteomic profiles of cells. Dip-pen nanolithography, devised by Chad Mirkin and coworkers at Northwestern University in Illinois, represents one such tool, in which an AFM tip is used as a kind of quill for writing monolayers of molecular ’ink’ with nanoscale precision.

Some groups have more ambitious plans for biological nanotech. NanoMateria is a US company that aims to apply the self-assembling nanostructures developed by Sam Stupp of Northwestern University, Illinois, US, for tissue engineering. Stupp has created chain-like molecules that aggregate like the amphiphilic molecules of cell membranes, but in ways that can be controlled by the molecular architecture. Gels formed from such molecules could serve as scaffolds for colonisation by cells to form new tissue, and could self-assemble after being injected into the body. ’We had interesting systems for the regeneration of the central nervous system, bone and cartilage, and for organ transplantation,’ says Stupp. ’There will be more to come, and I think it will take five years or more to develop them into products.’

While nanotechnology could benefit biology, the converse is perhaps even more true. Researchers are finding ingenious ways to adapt the nanoscale machinery of cells for technological ends. If we want to make nanomachines with moving parts, for example, it hardly seems worthwhile struggling to make tiny motors from scratch when they already exist in nature.

The corkscrew-like flagella that propel some bacteria are driven by one of the very few natural ’wheels’, a motor just 10 nm or so across made from proteins and powered by the flow of protons. No one has yet found a way to harness the flagella motor for nanotechnology, but that is not the case for another rotary protein motor, the enzyme ATP synthase. This device sits in a cell membrane and spins as it converts ADP to energy-rich ATP during metabolism or photosynthesis.

Carlo Montemagno, formerly at Cornell University, US, and coworkers have chemically modified ATP synthase so that it can be stuck by its rotating ’head’ to nanoscale pillars of nickel. This leaves the ’spindle’ of the device, which is normally embedded in a cell membrane, sticking up and free to spin. The researchers fixed nickel propellers 150 nm long to the spindle and watched them rotate as the motor was provided with ATP fuel. Montemagno’s group has genetically engineered a switch in the enzyme to turn it on and off, triggered by zinc ions.

Viola Vogel of the University of Washington in Seattle, US, Jonathon Howard of the Max Planck Institute for Cell Biology in Dresden, Germany, and their coworkers have used a linear motor protein, kinesin, to transport nanoscale objects around on a surface. Kinesin moves step-like along protein filaments called microtubules and kinesin molecules adsorbed onto a surface will pass microtubules between them. This motion can be controlled by confining the microtubules in lithographically defined nanoscale ravines, and Vogel and colleagues have attached nanoscale cargo to the microtubules.

Howard’s team has used this system to transport and stretch strands of DNA, and believes this might be a way to guide DNA components into place to make templates for, say, nanoscale circuits. Howard predicts that the first applications of this kind of naturally based nanotechnology will be found in biotechnology - for example, manipulating DNA for genetic analysis. But he adds that ’the main thing that interests me is whether biological principles of self-organisation - variation, selection and stabilisation - can be used in engineering’.

DNA is an ideal nanoscale building block because it can be programmed, via its base sequences, to self-assemble into complex architectures. Ned Seeman of New York University, US, who has pioneered this approach, has made polyhedral cages of interwoven double-stranded DNA, as well as two-dimensional tiling patterns that can clip together in such a way as to embody Boolean logic operations, permitting a kind of DNA computing.

And if you’re going to build with DNA, why not exploit its capabilities to the full? G&0x00FC;nter von Kiedrowski at the Ruhr University of Bochum, Germany, is exploring ways of creating DNA nanostructures that can replicate, and has already demonstrated that the chemical information in the arms of self-assembling molecular units can be copied.

Proteins too look set to become valuable nano building blocks. Using in vitro evolution techniques, they can be tuned to functions not found in nature. For example, Angela Belcher, now at the Massachusetts Institute of Technology, US, has developed peptide molecules that can selectively recognise and bind to the surfaces of a wide variety of semiconductors. These could be used to tailor motor proteins so that they transport particular types of inorganic nanoparticle.

And by attaching such selective ’hooks’ to the protein coats of viruses, Belcher and coworkers have been able to exploit the self-organisation of viruses into liquid-crystalline arrays to make ordered nanoparticle composites. ’You can put anything - organics, inorganics, biologicals - onto the tip of a virus and then self-assemble it into a multidimensional structure,’ says Belcher.

Like most commercialised nanotech today, it looks pretty quick and dirty compared with the latest dispatches from research labs. But such applications remind us that nanotechnology will become more sophisticated as we gain ever more control over the way the components are organised. In the same way, applications of carbon nanotubes might progress from composite materials in which they are more or less randomly dispersed as toughening elements in a binding matrix, to memory and logic devices in which they are organised into precise and ordered grids.

It is telling that, while the kind of top-down nanotechnology envisaged by the likes of Sematech faces the prospect of ever-escalating costs (and the danger of ever-diminishing returns), bottom-up approaches receive much of their impetus from the possibility of adopting cheap, ’wet’ and mild fabrication methods like those of soft lithography (see Box 3, p36). So we might ultimately see a fabulous synthesis of high and low technology: machines made in a bucket from beautifully engineered components. Which sounds a lot like the way things happen in nature.


Thanks to the George Whitesides’ research group for helpful advice during the preparation of the outline for this article.

Philip Ball

1. Nanoethics

Until 2002, nanoscientists had to worry only about getting the science to work. But then came the rumours that nanotechnology was the next threat to humankind: like GM crops, but maybe even scarier. Some environmental groups, notably the Canadian-based ETC Group, started calling for a moratorium on nanotech until its potential risks were more clearly known. The pot was stirred by Michael Crichton’s bestselling book Prey, in which nanoscale robots run amok and begin hunting and devouring anything that moves.

This scenario was lifted from Eric Drexler’s 1986 book Engines of Creation, which proselytised for nanotech but also suggested a terrifying danger. Drexler imagined that researchers might create ’nanobots’ that can replicate by pulling other (particularly carbon-based) materials apart and building copies of themselves from the molecular fragments. If these replicators got out of hand, they would reproduce relentlessly, transforming the world into a ’grey goo’.

Grey goo is a red herring, since no one is actually trying to make replicating nanobots along the lines that Drexler outlined, nor does anyone have the slightest idea how that might be done. But it sounded scary enough to send out ripples about the safety of nanotech, and has served as a focus for a variety of fears, some of them better grounded. For instance, it is not clear yet whether nanoparticles such as carbon nanotubes might pose health hazards akin to those of asbestos. Yet because they are not technically new chemicals, there is no formal requirement for their toxicity to be investigated.

In the face of such concerns, the scientific community has recognised a need to attend to the safety, ethical and societal questions raised by nanotechnology. The toxicology issues are now being studied in several labs, notably the Center for Biological and Environmental Nanotechnology at Rice University, US. The US Senate has called for the National Science Foundation to establish a centre for ’Societal, Ethical, Educational, Legal and Workforce Issues Related to Nanotechnology’, with funding of $5 m (ca ?3 m) per year.

In the UK, the Economic and Social Research Council has recently issued a report on the ’social and economic challenges of nanotechnology’, while the Royal Society and the Royal Academy of Engineering have been commissioned by the government to produce a wide-ranging report. on these issues, including an assessment where regulation needs to be applied.

2. Nanoparticle diagnostics

Quick genetic profiling is one of the major aims of post-genomic biology. Chad Mirkin’s group at Northwestern University, US, has formed a start-up company, Nanosphere, to commercialise a technique for the cheap, rapid detection of specific DNA sequences. Gold nanoparticles are tagged with short stretches of single-stranded DNA, with sequences that are complementary to that of the target strand. If present, the target pairs up with the tags and binds the nanoparticles into a colloidal network that scatters light and changes the colour of the solution.

This simple colour-change system can detect single base-pair mismatches in a sequence. Nanosphere claims that its current systems can provide diagnostic results in hours, rather than days. The company has won a US governmental contract to develop the technology for the detection of biological warfare agents.

Nanoparticles are also becoming widely used as labels to track biomolecules in cells. Gold nanoparticles, for example, are inert but clearly visible in the electron microscope. Semiconductor nanoparticles fluoresce at a wavelength determined by their band gap, which at the nanoscale is governed by quantum size effects. This means that particles can be tuned to a particular colour simply by controlling their size.

3. Soft lithography

One of the most fertile commercially applicable techniques for creating nanoscale structures sprung from George Whitesides’ laboratory at Harvard University, US. It is called soft lithography, because it replaces the high-vacuum conditions of traditional photolithography with a cheap, ’wet’ chemical process - while allowing for a remarkable improvement in resolution.

Whitesides and his colleagues perfected a technique for printing surfaces with an orderly monolayer of organic molecules transferred from a rubber stamp. These self-assembled monolayers (SAMs) are typically made from alkylthiols, which form strong chemical bonds with gold. The soft stamps can be used to transfer a pattern onto curved surfaces, unlike traditional microlithography. The stamp itself is cast from a mould patterned lithographically, and by using high-resolution techniques such as electron-beam etching it can be given features as small as 10 nm. These features are reproduced faithfully in the SAM imprinted on a surface, which then acts as an etching resist for patterning the substrate.

Whitesides’ collaborators have founded a Boston-based company called Surface Logix, which uses soft lithography to create patterned surfaces for biological assays - for example, for screening libraries of candidate drug molecules or detecting bioweapons. Another spin-off company from the Harvard group, called EM Logix, aims to use the method to make optical and electronic devices - but ’this is much tougher’, Whitesides admits. ’There is a strong technical case for it, but the venture community does not recognise it.’ Nonetheless, big electronics companies such as IBM, Lucent and Philips have all dabbled in soft lithography. ’I think these methods will be adopted in microelectronics’, says Whitesides. ’Come back in 10 years and it will be a successful technology.’

Stephen Quake at the California Institute of Technology, US, has seized on soft lithography for making cheap micropatterned surfaces for microfluidics. His San Francisco-based company Fluidigm is exploring the growth of hard-to-crystallise protein crystals from very small volumes of solution in a microfluidic system called Topaz, which is being developed with GlaxoSmithKline. Several other companies, such as GeneOhm and Aviva Biosciences (both in San Diego, US), are using soft lithographic patterning in combination with microfluidics or electronics for creating miniaturised assays for cells and DNA.

4. Nanotech timeline

1959: Richard Feynman gives a talk to the West Coast section of the America entitled ’There’s Plenty of Room at the Bottom’, now considered to be the founding text of nanotechnology.

1974: The word ’nanotechnology’ is coined by University of Tokyo, Japan, researcher Norio Taniguchi. Arieh Aviram and Mark Ratner launch the field of molecular electronics.

c.1981: The scanning tunnelling microscope is invented by Gerd Binnig and Heinrich R?hrer at IBM’s Zurich laboratories in Switzerland. It is later used to manipulate atoms one by one.

1985: C60 and the fullerenes are discovered. This establishes the idea that sheets of graphite-like carbon can be moulded into nanostructures.

1986: Publication of K. Eric Drexler’s Engines of Creation introduced the public to nanotechnology - albeit a particular, controversial vision of it.

1986: Gerd Binnig, Christoph Gerber and Calvin Quate devise the atomic force microscope, which can image non-conducting samples.

1986: Binnig and R?hrer are awarded the Nobel prize in physics for their invention of the STM.

1987: Charles Pedersen, Donald Cram and Jean-Marie Lehn are awarded the Nobel prize for their work on supramolecular chemistry, which established the basis of self-assembly, considered by many to be central to a bottom-up nanotechnology.

1990: Don Eigler and Erhard Schweizer at IBM Almaden in San Jose, US, write their company logo in xenon atoms using the STM.

1991: The discovery of carbon nanotubes by Sumio Iijima of NEC in Japan provides nanotechnology with one of its fundamental building blocks.

1993: Eigler’s group makes a ’quantum corral’ - a ring of iron atoms pushed into place with the STM.

1996: Richard Smalley, Harry Kroto and Bob Curl win the Nobel prize in chemistry for their discovery of C60.

1997: Paul Boyer, John Walker and Jens Skou receive the Nobel prize in chemistry for deducing the mechanism behind the action of ATP synthase, a nanoscale biological motor.

1998: Cees Dekker and coworkers at Delft Technical University in The Netherlands produce the first carbon nanotube transistor.

2001: Groups at IBM Yorktown Heights and at Delft report the first nanotube-based logic circuits. Mitsubishi announces plans to build an industrial-scale plant for manufacturing fullerenes. The plant is now working, and intends to ramp up production to 1500 tonnes per year. 

This article is a co-production of the RSC and the Gesellschaft Deutscher Chemiker (GDCh) and also published in Nachrichten aus der Chemie

Contact and Further Information

Philip Ball
Nature consultant editor
4-6 Crinan Street, London N1 9XW