Nanoparticles – small things, big...

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Nanoparticles – small things, big effects Opportunities and risks

Transcript of Nanoparticles – small things, big...

Nanoparticles – small things, big effectsOpportunities and risks

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Editors

VDI Technologiezentrum GmbH

Dr. Wolfgang Luther

Dr. Gerd Bachmann

Abt. Zukünftige Technologien Consulting

Author

Dr. Mathias Schulenburg, Cologne

Gestaltung Suzy Coppens,Cologne

www.bergerhof-studios.de

Printing

WAZ Druck, Duisburg

Bonn, Berlin 2008

Photo credits

TTitle page: Atomic meadow: Group Prof. Köhler, RUB Bochum; Gecko: Dr.

Stanislav Gorb, MPI für Metallforschung, Stuttgart; Menger Schwamm: University

of California, Berkeley, USA; nanoparticles: University of Notre Dame, Indiana,

USA; Pyramid: University of Karlsruhe (TH); Portrait, sky, montage: Suzy Coppens,

BergerhofStudios, Cologne

S. 5: Left from top: 1, 2: BergerhofStudios, Cologne; 3–5: REM Laboratory, University

of Basle; 6: University of Bielefeld, Chemistry Department; Centre: BergerhofStu-

dios, Cologne; Right from top: 1, 2: BergerhofStudios, Cologne; 3: REM Laboratory

University of Basle; 4: REM Laboratory University of Basle; 5: Centre for Nanotech-

nology, Münster; 6: Bernd Thaller, Advanced Visual Quantum Mechanics

P. 6: Background: Haseke GmbH & Co. KG, Porta Westfalica

P. 7: Left to right: Philipps University Marburg; Bundesinstitut für Risikobewertung,

Berlin; GSF-Forschungszentrum GmbH, Neuherberg; K/T GeoServices, Inc., USA

P. 8: Top: NASA/ ESA; Below: BergerhofStudios, Cologne

P. 9: Top: BergerhofStudios, Cologne; Below left: NASA/ESA ; Right: Institute for

Geophysiks, University of Munich

P. 10: Left: Saito Laboratory, Department of Quantum Engineering, Nagoya Univer-

sity, Japan; Right: Nanotechnology Cente, University of Duisburg-Essen

P. 11: Left: INM, Saarbrücken; Right: BergerhofStudios, Cologne

P. 12: BergerhofStudios, Cologne

P. 13: Left to right: 1–4,7,8: BergerhofStudios, Cologne; 5: Duales System Deutsch-

land GmbH, Cologne; 6: e-Letter University of Stuttgart

P. 14: From top down: Princeton Art Museum, Princeton, NJ; K/T GeoServices, Inc.;

Left: Musée Guimet, Paris; Right: Technical University of Dresden

P. 15: BergerhofStudios, Cologne

P. 16: Top: BergerhofStudios, Cologne; Below: Gezelter Lab, University of Notre

Dame, Indiana, USA

P. 17: Research Centre Rossendorf

P. 18: Left: Research Centre Rossendorf; Right: Evonik Industries AG, Essen

P. 19: Evonik Industries AG, Essen

P. 20: BergerhofStudios, Cologne

P. 21: Bio-Gate AG, Nürnberg

P. 22, 23: Evonik Industries AG, Essen

P. 24: Left: Institute for Physical Chemistry, University of Hamburg; Top: Institute

for Scientific Computing, TU Dresden; Below: University of Karlsruhe (TH)

P. 25: NASA; Department of Physics University of California, USA; Montage: Berger-

hofStudios, Cologne

P. 26: Capsulution NanoScience AG, Berlin

P. 27, 28: MagForce Nanotechnologies AG, Berlin

P. 29: BergerhofStudios, Cologne

P. 30: Aquanova AG, Darmstadt

P. 31: Top: BergerhofStudios, Cologne; Below: Fraunhofer Institute for Silicon

Technology, Itzehoe

P. 32–33: BergerhofStudios, Cologne

P. 34–37: GSF-Forschungszentrum GmbH, Neuherberg

P. 38: Beiersdorf AG, Hamburg

P. 38: Tilmann Butz

P. 40: Max-Planck-Institut für Biochemie and Max Planck Institute for Marine

Microbiology, Bremen

P. 41: Research Centre Karlsruhe and Max Planck Institute FKF Stuttgart

P. 43: Left: Daimler AG, Stuttgart; Right: GSF-Forschungszentrum GmbH, Neuher-

berg

P.44–45: BergerhofStudios, Cologne

P. 46: R. Wang, National Center for Electron Microscopy

P. 47: Flad & Flad Communication GmbH, Heroldsberg

P. 48: Empa - Materials Science & Technology, St. Gallen

P. 50: Bio-Gate AG, Nürnberg

P. 51: Source: Nanotechnologieportal Hessen; Graphics, BergerhofStudios, Cologne

P. 52–53: BergerhofStudios, Cologne

P. 54: University of Ulm

P. 55: Top left: University of Bielefeld, Chemistry Department; Top right: University

of Duisburg/Essen; Below left: Saito Laboratory, Department of Quantum Engi-

neering, Nagoya University, Japan; Below right: Saito Laboratory, Department of

Quantum Engineering, Nagoya University, Japan

Nanoparticles – small things, big effectsOpportunities and risks

Foreword

FOrEwOrd

Dr. Annette Schavan, MdBFederal Minister of Education and Research

Nanomaterials may be almost invisible, but it is difficult to imagine our everyday lives without them: Nanomaterials make our cars safer and more envi-ronmentally friendly, our medicines more effective and at the same time more gentle, and our mobile phones or laptops smaller and more efficient. In addition, nanotechnology offers great potential for protecting both the climate and natural resources. Thanks to nanotechnology, we now have a number of effective environmental technologies and can make more efficient use of regenerative sources of energy.

The “Nano Initiative – Action Plan 2010“, which was announced in 2006 as part of the High-Tech Stra-tegy, establishes the first ever common interdepart-mental framework of action which pools all aspects of nanotechnology under a single programme – ranging from funding for SMEs to new leading innovations and enhanced risk research to a compre-hensive dialogue with the public on opportunities and effects. This brochure provides an insight into the world of nanoparticles, explains their production and use and also describes their occurrence in nature. Fur-thermore, it provides information about the known effects of nanoparticles on health, about public perceptions and about genuine risks and precau-tions. It is our intention to contribute towards a solid and objective debate. Find out more about nanotechnology, learn about new findings in the world of nanoparticles and take part in the discussion on shaping nanotechno-logy, one of the most important technologies of the future. This brochure will provide you with impor-tant information and insights.

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Contents

Everything Nano, or what? 4

Infobox: Nanos in the summer meadow 5

Nanoparticle Zoo 7 How do nanoparticles come into the world? 8

Industrial production of nanoparticles 10 Unintentional creation of nanoparticles 12 Home-made nanoparticles 12 Material cycle 13 Nanoparticle technology of our ancestors 14

Nanoparticles in the technosphere 16

Palladium nanos on bacterium membranes for catalysis 17 Nanomaterials for new lithium ion accumulators 18 Use of nanoparticles: Silver as bacteria killer 20 Experience with the industrial manufacture of nanomaterials 22 Interview with Dr. Markus Pridöhl 22 Quantum dots 24 Exotic nanos: Graphenes 25

Nanoparticles in the biosphere 26

Nanotechnology for health and medical technology 26 Nanotechnology for food 28

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3CONtENts

Health effects of nanoparticles 32

Gateways for nanoparticles 32 Infobox: Asbestos – a story that must not be repeated 33 Nanoparticles – how dangerous? 34 Research on respirable aerosols 35 Risk to the heart and blood vessels 37 Effects of nanoparticles on the skin 38 Interview with Prof. Tilman Butz 38

Public awareness and social debate 40

Nano – the beginnings 40 Nano Hype 40 End of the Nanobots 41 Nano Fakes 42 Nano Myths 42 Nano Disputes 43

risk management in nanotechnology 46 Nanoanalysis as a basis for risk analysis 46 Nanotechnology activities of the Federal Government 47 Nano safety research of the BMBF: NanoCare 48 Interview with Prof. Dr. Harald Krug 48 Activities of industry 50

small particles, large effects – opportunities and risks

of nanoparticle technology 52

Glossary 54

small particles, large effects – opportunities and risks

of nanoparticle technology 56

Index of abbreviations 57

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Everything Nano, or what?

A nanometre is a millionth of a millimetre. that is already very small; atoms, the building blocks of matter, are only ten times smaller. well over 10 to the power of 10 dots with a diameter of a nanometre would fit in the dot on this i. that is more than 10,000,000,000.

Nanotechnology is the art of the knowing utilisation for our own purposes of structures possessing useful functions in the size range between 1 and 100 nano-metres. The word „knowing“ is important, otherwise even butter making would be nanotechnology, as milk contains countless nano-scale particles, but this knowledge is not necessary for churning butter. The cells of every living creature, every poppy flower, are packed full of nano-nature. Nanoparticle technology is restricted to synthetic particles. This is the technology with the most eco-nomic importance at present. Nano-scale particles are already found in paints which break down odour substances, on surgical instruments which keep themselves sterile, in sun creams which do not make one‘s nose white, in tablets which release their active constituents instantly and so on. The word „nano“ has become so attractive for many marketing mana-gers that they sometimes write „nano“ on the packet even when there is none inside. As a rule, nanoparti-cles possess other properties than the same material in coarser form. While the gold in a wedding ring shines yellow, gold nanoparticles can colour a wine glass red. In this case that is a consequence of the laws of quan-tum mechanics, which have different rules for very small things. Gold is also a very unreactive material on a large scale, but in the form of nanoclusters it can be catalytically active, like the platinum in the automobile catalytic converter. Nanoparticles are more reactive for geometrical reasons, as the proportion of surface atoms increases as the size of a particle decreases. Surface atoms are strongly inclined to make use of their bonding pos-sibilities. For this reason, some nanoparticles have to be stored in inert gas, as they would immediately burn up in the air. Dust explosions are also conceiva-ble, but that is not a nano characteristic, as they can also occur with flour dust. Expensive nano-dusts will

be contained securely for financial reasons alone, but even more so for reasons of work safety. The high proportion of surface atoms in nanoclu-sters and their high proportion of unsaturated che-mical bonds also make this material state especially interesting for catalysis - the acceleration of a chemi-cal reaction without consumption of the catalyst.Because nanoparticles are so reactive, they also tend to bond with each other. That must be prevented with special coatings if the nano-scale advantage is not to be lost. On the other hand, because of their bonding affinity, escaping nanoparticles usually neutralise each other by combining to form larger units. Even so, wherever inorganic solid, ceramic or metallic nanoparticles are concerned, there is a need for scientific research into their safety for humans. Lurking in the background is the horror word „asbe-stos“, the carcinogenic effects of which were denied for years, although clear evidence existed for its danger (see box on page 33). The Federal Ministry for Education and Research is therefore supporting safety research for nanopar-ticle technology in a number of projects. The risks of this technology are explained in more detail below, but also, in particular, the opportunities it offers. These are, in fact, so great that they should at least in part be able to neutralise the foreseeable risks of the clearly unavoidable industrialisation of the whole world in years to come. The possible risks should therefore be weighed against the opportunities to be missed by dispensing with the utilisation of nanopar-ticles. Binding statements on the extent of possible risks can naturally only be made after the conduct of nano-safety research. Until then, research and industry will make every effort to study and to avoid any possible harmful effects. Nanoparticles, by the way, are not confined to technology - they are building blocks of nature and are found in every flowering meadow.

EvErytHING NANO, Or wHAt?

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Cicadas, for example, protect themselves against both water and dirt by means of a coating containing innumerable „bro-chosomes“, airy protein globules, some of which are similar in form to the famous C60 fullerene, also known as buckyballs.Immediately after moulting its skin, a milky droplet is excreted from its abdomen and it spreads this with its legs over its whole body, where it hardens into a waxy protective coating.With a diameter of one nanome-tre, C60 buckminsterfullerene is a hundred times smaller than a brochosome. It also occurs in nature, in the air after a forest fire, for example, but filling it with a foreign atom, such as a nitrogen atom, has only succeeded in the laboratory.Exotic nanoparticles like this might one day become the com-puting elements for a quantum computer.

If we zoom in close enough to a snail‘s head, we see sub-micron scale, finely formed rasping teeth made of mineral components. Also bacteria of course. Their skins, like those of other cells, are covered with large numbers of nano-scale bumps, sensors for the outside world, the triggering of which initiates complex cascade reactions inside the cell.At the end of this journey stands a hydrogen atom, the smallest of all atoms, with a diameter of a tenth of a nanometre. If it is „excited“ by the input of energy, its electron cloud can become appreciably larger and assume extremely complicated structural forms. The hydrogen atom is where all nanotechnology ends, as we have no constructive access to the underlying structures.

Nature is full of nanotechnological subtleties.

Nanos in the summer meadow

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Nanoparticle Zoo

Nanoparticles come in many different vari-eties, which is exactly what makes them so technically attractive. And different proper-ties can be combined in one particle, for exa-mple hard mineral cores with water-repellent chemical skins. this can be used to make a non-scratch, water-repellent car finish.

Nanoparticles can be equipped with numerous refinements. For example, nanoparticles with a magnetic core can be given a first coating toxic for cancer cells, followed by a second coating of antibo-dies which only adhere to cancer cells. When that has taken place in the body of a patient („drug tar-geting“), alternating electromagnetic fields heat up the magnetic cores, which are now located exactly

where required, and the heat releases the anti-can-cer substance from the first coating. There are great and justified hopes that such sophisticated concepts will represent valuable therapeutic instruments in the near future. In any case, the nanoparticle con-cept opens up possibilities not possessed by classical materials chemical (see chapter Medical Technology on page 26). The immense number of variations in which nanoparticles can occur, on the other hand, makes life difficult for toxicologists. While, in the case of a simple chemical like sodium chloride (com-mon salt), the substance is defined by specifying the chemical formula, NaCl, and the degree of purity, in the case of a water-insoluble metal oxide nanopar-ticle, at least the size, the shape and the crystal class of the particles would have to be specified before toxicological studies were comparable, for all these properties can have an influence on the possible to-

Nanoparticles are widely used.

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xicity. In fact, the manufacturing process should also be specified, as this determines the impurities on the surface of the particle. Characterisation, the reliable recording of properties, is usually immensely more difficult than for classical chemicals. In fact, in order to explore all the possibilities of the nanoparticle concept, a multidimensional representation is nee-ded, perhaps a „morphological box“ like that of the deceased Swiss-American astrophysicist Fritz Zwicky.

This intellectual concept brought Zwicky many new discoveries in his time, some of which could be profi-tably patented. The diagram below is a first attempt.

Nanoparticles can be manufactured in countless variants.

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Nanoparticles are not a human invention. they also occur naturally, although mostly in forms other than those useful for industry. the sand in Mark Brandenburg, for example, originates from weathering of the so-called Baltic shield, a mountain range with peaks which once reached the cruising altitudes of today‘s large passenger planes. Its destruc-tion must have released millions of tonnes of nanometre fine particles into the environ-ment, for there is no law of nature which says that weathering should stop at the nanome-tre scale. Actually, weathering products at nanometre scale tend to combine together again to form larger parti-cles. Technical nanoparticles are generally protected against this by special coatings, so that the technical advantages of the nano-scale are not lost. At the same time, the dust storms of the Sahara, which blow so much sand over the ocean that the clouds can be seen from space, give an idea of the amount of nano-scale quartz, silicon dioxide (SiO2 ), which might

How do nanoparticles come into the world?

be on the move in the air, invisibly, of course.The Sahara dust also contains iron compounds which actually fertilise the regions of the ocean they fall on. Fast growing algae then emit dimethyl sulphi-

Elements like silicon are synthesised in stars, are found as nanoparticles in the stellar atmosphere and in interstellar space and fall continuously on the earth.

The Sahara releases huge quantities of mineral dust annually, including nano-scale particles. Such dust usually consists of mixed oxides of the elements silicon, aluminium, titanium, iron, potassium and calcium.

This dust even lands on German car roofs, but the nano-scale fraction is invisible.

de, which forms microscopic crystals in the air - no doubt also nanoparticles. When these reach high al-titudes, water droplets condense on them and clouds are formed: nanoparticles as rain makers.

HOw dO NANOPArtIClEs COME INtO tHE wOrld?

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layers with particularly good living conditions. The bacteria sink to the ocean bed in such masses that they are regarded as candidates for the formation of iron ore deposits. And when they sink to the seabed, they lay themselves parallel to the earth‘s magnetic field at the time, thus recording its orientation for posterity. So nanoparticles have become witnesses for so-called Sea Floor Spreading, the drifting apart of sections of the earth‘s crust on the seabed. There has never been a shortage of magnetite particles. Bathers can swallow them, even in fresh water, for magnetotactic bacteria are everywhere. Their nano-particles of magnetite are so perfect, by the way, that they are being researched for high-tech applications in medical technology.

Volcanic eruptions release huge quantities of nanoparticles.

Magnetotactic bacterium.

Sand deposits are the remains of weathered mountains. The weathering process also creates nanoparticles, mainly by wind erosion in the case of exposed sand.

HOw dO NANOPArtIClEs COME INtO tHE wOrld?

The iron in seawater also combines to form nano-particles, in magnetotactic bacteria. These form chains of nanometre fine magnetite crystals. They have a good reason, for the magnet chains act like compass needles which can guide the bacteria into different water layers according to the inclination of the earth‘s magnetic field. In this way, they reach

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Plasma reactor at the Nanotechnology Centre of the University of Duisburg-Essen. The yellowish glow in the upper part of the plasma flare is caused by the hot particles. Many nanoparticles are indus-trially manufactured in a similar way.

Left: Networks of carbon atoms can assume many different forms, in-cluding, starting at the top: C80 fullerene, cone, double-walled carbon nanotube (DWNT), triple-walled carbon nanotube (MWNT).

HOw dO NANOPArtIClEs COME INtO tHE wOrld?

Seemingly exotic particles are also created naturally. Just a forest fire is enough to produce the full palette of so-called fullerenes: Buckyballs, Buckytubes, Gra-phenes – everything worthy of a name in the latest carbon chemistry.

Industrial production of nanoparticles

There are two different principles for obtaining nanoparticles. A large piece of material can be con-tinually broken down until the fragments attain the dimension of nanometres. An example is the widely used industrial method of grinding mineral compo-nents with ball mills. In order to attain nano dimen-sions, powders with typical particle sizes of 50 μm are placed, together with balls of hardened steel or tungsten carbide, in a closed container which is then violently agitated. With this method, particle sizes from three to 25 nm can be achieved. Processes like this come under the heading „top-down“, i.e. from larger to smaller structures. This principle of minia-turisation has been applied in information techno-logy for decades to produce ever more powerful and handier electronic devices such as notebooks, mobile

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Homemade nanoparticles in mayonnaise. All you need is a powerful mixer. Most of the fat/vinegar droplets are on a micrometer scale, other-wise the mayonnaise would be clear.

Fit for the finest particles: Sol/Gel particle reactor.

HOw dO NANOPArtIClEs COME INtO tHE wOrld?

phones or MP3 players. The other method consists of building up nano-scale particles from the smallest available building blocks, atoms or molecules. Such methods are labelled „bottom-up“. That is nature‘s preferred method. An example of the „top down“ method: If nano-particles are to be manufactured from a specific ma-terial, suitable input substances must be found. For the production of iron nanoparticles, for instance, a compound of chlorine and iron, FeCl3, can be finely ground with sodium in an inert atmosphere in a ball mill. The two substances react together to form nano-scale iron and sodium chloride, common salt, which can be simply washed out with water. What remains are the iron nanoparticles. One particularly spectacular „top down“ method is the electro-explosion. Here, a very short, but very powerful pulse of current flows through a thin metal wire. The wire becomes so hot, 20,000 to 30,000 °C, that it breaks down into its atomic constituents, only continuing to exist as a glowing cloud of plasma, held together by the strong magnetic field accom-panying the current impulse. This all takes place in a closed, gas-filled container. The metal cloud then

reacts with this gas to form a compound; in the case of a noble gas, nanoparticles of pure metal are for-med. These particles bond so readily that they joint to form alloys at low temperatures; in this way, brass is formed from electro-exploded copper and zinc powders at only 200 °C. A very popular „bottom-up“ method, the so-called sol-gel technology, makes use of tricks reminiscent of kitchen practices like the making of mayonnaise. Mayonnaise consists of a mixture of ex-tremely fine vinegar droplets in oil, largely produced by vigorous stirring. Similar mixtures of substances are used in industry to create nanoparticles. When these particles are formed by the reaction of two

components, one of which can only exist in droplets, and the other is introduced through the carrier substance, the two substances react together in the limited reaction volumes of the droplets and the reaction stops when the particles are nano-scale.

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Even in the fireplace at home, fullerenes like Buckyballs or Buckytubes are formed when wood is burned.

Nanos when pouring lead: The soot of a candle flame contains hydrocar-bon particles in countless forms, including fullerenes and diamonds.

The unfiltered exhaust gases from diesel engines contain large quantities of potentially harmful nanoparticles from the incomplete combustion of fuel.

HOw dO NANOPArtIClEs COME INtO tHE wOrld?

Unintentional production of nanoparticles

There are numerous methods of producing nano-particles, and new ones are continually being found. On the question of the toxicity of intentionally and unintentionally produced nanoparticles, there currently exists – even – more reason to worry about unintentionally produced nanoparticles. A study by the European Union, „Industrial application of nano-materials – chances and risks“, states:

„Unintentionally released nanoparticles, created by combustion processes in traffic or in energy conversion, in mechanical wear processes or conventional industri-al processes, currently contribute more to anthropoge-nic nanoparticle emissions than industrial nanoparti-cle production.“

Homemade nanoparticles

Organic nanoparticles can be easily made with kit-chen utensils: just a powerful mixer, vinegar and oil. If you are aiming at the stars of today‘s nanoparticle scene, just pour some lead: the soot which condenses on the bottom of the spoon contains buckyballs, buckytubes, graphenes – and nanodiamonds.

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Material cycle

Humans can come into contact with nanoparticles at almost all points in the industrial material cycle. The aim of the safety research is to eliminate any risks which might accompany the many anticipated positive consequences of nanoparticle technology.What is more, by means of nanotechnology, many

proven harmful substances will be able to be re-placed by common, non-toxic substances, which can also be manufactured using less energy. Just one ex-ample: the replacement of toxicologically objection-able cobalt blue by a pigment made of clay particles and indigo according to an old Mayan recipe (see p. 14).

Nanoparticles in the material cycle.

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Damascus blades owe their hardness and strength to embedded carbon nanotubes.

The blue of this old Mexican figure is a highly stable nanocomposite of a porous clay mineral and an organic pigment. The nanopig-ment is now produced again as Mayacrom® and replaces toxic heavy metal compounds.

Top: Kaolinite particles under the electron micro-scope. The mineral is an important component of clay.

Left: Nanotechno-logy from the stone age, 3000 B.C.: Mehrgarh clay figu-rine, exhibited in the Musée Guimet.

the nanoparticle technology of our ancestors

Humans have been making technical use of the properties of nanoparticles since prehistory, but they did not know it. Perhaps the oldest examples are objects made of clay. Clay largely consists of the mineral kaolinite, which has a structure of very thin platelets, only a few tens of nanometres thick. These are white, soft and very malleable, but, most impor-tantly, they slide readily over each other when the mineral has absorbed water. That is why clay is so smeary and easily formed. Starting from the eighth century, the Mayas were able to paint their clay figures with a high-tech pigment which, once again, contained a clay mine-

ral, this time palygorskite. The translucent mineral sometimes forms felt-like mats at its deposit sites, so it is sometimes known as „mountain leather“. The mineral is perfused with nanometre thin channels which are filled with water. By heating the probably pulverised material and adding blue organic indigo pigment, the Mayas succeeded in synthesising an inorganic-organic composite material, a pigment of high stability which could resist the ravages of time. In the USA, the firm MCI Mayan Pigments, Inc. is now producing the old pigment once more. Damascus blades enjoyed great renown in the Middle Ages because of their filigree markings, their sharpness and, above all, their fracture toughness. For a long time, modern metallurgy was unable to find a scientific explanation for these properties; at the end of 2006, however, scientists of the Institute for Structural Physics at the Technological University of Dresden discovered the probable solution to the

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Amiens Cathedral. The red in the mediaeval windows is due to colloidal nano-scale gold.

puzzle: Damascus blades contain carbon nanotubes, so-called buckytubes, some of which are filled with cementite, a compound of iron and carbon. It is clearly this nanowire reinforcement which gives the Damascus blades their legendary properties, or at least explains their fracture toughness. The early smiths could not have known about the nanoscopic factor in their success, but researchers today believe they were skilled in experimenting with additives of wood and leaves and special iron ore from India. The mediaeval makers of stained glass windows also understood colouring with nanoparticles. The

brilliant red in church windows is caused by a colloi-dal, or in other words, an extremely fine, nano-scale dispersion of gold. This colour endures for centuries.

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Nanoparticles in the Technosphere

If all 800 million vehicles which now exist were to be converted to an environmentally friendly fuel cell technology requiring plati-num as a catalyst, the earth‘s economically useful platinum reserves would be exhausted within 15 years, estimate scientists.

Indium, which, among other things, is indispensable in the computer industry for the manufacture of flat screens, says the U.S. Geological Survey, could be the first high-tech element to run out, possibly in as soon as ten years. If not for all, for many of the high-tech elements which are becoming scarce, nanoparticle technolo-gy will be able to provide a complete replacement, largely made of inexhaustible elements such as carbon and silicon. Before that, it can research and utilise the sophisticated laws of the nanocosmos for improvements, increasing efficiencies and making massive savings in material, including platinum. Platinum is usually catalytically active (accelerating a chemical reaction without itself being consumed) in the form of submicroscopic crystals. In crystals the

elementary building blocks, atoms or molecules, are stacked regularly, like tomatoes at the greengrocer. Arrays of spheres packed like this cannot be divided

In a crystal, the atoms are stacked like fruit in a bazaar. If the tomatoes are to remain whole, only certain planes can be laid through the stack, these being more or less stepped according to inclination.

NANOPArtIClEs IN tHE tECHNOsPHErE

Computer simulation of a nanoparticle with a gold core and a silver skin. Preferred planes can also be recognised in the stacks of atoms.

Simulation of a gold cluster, including models of the crystal surfaces. In the basic state on the left, smooth atomic surfaces are formed by prefe-rence; the excited state on the right has rough atomic surfaces which, as a rule, would be more active in a catalyst.

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by planes at all angles because, unlike tomatoes, atoms cannot be cut through. Among the many boundary planes of the crystal which are still possi-ble, the atomically smooth are preferred by nature, in which as many surface atoms as possible have fixed bonding partners. Then, as a rule, however, the catalytic activity, for which free bonds („dangling bonds“) are mainly responsible, is not as high as that which occurs on atomically rough interfaces. These „exotic“ crystal surfaces can also be stabilised by alloying with different elements. Nano-scale particles also make it possible to resort to less active substances for catalysis, for at the nanometre scale even otherwise unreactive metals like gold become active, semiconductors become metals and metals become semiconductors. A particularly refined nanoparticle variant has now been synthesised by Peter Strasser at the Uni-versity of Houston, Texas, USA. These particles have a core of copper and cobalt and a skin of platinum and, in a fuel cell, have from four to five times the catalytic activity of pure platinum for the cleavage of oxygen required.

Palladium nanos on bacteria membranes for

catalysis

Sometimes nanoparticle technologists discover unexpected helpers, like Bacillus sphaericus JG-A12. This bacterium was discovered in 1997 by a team of biologists from the Research Centre Rossendorf (FZR) on the uranium ore waste heap at Johanngeor-genstadt in Saxony, where it had developed a very robust protein shell as protection against the heavy metal uranium. Large areas of the shell are cove-red with a very regular pattern of nanometre fine pores. When the FZR scientists placed the skin of the bacterium in contact with a salt solution of the noble metal palladium, using infrared spectroscopy, they observed a close bonding of the salt complexes with their substrate. Finally, when the palladium salt was chemically transformed into the pure metal, minute nanoclusters grew in the pores, small, regular collec-tives of atoms with only from 50 to 80 members. The-se nanoclusters display considerably higher catalytic activity than conventionally dispersed palladium, for example in the decontamination of vehicle exhaust gases.

Perfect palladium nanocrystals grow in the pores of a bacterium membrane.

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electrical energy in a short time. These do not exist yet, but their realisation appears likely if the develop-ment to date of the lithium ion rechargeable battery continues at the same pace. Optimism is justified by the refinement of certain details, such as the „sepa-rator“. Lithium ion accumulators require a separator layer which, on the one hand electrically separates two electrodes differently charged with lithium ions and, on the other hand, allows lithium ion to pass when required. A particularly attractive separator comes from Germany, made by Evonik Industries AG, formerly Degussa. The firm has developed a polymer fleece with microfine layers of aluminium oxide ceramic, made possible because nano-scale sintering agents allow the baking and sintering of the alumini-um oxide particles at relatively low temperatures. The composite material, contrary to the suggestion of the term „ceramic“, is so flexible that it can be manufac-tured and wound in a rolling process, like paper. This material, known as SEPARION®, promises to make lithium ion accumulators even safer and to increase dramatically the cycle stability (the number of charge

With nano-scale sintering agents, the foil can be burnt (sintered) at a re-latively low temperature and thus inexpensively produced „roll to roll“.

The FZR scientists want to extend their bacterial clustering method to other noble metals such as gold. As they have very precise knowledge of the nature and location of the bond between the noble metal and the skin of Bacillus sphaericus JG-A12, they should be able to trim the shell of the bacterium for the purpose by means of gene technology. Then, the uranium heap dwellers could even be used to ma-nufacture materials with new magnetic and optical properties. So surprises are possible at any time in the nano-cosmos. The nanoparticle technology will play a very crucial role in overcoming future material shortages.

Apart from this, the history of raw materials has always been very changeable. The 17th century, for example, was entirely untroubled by the lack of platinum. In the Columbian region of Chocó, the metal, which was recovered together with gold, was regarded as an undesirable impurity which had to be expensively sorted out by hand. In the end, howe-ver, they did find a use for it, even if an illegal one: A gold plated platinum bar could be sold as a gold bar, because the density of platinum is similar to that of gold. This made the deception hard to detect. In order to put an end to this problem, the government simply had large quantities of platinum collected and sunk in the Bogotá River.

Nanomaterials for new rechargeable lithium

batteries

The vehicles of the future would not necessarily have to be loaded with chemical fuels if accumula-tors existed which could take up large quantities of

Uranium ore waste heap, home of „Bacillus sphaericus JG-A12“, which possesses a tough skin with regular arrays of pores.

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Lithium ion accumulators of the latest generation have a ceramic se-parator foil which makes them very much more robust, both thermally and mechanically.

and discharge cycles possible without significant fall in quality). Evonik Industries AG claims ten thousand cycles for SEPARION® equipped accumulators, twen-ty times more than can be expected from a current notebook battery. However, even in new accumulators, the energy storage density leaves much to be desired. Here, with the help of nanoparticles, which can be produced in a plasma torch, there is hope of an improvement by a factor of three or more - if a number of complications can be sorted out. In the case of success, use for electri-cal vehicles would be the next step, particularly since inexpensive power electronics is now available for the efficient control of electric motors. There are also new magnetic materials for lightweight, high perfor-mance motors - also made possible by nanoparticle technology. The lithium ion accumulators would also

be supported by very fast charging and discharging supercapacitors (Supercaps) with nano-scale dielec-trics, with which power generated, for example, by braking of an electric vehicle could be immediately ta-ken up and then, appropriately regulated, passed on to the lithium ion accumulator. Conversely, supercaps would contribute to power surges for acceleration. The development of new lithium ion accumulators and supercapacitors is supported by the BMBF with considerable funds in the joint projects LiBaMobil and NanoCap. The high cycle stability of the new lithium ion accumulators would also make them suitable as effi-cient, mobile electricity storage for balancing power, thus simplifying the expansion of renewable energies such as wind and sun, with their natural fluctuations.

separator Negative electrode separator Positive electrode

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Use of nanoparticles: silver as a bacterium killer

Of the metals quoted in connection with nanopar-ticle technology, silver is currently the second most frequently mentioned, both in praise and in war-ning, by reputable and dubious sources. The metal is an old acquaintance in the history of technology and has been used for at least 8000 years. Alexander the Great is already said to have valued the sterilising effect of the metal and, therefore, to have favoured water containers of silver. In recent times, the anti-bacterial effects of silver, frequently used in the past, have been rediscovered, as the growing resistance of many organisms to standard antibiotics makes alternatives desirable. As in other metals, transformation of silver to its nanoparticle state changes a number of properties. In comparison with the tangible metal, for example, silver nanoparticles, have a stronger effect per mass on bacteria and viruses, merely because of the higher proportion of surface atoms. While sections of alter-native medicine ascribe to silver ions almost magical effects on body and soul, environmental protection organisations see a great danger in silver nanoparti-cles and are therefore demanding a halt to the sale of washing machines with built-in silver nanoparticle generators. The manufacturer points out that, while his PR „refers to silver nanoparticles, these do not possess any altered properties, but, from a chemical point of view, are still silver ions. However, these are ascribed the strongest anti-bacterial effect.“ The cacophony of disputing voices is a clear sign of one thing: the need for research and education. Without anticipating the results of the research con-cerned, it must be said that the industrialised coun-tries already have many years of experience with extremely finely dispersed silver in the environment, involuntarily and everywhere. In the year 2000, the City of Vienna alone complained of a silver loading of 1 tonne per year in its waste water, which passed into the sewage sludge, which was incinerated and the ashes of which were then spread over the fields as fertiliser. As the content of the sludge ash threa-tened to exceed the permitted limit of 50 mg silver per kilogramme ash, abandonment of the process was recommended. Elsewhere, including in Germa-ny, the spreading of unincinerated sewage sludge components as fertiliser is possible. These masses must inevitably contain finely dispersed silver. The

silver loadings in Vienna‘s waste water were caused, as also in the waste waters of other municipalities, by the discarded wastes from photochemical processes (fixing baths). These amounted worldwide to 500 tonnes of silver per year. No disastrous consequences have yet been reported. However, this figure represents an enormous waste. In 2005, the much quoted material scientist Armin Reller from the University of Aug-sburg estimated the reserves-to-production ratio of silver, calculated from demand, production and geological availability (all assumed as remaining constant), at only twelve years. If all the estimated 400,000 washing machines in Vienna were silver machines and if they emitted the 0.05 gram silver per year specified by the manufac-turer, this would amount to 20 kilograms per year or

Over the decades, through the fixation of black and white photographs alone, hundreds of tonnes of nano-scale silver have been released into the environment without detectable consequences.

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2 % of the silver annually tipped down the drain by thoughtless photo amateurs - before the advent of digital photography. A whole series of small and medium sized enter-prises are currently researching possibilities of using the anti-bacterial effects of colloidal silver for wor-thwhile products. One of these is Bio-Gate in Nurem-berg, which, in collaboration with scientists from the Fraunhofer Institute IFAM in Bremen, coats the surfaces of medical instruments with anti-bacterial silver. This can be very useful, since organisms can get into the body by way of contaminated catheters

and scalpels, leading in the worst case to a sepsis, extremely dangerous blood poisoning. More people die from inflammations caused by infected catheters than in road accidents. The potential risks of nanoparticle technology must always be balanced against the risks they elimi-nate.

Raster electron microscopic image of silver nanoparticles, mean prima-ry particle size 50-200 nm

Photo below: Prototype of a silver-coated catheter. The silver can also destroy organisms which have become resistant to antibiotics.

Photo above: Transmission electron microscopic images of silver nano-particles, embedded in a silicon oxide plasma polymer film.

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„the law says, put simply, that we have a duty to put products into circulation safely. And that is all it says. It does not matter whether the products are nano, micro or macro.“

dr. Markus Pridöhl, Coordinator of Nanotech-nology at Evonik Industries AG

How big is a nanoparticle?The current definition of a nanoparticle proposed by the International Standards Organisation, ISO, says: between approx. 1 and 100 nm. But „between 0.1 and 100 nm“ is also seen. The lower limit there would be in the range of the atoms? These definitions must be harmonised. If every institute has its own definition, we shall continue to talk at cross-purposes. That is why I am very much in favour of the consistent use of internationally stan-dardised terms in order to avoid misunderstandings and to make progress in the field. What does that mean for your products?According to this definition, Evonik Industries AG, formerly Degussa, does not make nanoparticles, but nanostructured materials in the form of aggregates. These aggregates are constructed of nano-sized buil-ding blocks and therefore display the same specific surface as nanoparticles, but they are much larger than the individual building blocks. Are there any other reasons for norms and stan-dards?ISO standards are also important for the preparation of nanomaterials and nanoparticles for toxicological tests. Very many references in the literature are of little practical use because the materials, for an in-halation or a cell culture test, for example, have not been reproducibly prepared. If you do not know how large these particles are or how they are dispersed, you cannot retroactively derive any effects related to particle size from these studies. It is therefore very important to introduce much higher quality stan-dards into scientific work of the subject of toxicolo-gy with nanoparticles or nanomaterials, and here standards in the field of sample preparation would also be helpful. „Nanoparticles“, „nanostructured materials“, is that really more than just splitting hairs?Absolutely. For instance, we manufacture our oxides in flame reactors. In these reactors, the nanoparticles just formed meet at such high temperatures in the gas phase that they melt and form aggregates which are really fused together. These aggregates possess a surface chemistry that leads to a further very strong

Interview with dr. Markus

Pridöhl, Coordinator of

Nanotechnology at Evonik

Industries AG

Experience with the industrial manufacture of

nanomaterials

Industry has decades of experience in the handling of nanomaterials, only they used not to be identified as such. The production volumes for the nanostruc-tured tyre filler carbon black, for example, amount to millions of tonnes per year. This great expertise naturally makes the standpoint of the industry parti-cularly interesting.

The separator foil in the lithium ion accumulator separates the materi-als of anode and cathode, applied to a copper or aluminium foil.

At the same time, one thing is very clearly in the interest of industry. The economic significance of the development is so great that any setbacks due, for example, to a lack of safety awareness would be very damaging – a warning example here is gene technology.

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mutual attraction and, as a result, they continue to agglomerate, becoming even larger. So, when you finally pack your powder into a sack and put it on a train, it is agglomerates, or larger particles?Exactly. What experience does Evonik have with the safe handling of your nanostructured materials? We have been producing the reinforcement fillers silicon oxide and carbon black for 60 years, and nanostructured titanium dioxide for more than 35 years. Today, we manufacture more than a million tonnes of these materials. So we really have extraor-dinarily wide and longstanding experience with our products, including their safe handling. Years ago, we founded a special department in which experts work on techniques for the low-dust handling of our products. With this knowledge, we first give our customers support with correct and safe handling. Secondly, however, it also contributes to reducing dust at the workplaces in our firm. For the manuf-acture of nanostructured products, we largely work in closed facilities, often additionally with negative pressure, which guarantees safety, even in the case of leaks. Our employees have also been subject to medical examinations for over 33 years. Among other things, these include lung function tests, resting ECG, blood pressure measurements and a normal anamnesis interview in which the employee is questioned about any health problems. The studies have given no indication of anomalies in comparison with the „normal“ population. What is so special about the titanium dioxide produced by Evonik?The special feature of our nanostructured titanium dioxide is that it is transparent for visible light, but absorbs or reflects UV radiation. These properties are used in cosmetic products, especially in sun creams. The advantage is that the sun cream cannot be seen on the skin, but the skin is particularly effectively protected against UV rays. Skin contact appears to be harmless! In fact, the safe use of titanium dioxide in cosmetic products has been documented by a large number of independent studies. How do you deal with open questions on safety?We take part in worldwide activities for the respon-sible handling of nanotechnology. Nationally, those are the BMBF project NanoCare for safety research and the corresponding VCI, DECHEMA and DIN wor-king groups. Internationally, the ECETOC, OECD and ISO should certainly be mentioned. In addition, we

conduct our own research projects as a complement to these activities or to establish the specific connec-tion with our products. What does that mean in concrete terms?For example, we investigated the question of whether our nanostructured products can break down in the lung into smaller nanoparticles. We tested, both with experiments and with theoretical calculations, using the example of titanium dioxide, what energy is needed to break down the agglome-rates. As a result, we could prove that the agglome-rates are stable in lung fluid. The lipids in the fluid, which enclose the agglomerates and could theoreti-cally disperse them into smaller nanoparticles, sim-ply cannot produce the energy input which would be necessary to break the bonding energy between the agglomerates, to say nothing of that between the aggregates. And we have been able to verify this in corresponding in-vitro experiments. But it has also been confirmed by current experiments carried out within the framework of NanoCare: The agglo-merates of titanium dioxide are found in the lungs of animals exactly as they were previously inhaled with careful measurement of the particle size in the gas phase. So there are a number of indications that these agglomerates do not break down in the lungs. For the macroscopic „mother substances“ of the nanoparticles, there are regulations such health and safety ordinances, toxicological classifications etc. Can these regulations be applied to the correspon-ding nanoparticles, to which new properties are ascribed?The law says, put simply, that we have a duty to put products into circulation safely. And that is all it says. It does not matter whether the products are nano, micro or macro. That means, we are obliged to assess products with regard to their safety, and that is what we do. So there is no need for additional regulati-on. There is a need, however, for the development of additional, refined testing methods. And that is the reason why we also participate very actively at different levels, national and international, in the development of corresponding refined methods.

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close to the ancient hair-dying method quantum dot high-tech can be. The researchers dipped a thin glass tube, 75 mi-crons in diameter, in a solution of lead sulphide na-nodots (PbS) they had obtained by heating a mixture

of oleic acid (the main constituent of olive oil), lead and sulphur compounds and then drying it all with a hot air blower. A uniform PbS quantum dot layer was deposited on the inner surface of the tube and the world‘s first liquid born infrared laser, in which the light spirals along the inner wall of the tube, thus becoming coherent laser light.

Quantum dots

Even the most modern of concepts, like the nano quantum dot, were already used, unknowingly, in ancient times. Two thousand year old Greek reci-pes for the darkening of unwanted fair or grey hair specify a paste of lead oxide and calcium hydroxide which, when used repeatedly, still darkens hair today. Researchers at the Centre de recherche et de re-stauration des musées de France have now been able, with the help of an electron microscope, to show why: the hair protein keratin obviously produces crystallisation pits (also see: Nanos on bacterium membranes, p. 9), in which quantum dots of lead sulphide form, nanocrystallites with a diameter of about 5 nanometres. The sulphur comes from the sulphurous amino acids in the keratin. Quantum dots, crystallites like those in ancient hair-dye, owe their special characteristics to the restraints presen-ted by their minute size for the motion possibilities of their electrons. While electrons can assume countless different energy states in an extended piece of metal, in a quantum dot, because of its size, only much more limited ranges are possible. This can make grey ma-terials brightly coloured, for example. Naturally, much more is hoped of quantum dots. They are seen as potential elements for a quantum computer, which should be able to solve certain classes of mathematical problems in a fraction of the time taken by any conceivable conventional computer. Self-organised quantum dots could be the memory elements of the terabyte hard discs of the next generation. If an iron-platinum compound is

vaporised on to a silicon wafer, it naturally forms tiny islands which can be influenced magnetically, so can carry one bit of information. In order to make tech-nical use of this effect, it must be possible to control the growth of these islands precisely, if possible with computer simulations. A team of scientists from To-ronto University, Canada, demonstrated in 2006 how

All glasses contain cadmium disele-nide nanoparticles, only the varying particle sizes producing the dif-ferent fluorescence colours.

The micron-sized „Optical Resonator“ contains quantum dots of nanometre size. With this structure, Karlsruhe scientists are studying light-material interactions.

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At the Institute for Scienti-fic Computation of the TU Dresden, within the fra-mework of the EU project „MagDot“, the researchers want to find out by mathe-matical simulation how regular quantum dot struc-tures can be manufactured - for tomorrow‘s terabyte memories.

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Exotic Nanos: Graphenes

In the course of the voyage of the natural sciences into the nanocosmos, real surprises continually come to light, things no one had expected. This includes the art, using only a soft pencil, of putting oneself in con-ditions similar to those at the edge of a neutron star, and that happens as follows: Graphite is pure carbon in a special crystalline form, consisting of stacks of carbon networks. Within a network, the carbon atoms are firmly fixed together, but the individual networks or layers are very loosely connected, so that they can easily slide over one ano-ther. That is how a pencil with a lead mainly consisting

that they are slightly crumpled, like paper which has been wrinkled and then flattened again. These crumpled graphite networks are currently regarded as really hot stuff in the physics world, not just because of their suitability for electron microsco-py, of course. The electrical properties of the monoa-tomic layers are even more amazing. They display the so-called quantum echo effect, for which Klaus von Klitzing still had to reach temperatures near absolu-te zero, at room temperature, along with a series of related effects. Then the constraint of conductivity to a layer only one atom thick imposes a bizarre kind of collective behaviour on the electrons. They form quasi-particles which appear as light speed electrons - the idea of superfast switches has already appeared in the literature. What is more, the electrical properties of the graphite flakelets are described using mathe-matics also applied to extreme conditions like those prevailing at the edge of a neutron star. Anyone wri-ting with a pencil produces large numbers of graphite flakelets, so pencils lead directly into highly stressed regions of the cosmos. The methods used for manufacturing free mo-noatomic graphite layers are at present not the kind to arouse the enthusiasm of the chip industry – one method is actually to apply adhesive tape to graphite layers and to peel them off until only one layer is left. But if larger, reliably reproducible, mass producible graphenes were available, they would certainly find numerous applications. The carbon networks should really be able to be structured photolithographically, so that any desired pattern could be applied. In this way, quantum mechanical model systems might be created for the most intricate of tasks, like the mathe-matical simulation of a neutron star. Not untypical for nano: From something as insi-gnificant as a pencil mark, through knowledge (and a relatively modest budget), the potential is created for something very big.

Graphenes are 0.15 nm thin networks of carbon atoms only. With their physics, phenomena at the edge of a neutron star in a galaxy can also be described.

of graphite can be „soft“. In writing, layer after layer is detached from the graphite crystals in the pencil lead.Naturally, scientists were not slow to think of isolating such a single-atom layer for study purposes. However, the theory predicted its immediate collapse. Without a supporting substrate, a single graphite layer known as a „graphene“ could not be made. Until 2004, that is, when such layers were discovered experimentally. In March 2007, experimenters, from the Max Planck Institute among others, were able to report free gra-phene flakelets with an area of a square micron and containing 30 million atoms. Such areas are tiny, but they could serve as networks for electron microscopes which do not cast a shadow in the electron beam and could possibly hold a single molecule for examinati-on. The graphene layers owe their stability to the fact

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Particularly great hopes are held for medi-cal applications of nanoparticle technology. Nanoparticles can be made multilayered or in the form of hollow spheres, so a large number of functions can be accommodated in the small particles. Here, their ability to move through the body without apparent obstructions is both an advantage and a disa-dvantage.

Nanotechnology for health and medicine

A major problem of conventionally packed drugs is that they mostly act not only at the point intended, but throughout the body. So most highly potent can-cer drugs also affect healthy tissue. Packed in nano-particles coated with antibodies, they could in future be released directly on the tumour. Another compli-cation: If drugs are not water soluble, they cannot be taken up (unpacked) by the blood and transported to their point of action. These and other problems can be tackled with new, highly variable encapsulation techniques which, for example, solve the problem of water insoluble active constituents as follows: First, the selected active constituents are reduced to nano-particles, which are suspended in a solution and coated with polyelectrolytes. A polyelectrolyte is a polymer whose individual building blocks carry an electrolyte which sheds ions in water. The remaining polyelectrolyte coating of the nanoparticle is then

electrically charged and the shell, with its contents, can move freely in the water, so, as a unit, it is now water soluble. There is no need to stop at one shell. The addition of a polyelectrolyte solution with oppo-site charge leads to the growth of a second coating, repetition of the procedure to a third and so on, layer by layer. Typical capsule walls have 4 to 20 layers and thicknesses between 8 and 50 nm. The technology, developed with support from the BMBF in a joint project, among others, at the Max Planck Institute for Colloidal and Interface Research in Potsdam and commercialised and patented by the spin-off firm Capsulution, permits the manufacture of nanocap-sules of different sizes with almost any pharmaceu-

Nanoparticles in the biosphere

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Nano-scale highlighters, an innovative diagnostics system for the highly sensitive and precise early detection of disorders.

Capsulution has also begun to develop drug delivery systems for the transport of active constituents into human cells, a matter of great importance for gene therapy, for example. In comparison with other products, in particular, greater precision in application and less side effects are claimed for these highly complex systems.

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tical, biochemical, electrical, optical and magnetic properties. Interest is correspondingly great.

Ambivalence on MagForce nanotechnologies

Nanoparticles are so small that, in watery tissue (and humans consist of 70 % water), they can move much more freely than larger particles. This much is known, but there is a lack of detailed studies of the mobility of nanoparticles in tissue. What is more, in the few studies available, unrealistically high parti-cle concentrations have been used, so that it is not clear for most nanoparticle types whether and how they are absorbed by the body, how they disperse in the body and how they change, congregate or are excreted. As far as the penetration and deposition of nano-particles are concerned, the lungs are regarded, for obvious reasons, as the organ most at risk. They pos-sess a very large internal surface for the exchange of gases which can be penetrated by any nanoparticles

in the air, so that the particles can then be distributed throughout the body by the circulation of the blood. Certain nanoparticles can pass through lipid double membranes, so they can penetrate cell organelles such as mitochondria or enter the nucleus of the cell. Negative consequences include inflammatory reactions, blood clotting irregularities, deposits such as plaques, heart rhythm disturbances and disorders of the respiratory tract. On the other hand, medicine has recently been attempting to make use of the absorbency of the lungs for nanoparticles for better medication, against lung cancer, for example. In this case, special organic nanocapsules introduce the enzyme telo-merase into the nuclei of lung cancer cells, stopping their division and the spread of the cancer. This dual character of nanoparticle technology, risk and opportunity, is not an isolated case. Particles containing iron, for example, regarded as toxicolo-gically questionable, are now also being tested, in special casing, for cancer therapy. At the Berlin firm MagForce Nanotechnologies, special iron com-pounds are so coated that cancer cells near which they are injected absorb them permanently. An externally applied alternating magnetic field then heats up the particle cores, and thus the tumour,

Precise planning in 3D: The physician can decide the quantity of nano-particles to be applied before the treatment.

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destroying it or rendering it more receptive for che-motherapies. This method, hope the developers, who are supported by the BMBF, will one day rank equally with radiological methods, but without their side effects. The technique should be especially helpful in the treatment of insidious brain tumours like the glioblastoma. Nanoparticles, which contain magnetic cores, like those synthesised by magnetotactic bacteria (see page 9), can even be dragged to their action site with special high-powered magnets which generate a particularly inhomogeneous field. Their shells would be loaded with active constituents. Application of a powerful ultrasonic field, which does not dama-ge healthy tissue, would then burst the shells and release the drug. There are many ideas like this. The umbrella term is drug targeting, the administration of drugs targeted at diseased tissue. Until now, it has been necessary and normal to expose the whole body to a drug for the treatment of a small inflammation, for example. With efficient drug targeting, the dose could be raised for this inflammation alone, with no fear of increased side effects.

High gradient magnet for the control of magnetic particles in the body. The magnet, developed within the framework of the BMBF project „Nanomagnetomedicine“, is light enough, at 47 kg, to be swivelled over the patient‘s bed. The previous magnet weighed 1.5 tonnes.

Nanotechnology for food

Nanotechnology is already used today in food tech-nology, even in unexpected sectors like the manufac-ture of luxury chocolates. Nanotechnology also has great potential in the food sector. Nanosensors, for example, will in future provide information on the age and condition of foodstuffs (see „Nanosensors for the food industry“, page 31). In industrialised countries, according to calculations by the BBC, 40 % of the food produced is thrown away. Reliable infor-mation on freshness and suitability for consumption can reduce such waste, for foods are today thrown away not because of their actual condition, but on the basis of the best by date alone. Great expectations are also associated with the use of nanomembranes in the field of sterilisation at low temperatures. In view of the potential risks of such a use, this deve-lopment is being closely watched by the Ministry for Consumer Protection and the Federal Institute for Risk Assessment. „Nanotechnology for food“ covers a wide variety of different areas of technology, some of which can be classified as naturally harmless.

Nanoparticles in tumour tissue: Left, the healthy cells, right the cancer cells which have been loaded with nanoparticles.

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A glass of wheat beer. The large bubbles grow at the expense of the small, a phenomenon widespread in nature.

Sieves, Filters, Membranes

Sieves, filters and membranes have long been a part of food technology; nanotechnology merely repre-sents a refinement in this sector. Filters with pore sizes of less than a micron can stop bacteria and finer ones can even stop viruses. This makes them suitable for the cold sterilisation of juices, milk and other liquids, while conserving important constituents like vitamins. Today, where particular reliability is required, even filters made of silicon wafers, like those for the manufacture of semiconductors, are used. Using photolithographic methods, submicro-scopic holes with very precisely defined dimensions are etched in these filters. Filters like this allow the exact mechanical type sorting of substance mixtures. As a rule, the membrane thicknesses are smaller than the diameters of the holes, resulting in substance throughputs two or three times greater than those with conventional filters. Conversely, filters like this can be used as nozzles for the production of stable mixtures of substances like fats and water which, in nature, tend to separate.

Such a mixture is found in ice-cream, for example, together with air, and if this remains for a long time in the freezer, it usually gets a coating of ice needles: the air, fat and water have partially separated. With nano-nozzles, however, ultrafine, uniform droplet mixtures can be made which break down much more slowly, so manufactured ice-cream would remain stable for longer. The reason for this is two rules which apply to fine substance mixtures, dispersed in droplets or foams: „The large swallow up the small“ and „If something very small wants to grow, it needs help“. Both rules can be studied in a glass of wheat beer. The initial-ly fairly homogeneous head of foam breaks down into bubbles of different sizes, the large ones visibly growing at the expense of the small ones. The main origins of the beer bubbles, when the great distur-bance of the pouring has settled down, are specific points on the glass wall, small faults, lint or corrosion pits, at which the so-called nucleation work for the formation of gas bubbles is reduced, for the energy balance for bubble growth only becomes positive at a specific minimum size. The faults reduce this mini-mum size, then it bubbles. So, in substance mixtures which should remain stable (like mayonnaise), care must be taken to ensure that the bubbles/droplets are very uniform and, if possible, remain below the critical size which allows them to grow.

Micelle, my Belle

Many healthy substances like omega-3 fatty acids do not taste good and fats and oils, the solvents and carriers of important vitamins, do not mix with water. Both problems could be solved with nano-en-capsulations with an outer skin which bonds readily with water and which only opens when it reaches the stomach, which is not sensitive to unpleasant fla-vours. Nano-capsules also have the great advantage that they cannot be seen with the naked eye, so they do not spoil the appearance. The manufacture of nano-encapsulations is now possible with a whole series of processes, including those using tensides. These have longish molecules, one end of which likes water and the other, fat. So the fat loving ends of the tenside molecules settle on the fat and the water loving ends on the water. The result is the formation of countless small fat globules, covered with tenside molecules like a hedgehog‘s prickles and suspended in the water like a mist - fat and water are mixed, which is not possible without

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tensides. According to this principle, refined formu-lae have been developed, protected by many patents, for enclosing various active constituents in capsules with a diameter of 30 nm.Another possible application of nano-encapsulation: Invisible, encapsulated vitamin C, technically known as ascorbic acid, as an anti-oxidant for edible oils. Nano-encapsulated, ascorbic acid can even protect milk and yoghurt products, so that they no longer go sour. This process is now subject to a trial under food legislation. The objections which have increasingly been heard recently in connection with nanopar-ticles in food may perhaps be worthy of discussion for mineral substances, but cannot apply to groups of substances like fats. The body itself works here with nanoparticles. Anyone who drinks milk or eats an egg swallows huge quantities of micelles and, furthermore, the ability to be broken down into the smallest particles is actually a precondition for the body‘s utilisation of nutrients.

Richard Jones, Professor at the University of Sheffield and author of a weighty study on the risks of nanotechnology, says,

„Most nutrients are naturally nanostructured or con-tain nanoparticles. Anyone who wants to avoid nano-particles cannot drink any more milk. ... At the moment when the constituents reach the bloodstream, they are all nano-scale.“

Controversial visions: Protein nutrition of the future

Three quarters of the available fresh water, a third of the agricultural land and a fifth of the energy used are currently utilised for food production. In the year 2050, 9 billion humans are expected, for whom, by the standards of the industrialised countries, 450 billion tonnes of meat must be provided per year - a meat cube with sides 700 m long. Meat production is very inefficient for inherent reasons. To produce one kilogramme of animal protein, it takes three to ten kilograms of vegetable protein. Some experts are therefore demanding a protein transition, which would not mean dispensing entirely with naturally grown meat, but its replacement with high quality vegetable protein in various foods. Acceptance will largely depend on the structure of the Novel Protein Foods (NPF). The advantages of such a technology for humans and the environment are not particularly convincing, but are being intensively researched by the food industry. The Netherlands hold the lead in this field (particularly the University of Wagenin-gen), for one very good reason, among others: Becau-se of its intensive animal husbandry, the country has a severe slurry problem.

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With chips from the Fraunhofer Institute for Silicon Technology, ISIT, fast DNA sensors for the detection of pathogenic bacteria and other biogenic substances are being developed.

The growing world population will have to place new, environmentally sounder forms of food production alongside the traditional methods. Corresponding technologies which include nanotechnology are being researched particularly intensively in the Netherlands, where the soil is unacceptably polluted with slurry.

Nanosensors for the food industry

Much food is thrown away merely because its best by date has expired. The best by date, however, is only a minimum estimate of keeping quality. If the food package had a cheap analytical device on board, that could signal the edibility instead of the best by date, permitting much more economical householding. On the other hand, rotten food is also sold. Nano-sensors could help with both problems, perhaps those with nano-wires of different materials, only a few millionths of a millimetre thick. When a foreign substance docks on such thin wires, their electrical characteristics change so dramatically that, in princi-ple, not just bacteria, but tiny viruses and even single molecules can be detected. What is measured depends on the coating of the nano-wire. If ammonia is to be detected, the coat should absorb ammonium molecules by preference, highly selectively if possible. Use can naturally also be made of antibodies which only bond with mat-ching antigens, thus making them quickly detecta-ble.

Nano-wire sensors would have the great advan-tage that they only consume very little energy, in the order of a picowatt, about a millionth of a millionth of the power of a torch. Energy levels like this can ea-sily be provided by transmission to RFID radio labels. With a combination of radio label, plastic display and nano-wire sensor, justice could at last be done to every single cheese on the supermarket shelf. The immature and over-ripe cheese would signal its condition with a lower price and the one which is just right with a higher price, and no more would be thrown away. True, in the corner shop, the grocer would have managed that with the help of his nose, but the grocer is no longer there.

NANOPArtIClEs IN tHE BIOsPHErE

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Health effects of nanoparticles

the closest attention is currently focussed on inorganic nanoparticles, in which there is great commercial interest, which could the-refore be manufactured in large quantities, which are also persistent enough to enrich themselves in living tissue or in the environ-ment and for which there are plausible paths into the environment and into humans.

Like all technologies, nanoparticle technology will show its good and bad sides. The special properties of specific nanoparticles make them interesting for use in a kind of nano-medicine on the other hand, while the same properties also mean that new risks can be anticipated. Harald Krug, Professor at the Institute for Toxicology and Genetics in the Research Centre Karlsruhe and Coordinator of the BMBF project NanoCare (see interview on p. 48), puts it like this in his lectures:

„We have learnt to work with metals, making tools to make our lives easier, but also weapons. We have invented the car and road traffic kills half a million people a year and injures a further 23 million. We have manufactured new substances like pesticides which, insofar as they are persistent, have an adverse effect on the environment and our quality of life. It may therefore be concluded that new, nano-scale materials will have at least some undesirable side effects.“

But in order for nanoparticles to cause side effects or health problems in the human body, they first have to get into it.

Gateways for nanoparticles

One large potential gateway, with an area of 2 m2, is the skin. However, studies have shown that healthy, unbroken skin presents a reliable barrier. It is ano-ther matter with skin that is broken or already da-maged, perhaps as a result of sunburn. Here, experts advise against avoidable exposure (see interview with Prof. Tilman Butz on page 38).

The gastro-intestinal tract (GIT) – the mouth, gullet and digestive apparatus, with its 2000 m2, of-fers a vastly greater area, but the research literature contains no cases of inorganic nanoparticles being absorbed or allowed to pass through the walls of the GIT except when they were especially prepared for the purpose. The same does not apply for nano-scale aggregates of fatty droplets, nutrients with which fine capillaries supply the cells. In the case of intravenous feeding, nano-scale droplets, artificially produced with high pressure nozzles, are also used. Nano-scale droplets are also planned for the trans-port of drugs. The olfactory epithelium, the mucous membrane in the nose, is small, with an area of 5 cm2, but it merits particular attention because of its closeness to the brain. The 140 m2 active area of the lungs is currently regarded as the most important gateway for inorga-nic nanoparticles. The particle mobility in the lungs is known from studies of smokers. There is a series of well researched clinical syndromes connected with dust contamination, which could also be significant for the epidemiology of nanoparticles.

The lungs have an internal area about the size of a tennis court, so they offer potentially dangerous particles the most important entry surface. The probability of entry also depends on the type of breathing; sport is unfavourable for particle exposure.

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brownish yellow or pale green.“ What was to make asbestos undesirable as a material in the industriali-sed societies was its „fibrous“ nature. When asbestos is mechanically stressed, fragments of this fibre are released into the air and if these are inhaled, they can have disastrous consequences, such as lung cancer. And asbestos was used in large quantities in the industrial societies. As early as 1820, the fibres were woven to produce fireproof clothing for firemen. In 1900, an Austrian patent was issued for so-called Eternite, a building material containing asbestos, out of which, from this date on, large quantities of roof tiles, corrugated roofing, pipes etc. were produced. The Eternite was not, as the name suggested, eternal, but weathered and released asbestos fibres. By 1900, asbestosis was recognised as a sickness, an inflamm-atory reaction of the lung tissue which damages them severely and, after a long period of latency, can finally lead to lung cancer. Among other things, buildings were lavishly coated with sprayed asbestos as fireproofing, like the Palace of the Republic in Berlin or the Deutsche Welle tower in Cologne in more recent times.In 1979, sprayed asbestos was prohibited in Germany, followed in 1993 by asbestos in general and, since 2005, there has also been an EU prohibition. The long latency period between exposure and onset of the disorder has ensured that asbestos will remain a topic for many years to come. In 2003, the health insurance bodies registered 3500 new occupationally caused disorders, with a rising trend. The annual costs of these disorders are now over €314 million. Such a story, everyone agrees, must never be repeated. The asbestos experience is an essential back-ground to the safety debate accompanying nano-particle technology. Important in this connection: Bonded asbestos, which lies in the earth or has been fixed with concrete, is harmless. Bonded synthetic nanoparticles may also be regarded as completely harmless. The following risk assessment relates exclusively to unbonded nanoparticles which could enter the human body through breathing, eating or other means.

The Cologne tower block formerly used by Deutsche Welle is a case for asbestos remediation.

Asbestos has a glorious history. The ancient Greeks used the variant known as „Carpathian stone flax“, plaited, as an indestructible wick for oil lamps. Kaiser Karl V. is said to have had a tablecloth woven of asbe-stos, which he liked to have thrown into the fire after a meal, only then to be retrieved undamaged to the astonishment of his guests. In the technology of the new age, asbestos was also regarded as a wonder material. With some justi-fication, as the substance possesses high strength, is an excellent thermal insulator, is heat and acid resi-stant and, depending on modification, is so mechani-cally hard that it could even be used in brake linings.Asbestos is a naturally occurring mineral, main-ly consisting of silicon and oxygen, with varying proportions of embedded calcium, magnesium, iron and nickel. So asbestos exists in many variants. As „simple asbestos“, Klockmann‘s Text Book of Mine-ralogy names chrysotile asbestos, „parallel fibrous masses of shimmering silky lustre, pale yellow,

HEAltH EFFECts OF NANOPArtIClEs

Asbestos – a story that must not be repeated

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Nanoparticles – how dangerous?

At present, the vast majority of nanoparticles with which people come into contact are unintentio-nally caused by industrial activities, in road traffic and through normal technological civilisation. Increasingly, however, attention is also turning to industrially produced nanoparticles: For 2007, the production of fullerenes, for example, was estimated at several thousand tonnes. What began as a labora-tory curiosity has now reached industrial scale, also making it interesting for the toxicology, the science of the tolerance to substances and, of course, for the protection of workers and consumers (see page 50). Nanoparticles are unique insofar as the physical models applicable to the particles begin to change at the transition into the nanometre dimension: While classical physics applies above 100 nm, quantum physics applies below this size, with quite different laws. The transition is blurred. As a result, magic can be performed with nanoparticles: merely by altering their size (depending on the material the particle is made of), properties such as solubility, transparency, colour, conductivity and melting point can be modi-fied. Furthermore, a large proportion of the atoms in nanoparticles are surface atoms. Thus, a spherical iron particle with a diameter of 5 nm would have about 27 % surface atoms, while a particle with a diameter of a micron would only have 0.15 %. But surface atoms are not bonded with neighbouring atoms around them, so they have free bonds and these are very reactive. Therefore they do not remain unbonded for long, attaching themselves to each other or to available free molecules or surfaces. This, as long-term air measurements in the town of Erfurt have shown, has the curious effect that a reduction of fine dust can increase the number of nanoparticles in the air and, thus, the concentration of ultrafine dust, for with less larger particles in the air, the finest particles lack possibilities for attaching themselves. The high number of surface atoms also increases the catalytic activity of these particles, that is the ability to accelerate chemical reactions without themselves being consumed, which makes them interesting for industry. Naturally, if the active surfaces cannot be shielded, the particles rapidly agglomerate to form larger, less active units and the interesting properties are lost. A large number of readily bonding, catalytical-ly active surface atoms may, of course, also have undesirable consequences and render nanoparticles

toxic. In some of the literature, it is even assumed that potential nanoparticle toxicity rises constantly as the size decreases. This relationship, however, cannot be strictly true, for molecules and atoms, the smallest compo-nents in material chemistry, would then have to be naturally toxic. But this is the matter of which we are made.

Particle analysis with the ATOFMS aerosol mass spectrometer. Individual particles are detected in the air and sorted according to size by light sensors. After subsequent vaporisation and ionisation, the composition of the particles can be determined in seconds, practically in real time.

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research on respirable aerosols

The most important source of information on the toxicity of nanoparticles is currently the literature gathered from aerosol research on the effects of fine dust PM10, which, however, cannot be equated with industrially manufactured nanoparticles. PM10 stands for particles with a diameter less than 10µm (1 micrometer = 1,000 nanometres). The body‘s own mechanisms for the neutralisation of particles of this size range in the respiratory tract - like embedding them in mucus, which is subsequently disposed of - fail in the case of nano-scale particles; one reason why the entry of such particles into the lungs is cur-rently receiving the greatest attention. The lung has an internal surface the size of a tennis court (approx. 140 square metres) and because it is designed for a rapid exchange of gas, the barriers to the blood cir-culation in the pulmonary alveoli are extraordinarily thin, so they may also be passable for nanoparticles. In fact, the aerosol research, which is mainly conducted in Germany by the GSF Research Centre for the Environment and Health in the Helmholtz community, has been able to prove that nanoparti-cles penetrate the lung epithelium and can get into the blood. It may therefore be assumed that nano-particles can, in themselves, represent a health risk, which would have consequences for the evaluation

of air quality. Then, in addition to the mass of the particles in the air, their number would also have to be measured, in order to determine how many portions, including nanoportions, a pollutant is divided into. The difference is important: with the mass of particles in the air as the criterion, the respi-ratory tracts of townspeople have three times the exposure of the population in the countryside, but if the number of particles is taken as the criterion, the

urban population comes off very much worse, with 19 times the exposure of those in rural areas. As sour-ces of manmade dust particles < 10 µm, the aerosol research identified industrial processes with 45 %, the trans-shipment of dry bulk goods with 21 % and dust particles emitted in road traffic with 17 % of total dust emissions. If abrasion from tyres, road surfaces and brakes are also counted, road traffic rises to 33 %. A good proportion of these particles are nanoparticles. If the inhalation of nanoparticles is dangerous and nanoparticles also occur frequently in nature without human intervention, then evolution must have given breathing organisms the ability to deal with nanoparticles. That is in fact the case, but the protection is imperfect. In humans, the nose repre-sents the first barrier. The curvature of the airways presents no obstacle to the free flow of the air, but, because of their momentum, particles larger than 2.5 µm go off course and land on the mucous memb-rane of the nose. Admittedly, this filter is absent in the case of breathing through the mouth, when airborne particles arrive practically unimpeded into the pharynx and bronchia. Particles larger than 5 µm and smaller than 10 nm largely settle here, while the rest flow further. Part is deposited in the bronchioles

Soot particles under the electron microscope.

Two-dimensional gas chromatography: In order to determine their chemical composition, aerosol samples are sorted according to two different principles: 1. Volatility, (x axis), 2. Polarity (y axis). Each peak of the xy chromatogram on the screen represents a chemical compound present in the aerosol. The height of the peak represents its relative frequency.

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and part in the alveoli. Strangely, particles with a diameter of about 500 nm are hardly deposited, but are mostly breathed out again. As their size decreases to 20 nm, the proportion of particles deposited in the periphery of the lungs rises sharply. Whether and how particles are deposited in the lungs also depends on the kind of breathing. Slow, deep breathing transports the most dust into the lungs. Once they are deposited, particles need not ne-cessarily remain permanently in the body. In heal-thy bronchia, for example, the epithelial cells are equipped with cilia under the mucus which, through synchronised waving, transport foreign bodies to the larynx, from where they pass into the gastro-intesti-nal tract and are digested or excreted. Another of the body‘s protective mechanisms: Macrophages move around in the respiratory tract, scavenger cells which not only attack particles they recognise as foreign, but also bacteria and viruses. Of course, tiny nanoparticles are often overlooked. Scientists from the Institute for Inhalation Bio-logy of the GSF have established that inhaled nano-scale particles - ultrafine particles in the jargon of

the aerosol researchers - can land in the livers, in the hearts and even in the brains of rats. The mechanis-ms by which the particles get into the blood circulati-on and internal organs are still strongly disputed, as is the extent to which the results from experimental laboratory and animal models can also be applied to humans. In discussion as possible transport paths, for example, are absorption through the nervous sy-stem (e.g. along the olfactory nerve into the brain), through the lymphatic system or into the blood-stream through the thin 0.5 µm barrier in the lungs between the alveoli and the capillaries. Already damaged lung tissue is considered more susceptible to the passage of nanoparticles into the organism. Its physicochemical nature has a great influence here on the behaviour of the particle in the organism. Ultrafine dusts do not behave in the same way as industrially manufactured nanomaterials - the exact facts will have to be clarified by future research.

With a gamma camera, it is possible to observe over a number of days where marked particles settle in the lung and how long they stay there.

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risk to the heart and blood vessels

It is known from fine dust research that when nano-particles get into the blood circulation, they would normally be arrested and made harmless by macro-phages, scavenger cells, the police of the immune system. Because of their minute size, however, that often does not happen. Then they can even have an effect on the heart. GSF scientists and veterinarians at the Ludwig-Maximilians University in München-Großhadern have investigated some unique relati-onships in this connection. Thus, epidemiological studies have shown a relationship between the fre-quency of heart attacks or sudden fatal cardiac arrest and unusually high particle concentrations in the air, such as those occurring on days of high traffic and atmospheric inversion conditions. A plausible cause and effect chain for this phenomenon cannot be sci-entifically formulated, but it is conjectured that fine and ultrafine dusts may play a role here. One possi-ble explanation: When, in an animal experiment, specific nanoparticles were injected in high con-centrations directly into the bloodstream, the blood

platelets reacted by clotting the blood faster, incre-asing the risk of thrombosis and making infarctions more likely. When, for the purposes of the fine dust investigation, typical nanoparticles acted directly on the cells of the heart‘s musculature and conduction system, a change occurred in the calcium balance, so that the heart muscle was no longer able to contract as strongly. As the bioelectrical activities which make the heart beat are also partly determined by the cal-cium ion concentration, nanoparticles could in prin-ciple contribute to heart rhythm disturbances. The extent to which these experiments can be applied to the real situation, however, is still fully unclear. The corresponding studies are controversial in the specialist scientific scene. But nanoparticles which do not leave the lung‘s alveoli can also have an effect on the heart by acting on receptors on the surface of the alveoli which influ-ence the vegetative nervous system and thus also the heart‘s rhythm. This may then become less variable, so that the heart can no longer react appropriately to changing performance requirements. As a third action chain for high nanoparticle concentrations, such as those which occur in unfa-vourable traffic conditions or forest fires, the scien-tists have identified inflammatory processes which are triggered by the particles in lung tissue and lead to the release of messengers. These increase the clot-ting capacity of the blood and the body mobilises its defences - processes which tend to speed up sclerosis of the arteries. It is therefore undisputed that certain dust particles which come into contact with the human organism over prolonged periods and in high con-centrations can have a harmful effect on health. This also applies for certain industrially manufactured nanoparticles, so the exposure of employees, consu-mers and the environment should, as far as possible, be avoided (see Risk Management p. 46 ff.)

Nanoparticles can cause inflammatory reactions in the human vascu-lar system.

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How can nanoparticles be detected in the skin?One very powerful method is high resolution trans-mission electron microscopy. For this purpose, you need skin cross-sections, so you have to take skin samples, biopsies, skin punch plugs, and slice these into very thin layers of skin. Very thin means about a thousandth of the width of a hair. With high resolu-tion transmission electron microscopy, you can then see individual nanoparticles. The nanoparticles in sun creams are typically about 20 nm in size, and, with the right equipment, you can also find out what these particles are made of. That is certainly not a routine method, as heavy equipment is required. Preparation of the samples is also very elaborate and there is a danger that preparation artefacts will then be visible. What is more, only very small details can be seen and you have no overview of the skin cross-sections; only one small, deep section.The next method I would mention is ion microscopy, better known by the name Particle Induced X-Ray Emission, PIXE. Here, ions, preferably protons, are fired at skin cross-sections, this time not quite as thin, but in the range of a few microns. Here it is no longer possible to detect individual particles, but the advantage is that large areas can be scanned and you can zoom in on areas of interest. Do protons have a greater penetration depth? Yes, the penetration of protons is much greater than that of electrons, so thicker samples can also be studied. A combination of these two microscopic techniques is already very good in my opinion. Then there is another method, so-called laser scanning microscopy, which requires you to have particles tagged with fluorescent markers to make them visi-ble. This is not unproblematic, because the fluores-cent markers must each be bonded stably to parti-cles, otherwise they would give false results. But, this apart, it is a very efficient method, which can also produce three-dimensional images with a certain degree of depth resolution. So these are the three techniques I consider most interesting. Another is the use of radioactive marked particles and autora-

Interview with Prof. dr.

tilman Butz, director of

the Institute for Nuclear

solid state Physics, Uni-

versity of leipzig, Coor-

dinator of the EU project

NANOdErM

Effects of nanoparticles on the skin

Nanoparticles are turning up in more and more pro-ducts, the express purpose of which is to come into close contact with the human body, like toothpaste or sun cream. NANODERM is an international project financed by the EU with the participation of twelve institutes and dedicated to research on possible risks in this connection.

Titanium dioxide particles in sun cream. The substance effectively filters out harmful UV light, without being visible. In European cosmetic products, the photocatalytic properties of the titanium dioxide desired elsewhere are suppressed by coating of the particles, with silicon for example.

Healthy skin is a reliable barrier against na-noparticle penetration. what we are not sure about is what really happens in skin badly damaged by sunburn and already peeling off, if you smear it on then. I cannot imagine that there is no contact with vital tissue, so I would strongly advise against doing anything of the kind.

Prof. dr. tilman Butz, Coordinator of the EU project NANOdErM

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diography. Naturally, that is only possible for skin explants. Little use has been made of this method up to now. What can be done if such elaborate techniques are not available?Very widespread is so-called tape stripping: you take some adhesive tape, like Tesa-Film, and can pull off the surface of the skin layer by layer and analyse what you have removed. Very simple and cheap, but in fact it gives little depth information because it also measures wrinkles, hair follicles and so on at the same time and it appears to show a deeper penetra-tion than is usually the case. The last technique uses so-called Franz diffusion cells. You take a skin explant and mount it in a cell. On one side, the material you want to apply to the skin is added and, on the other side, what passes through the skin is collected in a buffer medium. This procedure is standard but also very prone to errors. If you do not know the path by which the material penetrates the skin, the result is not very informative. Let us assume, you have cut into a hair follicle. Then, you have made a small channel through which the material can pass. Or you may have damaged the skin while mounting it, so it passes through the tear. So those are the relevant techniques. Others require you to take skin samples. That is not something you can do in vivo without damaging the skin. There is no technique as yet for doing this. Is healthy skin a reliable barrier?Yes, it is a reliable barrier against nanoparticle penetration. Everything we know indicates that the penetration into the epidermis is a mechanical pro-cess. The particles are rubbed in mechanically. The upper layer of the epidermis is similar to puff pastry, with loose layers of corneocytes, and the material is rubbed between them. The lower part of the epider-mis, the compactum, is more similar to the pages of a book which have not yet become wet. And we have not detected emigration into the compactum. So healthy skin is a reliable barrier. However, there are two or three publications which give cause for con-cern. In the case of severe mechanical stress, when the skin has been stretched a few thousand times at 45 ° in one direction and then at 45 ° in the other, deeper penetrations have been detected. And how does sick skin behave?Unfortunately, there is not much information about this yet. In the case of psoriasis, as may be imagined, the proliferation, that is the renewal of the skin, is drastically accelerated. As a result, instead of 15 µm of epidermis, you have over 100 µm, so it is much

thicker and contains dead cells alongside living ones. And when that is mechanically stressed, it is like spreading a cut French croissant, a flaky pastry, with cold butter from the freezer: it breaks into pieces. So you then have contact with living cells. Then lesions, microlesions, an open wound you yourself are not aware of because it is so small, is clearly a path where you can have nanoparticles in contact with vital tis-sue and also with vital cells. So, application on open wounds is certainly very unadvisable. What we are not sure about is what really happens in skin badly damaged by sunburn and already peeling off, if you smear it on then. I cannot imagine that there is no contact with vital tissue, so I would strongly advise against doing anything of the kind. There are naturally other paths under discussion, particularly the hair follicles. We have found na-noparticles in hair follicles, at a depth of about half a millimetre. But not in the vital tissue around the follicle. It seems that the cladding of the hair follicle is also a good barrier. The final possibility would be through the sweat glands or sebaceous glands. We have occasionally seen cross-sections of sweat and sebaceous glands, but not with particles in them. In the case of sweat glands, the milieu is certainly not suitable. The formulations of sun screen creams are hy-drophobic, more fatty, so it is almost inconceivable that anything could be rubbed into the sweat glands which would not immediately be flushed out again. In the sebaceous glands it would be more likely, but we have not seen it. In any case, I would say it has little relevance.

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Public awareness and social debate

PUBlIC AwArENEss ANd sOCIAl dEBAtE

Nanotechnology is often described as the art of purposefully using structures between one and 100 nanometres, which are indispensable for a specific function. From this perspective, physicists and chemists have been conduc-ting nanotechnology for a long time without giving it a name.

But regardless of exact definitions, such as those currently being formulated in standardisation committees, public perception of nanotechnology will be crucial for its further development. The term nanotechnology has developed through an interplay of new concepts and visions dealing with the utilisa-tion of the nanocosmos, accompanied by ever more efficient equipment and analytical technology.

Nano – the beginnings

The first to suspect the existence of real treasures in the nanocosmos was Richard Feynman, a legendary American physicist and Nobel Prize Winner. In his 1959 lecture, „There is Plenty of Room at the Bottom“, he sketched for a wondering public the outlines of a new cosmos, the nanocosmos:

„What would the properties of materials be if we could really arrange the atoms the way we want them? They would be very interesting to investigate theoretical-ly. I can‘t see exactly what would happen, but I can hardly doubt that when we have some control of the arrangement of things on a small scale we will get an enormously greater range of possible properties that substances can have, and of different things that we can do.“

Like making high-tech articles such as laser diodes from materials long considered to be undesi-rable impurities. The list of possibilities is very, very long.

The general public‘s idea of nanotechnology, however, was formed by a 1966 film, „The Fantastic Voyage“, in which a team, together with a submari-ne, was miniaturised a million times in order to pass through the needle of a syringe into the body of a be-arer of secrets, where a blood clot had to be removed. Scientifically, that was absolute nonsense, but since then there have been robots in the bloodstream. Then Gerd Binnig and Heinrich Rohrer developed the raster tunnel microscope, which won the Nobel Prize for Physics in 1986. The previously so abstract concept of the atom came within reach. In the same year, 1986, Eric Drexler, an American engineer and fantasy writer, published his book „Engines of Creati-on“, in which he presented the possibility of nano-scale robots, nanobots, also known as assemblers, which, if they got out of control, could potentially turn the world into grey goo. Because Drexler simul-taneously offered the prospect of a nanotechnologi-cal paradise, he nevertheless won a large community of disciples.

Cryo-electron tomography of the interior of a magnetotactic bacterium with a chain of magnetosomes. These are nanocrystals of magnetite in a „mould“ of proteins.

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Nano Hype

While it was Drexler‘s writings which were fol-lowed by the outburst of enthusiasm, the Polish engineering philosopher Stanislav Lem had already predicted nanobots in his book „The Scene of the Crime“ (also published as „Local Inspection“) in 1982. He called them „grippers“. In „ The Scene of the Crime“, at least the grippers only wanted to do good, and they were present everywhere, even in shirts. And if the possessor of one of these wanted to do an evil deed, to stab another human for example, the nanotechnological shirt stiffened so powerfully, thanks to masses of grippers locking together, that the evil intent was thwarted. The wittiest and most intelligent version of the nanotechnology preview was simultaneously the least widespread. Lem had not offered the prospect of a paradise.

End of the Nanobots

Drexler‘s movement received a severe damper in 2001, when Richard Smalley, Chemistry Nobel Laure-ate in 1996, made public his gripping parable of the fat and sticky fingers, as those of the atomic grippers must appear in the nanocosmos. If, at nano-scale, the grippers were as clumsy as the things to be gripped, there was no future for the nanobots, any more than shrimps could be peeled wearing oven gloves. Today (2007), Drexler agrees. The danger of mankind dissol-ving into grey goo has been banished for the time being. In 2002, the bestseller author Michael Crichton excited people‘s fantasy once more with his book „Prey“, in which swarms of nanobots turned on their creators with severe consequences. Stanislaw Lem had already described something similar in 1964 in his novel „The Invincible“, micro/nano as villain. The public remained undisturbed. Meanwhile, in 2000, powerful criticism came from an unexpected source. Bill Joy, Chief Scientist of Sun Microsystems, had published an extremely pessimistic article, „Why the future doesn‘t need us“, in the magazine „Wired“, on the consequences of modern technology, including nanotechnology:

„An immediate consequence of the Faustian bargain in obtaining the great power of nanotechnology is that

we run a grave risk - the risk that we might destroy the biosphere on which all life depends. „

The nanotechnology scene still believed at this time in the concept of self-replicating nanobots and that was precisely the point that had disturbed Bill Joy – which relativises the criticism. In any case, it can be countered that the technologies adopted from the 20th century are mostly unsuitable for the future and urgently need modernisation, according to the state of the art, also using nanotechnology. As Lem said,

„The only answer for a bad technology is a good techno-logy.“

But Bill Joys and other critics also had their good side: They started a serious, broad debate on the opportunities and risks of nanotechnology. And as experience has shown, all technologies depend on a critical accompaniment. Nanotechnology will be no exception. However, especially in the case of nano-technology, attention must be paid to which of its branches the criticism refers. A pair of glasses made scratch resistant with nano-coatings is hardly likely to represent a danger to mankind. And the responsi-bility for the consequences of nanoelectronics does not belong to toxicology, but to cultural criticism.

Tunnel microscopic image of self-organised, nanometre-sized molecule complexes on a copper surface (Background: Simulation).Nanotechnologists have great hopes for self-organisation processes like these, but this technology is far removed from the „assembler“ visions of Drexler.

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Meanwhile, for obvious reasons, one branch of nanotechnology deserves special attention: nano-particle technology. So this was also the main subject of the report „Nanotechnology: Small particles, great future?“, published in 2004 by the Swiss reinsurance company Swiss Re, attracting great interest:

„The mere presence of the particles, even if they should be present everywhere, does not, in itself, represent a danger to humans and the environment. Only if specific properties of the particles should turn out to be dan-gerous, would one have to speak of a danger. As there are no corresponding studies, however, it is hardly pos-sible today to say whether and to what extent nanopar-ticles or products manufactured using them represent a concrete risk.“

This was followed in June 2005 by an equally weigh-ty study by the Allianz Versicherungs-AG. The real risk of nanotechnology, Allianz found, was the gap which exists between its dynamic development and the knowledge of possible dangers and necessary safety standards for avoidance of negative effects.

Nano Fakes

Meanwhile, exaggerated expectations continued to be directed at nanotechnology, so that, together with the discussion of risks, public interest was aroused and made audible in media reports. So, in March 2006, the story of Magic Nano, a glass and ceramic care product which caused serious health disorders after inhalation of the spray, found an in-ternational media echo because it was called Magic Nano. However, the product contained no nanopar-ticles, as was confirmed by the Federal Institute for Risk Assessment after the questioning of experts and suppliers. The manufacturer said he had only wanted to point out that, after the spraying of his product, a very fine film was formed on glass and ceramic surfaces, so it was Nano. Magic Marketing would be a more accurate interpretation. Even the film was not nano, but micro. This case nurtured the fear, felt even by declared nanotechnology supporters, of the unregulated use of nanoparticles, for: What happens if an unthinking producer of cosmetics, for example, stirs nanopar-ticles into his formulae without any testing, just so he can advertise with Nano? Particles which subse-quently turn out to be harmful? The whole branch

would fall into disrepute and the attractive effect of the label Nano would turn into the opposite. But the critics should also be wary - of skating on thin ice and falling for nano-myths.

Nano Myths

Nanotechnology is so new, the nanotechnological personnel coverage – including critics – so thin, the safety debate so new, that a fruitful soil has been laid for myths. One example: In October 2004, in the Pro-ceedings of the Ninth Asia Pacific Physics Conference (9th APPC), Hanoi, Vietnam, 25-31, a publication appeared, according to which about 1200 rice grains of the variety Thai purple had been shot with low energy nitrogen ions - a routine procedure. Then the grains were germinated and the seedlings allowed to grow in the soil until they were ripe. Two of the plants had changed their genetic make-up. While the variety is usually purple, the leaves and stalks of the mutants were green. Now nanotechnology - completely innocent by all the rules of logic - received the killer punch. An author from the nanotechnology-critical Canadian organisation ETC wrote:

„The research project includes the boring of a nanome-tre-sized hole [...] through the wall and membrane of a rice cell in order to inject a nitrogen atom. The hole is bored with a beam of fast moving particles, then the nitrogen atom is shot through to alter the genetic sub-stance of the rice cell.“

This action, nothing to be ashamed of, but which had not taken place in this way, was taken by critics as an indication of the recklessness of nanotechnology research and, with this interpretation, even found its way into the risk assessments of major, reputable organisations. In fact, the radiation of seed in order to create mutations, which also frequently occurs in nature, but not in such close sequence, is routine. The Bava-rian State Agriculture Agency quoted in 2006, „To date, over 1800 new varieties have been put on the market with the help of mutation breeding. In Italy, durum wheat mutants (for pasta) cover about 70 % of the area used for durum cultivation.“ This may be criticised, although plant cultivators have always used mutants, but it cannot be blamed on nanotech-nology.

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Nano disputes

Environmental protection organisations

Naturally, the environmental protection organi-sations have also taken up the theme. Germany‘s largest, the Bund für Umwelt and Naturschutz Deutschland, BUND, calls - like others - for detailed studies on the safety of nanoparticles, but also sees extremely positive possibilities for nanotechnology and points out...„ ... that (superficial) effects for the relief of raw materials and the environment by means of new technologies have frequently only led to the masking of the changes in be-haviour actually necessary. An example is the introduc-tion of the catalyst since the mid-80s. In order to obtain similarly clean air, 80 % fewer cars would have had to be driven today. The superficial focus on technical solutions, which are sold as future technologies, diverts attenti-on from sustainable developments which must offer solutions based on the real causes, like the unsustainable lifestyles of the highly developed industrialised nations.“

they land on the shelves of German supermarkets. Nanotechnology will not change such capers as long as there is money to be made out of them.

Consumer Vote

A consumer conference held in the Federal Institute for Risk Assessment (BfR) on the application of nano-technology in the fields of foodstuffs, cosmetics and textiles arrives at the following statements, among others, in its closing document, the Consumer Vote:

„It is considered a cause for concern that hardly any measurement techniques exist. We find that, to date, there are no limits for the risk assessment of nanopar-ticles. In order to be able to carry out an exact control of nanoparticles, we call for the development of new analytical and measurement techniques and their stan-dardisation by independent institutions. In this way, standards can be set for occupational safety and end products, and risks can be avoided for the consumer. In the risk assessment, the whole life cycle of the product (manufacture, use and disposal) must be considered.“

Here too, the positive potential of nanotechnology is clearly seen.Another demand from the consumers:

„We are of the opinion that research must be conducted on really important topics in nanotechnology in the

So, little would actually be gained if, thanks to cold sterilisation using nano-sieves (now allowing trans-port over longer distances), milk were no longer only to be carried from the German Alpenvorland to Bran-denburg, which has its own cows, but over the Alps, as now happens with supposedly premium quality mineral water. For cost reasons, North Sea shrimps make a detour by way of Morocco for peeling before

The first hybrid Smart. In the USA, a pure electric version with Li-ion batteries is also supplied by hybrid technologies.

The elements in an aerosol sample can be determined using „proton induced x-ray emission“ (PIXE).

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field of foodstuffs (for example, improved drinking water treatment, quality monitoring and assurance, intelligent (smart) packaging and durability) and that products should be developed accordingly.“

Some demands would result in considerably higher costs for the industry involved:

„We demand a compulsory „Nano“ marking, firstly so that the consumer has a right of choice and, secondly, so that deception can be avoided for the consumer. We consider compulsory marking to be especially impor-tant in the food sector, since the substances here are in-troduced into the body directly. ... We need an approval procedure for nano-scale substances in foodstuffs and in their packaging. In this connection, we demand that substances already approved (silicon dioxide, titanium dioxide, aluminium silicates ...) be tested again if they are used in the nano-scale range (supplementary test).“

Association of the Chemical Industry, VCI

The Association of the Chemical Industry lists in its „Positions and recommendations for the handling of nanoparticles and nano-scale substances from a legal perspective“, among other things, (also see interview with Markus Pridöhl, p. 22):

„In the transition to sizes in the nanometre range, the properties of substances - both the physicochemical properties and the biological effects - change. This can be explained by the increase in the surface/volume ratio in comparison with coarser material, the higher surface energy and the smaller particle size. This change in the material characteristics in nanomaterials is currently leading all over the world to questioning whether the applicable legal regulations in materials law and other legal areas are also adequate for substances with di-mensions in the nano range or whether supplementary regulations are required. [...] We consider that existing

The earth‘s atmosphere has proven to be very vulnerable. For this reason alone, a modernisation of industrial society is urgently called for, including the use of nanotechnology.

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law is sufficient to ensure the protection of humans and the environment; amendments or supplements are unnecessary. [...] since the basis of applicable law is not the physical properties of specific substances, but the hazardous properties of substances and the exposure of humans and the environment. The resulting risk must be minimised by appropriate measures. These duties incorporated in the applicable law are not so narrowly formulated that they can only be applied to „conven-tional“ chemicals. In fact, they also cover the special features existing in nanoparticles and nano-scale substances.“

So, all in all, the reactions of those involved tend to moderation. Only the Canadian etc group (the Ac-tion Group on Erosion, Technology and Concentrati-on) demanded an immediate halt to the commercial production of new nanomaterials in 2003:

„In view of the concerns about the possible contami-nation of living organisms with nanoparticles, the etc Group proposes that the governments impose an immediate moratorium on the commercial production

of new nanomaterials and introduce a transparent global evaluation procedure for the consequences of this technology on the social economy, health and the environment.“

In practice, this would mean an end to the develop-ment of nanoparticle technology, which would not be practicable.

In nanotechnology, formerly separate disciplines, such as mechanics, electronics and biology, come together at the atomic level, making possible very many more elegant technical solutions.

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46 rIsk MANAGEMENt IN NANOtECHNOlOGy

Nanotechnology is based on different scien-tific disciplines, which means, among other things, that its statements are proven or rejected on the basis of reliable and objective measurements. the instrumentation needed for this purpose is growing from year to year.

much larger nanoparticles. Microscopes which work with potentially ionising beams also have the great advantage that not only the position of atoms can be determined, but also the elements of which they consist. For when, after ionisation, the atoms return to an electrically neutral state, they emit characteristic radiation or electrons with an energy which betrays their identity and their bonding status, if any.So there is a large number of instruments ready for nanoanalysis, but the scope for improvement is equally great. For electron microscopes and related instruments are large and expensive and, like the lar-ge number of scanning probe microscopes, they too can only examine tiny areas, which, on the one hand, is their purpose, but which makes the characterisati-on of a larger number of particles very time consu-ming. Time is admittedly short in industrial produc-tion, but any changes in the quality of nanoparticles produced must be immediately detected, and the risk assessment also wants quick results. So the exposure to fine dusts and nanoparticles at the workplace is measured with so-called SMPS de-vices (Scanning Mobility Particle Sizers), which allow determination of the number and size of particles in a specific volume of air. The elemental composi-tion of the particles and their shape, however, are determined from filtered out samples, using electron microscopes. Naturally, a cheap and handy device to supply all the information quickly and at once would be highly desirable. In some chemical processes, like heterogeneous catalysis, even the finest details on the surfaces of the nanoparticles used play a role, which is also impor-tant for the toxicity. Nanoanalysis can answer such questions; its improvement is regarded as a key ele-ment in nanotechnological development. In cataly-sis, to remain with the example, small enhancements can result in the saving of millions of Euros, in large quantities of avoided pollutants or even in a Nobel Prize for Chemistry, like that for Gerhard Ertl in 2007.

Nanoanalysis as a basis for risk analysis

Many aspects of nanotechnology were already known when Gerd Binnig and Heinrich Rohrer presented their raster tunnel microscope in 1981. The atomic model, for example, with a size of a tenth of a nanometre, was already long established in physics and chemistry, but with the scanning tunnelling microscope, individual atoms could now be mapped and even shifted around. The atomic force micro-scope subsequently developed by Binnig can now resolve subatomic details and map the oriented che-mical bonds which, for example, hold a silicon cry-stal together. These microscopes and their numerous offshoots represented a conceptual breakthrough which set an avalanche of ideas in motion and which, under the term „nanotechnology“ had a common denominator. Today, even classical electron microscopes are able to map individual atoms, to say nothing of the

Left: Computer reconstruction in seven million times magnifica-tion: a nanoparticle with a platinum shell and an iron core (green), a catalytically active nanomagnet. Modern high performance electron microscopes permit examination of objects well below one nanometre. Right: The original electron microscopic images.

Risk management in nanotechnology

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Nanotechnology activities of the Federal

Government

The high-tech strategy of the Federal Government has identified nanotechnology as one of the most promising fields of technology, from which, by 2015 at the latest, the large majority of all significant innovations will originate. With the „Nano Initiative – Action Plan 2010“, initiated in 2006, a uniform and multidisciplinary action framework was established, which also emphasises the responsible and safe use of nanomaterials. A series of relevant initiatives and programmes was started with the aim of making the undoubted toxic potential of nanomaterials mea-surable and thus controllable. A core element of the initiative is the cluster of projects, NanoCare, INOS and TRACER, in which science and industry work to-gether with public participation; funding until 2009: approx. €8 million. In cooperation with other ministries and the federal authorities, the BMU has initiated a nano dia-logue in which industry, scientists and participating social interest groups can identify the opportunities and risks in the handling of nanomaterials and esta-blish the open questions still requiring research and action. The Federal Institute for Risk Assessment, es-tablished in the business area of the German Federal Ministry of Food, Agriculture and Consumer Protec-tion (BMELV), has conducted expert surveys to study possible risks of nanotechnological applications in the everyday areas of foodstuffs, cosmetics and

consumer products and the attitude of consumers to the handling of nano products. In the business area of the Federal Health Ministry, the risks of nano-scale particles in drugs and medical products are being evaluated, also for clinical trials and approvals. In addition, the Federal Government is develo-ping an interdisciplinary research strategy, under the coordination of the Federal Agency for Safety and Health At Work, within the framework of which, in particular, the health and environmental risks of insoluble nanoparticles are addressed. The strategy includes, among other things, the development of standardised measurement techniques for nanopar-ticles, the collection of information on possible expo-sures, with their toxicological and eco-toxicological effects and the development of a risk related testing and evaluation strategy. The Federal Government attaches the greatest importance to a dialogue with a well informed public and, to this end, is supporting conferences, issuing newsletters, establishing Inter-net portals and publishing analyses and press articles containing information on the latest research results and risk debates. One instrument of information that is already becoming popular is the nanoTruck, which travels around Germany under the motto „nanoTruck: High tech from the nanocosmos“ and reaches more than 100,000 visitors per year. Also on board: the BMBF brochure „Nanotechnology – Innovations for the world of tomorrow“, already almost a standard work, translated by the European Union into all the languages of its member states and also into Arabic, Chinese and Russian. A good thing, for, in view of the complexity and far-reaching consequences of nanotechnology, international consultation is of particular importance. The Federal Government is therefore participating intensively in international activities connected with the responsible handling of nanomaterials, for example in the framework of the European Commission‘s action plan, the OECD „Wor-king Party on Manufactured Nanomaterials“ and the „International dialogue on responsible research and development of nanotechnology“. Its aim is to coor-dinate activities on the safety evaluation of nanoma-terials, which are meanwhile very extensive, and to establish internationally harmonised processes and standards.

The nanoTruck brings nano information to the people and attracts many visitors.

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What is special about the research project Nano-Care, and what is its objective?The objectives of NanoCare are special insofar as we have a very large, integrated research programme, essentially consisting of three parts. The first is the generation of knowledge. In other words, we are establishing relevant and evaluated testing systems to test nanoparticles which are already in use today and those currently in development for a possible biological risk. We standardise these tests within our consortium, which consist of nearly 10 partners which also work in the biological sector. That means that 10 different laboratories spread over Germany have to apply the same methods. So we have a large knowledge production section, in which we gene-rate completely new data on the possible risk and on possible exposure, including nanoparticles at the workplace. The second pillar is knowledge manage-ment, i.e. the knowledge gained is collected, com-piled, internally processed, and stored in an internal database, and then this processed information is transferred to the third pillar. That means that, at various events, also using publications and our own large database, we shall distribute the information in an appropriately presented form. In what areas of nanotechnology - and it is a large field - do you see a need for research as far as potenti-al risks are concerned?If we are talking about health risks, then all of those taking part in the corresponding research projects see the problems with the particles. As far as the need for research is concerned, we must carry out studies for all important materials to clarify possible exposures and their biological effects. In the case of nanotechnology and nanomaterials, we have the great difficulty that we have to assess each material individually and independently of others. Because, among the materials, there are just as many different variations, sizes and also surfaces which could be active. So the results cannot be generalised, but this already applies for many chemicals.

Interview with NanoCa-

re coordinator Prof. dr.

Harald krug from the

Institute for toxicology

and Genetics at the re-

search Centre karlsruhe.

Nano-safety research by the BMBF: NanoCare

In order to ensure the compatibility of nanomateri-als, the Federal Ministry for Education and Research, together with the industry, has established the re-search programme NanoCare. The BMBF will provide NanoCare with about €5 million over the next three years, while the industry will take part itself with a further €2.6 million. NanoCare will bring to light new scientific knowledge of the effects of nanoparti-cles on health and the environment and will commu-nicate this to the general public.

For this purpose, the project partners from indus-try and science want to manufacture new, strictly defined nanoparticles and study them for their toxi-cological effects in model systems. Fifteen partners are taking part. From the industry, these are Evonik Industries AG, BASF AG, Bayer MaterialScience AG, Solvay, ItN Nanovation AG and SusTech GmbH & Co. KG. Taking part from the scientific side are the Univer-sities of Münster, Bielefeld and Saarbrücken and the Research Centre Karlsruhe. Other partners are IUTA e. V., the Institute for the development and application of processes for biological emission analysis, and the Institute for Hazardous Substance Research at the Uni-versity of the Ruhr in Bochum. Responsibility for the active communication of the project results is shared by the VDI Technologiezentrum GmbH and Dechema. The project is coordinated by the Research Centre Karlsruhe.

„If we are talking about health risks, then all of those taking part in the corresponding research projects see the problems with the particles. As far as the need for research is con-cerned, we must carry out studies for all impor-tant materials to clarify possible exposures and their biological effects.“

Prof. dr. Harald krug, NanoCare Coordinator.

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So what is the difference between deliberately produced synthetic nanoparticles and natural or unintentionally released?In connection with the synthetically produced ma-terials, I see two essential aspects of risk. Firstly, that applies to the completely new things, like fullerenes or nanotubes, which do not occur naturally in large volumes. If I produce them in larger volumes, then, in practical terms, I have a completely new quality and a new pollution. And I can naturally only do that if I am sure that it will have no significant adverse consequences. So that is one point: New materials, where I really have something entirely new. The second point: There are also natural particles in the environment which are quite small enough to be designated as nanoparticles. And there is a lot of dust stirred up on the surface of the earth which, in part, consist of exactly the same materials which we also use, though in a very pure form, of course. Iron oxides, zinc oxide, titani-um dioxide and silicon dioxide are all materials we use, but which also occur in the earth‘s crust. So, in this connection, it should only be possible for pro-blems to arise if we manufacture and consume large quantities of the pure substance, since that naturally also increases the concentration. And that must then be tested in the same way to ensure that no adverse factors could arise. For me, those are the two most important points. Which products already contain specially produ-ced nanoparticles? Many cosmetics, like sunscreen creams and other vanishing creams with a sunscreen factor. These mostly contain zinc oxide or titanium dioxide particles. Then there is titanium dioxide at photocatalytic scale, that is really nano, for keeping surfaces clean. And nanoparti-cles are found in many varnishes, paints and lacquers. Then there is silicon dioxide as a viscosity regulator and also in adhesives, for example. Carbon, carbon nano-tubes, are now already contained as structure enhan-cers in a variety of plastics. Finally, there are nanoparti-cles in electrical accumulators; some nanoceramics are already in use for certain applications. But most of the applications I have mentioned up to now involve com-posite materials. In these, the nanoparticles are added to a base material, either melted or sintered into them. Very few applications use nanoparticles in their free form or in suspensions, like sun creams, for example.

And is the potential risk smaller in bonded form?The risk there is much lower. In this case, a potential risk depends rather on how the materials are dispo-sed of at the end of their life, shredded, weathered, dumped or incinerated. So it is rather the method of disposal which decides what might happen to them. It is very difficult to find general safety rules in this sector. Because there are so many different characteristics, do you have to test every substance individually?Because of the fact that we have so many different forms, sizes and materials to deal with, there are no uniform guidelines and regulations - this idea has to be abandoned. It is similar for chemicals, where there are also no uniform rules. It is only possible to find groups: this is flammable, that is explosive, this is water soluble, that is not water soluble - so groups like this can be formed and, within such groups, indi-vidual evaluation must naturally be carried out and that is also what will happen with nanoparticles. Can the environment be harmed by the release of nanoparticles?Yes, many things are conceivable, of course, but whether they all make sense is another matter. You have mentioned nano-pesticides. These are actu-ally pesticides packed in nanocapsules so that they can reach their point of action more accurately. This is really what is also sought after in human medicine. These capsules must be capable of being broken down in the biological setting, otherwise their contents would not be released. And from that point of view, I consider the risk due purely to the nanostructure to be very small. Under some cir-cumstances, there could be a new quality of toxicity - pesticides are, in themselves, toxic and that is why they are there. If, because of the nanocapsules, they are differently distributed in the environment, and if they became more concentrated at specific points, problems could arise.

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Activities of industry

Among the practical recommendations and proce-dural instructions in the industrial nanoparticle sec-tor is the „Guideline for activities with nanomaterials at the workplace“, jointly prepared by the Federal Agency for Health and Safety At Work (BAuA) and the Association of the Chemical Industry (VCI). The guideline clearly states:

„As a rule, in order to produce nanomaterials in the form of isolated nanoparticles, extremely elaborate chemical and physical processes are required. In most cases, however, in the products currently produced commercially at a larger scale, nanoparticles are not present as individual particles, but aggregated and ag-glomerated [see Glossary] as a group of several particles.Aggregates and agglomerates are not nanoparticles in the sense of the definition (see above), but nanostruc-tured materials in which the nanoparticles are joined together. The release of nanoparticles from these aggre-gates and agglomerates is often impossible without a major input of energy.Some nanomaterials are already processed by the ma-nufacturer to form granulates, formulations, dispersi-ons or composites. In many cases, in the course of their subsequent use, a release of isolated nanoparticles is extremely unlikely.“

However, where risks cannot be ruled out, recom-mendations are made which are largely identical with those for other substances classified as po-tentially hazardous, such as: Ascertain whether

substances or technical processes harmful to health can be replaced by less hazardous substances or less hazardous processes; production in closed systems, if possible with the capture, limitation and removal of dangerous gases, vapours and dusts at the point of origin; provision of suitable washing facilities, pro-tected storage of clothing not used at work, timing of working procedures, training and briefing, access and storage rules etc.; the use of personal protection equipment, such as breathing masks, protective gog-gles, gloves etc., in addition to technical and organi-sational measures. The potential risks of nanoparticle technology are not in question; in the nature of things, they are also to be expected. Particles which can initiate useful chemical reactions can reveal their potency just as well in unwanted reactions. In fact, there is a string of evidence, mainly from in vitro „test-tube“ experiments, whose transferability to living orga-

The particles embedded in plastic granulates ensure long-lasting effectiveness against bacteria and other microorganisms.

Silver nanoparticles are directly precipitated into liquid carriers in an integrated process. This process provides stable suspensions of isolated particles with a large specific surface area and characterised by high purity. Mean primary particle size 5 ... 50 nm

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nisms is disputed, however. Thus, functions of the cell nucleus are apparently disturbed by nanoparti-cles of silicon dioxide. C60 molecules and nano-scale titanium dioxide have a lethal effect on water fleas, even in relatively low doses. The British Royal Society and the Royal Academy of Engineering see a need for research on zinc oxide for use in sunscreen agents. The table enumerates a series of nanoparticles used in large numbers either now or in the near future and gives a rough assessment. A more solidly based classification is obvious-ly hindered by the lack of comparability of many studies due to insufficiently uniform methodologies. The correction of this and other deficiencies is the goal of a research strategy at present being worked out by the Federal Agency for Health and Safety At Work, the Federal Institute for Risk Assessment and the Federal Department for the Environment. How close together the old and the new can sometimes be is shown in the table by the example „Nanoclay“.

The expression refers to the clay mineral kaolinite, in use since the stone age, with which good pots can be baked. Under the electron microscope it can be seen that the mineral consists of stacks of flat nanocry-stals, similar to a roll of notes. When the nanocrystals are isolated by means of physicochemical tricks, the result is nanoclay, a versatile filler substance which, for example, makes PET bottles more impermeable to gas.

Approximate estimate of the risk potential of different nanoparticles.

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Small particles, large effects – opportunities and risks of nanoparticle technology

whenever Ottilia saxl opens a conference on nanotechnology - and, as Chair of the British Institute of Nanotechnology, she often has such an opportunity – the audience can look forward to a fervent plea for conservation of the environment. Ottilia saxl is not alone; many people who are engaged in nanotech-nology and therefore have a scientifically sober view of the matter are plagued by con-cern for the future.

The technology of the 20th century is obviously rea-ching its limits. Global climate change is only one of these, if also the most important. Perhaps nanotech-nologists express themselves so frankly because they do not have to leave their audience out the consolati-on that nanotechnology can help to ensure a future worth living in. By the provision of cheap electricity from sun-light, for example. At the beginning of 2007, in Cardiff, Wales, with the participation of the Ger-man firm BASF AG, the first factory for solar cells was established, working with nano-scale titanium dioxide particles and a special pigment. While their efficiency is only about half as great as that of mono-crystalline silicon solar cells, their manufacture, in which the active material is printed in a continuous process, roll for roll, on foils, promises to be very much cheaper. The time anticipated for recovery of the energy used for its production is one year, compared with four years for silicon solar cells. These Graetzel cells, named after their inventor, Michael Graetzel, Professor at the Eidgenössischen Polytech-nikum Lausanne, are intended for expansion of the telecommunications networks in Africa and India. But nanotechnology can also provide new solutions for conventional silicon solar cells. Thin added layers of nano-scale silicon have proven to be very effec-tive in raising their efficiency. The silicon solar cell technology also needs competition, for competition vitalises business and, with annual growth of nearly 40 %, there is enough to go around.

The recently deceased Nobel Laureate Richard Smalley assigned a key position to nanotechnology in the solution of the energy problem. One example here is the development of efficient energy storage. Acceptable lithium ion accumula-tors with adequate capacities, which are safe and can be recharged at an acceptable rate many thousands of times, will shortly come on to the market. These contain nanoparticles (see p. 18). For operation of an electric scooter equipped with these, a couple of square metres of modern solar panels would be quite sufficient. A lithium Smart could also be equipped for city traffic in this way. This development is inevitable. Asia‘s cities are vanishing in the smog from two-strokes, an electrical replacement for which will be pushed hard by the state as soon as an affordable technical alternative is available. Old European cities like London have created breathing space for themselves with a con-gestion charge, to the satisfaction of all in the end. The owners of electric vehicles need not pay the toll. Sockets are available for them to recharge at selected parking places. In the end, this will happen every-

The waste heaps of nature, deposits of sunken living creatures once pro-tected by chalky shells, become sightseeing destinations when geologi-cal forces raise them above the surface – like the white cliffs of Dover.

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where. There is no alternative to efficient electric motors. Very possibly, they will also contain nano-scale magnetic materials. Insofar as nanoparticles are toxic, ways and means will be found to bind them in or to make them safe in other ways. It all depends on the compound, as chemists have always known. The elements sodi-um and chlorine, for example, are both extremely unappetising, but together they give sodium chlori-de, common salt, which is indispensable for human life. With nanoparticles, the realisation of new ma-terials for everyday life will also be possible, which, at the end of their product life, will decompose non-toxically like any leaf from a tree, or will at least break down non-toxically in water. The urgency of this problem is shown by reports of the „Pacific gyre“, a whirlpool in the Pacific carrying plastic waste over an area as large as Central Europe, an estimated 3,000,000 tonnes and growing - bottles, toys, six-pack rings closely packed - a deadly danger for many marine creatures. An extinction of species has now started in the seas, comparable to that on land - a ca-tastrophe of geohistoric proportions. So scientists are urgently calling for the long overdue modernisation of the industrial societies. Nanotechnology can help here. Warnings of this kind, of course, have long ema-nated from reputedly sectarian circles, but they are now also found on the websites of the aerospace and armaments industry, wherever scientists are active.

When Sir Harold Kroto, who, together with Richard Smalley and Robert Curl, received the Nobel Prize for Chemistry for the discovery of the fullerenes, gave an address before a large audience, as at the Meeting of Nobel Laureates in Lindau on Lake Constance, he liked to quote J.R.R. Tolkien, the author of „Lord of the Rings“:

„All that is gold does not glitter, not all those who wander are lost ...“

Nanotechnologists can also be romantics. That is acknowledged by the young people with loud applause. The sensitivity of nanotechnologists to matters of nature certainly also has something to do with the fact that they have an overview of several fields of science, biology, physics and chemistry, so they have a feeling for the incredible technical ele-gance in many natural processes. Photosynthesis, for instance, mastered by every lime leaf, is still not completely explained because of its complexity, but land is in sight. With nanotechnology, accompanied by sensible safety research, mankind could succeed in transfer-ring the elegance of natural processes to technical processes and, in this way, in making the technical world sustainable.

A lime leaf, a disposable item in nature, masters the process of photosynthe-sis: How are energy-rich chemicals made from light, water, carbon dioxide and trace elements? Science is no longer very far from its complete decoding, which will open a gigantic field of work for nanotechnology - and will undoubtedly earn Nobel Prizes.

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Glossary

GlOssAry

Aerosols: Mixtures of solid or liquid particles with air. Because of potential damage to the human respiratory tract, aerosols are the subject of intensive research. Air can carry particles in the size range of particles, of which air itself consists, up to over 100 microns. Of primary importance for human health are particles <10 µm.

Agglomerates, Aggregates: These terms have long been used in powder technology to describe agglo-merations of particles, but not always uniformly, which sometimes leads to confusion. In German industry, the term „aggregate“, when applied to nanoparticles, means a group of a few particles ad-hering to each other through strong chemical bonds. „Agglomerates“, on the other hand, are collections of aggregates, mainly held together by the weaker Van-der-Waals bonding. There are smooth transi-tions between aggregates and agglomerates.

Bulk: In connection with nanoparticles, usually a designation for the coarsely structured mother sub-stance from which the nanoparticles are produced.

CdS: Cadmium sulphide, usually a synthetic com-pound, but also occurring as a natural mineral. Used among other things as a light fast pigment for paints and plastic parts, now out of favour because of its cadmium content.

CNT: Carbon NanoTubes for a large number of ap-plications. Added to plastic material, CNTs improve the mechanical properties of tennis racquets, for example, make the material electrically conductive, so prevent electrical charges (important for tank

facilities) and increase thermal conductivity. Also see SWNT and MWNT.

Computer tomography: The conversion of data from a specific volume (a rib cage, a cell) into plastic images. Best known are medical applications like x-ray computer tomography, while the most spectacu-lar technique is cryo-electron microscopy, which also permits the display of molecular nanomachines.

Dendrimers: New class of substances, polymers of supermolecular chemistry, „hyperbranched“ like a tree or bush, with ever more astonishing properties. On the numerous arms of such a molecule, a wide va-riety of tools can be coupled. Between the branches there is room for guest molecules, such as drugs for cancer therapy.

Epidemiology: Research of causes, consequences and spread of factors harmful to health for large population groups using statistical methods, among others.

Fine dust, ultrafine dust: Dust is ubiquitous and, in principle, unavoidable. However, technical activities, particularly combustion engines, have greatly incre-ased pollution of the air. According to the size of the particles, it is referred to as airborne dust, fine dust or ultrafine dust. Airborne dust has a size of more than 10 microns (1 micron – µm – is 1 millionth of a metre). Fine dust refers to a particle size between 0.1 µm (100 nanometres) and 10µm. Ultrafine dust has a particle size of less than 100 nanometres.

• Fine dust up to a size of 10 µm reaches the upper region of the lung; • Fine dust with particles <2.5 µm reach the central region of the lung.

Nanoparticles Aggregates Agglomerates

Dendrimer space-filling model. Between the branches of the molecule, other substances can be accommodated and functional groups can be attached to the ends of the branches.

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Plasma torch: Hot, highly ionised space in a gas discharge reactor, in which, through the injection of selected substances, many different kinds of nano-particles can be synthesised.

SWNT: Single Wall NanoTube – carbon nanotube (CNT) with a single layer wall.

TiO2: Titanium dioxide, among other things a white filler for wall paints and heavy paper, may have a starring career before it as a nano-scale component of solar cells (Graetzel cell). Nanoparticles of TiO2 convert components of the air into reactive sub-stances with a cleaning and sterilising effect when exposed to light (photocatalysis). Nano-scale TiO2 is a subject of nano-safety research, but is already used in large quantities in Japan as a photocatalyst. Normal TiO2 white pigment is completely non-toxic, is contained in toothpaste and gives white salami skin its desired floury feel, without being susceptible to microbic contamination.

ZnO : Zinc oxide, compound of zinc and oxygen. Its traditional designation „zinc white“ refers to its use in paint pigments. Because of its antiseptic effect, it is also used in ointments. Nanoparticles of ZnO serve as a UV screen in sun creams.

• Ultrafine dust is smaller than 100 nanometres and can even penetrate into the lung‘s alveoli and circu late further in the bloodstream.

Fullerenes: Group of molecules which owe their name to their similarity with the architectural elements of Buckminster Fuller (1895 – 1983). The fullerenes include the „football molecule“ C60, also know as a buckyball and hollow tubes of carbon atom networks, buckytubes. Fullerenes now repre-sent a large group of substances; it is also known that balls, networks and tubes can also be constructed using atoms other than carbon.

MWNT: Multiple Wall NanoTube – carbon nanotube (CNT) with a multilayer wall.

NanoClay: Filler substance, mainly consisting of nano-scale platelets of the mineral montmorillo-nite, which occurs in clay. With small additions, the properties of plastics, for cables, PE foam, interior and exterior parts for automobiles etc., can be much improved. Used in PET bottles, it increases their impermeability to gas, carbonised drinks remain sparkling for longer and protection against atmos-pheric oxygen is increased many times. Is also used in foils for food packaging.

GlOssAry

Hollow fullerene sphere, loaded with a guest atom (model).

Triple walled carbon nanotube

Plasma torch

Single walled carbon nanotubes.

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Further information

Internet addresses

Nanotechnology activities of the federal authori-ties• www.bmbf.de/de/nanotechnologie.php• www.baua.de/nanotechnologie• www.bmu.de/nanotechnologie• www.bfr.bund.de/cd/3862?index=78&indexid=7585• www.umweltbundesamt.de/gesundheit/stoffe/ nanopartikel.htm• http://www.bmelv.de/cln_044/nn_749972/DE/02- Verbraucherschutz/FAQNanotech.html

Nanotechnology risk research and communica-tion

• BMBF Project NanoCare: www.nanopartikel.info• BMBF Project INOS: www.nanotox.de• BMBF Project Tracer: www.nano-tracer.de • Info portal zu Nano regulation: www.nano-regulation.ch• Nanotechnology Standardisation ISO TC 229: www.iso.org• Information and data bases on the risk assess ment of nanomaterials: www.icon.rice.edu• Info portal Nano safety research: www.safenano.org

Other Internet portals

• High-Tech Strategy for Germany: www.ideen-zuenden.de• Nanotechnology portal of VDI TZ GmbH: www.nanonet.de• German Nanotechnology Competence Atlas: www.nano-map.de• Scientific communication on nanotechnology: www.nanotruck.de• Virtual voyage into the nanocosmos: www.nanoreisen.de• Educational opportunities in nanotechnology: http://nanobildung.tech-map.de

FUrtHEr INFOrMAtION

• European Nanotechnology Portal: www.nanoforum.org• Nanotechnology support from the EU: www.cordis.lu/nanotechnology

Brochures

• Nano Initiative – Action Plan 2010, BMBF 2006• Hochschulangebote im Bereich Nanotechnolo gie, VDI TZ GmbH 2006• Nanotechnology – Innovations for tomorrow’s world, BMBF 2006, 3. revised edition• Dual training in innovative fields of technology, BMBF 2005• Nanotechnology conquers markets, BMBF 2004

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Index of Abbreviations

INdEx OF ABBrEvIAtIONs

BAuA: Bundesanstalt für Arbeitsschutz und Arbeits-medizin (Federal Institute for Occupational Safety and Health)

BfR: Bundesinstitut für Risikobewertung (Federal Institute for Risk Assessment)

BMBF: Bundesministerium für Bildung und For-schung (German Federal Ministry for Research)

BMELV: Bundesministerium für Ernährung, Land-wirtschaft und Verbraucherschutz (German Federal Ministry for Consumer Protection)

BMU: Bundesumweltministerium (Federal Ministry for Environment)

CNT: Carbon Nanotubes

DECHEMA: Gesellschaft für Chemische Technik und Biotechnologie

DIN: Deutsches Institut für Normung (German Insti-tute for Standardisation)

DNA: Deoxyribonucleic Acid

ECETOC: European Centre for Ecotoxicology and Toxicology of Chemicals

EKG: Electrocardiogram

GSF: Deutsches Zentrum für Gesundheit und Umwelt

ISO: International Standardisation Organisation

OECD: Organisation for Economic Cooperation and Development

PM: Particulate Matter (dust)

PE: Polyethylene

PET: Polyethylene terephthalate

RFID: Radio Frequency Identification

VCI: Verband der Chemischen Industrie (Associaton of the German Chemical Industry)

VDI: Verein Deutscher Ingenieure (Association of Engineers)

UV: Ultraviolet

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