Nanotechnology is considered by many as the next logical step in science, integrating engineering with biology, chemistry and physics [1
]. It derives from the ongoing trend for miniaturisation in technology as described by Moore's Law and combination with other disciplines. Miniaturisation however has its limits and new approaches in manufacturing (bottom-up fabrication) have to be developed to reach anticipated milestones.
Nanotechnology can be considered as the application of science that "steps across the limit" of miniaturisation, where" new rules" become valid [2
] More specifically, when the dimensions of a piece of solid material become very small, its physical and chemical properties can become very different from those of the same material in larger bulk form. This is one of the hallmarks of Nanotechnology, which can be described as a research area in which this limit of new properties is reached and strategies are developed to exploit the regime of size-controlled properties.
In the last couple of years, the term Nanotechnology has been inflated and has almost become synonymous for things that are innovative and highly promising. On the other hand it is also the subject of considerable debate regarding the open question on toxicological and environmental impact of Nanoparticles and nanotubes [3
]. In this discussion a definition of Nanotechnology and its underlying sectors, applications and markets is important for the purpose of risk assessment and risk communication. Many definitions refer to the length scale (nano) of this new science but not all mention the new functionalities of materials and components at the nanoscale. A commonly-used working definition refers to the size and (changing) properties of materials in the size range between 1 nanometre (10 ) and 100 nm, but this gives rise to many uncertainties and inconsistencies which need to be resolved.
Although quite open and abstract the recent definition forwarded by a working group of the Europische Akademie [2
"Nanotechnology is dealing with functional systems based on the use of sub-units with specific size dependent properties of the individual sub-units or of a system of those"
The report by the Royal Society and Royal Academy of Engineering [5
] gives the following definitions of 'nanoscience' and 'nanotechnologies':
"Nanoscience is the study of phenomena and manipulation of materials at atomic, molecular and macromolular scales, where the properties differ significantly from those at a larger scale";
"Nanotechnologies are the design, characterisation, production and application of structures, devices and systems by controlling shape and size at nanometre scale".
Other definitions are more specific, such as the one used by Nanoforum:
Nanotechnology is made up of areas of technology where dimensions and tolerances in the range of 0.1 nm to 100 nm play a critical role
Or very simple, as defined by [6
]Nanotechnology – the manipulation, precision placement, measurement, modelling or manufacture of sub-100 nanometre scale matter
1.2 Major applications and markets in nanotechnology
The nanotechnology market can be broadly divided into 3 segments, viz. Materials, Tools and Devices:
1. Nanomaterials – used to describe materials with one or more components that have at least one dimension in the range of 1 to 100 nm and include Nanoparticles, nanofibres and nanotubes, composite materials and nano-structured surfaces. These include Nanoparticles (NP) as a subset of nanomaterials currently defined by consensus as single particles with a diameter < 100 nm. Agglomerates of NP can be larger than 100 nm in diameter but will be included in the discussion since they may break down on weak mechanical forces or in solvents. Nanofibres are a sub-class of nanoparticles (include nanotubes) which have two dimensions <100 nm but the third (axial) dimension can be much larger.
2. Nanotools – tools and techniques for synthesising nanomaterials, manipulating atoms and fabricating device structures, and – very importantly – for measuring and characterising materials and devices at the nanoscale;
3. Nanodevices – making devices at the nanoscale, important in microelectronics and optoelectronics at the present time, and at the interface with biotechnology where the aim is to mimic the action of biological systems such as cellular motors. This latter area is the most futuristic, and excites the greatest public reaction.
This report will primarily focus on the risks of manufactured Nanoparticles and nanofibres
, because this area of nanotechnology should achieve volume production in the near term and it is also the aspect that raises greatest public concern about potential risks to health. However the distinction from composite nanomaterials and tools and devices becomes vague when nanoscale materials are combined for medical applications. In the nearer term, certain Nanoparticles offer opportunities to develop smart drug delivery vehicles that can move through the body to target sites, or sensor and diagnostic systems operating inside cells. Nanomaterials could also be used to synthesise structures for implant into the body that have properties that closely resemble the properties of natural materials. Tissue scaffolds that use biocompatible nanomaterials to control cell growth and adhesion are under development, and in the future artificial organs that mimic the porosity and capillary structure of natural organs such as the heart and liver may become reality [7
]. These applications are not the subject of this study, but a working group of the European Science Foundation on this subject [7
]. Nanomaterials constitute by far the most significant market opportunity in the foreseeable future. A 2002 market survey forecasts that by 2015 the total world industrial output in sectors likely to be influenced
by nanomaterials will be in excess of $10,000 Billion (Realis http://www.inrealis.com
). The same survey suggests that by then about 10% of the output from the chemicals sector will be nano-influenced. The impact of nanotechnology will be seen particularly by enabling innovation in the areas of speciality and fine chemicals, and in materials for pharmaceuticals and personal care products. Nanoparticles and nanofibres will be particularly important in these applications.
The unique size-dependent properties of nanomaterials mean that in some ways they behave like new chemical substances. For example, Nanoparticles can scatter and absorb short-wavelength UV radiation but leave longer-wavelength visible light virtually unaffected. This property is exploited in transparent sunscreens. When fluorescent Nanoparticles absorb UV radiation they emit visible light, and the colour of the emitted light is different for Nanoparticles of different diameters. This effect is exploited when Nanoparticles are designed as colour-coded fluorescent labels that can be attached to target molecules or used as diagnostic markers. The changes in optical and transport properties become very pronounced for Nanoparticles smaller than about 30 nm. Particles in this range are often called 'quantum dots' because size is then controlling the separation (or quantisation) of energy levels inside the particle.
Some nanomaterials have been in volume production for a very long time. Carbon blacks in the nanoparticles size have been in production for more than a century, and are used for manufacture of rubber products and pigments. Fumed silica and other oxides such as titanium, alumina and zirconium have been produced as nanomaterials for over half a century and used as thixotropic agents in pigments and cosmetics, and more recently as the basis for fine polishing powders used in the microelectronics industry. Much of this high volume production is based on vapour phase flame or plasma reactions carried out under highly controlled conditions.
New nanomaterials are now being developed for many different applications, using new preparation techniques. Volumes are low, often on a laboratory scale producing <10 kg per day. Examples are magnetic materials for electric motors and generators as well as high density data storage, high current electrode materials for fuel cells, batteries and electrochromic displays, and materials with new surface properties for paints, coatings for self-cleaning windows, stain-resistant textiles etc. These materials are more expensive to produce than conventional materials, and must therefore offer very high performance or similar benefits to users to justify the additional cost. As manufacturing costs fall with increasing volumes and the maturing of nanotechnology methods, it can be predicted that the advantages of nanomaterials will lead to steady displacement of conventional materials in many high value applications.
Surfaces and interfaces are very important for new nanomaterials. As particles become smaller, the proportion of atoms found at the surface increases relative to the proportion inside its volume. This means that Nanoparticles can be more reactive, for example creating more effective catalysts or more efficient filler materials that allow weight reduction in composite materials. The higher surface energy can also make Nanoparticles interact strongly and stick together. If nanomaterial building blocks are synthesised in such a way that parts of the surface are sticky but other parts are passive and non-sticky, then random Brownian motion in a fluid can cause the blocks to stick together in defined ways to make larger structures. This is the basis of so-called 'bottom-up' self-assembly methods.
The chemicals industry is a key actor in exploiting nanotechnology because the nanomaterials that it produces are the basis for product innovation across many industrial sectors. The In Realis market survey highlights transportation equipment, electronic and electrical equipment, industrial machinery and instrumentation, rubber and plastic products, metal industries, and printing and publishing as sectors where nanotechnology is expected to have a large impact.
The study of materials such as ceramics, metals, colloids and polymers has always involved science at the nanoscale, and it is in these areas that the introduction of nanotechnology as an engineering discipline will have the earliest commercial impact. Advanced ceramics combine well-controlled microstructures with complex compositions and crystal structures. The use of nanoscale ceramic powders of narrow size distribution and high purity will allow compacting into ordered and uniform arrays, and sintering at lower temperatures, to produce tightly-controlled ceramic products for microelectronics, magnetic recording, chemical applications etc.
Nanocomposites combine polymers with nanomaterials to produce new thermoplastic and thermosetting materials. The high surface area-to-weight ratio for nanomaterials, the high surface reactivity and the matching of scale with polymer molecule dimensions can all contributes towards improving composite properties. For example, nanocomposites can have higher tensile strength or heat distortion temperature than similar materials using conventional fillers. These properties might be achieved with lower loading of nanomaterial filler, reducing the weight and increasing the transparency of nanocomposites compared with conventional composites. The use of carbon nanomaterials such as C60 fullerenes and nanotubes is a particularly promising way of reinforcing composite materials and perhaps making them lighter, stronger and electrically and optically active at the same time.
1.3 Standards and terminology
It is widely accepted that there is an urgent need for standards in nanotechnology to support legislation and regulation, risk analysis and communication, IP protection, and methods for sampling and measurement. In October 2004 the Technical Board Working Group on Nanotechnologies of the European Committee for Standardisation (CEN/BT/WG 166) launched a stakeholder consultation involving questionnaires for industry and non-industry groups.
The American National Standards Institute http://www.ansi.org
has formed a Nanotechnology Standards Panel (ANSI-NSP), which issued a set of priority recommendations. Four areas were deemed to be most urgent for the next 12 months, and within each area 3 topics were identified as having greatest importance. These groupings of priorities for nanotechnology standardisation are:
Group 1: Systematic terminology for materials composition and features
Group 2: General terminology for nanoscience and technology
• Definition of the term 'nano'
• Consideration of impact on intellectual property/other issues
• Sensitivity to existing conventions
Group 3: Metrology/methods of analysis/standard test methods
• Particle size and shape
• Particle number and distribution
• Particle mass
Group 4: Toxicity effects/environmental impact/risk assessment
• Environmental health and safety
• Reference standards for testing and controls
• Testing methods for toxicity
Standards for the areas of 'Manufacturing and Processing' and for 'Modelling and Simulation' were considered less urgent (3–5 year timeframe).
As outlined in Group 4 above, the greatest current risk is to the occupational health of workers involved in research and manufacture of Nanoparticles and nanofibres. However, as applications of nanomaterials increase, the risk of exposure to the general public will grow. It will be necessary to monitor products that incorporate Nanoparticles and nanofibres throughout their life, from manufacture to disposal, in order to estimate the probability of environmental emissions particularly from disposal and waste management processes. Some products will involve direct delivery of Nanoparticles to humans, for example injection of smart drug delivery systems and diagnostic markers and application of cosmetics to the skin. In some cases there could be unintentional uptake, for example ingestion of Nanoparticles used in food packaging technology.
The wide variety of routes by which Nanoparticles could be taken up by the body complicates the definition of Nanoparticles to be used in risk assessment and regulation. It is probably necessary to consider multi-component and multi-phase particles of any size and composition that can be absorbed by the body and then break up to deliver Nanoparticles or nanofibres to target organs. Nanocoatings on implanted medical devices that could shed Nanoparticles or nanofibres through use or wear should also be included. The overall risk of exposure to nanofibres may be lower than for Nanoparticles because it appears to be more difficult to generate aerosols of nanofibres.
1.4 Sources of nanoparticles
1.4.1. Unintentionally produced nanoparticles
Epidemiological studies consistently show that increases in atmospheric particulate concentrations lead to short-term increases in morbidity and mortality. Inhalation is the most significant exposure route for those unintentionally- generated particles,. Regulation is aimed mainly at particulate matter <10 μm in diameter (PM10
) in the atmosphere, but there is evidence that the adverse health effects are greater for the fine particle fraction, defined as having diameter <2.5 μm (PM2.5
). Improvements in measurement techniques have focused attention more recently on ultrafine particles
(UFPs), whose diameters < 0.1 μm (PM0.1
) is consistent with nanoparticles definitions. UFPs dominate the number concentration of the ambient particle cloud, but represent only a small fraction of the total mass concentration. The large number concentration of UFPs existing in the atmosphere generates a background against which emissions of manufactured Nanoparticles and nanofibres will have to be measured and monitored. The relative importance of different sources of atmospheric UFP emission in the UK during 1996 was identified in the report of the Airborne Particles Expert Group [8
]. The major source of primary UFP was road transport (60%), followed by combustion processes (23%, combining industrial, commercial, residential combustion and energy production).
Particles in the atmosphere are defined as either primary or secondary particles.
• Primary particles are emitted directly from sources or processes, which might be natural (fires, volcanoes, sea spray, erosion) or anthropogenic (traffic, industry).
• Secondary particles are formed in the atmosphere by gas-to-particle conversions. Immediately following nucleation the secondary particles are very small (~1–10 nm), and grow by coagulation or condense onto existing submicrometer particles. Homogenous nucleation, the formation of very small particles may occur in hot combustion gases and in metallurgical processes, including welding.
1.4.2 Intentional production of nanoparticles
On the other hand, for decades industry has been intentionally producing different kinds of manufactured Nanoparticles, for use in existing applications such as pigments, resins and cosmetics. In addition, nanotechnology will increasingly generate new materials and products that are based on Nanoparticles, devices and tools. It is the sum of existing and newly developed, intentionally produced (= manufactured) Nanoparticles that form the primary target of risk assessment in this review.
It may be that the emission of manufactured Nanoparticles and nanofibres will add to the load of primary UFPs in the atmosphere. The subsequent formation of agglomerates of Nanoparticles and fibres, or of multi-component particulate matter containing adsorbed Nanoparticles, will add to the load of atmospheric PM2.5 or PM10. The formation of large complex particles incorporating nanoscale components will need to be considered in the risk assessment for nanotechnology because they create a potential route for uptake of Nanoparticles and fibres. The probability that emissions of manufactured Nanoparticles might occur where there are already high concentrations of UFPs in the atmosphere will require study to assess the rates of interaction between the different types of particle, and the likely products. Of course, the application of new manufactured Nanoparticles and nanofibres in products that are used directly by consumers means that other routes of uptake for manufactured nanomaterials must be considered in addition to inhalation, e.g. ingestion and dermal absorption.
For most manufactured NP no toxicity data are available. Most of the experimental, toxicological work on NP has been generated with a small set of Nanoparticles, such as carbon black (CB), titanium dioxide (TiO2
), iron oxides and amorphous silica. These NP have been manufactured by the chemicals industry for some decades and are produced in many tons per year. These NP were considered to be so-called nuisance dusts until it was observed that upon prolonged exposure in rats, inflammation and lung tumours can occur. The discussion on the risks of manufactured NP is mainly driven by epidemiological studies that estimated that per 10 μg/m3
increase in the concentration of environmental particles (PM2.5
), overall mortality increases by 0.9%, while deaths from specific respiratory diseases can increase by as much as 2.7% [9
]. Experimental toxicological studies (with CB, TiO2
) have indicated that NP cause such adverse effects at lower dose levels than their fine counterparts, but so far few human studies have been able to investigate this. In summary, these findings set the stage for the current discussion on risks of Nanoparticles illustrated as the scheme in Figure . The key-question is whether and how the different pieces of toxicological and epidemiological evidence on different NP can be mutually used or whether a more targeted and systematic approach is necessary.
Figure 1 Illustration of the different sources and applications of ultrafine and Nanoparticles (NP). Epidemiology and toxicology have demonstrated acute effects of anthropogenic NP (= UFP) in humans, as well chronic effects of existing, manufactured NP in animals. (more ...)
1.5 Production of manufactured nanoparticles
According to the National Nanotechnology Initiative (USA), the largest production volume in 2004 was for chemical-mechanical polisher (CMP) for semiconductor wafers, for example ammonia-stabilized 40 nm colloidal silica (sold under the name OX-200; no specific quantities given). Thousands of tons of silica, alumina and ceria, in the form of ultrafine abrasive particle mixtures that include Nanoparticles, are used each year in slurries for precision polishing of silicon wafers. Cabot Microelectronics, the leading producer of CMP slurries, recently announced that it has been working with Nano Products Corporation for 2 years to develop specially engineered Nanoparticles to improve the performance of next generation polishing products.
The manufacture of Fullerenes could soon match the engineered metal oxide Nanoparticles in production quantities, with the Kitakyushu plant (Mitsubishi, Japan) estimating an annual production of 1500 tonnes of C60
by 2007. Other manufacturing facilities also anticipate increased production of fullerenes, and therefore the sum production could be several thousands of tons of fullerenes by 2007. In 2003, Single-Walled and Multi-Walled Nanotubes had a world-wide production of approximately 3000 kg (3 tonnes). However, the Carbon Nanotechnology Research Institute (Japan) plans on expanding their production from ~ 1000 kg in 2003 to 120,000 kg per year within the next five years. The worldwide production capacity
for single-wall and multi-wall carbon nanotubes is estimated to be about 100 tons in 2004 [10
], increasing to about 500 tons in 2008. Capacity for single-wall nanotubes (SWNT) currently comprises less than 10% of the total, but is predicted to double as a proportion of total capacity by 2008.
The likely global production for specially-engineered nanomaterials is summarised in Table , using recently-published data [10
] based on review of chemistry journals and market research:
Estimated global production for engineered nanomaterials
The increase in production of engineered nanomaterials is being fuelled by a worldwide growth in R&D, which is seen as key to industrial innovation in many sectors. The scale of investment in nano-related R&D is illustrated by data taken from two recent publications, referenced in Tables and .
Although current production of engineered nanomaterials is small, it is evident that as a result of increased R&D the rate of production will accelerate in the next few years. Considering the tons of engineered nanomaterial planned for production, it is likely that some of these materials will enter the environment during the product's Life Cycle (manufacture, use, disposal). In addition to these specifically engineered nanomaterials, it is estimated that 50,000 kg/year of nano-sized materials are being produced through these un-intended anthropogenic sources such as diesel-exhaust and other combustion processes. Given the large surface area to mass ratio of nano-sized materials, this is quite a large amount of reactive surface area.
1.6 Roadmaps for future manufacture and applications of nanomaterials
There are two distinct approaches to making products with nanoscale features and attributes.
Top-down fabrication is the method used in the microelectronics industry, where small features are created on large substrates by repeated pattern transfer steps involving lithographic methods. Extreme UV photolithography can produce patterns with feature sizes down to 100 nm, and electron beam lithography can be used for features down to 30 nm.
Bottom-up fabrication is directly relevant to the chemicals industry. This method starts with very small units, often individual molecules or even atoms, and assembles these building-block units into larger structures – clearly the domain of chemistry. What nanotechnology brings is the idea that the assembly can be hierarchical and controlled in specific ways. Some recent reports give a vision of how manufacture and applications of nanomaterials could evolve in the next 10–20 years:
'Nanomaterials by Design'
This report was prepared by a working group representing the US chemical industry. It proposes actions that by 2020 will enable the industry to offer a library of nanomaterial building blocks with well-characterised compositions, stable architectures and predicted properties. There will be safe, reproducible and cost-effective 'bottom-up' manufacturing and assembly methods to incorporate these nanomaterial building blocks into devices and systems designed to perform specific functions whilst retaining the nanoscale attributes.
'Vision 2020 – nanoelectronics at the centre of change'
] This report was prepared by representatives of European industrial and research organisations as a roadmap for development of microelectronics in Europe. Break-through applications enabled by nanomaterials could include new data storage devices, flexible displays, molecular transistors and novel sensor and actuator devices.
'Nanotechnology – innovation for tomorrow's world'
The German Association of Engineers- Technology Centre (VDI-TZ) for the German government prepared this report. It describes the scientific background to nanotechnology developments and future areas of application. It contains many illustrations of how everyday objects and activities will be affected by the use of nanomaterials, and how this could change people's lives for the better.