Nanotoxicology-Fundamental concepts-Nanomaterials

Nanotechnology or, for short, nanotech, refers to a field of applied science whose theme is the control of matter on an atomic and molecular scale. Generally nanotechnology deals with structures 100 nanometers or smaller, and involves developing materials or devices within that size.

Nanotechnology is an extremely diverse and multidisciplinary field, ranging from novel extensions of conventional device physics, to completely new approaches based upon molecular self-assembly, to developing new materials with dimensions on the nanoscale, or the scale of nothing, even to speculation on whether we can directly control matter on the atomic scale.

There has been much debate on the future implications of nanotechnology. Nanotechnology has the potential to create many new materials and devices with wide-ranging applications, such as in medicine, electronics, and energy production. On the other hand, nanotechnology raises many of the same issues as with any introduction of new technology, including concerns about the toxicity and environmental impact of nanomaterials, and their potential effects on global economics, as well as speculation about various doomsday scenarios. These concerns have lead to a debate among advocacy groups and governments on whether special regulation of nanotechnology is warranted.


Origins


Buckminsterfullerene C60, also known as the buckyball, is the simplest of the carbon structures known as fullerenes. Members of the fullerene family are a major subject of research falling under the nanotechnology umbrella.
Buckminsterfullerene C60, also known as the buckyball, is the simplest of the carbon structures known as fullerenes. Members of the fullerene family are a major subject of research falling under the nanotechnology umbrella.


The first use of the concepts in 'nano-technology' (but predating use of that name) was in "There's Plenty of Room at the Bottom," a talk given by physicist Richard Feynman at an American Physical Society meeting at Caltech on December 29, 1959. Feynman described a process by which the ability to manipulate individual atoms and molecules might be developed, using one set of precise tools to build and operate another proportionally smaller set, so on down to the needed scale. In the course of this, he noted, scaling issues would arise from the changing magnitude of various physical phenomena: gravity would become less important, surface tension and Van der Waals attraction would become more important, etc. This basic idea appears plausible, and exponential assembly enhances it with parallelism to produce a useful quantity of end products. The term "nanotechnology" was defined by Tokyo Science University Professor Norio Taniguchi in a 1974 paper as follows: "'Nano-technology' mainly consists of the processing of, separation, consolidation, and deformation of materials by one atom or by one molecule." In the 1980s the basic idea of this definition was explored in much more depth by Dr. K. Eric Drexler, who promoted the technological significance of nano-scale phenomena and devices through speeches and the books Engines of Creation: The Coming Era of Nanotechnology (1986) and Nanosystems: Molecular Machinery, Manufacturing, and Computation, and so the term acquired its current sense. Engines of Creation: The Coming Era of Nanotechnology is considered the first book on the topic of nanotechnology. Nanotechnology and nanoscience got started in the early 1980s with two major developments; the birth of cluster science and the invention of the scanning tunneling microscope (STM). This development led to the discovery of fullerenes in 1986 and carbon nanotubes a few years later. In another development, the synthesis and properties of semiconductor nanocrystals was studied; This led to a fast increasing number of metal oxide nanoparticles of quantum dots. The atomic force microscope was invented six years after the STM was invented. In 2000, the United States National Nanotechnology Initiative was founded to coordinate Federal nanotechnology research and development.

Fundamental concepts

One nanometer (nm) is one billionth, or 10-9 of a meter. By comparison, typical carbon-carbon bond lengths, or the spacing between these atoms in a molecule, are in the range 0.12-0.15 nm, and a DNA double-helix has a diameter around 2 nm. On the other hand, the smallest cellular lifeforms, the bacteria of the genus Mycoplasma, are around 200 nm in length.

To put that scale in another context, the comparative size of a nanometer to a meter is the same as that of a marble to the size of the earth. Or another way of putting it: a nanometer is the amount a man's beard grows in the time it takes him to raise the razor to his face.

Two main approaches are used in nanotechnology. In the "bottom-up" approach, materials and devices are built from molecular components which assemble themselves chemically by principles of molecular recognition. In the "top-down" approach, nano-objects are constructed from larger entities without atomic-level control.

Larger to smaller: a materials perspective

Image of reconstruction on a clean Au(100) surface, as visualized using scanning tunneling microscopy. The positions of the individual atoms composing the surface are visible.
Image of reconstruction on a clean Au(100) surface, as visualized using scanning tunneling microscopy. The positions of the individual atoms composing the surface are visible.



A number of physical phenomena become pronounced as the size of the system decreases. These include statistical mechanical effects, as well as quantum mechanical effects, for example the “quantum size effect” where the electronic properties of solids are altered with great reductions in particle size. This effect does not come into play by going from macro to micro dimensions. However, it becomes dominant when the nanometer size range is reached. Additionally, a number of physical (mechanical, electrical, optical, etc.) properties change when compared to macroscopic systems. One example is the increase in surface area to volume ratio altering mechanical, thermal and catalytic properties of materials. Novel mechanical properties of nanosystems are of interest in the nanomechanics research. The catalytic activity of nanomaterials also opens potential risks in their interaction with biomaterials.

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

Simple to complex: a molecular perspective


Modern synthetic chemistry has reached the point where it is possible to prepare small molecules to almost any structure. These methods are used today to produce a wide variety of useful chemicals such as pharmaceuticals or commercial polymers. This ability raises the question of extending this kind of control to the next-larger level, seeking methods to assemble these single molecules into supramolecular assemblies consisting of many molecules arranged in a well defined manner.

These approaches utilize the concepts of molecular self-assembly and/or supramolecular chemistry to automatically arrange themselves into some useful conformation through a bottom-up approach. The concept of molecular recognition is especially important: molecules can be designed so that a specific conformation or arrangement is favored due to non-covalent intermolecular forces. The Watson-Crick basepairing rules are a direct result of this, as is the specificity of an enzyme being targeted to a single substrate, or the specific folding of the protein itself. Thus, two or more components can be designed to be complementary and mutually attractive so that they make a more complex and useful whole.

Such bottom-up approaches should be able to produce devices in parallel and much cheaper than top-down methods, but could potentially be overwhelmed as the size and complexity of the desired assembly increases. Most useful structures require complex and thermodynamically unlikely arrangements of atoms. Nevertheless, there are many examples of self-assembly based on molecular recognition in biology, most notably Watson-Crick basepairing and enzyme-substrate interactions. The challenge for nanotechnology is whether these principles can be used to engineer novel constructs in addition to natural ones.

Molecular nanotechnology: a long-term view


Molecular nanotechnology, sometimes called molecular manufacturing, is a term given to the concept of engineered nanosystems (nanoscale machines) operating on the molecular scale. It is especially associated with the concept of a molecular assembler, a machine that can produce a desired structure or device atom-by-atom using the principles of mechanosynthesis. Manufacturing in the context of productive nanosystems is not related to, and should be clearly distinguished from, the conventional technologies used to manufacture nanomaterials such as carbon nanotubes and nanoparticles.

When the term "nanotechnology" was independently coined and popularized by Eric Drexler (who at the time was unaware of an earlier usage by Norio Taniguchi) it referred to a future manufacturing technology based on molecular machine systems. The premise was that molecular scale biological analogies of traditional machine components demonstrated molecular machines were possible: by the countless examples found in biology, it is known that sophisticated, stochastically optimised biological machines can be produced..

It is hoped that developments in nanotechnology will make possible their construction by some other means, perhaps using biomimetic principles. However, Drexler and other researchers have proposed that advanced nanotechnology, although perhaps initially implemented by biomimetic means, ultimately could be based on mechanical engineering principles, namely, a manufacturing technology based on the mechanical functionality of these components (such as gears, bearings, motors, and structural members) that would enable programmable, positional assembly to atomic specification (PNAS-1981). The physics and engineering performance of exemplar designs were analyzed in Drexler's book Nanosystems.

In general it is very difficult to assemble devices on the atomic scale, as all one has to position atoms are other atoms of comparable size and stickyness. Another view, put forth by Carlo Montemagno, is that future nanosystems will be hybrids of silicon technology and biological molecular machines. Yet another view, put forward by the late Richard Smalley, is that mechanosynthesis is impossible due to the difficulties in mechanically manipulating individual molecules.

This led to an exchange of letters in the ACS publication Chemical & Engineering News in 2003. Though biology clearly demonstrates that molecular machine systems are possible, non-biological molecular machines are today only in their infancy. Leaders in research on non-biological molecular machines are Dr. Alex Zettl and his colleagues at Lawrence Berkeley Laboratories and UC Berkeley. They have constructed at least three distinct molecular devices whose motion is controlled from the desktop with changing voltage: a nanotube nanomotor, a molecular actuator, and a nanoelectromechanical relaxation oscillator.

An experiment indicating that positional molecular assembly is possible was performed by Ho and Lee at Cornell University in 1999. They used a scanning tunneling microscope to move an individual carbon monoxide molecule (CO) to an individual iron atom (Fe) sitting on a flat silver crystal, and chemically bound the CO to the Fe by applying a voltage.

Current research


Graphical representation of a rotaxane, useful as a molecular switch.
Graphical representation of a rotaxane, useful as a molecular switch.
This device transfers energy from nano-thin layers of quantum wells to nanocrystals above them, causing the nanocrystals to emit visible light.
This device transfers energy from nano-thin layers of quantum wells to nanocrystals above them, causing the nanocrystals to emit visible light.

Nanomaterials

This includes subfields which develop or study materials having unique properties arising from their nanoscale dimensions.

* Interface and Colloid Science has given rise to many materials which may be useful in nanotechnology, such as carbon nanotubes and other fullerenes, and various nanoparticles and nanorods.
* Nanoscale materials can also be used for bulk applications; most present commercial applications of nanotechnology are of this flavor.
* Progress has been made in using these materials for medical applications; see Nanomedicine.

Bottom-up approaches

These seek to arrange smaller components into more complex assemblies.

* DNA nanotechnology utilizes the specificity of Watson-Crick basepairing to construct well-defined structures out of DNA and other nucleic acids.
* Approaches from the field of "classical" chemical synthesis also aim at designing molecules with well-defined shape (e.g. bis-peptides).
* More generally, molecular self-assembly seeks to use concepts of supramolecular chemistry, and molecular recognition in particular, to cause single-molecule components to automatically arrange themselves into some useful conformation.

Top-down approaches

These seek to create smaller devices by using larger ones to direct their assembly.

* Many technologies descended from conventional solid-state silicon methods for fabricating microprocessors are now capable of creating features smaller than 100 nm, falling under the definition of nanotechnology. Giant magnetoresistance-based hard drives already on the market fit this description,[10] as do atomic layer deposition (ALD) techniques. Peter Grünberg and Albert Fert received the Nobel Prize in Physics for their discovery of Giant magnetoresistance and contributions to the field of spintronics in 2007.

* Solid-state techniques can also be used to create devices known as nanoelectromechanical systems or NEMS, which are related to microelectromechanical systems or MEMS.
* Atomic force microscope tips can be used as a nanoscale "write head" to deposit a chemical upon a surface in a desired pattern in a process called dip pen nanolithography. This fits into the larger subfield of nanolithography.

Functional approaches

These seek to develop components of a desired functionality without regard to how they might be assembled.

* Molecular electronics seeks to develop molecules with useful electronic properties. These could then be used as single-molecule components in a nanoelectronic device. For an example see rotaxane.
* Synthetic chemical methods can also be used to create synthetic molecular motors, such as in a so-called nanocar.

Speculative

These subfields seek to anticipate what inventions nanotechnology might yield, or attempt to propose an agenda along which inquiry might progress. These often take a big-picture view of nanotechnology, with more emphasis on its societal implications than the details of how such inventions could actually be created.

* Molecular nanotechnology is a proposed approach which involves manipulating single molecules in finely controlled, deterministic ways. This is more theoretical than the other subfields and is beyond current capabilities.
* Nanorobotics centers on self-sufficient machines of some functionality operating at the nanoscale. There are hopes for applying nanorobots in medicine, but it may not be easy to do such a thing because of several drawbacks of such devices. Nevertheless, progress on innovative materials and methodologies has been demonstrated with some patents granted about new nanomanufacturing devices for future commercial applications, which also progressively helps in the development towards nanorobots with the use of embedded nanobioelectronics concept.
* Programmable matter based on artificial atoms seeks to design materials whose properties can be easily, reversibly and externally controlled.
* Due to the popularity and media exposure of the term nanotechnology, the words picotechnology and femtotechnology have been coined in analogy to it, although these are only used rarely and informally.

Tools and techniques

Typical AFM setup. A microfabricated cantilever with a sharp tip is deflected by features on a sample surface, much like in a phonograph but on a much smaller scale. A laser beam reflects off the backside of the cantilever into a set of photodetectors, allowing the deflection to be measured and assembled into an image of the surface.
Typical AFM setup. A microfabricated cantilever with a sharp tip is deflected by features on a sample surface, much like in a phonograph but on a much smaller scale. A laser beam reflects off the backside of the cantilever into a set of photodetectors, allowing the deflection to be measured and assembled into an image of the surface.

The first observations and size measurements of nano-particles were made during the first decade of the 20th century. They are mostly associated with the name of Zsigmondy who made detailed studies of gold sols and other nanomaterials with sizes down to 10 nm and less. He published a book in 1914. He used ultramicroscope that employs a dark field method for seeing particles with sizes much less than light wavelength.

There are traditional techniques developed during 20th century in Interface and Colloid Science for characterizing nanomaterials. These are widely used for first generation passive nanomaterials specified in the next section.

These methods include several different techniques for characterizing particle size distribution. This characterization is imperative because many materials that are expected to be nano-sized are actually aggregated in solutions. Some of methods are based on light scattering. Other apply ultrasound, such as ultrasound attenuation spectroscopy for testing concentrated nano-dispersions and microemulsions.

There is also a group of traditional techniques for characterizing surface charge or zeta potential of nano-particles in solutions. This information is required for proper system stabilzation, preventing its aggregation or flocculation. These methods include microelectrophoresis, electrophoretic light scattering and electroacoustics. The last one, for instance colloid vibration current method is suitable for characterizing concentrated systems.

Next group of nanotechnological techniques include those used for fabrication of nanowires, those used in semiconductor fabrication such as deep ultraviolet lithography, electron beam lithography, focused ion beam machining, nanoimprint lithography, atomic layer deposition, and molecular vapor deposition, and further including molecular self-assembly techniques such as those employing di-block copolymers. However, all of these techniques preceded the nanotech era, and are extensions in the development of scientific advancements rather than techniques which were devised with the sole purpose of creating nanotechnology and which were results of nanotechnology research.

There are several important modern developments. The atomic force microscope (AFM) and the Scanning Tunneling Microscope (STM) are two early versions of scanning probes that launched nanotechnology. There are other types of scanning probe microscopy, all flowing from the ideas of the scanning confocal microscope developed by Marvin Minsky in 1961 and the scanning acoustic microscope (SAM) developed by Calvin Quate and coworkers in the 1970s, that made it possible to see structures at the nanoscale. The tip of a scanning probe can also be used to manipulate nanostructures (a process called positional assembly). Feature-oriented scanning-positioning methodology suggested by Rostislav Lapshin appears to be a promising way to implement these nanomanipulations in automatic mode. However, this is still a slow process because of low scanning velocity of the microscope. Various techniques of nanolithography such as dip pen nanolithography, electron beam lithography or nanoimprint lithography were also developed. Lithography is a top-down fabrication technique where a bulk material is reduced in size to nanoscale pattern.

The top-down approach anticipates nanodevices that must be built piece by piece in stages, much as manufactured items are made. Scanning probe microscopy is an important technique both for characterization and synthesis of nanomaterials. Atomic force microscopes and scanning tunneling microscopes can be used to look at surfaces and to move atoms around. By designing different tips for these microscopes, they can be used for carving out structures on surfaces and to help guide self-assembling structures. By using, for example, feature-oriented scanning-positioning approach, atoms can be moved around on a surface with scanning probe microscopy techniques. At present, it is expensive and time-consuming for mass production but very suitable for laboratory experimentation.

In contrast, bottom-up techniques build or grow larger structures atom by atom or molecule by molecule. These techniques include chemical synthesis, self-assembly and positional assembly. Another variation of the bottom-up approach is molecular beam epitaxy or MBE. Researchers at Bell Telephone Laboratories like John R. Arthur. Alfred Y. Cho, and Art C. Gossard developed and implemented MBE as a research tool in the late 1960s and 1970s. Samples made by MBE were key to the discovery of the fractional quantum Hall effect for which the 1998 Nobel Prize in Physics was awarded. MBE allows scientists to lay down atomically-precise layers of atoms and, in the process, build up complex structures. Important for research on semiconductors, MBE is also widely used to make samples and devices for the newly emerging field of spintronics.

Newer techniques such as Dual Polarisation Interferometry are enabling scientists to measure quantitatively the molecular interactions that take place at the nano-scale.

However, new therapeutic products, based on responsive nanomaterials, such as the ultradeformable, stress-sensitive Transfersome vesicles, are under development and already approved for human use in some countries.

Applications


As of April 24, 2008 The Project on Emerging Nanotechnologies claims that over 609 nanotech products exist, with new ones hitting the market at a pace of 3-4 per week. The project lists all of the products in a database. Most applications are limited to the use of "first generation" passive nanomaterials which includes titanium dioxide in sunscreen, cosmetics and some food products; Carbon allotropes used to produce gecko tape; silver in food packaging, clothing, disinfectants and household appliances; zinc oxide in sunscreens and cosmetics, surface coatings, paints and outdoor furniture varnishes; and cerium oxide as a fuel catalyst.

The National Science Foundation (a major source of funding for nanotechnology in the United States) funded researcher David Berube to study the field of nanotechnology. His findings are published in the monograph “Nano-Hype: The Truth Behind the Nanotechnology Buzz". This published study (with a foreword by Anwar Mikhail, Senior Advisor for Nanotechnology at the National Science Foundation) concludes that much of what is sold as “nanotechnology” is in fact a recasting of straightforward materials science, which is leading to a “nanotech industry built solely on selling nanotubes, nanowires, and the like” which will “end up with a few suppliers selling low margin products in huge volumes." Further applications which require actual manipulation or arrangement of nanoscale components await further research. Though technologies branded with the term 'nano' are sometimes little related to and fall far short of the most ambitious and transformative technological goals of the sort in molecular manufacturing proposals, the term still connotes such ideas. Thus there may be a danger that a "nano bubble" will form, or is forming already, from the use of the term by scientists and entrepreneurs to garner funding, regardless of interest in the transformative possibilities of more ambitious and far-sighted work.

Implications

Due to the far-ranging claims that have been made about potential applications of nanotechnology, a number of serious concerns have been raised about what effects these will have on our society if realized, and what action if any is appropriate to mitigate these risks.

One area of concern is the effect that industrial-scale manufacturing and use of nanomaterials would have on human health and the environment, as suggested by nanotoxicology research. Groups such as the Center for Responsible Nanotechnology have advocated that nanotechnology should be specially regulated by governments for these reasons. Others counter that overregulation would stifle scientific research and the development of innovations which could greatly benefit mankind.

Other experts, including director of the Woodrow Wilson Center's Project on Emerging Nanotechnologies David Rejeski, have testified that successful commercialization depends on adequate oversight, risk research strategy, and public engagement. More recently local municipalities have passed (Berkeley, CA) or are considering (Cambridge, MA) - ordinances requiring nanomaterial manufacturers to disclose the known risks of their products.

The National Institute for Occupational Safety and Health is conducting research on how nanoparticles interact with the body’s systems and how workers might be exposed to nano-sized particles in the manufacturing or industrial use of nanomaterials. NIOSH offers interim guidelines for working with nanomaterials consistent with the best scientific knowledge.

Longer-term concerns center on the implications that new technologies will have for society at large, and whether these could possibly lead to either a post scarcity economy, or alternatively exacerbate the wealth gap between developed and developing nations. The effects of nanotechnology on the society as a whole, on human health and the environment, on trade, on security, on food systems and even on the definition of "human", have not been characterized or politicized.

Health and environmental concerns



Some of the recently developed nanoparticle products may have unintended consequences. Researchers have discovered that silver nanoparticles used in socks to reduce foot odor are being released in the wash with possible negative consequences. Silver nanoparticles, which are bacteriostatic, may then destroy beneficial bacteria which are important for breaking down organic matter in waste treatment plants or farms.

A study at the University of Rochester found that when rats breathed in nanoparticles, the particles settled in the brain and lungs, which lead to significant increases in biomarkers for inflammation and stress response.

A major study published more recently in Nature nanotechnology suggests some forms of carbon nanotubes – a poster child for the “nanotechnology revolution” – could be as harmful as asbestos if inhaled in sufficient quantities. Anthony Seaton of the Institute of Occupational Medicine in Edinburgh, Scotland, who contributed to the article on carbon nanotubes said "We know that some of them probably have the potential to cause mesothelioma. So those sorts of materials need to be handled very carefully." In the absence of specific nano-regulation forthcoming from governments, Paull and Lyons (2008) have called for an exclusion of engineered nanoparticles from organic food.

Regulation

Calls for tighter regulation of nanotechnology have occurred alongside a growing debate related to the human health and safety risks associated with nanotechnology. Further, there is significant debate about who is responsible for the regulation of nanotechnology. While some non-nanotechnology specific regulatory agencies currently cover some products and processes (to varying degrees) – by “bolting on” nanotechnology to existing regulations – there are clear gaps in these regimes.

Stakeholders concerned by the lack of a regulatory framework to assess and control risks associated with the release of nanoparticles and nanotubes have drawn parallels with bovine spongiform encephalopathy (‘mad cow’s disease), thalidomide, genetically modified food, nuclear energy, reproductive technologies, biotechnology, and asbestosis. The Woodrow Wilson Centre’s Project on Emerging Technologies conclude (among others) that there is insufficient funding for human health and safety research, and as a result there is currently limited understanding of the human health and safety risks associated with nanotechnology.

The Royal Society report identified a risk of nanoparticles or nanotubes being released during disposal, destruction and recycling, and recommended that “manufacturers of products that fall under extended producer responsibility regimes such as end-of-life regulations publish procedures outlining how these materials will be managed to minimize possible human and environmental exposure” (p.xiii). Reflecting the challenges for ensuring responsible life cycle regulation, the Institute for Food and Agricultural Standards has proposed standards for nanotechnology research and development should be integrated across consumer, worker and environmental standards. They also propose that NGOs and other citizen groups play a meaningful role in the development of these standards.