Wednesday, May 4, 2011

Nanotechnology in Biotechnology!!!

Nanotechnology (sometimes shortened to "nanotech") is the study of manipulating matter on an atomic and molecular scale. Generally, nanotechnology deals with structures sized between 1 to 100 nanometre in at least one dimension, and involves developing materials or devices possessing at least one dimension within that size. Quantum mechanical effects are very important at this scale, which is in the quantum realm.
Nanotechnology is very diverse, ranging from extensions of conventional device physics to completely new approaches based upon molecular self-assembly, from developing new materials with dimensions on the nanoscale to investigating whether we can directly control matter on the atomic scale.
The first use of the concepts found in 'nano-technology' (but pre-dating 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 California Institute of Technology (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, and 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 increasingly more significant, etc. This basic idea appeared plausible, and exponential assembly enhances it with parallelism to produce a useful quantity of end products. The term "nanotechnology" was defined by Tokyo University of Science 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 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 1985 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 and metal oxide nanoparticles and quantum dots. The atomic force microscope (AFM or SFM) 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 and is evaluated by the President's Council of Advisors on Science and Technology.

Fundamental concepts

Nanotechnology is the engineering of functional systems at the molecular scale. This covers both current work and concepts that are more advanced. In its original sense, nanotechnology refers to the projected ability to construct items from the bottom up, using techniques and tools being developed today to make complete, high performance products.
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 life-forms, the bacteria of the genus Mycoplasma, are around 200 nm in length. By convention, nanotechnology is taken as the scale range 1 to 100 nm following the definition used by the National Nanotechnology Initiative in the US. The lower limit is set by the size of atoms (hydrogen has the smallest atoms, which are approximately a quarter of a nm diameter) since nanotechnology must build its devices from atoms and molecules. The upper limit is more or less arbitrary but is around the size that phenomena not observed in larger structures start to become apparent and can be made use of in the nano device. These new phenomena make nanotechnology distinct from devices which are merely miniaturised versions of an equivalent macroscopic device; such devices are on a larger scale and come under the description of microtechnology.
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 an average 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.
Areas of physics such as nanoelectronics, nanomechanics, nanophotonics and nanoionics have evolved during the last few decades to provide a basic scientific foundation of nanotechnology.

Larger to smaller: a materials perspective


Image of reconstruction on a clean Gold(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, quantum effects become dominant when the nanometer size range is reached, typically at distances of 100 nanometers or less, the so called quantum realm. 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. Diffusion and reactions at nanoscale, nanostructures materials and nanodevices with fast ion transport are generally referred to nanoionics. 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); insoluble materials become soluble (gold). 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

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 configuration 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 capable of producing devices in parallel and be 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 new constructs in addition to natural ones.

Molecular nanotechnology: a long-term view

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. 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 on other atoms of comparable size and stickiness. 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. See nanotube nanomotor for more examples.
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.

This DNA tetrahedron is an artificially designed nanostructure of the type made in the field of DNA nanotechnology. Each edge of the tetrahedron is a 20 base pair DNA double helix, and each vertex is a three-arm junction.

This device transfers energy from nano-thin layers of quantum wells to nanocrystals above them, causing the nanocrystals to emit visible light.

Nanomaterials

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

Bottom-up approaches

These seek to arrange smaller components into more complex assemblies.

Top-down approaches

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

Functional approaches

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

Biomimetic approaches

  • Bionics or biomimicry seeks to apply biological methods and systems found in nature, to the study and design of engineering systems and modern technology. Biomineralization is one example of the systems studied.

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 concepts.
  • Productive nanosystems are "systems of nanosystems" which will be complex nanosystems that produce atomically precise parts for other nanosystems, not necessarily using novel nanoscale-emergent properties, but well-understood fundamentals of manufacturing. Because of the discrete (i.e. atomic) nature of matter and the possibility of exponential growth, this stage is seen as the basis of another industrial revolution. Mihail Roco, one of the architects of the USA's National Nanotechnology Initiative, has proposed four states of nanotechnology that seem to parallel the technical progress of the Industrial Revolution, progressing from passive nanostructures to active nanodevices to complex nanomachines and ultimately to productive nanosystems.
  • Programmable matter seeks to design materials whose properties can be easily, reversibly and externally controlled though a fusion of information science and materials science.
  • 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.
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 optical lithography, X-ray lithography 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.
Another 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.
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. Dual polarisation interferometry is one tool suitable for characterisation of self assembled thin films. 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.
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


One of the major applications of nanotechnology is in the area of nanoelectronics with MOSFET's being made of small nanowires ~10 nm in length. Here is a simulation of such a nanowire.
The National Science Foundation (a major distributor for nanotechnology research 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 study 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. According to Berube, 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

There are possible dangers that arise with the development of nanotechnology. The Center for Responsible Nanotechnology suggests that new developments could result, among other things, in untraceable weapons of mass destruction, networked cameras for use by the government, and weapons developments fast enough to destabilize arms races ("Nanotechnology Basics").
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. Berkeley, California is currently the only city in the United States to regulate nanotechnology; Cambridge, Massachusetts in 2008 considered enacting a similar law, but ultimately rejected this.

Health and environmental concerns

A study at the University of Rochester found that when rats breathed in nanoparticles, the particles settled in the brain and lungs, which led to significant increases in biomarkers for inflammation and stress response. A study in China indicated that nanoparticles induce skin aging through oxidative stress in hairless mice.
A two-year study at UCLA's School of Public Health found lab mice consuming nano-titanium dioxide showed DNA and chromosome damage to a degree "linked to all the big killers of man, namely cancer, heart disease, neurological disease and aging".
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. A newspaper article reports that workers in a paint factory developed serious lung disease and nanoparticles were found in their lungs.

Regulation

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. Dr. Andrew Maynard, chief science advisor to the Woodrow Wilson Center’s Project on Emerging Nanotechnologies, concludes (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. As a result, some academics have called for stricter application of the precautionary principle, with delayed marketing approval, enhanced labelling and additional safety data development requirements in relation to certain forms of 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.

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