Nanobiotechnology

Nanobiotechnology is the branch of nanotechnology with biological and biochemical applications or uses. Nanobiotechnology often studies existing elements of nature in order to fabricate new devices
The term bionanotechnology is often used interchangeably with nanobiotechnology, though a distinction is sometimes drawn between the two. If the two are distinguished, nanobiotechnology usually refers to the use of nanotechnology to further the goals of biotechnology, while bionanotechnology might refer to any overlap between biology and nanotechnology, including the use of biomolecules as part of or as an inspiration for nanotechnological devices.
Examples

One example of current nanobiotechnological research involves nanospheres coated with fluorescent polymers. Researchers are seeking to design polymers whose fluorescence is quenched when they encounter specific molecules. Different polymers would detect different metabolites. The polymer-coated spheres could become part of new biological assays, and the technology might someday lead to particles that could be introduced into the human body to track down metabolites associated with tumors and other health problems.

Antibody-Nanoparticle Computational Modeling

The conjugation of antibodies and nanoparticles with high affinity & specificity through receptor-ligand recognition modes is of paramount importance in the development of vehicles which can be used for diagnosis, treatment of cancer and various other diseases, application of immudiagnostic nano-biosensors etc. The bio-nanocomplex formed by an artificial nanomaterial (nanoliposomes , nanoparticles ) and a biological entity such as an antibody is brought about by the formation of covalent bonds based on their specific chemical and structural properties such as water solubility, biocompatibility, and biodegradability. There is a requirement of a comprehensive understanding of the relationship of the thermodynamic & kinetic aspects of antibody-membrane association, translational , rotational mobilities of membrane bound antibodies, interactions with the diverse cell surface , circulating molecules and various artificial nanomolecules as well as the conformation. These details are of great importance in the development, application of various nanoscale immunodiagnostic devices. The association of antibodies with cell surfaces is a key molecular event in antibody-mediated immune mechanisms such as phagocytosis, antibody mediated immune dependent cell-mediated cytotoxicity.

The interfacial properties, especially the dynamic, thermodynamic, and mechanical properties, at different spatial and temporal resolutions of these bio-nano systems can be readily investigated with the aid of computer simulations, which consist of studies of interactions of the proteins as well as those of various nanomaterials with organic biological molecules such as proteins, nucleic acids, membrane lipids, and water and of significance importance is the study of the interactions of nanoparticles in the protein binding sites and optimization of the same for improved bio-nano recognition. Recently it has been noted that there exists certain natural proteins, antibodies, that can recognize specific nanoparticles . For example, a specific antibody from the mouse immune system can specifically recognize derivatized C60 fullerenes with a binding affinity of about 25 nM [ From the studies carried out by Noon et al, it is hypothized that the fullerene-binding site is formed at the interface of the light and heavy chains lined with a cluster of shape-complementary hydrophobic amino acid residues. As the covalent modifications of the functionalized fullerenes, occupy only a small fraction of the particle surface area , the largely unoccupied surface would be free to interact with the antibody. Therefore, in order to gain in-depth understanding of the detailed interactions of the nps and the antibody, molecular dynamics simulation is carried out using molecular dynamics simulation; the purpose of our theoretical modeling studies is to be able to identify the energetically favorable binding modes. [

For the modeling study, the initial coordinates of the antibody can be made available from the Protein Data Bank (PDB). [ [ The coordinates of the nanoparticle in this case , would be obtained from the AFM, TEM studies carried out at the AMERI and Nano-biotechnology laboratory, FIU, Miami. The CHARMm (Chemistry at HARvard Macromolecular Mechanics) an Unix-based commercialized software using Fortran 77 source codes uses set of force fields for molecular dynamics for simulation and analysis.

The basic assumptions, as a first approximation, during the modeling study would be that the hydrophilic derivatizations do not play a critical role in the predominantly hydrophobic nanomaterial-antibody interactions and that the electronic structure remains undisturbed during the conjugation. The nanoparticle is docked into a suggested binding site from the previously done literature studies.[ Polar-hydrogen potential function (PARAM19) and a modified TIP3P water solvent model for the protein is used.

The simulation involves approximately about 300 steps of minimization, using the Steepest Descent and the Newton Raphson method. To reduce the necessary simulation time, a highly efficient method for simulating the localized interactions in the active site of a protein, the stochastic boundary molecular dynamics (SBMD) is used. The reference point for partitioning the system in SBMD was chosen to be near the center of the nanomaterials, which is assumed to be an uniform sphere. The complex nano-bio system can be assumed to be separated into spherical reservoir and reaction zones; the latter is further sub-divided into a reaction region and a buffer region. The atoms in the reaction region are propagated by molecular dynamics, whereas those in the buffer region involve Langevin dynamics are retained using harmonic restoring forces.

Implications of nanotechnology

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.

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[28] that successful commercialization depends on adequate oversight, risk research strategy, and public engagement. More recently local municipalities have passed (Berkeley, CA)[29] or are considering (Cambridge, MA)[30] - 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.[31]

In "The Consumer Product Safety Commission and Nanotechnology,"[32] E. Marla Felcher suggests that the Consumer Product Safety Commission, which is charged with protecting the public against unreasonable risks of injury or death associated with consumer products, is ill-equipped to oversee the safety of complex, high-tech products made using nanotechnology.

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.

Nanotechnology - Applications

As of August 21, 2008, the Project on Emerging Nanotechnologies estimates that over 800 manufacturer-identified nanotech products are publicly available, with new ones hitting the market at a pace of 3-4 per week.[26] The project lists all of the products in a publicly accessible online inventory. 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.[27]

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 published study (with a foreword by [Mikhail Roco], 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. 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.

Nano-membranes have been produced that are portable and easily-cleaned systems that purify, detoxify and desalinate water meaning that third-world countries could get clean water, solving many water related health issues.

Nanotechnology - Tools and techniques

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.

Nanotechnology - 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 life-forms, 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. 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.

[edit] 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.
Main article: Nanomaterials

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. Diffusion and reactions at nanoscale, nanostructures materials and nanodevices with fast ion transport are generally referred to nanoionics. 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.

[edit] Simple to complex: a molecular perspective
Main article: Molecular self-assembly

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.

[edit] Molecular nanotechnology: a long-term view
Main article: Molecular nanotechnology

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[8] 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,[9] 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.[10] 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.

Nanotechnology - Origin

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[2] 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,[3] 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.

Nanotechnology

Nanotechnology, shortened to "Nanotech", is the study of the control of matter on an atomic and molecular scale. Generally nanotechnology deals with structures of the size 100 nanometers or smaller, and involves developing materials or devices within that size.

Nanotechnology is extremely diverse, 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, even to speculation on whether we can directly control matter on the atomic scale.

There has been much debate on the future of 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. Despite this promise, there are few examples of nanotechnology that have moved beyond fundamental research and into the marketplace (with most examples limited to bulk nanopowders). Nanotechnology also 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 led to a debate among advocacy groups and governments on whether special regulation of nanotechnology is warranted.

Cancer Treatment

A technique thought to be a promising cancer treatment is also being investigated as the basis for a Taser-like weapon that stuns for longer, New Scientist has learned.

The technology involves short, nanosecond-long pulses of extreme voltage.

Microsecond pulses have been used for years to punch temporary holes in cell membranes, to shove genes or drugs into cells. But the nanosecond pulses have similar effects on individual organelles inside a cell, such as the nucleus.

For reasons as yet unknown, this can cause a cell to destroy itself in a process known as apoptosis, something being investigated as a cancer treatment. But the nanosecond pulses are also being researched as a way to temporarily disable human muscles.

Incapacitating effects

Much research to date on nanosecond pulses has come from the Frank Reidy Research Centre for Bioelectrics at Old Dominion University in Norfolk, Virginia, where some research is sponsored by the Pentagon's Joint Non-Lethal Weapons Directorate (JNLWD) of Quantico, Virginia.

"Efforts are ongoing as part of our Human Electro-Muscular Incapacitation bio-effects research," confirms David B Law, technology division chief at the JNLWD.

"The short-pulse simulations and research appear to be demonstrating a degree of voluntary muscular impairment or inhibition, that remains in effect for durations longer than the exposure period," he adds.

Existing Tasers use multiple electric shocks of a few microseconds over a five-second cycle. The shocks are delivered to the body through twin electrodes fired in a dart.

The pulsing electric field created inside the body disrupts the electrical activity of nerve cell membranes. These are responsible for carrying instructions and feedback around the body.

The effects wear off almost immediately, according to Taser spokesman Steve Tuttle, so that a suspect is incapacitated for just long enough to make an arrest.
Stunned for longer

Even shorter, nanosecond pulses have the potential to cause similar but longer lasting stunning, research from the Frank Reidy centre suggests.

One study on cells in vitro indicated that 60-nanosecond pulses caused "profound and long-lasting loss" of the electrical activity in the membranes of cells similar to nerve cells. The effect lasted fifteen minutes.

So far, research investigating the potential to disable muscles using nanopulses has been limited to tests on tissue samples in vitro and theoretical studies that claim the ultrashort shocks should be able to disable a whole animal.

However, Law says that plans for testing on live subjects are "proceeding at appropriate institutions." He declined to be more specific or say when human testing might take place.

"The medical and biological effects of such ultra-short electrical shocks in such a weapon are presently unknown," highlights Amnesty International researcher Angela Wright, saying the organisation is already concerned that evidence is emerging that Tasers and other shock devices have long-term health effects.

She thinks that the different effects of even shorter pulses may also have unpredicted effects.