Kinkajou : So how dangerous is all this medical nanotechnology? I think Nano-toxicology is the science that looks at assessing how dangerous these particles may be to organisms such as the human being.
Erasmus : Nano-toxicology studies possible deleterious effects of nano materials on biological systems. For example even inert elements like gold can interact very differently with the body when they exist at nano dimensions.
Size and shape of particles at quantum dimensions can result in interaction profiles related to these parameters not just to chemical composition. Other potentially important factors include chemical composition, surface structure, hydrophobic or hydrophilic surface structure, ionic nature, flocculation and solubility as determinants of potential toxicity.
Nanoparticles such as graphene or Carbon rods have been likened to asbestos, raising concerns about their interaction with cellular components and immune system of the body. Whether other nano particle fibres can cause lung damage remains to be seen.
Mad cow disease (bovine spongiform encephalopathy) is caused by the accumulation of protein nano- particles that cannot be metabolized within nerve cells in the brain. The particles build up, eventually killing the cell. Eventually the cell death reaches a point where the functioning of the brain becomes an effect at a "macro" level.
The catalytic activity of nano-materials also opens potential risks in their interaction with biological constituent such as protein, DNA and other microcellular structures and enzyme systems.
The difficulties with Nano-toxicology studies focus on how to identify key parameters involved in cellular or sub- cellular damage. In asbestos, a comparable example, only particular fibres of particular asbestos species are especially dangerous.
Cell fibres are dangerous to biological systems with active immune systems. So studies based on cellular assays in vitro are unlikely to identify risks. Also nano particles tend to absorb to specific cellular systems,in the case of asbestos it being lung tissue that is damaged. So it may be the indirect effects that are important in assessing nano particle toxicology.
Nanoparticles of silica found in Maggi's Roast Meat Gravy.
Kinkajou : Labeling criteria often fail to identify nano particles within foods, as they are often simply identified as equivalent to their macro chemical constituents, in effect failing to recognize they may have unique metabolic, immune and interaction profiles to larger dimension substances.
Erasmus : One environmental group tested a range of popular foodstuffs at common suburban stores and found nanoparticles of titanium oxide and silica in a number of popular products, even though labeling did not admit their presence.
The Food Standards code does not require nanoparticles to be declared on labelling. Nano-titanium dioxide (E171) can be simply described as the "Colour (171)", not nano E1 71. Nano-silica (E551) can be listed as “Anti-caking agent (551)", without any recognition of size related alterations of its properties. Nanotechnology has been found in popular foods, despite repeated denials by regulators.
Nanoparticles of titanium dioxide found in Mentos Pure Fresh Gum.
Nano-toxicological studies are intended to determine whether and to what extent these properties may pose a threat to the environment and to human beings. Knowing what the significant properties to test are is very difficult.
Many toxicology studies focus on the use of bacterial and then mammalian test systems such as mice or rats. However, consider is the danger posed by diesel nanoparticles for carcinogenesis in mouse study systems, really relevant to human beings? Mice and rats in many aspects have very different immune systems to human beings. Findings in these types of studies may not be relevant to findings in human beings.
Kinkajou : Any other comments on the Safety of nanoparticles?
Erasmus : Nanoparticles created adventitiously (e.g., through the rubbing of prostheses) have long been known to be a health hazard,
Iron oxide nanoparticles caused little DNA damage and were non-toxic.
Zinc oxide nanoparticles were slightly worse.
Titanium dioxide caused only DNA damage.
Carbon nanotubes caused DNA damage at low levels.
Copper oxide was found to be the worst offender, and was the only nanomaterial identified by the researchers as a clear health risk
There is no conclusive evidence that nano-titanium dioxide, which whitens and brightens, and nano-silica, which prevents caking, is completely safe to eat. They have been shown in some studies to interfere with the immune system and cause cell damage.
Kinkajou: Consequently there have been a number of calls for increased regulation of the incorporation of nanoparticles in foods, calls for standards to be created covering the disposal, destruction or recycling of nano materials, and suggestions that guidelines are set on how to manage materials and minimise possible human and environmental exposure to them.
Nono Particle Related Disease
Kinkajou : Is there a difference between natural and artificial nanoparticles? Are there any examples of the ability of nanoparticles to move through the body or to cause inflammation within the body?
Erasmus : Nanoparticles can be divided into combustion-derived nanoparticles (like diesel soot), manufactured nanoparticles like carbon nanotubes and naturally occurring nanoparticles from volcanic eruptions, atmospheric chemistry etc. The type of production process can be significant. Take the example of carbon nanotubes.
Some concerns have been raised about the toxicity of carbon nanotubes. Studies have suggested that it is the chemical contaminants (tetrahydrofuran) built into graphene nano structures that cause most of this toxicity.
Reactive oxygen species and free radicals can be produced from some nanoparticles including graphene derivatives and nano particle metal oxides.
Whether oxidative stress derived from the presence of reactive oxygen species can cause damage to proteins, cell membranes and DNA as well as initiating inflammation remains to be seen. Fullerenes have been shown to be toxic in some fish species.
Typical nanoparticles that have been studied are titanium dioxide, alumina, zinc oxide, carbon black, and carbon nanotubes, and "nano-C60". Nanoparticles have much larger surface area to unit mass ratios which in some cases may lead to greater pro-inflammatory effects (in, for example, lung tissue).
In addition, some nanoparticles seem to be able to translocate from their site of deposition to distant sites such as the blood and the brain.
Phagocytes (white blood cells) are often able to ingest and transfer nano particles throughout the body. Studies (on the eggs and adult bodies of a species of fish, known as the see-through medaka (Oryzias latipes)), have shown that nanoparticles readily transfer through the bloodstream to sites in the gills, intestine, liver, brain and even into the yolks of the fish eggs.
Environmental salinity assists the transfer of these particles through the bodies of the fish. Whether the fish represent a suitable model for the pathogenesis of these nanoparticles in humans however remains to be seen.
Many different cell types (that is cells from different organs), should be studied in order to know if a nanostructure induces toxicity. Human cells can internalize aggregated nanoparticles. Moreover, it is important to take into account that many nanostructures aggregate in biological fluids.
Nano particle toxicology can also include simple mundane aspects such as pollution. For example incorporating silver nanoparticles in socks to reduce foot over or in dressings to reduce infection seems sensible.
However when these materials (heavy metals) enter into the waste stream, silver acting as a simple heavy metal can cause toxicity and can enter the environment via the waste treatment system.
Kinkajou : I have heard that green nanoparticles may be less dangerous than other nanoparticles.
Erasmus : I think what you’re talking about is green nanotechnology.
Green nanotechnology states the goal of producing nano materials that minimise harm to human health and minimise harm to the environment. It also seeks to improve manufacturing processes so that they are more environmentally friendly and to improve recycling methods.
Suggested roles include,
- developing catalysts to improve efficiency and reduced waste for many chemical processes
- developing sensors
- developing photovoltaic technology, LEDs and fuel cells,
- Producing products that require less maintenance (avoiding the production of materials that are less environmentally friendly).
- Water desalination technology, technology for treatment of groundwater and wastewater
- reducing heavy metal scattering in the environment
- developing nano biocides for the control of bacteria and other microorganisms
Kinkajou : So what about the frontier of nano technological synthesis of molecules or mechanical mechanisms?
Erasmus : Let’s talk about Molecular nanotechnology (MNT).
The challenge in synthesising molecules using molecular nano technology can be thought of as being simply about yield.
In Mechano-synthesis mechanical constraints on chemical reactions direct reactive molecules to specific molecular sites to form specific molecules. Most chemical reactions occur at random, with the specific energy of the reaction being the driving force for the chemical process.
To date, the only existing example which introduces purpose in atomic construction is the atomic placement of atoms using the scanning tunneling microscope.
In practice, getting exactly one molecule to a known place on the microscope's tip is possible, but has proven difficult to automate. Since practical products require at least several hundred million atoms, this technique has not yet proven practical in forming a real product.
Many writers have hypothesized that reactive molecules can be built into molecular mechanical systems. The molecular mechanical systems would bring these reactive groups together in specific positions, orientations and in planned sequences.
Unwanted reactions could be controlled by keeping potential reactants apart. Favoured reactions could be facilitated in a molecular mechanical process. Currently the most obvious example of a programmable mechanic synthetic device is the operation of ribosomes as nano- factories in transcribing and assembling amino acids and proteins.
What will nanotech look like in the future?
Kinkajou: I can see some problems with molecular synthetic nanotechnology already. What about you?
Erasmus : Where molecules are of a low complexity, bulk chemical synthetic reactions are able to economically produce large quantities cheaply.
(An example is Diamond synthesis using nano mechanic synthetic methods. Bulk industrial diamond production is an established production method with known costs and yields. It is unlikely that a high energy high complexity method of production can perform better than simple chemistry.
Where simple bulk reactions would prove inadequate, is where the diamond synthetic constructed needs to be doped with specific atoms and specific configurations. In this case, molecular nanotechnology may well be the answer). Automating this type of production technology is probably as much of a challenge as actually conceiving and synthesising a single molecule manually.
Erasmus: The challenges in Mechano- synthesis are multiple:
- Synthesising tools required for operations
- Providing tools with feedstock atoms molecules
- Removing end products
- Powering and controlling desired reactions or synthetic processes.
Erasmus : Where specific technology exists for programmed synthesis (such as the DNA coded synthesis of proteins via ribosomes /mRNA), again bulk synthetic reactions are able to economically produce large quantities cheaply.
(Here, for example, a DNA strand serves as a template for standard biological replication machinery to copy. Why would anyone attempt to assemble such a molecule each time it was required, when it is so much easier to simply copy existing molecules ?)
In molecular self-assembly many molecules will spontaneously assemble. Examples include spontaneous proteins folding, formations of micelles or liposomes from lipid bilayers, and many ionic molecular interactions.
Molecular self-assembly is known as bottom-up technology as large elements are synthesised from smaller ones. This is in contrast to lithography where small objects are “cut” from larger blocks.
However, where complex molecules must be synthesised (for example, a novel DNA strand), yields are predictably low. This is because synthesis of complex molecules involves sequential iterations of processes designed to add specific molecular groups, each with a less than perfect yield.
For example, if a process has a 90% yield but must be repeated hundred times, the final yield could well be 0.0027%. This represents approximately 27 mg from an input of 1 kg of feedstock. It is obvious that alternate methods of production may be required.
The process of assembling molecules is called molecular mechano- synthesis. The Holy Grail is to control molecular reactions in positionally specified locations and orientations to obtain desired chemical outputs, and then to utilise the systems to further assemble the products of these reactions.
Erasmus : Targets of synthesis can include:
- Novel complex molecules such as DNA strands, proteins proving difficult to fold, complex organic molecules,
- Nano robots: Medical applications include as sensors, repair mechanisms, cancer cell fighting agents and pharmaceutical carrier mechanisms.
- Utility fog agents: cloud of networked microscopic robots or assemblers which can change their shape and properties to form microscopic objects and tools in response to high-level commands. If these objects can be enlarged efficiently than they may even replace many current physical objects.
Diagram of a 100 micrometer foglet
- Display arrays: nano objects located within phased arrays could be commanded to output many different types of optical out puts, creating virtual scenes.
- Intelligent elements capable of combining at the quantum level or nano-scopic level to serve as computers, smart materials, sensors, responsive control systems.
- Nano Weapons fabrication: the classical sci-fi description would involve the “grey goo” /” ecophagy” scenario. .
Erasmus : Many people worry about security. However, I will give the computer parallel about Internet security. With computers and the Internet, many people worry about how to stop the wild unknown forces existing within Internet from accessing their computer. Many people think they are powerless to prevent intruders.
The reality is by simply pulling the plug on the computer, it can be rendered absolutely safe under any circumstances.
Kinkajou: The trick is to maintain safety while maintaining power and maintaining operation.
Although many science fiction authors propose molecular nanotechnology be used to create self-replicating nano bots, ethical and commonsense considerations probably preclude this direction.
The likelihood is that molecular nanotechnology will tend towards biomimetic functions as a way forward for production of functional nano devices able to cope with nanoscale challenges such as interatomic forces, surface tension effects, wetness, Brownian motion, high friction and high viscosity effects.
Top, a molecular propeller.
A molecular planetary gear system.
Erasmus : Another form of molecular nanotechnology is where nano materials or nano particles (e.g. carbon nanotubes) can be added to a bulk material to alter existing properties such as electrical conductance, weight or density, porosity, resistance to crack propagation, sintering profile, light scattering characteristics or elasticity, stiffness, thermal profiles, and chemical reactivity including capacity for affecting flocculation.
Developing or altering nano materials to act as catalysts for current existing industrial chemical applications is another direction for development.
Kinkajou : I think at this stage much remains to be known that the practicality of molecular synthesis or nano mechanical engineering.
Until we fabricate the machinery and start the process rolling, we can only guess at the attainable range of chemical reactions, error rates, throughput speed and energy efficiency of the processes that we are undertaking. Only then can we compare the successes of nanotechnology against that of nature, or against that of simple bulk chemistry.
Protein Folding Control
Kinkajou: So tell us about nano engineering?
Erasmus : Nano-engineering is the science of performing engineering tasks in nanoscale dimensions. Nano engineering emphasizes the engineering and production aspects of science, rather than just the achievements of the technology itself.
Kinkajou : So what might these people do?
Erasmus : Engineers that work with nano-electronics will create smaller, more efficient chips, cards, and even smaller computer parts to make products that can do as much as bigger products without so much e-waste.
Engineers involved with bio-systems will create ways to store the tiniest amounts of DNA or other biological fragments for testing and manipulation.
Engineers can work with pollution. These they can design Innovative ways to test for contaminants and pollutants in the air, ground, and water -- even small amounts that were once before considered untraceable.
They may also choose to work in the medical field creating new gadgets that can fix problems on a scale as small as the molecular level.
Nanomachine in Blood
Erasmus : In Mechano-synthesis. Nanotechnology engineers and other nano technical specialists combine to construct molecular sized machines.
Machines that have been constructed to date include:
- nano generators
- nano tube nano motors
- nano electromechanical oscillators
- molecular actuators
- molecular motors
- Sensor switches less than 2 nm in size capable of counting specific molecules in a chemical sample.
Graphical representation of arotaxane useful as a type of molecular switch. Nanoscale Switch
Erasmus : Consider an imaginary nano factory construction line. Imagine MECHANOSYNTHETIC REACTIONS Based on quantum chemistry to deposit carbon, a device moves a vinylidenecarbene along a barrier-free path to bond to a diamond (100) surface dimer, twists 90° to break a pi bond, and then pulls to cleave the remaining sigma bond.
Thermal effects are important at nano scale and can cause microscopic structures to bend. Also the strengths of chemical reactions in covalent bonds are extremely strong. So assembler arms need to be stiff enough and resistive enough to enable these processes to occur.
For most processes, positional uncertainty for tool tips is a simple function of temperature and stiffness. The challenge is reliability. Worm drive shafts, gears, nano generators, struts, clamps, bearings, actuators/motors all need to be part of the mix.
A potential energy barrier between reactions strands/lines needs to be maintained to prevent quantum effects such as quantum tunnelling. In effect atomic scale moving parts are bumpy.
Thermal noise and friction need to be accounted for. While thermal effects are important, cooling is unlikely to be an issue due to the extremely high surface area to volume ratio of nano devices.
Precision is critical. An error rate greater than 1 million, where there are hundred million components in a device may well be unacceptable, effectively compromising the device’s function. Covalent bonds are generally stable at room temperature; background radiation damage can be significant in factory production, perhaps causing damage of up to several percent per year per cubic micron of output.
Kinkajou : How does bottom-up technology impact on nano manufacturing?
Erasmus : The “bottom up” approach for nano mechanic- synthesis involves the assembly of molecular components into larger structures. They fall into two categories chaotic and controlled.
Chaotic processes rely on increasing the energy level of atoms or molecules so that they enter an energetic chaotic state. When conditions are changed, the collapse from the chaotic state causes the desired effect. This is a method used to generate fullerenes and carbon nanotubes. Control can be difficult.
Controlled processes, in contrast, control the delivery and combination of atoms or molecules to produce nano materials. Examples are DNA nano assembly, chemical proteins synthesis from amino acids, atomic force microscope deposition of chemicals on surfaces in specific patterns (nanolithography).
“Top down” methods for nano mechanics synthesis seeks to create smaller devices from larger ones. Bulk material is reduced in size to nanoscale patterns. In the classical example, our nano lithographic techniques are used to fabricate integrated circuits on silicon chips. Many lithographic techniques have been developed including optical, x-ray, ultraviolet, electron beam and iron beam cutting techniques, atomic layer deposition, and molecular vapour deposition, and imprinting procedures.
Bio-mimetic techniques may also be used in nano mechano- synthesis. Systems are designed using existing biotechnology derived from bacteria and other designed for specific purposes. Bio- chips have been suggested for fuel cell applications, sensor applications and even for waste disposal.
Illustration: This device transfers energy from nano-thin layers of quantum wells to nano-crystals , above them, causing the nano-crystals to emit visible light.
Kinkajou : So what about nano robotics? I have also heard about some other names such as Nubot, nanobots, nanoids, nanites, nanomachines, or nanomites have been used to describe these devices.
Erasmus : A Nubot is a nanoscale DNA based structure, effectively described as a "nucleic acid robot”. So far just imagination.
Synthetic molecular motors and nano power generators have been built as one step towards the development of nano robots. It has been suggested that bacterial elements such as Flagella can be incorporated into nano robot structures. Other Virus-based structures have been studied for their ability to penetrate cell walls and membranes.
One of the purposes of nano robotics is the development of nano factories, capable of building nano constructs.
The field is developing quickly. Ninja particles: are one suggested development.