NANOTECH INNOVATIONS

Bionanotechnology, nanobiotechnology, and nanobiology are terms that refer to the intersection of nanotechnology and biology. Given that the subject is one that has only emerged very recently, bionanotechnology and nanobiotechnology serve as blanket terms for various related technologies.

This discipline helps to indicate the merger of biological research with various fields of nanotechnology. Concepts that are enhanced through nanobiology include: nanodevices, nanoparticles, and nanoscale phenomena that occurs within the discipline of nanotechnology. This technical approach to biology allows scientists to imagine and create systems that can be used for biological research. Biologically inspired nanotechnology uses biological systems as the inspirations for technologies not yet created. We can learn from eons of evolution that have resulted in elegant systems that are naturally created.

The most important objectives that are frequently found in nanobiology involve applying nanotools to relevant medical/biological problems and refining these applications. Developing new tools for the medical and biological fields is another primary objective in nanotechnology. New nanotools are often made by refining the applications of the nanotools that are already being used. The imaging of native biomolecules, biological membranes, and tissues is also a major topic for the nanobiology researchers. Other topics concerning nanobiology include the use of cantilever array sensors and the application of nanophotonics for manipulating molecular processes in living cells.

Recently, the use of microorganisms to synthesize functional nanoparticles has been of great interest. Microorganisms can change the oxidation state of metals. These microbial processes have opened up new opportunities for us to explore novel applications, for example, the biosynthesis of metal nanomaterials. In contrast to chemical and physical methods, microbial processes for synthesizing nanomaterials can be achieved in aqueous phase under gentle and environmentally benign conditions. This approach has become an attractive focus in current green bionanotechnology research towards sustainable development.

As with nanotechnology and biotechnology, bionanotechnology has many potential ethical issues associated with it.

Terminology

The terms are often used interchangeably. When a distinction is intended, though, it is based on whether the focus is on applying biological ideas or on studying biology with nanotechnology. Bionanotechnology generally refers to the study of how the goals of nanotechnology can be guided by studying how biological "machines" work and adapting these biological motifs into improving existing nanotechnologies or creating new ones. Nanobiotechnology, on the other hand, refers to the ways that nanotechnology is used to create devices to study biological systems.

In other words, nanobiotechnology is essentially miniaturized biotechnology, whereas bionanotechnology is a specific application of nanotechnology. For example, DNA nanotechnology or cellular engineering would be classified as bionanotechnology because they involve working with biomolecules on the nanoscale. Conversely, many new medical technologies involving nanoparticles as delivery systems or as sensors would be examples of nanobiotechnology since they involve using nanotechnology to advance the goals of biology.

The definitions enumerated above will be utilized whenever a distinction between nanobio and bionano is made in this article. However, given the overlapping usage of the terms in modern parlance, individual technologies may need to be evaluated to determine which term is more fitting. As such, they are best discussed in parallel.

Concepts

Most of the scientific concepts in bionanotechnology are derived from other fields. Biochemical principles that are used to understand the material properties of biological systems are central in bionanotechnology because those same principles are to be used to create new technologies. Material properties and applications studied in bionanoscience include mechanical properties(e.g. deformation, adhesion, failure), electrical/electronic (e.g. electromechanical stimulation, capacitors, energy storage/batteries), optical (e.g. absorption, luminescence, photochemistry), thermal (e.g. thermomutability, thermal management), biological (e.g. how cells interact with nanomaterials, molecular flaws/defects, biosensing, biological mechanisms s.a. mechanosensing), nanoscience of disease (e.g. genetic disease, cancer, organ/tissue failure), as well as computing (e.g. DNA computing). The impact of bionanoscience, achieved through structural and mechanistic analyses of biological processes at nanoscale, is their translation into synthetic and technological applications through nanotechnology.

Nanobiotechnology takes most of its fundamentals from nanotechnology. Most of the devices designed for nanobiotechnological use are directly based on other existing nanotechnologies. Nanobiotechnology is often used to describe the overlapping multidisciplinary activities associated with biosensors, particularly where photonics, chemistry, biology, biophysics, nanomedicine, and engineering converge. Measurement in biology using waveguide techniques, such as dual polarisation interferometry, are another example.

Applications

Applications of bionanotechnology are extremely widespread. Insofar as the distinction holds, nanobiotechnology is much more commonplace in that it simply provides more tools for the study of biology. Bionanotechnology, on the other hand, promises to recreate biological mechanisms and pathways in a form that is useful in other ways.

Nanobiotechnology

Nanobiotechnology (sometimes referred to as nanobiology) is best described as helping modern medicine progress from treating symptoms to generating cures and regenerating biological tissues. Three American patients have received whole cultured bladders with the help of doctors who use nanobiology techniques in their practice. Also, it has been demonstrated in animal studies that a uterus can be grown outside the body and then placed in the body in order to produce a baby. Stem cell treatments have been used to fix diseases that are found in the human heart and are in clinical trials in the United States. There is also funding for research into allowing people to have new limbs without having to resort to prosthesis. Artificial proteins might also become available to manufacture without the need for harsh chemicals and expensive machines. It has even been surmised that by the year 2055, computers may be made out of biochemicals and organic salts.

Another 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 which could be introduced into the human body to track down metabolites associated with tumors and other health problems. Another example, from a different perspective, would be evaluation and therapy at the nanoscopic level, i.e. the treatment of Nanobacteria (25-200 nm sized) as is done by NanoBiotech Pharma.

While nanobiology is in its infancy, there are a lot of promising methods that will rely on nanobiology in the future. Biological systems are inherently nano in scale; nanoscience must merge with biology in order to deliver biomacromolecules and molecular machines that are similar to nature. Controlling and mimicking the devices and processes that are constructed from molecules is a tremendous challenge to face the converging disciplines of nanotechnology. All living things, including humans, can be considered to be nanofoundries. Natural evolution has optimized the "natural" form of nanobiology over millions of years. In the 21st century, humans have developed the technology to artificially tap into nanobiology. This process is best described as "organic merging with synthetic." Colonies of live neurons can live together on a biochip device; according to research from Dr. Gunther Gross at the University of North Texas. Self-assembling nanotubes have the ability to be used as a structural system. They would be composed together with rhodopsins; which would facilitate the optical computing process and help with the storage of biological materials. DNA (as the software for all living things) can be used as a structural proteomic system - a logical component for molecular computing. Ned Seeman - a researcher at New York University - along with other researchers are currently researching concepts that are similar to each other.

Bionanotechnology

DNA nanotechnology is one important example of bionanotechnology. The utilization of the inherent properties of nucleic acids like DNA to create useful materials is a promising area of modern research. Another important area of research involves taking advantage of membrane properties to generate synthetic membranes. Protein folding studies provide a third important avenue of research, but one that has been largely inhibited by our inability to predict protein folding with a sufficiently high degree of accuracy. Given the myriad uses that biological systems have for proteins, though, research into understanding protein folding is of high importance and could prove fruitful for bionanotechnology in the future.

Tools

This field relies on a variety of research methods, including experimental tools (e.g. imaging, characterization via AFM/optical tweezers etc., x-ray diffraction based tools, synthesis via self-assembly, characterization of self-assembly (using e.g. dual polarization interferometry, recombinant DNA methods, etc.), theory (e.g. statistical mechanics, nanomechanics, etc.), as well as computational approaches (bottom-up multi-scale simulation, supercomputing).

Nanotechnology is a technology based on the understanding of what happens at the scale of 10-9 meters, the scale of atoms and molecules, and also the scale at which food, like everything else we see about us, acquires its recognisable properties of flavour, aroma, texture and so on.

There are several key areas where the food industry is particularly working on the development of new techniques, including the following:

Nanotechnology is the basis of many novel and functional foods. For example, food colours, flavours and textures can all be manipulated and altered at the nanoscale.

An important nano technique is encapsulation, which has been derived from the pharmaceutical industry. Encapsulation is critical to the delivery of flavours or nutrients in products tailored to suit consumer preferences or health requirements.

Encapsulation is also used to improve the stability of a mix of ingredients, and to create novel textures and tastes, as well as disguising unpleasant flavours, such as fish oil.

Nanotechnology also has a role to play in altering the colour and flavour of foods. For example, differently ‘twisted’ molecules (the direction of chirality) can determine whether the flavour imparted is ‘lemon’ or ‘orange’.

Another example is the use of mineral nano particles. For those of us that love the taste of salt but are worried about its health implications, nanoparticulate salt gives a salty taste to foodstuffs, but much less is required than if conventionally sized salt grains are used. This has been the subject of much research by Leatherhead Food Research, which is supporting the use of nanoscale salt by food companies in their bid to bring their products in line with daily intake guidelines.

Flavour Burst

Many foods and beverages contain naturally occurring nanoscale colloidal components (dairy for example), and these components can also be manipulated by food companies to add novelty and/or improve the longevity, taste, flavour and calorific content of their products.

Nano also has a role to play in providing a burst of a specific flavour. At the University of Nottingham, scientists investigating nanoscale aroma release have shown that this ‘flavour burst’ is related to the physical and chemical characteristics of the flavants at the nano and micro scale.

Food processing nanotechnologies also offer many improvements for the food processing industry. One example is in relation to the customisation of emulsions, important in many areas such as sauces, ready-made meals and puddings.

Nanoparticles can also be used as thickeners. Some processing utilises nano-structured, porous membranes to create specific-shape holes that allow the size of, say, oil droplets to be controlled to a very high degree, for example, in emulsification. This enables manufacturers to develop double, triple or even multiple emulsions as the basis for many new products, allowing multiple components to be enclosed in a single oil droplet.

Nanoscale membranes can also provide filtration and purification for air and water, and nano-modified surfaces, coatings and finishes provide antibacterial properties and dirt repellency, all very useful in food preparation.

Food safety

With regard to safety, nanofilters can also be used to remove toxins such as pesticides. The Dutch company Aquamarijn produces microsieves with fine-tuned nanopores that act as filters for a variety of applications.

The critical need for food safety provides an opening for many new techniques based on nanotechnology. For example, in food preparation areas, nano filters are used to clean the environment, and there are nano-enhanced antibacterial surfaces, while nano coatings on tools and equipment make them sharper, longer lasting and easier to clean.

Novel nanobiosensors, developed by other industries including medicine and defence, can rapidly detect the presence of pathogens, pollutants and toxins in the processing of foods. These tiny sensors are cheap to produce, have high sensitivity, specificity, robustness, reliability and are more easily integrated into food production systems.

They are replacing bit-by-bit, the more expensive and time-consuming analytical methods that involve sending samples to a laboratory.

Nanosens in the Netherlands is already making portable sensing systems for the rapid detection of biological and chemical contaminants in food and other application areas.

Encapsulation techniques

There is a large and increasing market for foodstuffs with enhanced vitamin and other supplements, where nano encapsulation can again have a major impact.

Through using encapsulation techniques, nanotechnology enables the production of ‘healthy’ foods such as low-fat dairy and non-dairy oils, low salt and sugar products, and foods that can counteract certain diseases by the incorporation of specific vitamins and minerals, and by making them more easily absorbable in nanoparticulate form.

Other nanoscale phenomena, such as those included within the term ‘colloid science’, are also exploited in nutraceutical and functional food formulations, manufacturing and processing.

A number of companies are active here, for example Nutralease, based in Israel, has created nano-sized concentrates of vitamins E, D, A, K and isoflavones.

Sports foods and drinks

The active ingredients in sports drinks need to be absorbed quickly to assist performance and maintain the health of the athlete. These benefits can be achieved by including these ingredients in nanoparticulate form (this is also the way that less soluble medicines are administered).

The kinds of nano techniques used in sports foods and drinks, such as improved bioavailability of vitamins and minerals and encapsulation and release of energy-generating foodstuffs, are also widely used in those drinks that offer a quick ‘kick’, and in certain foods where the release of fats, sugars, proteins, vitamins and minerals can be programmed to suit the activity levels of the consumer.

Advanced Sports Nutrition (ASN) is one company that offers a sports drink with nanoscale ingredients. Its product, HPC - High Performance Creatine ‘uses nanotechnology, and … ingredients that have been scientifically proven to maximise uptake of creatine into muscle cells and also provide optimal hydration and support for maximum performance during exercise and nutrient uptake after exercise’.

Food packaging is an area of the industry where nanotechnology has been most rapidly embraced, as it offers many benefits ranging from improving barrier properties, thus preventing contamination of foodstuffs by specific gases (eg oxygen) or unwelcome scents, to using in-built nano sensors that can detect when perishable contents are spoiling and change colour to warn consumers.

Similarly, ‘smart’ packaging can maintain an internal ambient temperature for longer, increasing the lifespan of the contents.

Some packaging also has antibacterial and sun-blocking properties based on the application of nanotechnology, and nano devices placed in packaging would enable easy tracking of large quantities of product and act as a deterrent to counterfeiters.

Who is monitoring nano in foods? The European Commission (EC) considers that current regulations suffice for nanotechnologies. A review of the Novel Foods Regulation that was designed to ‘allow for safe and innovative foods to reach the European market faster’ and to ‘encourage the development of new types of foods and food production techniques (such as nanotechnologies)’, collapsed in 2011 (29 March).

While the collapse of this amendment wasn't related specifically to the provisions for nanotechnologies (it was related to genetically modified livestock), the impact of this collapse is that nano-foods remain unregulated and are not subject to European labelling.

In early 2010, the mandatory labelling of nanomaterials in cosmetics came into force. Although in a different sector, it set a precedent that could spread to other sectors.

In April 2012, the US Food and Drug Administration issued guidance documents that address the use of nanotechnology in the food and cosmetics sectors.

Companies are ‘encouraged’ to contact the FDA about nano-enabled food items as they no longer fall under the automatic heading of ‘generally recognised as safe’, as was previously the case.

Without a clear regulatory landscape calibrated to standards, there is limited incentive for industry to invest in developing nano-food innovations. This is in part because of liability issues, but is also due to the risk of being seen as less than cautious by watchdogs and consumer groups, which are already anxious about new food technologies and their safety.

There are significant challenges for the food industry in its adoption of the technology in terms of potential legislative and consumer acceptance hurdles. However, nanotechnology may hold the key to solving many critical issues facing the world’s food supply today. Only time will tell how this technology will continue to develop in the future.

DNA is a powerful biomaterial for creating rationally designed and functionally enhanced nanostructures. Emerging DNA nanotechnology employs DNA as a programmable building material for self-assembled, nanoscale structures (read more: "Reality check for DNA nanotechnology"). Researchers have also shown that DNA nanotechnology can be integrated with traditional silicon processing. DNA nanoarchitectures positioned at substrate interfaces can offer unique advantages leading to improved surface properties relevant to biosensing (for instance, graphene and DNA can combine to create a stable and accurate biosensor), nanotechnology, materials science, and cell biology.

A new Perspectives article in Langmuir ("DNA Nanoarchitectonics: Assembled DNA at Interfaces") by Stefan Howorka, an associate professor in the Department of Chemistry at University College London, highlights the benefits and challenges of using assembled DNA as a nanoscale building block for interfacial layers.

After assessing how assembled DNA compares to more conventional polymeric building blocks, Howorka discusses three areas of applications of DNA nanoarchitectonics: homogeneous films with an emphasis on biomolecular recognition; 2D nanopatterns that are produced via the bottom-up route in optional combination with top-down nanofabrication; and 3D superlattices of nanoparticles. In a concluding section he identifies some possible areas of future research for interfacial DNA nanostructures.

Thin-films and surface coatings

Efficient and correct binding of biomolecules is relevant in biosensing, purification, and biophysics. However, the specific interaction of molecules at interfaces can be impaired by restricted target accessibility caused by imperfectly packed receptors on locally crowded surfaces.

Homogeneous films made up of DNA nanoarchitectures were able to overcome some of these problems and molecularly thin and laterally dense films composed of DNA structures have been constructed to improve the biomolecular recognition at biointerfaces.

Bottom-up nanopatterning

In addition to the homogeneous coatings of substrates, DNA nanoarchitectures are predominately utilized to pattern surfaces on the nanoscale. In principle, nanopatterning with DNA can be achieved either in a bottom-up fashion or in combination with top-down approaches. In both cases, producing nanopatterns can open up many applications in nanotechnology, biophysics, and cell biology.

Bottom-up nanopatterning is done with DNA tiles (see: "Scientists develop nanodevice manufacturing strategy using DNA building blocks") that can be programmed to assemble themselves into precisely designed shapes, such as letters and emoticons. Further development of the technology could enable the creation of new nanoscale devices, such as those that deliver drugs directly to disease sites.

It can also be done with DNA origami, a technique that addresses some of the limitations of DNA tiles. DNA origami is a method for folding long strands of DNA into whatever very small shape or pattern you desire. Using a computer-aided design program a scientist can design the desired nanoscale shape (typically about 100 nanometers across) and the computer designs a set of short DNA strands that can be ordered from a company that specializes in synthesizing DNA strands. The short DNA strands get mixed with the long DNA strands, heated up to nearly boiling, and cooled to room temperature over the course of a couple hours. In a single drop of water one then has 100 billion copies of the desired shape, or shape with a pattern on top. In the first DNA origami made were shapes like triangles and smiley faces, and patterns like maps of the western hemisphere, snowflakes, etc.

DNA origami is also versatile with regard to the substrates onto which they can bind, as shown for gold, silicon, and graphene.

Nanopatterns generated by combining bottom-up DNA nanoarchitectures and physical top-down routes. (A) Generation of patterns of DNA triangles. (a) Synthesis scheme for DNA origami triangles and atomic force microscopy height image showing random deposition on mica. Scale bar, 100 nm. (b) Fabrication of DNA origami binding sites via photolithography. The inset highlights the differentiation of the background and features (background/features) for the trimethylsilyl (TMS) monolayer and diamondlike carbon (DLC) films. Silanol groups occur in oxidized areas of the TMS monolayers. Features etched into the DLC template layer are 0.5-1.5 nm deep. DNA triangles can bind into the templated layer featuring complementary-shaped binding sites as illustrated by the AFM height image (right) of DNA triangles on 110 nm patterned triangle sites on a DLC/DLC surfaces. (B) Two-dimensional nanoparticle arrays are formed by binding DNA-coated nanocrystals (green with a golden core) onto the edges of DNA origami triangles via hybridization. The hybrid structures adsorb onto the electron-beam lithographically nanopatterned surface that features hydrophilic triangular binding sites (gray) surrounded by a hydrophobic coating (orange). AFM image of gold-nanoparticlefunctionalized origami triangles bound to top-down generated columns of equilateral triangles with sides of 100 nm, alternately oriented up and down. Scale bar, 500 nm. (C) Block-copolymer-patterned arrays of 5 nm gold nanoparticles (red) were connected with DNA origami (green). The connection was mediated by hybridization between the single-stranded DNA-thiol-modified gold nanoparticles and the sticky end-modified DNA origami. (D) Structures formed by connecting lithographically generated gold islands with DNA origami tubes: (a) triangle, (b) hexagon, (c) square, and (d) z shape. All scale bars are 300 nm. The DNA origami nanotubes of approximately 380 nm in length were composed of six DNA helices bundled with a hexagonal cross section and carried thiolated groups near their termini. The distance between the thiolated groups located near each end is approximately 320 nm. (Reprinted with permission from American Chemical Society)

The alternative route to nanopatterned surfaces combines bottom-up DNA materials with a top-down nanofabrication approach. This combination is highly synergistic because the separate strategies cover two different length scales. Whereas the physical top-down approach can pattern microscale areas with feature sizes frequently down to 10-100 nm, the bottom-up approach can afford atomically precise DNA nanostructures of up to but not beyond overall dimensions of a few hundred nanometers.

3D nanoparticle lattices

Howorka writes that another exciting area of DNA nanoarchitectonics is concerned with colloids and suspensions of nanoparticles. The nanobio interface at spherical substrates is of great interest because it provides several unique advantages and characteristics not available at flat substrates, such as the ability to self-assemble nanoparticles into complex 3D supramolecular arrays.

In concluding his article, Howorka points to two growth areas for DNA nanoarchitectonics: One area is the increased exploitation of DNA origami for 3D lattices of nanoparticles. In the future, this might lead to the creation of photonic crystals with switchable collective properties that are controlled by DNA interparticle spacers of tunable distance. In more general terms, DNA nanostructures at interfaces could be integrated into functional devices whose properties can be actuated by external triggers.

He points out that an increasing trend in DNA nanotechnology is a focus on applications that ultimately lead to commercially viable products. "Although an emphasis on real-world applications is understandable, one should also consider that DNA nanoarchitectonics at interfaces is a relatively new research area compared to that of very established polymeric film coatings. Nevertheless, research activities are underway toward high added-value devices where the higher costs of DNA scaffolds are justified. In conclusion, DNA architectonics at interfaces is a highly interdisciplinary field that spans the nano- and microscale with numerous applications in materials and life science."