Nanobiomechanics

From Wikipedia, the free encyclopedia

Nanobiomechanics (also bionanomechanics) is an emerging field in nanoscience and biomechanics that combines the powerful tools of nanomechanics to explore fundamental science of biomaterials and biomechanics.

Since the introduction by its founder Yuan-Cheng Fung, the field of biomechanics has become one of the branches of mechanics and bioscience. For many years, biomechanics has examined tissue. Through advancements in nanoscience, the scale of the forces that could be measured and also the scale of observation of biomaterials was reduced to "nano" and "pico" level. Consequently it became possible to measure the mechanical properties of biological materials at nanoscale.

Most of the biological materials have different hierarchical levels, and the smallest ones refer to the nanoscale. For example bone has up to seven levels of biological organization, and the smallest level, i.e., single collagen fibril and hydroxylapatite minerals have dimensions well below 100 nm. Therefore, being able to probe properties at this small scales provides a great opportunity for better understanding the fundamental properties of these materials. For example, measurements have shown that nanomechanical heterogeneity exists even within single collagen fibrils as small as 100 nm.^[1]

One of the other most relevant topics in this field is measurement of tiny forces on living cells to recognize changes caused by different diseases. For example, it has been shown that red blood cells infected by malaria are 10 times stiffer than normal cells.^[2] Likewise, it has been shown that cancer cells are 70 percent softer than normal cells.^[3] Early signs of aging cartilage and osteoarthritis has been shown by looking at the changes in the tissue at the nanoscale.^[4]

§Methods and Instrumentation

The common methods in nanobiomechanics are summarized below:

• Atomic force microscope
• Optical tweezers
• Magnetic twisting cytometry

§Examples of relevant materials

High resolution AFM image of cortical bone and single collagen fibril (inset)

• bone^[5] and its hierarchical constituents such as single collagen fibrils
• single living cells
• actin filaments and microtubules^[6]
• synthetic peptide nanotubes

§Computational nanobiomechanics

In addition to experimental aspect, research has been expanding through computational methods. Molecular dynamics (MD) simulations have provided a wealth of knowledge in this area. Although, the MD simulation are still limited to a small number of atoms and molecules, due to limitation in the computational performance, they have proved to be an instrumental branch of this emerging field.

Nanobiotechnology

From Wikipedia, the free encyclopedia

Nanobiotechnology, bionanotechnology, 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. However, as with nanotechnology and biotechnology, bionanotechnology does have many potential ethical issues associated with it.

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, such as peptoid nanosheets, for medical and biological purposes 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.

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.

Nano-biotechnology takes most of its fundamentals from nanotechnology. Most of the devices designed for nano-biotechnological use are directly based on other existing nanotechnologies. Nano-biotechnology is often used to describe the overlapping multidisciplinary activities associated with biosensors, particularly where photonics, chemistry, biology, biophysics, nano-medicine, and engineering converge. Measurement in biology using wave guide techniques, such as dual polarization 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. Proteins that self-assemble to generate functional materials could be used as a novel approach for the large-scale production of programmable nanomaterials. One example is the development of amyloids found in bacterial biofilms as engineered nanomaterials that can be programmed genetically to have different properties. 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.

Lipid nanotechnology is another major area of research in bionanotechnology, where physico-chemical properties of lipids such as their antifouling and self-assembly is exploited to build nanodevices with applications in medicine and engineering.

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).

Nanomedicine

From Wikipedia, the free encyclopedia

Nanomedicine is the medical application of nanotechnology.^[1] Nanomedicine ranges from the medical applications of nanomaterials, to nanoelectronic biosensors, and even possible future applications of molecular nanotechnology. Current problems for nanomedicine involve understanding the issues related to toxicity and environmental impact of nanoscale materials (materials whose structure is on the scale of nanometers, i.e. billionths of a meter).

Functionalities can be added to nanomaterials by interfacing them with biological molecules or structures. The size of nanomaterials is similar to that of most biological molecules and structures; therefore, nanomaterials can be useful for both in vivo and in vitro biomedical research and applications. Thus far, the integration of nanomaterials with biology has led to the development of diagnostic devices, contrast agents, analytical tools, physical therapy applications, and drug delivery vehicles.

Nanomedicine seeks to deliver a valuable set of research tools and clinically useful devices in the near future.^[2][3] The National Nanotechnology Initiative expects new commercial applications in the pharmaceutical industry that may include advanced drug delivery systems, new therapies, and in vivo imaging.^[4] Nanomedicine research is receiving funding from the US National Institutes of Health, including the funding in 2005 of a five-year plan to set up four nanomedicine centers.

Nanomedicine is a large industry, with nanomedicine sales reaching $6.8 billion in 2004, and with over 200 companies and 38 products worldwide, a minimum of $3.8 billion in nanotechnology R&D is being invested every year.^[5] In April 2006, the journal Nature Materials estimated that 130 nanotech-based drugs and delivery systems were being developed worldwide.^[6] As the nanomedicine industry continues to grow, it is expected to have a significant impact on the economy.

Drug delivery

Nanoparticles (top), liposomes (middle), and dendrimers (bottom) are some nanomaterials being investigated for use in nanomedicine.

Nanotechnology has provided the possibility of delivering drugs to specific cells using nanoparticles.

The overall drug consumption and side-effects may be lowered significantly by depositing the active agent in the morbid region only and in no higher dose than needed. Targeted drug delivery is intended to reduce the side effects of drugs with concomitant decreases in consumption and treatment expenses. Drug delivery focuses on maximizing bioavailability both at specific places in the body and over a period of time. This can potentially be achieved by molecular targeting by nanoengineered devices.^[7][8] More than $65 billion are wasted each year due to poor bioavailability.^{[citation needed]} A benefit of using nanoscale for medical technologies is that smaller devices are less invasive and can possibly be implanted inside the body, plus biochemical reaction times are much shorter. These devices are faster and more sensitive than typical drug delivery.^[9] The efficacy of drug delivery through nanomedicine is largely based upon: a) efficient encapsulation of the drugs, b) successful delivery of drug to the targeted region of the body, and c) successful release of the drug.^{[citation needed]}

Drug delivery systems, lipid- ^[10] or polymer-based nanoparticles,^[11] can be designed to improve the pharmacokinetics and biodistribution of the drug.^[12][13][14] However, the pharmacokinetics and pharmacodynamics of nanomedicine is highly variable among different patients.^[15] When designed to avoid the body's defence mechanisms,^[16] nanoparticles have beneficial properties that can be used to improve drug delivery. Complex drug delivery mechanisms are being developed, including the ability to get drugs through cell membranes and into cell cytoplasm. Triggered response is one way for drug molecules to be used more efficiently. Drugs are placed in the body and only activate on encountering a particular signal. For example, a drug with poor solubility will be replaced by a drug delivery system where both hydrophilic and hydrophobic environments exist, improving the solubility.^[17] Drug delivery systems may also be able to prevent tissue damage through regulated drug release; reduce drug clearance rates; or lower the volume of distribution and reduce the effect on non-target tissue. However, the biodistribution of these nanoparticles is still imperfect due to the complex host's reactions to nano- and microsized materials^[16] and the difficulty in targeting specific organs in the body. Nevertheless, a lot of work is still ongoing to optimize and better understand the potential and limitations of nanoparticulate systems. While advancement of research proves that targeting and distribution can be augmented by nanoparticles, the dangers of nanotoxicity become an important next step in further understanding of their medical uses.^[18]

Nanoparticles can be used in combination therapy for decreasing antibiotic resistance or for their antimicrobial properties.^[19][20][21] Nanoparticles might also used to circumvent multidrug resistance (MDR) mechanisms.^[22]

Types of systems used

Two forms of nanomedicine that have already been tested in mice and are awaiting human trials that will be using gold nanoshells to help diagnose and treat cancer,^[23] and using liposomes as vaccine adjuvants and as vehicles for drug transport.^[24][25] Similarly, drug detoxification is also another application for nanomedicine which has shown promising results in rats.^[26] Advances in Lipid nanotechnology was also instrumental in engineering medical nanodevices and novel drug delivery systems as well as in developing sensing applications.^[27] Another example can be found in dendrimers and nanoporous materials. Another example is to use block co-polymers, which form micelles for drug encapsulation.^[11]

Polymeric nano-particles are a competing technology to lipidic (based mainly on Phospholipids) nano-particles. There is an additional risk of toxicity associated with polymers not widely studied or understood. The major advantages of polymers is stability, lower cost and predictable characterisation. However, in the patient's body this very stability (slow degradation) is a negative factor. Phospholipids on the other hand are membrane lipids (already present in the body and surrounding each cell), have a GRAS (Generally Recognised As Safe) status from FDA and are derived from natural sources without any complex chemistry involved. They are not metabolised but rather absorbed by the body and the degradation products are themselves nutrients (fats or micronutrients).

Protein and peptides exert multiple biological actions in the human body and they have been identified as showing great promise for treatment of various diseases and disorders. These macromolecules are called biopharmaceuticals. Targeted and/or controlled delivery of these biopharmaceuticals using nanomaterials like nanoparticles and Dendrimers is an emerging field called nanobiopharmaceutics, and these products are called nanobiopharmaceuticals.

Another vision is based on small electromechanical systems; nanoelectromechanical systems are being investigated for the active release of drugs. Some potentially important applications include cancer treatment with iron nanoparticles or gold shells.Nanotechnology is also opening up new opportunities in implantable delivery systems, which are often preferable to the use of injectable drugs, because the latter frequently display first-order kinetics (the blood concentration goes up rapidly, but drops exponentially over time). This rapid rise may cause difficulties with toxicity, and drug efficacy can diminish as the drug concentration falls below the targeted range.^{[citation needed]}

Applications

Some nanotechnology-based drugs that are commercially available or in human clinical trials include:

• Abraxane, approved by the U.S. Food and Drug Administration (FDA) to treat breast cancer,^[28] non-small- cell lung cancer (NSCLC)^[29] and pancreatic cancer,^[30] is the nanoparticle albumin bound paclitaxel.
• Doxil was originally approved by the FDA for the use on HIV-related Kaposi's sarcoma. It is now being used to also treat ovarian cancer and multiple myeloma. The drug is encased in liposomes, which helps to extend the life of the drug that is being distributed. Liposomes are self-assembling, spherical, closed colloidal structures that are composed of lipid bilayers that surround an aqueous space. The liposomes also help to increase the functionality and it helps to decrease the damage that the drug does to the heart muscles specifically.^[31]
• C-dots (Cornell dots) are the smallest silica-based nanoparticles with the size <10 nm. The particles are infused with organic dye which will light up with fluorescence. Clinical trial is underway since 2011 to use the C-dots as diagnostic tool to assist surgeons to identify the location of tumor cells.^[32]
• An early phase clinical trial using the platform of ‘Minicell’ nanoparticle for drug delivery have been tested on patients with advanced and untreatable cancer. Built from the membranes of mutant bacteria, the minicells were loaded with paclitaxel and coated with cetuximab, antibodies that bind the epidermal growth factor receptor (EGFR) which is often overexpressed in a number of cancers, as a 'homing' device to the tumor cells. The tumor cells recognize the bacteria from which the minicells have been derived, regard it as invading microorganism and engulf it. Once inside, the payload of anti-cancer drug kills the tumor cells. Measured at 400 nanometers, the minicell is bigger than synthetic particles developed for drug delivery. The researchers indicated that this larger size gives the minicells a better profile in side-effects because the minicells will preferentially leak out of the porous blood vessels around the tumor cells and do not reach the liver, digestive system and skin. This Phase 1 clinical trial demonstrated that this treatment is well tolerated by the patients. As a platform technology, the minicell drug delivery system can be used to treat a number of different cancers with different anti-cancer drugs with the benefit of lower dose and less side-effects.^[33][34]

Cancer

A schematic illustration showing how nanoparticles or other cancer drugs might be used to treat cancer.

Another nanoproperty, high surface area to volume ratio, allows many functional groups to be attached to a nanoparticle, which can seek out and bind to certain tumor cells. Additionally, the small size of nanoparticles (10 to 100 nanometers), allows them to preferentially accumulate at tumor sites (because tumors lack an effective lymphatic drainage system).^[35] Limitations to conventional cancer chemotherapy include drug resistance, lack of selectivity, and lack of solubility. Nanoparticles have the potential to overcome these problems.^[36]

In photodynamic therapy, a particle is placed within the body and is illuminated with light from the outside. The light gets absorbed by the particle and if the particle is metal, energy from the light will heat the particle and surrounding tissue. Light may also be used to produce high energy oxygen molecules which will chemically react with and destroy most organic molecules that are next to them (like tumors). This therapy is appealing for many reasons. It does not leave a "toxic trail" of reactive molecules throughout the body (chemotherapy) because it is directed where only the light is shined and the particles exist. Photodynamic therapy has potential for a noninvasive procedure for dealing with diseases, growth and tumors. Kanzius RF therapy is one example of such therapy.^{[citation needed]} Also, gold nanoparticles have the potential to join numerous therapeutic functions into a single platform, by targeting specific tumor cells, tissues and organs.^[37][38]

Visualization

In vivo imaging is another area where tools and devices are being developed. Using nanoparticle contrast agents, images such as ultrasound and MRI have a favorable distribution and improved contrast. This might be accomplished by self assembled biocompatible nanodevices that will detect, evaluate, treat and report to the clinical doctor automatically.

The small size of nanoparticles endows them with properties that can be very useful in oncology, particularly in imaging. Quantum dots (nanoparticles with quantum confinement properties, such as size-tunable light emission), when used in conjunction with MRI (magnetic resonance imaging), can produce exceptional images of tumor sites. Nanoparticles of cadmium selenide (quantum dots) glow when exposed to ultraviolet light. When injected, they seep into cancer tumors. The surgeon can see the glowing tumor, and use it as a guide for more accurate tumor removal.These nanoparticles are much brighter than organic dyes and only need one light source for excitation. This means that the use of fluorescent quantum dots could produce a higher contrast image and at a lower cost than today's organic dyes used as contrast media. The downside, however, is that quantum dots are usually made of quite toxic elements.^{[citation needed]}

Tracking movement can help determine how well drugs are being distributed or how substances are metabolized. It is difficult to track a small group of cells throughout the body, so scientists used to dye the cells. These dyes needed to be excited by light of a certain wavelength in order for them to light up. While different color dyes absorb different frequencies of light, there was a need for as many light sources as cells. A way around this problem is with luminescent tags. These tags are quantum dots attached to proteins that penetrate cell membranes. The dots can be random in size, can be made of bio-inert material, and they demonstrate the nanoscale property that color is size-dependent. As a result, sizes are selected so that the frequency of light used to make a group of quantum dots fluoresce is an even multiple of the frequency required to make another group incandesce. Then both groups can be lit with a single light source. They have also found a way to insert nanoparticles^[39] into the affected parts of the body so that those parts of the body will glow showing the tumor growth or shrinkage or also organ trouble.^[40]

Sensing

Nanotechnology-on-a-chip is one more dimension of lab-on-a-chip technology. Magnetic nanoparticles, bound to a suitable antibody, are used to label specific molecules, structures or microorganisms. Gold nanoparticles tagged with short segments of DNA can be used for detection of genetic sequence in a sample. Multicolor optical coding for biological assays has been achieved by embedding different-sized quantum dots into polymeric microbeads. Nanopore technology for analysis of nucleic acids converts strings of nucleotides directly into electronic signatures.^{[citation needed]}
Sensor test chips containing thousands of nanowires, able to detect proteins and other biomarkers left behind by cancer cells, could enable the detection and diagnosis of cancer in the early stages from a few drops of a patient's blood.^[41]Nanotechnology is helping to advance the use of arthroscopes, which are pencil-sized devices that are used in surgeries with lights and cameras so surgeons can do the surgeries with smaller incisions. The smaller the incisions the faster the healing time which is better for the patients. It is also helping to find a way to make an arthroscope smaller than a strand of hair.^[42]

Tissue engineering

Nanotechnology may be used as part of tissue engineering to help reproduce or repair damaged tissue using suitable nanomaterial-based scaffolds and growth factors. Tissue engineering if successful may replace conventional treatments like organ transplants or artificial implants. Nanoparticles such as graphene, carbon nanotubes, molybdenum disulfide and tungsten disulfide are being used as reinforcing agents to fabricate mechanically strong biodegradable polymeric nanocomposites for bone tissue engineering applications. The addition of these nanoparticles in the polymer matrix at low concentrations (~0.2 weight %) leads to significant improvements in the compressive and flexural mechanical properties of polymeric nanocomposites.^[43][44] Potentially, these nanocomposites may be used as a novel, mechanically strong, light weight composite as bone implants.

For example, a flesh welder was demonstrated to fuse two pieces of chicken meat into a single piece using a suspension of gold-coated nanoshells activated by an infrared laser. This could be used to weld arteries during surgery.^[45] Another example is nanonephrology, the use of nanomedicine on the kidney.

Medical devices

Neuro-electronic interfacing is a visionary goal dealing with the construction of nanodevices that will permit computers to be joined and linked to the nervous system. This idea requires the building of a molecular structure that will permit control and detection of nerve impulses by an external computer. A refuelable strategy implies energy is refilled continuously or periodically with external sonic, chemical, tethered, magnetic, or biological electrical sources, while a nonrefuelable strategy implies that all power is drawn from internal energy storage which would stop when all energy is drained. A nanoscale enzymatic biofuel cell for self-powered nanodevices have been developed that uses glucose from biofluids including human blood and watermelons.^[46] One limitation to this innovation is the fact that electrical interference or leakage or overheating from power consumption is possible. The wiring of the structure is extremely difficult because they must be positioned precisely in the nervous system. The structures that will provide the interface must also be compatible with the body's immune system.^[47]

Molecular nanotechnology is a speculative subfield of nanotechnology regarding the possibility of engineering molecular assemblers, machines which could re-order matter at a molecular or atomic scale. Nanomedicine would make use of these nanorobots, introduced into the body, to repair or detect damages and infections. Molecular nanotechnology is highly theoretical, seeking to anticipate what inventions nanotechnology might yield and to propose an agenda for future inquiry. The proposed elements of molecular nanotechnology, such as molecular assemblers and nanorobots are far beyond current capabilities.^{[1][47][48][49]}

Nanorobotics

From Wikipedia, the free encyclopedia

Nanorobotics is the emerging technology field creating machines or robots whose components are at or close to the scale of a nanometer (10⁻⁹ meters).^[1][2][3] More specifically, nanorobotics refers to the nanotechnology engineering discipline of designing and building nanorobots, with devices ranging in size from 0.1–10 micrometers and constructed of nanoscale or molecular components.^[4][5] The names nanobots, nanoids, nanites, nanomachines, or nanomites have also been used to describe these devices currently under research and development.^[6][7]

Nanomachines are largely in the research-and-development phase,^[8] but some primitive molecular machines and nanomotors have been tested. An example is a sensor having a switch approximately 1.5 nanometers across, capable of counting specific molecules in a chemical sample. The first useful applications of nanomachines might be in medical technology,^[9] which could be used to identify and destroy cancer cells.^[10][11] Another potential application is the detection of toxic chemicals, and the measurement of their concentrations, in the environment. Rice University has demonstrated a single-molecule car developed by a chemical process and including buckyballs for wheels. It is actuated by controlling the environmental temperature and by positioning a scanning tunneling microscope tip.

Another definition is a robot that allows precision interactions with nanoscale objects, or can manipulate with nanoscale resolution. Such devices are more related to microscopy or scanning probe microscopy, instead of the description of nanorobots as molecular machine. Following the microscopy definition even a large apparatus such as an atomic force microscope can be considered a nanorobotic instrument when configured to perform nanomanipulation. For this perspective, macroscale robots or microrobots that can move with nanoscale precision can also be considered nanorobots.

Nanorobotics theory

According to Richard Feynman, it was his former graduate student and collaborator Albert Hibbs who originally suggested to him (circa 1959) the idea of a medical use for Feynman's theoretical micromachines (see nanotechnology). Hibbs suggested that certain repair machines might one day be reduced in size to the point that it would, in theory, be possible to (as Feynman put it) "swallow the doctor". The idea was incorporated into Feynman's 1959 essay There's Plenty of Room at the Bottom.^[12]

Since nanorobots would be microscopic in size, it would probably be necessary for very large numbers of them to work together to perform microscopic and macroscopic tasks. These nanorobot swarms, both those incapable of replication (as in utility fog) and those capable of unconstrained replication in the natural environment (as in grey goo and its less common variants^{[clarification needed]}), are found in many science fiction stories, such as the Borg nanoprobes in Star Trek and The Outer Limits episode The New Breed.

Some proponents of nanorobotics, in reaction to the grey goo scenarios that they earlier helped to propagate, hold the view that nanorobots capable of replication outside of a restricted factory environment do not form a necessary part of a purported productive nanotechnology, and that the process of self-replication, if it were ever to be developed, could be made inherently safe. They further assert that their current plans for developing and using molecular manufacturing do not in fact include free-foraging replicators.^[13][14]

The most detailed theoretical discussion of nanorobotics, including specific design issues such as sensing, power communication, navigation, manipulation, locomotion, and onboard computation, has been presented in the medical context of nanomedicine by Robert Freitas. Some of these discussions remain at the level of unbuildable generality and do not approach the level of detailed engineering.

Approaches

Biochip

The joint use of nanoelectronics, photolithography, and new biomaterials provides a possible approach to manufacturing nanorobots for common medical applications, such as for surgical instrumentation, diagnosis and drug delivery.^[15][16][17] This method for manufacturing on nanotechnology scale is currently in use in the electronics industry.^[18] So, practical nanorobots should be integrated as nanoelectronics devices, which will allow tele-operation and advanced capabilities for medical instrumentation.^[19][20]

Nubots

Nubot is an abbreviation for "nucleic acid robot." Nubots are organic molecular machines at the nanoscale.^[21] DNA structure can provide means to assemble 2D and 3D nanomechanical devices. DNA based machines can be activated using small molecules, proteins and other molecules of DNA.^[22][23][24] Biological circuit gates based on DNA materials have been engineered as molecular machines to allow in-vitro drug delivery for targeted health problems.^[25] Such material based systems would work most closely to smart biomaterial drug system delivery,^[26] while not allowing precise in vivo teleoperation of such engineered prototypes.

Surface-bound systems

A number of reports have demonstrated the attachment of synthetic molecular motors to surfaces.^[27][28] These primitive nanomachines have been shown to undergo machine-like motions when confined to the surface of a macroscopic material. The surface anchored motors could potentially be used to move and position nanoscale materials on a surface in the manner of a conveyor belt.

Positional nanoassembly

Nanofactory Collaboration,^[29] founded by Robert Freitas and Ralph Merkle in 2000 and involving 23 researchers from 10 organizations and 4 countries, focuses on developing a practical research agenda^[30] specifically aimed at developing positionally-controlled diamond mechanosynthesis and a diamondoid nanofactory that would have the capability of building diamondoid medical nanorobots.

Bacteria-based

This approach proposes the use of biological microorganisms, like the bacterium Escherichia coli.^[31] Thus the model uses a flagellum for propulsion purposes. Electromagnetic fields normally control the motion of this kind of biological integrated device.^[32] Chemists at the University of Nebraska have created a humidity gauge by fusing a bacteria to a silicone computer chip.^[33]

Virus-based

Retroviruses can be retrained to attach to cells and replace DNA. They go through a process called reverse transcription to deliver genetic packaging in a vector.^[34] Usually, these devices are Pol – Gag genes of the virus for the Capsid and Delivery system. This process is called retroviral Gene Therapy, having the ability to re-engineer cellular DNA by usage of viral vectors.^[35] This approach has appeared in the form of Retroviral, Adenoviral, and Lentiviral gene delivery systems.^[36] These Gene Therapy vectors have been used in cats to send genes into the genetic modified animal "GMO" causing it display the trait. ^[37]

Open technology

A document with a proposal on nanobiotech development using open technology approaches has been addressed to the United Nations General Assembly.^[38] According to the document sent to the UN, in the same way that Open Source has in recent years accelerated the development of computer systems, a similar approach should benefit the society at large and accelerate nanorobotics development. The use of nanobiotechnology should be established as a human heritage for the coming generations, and developed as an open technology based on ethical practices for peaceful purposes. Open technology is stated as a fundamental key for such an aim.

Nanorobot race

In the same ways that technology development had the space race and nuclear arms race, a race for nanorobots is occurring.^{[39][40][41][42][43]} There is plenty of ground allowing nanorobots to be included among the emerging technologies.^[44] Some of the reasons are that large corporations, such as General Electric, Hewlett-Packard, Synopsys, Northrop Grumman and Siemens have been recently working in the development and research of nanorobots;^{[45][46][47][48][49]} surgeons are getting involved and starting to propose ways to apply nanorobots for common medical procedures;^[50] universities and research institutes were granted funds by government agencies exceeding $2 billion towards research developing nanodevices for medicine;^[51][52] bankers are also strategically investing with the intent to acquire beforehand rights and royalties on future nanorobots commercialization.^[53]
Some aspects of nanorobot litigation and related issues linked to monopoly have already arisen.^[54][55][56] A large number of patents has been granted recently on nanorobots, done mostly for patent agents, companies specialized solely on building patent portfolio, and lawyers. After a long series of patents and eventually litigations, see for example the Invention of Radio or about the War of Currents, emerging fields of technology tend to become a monopoly, which normally is dominated by large corporations.^[57]

Potential applications

Nanomedicine

Potential applications for nanorobotics in medicine include early diagnosis and targeted drug-delivery for cancer,^[58][59][60] biomedical instrumentation,^[61] surgery,^[62][63] pharmacokinetics,^[10] monitoring of diabetes,^[64][65][66] and health care.
In such plans, future medical nanotechnology is expected to employ nanorobots injected into the patient to perform work at a cellular level. Such nanorobots intended for use in medicine should be non-replicating, as replication would needlessly increase device complexity, reduce reliability, and interfere with the medical mission.

Nanotechnology provides a wide range of new technologies for developing customized solutions that optimize the delivery of pharmaceutical products. Today, harmful side effects of treatments such as chemotherapy are commonly a result of drug delivery methods that don't pinpoint their intended target cells accurately.^[67] Researchers at Harvard and MIT, however, have been able to attach special RNA strands, measuring nearly 10 nm in diameter, to nano-particles, filling them with a chemotherapy drug. These RNA strands are attracted to cancer cells. When the nanoparticle encounters a cancer cell, it adheres to it, and releases the drug into the cancer cell.^[68] This directed method of drug delivery has great potential for treating cancer patients while avoiding negative effects (commonly associated with improper drug delivery).^[67][69] The first demonstration of nanomotors operating in living organism was carried out in 2014 at UCSD, San Diego.^[70]

Another useful application of nanorobots is assisting in the repair of tissue cells alongside white blood cells.^[71] The recruitment of inflammatory cells or white blood cells (which include neutrophils, lymphocytes, monocytes and mast cells) to the affected area is the first response of tissues to injury.^[72] Because of their small size nanorobots could attach themselves to the surface of recruited white cells, to squeeze their way out through the walls of blood vessels and arrive at the injury site, where they can assist in the tissue repair process. Certain substances could possibly be utilized to accelerate the recovery.

The science behind this mechanism is quite complex. Passage of cells across the blood endothelium, a process known as transmigration, is a mechanism involving engagement of cell surface receptors to adhesion molecules, active force exertion and dilation of the vessel walls and physical deformation of the migrating cells. By attaching themselves to migrating inflammatory cells, the robots can in effect “hitch a ride” across the blood vessels, bypassing the need for a complex transmigration mechanism of their own.^[71]

The US FDA currently regulates nanotechnology on the basis of size.^[73] The FDA also regulates that which acts by chemical means as a drug, and that which acts by physical means as a device.^[74] Single molecules can also be used as Turing machines, like their larger paper tape counterparts, capable of universal computation and exerting physical (or chemical) forces as a result of that computation. Safety systems are being developed so that if a drug payload were to be accidentally released, the payload would either be inert or another drug would be then released to counteract the first. Toxicological testing becomes convolved with software validation in such circumstances.With new advances in nanotechnology these small devices are being created with the ability to self-regulate and be ‘smarter’ than previous generations. As nanotechnology becomes more complex, how will regulatory agencies distinguish a drug from a device?^[74] Drug molecules must undergo slower and more expensive testing (for example, preclinical toxicological testing) than devices, and the regulatory pathways for devices are simpler than for drugs. Perhaps smartness, if smart enough, will someday be used to justify a device classification for a single molecule nanomachine. Devices are generally approved more quickly than drugs, so device classification could be beneficial to patients and manufacturers.

Biorobotics

From Wikipedia, the free encyclopedia

Biorobotics is a term that loosely covers the fields of cybernetics, bionics and even genetic engineering as a collective study.

Biorobotics is often used to refer to a real subfield of robotics: studying how to make robots that emulate or simulate living biological organisms mechanically or even chemically. The term is also used in a reverse definition: making biological organisms as manipulatable and functional as robots, or making biological organisms as components of robots.

In the latter sense, biorobotics can be referred to as a theoretical discipline of comprehensive genetic engineering in which organisms are created and designed by artificial means. The creation of life from non-living matter for example, would be biorobotics. The field is in its infancy and is sometimes known as synthetic biology or bionanotechnology.

In fiction, biorobotics makes many appearances, like the biots of the novel Rendezvous with Rama or the replicants of the film Blade Runner.

Biorobotics in Fiction

Biorobotics has made many appearances in works of fiction, often in the form of synthetic biological organisms.

Augmentations feature as a major plot device in Deus Ex and its prequel Deus Ex: Human Revolution, with nano and mechanical variations, respectively. The advent of such augmentation that is conducive to previously inhuman feats results in widespread civil unrest, fundamentally challenging the self-perception and identity of humanity.

The robots featured in Rossum's Universal Robots, the play that originally coined the term robot, are presented as synthetic biological entities closer to biological organisms than the mechanical objects that the term robot came to refer to. The replicants in the film Blade Runner are biological in nature: they are organisms of living tissue and cells created artificially. In the novel The Windup Girl by Paolo Bacigalupi, "windups" or "New People" are genetically engineered organisms.

The word biot, a portmanteau of "biological robot", was originally coined by Arthur C. Clarke in his 1972 novel Rendezvous with Rama. Biots are depicted as artificial biological organisms created to perform specific tasks on the space vessel Rama. This affects their physical attributes and cognitive abilities.

Humanoid Cylons in the 2004 television series Battlestar Galactica are another example of biological robots in fictions. Almost undistinguishable from humans, they are artificial creations created by mechanical cylons.

The authors of the Star Wars book series The New Jedi Order reprised the term biot. The Yuuzhan Vong uses the term to designate their biotechnology.

The term bioroid, or biological android, as also been used to designate artificial biological organisms, like in the manga Appleseed. In 1985 the animated Robotech television series popularized the term when it reused the term from the 1984 Japanese series The Super Dimension Cavalry Southern Cross.

The term reploid, or replicate-android, is used in the Capcom video game series Mega ManX. Much like Blade Runner's replicants these beings are more human in thinking and emotional awareness then previous generations, despite some being made into animal shapes to purposely distinguish them from humans. Another further future form of these robots, seen in Mega Man Zero, have them being so close to humans that they can actually eat, sleep, and reproduce. The only thing setting them apart is their semi-inorganic skeletal systems. In another farther flung future version and evolution of these bio-machines in the series Mega Man ZX humans and robots have merged seemingly so closely they are no longer a separate race but in-fact two parts to a whole new race. The final future of the game series is Mega Man Legends where humans and robots are one being to the point they can actually get together and reproduce offspring without effort.

In Warhammer 40k Imperium (Warhammer 40,000) uses servitors, vat-grown humans with cybernetic parts replacing most parts of the body.They lack emotions or intelligence and are only capable of simple tasks. A more advanced imperial robots are used by the imperium, instead of using humans they are mostly machine and has biological brain and some other biological parts. Unlike servitors they are capable of having programmed instincts when killing but still they lack any true intelligence.

Practical experimentation

A biological brain, grown from cultured neurons which were originally separated, has been developed as the neurological entity subsequently embodied within a robot body by Kevin Warwick and his team at University of Reading. The brain receives input from sensors on the robot body and the resultant output from the brain provides the robot's only motor signals. The biological brain is the only brain of the robot.^[1]