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Thursday, April 18, 2019

Nanoparticle–biomolecule conjugate

From Wikipedia, the free encyclopedia

Attachments on nanoparticles make them more biocompatible.
 
A nanoparticle–biomolecule conjugate is a nanoparticle with biomolecules attached to its surface. Nanoparticles are minuscule particles, typically measured in nanometers (nm), that are used in nanobiotechnology to explore the functions of biomolecules. Properties of the ultrafine particles are characterized by the components on their surfaces more so than larger structures, such as cells, due to large surface area-to-volume ratios. Large surface area-to-volume-ratios of nanoparticles optimize the potential for interactions with biomolecules.

Characterization

Major characteristics of nanoparticles include volume, structure, and visual properties that make them valuable in nanobiotechnology. Depending on specific properties of size, structure, and luminescence, nanoparticles can be used for different applications. Imaging techniques are used to identify such properties and give more information about the tested sample. Techniques used to characterize nanoparticles are also useful in studying how nanoparticles interact with biomolecules, such as amino acids or DNA, and include magnetic resonance imaging (MRI), denoted by the solubility of the nanoparticles in water and fluorescent. MRI can be applied in the medical field to visualize structures; atomic force microscopy (AFM) that gives a topographic view of the sample on a substrate; transmission electron microscopy (TEM) that gives a top view, but with a different technique then that of atomic force microscopy; Raman spectroscopy or surface enhanced Raman spectroscopy (SERS) gives information about wavelengths and energy in the sample. ultraviolet-visible spectroscopy (UV-Vis) measures the wavelengths where light is absorbed; X-ray diffraction (XRD) generally gives an idea of the chemical composition of the sample.

Chemistry

Physical

Nanomolecules can be created from virtually any element, but the majority produced in today's industry use carbon as the basis upon which the molecules are built around. Carbon can bond with nearly any element, allowing many possibilities when it comes to creating a specific molecule. Scientists can create thousands upon thousands of individual nanomolecules from a simple carbon basis. Some of the most famous nanomolecules currently in existence are solely carbon; these include carbon nanotubes and buckminsterfullerenes. In contrast with nanomolecules, the chemical components of nanoparticles usually consist of metals, such as iron, gold, silver, and platinum.

Interactions between nanoparticles and molecules change depending on the nanoparticle's core. Nanoparticle properties depend not only on the composition of the core material, but also on varying thicknesses of material used. Magnetic properties are particularly useful in molecule manipulation, and thus metals are often used as core material. Metals contain inherent magnetic properties that allow for manipulation of molecular assembly. As nanoparticles interact with molecules via ligand properties, molecular assembly can be controlled by external magnetic fields interacting with magnetic properties in the nanoparticles. Significant problems with producing nanoparticles initially arise once these nanoparticles are generated in solution. Without the use of a stabilizing agent, nanoparticles tend to stick together once the stirring is stopped. In order to counteract this, a certain collidial stabilizer is generally added. These stabilizers bind to the nanoparticles in a way that prevents other particles from bonding with them. Some effective stabilizers found so far include citrate, cellulose, and sodium borohydride.

Application chemistry

Nanoparticles are desirable in today's industry for their high surface area-to-volume ratio in comparison with larger particles of the same elements. Because chemical reactions occur at a rate directly proportional to the available surface area of reactant compounds, nanoparticles can generate reactions at a much faster rate than larger particles of equal mass. Nanoparticles therefore are among the most efficient means of producing reactions and are inherently valuable in the chemical industry. The same property makes them valuable in interactions with molecules.

Applications with biomolecules and biological processes

Nanoparticles have the potential to greatly influence biological processes. The potency of a nanoparticle increases as its surface area-to-volume-ratio does. Attachments of ligands to the surface of nanoparticles allow them to interact with biomolecules.

Identification of biomolecules

Nanoparticles are valuable tools in identification of biomolecules, through the use of bio-tagging or labeling. Attachments of ligands or molecular coatings to the surface of a nanoparticle facilitate nanoparticle-molecule interaction, and make them biocompatible. Conjugation can be achieved through intermolecular attractions between the nanoparticle and biomolecule such as covalent bonding, chemisorption, and noncovalent interactions.

To enhance visualization, nanoparticles can also be made to fluoresce by controlling the size and shape of a nanoparticle probe. Fluorescence increases luminescence by increasing the range of wavelengths the emitted light can reach, allowing for biomarkers with a variety of colors. This technique is used to track the efficacy of protein transfer both in vivo and in vitro in terms of genetic alternations.

Biological process control

Biological processes can be controlled through transcription regulation, gene regulation, and enzyme inhibition processes that can be regulated using nanoparticles. Nanoparticles can play a part in gene regulation through ionic bonding between positively charged cationic ligands on the surfaces of nanoparticles and negatively charged anionic nucleic acids present in DNA. In an experiment, a nanoparticle-DNA complex inhibited transcription by T7 RNA polymerase, signifying strong bonding in the complex. A high affinity of the nanoparticle-DNA complex indicates strong bonding and a favorable use of nanoparticles. Attaching ionic ligands to nanoparticles allows control over enzyme activity. An example of enzyme inhibition is given by binding of a-chymotrypsin (ChT), an enzyme with a largely cationic active site. When a-chymotrypsin is incubated with anionic (negatively charged) nanoparticles, ChT activity is inhibited as anionic nanoparticles bind to the active site. Enzyme activity can be restored by the addition of cationic surfactants. Alkyl surfactants form a bilayer around ChT, whereas thiol and alcohol surfactants alter the surface of ChT such that interactions with nanoparticles are interrupted. Though formation of a protein-nanoparticle complex can inhibit enzyme activity, studies show that it can also stabilize protein structure, and significantly protect the protein from denaturization. Attachments of ligands to segments of nanoparticles selected for functionalization of metallic properties can be used to generate a magnetic nanowire, which generates a magnetic field that allows for the manipulation of cellular assemblies.

Genetic alteration

Nanoparticles can also be used in conjunction with DNA to perform genetic alterations. These are frequently monitored through the use of fluorescent materials, allowing scientists to judge if these tagged proteins have successfully been transmitted—for example green fluorescent protein, or GFP. Nanoparticles are significantly less cytotoxic than currently used organic methods, providing a more efficient method of monitoring genetic alternations. They also do not degrade or bleach with time, as organic dyes do. Suspensions of nanoparticles with the same size and shapes (mono-dispersed) with functional groups attached to their surfaces can also electrostatically bind to DNA, protecting them from several types of degradation. Because the fluorescence of these nanoparticles does not degrade, cellular localization can be tracked without the use of additional tagging, with GFPs or other methods. The 'unpacking' of the DNA can be detected in live cells using luminescence resonance energy transfer (LRET) technology.

Medical implications

Small molecules in vivo have a short retention time, but the use of larger nanoparticles does not. These nanoparticles can be used to avoid immune response, which aids in the treatment of chronic diseases. It has been investigated as a potential cancer therapy and also has the potential to affect the understanding of genetic disorders. Nanoparticles also have the potential to aid in site-specific drug delivery by improving the amount of unmodified drug that is circulated within the system, which also decreases the necessary dosage frequency. The targeted nature of nanoparticles also means that non-targeted organs are much less likely to experience side effects of drugs intended for other areas.

Studying cell interactions

Cellular interactions occur at a microscopic level and cannot be easily observed even with the advanced microscopes available today. Due to difficulties observing reactions at the molecular level, indirect methods are used which greatly limits the scope of the understanding that can be gained by studying these processes essential to life. Advances in the material industry has evolved a new field known as nanobiotechnology, that uses nanoparticles to study interactions at the biomolecular level.

One area of research featuring nanobiotechnology is the extracellular matrices of cells (ECM). The ECM is primarily composed of interwoven fibers of collagen and elastin that have diameters ranging from 10–300 nm. In addition to holding the cell in place, the ECM has a variety of other functions including providing a point of attachment for the ECM of other cells and transmembrane receptors that are essential for life. Until recently it has been nearly impossible to study the physical forces that help cells maintain their functionality, but nanobiotechnology has given us the ability to learn more about these interactions. Using the unique properties of nanoparticles, it is possible to control how the nanoparticles adhere to certain patterns present in the ECM, and as a result can understand how changes in the ECM's shape can affect cell functionality.

Using nanobiotechnology to study the ECM allows scientists to investigate the binding interactions that occur between the ECM and its supporting environment. Investigators were able to study these interactions by utilizing tools such as optical tweezers, which have the ability to trap nano-scale objects with focused light. The tweezers can affect the binding of a substrate to the ECM by attempting to draw the substrate away from it. The light emitted from the tweezers was used to restrain ECM-coated microbeads, and the changes in the force exerted by the ECM onto the substrate were studied by modulating the effect of the optical tweezers. Experiments showed that the force exerted by the ECM on the substrate positively correlated with the force of the tweezers, which led to the subsequent discovery that the ECM and the transmembrane proteins are able to sense external forces, and can adapt to overcome these forces.

Nanotechnology crossing the blood-brain barrier

The blood-brain barrier (BBB) is composed of a system of capillaries that has an especially dense lining of endothelial cells which protects the central nervous system (CNS) against the diffusion of foreign substances into the cerebrospinal fluid. These harmful objects include microscopic bacteria, large hydrophobic molecules, certain hormones and neurotransmitters, and low-lipid-soluble molecules. The BBB prevents these harmful particles from entering the brain via tight junctions between endothelial cells and metabolic barriers. The thoroughness with which the BBB does its job makes it difficult to treat diseases of the brain such as cancer, Alzheimer's, and autism, because it is very difficult to transport drugs across the BBB. Currently, in order to deliver therapeutic molecules into the brain, doctors must use highly invasive techniques such as drilling directly into the brain, or sabotaging the integrity of the BBB through biochemical means. Due to their small size and large surface area, nanoparticles offer a promising solution for neurotherapeutics. 

Nanotechnology is helpful in delivering drugs and other molecules across the blood-brain barrier (BBB). Nanoparticles allow drugs, or other foreign molecules, to efficiently cross the BBB by camouflaging themselves and tricking the brain into providing them with the ability to cross the BBB in a process called the Trojan Horse Method. Using nanotechnology is advantageous because only the engineered complex is necessary whereas in ordinary applications the active compound must carry out the reaction. This allows for maximum efficacy of the active drug. Also, the use of nanoparticles results in the attraction of proteins to the surfaces of cells, giving cell membranes a biological identity. They also use endogenous active transport where transferrin, an iron binding protein, is linked to rod-shaped semiconductor nanocrystals, in order to move across the BBB into the brain. This discovery is a promising development towards designing an efficient nanoparticle-based drug delivery system.

Nanoparticle

From Wikipedia, the free encyclopedia

TEM (a, b, and c) images of prepared mesoporous silica nanoparticles with mean outer diameter: (a) 20nm, (b) 45nm, and (c) 80nm. SEM (d) image corresponding to (b). The insets are a high magnification of mesoporous silica particle.
 
Nanoparticles are particles between 1 and 100 nanometres (nm) in size with a surrounding interfacial layer. The interfacial layer is an integral part of nanoscale matter, fundamentally affecting all of its properties. The interfacial layer typically consists of ions, inorganic and organic molecules. Organic molecules coating inorganic nanoparticles are known as stabilizers, capping and surface ligands, or passivating agents. In nanotechnology, a particle is defined as a small object that behaves as a whole unit with respect to its transport and properties. Particles are further classified according to diameter.

Definition

IUPAC definition
 
Particle of any shape with dimensions in the 1 × 10−9 and 1 × 10−7 m range.
 Note 1: Modified from definitions of nanoparticle and nanogel.

Note 2: The basis of the 100-nm limit is the fact that novel properties that
differentiate particles from the bulk material typically develop at a critical
length scale of under 100 nm.


Note 3: Because other phenomena (transparency or turbidity, ultrafiltration,
stable dispersion, etc.) that extend the upper limit are occasionally considered,
the use of the prefix nano is accepted for dimensions smaller than 500 nm,
provided reference to the definition is indicated.

 
Note 4: Tubes and fibers with only two dimensions below 100 nm are also
nanoparticles.

The term "nanoparticle" is not usually applied to individual molecules; it usually refers to inorganic materials. 

Ultrafine particles are the same as nanoparticles and between 1 and 100 nm in size, as opposed to fine particles are sized between 100 and 2,500 nm, and coarse particles cover a range between 2,500 and 10,000 nm. The reason for the synonymous definition of nanoparticles and ultrafine particles is that, during the 1970s and 80s, when the first thorough fundamental studies with "nanoparticles" were underway in the USA (by Granqvist and Buhrman) and Japan, (within an ERATO Project) they were called "ultrafine particles" (UFP). However, during the 1990s before the National Nanotechnology Initiative was launched in the USA, the new name, "nanoparticle," had become more common (for example, see the same senior author's paper 20 years later addressing the same issue, lognormal distribution of sizes). Nanoparticles can exhibit size-related properties significantly different from those of either fine particles or bulk materials.

Nanoclusters have at least one dimension between 1 and 10 nanometers and a narrow size distribution. Nanopowders are agglomerates of ultrafine particles, nanoparticles, or nanoclusters. Nanometer-sized single crystals, or single-domain ultrafine particles, are often referred to as nanocrystals

According to ISO Technical Specification 80004, a nanoparticle is defined as a nano-object with all three external dimensions in the nanoscale, whose longest and shortest axes do not differ significantly, with a significant difference typically being a factor of at least 3.

The terms colloid and nanoparticle are not interchangeable. A colloid is a mixture which has solid particles dispersed in a liquid medium. The term applies only if the particles are larger than atomic dimensions but small enough to exhibit Brownian motion, with the critical size range (or particle diameter) typically ranging from nanometers (10−9 m) to micrometers (10−6 m). Colloids can contain particles too large to be nanoparticles, and nanoparticles can exist in non-colloidal form, for examples as a powder or in a solid matrix.

History

Although nanoparticles are associated with modern science, they have a long history. Nanoparticles were used by artisans as far back as Rome in the fourth century in the famous Lycurgus cup made of dichroic glass as well as the ninth century in Mesopotamia for creating a glittering effect on the surface of pots. In modern times, pottery from the Middle Ages and Renaissance often retains a distinct gold- or copper-colored metallic glitter. This luster is caused by a metallic film that was applied to the transparent surface of a glazing. The luster can still be visible if the film has resisted atmospheric oxidation and other weathering.

The luster originates within the film itself, which contains silver and copper nanoparticles dispersed homogeneously in the glassy matrix of the ceramic glaze. These nanoparticles are created by the artisans by adding copper and silver salts and oxides together with vinegar, ochre, and clay on the surface of previously-glazed pottery. The object is then placed into a kiln and heated to about 600 °C in a reducing atmosphere. In heat the glaze softens, causing the copper and silver ions to migrate into the outer layers of the glaze. There the reducing atmosphere reduced the ions back to metals, which then came together forming the nanoparticles that give the color and optical effects. Luster technique showed that ancient craftsmen had a sophisticated empirical knowledge of materials. The technique originated in the Muslim world. As Muslims were not allowed to use gold in artistic representations, they sought a way to create a similar effect without using real gold. The solution they found was using luster.

Michael Faraday provided the first description, in scientific terms, of the optical properties of nanometer-scale metals in his classic 1857 paper. In a subsequent paper, the author (Turner) points out that: "It is well known that when thin leaves of gold or silver are mounted upon glass and heated to a temperature that is well below a red heat (~500 °C), a remarkable change of properties takes place, whereby the continuity of the metallic film is destroyed. The result is that white light is now freely transmitted, reflection is correspondingly diminished, while the electrical resistivity is enormously increased."

Properties

Silicon nanopowder
 
1 kg of particles of 1 mm3 has the same surface area as 1 mg of particles of 1 nm3
 
Nanoparticles are of great scientific interest as they are, in effect, a bridge between bulk materials and atomic or molecular structures. A bulk material should have constant physical properties regardless of its size, but at the nano-scale size-dependent properties are often observed. Thus, the properties of materials change as their size approaches the nanoscale and as the percentage of the surface in relation to the percentage of the volume of a material becomes significant. For bulk materials larger than one micrometer (or micron), the percentage of the surface is insignificant in relation to the volume in the bulk of the material. The interesting and sometimes unexpected properties of nanoparticles are therefore largely due to the large surface area of the material, which dominates the contributions made by the small bulk of the material

Nanoparticles often possess unexpected optical properties as they are small enough to confine their electrons and produce quantum effects. For example, gold nanoparticles appear deep-red to black in solution. Nanoparticles of yellow gold and grey silicon are red in color. Gold nanoparticles melt at much lower temperatures (~300 °C for 2.5 nm size) than the gold slabs (1064 °C);. Absorption of solar radiation is much higher in materials composed of nanoparticles than it is in thin films of continuous sheets of material. In both solar PV and solar thermal applications, controlling the size, shape, and material of the particles, it is possible to control solar absorption. Recently, the core (metal)-shell (dielectric) nanoparticle has demonstrated a zero backward scattering with enhanced forward scattering on Si substrate when surface plasmon is located in front of a solar cell. The core-shell nanoparticles can support simultaneously both electric and magnetic resonances, demonstrating entirely new properties when compared with bare metallic nanoparticles if the resonances are properly engineered. 

Other size-dependent property changes include quantum confinement in semiconductor particles, surface plasmon resonance in some metal particles and superparamagnetism in magnetic materials. What would appear ironic is that the changes in physical properties are not always desirable. Ferromagnetic materials smaller than 10 nm can switch their magnetisation direction using room temperature thermal energy, thus making them unsuitable for memory storage.

Suspensions of nanoparticles are possible since the interaction of the particle surface with the solvent is strong enough to overcome density differences, which otherwise usually result in a material either sinking or floating in a liquid. 

The high surface area to volume ratio of nanoparticles provides a tremendous driving force for diffusion, especially at elevated temperatures. Sintering can take place at lower temperatures, over shorter time scales than for larger particles. In theory, this does not affect the density of the final product, though flow difficulties and the tendency of nanoparticles to agglomerate complicates matters. Moreover, nanoparticles have been found to impart some extra properties to various day to day products. For example, the presence of titanium dioxide nanoparticles imparts what we call the self-cleaning effect, and, the size being nano-range, the particles cannot be observed. Zinc oxide particles have been found to have superior UV blocking properties compared to its bulk substitute. This is one of the reasons why it is often used in the preparation of sunscreen lotions, is completely photostable, and toxic [DJS -- ??].

Clay nanoparticles when incorporated into polymer matrices increase reinforcement, leading to stronger plastics, verifiable by a higher glass transition temperature and other mechanical property tests. These nanoparticles are hard, and impart their properties to the polymer (plastic). Nanoparticles have also been attached to textile fibers in order to create smart and functional clothing.

Metal, dielectric, and semiconductor nanoparticles have been formed, as well as hybrid structures (e.g., core–shell nanoparticles). Nanoparticles made of semiconducting material may also be labeled quantum dots if they are small enough (typically sub 10 nm) that quantization of electronic energy levels occurs. Such nanoscale particles are used in biomedical applications as drug carriers or imaging agents with work being done to try to understand the fluid dynamic properties (e.g. drag forces) in nanoscale applications. This has shown the relationship between the fluid forces on nanoparticles and the fluid Reynolds and Knudsen numbers.

Semiconductor nanoparticle (quantum dot) of lead sulfide with complete passivation by oleic acid, oleyl amine and hydroxyl ligands (size ~5nm)
 
Semi-solid and soft nanoparticles have been manufactured. A prototype nanoparticle of semi-solid nature is the liposome. Various types of liposome nanoparticles are currently used clinically as delivery systems for anticancer drugs and vaccines. 

Nanoparticles with one half hydrophilic and the other half hydrophobic are termed Janus particles and are particularly effective for stabilizing emulsions. They can self-assemble at water/oil interfaces and act as solid surfactants.

Hydrogel nanoparticles made of N-isopropylacrylamide hydrogel core shell can be dyed with affinity baits, internally. These affinity baits allow the nanoparticles to isolate and remove undesirable proteins while enhancing the target analytes.

Variation in properties

The chemical processing and synthesis of high-performance technological components for the private, industrial, and military sectors requires the use of high-purity ceramics (oxide ceramics, such as aluminium oxide or copper(II) oxide), polymers, glass-ceramics, and composite materials, as metal carbides (SiC), nitrides (Aluminum nitrides, Silicon nitride), metals (Al, Cu), non-metals (graphite, carbon nanotubes) and layered (Al + Aluminium carbonate, Cu + C). In condensed bodies formed from fine powders, the irregular particle sizes and shapes in a typical powder often lead to non-uniform packing morphologies that result in packing density variations in the powder compact.

Uncontrolled agglomeration of powders due to attractive van der Waals forces can also give rise to microstructural heterogeneity. Differential stresses that develop as a result of non-uniform drying shrinkage are directly related to the rate at which the solvent can be removed, and thus highly dependent upon the distribution of porosity. Such stresses have been associated with a plastic-to-brittle transition in consolidated bodies, and can yield to crack propagation in the unfired body if not relieved.

In addition, any fluctuations in packing density in the compact as it is prepared for the kiln are often amplified during the sintering process, yielding inhomogeneous densification. Some pores and other structural defects associated with density variations have been shown to play a detrimental role in the sintering process by growing and thus limiting end-point densities. Differential stresses arising from inhomogeneous densification have also been shown to result in the propagation of internal cracks, thus becoming the strength-controlling flaws.

Inert gas evaporation and inert gas deposition are free many of these defects due to the distillation (cf. purification) nature of the process and having enough time to form single crystal particles, however even their non-aggreated deposits have lognormal size distribution, which is typical with nanoparticles. The reason why modern gas evaporation techniques can produce a relatively narrow size distribution is that aggregation can be avoided. However, even in this case, random residence times in the growth zone, due to the combination of drift and diffusion, result in a size distribution appearing lognormal.

It would, therefore, appear desirable to process a material in such a way that it is physically uniform with regard to the distribution of components and porosity, rather than using particle size distributions that will maximize the green density. The containment of a uniformly dispersed assembly of strongly interacting particles in suspension requires total control over interparticle forces. Monodisperse nanoparticles and colloids provide this potential.

Monodisperse powders of colloidal silica, for example, may therefore be stabilized sufficiently to ensure a high degree of order in the colloidal crystal or polycrystalline colloidal solid that results from aggregation. The degree of order appears to be limited by the time and space allowed for longer-range correlations to be established. Such defective polycrystalline colloidal structures would appear to be the basic elements of submicrometer colloidal materials science and, therefore, provide the first step in developing a more rigorous understanding of the mechanisms involved in microstructural evolution in high performance materials and components.

Synthesis

There are several methods for creating nanoparticles, including gas condensation, attrition, chemical precipitation, ion implantation, pyrolysis and hydrothermal synthesis. In attrition, macro- or micro-scale particles are ground in a ball mill, a planetary ball mill, or other size-reducing mechanism. The resulting particles are air classified to recover nanoparticles. In pyrolysis, a vaporous precursor (liquid or gas) is forced through an orifice at high pressure and burned. The resulting solid (a version of soot) is air classified to recover oxide particles from by-product gases. Traditional pyrolysis often results in aggregates and agglomerates rather than single primary particles. Ultrasonic nozzle spray pyrolysis (USP) on the other hand aids in preventing agglomerates from forming.

A thermal plasma can deliver the energy to vaporize small micrometer-size particles. The thermal plasma temperatures are in the order of 10,000 K, so that solid powder easily evaporates. Nanoparticles are formed upon cooling while exiting the plasma region. The main types of the thermal plasma torches used to produce nanoparticles are dc plasma jet, dc arc plasma, and radio frequency (RF) induction plasmas. In the arc plasma reactors, the energy necessary for evaporation and reaction is provided by an electric arc formed between the anode and the cathode. For example, silica sand can be vaporized with an arc plasma at atmospheric pressure, or thin aluminum wires can be vaporized by exploding wire method. The resulting mixture of plasma gas and silica vapour can be rapidly cooled by quenching with oxygen, thus ensuring the quality of the fumed silica produced.

In RF induction plasma torches, energy coupling to the plasma is accomplished through the electromagnetic field generated by the induction coil. The plasma gas does not come in contact with electrodes, thus eliminating possible sources of contamination and allowing the operation of such plasma torches with a wide range of gases including inert, reducing, oxidizing, and other corrosive atmospheres. The working frequency is typically between 200 kHz and 40 MHz. Laboratory units run at power levels in the order of 30–50 kW, whereas the large-scale industrial units have been tested at power levels up to 1 MW. As the residence time of the injected feed droplets in the plasma is very short, it is important that the droplet sizes are small enough in order to obtain complete evaporation. The RF plasma method has been used to synthesize different nanoparticle materials, for example synthesis of various ceramic nanoparticles such as oxides, carbours/carbides, and nitrides of Ti and Si.

Inert gas condensation

Inert-gas condensation is frequently used to produce metallic nanoparticles. The metal is evaporated in a vacuum chamber containing a reduced atmosphere of an inert gas. Condensation of the supersaturated metal vapor results in creation of nanometer-size particles, which can be entrained in the inert gas stream and deposited on a substrate or studied in situ. Early studies were based on thermal evaporation. Using magnetron sputtering to create the metal vapor allows to achieve higher yields. The method can easily be generalized to alloy nanoparticles by choosing appropriate metallic targets. The use of sequential growth schemes, where the particles travel through a second metallic vapor, results in growth of core-shell (CS) structures.

Radiolysis method

Left) Transmission electron microscopy (TEM) image of Hf nanoparticles grown by magnetron-sputtering inert-gas condensation (inset: size distribution) and right) energy dispersive x-ray (EDX) mapping of Ni and Ni@Cu core@shell nanoparticles.
 
Nanoparticles can also be formed using radiation chemistry. Radiolysis from gamma rays can create strongly active free radicals in solution. This relatively simple technique uses a minimum number of chemicals. These including water, a soluble metallic salt, a radical scavenger (often a secondary alcohol), and a surfactant (organic capping agent). High gamma doses on the order of 104 Gray are required. In this process, reducing radicals will drop metallic ions down to the zero-valence state. A scavenger chemical will preferentially interact with oxidizing radicals to prevent the re-oxidation of the metal. Once in the zero-valence state, metal atoms begin to coalesce into particles. A chemical surfactant surrounds the particle during formation and regulates its growth. In sufficient concentrations, the surfactant molecules stay attached to the particle. This prevents it from dissociating or forming clusters with other particles. Formation of nanoparticles using the radiolysis method allows for tailoring of particle size and shape by adjusting precursor concentrations and gamma dose.

Sol–gel

The sol–gel process is a wet-chemical technique (also known as chemical solution deposition) widely used recently in the fields of materials science and ceramic engineering. Such methods are used primarily for the fabrication of materials (typically a metal oxide) starting from a chemical solution (sol, short for solution), which acts as the precursor for an integrated network (or gel) of either discrete particles or network polymers

Typical precursors are metal alkoxides and metal chlorides, which undergo hydrolysis and polycondensation reactions to form either a network "elastic solid" or a colloidal suspension (or dispersion) – a system composed of discrete (often amorphous) submicrometer particles dispersed to various degrees in a host fluid. Formation of a metal oxide involves connecting the metal centers with oxo (M-O-M) or hydroxo (M-OH-M) bridges, therefore generating metal-oxo or metal-hydroxo polymers in solution. Thus, the sol evolves toward the formation of a gel-like diphasic system containing both a liquid phase and solid phase whose morphologies range from discrete particles to continuous polymer networks.

In the case of the colloid, the volume fraction of particles (or particle density) may be so low that a significant amount of fluid may need to be removed initially for the gel-like properties to be recognized. This can be accomplished in a number of ways. The most simple method is to allow time for sedimentation to occur, and then pour off the remaining liquid. Centrifugation can also be used to accelerate the process of phase separation.

Removal of the remaining liquid (solvent) phase requires a drying process, which typically causes shrinkage and densification. The rate at which the solvent can be removed is ultimately determined by the distribution of porosity in the gel. The ultimate microstructure of the final component will clearly be strongly influenced by changes implemented during this phase of processing. Afterward, a thermal treatment, or firing process, is often necessary in order to favor further polycondensation and enhance mechanical properties and structural stability via final sintering, densification, and grain growth. One of the distinct advantages of using this methodology as opposed to the more traditional processing techniques is that densification is often achieved at a much lower temperature.

The precursor sol can be either deposited on a substrate to form a film (e.g., by dip-coating or spin-coating), cast into a suitable container with the desired shape (e.g., to obtain a monolithic ceramics, glasses, fibers, membranes, aerogels), or used to synthesize powders (e.g., microspheres, nanospheres). The sol–gel approach is a cheap and low-temperature technique that allows for the fine control of the product’s chemical composition. Even small quantities of dopants, such as organic dyes and rare earth metals, can be introduced in the sol and end up uniformly dispersed in the final product. It can be used in ceramics processing and manufacturing as an investment casting material, or as a means of producing very thin films of metal oxides for various purposes. Sol–gel derived materials have diverse applications in optics, electronics, energy, space, (bio)sensors, medicine (e.g., controlled drug release) and separation (e.g., chromatography) technology.

Ion implantation

Ion implantation may be used to treat the surfaces of dielectric materials such as sapphire and silica to make composites with near-surface dispersions of metal or oxide nanoparticles.

Morphology

Nanostars of vanadium(IV) oxide
 
Scientists have taken to naming their particles after the real-world shapes that they might represent. Nanospheres, nanochains, nanoreefs, nanoboxes, and more have appeared in the literature. These morphologies sometimes arise spontaneously as an effect of a templating or directing agent present in the synthesis such as miscellar emulsions or anodized alumina pores, or from the innate crystallographic growth patterns of the materials themselves. Some of these morphologies may serve a purpose, such as long carbon nanotubes used to bridge an electrical junction, or just a scientific curiosity like the stars shown at right. 

Amorphous particles usually adopt a spherical shape (due to their microstructural isotropy), whereas the shape of anisotropic microcrystalline whiskers corresponds to their particular crystal habit. At the small end of the size range, nanoparticles are often referred to as clusters. Spheres, rods, fibers, and cups are just a few of the shapes that have been grown. The study of fine particles is called micromeritics.

Characterization

Nanoparticles have different analytical requirements than conventional chemicals, for which chemical composition and concentration are sufficient metrics. Nanoparticles have other physical properties that must be measured for a complete description, such as size, shape, surface properties, crystallinity, and dispersion state. Additionally, sampling and laboratory procedures can perturb their dispersion state or bias the distribution of other properties. In environmental contexts, an additional challenge is that many methods cannot detect low concentrations of nanoparticles that may still have an adverse effect. For some applications, nanoparticles may be characterized in complex matrices such as water, soil, food, polymers, inks, complex mixtures of organic liquids such as in cosmetics, or blood.

There are several overall categories of methods used to characterize nanoparticles. Microscopy methods generate images of individual nanoparticles to characterize their shape, size, and location. Electron microscopy and scanning probe microscopy are the dominant methods. Because nanoparticles have a size below the diffraction limit of visible light, conventional optical microscopy is not useful. Electron microscopes can be coupled to spectroscopic methods that can perform elemental analysis. Microscopy methods are destructive, and can be prone to undesirable artifacts from sample preparation, or from probe tip geometry in the case of scanning probe microscopy. Additionally, microscopy is based on single-particle measurements, meaning that large numbers of individual particles must be characterized to estimate their bulk properties.

Spectroscopy, which measures the particles' interaction with electromagnetic radiation as a function of wavelength, is useful for some classes of nanoparticles to characterize concentration, size, and shape. X-ray, ultraviolet–visible, infrared, and nuclear magnetic resonance spectroscopy can be used with nanoparticles. Light scattering methods using laser light, X-rays, or neutron scattering are used to determine particle size, with each method suitable for different size ranges and particle compositions. Some miscellaneous methods are electrophoresis for surface charge, the Brunauer–Emmett–Teller method for surface area, and X-ray diffraction for crystal structure, as well as mass spectrometry for particle mass, and particle counters for particle number. Chromatography, centrifugation, and filtration techniques can be used to separate nanoparticles by size or other physical properties before or during characterization.

Functionalization

Functionalization is the introduction of organic molecules or polymers on the surface of the nanoparticle. The surface coating of nanoparticles determines many of their physical and chemical properties, notably stability, solubility, and targeting. A coating that is multivalent or polymeric confers high stability. Functionalized nanomaterial-based catalysts can be used for catalysis of many known organic reactions.

Surface coating for biological applications

For biological applications, the surface coating should be polar to give high aqueous solubility and prevent nanoparticle aggregation. In serum or on the cell surface, highly charged coatings promote non-specific binding, whereas polyethylene glycol linked to terminal hydroxyl or methoxy groups repel non-specific interactions. Nanoparticles can be linked to biological molecules that can act as address tags, to direct the nanoparticles to specific sites within the body, specific organelles within the cell, or to follow specifically the movement of individual protein or RNA molecules in living cells. Common address tags are monoclonal antibodies, aptamers, streptavidin or peptides. These targeting agents should ideally be covalently linked to the nanoparticle and should be present in a controlled number per nanoparticle. Multivalent nanoparticles, bearing multiple targeting groups, can cluster receptors, which can activate cellular signaling pathways, and give stronger anchoring. Monovalent nanoparticles, bearing a single binding site, avoid clustering and so are preferable for tracking the behavior of individual proteins. 

Red blood cell coatings can help nanoparticles evade the immune system.

Health and safety

Nanoparticles present possible dangers, both medically and environmentally. Most of these are due to the high surface to volume ratio, which can make the particles very reactive or catalytic. They are also able to pass through cell membranes in organisms, and their interactions with biological systems are relatively unknown. However, it is unlikely the particles would enter the cell nucleus, Golgi complex, endoplasmic reticulum or other internal cellular components due to the particle size and intercellular agglomeration. A recent study looking at the effects of ZnO nanoparticles on human immune cells has found varying levels of susceptibility to cytotoxicity. There are concerns that pharmaceutical companies, seeking regulatory approval for nano-reformulations of existing medicines, are relying on safety data produced during clinical studies of the earlier, pre-reformulation version of the medicine. This could result in regulatory bodies, such as the FDA, missing new side effects that are specific to the nano-reformulation.

Whether cosmetics and sunscreens containing nanomaterials pose health risks remains largely unknown at this stage. However considerable research has demonstrated that zinc nanoparticles are not absorbed into the bloodstream in vivo.

Concern has also been raised over the health effects of respirable nanoparticles from certain combustion processes. As of 2013 the U.S. Environmental Protection Agency was investigating the safety of the following nanoparticles:
  • Carbon Nanotubes: Carbon materials have a wide range of uses, ranging from composites for use in vehicles and sports equipment to integrated circuits for electronic components. The interactions between nanomaterials such as carbon nanotubes and natural organic matter strongly influence both their aggregation and deposition, which strongly affects their transport, transformation, and exposure in aquatic environments. In past research, carbon nanotubes exhibited some toxicological impacts that will be evaluated in various environmental settings in current EPA chemical safety research. EPA research will provide data, models, test methods, and best practices to discover the acute health effects of carbon nanotubes and identify methods to predict them.
  • Cerium oxide: Nanoscale cerium oxide is used in electronics, biomedical supplies, energy, and fuel additives. Many applications of engineered cerium oxide nanoparticles naturally disperse themselves into the environment, which increases the risk of exposure. There is ongoing exposure to new diesel emissions using fuel additives containing CeO2 nanoparticles, and the environmental and public health impacts of this new technology are unknown. EPA’s chemical safety research is assessing the environmental, ecological, and health implications of nanotechnology-enabled diesel fuel additives.
  • Titanium dioxide: Nano titanium dioxide is currently used in many products. Depending on the type of particle, it may be found in sunscreens, cosmetics, and paints and coatings. It is also being investigated for use in removing contaminants from drinking water.
  • Nano Silver: Nano silver is being incorporated into textiles, clothing, food packaging, and other materials to eliminate bacteria. EPA and the U.S. Consumer Product Safety Commission are studying certain products to see whether they transfer nano-size silver particles in real-world scenarios. EPA is researching this topic to better understand how much nano-silver children come in contact with in their environments.
  • Iron: While nano-scale iron is being investigated for many uses, including “smart fluids” for uses such as optics polishing and as a better-absorbed iron nutrient supplement, one of its more prominent current uses is to remove contamination from groundwater. This use, supported by EPA research, is being piloted at a number of sites across the United States.

Regulation

As of 2016, the U.S. Environmental Protection Agency had conditionally registered, for a period of four years, only two nanomaterial pesticides as ingredients. The EPA differentiates nanoscale ingredients from non-nanoscale forms of the ingredient, but there is little scientific data about potential variation in toxicity. Testing protocols still need to be developed.

Applications

As the most prevalent morphology of nanomaterials used in consumer products, nanoparticles have potential and actual applications in all industries. Table below summarizes the most common nanoparticles used in various product types available on the global markets.

Various nanoparticles which are commonly used in the consumer products by industrial sectors
No. Industrial sectors Nanoparticles
1 agriculture silver, silicon dioxide, potassium, calcium, iron, zinc, phosphorus, boron, zinc oxide and molybdenum
2 automotive tungsten, disulfidesilicon dioxide, clay, titanium dioxide, diamond, copper, cobalt oxide, zinc oxide, boron nitride, zirconium dioxide, tungsten, γ-aluminium oxide, boron, palladium, platinum, cerium(IV) oxide, carnauba, aluminium oxide, silver, calcium carbonate and calcium sulfonate
3 construction titanium, dioxidesilicon dioxide, silver, clay, aluminium oxide, calcium carbonate calcium silicate hydrate, carbon, aluminium phosphate cerium(IV) oxide and calcium hydroxide
4 cosmetics silver, titanium dioxide, gold, carbon, zinc oxide, silicon dioxide, clay, sodium silicate, kojic acid and hydroxy acid
5 electronics silver, aluminum, silicon dioxide and palladium
6 environment silver, titanium dioxide, carbonmanganese oxide, clay, gold and selenium
7 food silver, clay, titanium dioxide, gold, zinc oxide, silicon dioxide, calcium, copper, zinc, platinum, manganese, palladium and carbon
8 home appliance silver, zinc oxide, silicon dioxide, diamond and titanium dioxide
9 medicine silver, gold, hydroxyapatite, clay, titanium dioxide, silicon dioxide, zirconium dioxide, carbon, diamond, aluminium oxide and ytterbium trifluoride
10 petroleum tungsten, disulfidezinc oxide, silicon dioxide, diamond, clay, boron, boron nitride, silver, titanium dioxide, tungsten, γ-aluminium oxide, carbon, molybdenum disulfide and γ-aluminium oxide
11 printing toner, deposited by a printer onto paper or other substrate
12 renewable energies titanium, palladium, tungsten disulfide, silicon dioxide, clay, graphite, zirconium(IV) oxide-yttria stabilized, carbon, gd-doped-cerium(IV) oxide, nickel cobalt oxide, nickel(II) oxide, rhodium, sm-doped-cerium(IV) oxide, barium strontium titanate and silver
13 sports and fitness silver, titanium dioxide, gold, clay and carbon
14 textile silver, carbon, titanium dioxide, copper sulfide, clay, gold, polyethylene terephthalate and silicon dioxide

Scientific research on nanoparticles is intense as they have many potential applications in medicine, physics, optics, and electronics. The U.S. National Nanotechnology Initiative offers government funding focused on nanoparticle research.|The use of nanoparticles in laser dye-doped poly(methyl methacrylate) (PMMA) laser gain media was demonstrated in 2003 and it has been shown to improve conversion efficiencies and to decrease laser beam divergence. Researchers attribute the reduction in beam divergence to improved dn/dT characteristics of the organic-inorganic dye-doped nanocomposite. The optimum composition reported by these researchers is 30% w/w of SiO2 (~ 12 nm) in dye-doped PMMA.|Nanoparticles are being investigated as potential drug delivery system. Drugs, growth factors or other biomolecules can be conjugated to nano particles to aid targeted delivery. This nanoparticle-assisted delivery allows for spatial and temporal controls of the loaded drugs to achieve the most desirable biological outcome.|Nanoparticles are also studied for possible applications as dietary supplements for delivery of biologically active substances, for example mineral elements.

Classical radicalism

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