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Nanomaterials (NMs) like carbon nanotubes, fullerenes, nanowires , nanocrystals and quatum dots are being used in various medical applications as discussed. The generic methods that are undertaken for manufacturing of nanomaterials are identification, Charecterisation, processing and attaining final product (Figure).
The charecterisation of the size, shape, distribution, chemical and mechanical properties of materials is an important part of industrial process. The large scale manufacturing of these NMs is a challenging task for many manufacturing companies. Nanomaterials can be formed in two ways: top-down approach and bottom-up approach (Moriarty et al., 2004). In a top-down approach, mechanical, chemical and other forms of energy are used to break down the bulk materials into smaller ones. While a bottom-up approach uses various chemical reactions to synthesize to synthesize the materials from atomic or molecular levels (Figure).
Both these approaches can be carried out in either solid, liquid, gas or in vacuum. Particle size, particle shape and composition, size distribution and agglomeration are the main factors to be controlled while manufacturing the nanomaterials. The most common approach being used today to manufacture nanoproducts is top down approach. However, they are believed to be most time consuming methods and have drawbacks such as use of intensive energy, introduction of impurities and waste-producing. Bottom up techniques on the other hand, are likely to become an integral part of nanomaterial manufacturing and requires deep understanding of individual molecules, their structures and assembly properties. The major methods used in manufacturing nanoproducts are summarised in the table below.
Conventional (photolithography, E-beam lithography)
Next-generation (Immersion, X-ray, Extreme ultraviolet lithography)
Nanoparticle/nanostructured synthesis techniques
Dry Ethcing (Reactive ion etching, plasma etching and Sputtering)
Solvo thermal and Sonochemical synthesis
Milling (Mechanical and Cryomilling)
Electro static self assembly
Self Assembled Monolayers (SAMs)
Substantial advances in manufacturing of nanomaterials for medical purposes is achieved which include fabrication of nanofiber materials for tissue engineering and cell culture, fabrication of peptide, protein and lipid scaffolds, creation of living microlenses, assembly of peptide or protein nanotubes and helical ribbons and metal nanowire synthesis for biosensing. This chapter focuses on generic methods of nanomaterial manufacturing and their use in medicine.
It starts with a large piece of material and reducing it to nanoproduct by using high-energy techniques such as milling, etching, sputtering and laser-ablation which are discusses in detail below.
Mechanical milling: In this method, prealloyed powders with a diameter of 50ÂÂµm are placed in a sealed container along with a number of tungsten carbide coated or hardened steel balls. The container is then shaken or agitated violently resulting in a continuous refinement of the powdered particles to nanomaterials. There are generally two ways in producing nanopowders using high energy mechanical milling: mechanochemical process and milling a single phase powder. In the production of specific nanomaterials, suitable precursors such as oxides, sulphides, carbonates, fluorides, chlorides and other compounds are chosen. This is then milled with an appropriate reactant resulting in individual nanometer sized grains in by-product which is later removed, leaving the non-agglomerated and pure nanopowder (Froes et al., 2001).
Etching (Chemical): This method is mainly used for the production of nanoarrays for biomolecular analysis. Regular nano-meter sized arrays can be produced on a planar substrate by combining elctrochemical or photo-electrochemical etching with lithographically defined patterning.
Sputtering (Kinetic): A process where the atoms or ions are ejected from target material when the target is bombarded with energetic particles. It is done on a cold substrate at low-pressure. Although itââ‚¬â„¢s a vapour- phase technique, there is no melting of the material.
Laser-ablation (Thermal): It is done by focusing a pulsed light from a excimer laser onto a solid target in a vaccum chamber to boil off energetic atoms from the target leaving a thin film deposit on the positioned substrate (Ullman et al., 2002). For example, Carbon nanotubes (CNT) are grown by laser-ablation of metal doped graphite targets. This method is considered to be advantageous for manufacturing nanomaterials for various reasons such as high production rate, permit change in the fabrication parameters over a wide range and ability to evaporate all materials.
It involves building of the structures atom-by-atom or molecule-by-molecule. This can be achieved by various processes such as Sol-gel processing, Aerosol deposition, Atomic or molecular condensation and self assembly.
Sol-gel processing: A cost-effective, versatile and long-established industrial process for the production of advanced nanomaterials and coatings (Yu, 2001). Oxide nanoparticles and composite nanopowders are well synthesized by using sol-gel technique. Low temeperature processing and flexible rheology are the main advantages of using this technique. It also offers access to organic-inorganic materials.
Aerosol based processes: Aerosols are solid or liquid particles in gaseous phase. This is the most common method for industrial production of nanoparticles and is done by spraying the precursor chemicals into hot air or surface resulting in precursor pyrolysis and formation of nanoparticles (Kammler, 2001).
Chemical Vapour deposition (CVD): It is done by activation of a chemical reaction between a gaseous precursor and a substrate surface with temperature (thermal CVD) or plasma (PECVD). Carbon nanotubes (CNTââ‚¬â„¢s) can also be produced by this method (Meyyappan et al., 2003).
Atomic or molecular condensation: This method is used for the production of metal containing nanoparticles. The metal is first placed on a heated surface and is allowed to melt. The evaporated metal is moved away from the hot element by the continuous gas (inert) flow in the chamber. The gas is then cooled to form the nanosized metal particles which are still in liquid phase. They are then cooled under controlled environment to become solid and grow no longer.
Electro-Spinning: It is used for the production of thin polymer fibres. Dilute polymer solutions are spun in a high voltage electric field resulting in a bundle of polymer fibres. The setup contains a syringe to pump the polymer solution which is connected to a high voltage source (Figure). As the tip of the needle pumps a droplet, long fibres are formed due to electrostatic repulsions which are collected onto a metal plate in the form of a nanofibrous mat. These nanofibres are used in drug delivery and tissue engineering applications (Li et al., 2005).
Self-assembly: This technique is emerging as an elegant approach for manufacturing nanoparticles. A variety of nanomaterials including organic and biological compounds can be processed by chemical self-assembly techniques (Shimizu, 2003). They utilize various techniques such as selective attachment of molecules to specific surfaces, biomolecular recognition and self-ordering techniques, reverse micelle, photochemical synthesis and sonochemical to realise the self-assembled 1-D, 2-D, and 3-D nanostructures. The molecules are built in a perfect order without any driving force. This technique is still in its infancy and is believed to offer great potential in the development of biomimetic materials.
After the primary processing step of nanomaterials which is done by any of the one above mentioned methods, the nanoparticles are highly reactive and have a high tendency to form agglomerates. Hence, it is often required to stabilize them with additional treatments. The commercial success or failure of the produced nanomaterials depends mostly on their stability in water or organic fluids with controlled rheology. This is achieved by coating the nanoparticles with other materials of nano-scale dimension or encapsulating them with a thin molecular or a polymeric layer (Bourgeat-Lammi, 2002). Another way to attain stability is by collecting the nanoparticles in liquid suspensions (Sailor et al., 1997).
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