# Exploitation of Antimicrobial Nanoparticles and Their Applications in Biomedical Engineering
## 2 Nanomaterials
### Nanoparticle Synthesis and Processing Methods
#### 2.1.2 Top-down  
On the other hand, the top-down approach involves more mechanical and physical techniques, such as mechanical milling. The size of particles is decomposed by milling from the micro dimensions to the nanoscale with strong mechanical shear forces and post-annealing in an inert atmosphere [43]. The main problem of this method is the contamination of the nanomaterial from milling media and/or the atmosphere and powder consolidation, especially for highly energetic mills. For instance, continuous grinding using high-energy shaker mills can cause more than 10% Fe contamination from steel balls and containers [43]. Furthermore, if milling is to be carried out under atmospheric pressure, air (i.e., N\({}_{2}\) and O\({}_{2}\)) can easily react with the milling media, such as metallic Al, Ti, Zr [43,44]. Hence, there are limitations to the type of nanomaterials that can be manufactured using this method.  
Spray pyrolysis is alternatively used in industry for largescale production of nanoparticles, and such method involves burning a bulk precursor in either liquid or vapour form at high pressure and/or temperature, where the precursor is fed into the furnace through a hole or opening [45]. Some of the furnaces use laser and plasma instead of flame to deliver the energy that is required to perform complete evaporation of small micrometresized particles [46]. The advantages of using pyrolysis are that apparatus set-up can be quite simple, the production process can be very efficient and cost-effective, nanomaterials can be manufactured under a continuous process with high production yield. [PERSON] et al. evaluated the physical and antimicrobial properties of Copper oxide nanoparticles (CuO NPs) that were engineered using the Tesima(tm) plasma process, as shown in Figure 2[47]. TEM demonstrated particle sizes of CuO NPs generated using this method were in the range of 20 to 95 nm. These CuO NPs were also shown to inhibit a range of pathogenic bacteria (i.e., MRSA and _E. coli_). Although these techniques can be properly established for large-scale manufacturing processes, it does require large energy consumption and an intensive cleaning protocol in order to produce the desired materials in a highly pure state. It was also reported that materials produced using such an approach were more likely to agglomerate and be susceptible to surface contamination [23,48].  
Once the desired nanopowder is produced, it can be treated and further processed into different forms to fit application purposes. Nanopowder can be dispersed into colloidal suspensions in different surfactants for coating/impregnating solid substrates to produce antimicrobial functions. They can be formulated into air-stable aerosols; Ag NPs containing aerosols are currently marketed as surface disinfectants, deodorisers, etc. [49]. Nanomaterials can also be formulated into an emulsion for pharmaceutical applications. For example,  
Figure 2: Schematic diagram of TesimaTM plasma process. Reproduced with permission from [PERSON] et al., _International Journal of Antimicrobial Agents_; published by Elsevier, 2009. [47].  
suncreens containing TiO\({}_{2}\) and ZnO nanoparticles are one of the most common emulsions with effectively protect skin by broadband ultraviolet (UV) radiation, whilst the application on the skin remains transparent [50].