From easy lighting to disease fighting

Could plasma technology be the key to improving the surfaces of everyday healthcare items?

Plasma, the fourth state of matter, is more abundant than many believe. On a universal scale, plasmas actually account for 99% of visible matter and can be blandly classified as ‘ionised gases’¹. They can be best described though as ‘conductive assemblies of charged particles, neutrals and fields that exhibit collective effects’². Such unique properties have made plasmas extremely versatile in many everyday settings, for example fluorescent and arc lighting as well as plasma television and computer screens. However, these uses only account for a small percentage of the applications for plasmas; they are used on an industrial scale for many procedures from semiconductor etching to thick and thin film depositon1. A new cold plasma-based surface modification process though, developed by the UK Defence Science and Technology Laboratory (DSTL) and the University of Durham, is likely to impact on many peoples’ lives. The potential for this technology is being realised by Porton Plasma Innovations (P2i), based at Porton Down in Wiltshire, UK, who are developing a number of treatments for clothing, electronics and more importantly medical equipment.

Cold plasma
It is worth describing the basis of the treatment process and some common applications before introducing the more healthcare oriented uses. In classical treatments, plasma is accelerated and directed at the target using magnets, producing a variety of different coating procedures. The cold plasma process on the other hand, places the target in the plasma field and is therefore considerable cheaper. To achieve this P2i use pulses of radio frequency (RF) energy to activate vapours of a range of special precursor chemicals within a carefully designed chamber. The molecules in the plasma polymerise and bind to products placed in the vessel. This results in the surfaces gaining the properties of the deposited polymer, while leaving the inherent nature of the product unchanged. The advantage of using a plasma process to deposit polymers is that the precursor molecules in the plasma can infuse into any porous or complex object. The chemicals penetrate deep into materials and bind to surfaces at the molecular level creating an invisible protective layer only molecules thick. Due to the deep penetration, the process can be considered more of a ‘surface enhancement’ than a coating.

More repellent
Coatings are usually applied to materials to provide them with a specific property, e.g. water repellence, either pre- or post-production. For example Teflon (PTFE) is added to fibres which will subsequently be used to make a garment, whereas wax is sprayed onto the finished product: The result in both cases is water repellency. Each of these processes though, has benefits and shortfalls which restrict their use in various situations. Cold plasma treatment can treat both pre- and post-production items and is therefore applicable to virtually any product. In addition it is a more efficient process, using small quantities of chemical with very little waste, providing a much safer working environment.

In the case of water repellency, cold plasma surface enhancement can produce a surface energy three times lower than Teflon and can repel 100% isopropylalcohol (IPA) and oils. The process can even make difficult areas, such as seams and zips, repellent. Due to the non-spray nature of the process, items such as mobile phones and handheld computers can also be treated using the technology.

Winning healthcare - Silver: Gold: Plasma!
This surface enhancement process also means that a wider variety of chemicals can be used to provide desirable properties. For example, in the fight against healthcare acquired infections (HAIs) silver and copper coatings on catheters and other products, have shown excellent ability to reduce infection rates since they are able to kill the bacteria that lead to infections. They achieve this by ripping holes in the bacterial membranes, killing bacteria virtually on contact. These metals though, leach into the environment and have noted pathological side effects. Chemicals such as diaphanous pyridinium-type quaternary ammonium salts have a similar, but more efficient, mode of action against bacteria, without being environmentally or clinically damaging3. Such antimicrobial compounds can be made into plasmas and used to enhance products e.g. catheters. More importantly other items that may require bactericidal properties: sheets, cloths, uniforms, equipment etc. can also be treated, whereas this is not presently viable using silver or copper. Since bacteria are killed on contact, dead cells can accumulate, but are easily removed from the surfaces by simply wiping them away with water, leaving the surface fully active. The process is economical and could therefore be applied to every catheter, gown and piece of equipment, instead of just special order items.

Biomolecular arrays, used increasingly in diagnostic medicine to test for the presence of pathogens and mutated genes such as cancer oncogenes, rely to some extent on the unique interactions between DNA and gold. Gold is used to attach known DNA ‘capture’ molecules to a slide or microplate well. These DNA capture molecules are specific for a known sequence of target DNA and are therefore used to precisely detect the presence of unwanted organisms even at low concentrations. Gold though, is an expensive substrate and the coating process used is highly inefficient. It is possible to remove the need to use gold, since modern techniques can produce DNA with many different binding modifications. These provide the ability to ligate DNA to a number of different substrates depending on the requirements. When this flexibility is coupled with the cold plasma process, biochemical interactions can be used to produce novel arrays. For example, aldehyde-based molecules with better DNA binding properties than gold can be very efficiently coated onto a variety of surfaces, including micro-spheres. These molecules can immobilise DNA via the Schiff-Base condensation reaction. During this, the free NH2 group of the DNA amine terminus, donates a proton (H) to the hydroxyl group (OH) of the aldehyde to form water (H2O). This importantly allows the DNA molecule to attach to the main body of the aldehyde. The sensitivity of the resultant arrays far exceeds that generated using gold.

More importantly by coating surfaces in chemicals with free thiol (-SH) groups, proteins and DNA can be immobilised onto the substrate via the reversible formation of disulphide bridges. These bonds are easily controlled using changes in pH or redox potential, producing technology that lends itself particularly well to re-usable arrays but also to the development of DNA computers.

Foul no more
Another type of plasma coating is effective in preventing the build up of proteins and other macromolecules on items such as stents and catheters. Traditional coatings based on polyethylene oxide (PEO) are effective but degrade within a few months, especially if exposed to ultraviolet light. This new coating will allow long-term use of stents and catheters, with much reduced risk of fouling. Keeping a line clear is of great importance if patients are to be allowed home, since blockages can lead to treatment and wound drainage issues prolonging the overall disease management process and hospitalisation time. Build-ups of protein and other macromolecules in a stent can also provide a good media for microbial infection growth, and thus preventing deposition greatly reduces the possibility of infections forming outside the reach of the immune system.

Conclusions
Plasma technology has been used for many years to improve the surfaces of semiconductors, engine components and even space shuttle parts, but until recently has not been applicable to everyday healthcare or consumer items. The new cold plasma treatment from Porton Plasma Innovations (P2i) is set to change this. Using this process, many different chemicals with superior properties to present coatings, can be used to enhance products either pre- or post-production. Due to the nature of the process, even delicate electronic components and fine tubes can be efficiently treated to gain properties such as; microbial resistance, reduced protein deposition and macromolecular binding. Catheters and stents for example, can now be enhanced cheaply and efficiently with diaphanous pyridinium-type quaternary ammonium salts, which are better than silver and copper presently used in some products. They can also be kept patent with a different coating, which will ensure that treatment proceeds without fouling and that microbes cannot establish in the tubes to start with. Another novel set of chemicals allows biomolecules to ‘stick’ to substrates and act as captors for biomolecular screening of pathogens and disease genes. These biomolecular arrays can also be made reversible by changing the interaction used to attach the DNA to the substrate, and are forming the basis of DNA computer technology.

Plasma is not only the most common state of matter on a universal scale, it is also set to be an essential process in many industries including healthcare. The cold plasma process has also been shown to have great potential for making surfaces water repellent, fire retardant, anti-static, electrically conductive and electrically resistant.

By Dr Stephen Coulson, Technical Director, P2i Ltd and Quentin Compton Bishop, Chief Executive Officer, P2i Ltd

 
References:
1: Glanz, J. ‘The pervasive plasma state’. Interdivisional and Public Affairs Committee Division of Plasma Physics the American Physical Society.
2: http://www.plasmas.org/basics.htm
3: A. M. Klibanov et al, Biotechnol. Lett. 2002, 24, 801