Medical Device Link.

DESIGN

Unmet material demands

There are hundreds of different medical materials, many of which have been used for decades. At the same time there is an ever-increasing demand for new or highly functionalised materials to meet a variety of medical needs, including

• cleanability
• sterilisability
• biocompatibility
• resistance to bacterial growth
• surfaces that promote cell adhesion
• hydrophilic or hydrophobic surfaces
• low friction or slippery surfaces
• resistance to abrasion.

This article examines a few of the contributions the rapidly expanding field of plasma treatment can make towards creating new materials with these desirable properties or adding new functionalities to existing medical materials. A number of different types of plasma technology are now appearing that utilise a variety of gases and coating materials at low temperature, which is more suitable for functionalisation of medical materials, and achieve their action by complex interactions at the substrate surface.

What is a plasma?

Plasma is commonly referred to as the fourth state of matter after solids, liquids and gases. Plasmas are the most common form of matter accounting for more than 99% of the matter in the apparent universe including interstellar space. A plasma can be considered to be a gas that contains charged and neutral species including electrons, positive ions (cations), negative ions (anions), and molecules and atoms (radicals).

A plasma is generated by applying an energy source, for example, an electrical field or high frequency (KHz, MHz or microwave) generator, to the gas or a mixture of gases. The input must be maintained to sustain the plasma because charged particles are lost through recombination, diffusion and convection. Typically, a plasma carries an overall neutral charge and may be formed at both low and atmospheric pressures. Examples of natural plasmas, moving from low temperature to extremely high temperatures include interstellar space, the aurora borealis, the solar wind, flames, the solar corona and the solar core. Examples of commonplace manmade plasmas include those in neon signs, fluorescent lighting tubes and welding arcs.

Exploiting plasmas in industry

Plasmas may be exploited industrially by taking advantage of their thermal energy, photonic energy, kinetic energy and chemical reactivity. By manipulating these different properties, a plasma may be made to interact with a substrate to

• ablate or remove materials, for example in cleaning, sterilising or etching processes
• add materials or functionality by temporarily activating a surface by adding energy
• permanently functionalise a surface by adding chemical groups, or by depositing a coating or material.

Various types of materials may be added to the plasma by including a precursor in the plasma gas stream. The basic prerequisites for a plasma system are a power source (frequency: from direct current to microwave, continuous or pulsed); a mass flow controller to inject gases and precursors; coupling elements such as electrodes, antennae, waveguides or dielectric elements; a substrate holder; and, in the case of low pressure plasmas, a vacuum chamber.

Some advantages of using plasma for the treatment of medical materials include:

• its suitability for application at low temperatures, which makes it ideal for plastics, polymers and other types of substrates.
• the possibility to fabricate metastable materials
• the possibility to act and impart changes or functional properties only to the material surface without acting on the bulk of the material
• the ability to apply anisotropy or preferential orientation of desired features
• the ability to create a variety of different nanoscale features such as nanodomes, nanopillars, nanocraters and nanopores, or features at the microscale, for example, channels that can be used to guide cell growth on implants or tissue engineering substrates
• the ability to create cost-effective and efficient processes, for example, the use of low quantities of gases and precursors, sometimes more than 800 times less in low pressure plasma systems
• the fact that plasma processes are an intrinsically “dry” technology and therefore ecologically and environment friendly.

Imparting new properties

Cleaning and sterilising. Organic material may be readily removed from a surface at relatively low plasma energies, typically using an oxygen–argon gas mixture or by incorporating hydrogen peroxide into the gas stream. Typical systems use an inductively coupled low-pressure plasma source. Organic molecules are decomposed into gases by the actions of highly reactive oxygen radicals and ablation by oxygen ions in the plasma and are removed by means of a vacuum pump. If the material or device is thermally sensitive or prone to degradation by ethylene oxide or irradiation, plasma may be the only feasible means of sterilisation because it works at approximately 50 °C. Processing time is generally short, typically less than 60 minutes.

Surface activation, modification

and functionalisation. Surface activation is achieved by temporarily increasing the energy of the surface being treated, typically using an oxygen or air plasma. This may be useful, for example, to improve the hydrophilicity or hydrophobicity of a surface (depending on the process and substrate) by means of modification of the contact angle, or to prepare it for glueing or bonding. Depending on the gas mixture, with a medical polymer the plasma process will typically remove surface layers of low molecular weight, oxidise or hydroxylate the uppermost atomic layers, promote the cross bonding of polymer molecules and increase polar groups, which improve adhesion properties.

Surface modification and functionalisation can be achieved by permanently changing the surface through the interaction of energetic particles, photons and free radicals, or through the introduction of
specific chemical groups. This can lead also to the formation of covalent bonds suitable to attach further coatings. Different mixtures of gases or precursors in the plasma system may be used to impart a range of desired properties.

Coatings. Plasma technology may be utilised to apply a range of coatings, using a variety of gases and additives. Examples of the properties these coatings provide are:

• lubricity or low friction, for example, to ease the insertion of a catheter or probe
• antibacterial properties whereby additives such as silver nanoparticles and certain high molecular weight cationic polymers prevent the growth of microbes
  
• wear resistance, for example, using silicon dioxide nanoparticles or by cross-linking polymer surfaces, hard coating for the bearing surfaces of orthopaedic implants
• barrier properties, for example, on polyethylene
• prevention of biofilm formation or the attachment of proteins or cells, for example certain perfluorocarbons
• electrical conductance
• chemical resistance to protect against corrosion in the harsh internal environment of the body
• thermal resistance.

Recent advances in plasma technology include the ability to coat complex three dimensional surfaces such as stents to inhibit restenosis.¹

Creating features at the nanoscale. Plasma techniques are being increasingly used to impart a variety of nanoscale features to medical materials and thereby provide new properties. These include the ability of cells to adhere or grow in an organised manner on the surface, or features that may be used for biosensing or diagnosis.

As well as the application of photolithography, which is an important process in the production of microelectronic components, techniques such as block copolymer self-assembly, soft lithography and ultraviolet lithography may be applied to create an organic film-based image that can be transferred by plasma etching to a substrate to produce nanoscale features. This, however, requires much greater understanding of the interactions between the plasma and the molecules within the image and how these affect the production of nanoscale features in the substrate.²

One well-known example where a plasma process can create features not produced by other processes is that of carbon nanotubes, which grow vertically aligned in a plasma. The nanotubes comprise acetylene as the carbon source and ammonia as a catalyst, but remain disordered in a neutral gas process.

A recent study³ has identified the following as some of the important benefits that can be achieved by low-temperature plasma techniques in nanoscale surface engineering:

• vertical alignment of nanostructures
• directionality and better penetration of ionic species
• processing of temperature-sensitive materials such as polymers, paper and biological tissues
• large-scale, high-rate nanoparticle/ nanotube production in thermal plasmas
• crystallisation and surface preparation at low process temperatures
• a broad range of available species such as atoms, radicals and clusters that can be used for a variety of purposes
• precisely controlled, and higher, growth rates
• better, for example, ion-improved, crystallisation on surfaces at low temperatures
• conformal nanolayers
• selected area functionalisation, doping and post processing in areas inaccessible by neutral species
• Exploitation of charge- and electric field-related effects in the growth of self-organised nanodot arrays
• A variety of options for surface activation and catalyst preparation
• Environmentally clean processes.

Furthermore, the authors of the study foresee that plasma technology offer a virtually unlimited and highly effective toolbox for nanoscale surface engineering with processes ranging from the deposition of a variety of nanofilm, nanotexturing, ultrafine doping/functionalisation and even self-organised growth of quantum dot arrays.

The ACTECO FP6 project

The practical application of plasma technology, particularly at the level of detail required at the nanoscale, requires the commercial development of accurate, reliable and versatile plasma systems. ACTECO is an Integrated Project within Framework Programme 6 of the European Union.⁴ Its objectives are to develop breakthrough efficient plasma technology systems and processes to produce hyperfunctional surfaces with applications in the textile, food packaging and biomedical industry. Another important project objective is to replace “wet textile treatment” technologies, characterised by the consumption of large amounts of water and solvents, with so-called “dry” and environmentally friendly technology. The project is due to run until the end of April 2009. A project report will then be published and made publicly available with the aim of disseminating the results of the collaborative research to industry with a particular emphasis on small and medium-sized companies.

Richard Moore is Manager, Nanomedicine and Life Sciences, at the Institute of Nanotechnology, Suite 5/9 Scion House, Stirling University Innovation Park, Stirling FK9 4NF, UK, e-mail: richard.moore@nano.org.uk tel. +44 1786 458 020, www.nano.org.uk, www.nanomednet.org