**2. Non-thermal plasma technology**

#### **2.1. History and definitions**

A plasma is a gaseous mixture of ions, radicals, electrons and neutrals. Plasma is often referred to as the fourth state of matter, as its properties fundamentally differ from solids, liquids and gasses and the change of state can be obtained by adding energy to a gas, similar to the transition from solid to liquid to gas. In 1929, Langmuir was the first to actually define a plasma, but already in the 19th century plasma was used on an industrial scale for the generation of ozone (Siemens) [15].

Plasma itself can be divided up into two categories: 1) thermal or equilibrium and 2) nonthermal or non-equilibrium plasma. Thermal or hot plasmas have temperatures of 4000 K or higher and are considered to be in a thermal equilibrium, meaning that both heavy ions and electrons have the same temperatures. Well known applications include plasma spraying, wide arc spraying, and thermal plasma chemical vapour deposition (TPCVD), thermal plasma synthesis of fine powders (nm), thermal plasma (toxic) waste destruction, thermal plasma densification of powders, thermal plasma metallurgy, thermal plasma extractive metallurgy etc. For non-thermal or cold plasma, only the electrons are accelerated via e.g. an applied electrical field, causing a thermal inequilibrium between the electrons and the heavy particles. This results in the formation of a plasma at lower temperatures. Due to this difference in operating temperature between thermal and non-thermal plasmas, they are often referred to as 'hot' and 'cold' plasmas respectively. Although referred to as cold plasma, temperatures of up to 1000 K can be reached. For biomedical applications, non-thermal plasma treatments are preferred with a degree of ionization of 1% or lower as this results in a discharge that can be sustained at room temperature (290-330 K), thus avoiding thermal degradation of thermosensitive materials. In the next paragraphs, the focus will be on the sources that are used to drive the discharge, as they are an excellent way to distinguish between the ways a plasma can be generated, independent of the set-ups possible.

#### **2.2. Plasma discharges**

produced textile [8-14]. Alongside the growing interest in tissue engineering and the booming of the electrospinning industry at the end of last century, non-thermal plasma technology found its way into the biomedical field. Today non-thermal plasma treatment can be consid‐

Before the start of the 21st century, the majority of contributions to scientific literature was focussing on oxygen plasma treatments at low pressures and the corresponding response on cell adhesion, growth and proliferation. Although today there is still a steady stream of publications on these low pressure oxygen plasmas, there is a growing interest in atmospheric pressure plasma treatments as they offer a number of practical advantages. In the next chapter part, a detailed overview will be given on plasma technology in general and the different treatments possible. After that, the chapter will continue on the use of plasma technology for (bio)medical textiles, according to the application. At the end there will be a critical conclusion and a look forward to the possible future of plasma technology for the biomedical textile

A plasma is a gaseous mixture of ions, radicals, electrons and neutrals. Plasma is often referred to as the fourth state of matter, as its properties fundamentally differ from solids, liquids and gasses and the change of state can be obtained by adding energy to a gas, similar to the transition from solid to liquid to gas. In 1929, Langmuir was the first to actually define a plasma, but already in the 19th century plasma was used on an industrial scale for the generation of

Plasma itself can be divided up into two categories: 1) thermal or equilibrium and 2) nonthermal or non-equilibrium plasma. Thermal or hot plasmas have temperatures of 4000 K or higher and are considered to be in a thermal equilibrium, meaning that both heavy ions and electrons have the same temperatures. Well known applications include plasma spraying, wide arc spraying, and thermal plasma chemical vapour deposition (TPCVD), thermal plasma synthesis of fine powders (nm), thermal plasma (toxic) waste destruction, thermal plasma densification of powders, thermal plasma metallurgy, thermal plasma extractive metallurgy etc. For non-thermal or cold plasma, only the electrons are accelerated via e.g. an applied electrical field, causing a thermal inequilibrium between the electrons and the heavy particles. This results in the formation of a plasma at lower temperatures. Due to this difference in operating temperature between thermal and non-thermal plasmas, they are often referred to as 'hot' and 'cold' plasmas respectively. Although referred to as cold plasma, temperatures of up to 1000 K can be reached. For biomedical applications, non-thermal plasma treatments are preferred with a degree of ionization of 1% or lower as this results in a discharge that can be sustained at room temperature (290-330 K), thus avoiding thermal degradation of thermosensitive materials. In the next paragraphs, the focus will be on the sources that are used to

ered as a well-established technique for the surface treatment of (bio)materials.

industry.

118 Advances in Bioengineering

**2. Non-thermal plasma technology**

**2.1. History and definitions**

ozone (Siemens) [15].

The different non-thermal or cold discharges discussed in the following parts have all proven their usefulness as well as their limitations. Over time, applications have been found for each different type of discharge in all branches of the industry: automotive, packaging, textiles, aerospace, catalysis, waste treatment, (bio)medical etc. [9, 13, 16-18]. The number of plasma reactor designs is nearly limitless and complete reviews have been written on that topic alone, as design changes are made to optimize the plasma treatment for their specific application [19]. Most of the designs available today can be linked to one of the plasma sources discussed here.

## *2.2.1. Corona and silent discharge*

A corona discharge reactor typically consists out of a cathode wire and an anode, which is normally the material that needs treatment. The first developed systems were powered by a DC source working in a pulsed mode and were operated at atmospheric pressure. When turned on, the system generates a lighting crown build out of many streamers, hence the name corona [9]. Pulses are used that are shorter than the time necessary to form an arc, thus avoiding the transition to the spark regime. In the middle of 20th century, the first corona discharge systems were patented for the incorporation into industrial textile production systems [20]. Later on, the systems were adapted to work with high frequency sources (radio-frequency (RF), microwave (MW) and AC) and today a number of commercial systems are available from companies such as Tech Sales Company, Air Liquide, Acxys Technologies etc. These modern high-tech set-ups are able to quickly and efficiently treat delicate structures such as electrospun sheets. One of the main disadvantages of corona treatment is that the streamers always form at the same sports, resulting in an inhomogeneous treatment of the exposed surfaces. To solve this particular problem, there has been a shift to the usage of silent discharges [16].

A silent discharge, also known as a dielectric barrier discharge (DBD), is powered either via a high frequency AC or an RF source. What makes the DBD stand out against other systems, is its higher and broad pressure operating range (5-105 Pa) [21, 22]. In 1857, Siemens was the first to use a DBD in a successful attempt to generate ozone and to this day it remains one of the most important industrial applications of the DBD [15].

A DBD reactor typically consists of 2 electrodes, of which at least 1 is covered with a dielectric material such as glass, ceramic or quartz. The voltage used to drive the discharge can start as low as 0.5 kV and can be increased up to a few 100 kV. The generated plasma is a collection of many small micro-discharges or streamers. The dielectric material is able to limit the discharge current, giving cause to very short-lived micro-discharges (1-10 ns) that are distributed homogeneously across the electrode. In some specific cases, the streamers can be avoided altogether and a true glow regime can be obtained, which is considered the best case for homogeneous treatments [9].

DBD set-ups have one major advantage compared to most other systems: the possibility to operate in a higher pressure range makes it possible to avoid extensive vacuum equipment. This results in a lower operating cost and faster treatment cycles, thus allowing them to be implemented in industrial surface modification processes. The low heat generation at elevated pressures allows for a wider range of applications, including plasma chemistry, grafting, polymerization, cleaning... These applications are not always as easily feasible in systems powered with a different source.

It should be noted that occasionally in literature also the term corona discharge or corona treatment is used in connection with DBDs, although most authors prefer to use this term only for discharges between bare metal electrodes without dielectric.

#### *2.2.2. DC discharge*

Non-thermal plasmas generated via a DC discharge are in most cases formed in a closed setup between two electrodes at very low pressures (10-1 – 10 pa) [21, 22]. As the current is increased, different types of discharges can be obtained. The Townsend discharge is a selfsustaining discharge, typically characterized by a low current. A higher current results in a drop of voltage and a glow discharge is generated. The glow discharge regime is the desired regime for surface modifications, as it guarantees a homogeneous treatment al throughout the reactor. Increasing the discharge current still further results in a fast increase of voltage until an arc is formed, allowing for the charge to dissipate and the voltage drops almost completely. One of the biggest advantages today of DC discharges, is that it is a well understood process, allowing for a high control over the process and its different parameters.

The DC current can be driven through the system in a continuous manner, or it can be pulsed. For biomedical applications in general, there are two advantages in doing the latter: first of, higher discharge powers can be applied without the otherwise inevitable thermal damage caused by the heating of the electrodes and secondly, if used for the coating applications, it renders a more homogeneous coating. One of the main disadvantages of the DC driven systems is the direct exposure of the electrodes to the plasma environment, making them prone to corrosion if exposed to certain reactive monomers.

#### *2.2.3. Radiofrequency and microwave discharges*

Radiofrequency (RF) and microwave (MW) discharges are generated using high frequency electromagnetic fields [21-23]. RF discharges have a relatively wide frequency operating range between 1 – 100 MHz, but in most cases a fixed frequency of 13.56 MHz is applied. Concerning the operating pressure, a wider range, compared to DC systems, (1-103 Pa) is possible, but with the exception of a few, high-vacuum equipment is needed, which is expensive, drastically increases treatment times and are hard to implement in continuous production processes. For the treatment of biomedical materials, it is most likely the most applied discharge, as it is the plasma treatment technique of choice for the popular oxygen plasma treatments and several systems are commercially available.

Microwave discharges are operated at a higher frequency range, usually fixed at 2.45 GHz. The pressure range is more versatile compared to RF and DC discharges, with a range between 1 Pa and 105 Pa. Higher pressures lead in most cases to an increase of heat transfer from the electrodes to the substrate, making it a less than ideal situation for the treatment of textiles and nonwovens. This limitation results in the same treatment restrictions as the previously discussed discharges.

### *2.2.4. Atmospheric pressure plasma jets*

DBD set-ups have one major advantage compared to most other systems: the possibility to operate in a higher pressure range makes it possible to avoid extensive vacuum equipment. This results in a lower operating cost and faster treatment cycles, thus allowing them to be implemented in industrial surface modification processes. The low heat generation at elevated pressures allows for a wider range of applications, including plasma chemistry, grafting, polymerization, cleaning... These applications are not always as easily feasible in systems

It should be noted that occasionally in literature also the term corona discharge or corona treatment is used in connection with DBDs, although most authors prefer to use this term only

Non-thermal plasmas generated via a DC discharge are in most cases formed in a closed setup between two electrodes at very low pressures (10-1 – 10 pa) [21, 22]. As the current is increased, different types of discharges can be obtained. The Townsend discharge is a selfsustaining discharge, typically characterized by a low current. A higher current results in a drop of voltage and a glow discharge is generated. The glow discharge regime is the desired regime for surface modifications, as it guarantees a homogeneous treatment al throughout the reactor. Increasing the discharge current still further results in a fast increase of voltage until an arc is formed, allowing for the charge to dissipate and the voltage drops almost completely. One of the biggest advantages today of DC discharges, is that it is a well understood process,

The DC current can be driven through the system in a continuous manner, or it can be pulsed. For biomedical applications in general, there are two advantages in doing the latter: first of, higher discharge powers can be applied without the otherwise inevitable thermal damage caused by the heating of the electrodes and secondly, if used for the coating applications, it renders a more homogeneous coating. One of the main disadvantages of the DC driven systems is the direct exposure of the electrodes to the plasma environment, making them prone to

Radiofrequency (RF) and microwave (MW) discharges are generated using high frequency electromagnetic fields [21-23]. RF discharges have a relatively wide frequency operating range between 1 – 100 MHz, but in most cases a fixed frequency of 13.56 MHz is applied. Concerning

the exception of a few, high-vacuum equipment is needed, which is expensive, drastically increases treatment times and are hard to implement in continuous production processes. For the treatment of biomedical materials, it is most likely the most applied discharge, as it is the plasma treatment technique of choice for the popular oxygen plasma treatments and several

Pa) is possible, but with

for discharges between bare metal electrodes without dielectric.

allowing for a high control over the process and its different parameters.

the operating pressure, a wider range, compared to DC systems, (1-103

corrosion if exposed to certain reactive monomers.

*2.2.3. Radiofrequency and microwave discharges*

systems are commercially available.

powered with a different source.

*2.2.2. DC discharge*

120 Advances in Bioengineering

To finalize this chapter part on plasma technology, some special attention will be given to atmospheric pressure plasma jets (APPJ's). Operating a plasma in a confined space has certain advantages when it comes to the control of the physics and chemistry taking place, but sometimes there are cases where it would be more desirable if the plasma could be free from any geometrical confinements. APPJ's, also referred to as plasma plumes are an ideal solution and are excellent tools for the treatment of geometrically larger and more complex surfaces such as textile fibers [24].

APPJ's can be powered with any of the sources discussed before, but all deal with the same problem: how to avoid the transition from glow to arc. For DC sources this can either be achieved via the use of hollow cathode discharges with sub mm dimension or the use of resistive barrier discharges. For the DBD systems driven by high frequency AC sources, the dielectric barrier itself is the solution, as it prevents the discharge current to increase to the point of arcing. Under some special circumstances the DBD's can generate an uniform diffuse plasma that is filament free. For the RF powered APPJ, either a set-up similar to the DBD setup can be used, or the metal electrodes are left bare. For the latter, cooling of the electrodes is required, as well as an excellent control of the flow rate in order to minimise the risk of arcing [24]. Finally it is also possible to generate a plasma plume, using a microwaves to drive the plasma, but it is limited to a strict set of geometrical parameters which has been described in more detail by Park et al. [25].

It would be possible to give an extended description on the different set-ups available today, but it would lead to far out of the scope of this chapter. Laroussi and Akan already wrote a complete review on the different set-ups available. Also Shütze el al. wrote a compact review on the physics behind several set-ups [22]. Since that time also a number of commercial systems have become available on the market (crf Plasmatreat®, PlasmaSpot®, PlasmaStream®...). The applicability of the APPJ for the treatment of biomedical textile will be covered in the following chapter part 3: Plasma and textile: the biomedical applications.

#### **2.3. Plasma-material interactions**

In order to have an understanding of what is happening at the plasma-material interface, it is critical to have a basic knowledge about the possible effects the different active species have on a substrate exposed to them.

#### *2.3.1. Plasma cleaning and etching*

During the production process and storage of (bio)materials, they can be exposed to a number of solvents, greases, volatiles components etc. These contaminants will adsorb and accumulate on the material surface over time, resulting in an altered, non-reproducible surface with a likely reduced product performance. A typical example in the biomedical field, is the adsorption of low molecular weight carbon species onto a pristine titanium sample, when exposed to ambient air. When used as an implant material, this surface pollution results in a reduced cell adhesion, proliferation and growth and in some cases even results in cell death [26, 27].

Any volatile surface contamination that is exposed to a non-thermal plasma, will be removed in a few seconds [28]. Prolonged exposure to the plasma will not only result in the removal of the adsorbed contamination but will cause etching of the top layers of the material surface [29-32]. Depending on the density and hardness of the exposed material, more intense discharges and/or extended exposure are required to obtain a notable effect. As (biomedical) textiles are in most cases build out of relatively soft materials, the etching effect cannot be overseen and will introduce a certain nano-roughness on the fiber surface. For in-vitro and invivo applications this change in surface topography can have a benign effect, as it can amplify the other effects plasma has on cell adhesion and proliferation [33-35].

#### *2.3.2. Plasma activation*

Plasma activation or plasma treatment is the exposure of a surface to the reactive particles present in the plasma. This mixture of reactive particles will result in the incorporation of radical sites on the surface, up to the depth of a few 10 nm. Depending on the gas used to maintain the plasma, these sites will react (in)directly with other radicals present, recombining into a broad variety of functional groups. These new functional groups have a high impact on surface properties such as wettability and surface free energy, which in turn might have a positive effect on material-material and material-cell interactions.

In most cases an increase in hydrophilicity is pursued to enhance the materials histological performance. For some applications such as the surface of heart valves, the insides of needles and tubes or artificial stents, any adhesion of cells and proteins is highly unwanted, as it can lead to blockages resulting in premature failure of the biomedical device. Instead of using typical gas feeds for plasma treatment (noble gasses, oxygen, dry air, nitrogen...), fluorinated gasses such as CF4 are used which result in the formation of super hydrophobic surfaces with water contact angles of 150° and higher. These fluorinated surfaces prevent cells and proteins from effectively adhering on the surface and thus guaranteeing an optimal performance of the implant material [11, 36, 37].

Plasma activation is definitely not the only technique available for the introduction of new functional groups onto a surface, but as it is non-invasive and chemical-free, it guarantees the preservation of even the most delicate structures.

#### *2.3.3. Plasma grafting and polymerization*

Non-thermal plasmas are not only applied for plasma treatments, but can also be used as an initiation medium for radical polymerization, resulting in the deposition of a wide variety of thin films. In order to optimize the bonding between the thin film and the biomaterial, the deposition process is preceded by a plasma treatment, introducing radical sites that allow covalent bonding of the polymer to the substrate surface. The polymerization process itself can happen via two different reaction pathways: plasma polymer grafting simply uses the radical sites introduced via plasma treatment to initiate the chain reaction. In other words, during the polymerization process itself, no plasma is used and the monomer is not exposed to the plasma. This results in the incorporation of the monomer as such, thus preserving its functional groups.

For plasma polymerization this is not the case. The plasma is used as an initiation medium and remains active during the entire polymerization reaction. This has as a consequence that the monomer is exposed to the reactive plasma, forming initiation sites on both the substrate surface as well as on the monomer. In contrast to chemical initiation, plasma is not as specific as to where the radicals are formed, using any functional groups of the polymer precursor as well to initiate the chain reaction. This results in a highly cross-linked, pinhole free and completely amorphous thin film that significantly differs from its traditional counterpart and adheres to almost any surface. Varying the discharge power gives a high control over the amount of functionalities preserved in the film. From a biomedical viewpoint this is an interesting application, as functional group density plays a critical role in the growth and proliferation of cells and differs for the type of cells used.
