MANUFACTURING
Capabilities of the technology
Cleanliness, surface chemistry, topography and the physical nature of the surface all play an important role in efficient and reliable product performance. Plasma processing offers a clean and controlled way to modify surfaces and give the bulk materials enhanced properties.
One application area where it can provide advantages is drug delivery. The need to develop novel ways of drug delivery has led to slow drug release coatings on, for example, cardiovascular stents. There is also increasing interest in employing coatings in pulmonary drug delivery devices where affinity of drug to the delivery device may adversely affect the delivered dosage. Here, particle size and bulk density are carefully controlled to ensure the correct therapeutic dose deep into the lung. With particle sizes of <5 µm and the quest for higher potency drugs with submicron particle size, demands are put on the drug delivery device to administer and deliver an accurate dosage. This inevitably means eliminating the affinity of the drug to the materials the delivery device is made from, whether dry powder technology or liquefied media are used. Plasma processing offers a unique way of giving surfaces enhanced hydrophobicity, regardless of shape and therefore repellency.
One plasma processin-g technology for hydrophobicity utilises fluorocarbon (CxFy, where x and y are integers) chemistry. By choosing the correct gas or fluid precursor, surfaces with high fluorine concentration and CxFy chemical functionality can be prepared. With good process equipment geometry and design, processing temperatures close to room temperature can be employed for use on temperature-sensitive materials. For drug delivery devices, coatings and treatments with a fluorine to carbon (F:C) ratio of 1.3:1, stable dynamic contact angles of 140° can be achieved, which can result in high repellancy of drugs in contact with elastomers and polymers. With correct material plasma pretreatment, good stability and adhesion are maintained, which makes this type of surface modification treatment suitable for a range of medical device applications in addition to drug delivery. For example, linear low-density polyethylene can be readily treated to provide low friction materials for use in noninvasive cardiovascular treatments such as balloon angioplasty or urinary catheters treated for ease of insertion. Other potential areas include surgical instrument coating for low protein adhesion and ease of cleaning, and other short-term contact or implantable devices where biofilm build up needs to be minimised.
The plasma process
Plasmas are created by energising a gas in a controlled environment. For the fluorination processes described here, this is done in a vacuum chamber where parts to be treated are placed prior to evacuation of the chamber. The chamber is then backfilled with the chosen gas precursor to the desired working pressure (0.1–0.5 mbar) and energised using an electric field of direct current, radio frequency (RF) or microwave to form a nonequilibrium plasma. The films formed here utilise RF.
Nonequilibrium plasmas are often described as the fourth state of matter, that is, a fluid that is in a highly excited state containing excited atoms, meta-stable molecules, ions and electrons (as well as photons) at temperatures of several thousand degrees Kelvin. The process of surface modification operates at process temperatures that are controlled to be not much higher than room temperature, which makes the process suitable for polymers and other temperature-
sensitive materials.
A plasma contains a large concentration of free electrons and metastable particles that collide with, for example, a polymer surface placed in the plasma environment. The action of this bombardment breaks down covalent bonds creating free radicals on the substrate surface. Depending on the gas or precursor being used, these free radicals undergo reactions with the species of the plasma to produce surfaces with properties that are different from the bulk material, that is, more hydrophobic, hydrophilic or densely cross-linked by changing surface chemistry. If the precursor is nonreactive when ions of sufficient energy reach the surface material, removal or ablation is achieved. Combinations of film-forming and etching precursors can be adopted to achieve some interesting chemical modifications.
Important system features
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For the fluorocarbon polymerisation processes explained here, the plasma system employs a capacitive RF system with a rotating barrel configuration. The standard vacuum system has a cylindrical RF electrode and a barrel to tumble components through the plasma species (Figure 1). The equipment design and electrode geometry is changed depending on the coating requirements and part form. The design of RF plasma polymerisation equipment is critical to good process uniformity and hence repeatable coatings and medical device stability. Good process gas mixing (where more than one precursor is utilised), the geometric relationship between gas inlet and pumping ports, component stacking or packing density, electrode design, pressure and power control all play important roles in providing an efficient controllable process. Changing one parameter usually changes another to varying degrees. For example, changing the ratio of powered RF electrode area to earthed chamber area can significantly affect the density of ions in the plasma field and the rate and density of deposition. For higher energy species, the effects can result in a shift from polymerisation to etching and hence lower power levels are required to compensate, and visa versa. Gas pressure also affects polymerisation rate. Higher pressures can result in higher deposition rates and reduced density, thus a balance has to be achieved.
Fluorocarbon polymerisation process
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Table I. (click to enlarge) [5] Fluorine functionality of three different processes (P) determined by XPS.
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Fluorocarbons in plasma processes have been used in the semiconductor industry for many years for silicon wafer etching. Various chemistries have been utilised in the etching process (usually dissociated or broken down to form the plasma species with oxygen), including CF4, C2F6 and C3F6. When the oxygen is removed from the process, polymeric fluorocarbon films are deposited to varying degrees from these precursors. Deposition efficiency rises with increase in the molecular weight of the precursor and a decrease in its F:C ratio. In many cases, this makes CF4 redundant as an efficient polymerisation precursor, because of its high F content and mainly saturated species (CnF2n+2); these are not active and will not generally react with the surface to form a stable film.
The key to success is creating active unsaturated polymer species that subsequently adhere to the plasma-prepared surface to form film growth. CnF2n+2 precursors, where n is as high as 8 or 10, have been utilised in plasma deposition.
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Figure 2. (click to enlarge) [6] XPS high resolution spectra for alternative process.
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Film properties
The polymerised films that are produced after treatment with the fluorocarbon plasma process can be assessed in many ways. Thickness, contact angle, outermost chemical functionality and changes in properties when subjected to the intended environment all affect overall performance. The most common ways of assessing film chemical properties and performance are to routinely use X-ray photoelectron spectroscopy (XPS) for chemical functionality characterisation, secondary ion mass spectrometry (SIMS) for molecular speciation and chemical mapping (both surface and thickness) and dynamic contact angle for hydrophobicity performance.
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Figure 3. (click to enlarge) [7] Relationship between power, coating thickness and F:C ratio.
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For coatings with good performance, the F:C ratio needs to be in excess of 1.2:1 with all fluorine tied up or reacted as CFn functionality, which is determined by XPS. These properties can be readily determined by the process parameters and precursors employed, and the correct design and configuration of coating system. In many cases, substrate geometry influences the success of these surface properties. However, these influences are well understood and gas flow rates, pressure and power can be independently controlled to achieve repeatability on multiple geometries. Table I [5] shows XPS data from three different processes and the controlled variability in F:C ratio and change in CFn for desired properties. Figure 2 [6] shows typical XPS spectra obtained for a fluorination process, which is an alternative process that incorporates additional gas precursors.
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Figure 4. (click to enlarge) [8] Relationship between power, coating thickness and CF2 content.
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Figures 3 [7] and 4 [8] show the general trend for the relationship between processing power and F:C ratio, and power and CF2 content. In each case the treatment time is fixed. Optimised polymerisations in terms of hydrophobicity are found when deposition thickness (polymerisation rate) is greatest whilst maintaining high F:C and CF2 content, that is, at the cross over point observed on the graphs. The range of processes described allow stable dynamic contact angles of 133–145° and highly hydrophobic surfaces are formed. Figure 5 shows a SIMS image of a typical surface that is created. The magenta pixels indicate F and green general hydrocarbon, CxHy, from the underlying polymer substrate. The image shows uniform distribution on a sharp corner as a result of optimised process parameters. For higher powers, surface roughing effects usually take place and the contact angle is significantly reduced to, for example 90–98°, with similar outermost surface chemical properties. Lower powers often result in porous coatings with a similar effect on long-term hydrophobicity.
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Figure 5. SIMS image of fluorocarbon polymerisation (fluorine = magenta, CxHy from substrate = green).
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Application prospects
The implications for high potency drug delivery systems are great. With surfaces showing greater hydrophobicity compared with the parent bulk material, the affinity of certain dry-powder and liquid drug formulations to materials can be reduced. Advantages of the clean, solvent free, no waste process coupled with the fact that almost any substrate material can be modified, mean that the process is gaining wider usage in the medical device industry. This type of polymerised coating has wider reaching applications for other polymer devices where repellancy from the surface is required for increased performance. In addition, the coatings are showing good promise as barrier films where permeation issues are encountered and in treating soft silicones to reduce tack.
Dr Paul Stevenson is Managing Director of Innovatek Medical Ltd, Ty-Mawr Enterprise Park, Llysfaen, Colwyn Bay LL29 8UE, UK, tel. 1492 513 100, e-mail: paul@innovatekmedical.co.uk [9] www.innovatekmedical.co.uk [10]