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WHITE PAPERS
PLASMA TREATMENT FOR MEDICAL DEVICE ASSEMBLY
April 7, 2006
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MOLL INDUSTRIES, INC. - SEAGROVE DIVISION
PLASMA TREATMENT FOR MEDICAL DEVICE ASSEMBLY
White Paper Report - April 7, 2006
The use of plasma technologies to enhance cell adhesion, protein binding and implants has become a dominant choice for medical device surface modi.cation. This diversifed technology allows designers and manufacturers to achieve increased wettability, hydrophobicity, biocompatibility, biofunctionlity and adhesion. Moll plasma processes treat an assortment of in vitro cell culture kits for various customers.
Ultra Purification
Plasma treatment removes organic surface contamination at a molecular level. Gas plasma also known as the 4th state of matter is created by a gas in a vacuum with an applied RF power across electrodes. Plasma treatment breaks covalent bonds and removes them with vacuum as volatile by-products. Organic contamination can compromise biocompatibility and surface properties for cell growth and adhesion.
 A Plasma Treatment Process at Moll Seagrove Division
Surface Activation and Adhesion Promotion
Plasma treatment has been shown to promote cell adhesion, often a prerequisite to cell growth which may not otherwise occur in harsh cell culture conditions. Plasma treatment can also typically increase wettability while etching the substrate surface (increasing Ra) for improved cellular functions such as proliferation, differentiation and adhesion. Many polymers such as Teflon, Polypropylene, PETG, PET, Polystyrene and Polyethylene have inherently hydrophobic surface properties. Oxygen and Nitrous Oxide plasma gases can create polar functional groups and etch the surface of the substrate improving wettability. Surface tension changes of 15 dynes/cm to >70 dynes/cm are not uncommon after plasma treatment for such materials.
Surface Modification Characterization
The challenge for designers and manufacturers that utilize plasma surface modification is that the desired surface properties can be achieved by an endless number of plasma process methods coupled with substrate choices. Cross-linking can be achieved with Argon gas plasma. Various monomers can also be converted to polymers and deposited for selective surface properties and etc. Adding to the above complexity, surface modification validation and quantitative analysis can be done with numerous methods all dependent on the specific needs of the application.
The molecular force interaction of the substrate surface and contact media is what is known as surface energy. The direct surface energy is measured with quantitative observational measurements such as wetting tension and contact angle. Wetting tension is the maximum liquid surface tension that will spread rather than bead up on the substrate surface and is reported in dynes/cm. In principle, if one were looking for hydrophilic or good wetting substrate properties, the substrate should have a higher surface tension (dynes/cm) than the applied liquid or contact media to overcome the molecular forces. For example, deionized water itself has a surface tension of 73 dynes/cm and would require a substrate surface tension of >72 dynes/cm to spread or wet out properly. One inexpensive way to measure substrate surface tension is with dyne test marker/pens. Dyne test pens can be purchased in an assortment of dyne/cm solution ranges and is typically accurate up to +/- 2 dynes/cm. This method works on the same principle as wetting tension. For example, if a 50 dyne/cm pen beads up on the surface of the substrate then a 52 dye/cm pen would be used next. This process is repeated until a pen rated at a certain surface tension flattens or wets-out. The first pen the wets-out would be your reported value in dyne/cm.
To make matters more confusing, contact angle is also widely reported within the surface modification industry instead of surface tension in dynes/cm. Although the scale for surface tension reported in dynes/cm and contact angle are roughly the same, the relationship for hydrophobicity is reversed. For results reported in contact angle surface energy, the lower the value, the more hydrophilic the substrate becomes. This relationship can be seen on figure 1. Figure 1 also shows typical changes in properties after materials go through plasma treatment. Surface energy reported in contact angle is based on Youg's equation and is measured on a Goniometer. A droplet of sterile water is placed on the substrate to be measured and either the water will form a drop or flatten on the substrate depending on the amount of interfacial surface energy between the liquid and the substrate. The profile of the drop is then photographed with a microscope and marked via instrument software. The contact angle of the droplet on the substrate is then calculated with Young's equation and is reported in degrees. This method is much accurate and precise when compared to the dyne marker/pen test. Depending on equipment expense, this method can also be used with different dyne/cm solutions and converted into dyne/cm reporting capabilities via instrument software.
Just as important as substrate surface tension, the liquid or contact media surface tension must be known to establish substrate performance and functionality. This is generally done with two methods, the du Noüy ring Tensiometer method and the Young-Laplace pendant drop Tensiometer method. The du Noüy method uses a calibrated ring to measure liquid interfacial surface tension and is reported in dynes/cm. The sample liquid is generally placed in a dish and the ring is immersed in the liquid. The ring is then slowly lifted until it breaks contact at the surface of the liquid. The point or moment it releases contact with the liquid is recorded as dynes/cm surface tension. The Young-Laplace pendant drop method analyzes a drop of liquid dispersed at the end of a syringe. The profile of the drop is then photographed with a microscope and marked via instrument software. The surface tension of the droplet is then calculated with the Young-Laplace equation and is reported in dynes/cm surface tension. The Young-Laplace pendant drop Tensiometer method is very accurate and can be performed at various temperatures and pressures.
Another critical but sometimes over looked measurement is substrate surface morphology or topography. Although plasma treatment can create polar hydrophilic functional groups at the surface of the substrate, it also etches the surface further enhancing wettability and cell adhesion. This substrate surface roughness measurement is referred to as "Ra" and can be reported in micron peaks with changes across the surface. The instrument itself is referred to as a Profilometer and utilizes a stylus that is dragged across the substrate surface. Depending on the expense of the equipment, it can show substrate topography in 3D with an average and range micron peak.
Substrate Plasma Modification Stability
Along with plasma treatment's diverse applications, its long term substrate stability is just as diverse. Generally, plasma processes that utilize cross-linking and deposition tend to be very stable over the shelf life of the product. Certain materials like Polystyrene and PVC with Oxygen plasma treatment also exhibit decent stability over time. Some materials like PETG and Teflon can with certain plasma gases have limited shelf life. Some of them are very extreme. It is well known in the electronics industry that some PCB processes that utilize plasma treatment only have a process window of 48 hours after plasma treatment (during work in progress).
Plasma treatment can exhibit some very unique phenomena. It has been shown that polar functional groups created by plasma treatment can migrate into the bulk of the substrate thus changing the surface tension and can be recovered to a degree after the substrate is soaked in water. The following results are of a PETG experiment conducted at Moll in which the samples were subjected to various environmental conditions over 60 days. The purpose of this study was to better understand the surface tension decay rate after plasma treatment due to the movement of polar groups from modified chains into the bulk of the polymer and environment. The migration of polar functional groups into the bulk can be measured by placing a decayed sample into an aqueous environment to draw it back to the surface (affinity to polar hydrophilic groups) and re-measure for contact angle. It also shows how PETG soaked in water can slow the decay rate down and preserve the PETG substrate. For each sample condition, three 2-inch samples were cut out of a PETG and measured for contact angle in subgroups of 5. The 15 measurements were then averaged for each condition. Figure 2 illustrates a comparison of samples that were kept in water vs. air. Figure 3 illustrates the recovery from the bulk in samples that were left in air for so days and then soaked in water for 5 days. The importance of such information is that if you have a cell culture device that is incubating it may recover some of it's characteristics during processing and extend its true shelf life.
Accelerated aging studies should be performed in parallel to real time shelf life validations on any substrate material that has been plasma treated. This can be accomplished using Von't Hoffs theory where for every 10 degrees Celsius there is a 2x change in chemical reaction. Figure 4 is an example of accelerated aging performed at Moll with plasma treated PVC. It is typically a good idea to perform this test three times at 45, 55, and 65 Celsius. This will enable the designer to gage the effects of storage conditions/limits over time. The following results were measured with a dyne test pen kit.
Although synthetic materials may improve manufacturability, cost, and durability, they can also create adverse physiological reactions. Many of the innovations made in medical device materials are attributed gas plasma surface modifications. It can promote biocompatibility, improve bond strength, render hydrophilic or hydrophobic, all without changing the desired bulk properties and strength of the material. It is also very cost effective and environmentally friendly when compared to other surface modification processes such as chemical.
Moll Industries is a full-service contract manufacturer of custom injection plastic molding. The company possesses extensive experience manufacturing Class 1, 2, & 3 Medical Device components and assemblies in conjunction with Validation & Verification studies, IQ-OQ-PQ protocols and requirements found in GMP 21 CFR - Part 820. Moll's operations also include Plasma Treatment and EMABOND® processes that augment core production technologies of value-added assembly, two-shot, insert molding, post mold decorating and over molding.
Article written by: Matthew Manges
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