Originally published January 1996
The issue of biostability has long been a critical concern for manufacturers of medical implants and surgical components. Products ranging from bone pins and prosthetic hardware to catheters, cardiac pacemakers, needles, medical probes, and various implants must be chemically inert for the protection of both the device and the patient. Lack of biostability in such materials, which come into direct and prolonged contact with body tissue, corrosive body fluids, electrolytes, proteins, enzymes, lipids, and so on, can result in serious substrate degradation and a potentially dangerous compromising of therapeutic efficacy.
In order to function properly and safely, medical components that are not intrinsically biostable must be protectively coated in a manner that does not adversely affect mechanical tolerances or other critical performance characteristics. Protective coating of a biomedical surface may be required for a number of reasons, including physical isolation from moisture, chemicals, and other substances; surface passivation; electrical insulation; tie-down of microscopic particles; and reduction of friction. One material currently used to protect a wide variety of mechanical devices is parylene, a vacuum-deposited polymer coating. Transparent and flexible, parylene meets the requirements of a USP Class VI plastic and can be applied as a film in layers as thin as 0.1 mil to provide pinhole-free and conformal coating, even on complex surfaces.
Traditional conformal coatings are solvent-based liquid resins such as epoxies, silicones, acrylics, and urethanes. Some liquid coatings are also available in 100%-solid form without solvents. However, all such materials exhibit liquid properties (pooling, meniscus, etc.) that may make them unsuitable for some medical coating applications. In addition, liquid coatings may not meet toxicity or biocompatibility requirements, and cannot be applied with precise process control.
Unlike conventional liquid coatings, parylene is applied by gas-phase polymerization to form a thin, transparent film of infinitely controllable thickness. The material's unique properties include absolute conformance to substrate topography, pinhole-free coverage even in very thin applications, and the ability to penetrate and coat complex geometries. When deposited as a conformal coating, parylene film resists chemical attack from organic solvents, inorganic reagents, and acids; adheres well to plastics, ceramics, glass, and metal; and offers dielectric strength above 5000 V dc per mil of coating thickness. For example, parylene-coated semiconductor devices have been shown to be operable after more than 300 days of complete immersion in saline solutions, with no change in measured input bias when compared with dry operation. Devices coated in this manner can be sterilized with steam, peracetic acid, EtO, or radiation.
The demands made on medical coatings vary greatly, depending on the form and function of the substrate; in most cases, these requirements cannot be met with conventional liquid coatings. For example, cannulae may require the application of dielectric insulation, whereas medical seals and catheters demand lubricity and inertness, and stents require biocompatible surface protection. For all these components, extremely consistent coating thickness is critical, and the coating must have as little impact as possible on component dimensions, durometer values, and physical/mechanical properties.
One important attribute of parylene for medical coatings is its superior dry-film lubricity, with static and dynamic coefficients of friction (in the range of 0.25 to 0.33 per ASTM D 1894) approaching those of Teflon. A typical application in this regard would be the coating of tiny lead wires, used inside flexible catheters, which must be electrically insulated, chemically protected, and capable of moving easily against the catheter surfaces in extremely tight quarters. Prosthetic components such as bone pins also benefit from the lubrication properties of parylene, and treatment of the screws and nuts used with temporary bone pins and plates can prevent seizing, corrosion, and metal fragmentation. In addition, parylene's hydrophobic and lubricious nature can minimize residual fluid buildup on both the inner and outer surfaces of needles and other medical components, thus aiding cleanup. The coating is especially effective in sealing the micropores of certain metals, which could otherwise trap and retain contaminants ranging from dust particles to bacteria.
BIOCOMPATIBILITY AND BIOSTABILITY
Parylene is a pure, crystal-clear, polycrystalline, and amorphous linear polymer that represents a viable option for medical coating applications because of its biocompatibility and biostability. Transparent parylene film is formed from a pure molecular precursor (a monomer gas), ensuring that the finished film has no contaminating inclusions. Because the conversion from monomeric gas to polymer film is direct, no solvents, plasticizers, catalysts, or accelerants are used. The resulting film has very low thrombogenic properties and low potential to trigger an immune response. Parylene has been shown to be highly resistant to the potentially damaging effects of corrosive body fluids, electrolytes, proteins, enzymes, and lipids. The film also forms an effective barrier against the passage of contaminants from a coated substrate to the body or surrounding environment.
Specialty Coating Systems maintains both drug and device master files with FDA for the parylene polymers. This information is available on request, and includes data on body-tissue and blood-compatibility studies carried out at the Battelle Memorial Institute, the University of North Carolina, Johns Hopkins Hospital, the University of California, Carnegie Mellon University, the University of Michigan, and other institutions. Experiments have also been conducted by the National Heart, Lung, and Blood Institute on parylene-coated fabrics used as linings for circulatory-assist devices. In vitro tissue-culture studies have shown that human cell types will readily proliferate on parylene-coated surfaces to produce thin, adherent layers of morphologically normal tissue. Successful in vivo cell-growth studies have been carried out in animals. In addition, deposition of a thin film of parylene over a toxic surface has been shown to render it atraumatic to cells. The polymer's minimal disturbance of cells growing in its vicinity can be ascribed to the high purity of the material and its ability to slow down impurity species that might otherwise diffuse out of a substrate. The parylene itself cannot be hydrolytically degraded, and it is also unaffected by corrosive biological environments.
Three different parylene feedstock materials produce distinct active species and resultant polymer films having differing desirable properties. There are two primary variants for medical conformal coating applications: parylene C and parylene N. The third, parylene D, is more suited to industrial use. All three begin as granular powdered material called dimer (di-para-xylylene). This dimer is converted under heat and vacuum to a gaseous polymerizing monomer that can be deposited on substrates at room temperature. Figure 1 shows the molecular structure of each parylene variant, and Table I lists the primary differences among parylenes C and N.
Parylene N has the smallest and most active molecule, which results in the greatest molecular activity during vacuum deposition and, consequently, the best crevice- penetration capability. This variant also has the lowest coefficient of friction, the lowest elongation, the best dielectric strength, and the lowest dissipation factor of the three primary parylenes. Its combination of properties makes parylene N the dimer of choice for applications requiring good crevice penetration; dry-film lubricating ability; complete, pinhole-free coverage in very thin layers (less than 0.5 mil or 10 µm); and suitability for use in high-frequency fields such as microwave circuits.
Because of its molecular activity in the monomer state, parylene N poses the greatest masking challenge. Care must be taken to prevent film deposition in areas that are to remain uncoated. This material requires the longest deposition dwell time, and has less thermal stability and chemical and moisture resistance than does parylene C.
As Figure 1 shows, parylene C has a single chlorine atom on the benzene ring. This structure gives parylene C polymer many of the useful properties of parylene N, along with certain advantages. For example, it creates the best moisture barrier of all the parylenes, and it can be deposited relatively quickly, with good thickness control. Its dielectric strength is slightly less than that of parylene N, as is its crevice-penetration ability. Dielectric losses are moderate, and chemical resistance is excellent. The most cost-effective of the three primary parylene dimers, parylene C is recommended when a good general combination of conformal coating properties is required, and particularly when a thicker film (greater than 0.5 mil) is desired.
Parylene D has two chlorine atoms on the benzene ring, making it the largest molecule and the one with the lowest crevice-penetration ability of the three parylenes. The D variant forms the hardest surface, undergoes the least elongation, and has the greatest temperature stability. This parylene form is used for industrial applications in which physical toughness, thermal stability, and chemical resistance are of primary importance.
The characteristics listed in Table I help define the rationale for selecting a particular parylene for medical substrate applications. To recapitulate, parylene N is generally selected when lubricity and high crevice penetration are of primary importance, whereas parylene C is appropriate to most other applications because of its moisture-barrier properties, low gas permeability, and strongest overall performance.
THE PARYLENE PROCESS
The critical conformal nature of parylene coating is related to the means by which it is applied. Parylene deposition takes place in a vacuum using a gas-phase process that converts a solid crystalline dimer--a granular powder--to a gaseous form, then to a stable monomeric gas, and finally to a polymer (see Figure 2). The powder is first vaporized at about 150°C in a 1.0-torr vacuum, with the resulting dimer gas then heated to approximately 680°C at 0.5 torr to yield the monomeric diradical para-xylylene. In the last step, the monomer gas enters an ambient-temperature deposition chamber where it is simultaneously adsorbed as it polymerizes on the substrate.
The mean free path of gas molecules in the deposition chamber is in the order of 0.1 cm, which means that--unlike processes such as vacuum metallizing--the deposition in not line-of-sight and thus all sides of an object to be encapsulated (including inside surfaces) are uniformly impinged by the gaseous monomer. Parylene C coating builds up at the rate of about 0.2 µm/min, with the other two versions accreting somewhat more slowly. The entire polymerization process is accomplished without solvent emissions, and because deposition occurs at ambient temperature, no thermal, mechanical, or chemical cure stresses are created. Unlike liquid coatings applied by spraying, dipping, or brushing, parylene does not pool, pull away from edges, bridge between adjacent surfaces, or exhibit meniscus forces. And because buildup is consistent and even, physical and electrical protection can be achieved with a substantially thinner layer of parylene as compared with resinous coatings, which often require heavier application to overcome coating imperfections. For example, MIL-SPEC-I-46058C for conformal coatings allows for parylene as thin as 0.5 mil, whereas liquid coatings must be applied between 1 and 3 mil thick.
Objects are prepared for parylene coating by cleaning to remove oils and other surface contaminants. Pretreatment with a multimolecular layer of organosilane for adhesion promotion enables parylene to be applied to virtually any vacuum-stable material. If a component is to be only partially coated, it must be masked with tape or Silastic material to prevent the film from covering electrical contacts, switches, or other surfaces that must remain uncoated. Fixturing can be used to support items in the vacuum chamber during coating. In some cases, fixtures also serve to mask selected substrate areas, thereby minimizing handling. Large quantities of small parts can often be tumble-coated in a rotating chamber, which eliminates the need for fixturing and ensures that all surfaces are covered evenly. Another advantage of the parylene coating process is that it can be adapted to meet the special needs of large or unusually shaped objects. For example, Specialty Coating Systems has constructed and operates a custom deposition chamber that allows complete one-step coating of catheters greater than 11 ft in length.
Following the parylene deposition cycle, objects are removed from fixtures, demasked, and inspected. Thickness is confirmed by measuring film on witness strips or slides that accompany each coating batch. Quality control steps in the process include monitoring of temperature and pressure variables during the deposition cycle, chemical analysis of the dimer, monitoring and filtration of the cleaning baths with mass spectroscopy, careful visual inspection of coated substrates for uniformity, verification of parylene cut-through resistance, and adhesion and dielectric testing of coated samples. Since there is no cure cycle with parylene, substrates are not subject to cure forces, solvents, liquid-phase effects, or elevated temperatures, and no testing is required to confirm that full cure has occurred. Because substrates are placed under vacuum prior to coating, any volatiles that might be present are extracted. Once the film is in place, the movement of higher-molecular-weight contaminants into or out of the substrate is greatly inhibited or prevented altogether, depending on the nature of the material being coated.
Most often, prospective medical products for parylene treatment are initially sent to a coating-service supplier to allow for performance testing and cost analysis. The manufacturer then has the option of either purchasing volume parylene services or installing and operating its own on-site coating system.
It is apparent that the parylene family of polymers will continue to find increased use in critical biomedical applications, for two primary reasons. The extreme inertness and purity of the end product make parylenes a logical choice for both functional and safety considerations. And the unique ability of these polymers to be formed from a molecular state ensures that the technology will be able to respond to the increasing complexity and ever-shrinking geometries of the medical device field.
Bruce Humphrey is manager of special projects at Specialty Coating Systems, Inc. (Clear Lake, WI), where he is involved in coordinating medical coating applications.