or plasma physics. Also, some 100 investigators in the United States are pursuing similar endeavors. The research topics range from very fundamental mechanistic considerations to plasma technology, processing and applications. This work encompasses almost every field of engineering and science. To date, little has been reported on the application of plasma deposited polymers as a biomaterial. This paper summarizes the authors' bioapplications work which includes three main areas of plasma deposited polymers: (1) synthesis and characterization, (2) polymerization mechanisms and (3) applications.

When discussing biomedical applications, it is important to understand the differences between conventional linear polymers and those polymers formed in a plasma from the same monomers. For instance, conventional linear polymers, such as those derived from styrene, methyl methacrylate, vinyl acetate, and vinyl chloride, are produced by either free radical or ionic mechanisms. The resulting polymers consist of coiled chains having molecular weight distributions as low as two and as high as 10. When these polymers are placed in good thermodynamic solvents, they begin to swell and dissolve. Linear polymers can be melted and extruded and can also be made to decompose at fairly low temperatures. Outside of the normal branching found in most linear polymers, the repeat group is predictable.

By comparison, plasma polymers from the same monomers are formed by a multitude of mechanisms, all occurring simultaneously. The plasma deposited polymers are randomly branched, highly crosslinked, intertwined networks. The polymer resulting from formulation in the plasma is no longer soluble in good thermodynamic organic solvents.

Plasma deposited polymers are not even swollen. In fact, plasma polymers have been refluxed in boiling organic solvents for up to 7 days with only a 1-2 percent weight loss. Plasma deposited polymers do not melt, therefore cannot be extruded, but only decompose at comparatively higher temperatures. Also, plasma deposited polymers have shown. considerably higher chemical resistance to reducing or oxidizing environments. than conventional polymers. This resistance could be taken, at times, as inertness. Chiefly for the last two properties, minimal solubility and maximum chemical resistance, plasma deposited polymers deserve consideration as biomaterials.

2. Historical

A plasma was first defined by Langmuir in the early 1930's as a state a gas achieves when it is excited to the point of ionization. Plasma is more correctly defined as the region in which the active species are actually formed. Faraday and Crookes are perhaps the first to report observing a plasma glow. De la Rue and Muller reported a relationship

between pressure, the type of glow and the resistance of the gas in the discharge. Crookes stated in 1879 that a plasma was a fourth state of matter. C. T. R. Wilson reported in the early 1900's that the electrical conductivity of plasmas was due to ionization of gas molecules by collisions with themselves. In 1910 Dewar and Jones reported the first silent discharge from a DC discharge in an evacuated Wood's tube. The silent discharge operated at much lower temperatures and would prove to be much more useful in chemical synthesis [1].1

Shortly after plasmas were observed, fundamental studies of their behavior were carried out primarily by physicists with little regard for the chemical aspects or possible applications of these plasmas. De Wilde [2] and A. Thenard [3] in 1874 reported simultaneously that acetylene reacted readily in a silent discharge leaving no gaseous residue and forming a hard, brittle solid which was insoluble in common solvents. This was the first report of plasma polymerization; however, no effort was made to study the phenomenon beyond this point. At this point in the history of chemistry, polymers were considered to be undesirable byproducts and were of no interest.

The first and the oldest form of a plasma is the disruptive discharge, the arc and spark. These discharges produce very high temperatures since they operate with a high voltage source at either atmospheric or higher pressures. They are not useful in organic chemical synthesis since they operate at several thousand degrees Kelvin.

The other type of plasma is the silent plasma which operates in a vacuum and over a large temperature range which may be controlled by the power input to the plasma generator. There are five important types of the silent or nondisruptive discharge. The first is the glow discharge which is established in low pressure gases by low frequency rf applied across electrodes sealed into the reaction tube. Second is the electrodeless discharge which is formed by passing radio frequency current through a coil surrounding the tube. Third, the point discharges are established between conductive points operating at a high voltage, but arranged so as not to cause an arc. Fourth is the corona discharge which is similar to the point discharge except a fine wire is used in place of a conductive point. The fifth type is a variation of the corona and is widely used to produce ozone and thus is known as an

ozonizer.

Both the glow and electrodeless discharge can operate at rather high power levels and remain at essentially ambient temperatures. For this reason they are usually chosen for organic synthesis studies.

Plasma Mechanisms. The initial discharge occurs as a result of the free electrons being acceler

1 Figures in brackets indicate the literature references at the end of the paper.

ated in an electric field until they can cause the gas molecules to ionize. The electrons that are released as a result of this ionization are further accelerated and cause subsequent ionization. This type of chain reaction will soon cause the gas to become conductive; the current or flux in the gas rises and a discharge is started. An equilibrium is established almost immediately where rate of ion formation is equal to the rate of recombination of the species. For an example of these reactions, let us consider the possible reactions of molecule AB which can be given by the following equations:

Brinton's reactions terminated before polymer was formed; however, there seems to be no reason why eq (18) could not occur.

Investigations involving polymer plasma chemistry reported to date fall into two classifications: treatment of conventional polymer films in a plasma [6, 7] and actual polymerization of monomers using the plasma as an initiator [8-11].

Hanson et al. [12], reported that when several polymers (polyethylenes) were treated in a mild oxygen plasma, the bulk properties of the polymers were unaltered as the penetration was restricted to the first few hundred Angstroms of the films. In other cases surface ablation of the polymers was reported. With alkane polymers a highly oxidized surface was created which had vastly improved wettability characteristics. Hanson and Schonhorn [13] reported that treatment of polymer films of polyethylene and teflon in an oxygen plasma increased their adhesion properties. Weininger [14, 15] studied the effect of active nitrogen on polyethylene and polypropylene and found increased cross-linking and increased unsaturation resulting from the treatment. Hollahan, Stafford, Balk and Payne [16] reported that amino acid groups could be attached to polymer surfaces by treating the films with nitrogen and hydrogen plasmas. Bazzarree and Lin [17] treated fiberglas filaments with various vinyl type monomers (vinyltriacetoxysilane and vinyltriethoxysilane) in an attempt to increase their tensile strengths.

Shaw polymerized a silicone oil on the surface of small electronic devices and produced an im

permeable, insulating, thin film. He used a medium power four megahertz capacitively-coupled plasma [18]. Ozawa [19] employed plasma polymerization techniques using styrene and tetrafluoroethylene to make thin film insulators for micro capacitors. He used an alternating current (low frequency) electrode discharge plasma in a long glass tube. He found a more uniform coating was formed when the substrates to be coated were placed away from the electrodes in the plasma glow. Mearns [20] published a review which includes the use of plasma polymerization in the production of thin insulating films.

Some work with vinyl type monomers has been reported. Goodman [21] described the formation of uniform thin (0.1 to 2 μm) polymer films with a plasma from a high voltage alternating current discharge between two parallel plates. Some of the monomers used were styrene, methyl methacrylate, tetrafluoroethylene, monochlorotrifluoroethylene, and difluoroethylene as well as some nonvinyl compounds such as benzene, toluene, and chlorodifluoromethane. Williams and Hayes [22] also reported the flow discharge polymerization of several vinyl type monomers. Denaro, Owens, and Crawshaw [23] investigated the flow discharge polymerization of styrene. This is the more comprehensive plasma polymerization study reported.

The initial work summarized above led to many investigations both basic and applied. The following investigations represent only those which interface the work of the authors and, thus, are not to be considered as a comprehensive list. Several books [24-26] and one general review [27] related to plasma chemistry have been published. Suhr [28] and Stille, [30-31] among others, have investigated some basic organic synthesis using plasmas. Other investigations have looked into oxidation [32] and decomposition [33-36] of various materials in plasmas. A number of investigators have looked into the polymerization aspects of plasma chemistry [37-44]. Others have looked at specifics in the polymeric films which are usually produced [45, 46]. Some specific applications of these films have recently begun to appear in the literature [47-49]. The authors and others [50] have been investigating acceptability of the plasma-deposited polymeric films to biomedical applications.

3. Plasma Reaction Procedures

Before discussing some of the specifics of biomaterials work with the plasma polymers, the actual physical and chemical processes involved in their formation should be described in general terms. Figures 1 and 2 show block diagrams of the reactor system. Figure 3 is a photograph showing one of our more refined reactor systems where basic studies are performed. Figure 4 shows a low cost reactor which was designed and constructed in our laboratories to be utilized in the applications research.

The reactors can all be characterized simply as glass tubes wrapped with a copper coil which serves to direct the incident rf power into the tube volume. One end of the reactor contains the inlet system which is one or more leak valves. The other end is connected to a cold trap and then to a vacuum system. The electronics for the rf power are a straightforward application of conventional ham radio parts.

The first step in the process involves consideration of the type of substrate to be either coated, cleaned, or converted. Substrate preparation and cleaning procedures used vary considerably with the type of material to be coated. The cleaning procedures may vary from rinsing with residue free solvents to chemical etching followed by thorough distilled water rinses. In some cases we have resorted to ESCA and Auger spectroscopy to determine the effectiveness of overall surface preparation prior to deposition of plasma polymer films with regard to resulting film adhesion. An example would be a glass substrate. The structure of the cleaned glass substrate and subsequent adherence of the plasma polymer is a function of the chemical composition of the glass. Each material (metals, ceramic, polymer) presents its own unique problems which must be worked out for each application. After the samples to be coated have been cleaned, care is taken not to contaminate the surface through improper storage or handling.

power level than for polymerization, it is possible, in many instances, to obtain additional substrate cleaning through the interactions of the ionized gas and the substrate. Similar treatments have also been effective in removing impurities from the surfaces of implant devices. This interaction step can be a prelude to sterilization. At this point the monomeric gas of choice can be introduced simultaneously with the inert gas flow or the inert gas can be discontinued and simply replaced with monomeric gas. The pressure and power are adjusted to their final values, respectively, by setting the leak valves and tuning and matching the rf transmitter and load.

The coating process then proceeds until the desired thickness of material is obtained. Relatively pure polymer films with thicknesses of 0.5 to 10 μm can be formed effectively by this means. These films, as will be noted in part 2, have little or no tissue reactions. Any tissue reactions which may occur can be assigned to the polymer structure itself and not to the impurities present in most conventional polymer systems. This assignment can be made because it is inherent to this coating process that all monomers enter the reactor as gases. Thus, the gases can be considered to be essentially purified by their being distilled away from any initiators, catalysts, or inhibitors which normally appear as contaminants in the product. Also, no sensitizers, initiators or catalysts are needed in the reaction.

The total time for deposition can vary from 15 minutes to 12 hours. The rate of polymer deposition is largely dependent on the power input to the load coil, the effective concentration of the monomer gas or gases and reactivity of the particular monomer involved. After polymerization, the reactor is returned to atmospheric pressure by slowly introducing the desired terminating gas.

Recent work in the authors' laboratories has shown that an alternate embodiment of the above procedure can also lead to useful polymer films. After proper cleaning, the substrate is coated with a thin film of a nonvolatile low molecular weight polymer or a nonvolatile high molecular weight monomer where both are generally in the form of a liquid. After evacuation of the reaction vessel, a nonpolymerizing gas is introduced into and excited in the rf field through proper adjustment of the reaction parameters. The liquid film is converted to a solid insoluble polymer having properties similar to those contained in the gas phase deposition. Several interesting systems have been developed through this special synthesis technique.

Other related work has been completed recently which involves linear polymer film interactions with plasmas. Both plasmas of polymerizable and nonpolymerizable gases were used. In both cases, the result is that the surface of the linear polymer film is converted to material similar to that obtained in the previously discussed liquid phase-plasma interactions.