Field of the Invention

The present invention relates to coated medical devices and to methods for coating those devices. The coating is biocompatible, non-biodegradable and inhibits formation of biofilms thereon.

Background to the Invention

Biofilm formation is a well-known phenomenon in which cells of a microorganism stick to each other and form a film on a surface.

Biofilm formation is a particular problem when it occurs on the surface of medical devices which are inserted or implanted in patients, such as catheters, respirators, artificial cardiovascular implants, prosthetic joints, gynaecological devices, cosmetic implants, devices used in surgery and contact lenses. That is because bacteria, such as Staphylococcus

epidermidis, which are present in the biofilm can cause infections when the biofilm comes into contact with patient.

The problem is particular acute with medical devices which are implanted into patients and become indwelling. Even if the medical device is free from biofilm prior to implantation, there is tendency for Staphylococcus epidermidis present on the skin of the patient to colonise the surface of the medical device such that a biofilm forms. It is thought that around two thirds of the biofilm formation on indwelling devices is caused by Staphylococcus epidermidis.

Biofilms are a leading cause of nosocomial infections, and thus create a significant burden on healthcare systems worldwide due to the additional costs involved in treating patients who have contracted infections. Bacteria in biofilms are highly resistant to antibiotic treatment, which, in combination with the increasing prevalence of antibiotic resistance among human pathogens, makes the treatment of biofilm-related infections difficult.

It would therefore be beneficial to coat the surfaces of medical devices with coatings that inhibit the formation of biofilms, but are also biocompatible, such that the medical devices can be safely inserted or implanted into patients and biofilm-related infections are reduced. Summary of the Invention

The present inventors have surprisingly found that organosilicon compounds can be deposited by plasma deposition to provide multi-layer coatings that provide high levels of resistance to biofilm formation. The coatings are biocompatible, and are thus suitable for implantation or insertion into patients. These properties mean that the coatings can be used to coat medical devices, and thereby reduce the risk of biofilm-related infections occurring when the medical devices are implanted or inserted into patients. This finding means that the prevalence of nosocomial infections could potentially be reduced, which would be beneficial for patients and would result in significant savings in healthcare costs. It is also a finding of the present invention that if the first layer of the of the multi-layer coating, which is in contact with the at least one surface of the medical device, is organic, then the multi-layer coating will adhere well to the surface of the medical device. This means that it is generally not necessary to perform a separate pre- or post-treatment step to improve adhesion of the coating to surface of the medical device.

Accordingly, the present invention provides a medical device suitable for insertion or implantation in a patient, said medical device having a multi-layer coating on at least one surface of the medical device, wherein:

each layer of the multi-layer coating is obtainable by plasma deposition of a precursor mixture comprising (a) one or more organosilicon compounds, (b) optionally O2, N2O, NO2, ¾, NH3, N ₂ , S1F4 and/or hexafluoropropylene (HFP), (c) optionally He, Ar and/or Kr, and (d) optionally silver, gold, titanium, platinum and/or palladium; and

the first/lowest layer of the multi-layer coating, which is in contact with the at least one surface of the medical device, is organic.

The invention further provides a method for reducing biofilm formation on at least one surface of a medical device suitable for insertion or implantation in a patient, which method comprises depositing a multi-layer coating of the invention as defined herein onto the at least one surface by plasma deposition.

The invention further provides use of a multi-layer coating of the invention as defined herein to reduce biofilm formation on a surface of a medical device suitable for insertion or implantation in a patient. Brief Description of the Figures

Figures 1 to 3 show cross sections through preferred examples of multi-layer coatings of the invention.

Figure 4 shows the Fourier transform infrared (FTIR) spectrum for the coating prepared in Example 1.

Figure 5 shows the FTIR spectrum for the coating prepared in Example 3.

Figure 6 shows the results from Example 5, in which combs were coated with various multi-layer coatings and then tested for electrical resistance using a liquid (deionised water) drop test. These results demonstrate the ability of the multi-layer coatings tested to resist degradation caused by water. These tests were accelerated tests in which the components were biased at 5V; to assess the barrier properties of the coatings and the adhesion of the coatings to the surface.

Detailed Description of the Invention

The present invention is concerned a medical device suitable for insertion or implantation in a patient. The medical device has a multi-layer coating on at least one surface of the medical device. The multi-layer coating is produced by plasma deposition, and is both biocompatible and capable of inhibiting, and thereby preventing, formation of a biofilm thereon.

Medical devices

The medical devices that are coated according to the present invention are suitable for insertion or implantation in patients. Any medical device that is suitable for insertion or implantation in patients can be conveniently coated according to the methods described herein. Some non-exhaustive examples of suitable medical devices include hearing aid components, catheters, respirators, artificial cardiovascular implants, prosthetic joints, bone implants, gynaecological devices, cosmetic implants, devices used in surgery (such as scalpels) and contact lenses.

At least one surface of the medical device is coated with a multi-layer coating as herein defined. Typically, the at least one surface of the medical device is a surface that comes into contact with the patient when that medical device is inserted or implanted into the patient. For devices that are implanted and thus become indwelling, the at least one surface of the medical device is typically a surface that is in contact with the patient when the device is in situ. These surfaces are those that are most at risk of biofilm formation, and so the multi-layer coating of the invention can act to prevent or reduce the risk of biofilm formation on those surfaces.

Preferably all surfaces of the medical device that comes into contact with the patient when that medical device is inserted or implanted into the patient are coated with the multi-layer coating of the invention. For medical devices that are implanted and thus become indwelling, it is preferred that all surfaces that are in contact with the patient when the medical device is in situ are coated with the multi-layer coating of the invention. Thus, for a medical device suitable for implantation, it is particular preferred that all surfaces that comes into contact with the patient when the medical device implanted and all surfaces that are in contact with the patient when the medical device is in situ are coated with the multi-layer coating of the invention. A surface that is contact with the patient is typically a surface that touches, or is exposed to, tissues or fluids in the patient.

The multi-layer coating

The multi-layer coating of the invention comprises multiple layers, each of which is obtainable by plasma deposition of organosilicon compounds. The organosilicon compound(s) can be deposited in the presence or absence of reactive gases and/or non-reactive gases. The resulting layers deposited have general formula SiO _x HyCzF _a NbMc , wherein the values of x, y, z, a, b and c depend upon (a) the specific organosilicon compound(s) used, (b) the specific metal containing co-precursor(s) used, (c) whether or not a reactive gas is present and the identify of that reactive gas, and (d) whether or not a non-reactive gas is present, and the identify of that non-reactive gas. For example, if no fluorine or nitrogen is present in the organosilicon compound(s) and a reactive gas containing fluorine or nitrogen is not used, then the values of a and b will be 0. As will be discussed in further detail below, the values of x, y, z, a and b can be tuned by selecting appropriate organosilicon compound(s) and/or reactive gases, and the properties of each layer and the overall coating controlled accordingly. In formula

SiOxHyCzFaN Mc, M represents silver, gold, titanium, platinum and/or palladium, which can optionally be incorporated into the coating. The value of c will be 0 when metal is omitted, and can be tuned by, for example, by varying the amount of metal precursor/co-precursor(s) present in the precursor mixture used for plasma deposition.

For the avoidance of doubt, it will be appreciated that each layer of the multi-layer coating of the invention may have organic or inorganic character, depending upon the exact precursor mixture, despite the organic nature of the precursor mixtures used to form those layers. In an organic layer of general formula SiO _x HyCzF _a NbMc, the values of y and z will be greater than zero, whereas in an inorganic layer of general formula SiO _x HyCzF _a NbMc the values of y and z will tend towards zero. The organic nature of a layer can easily be determined by a skilled person using routine analytical techniques, such as by detecting the presence of carbon-hydrogen and/or carbon-carbon bonds using spectroscopic techniques well known to those skilled in the art. For example, carbon-hydrogen bonds can be detected using Fourier transform infrared spectroscopy. Similarly, the inorganic nature of a layer can easily be determined by a skilled person using routine analytical techniques, such as by detecting the absence of carbon-hydrogen and/or carbon-carbon bonds using spectroscopic techniques well known to those skilled in the art. For example, the absence of carbon-hydrogen bonds can be assessed using Fourier transform infrared spectroscopy.

Plasma deposition process

The layers present in the multi-layer coatings of the invention are obtainable by plasma deposition, typically plasma enhanced chemical vapour deposition (PECVD) or plasma enhanced physical vapour deposition (PEPVD), preferably PECVD, of a precursor mixture. The plasma deposition process is typically carried out at a reduced pressure, typically 0.001 to 10 mbar, preferably 0.01 to 1 mbar, for example about 0.7 mbar. The deposition reactions occur in situ on the surface of the medical device, or on the surface of layers that have already been deposited.

Plasma deposition is typically carried out in a reactor that generates plasma which comprises ionized and neutral feed gases/precursors, ions, electrons, atoms, radicals and/or other plasma generated neutral species. A reactor typically comprises a chamber, a vacuum system, and one or more energy sources, although any suitable type of reactor configured to generate plasma may be used. The energy source may include any suitable device configured to convert one or more gases to a plasma. Preferably the energy source comprises a heater, radio frequency (RF) generator, and/or microwave generator.

Plasma deposition results in a unique class of materials which cannot be prepared using other techniques. Plasma deposited materials have a highly disordered structure and are generally highly cross-linked, contain random branching and retain some reactive sites. These chemical and physical distinctions are well known and are described, for example in Plasma Polymer Films, Hynek Biederman, Imperial College Press 2004 and Principles of Plasma Discharges and Materials Processing, 2 ^nd Edition, Michael A. Lieberman, Alan J. Lichtenberg, Wiley 2005.

Typically, the medical device to which the multi-layer coating is to be applied is placed in the chamber of a reactor and a vacuum system is used to pump the chamber down to pressures in the range of 10 ^"3 to 10 mbar. One or more gases is typically then injected (at controlled flow rate) into the chamber and an energy source generates a stable gas plasma. One or more precursor compounds is typically then be introduced, as gases and/or vapours, into the plasma phase in the chamber. Alternatively, the precursor compound may be introduced first, with the stable gas plasma generated second. When introduced into the plasma phase, the precursor compounds are typically decomposed (and/or ionized) to generate a range of active species (i.e. radicals) in the plasma that is deposited onto and forms a layer on the exposed surface of the medical device.

The exact nature and composition of the material deposited typically depends on one or more of the following conditions (i) the plasma gas selected; (ii) the particular precursor compound(s) used; (iii) the amount of precursor compound(s) [which may be determined by the combination of the pressure of precursor compound(s), the flow rate and the manner of gas injection]; (iv) the ratio of precursor compound(s); (v) the sequence of precursor compound(s); (vi) the plasma pressure; (vii) the plasma drive frequency; (viii) the power pulse and the pulse width timing; (ix) the coating time; (x) the plasma power (including the peak and/or average plasma power); (xi) the chamber electrode arrangement; (xii) temperature and bias voltage control on the electrodes; and/or (xiii) the preparation of the incoming assembly.

Typically the plasma drive frequency is 50 Hz to 4 GHz. Typically the plasma power density is 0.001 to 50 W/cm ² , preferably 0.01 W/cm ² to 0.02 W/cm ² , for example about 0.0175 W/cm ² . Typically the mass flow rate is 5 to 1000 seem, preferably 5 to 20 seem, for example about 10 seem. Typically the operating pressure is 0.001 to 10 mbar, preferably 0.01 to 1 mbar, for example about 0.7 mbar. Typically the coating time is 10 seconds to > 60 minutes, for example 10 seconds to 60 minutes.

Plasma processing can be easily scaled up, by using a larger plasma chamber. However, as a skilled person will appreciate, the preferred conditions will be dependent on the size and geometry of the plasma chamber. Thus, depending on the specific plasma chamber that is being used, it may be beneficial for the skilled person to modify the operating conditions.

It is an advantageous feature of the plasma deposition processes used in the invention that the properties of the individual layers, and those of the multi-layer coating, can be modified (for example to optimise adhesion, hydrophobicity/hydrophilicity, oleophobicity or hardness) by selecting an appropriate precursor mixture, as discussed in further detail below. This means that pre-treatment steps (of the medical device prior to coating) or post-treatment steps (of each layer and/or of the entire coating after deposition) are thus not necessary in order to achieve the desired properties. Pre- and post-treatment steps that have previously been used with the aim of improving the properties of coatings include plasma treatment with gases such as 0 ₂ , O3, NH3, NO, NO2, N2O or N2O4, or with liquids such as H2O2 or H2O, in the absence of precursor compound that will actually be deposited (i.e. in the case of the present invention the one or more organosilicon compounds) onto the substrate.

Precursor compounds

The multi-layer coatings of the invention comprise layers which are obtainable by plasma deposition of a precursor mixture. The precursor mixture comprises one or more organosilicon compounds, and optionally further comprises a reactive gas (such as O2) and/or a non-reactive gas (such as Ar). The resulting layers deposited have general formula SiO _x HyCzF _a NbMc, wherein the values of x, y, z, a and b depend upon (i) the specific organosilicon compound(s) used, and (ii) whether or not a reactive gas is present and the identify of that reactive gas.

Typically the precursor mixture consists, or consists essentially, of the one or more organosilicon compounds, the optional reactive gas(es) and the optional non-reactive gas(es). As used herein, the term "consists essentially of refers to a precursor mixture comprising the components of which it consists essentially as well as other components, provided that the other components do not materially affect the essential characteristics of the resulting layer formed from the precursor mixture. Typically, a precursor mixture consisting essentially of certain components will contain greater than or equal to 95 wt% of those components, preferably greater than or equal to 99 wt% of those components.

When the one or more organosilicon compounds are plasma deposited in the absence of an excess of oxygen and nitrogen-containing reactive gas (such as N¾, 0 ₂ , N2O or NO2), the resulting layer will be organic in nature and will be of general formula SiO _x HyCzF _a NbMc. The values of y and z will be greater than 0. The values of x, a and b will be greater than 0 if O, F or N is present in the precursor mixture, either as part of the organosilicon compound(s) or as a reactive gas.

When the one or more organosilicon compounds are plasma deposited in the presence of oxygen-containing reactive gas (such as O2 or N2O or NO2), the hydrocarbon moieties in the organosilicon precursor react with the oxygen-containing reactive gas to form CO2 and H2O. This will increase the inorganic nature of the resulting layer. If sufficient oxygen-containing reactive gas is present, all of the hydrocarbon moieties maybe removed, such that resulting layer is substantially inorganic/ceramic in nature (in which in the general formula SiO _x HyCzF _a Nb, y, z, a and b will have negligible values tending to zero). The hydrogen content can be reduced further by increasing RF power density and decreasing plasma pressure, thus enhancing the oxidation process and leading to a dense inorganic layer (in which in the general formula SiOxHyCzFaN , x is as high as 2 with y, z, a and b will have negligible values tending to zero).

Typically, the precursor mixture comprises one organosilicon compound, but it may be desirable under some circumstances to use two or more different organosilicon compounds, for example two, three or four different organosilicon compounds.

Typically, the organosilicon compound is an organosiloxane, an organosilane, a nitrogen- containing organosilicon compound such as a silazane or an aminosilane, or a halogen- containing organosilicon compound such as a halogen-containing organosilane. The

organosilicon compound may be linear or cyclic.

The organosilicon compound may be a compound of formula (I): wherein each of Ri to Rs independently represents a d-Ce alkyl group, a C2-C6 alkenyl group or hydrogen, provided that at least one of Ri to Rs does not represent hydrogen. Preferably, each of Ri to Rs independently represents a C1-C3 alkyl group, a C2-C4 alkenyl group or hydrogen, for example methyl, ethyl, vinyl, allyl or hydrogen, provided that at least one of Ri to Rs does not represent hydrogen. Preferably at least two or three, for example four, five or six, of Ri to Rs do not represent hydrogen. Preferred examples include hexamethyldisiloxane (HMDSO), tetramethyldisiloxane (TMDSO), 1,3-divinyltetramethyldisiloxane (DVTMDSO) and hexavinyldisiloxane (HVDSO). Hexamethyldisiloxane (HMDSO) and tetramethyldisiloxane (TMDSO) are particularly preferred, with hexamethyldisiloxane (HMDSO) most preferred.

Alternatively, the organosilicon compound may be a compound of formula (II):

wherein each of R7 to Rio independently represents a Ci-C ₆ alkyl group, a Ci-C ₆ alkoxy group, a C2-C6 alkenyl group, hydrogen, or a -(CH2)i-4NR'R" group in which R' and R" independently represent a Ci-C ₆ alkyl group, provided that at least one of R7 to Rio does not represent hydrogen. Preferably each of R7 to Rio independently represents a C1-C3 alkyl group, C1-C3 alkoxy group, a C2-C4 alkenyl group, hydrogen or a -(CH2)2-3NR'R" group in which R' and R" independently represent a methyl or ethyl group, for example methyl, ethyl, isopropyl, methoxy, ethoxy, vinyl, allyl, hydrogen or -CH2CH2CH2N(CH2CH3)2, provided that at least one of R7 to Rio does not represent hydrogen. Preferably at least two, for example three or four, of R7 to Rio do not represent hydrogen. Preferred examples include allyltrimethylsilane,

allyltrimethoxysilane (ATMOS), tetraethylorthosilicate (TEOS), 3 -(diethylamino) propyl- trimethoxysilane, trimethylsilane (TMS) and triisopropylsilane (TiPS).

Alternatively, the organosilicon compound may be a cyclic compound of formula (III):

(III) wherein n represents 3 or 4, and each of Rn and R12 each independently represents a Ci-Ce alkyl group, a C2-C6 alkenyl group or hydrogen, provided that at least one of Rn and R12 does not represent hydrogen. Preferably, each of Rn and R12 independently represents a C1-C3 alkyl group, a C2-C4 alkenyl group or hydrogen, for example methyl, ethyl, vinyl, allyl or hydrogen, provided that at least one of Rn and R12 does not represent hydrogen. Preferred examples include trivinyl-trimethyl-cyclotrisiloxane (V3D3), tetravinyl-tetramethyl-cyclotetrasiloxane (V4D4), tetramethylcyclotetrasiloxane (TMCS) and octamethylcyclotetrasiloxane (OMCTS).

Alternatively, the organosilicon compound may be a compound of formula (IV):

(IV) wherein each of Xi to X ₆ independently represents a Ci-C ₆ alkyl group, a C2-C6 alkenyl group or hydrogen, provided that at least one of Xi to X ₆ does not represent hydrogen. Preferably each of

Xi to X ₆ independently represents a C1-C3 alkyl group, a C2-C4 alkenyl group or hydrogen, for example methyl, ethyl, vinyl, allyl or hydrogen, provided that at least one of Xi to X ₆ does not represent hydrogen. Preferably at least two or three, for example four, five or six, of Xi to X ₆ do not represent hydrogen. A preferred example is hexamethyldisilazane (HMDSN).

Alternatively, the organosilicon compound may be a cyclic compound of formula (V):

(V) wherein m represents 3 or 4, and each of X ₇ and Xs independently represents a Ci-C ₆ alkyl group, a C2-C6 alkenyl group or hydrogen, provided that at least one of X ₇ and Xs does not represent hydrogen. Preferably, each of X ₇ and Xs independently represents a C1-C3 alkyl group, a C2-C4 alkenyl group or hydrogen, for example methyl, ethyl, vinyl, allyl or hydrogen, provided that at least one of X ₇ and Xs does not represent hydrogen. A preferred example is 2,4,6- trimethyl-2,4,6-trivinylcyclotrisilazane.

Alternatively, the organosilicon compound may be a compound of formula (VI):

H _a (X ⁹ )bSl(N(X ¹⁰ ) ₂ )4-a-b

(VI) wherein X ⁹ and X ¹⁰ independently represent Ci-C ₆ alkyl groups, a represents 0, 1 or 2, b represents 1 , 2 or 3, and the sum of a and b is 1 , 2 or 3. Typically, X ⁹ and X ¹⁰ represent a C1-C3 alkyl group, for example methyl or ethyl. Preferred examples are dimethylamino-trimethylsilane (DMATMS), bis(dimethylamino)dimethylsilane (BDMADMS) and

tris(dimethylamino)methylsilane (TDMAMS).

Alternatively, the organosilicon compound may be a compound of formula (VII):

(VII) wherein each of Yi to Y ₄ independently represents a Ci-Cs haloalkyl group, a Ci-C ₆ alkyl group, Ci-C ₆ alkoxy group, or a C2-C6 alkenyl group or hydrogen, provided that at least one of Yi to Y ₄ represents a Ci-Cs haloalkyl group. Preferably, each of Yi to Y ₄ independently represents a Ci- C3 alkyl group, C1-C3 alkoxy group, a C2-C4 alkenyl group or a Ci-Cs haloalkyl group, for example methyl, ethyl, methoxy, ethoxy, vinyl, allyl, trifluoromethyl or 1H,1H,2H,2H- perfluorooctyl, provided that at least one of Yi to Y ₄ represents a haloalkyl group. Preferred examples are trimethyl(trifluoromethyl)silane and lH,lH,2H,2H-perfluorooctyltriethoxysilane.

Preferably the organosilicon compound is hexamethyldisiloxane (HMDSO),

tetramethyldisiloxane (TMDSO), 1,3-divinyltetramethyldisiloxane (DVTMDSO),

hexavinyldisiloxane (HVDSO allyltrimethylsilane, allyltrimethoxysilane (ATMOS),

tetraethylorthosilicate (TEOS), 3-(diethylamino)propyl-trimethoxysilane, trimethylsilane (TMS), triisopropylsilane (TiPS), trivinyl-trimethyl-cyclotrisiloxane (V3D3), tetravinyl-tetramethyl- cyclotetrasiloxane (V4D4), tetramethylcyclotetrasiloxane (TMCS), octamethylcyclotetrasiloxane (OMCTS), hexamethyldisilazane (HMDSN), 2,4,6-trimethyl-2,4,6-trivinylcyclotrisilazane, dimethylamino-trimethylsilane (DMATMS), bis(dimethylamino)dimethylsilane, (BDMADMS), tris(dimethylamino)methylsilane (TDMAMS), trimethyl(trifluoromethyl)silane or 1H,1H,2H,2H- perfluorooctyltriethoxysilane. Hexamethyldisiloxane (HMDSO) and tetramethyldisiloxane (TMDSO) are particularly preferred, with hexamethyldisiloxane (HMDSO) most preferred.

As used herein, the term Ci-C ₆ alkyl embraces a linear or branched hydrocarbon groups having 1 to 6, preferably 1 to 3 carbon atoms. Examples include methyl, ethyl, n-propyl and i- propyl, butyl, pentyl and hexyl.

As used herein, the term C2-C6 alkenyl embraces a linear or branched hydrocarbon groups having 2 or 6 carbon atoms, preferably 2 to 4 carbon atoms, and a carbon-carbon double bond. Preferred examples include vinyl and allyl. As used herein, a halogen is typically chlorine, fluorine, bromine or iodine and is preferably chlorine, bromine or fluorine, most preferably fluorine.

As used herein, the term Ci-C ₆ haloalkyl embraces a said Ci-C ₆ alkyl substituted by one or more said halogen atoms. Typically, it is substituted by 1, 2 or 3 said halogen atoms.

Particularly preferred haloalkyl groups are -CF3 and -CCI3.

As used herein, the term Ci-C ₆ alkoxy group is a said alkyl group which is attached to an oxygen atom. Preferred examples include methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, tert-butoxy, pentoxy and hexoxy.

The precursor mixture optionally further comprises a reactive gas. The reactive gas is selected from O2, N2O, NO2, ¾, NH3, N ₂ , S1F4 and/or hexafluoropropylene (HFP). These reactive gases are generally involved chemically in the plasma deposition mechanism, and so can be considered to be co-precursors.

O2, N2O and NO2 are oxygen-containing co-precursors, and are typically added in order to increase the inorganic character of the resulting layer deposited. This process is discussed above. N2O and NO2 are also nitrogen-containing co-precursors, and are typically added in order to increase additionally the nitrogen content of the resulting layer deposited (and consequently the value of b in the general formula SiO _x HyCzF _a Nb is increased).

H2 is a reducing co-precursor, and is typically added in order to reduce the oxygen content (and consequently the value of x in the general formula SiO _x HyCzF _a Nb) of the resulting layer deposited. Under such reducing conditions, the carbon and hydrogen are also generally removed from the resulting layer deposited (and consequently the values of y and z in the general formula SiOxHyCzFaNb are also reduced). Addition of H2 as a co-precursor increases the level of cross-linking in the resulting layer deposited.

N2 is a nitrogen-containing co-precursor, and is typically added in order to increase the nitrogen content of the resulting layer deposited (and consequently the value of b in the general formula SiO _x HyCzF _a Nb is increased).

NH3 is also a nitrogen-containing co-precursor, and so is typically added in order to increase the nitrogen content of the resulting layer deposited (and consequently the value of b in the general formula SiO _x H _y CzF _a Nb is increased). However, NH3 additionally has reducing properties. As with the addition of ¾, this means that when NH3 is used as a co-precursor, oxygen, carbon and hydrogen are generally removed from the resulting layer deposited (and consequently the values of x, y and z in the general formula SiOxH _y CzF _a Nb are reduced).

Addition of N¾ as a co-precursor increases the level of cross-linking in the resulting layer deposited. The resulting layer tends towards a silicon nitride structure.

S1F4 and hexafluoropropylene (HFP) are fluorine-containing co-precursors, and typically added in order to increase the fluorine content of the resulting layer deposited (and consequently the value of a in the general formula SiO _x HyCzF _a Nb is increased).

A skilled person can easily adjust the ratio of reactive gas to organosilicon compound(s) at any applied power density, in order to achieve the desired modification of the resulting layer deposited.

The precursor mixture also optionally further comprises a non-reactive gas. The non- reactive gas is He, Ar or Kr. The non-reactive gas is not involved chemically in the plasma deposition mechanism, but does generally influence the physical properties of the resulting material. For example, addition of He, Ar or Kr will generally increase the density of the resulting layer, and thus its hardness. Addition of He, Ar or Kr also increases cross-linking of the resulting deposited material.

The precursor mixture also optionally further comprises silver, gold, titanium, platinum and/or palladium. When these metals are present in the precursor mixture, the resulting layer deposited will contain the metal. This is desirable because these metals are known to have antimicrobial and anti-bacterial properties, and can thus enhance the ability of the coatings of the invention to inhibit biofilm formation. The silver, gold, titanium, platinum and/or palladium is typically present in precursor mixture as a complex or co-precursor, preferably as a co-precursor, such as trimethylphosphine- (hexafluoroacetylacetonato) silver(I), 2,2-dimethyl-6, 6,7,7,8, 8- heptafluorooctane-3,5-dionato)silver(I)triethylphosphine, Dimethyl(acetylacetonate)gold(III), Dimethyl(trifluoroacetylacetonate)gold(III), Titanium(IV) isopropoxide,

Tetrakis(dimethylamido)titanium(IV), Trimethyl(methylcyclopentadienyl)platinum(IV), or Pd(hfac)2 (wherein hfac is hexafluoroacetylacetonate).

The preferred metals for inclusion in the precursor mixture are silver and/or gold, with silver most preferred. As will be discussed in further detail below, it is generally preferred that silver, gold, titanium, platinum and/or palladium are only present in the precursor mixture used to produce the uppermost layer of the multi-layer coating, and are absent from the precursor mixtures used to form other layers of the multi-layer coating.

Structure and properties of the multi-layer coating

The multi-layer coating of the invention comprises at least two layers. The first, or lowest layer, in the multi-layer coating is in contact with the surface of the medical device. The final, or uppermost layer, in the multi-layer coating is in contact with the environment. When the multi-layer coating comprises more than two layers, then those additional layers will be located between the first/lowest and final/uppermost layers.

Typically, the multi-layer coating comprises from two to ten layers. Thus, the multilayer coating may have two, three, four, five, six, seven, eight, nine or ten layers. Preferably, the multi-layer coating has from two to eight layers, for example from two to six layers, or from three to seven layers, or from four to eight layers.

The boundary between each layer may be discrete or graded. In a multi-layer coating that has more than two layers, each boundary between layers may be either discrete or graded. Thus, all of the boundaries may be discrete, or all of the boundaries may be graded, or there may be both discrete and graded boundaries with the coating.

A graded boundary between two layers can be achieved by switching gradually over time during the plasma deposition process from the precursor mixture required to form the first of the two layers to the precursor mixture required to form the second of the two layers. The thickness of the graded region between the two layers can be adjusted by altering the time period over which the switch from the first precursor mixture to the second precursor mixture occurs. Under some circumstances graded boundaries can be advantageous, as the adhesion between layers is generally increased by a graded boundary.

A discrete boundary between two layers can be achieved by switching immediately during the plasma deposition process from the precursor mixture required to form the first of the two layers to the precursor mixture required to form the second of the two layers.

Different layers are deposited by varying the precursor mixture and/or the plasma deposition conditions in order to obtain layers which have the desired properties. The properties of each individual layer are selected such that the resulting multi-layer coating has the desired properties.

Generally, all layers of the multi-layer coatings of the invention are obtainable by plasma deposition of precursor mixtures as herein defined which contain one or more organosilicon compounds. Thus, the multi-layer coatings of the invention preferably do not contain other layers which are not obtainable by plasma deposition of precursor mixtures as herein defined, such as layers of organosilicon compound formed by non-plasma methods such as dipping.

Properties of first/lowest layer

It is generally desirable for the multi-layer coating to show excellent adhesion, both to the surface of the medical device and between layers within the coating. This is desirable so that the multi-layer coating is robust during use. Adhesion can be tested using tests known to those skilled in the art, such as a Scotch tape test or a scratch adhesion test or Rockwell C indentation test as prescribed under VDI 3198 norms (Verein Deutscher Ingenieure Normen, VDI 3198, VDI-Verlag, Dusseldorf, 1991).

It is preferable, therefore, that the first/lowest layer of the multi-layer coating, which is in contact with the surface of the medical device, is formed from a precursor mixture that results in a layer that adheres well to the surface of that medical device. The exact precursor mixture that is required will depend upon the specific material(s) from which the surface of the medical device is made, and a skilled person will be able to adjust the precursor mixture accordingly. It is a finding of the present invention that layers which are organic in character adhere well to the surfaces of medical devices. A layer with organic character can be achieved by using a precursor mixture that contains no, or substantially no, oxygen-containing reactive gas (i.e. no, or substantially no, or 0 ₂ , N2O or NO2). It is thus preferable that the first/lowest layer of the multilayer coating is deposited using a precursor mixture that contains no, or substantially no, O2, N2O or N0 ₂ .

As used herein, the reference to a precursor mixture containing "substantially no" specified component(s) refers to a precursor mixture that may contain trace amounts of the specified component(s), provided that the specified component(s) do not materially affect the essential characteristics of the resulting layer formed from the precursor mixture. Typically, therefore a precursor mixture that contains substantially no specified component(s) contains less than 5 wt% of the specified component(s), preferably less than 1 wt% of the specified component(s), most preferably less than 0.1 wt% of the specified component(s).

Layers which contain no, or substantially no, fluorine also typically adhere well to the surface of the substrate. A layer which contains no, or substantially no, fluorine can be achieved by using a precursor mixture that contains no, or substantially no, fluorine-containing

organosilicon compound and no, or substantially no, fluorine-containing reactive gas (ie. no, or substantially no, SiF ₄ or HFP). It is thus preferable that the first/lowest layer of the multi-layer coating is deposited using a precursor mixture that contains no, or substantially no, fluorine- containing organosilicon compound, SiF ₄ or HFP.

Accordingly, it is particularly preferred that the first/lowest layer of the multi-layer coating is deposited using a precursor mixture that contains no, or substantially no, O2, N2O, NO2, fluorine-containing organosilicon compound, SiF ₄ or HFP. The resulting coating will be organic in character and contain no fluorine, and so will adhere well to the surface of the medical device.

The first/lowest layer of the multi-layer coating typically does not contain any silver, gold, titanium, platinum or palladium. That is because the anti-microbial properties of these metals are not required for the first/lowest layer of the multi-layer coating. The first/lowest layer of the multi-layer coating is therefore typically deposited using a precursor mixture that contains no, or substantially no, silver, gold, titanium, platinum and/or palladium.

It is also generally desirable for the first/lowest layer of the multi-layer coating to be capable of absorbing any residual moisture present on the surface of the medical device prior to deposition of the coating. The first/lowest layer will then generally retain the residual moisture within the coating, and thereby reduce the nucleation of corrosion and erosion sites on the surface of the medical device.

The adhesion of coating on substrate is very important for medical devices, be it implantable medical devices or surgical devices. The integrity of coating on substrate is important to avoid malfunction/biofouling, and further any delamination may potentially be life- threatening for a patient. The adhesion of the coatings of the invention is typically assessed using VDI 3198, where adhesion of at least HF2 is preferable. It is an advantageous feature of the multi-layer coatings of the invention that the excellent adhesion of the first/lowest layer, which is organic, to the surface of the medical device, and also the excellent adhesion between layers within the multi-layer coating, means that it is generally not necessary to perform either a pre-treatment step (before deposition of the coating) or a post- treatment step (after deposition of the coating) in order to achieve acceptable levels of adhesion.

Properties of the final/uppermost layer

The final/uppermost layer of the multi-layer coating, that is to say the layer that is exposed to and/or comes into contact with the patient during implantation, insertion and/or indwelling, is biocompatible and inhibits formation of biofilms thereon.

The ability of the final/uppermost layer of the multi-layer coating to inhibit formation of biofilms thereon can generally be increased by inclusion of silver, gold, titanium, platinum and/or palladium in the layer. This can be achieved by including silver, gold, titanium, platinum and/or palladium, typically present in the precursor mixture that is used to produce the final/uppermost layer of the multi-layer coating as a complex or co-precursor or mixture thereof. It is thus preferable that the final/uppermost layer of the multi-layer coating is deposited using a precursor mixture that contains silver, gold, titanium, platinum and/or palladium.

It is also desirable that the final/uppermost layer of the multi-layer coating has anti- fouling and anti-corrosive properties in general, in addition to the specific ability to inhibit formation of biofilms. For the Si-based material in the present invention, a layer with organic character will typically show high levels of anti-fouling and anti-corrosive properties. Typically, therefore, the final/uppermost layer of the multi-layer coating is organic. Organic character can be achieved by using a precursor mixture that contains no, or substantially no, oxygen-containing reactive gas (i.e. no, or substantially no, or 0 ₂ , N2O or NO2). It is thus preferable that the final/uppermost layer of the multi-layer coating is deposited using a precursor mixture that contains no, or substantially no, O2, N2O or NO2. The pre-cursor mixture may optionally contain a halogen-containing organosilicon compound, S1F4 and/or HFP, thereby increasing the fluorine- content of the layer, which typically further increases anti-fouling and anti-corrosive properties.

It is also generally desirable for the final/uppermost layer of the multi-layer coating to be hydrophobic. Hydrophobicity can be determined by measuring the water contact angle (WCA) using standard techniques. Typically, the WCA of the final/uppermost layer of the multi-layer coating is >90°, preferably from 95° to 115°, more preferably from 100° to 110°.

The hydrophobicity of a layer can be modified by adjusting the precursor mixture. For example, a layer which has organic character will generally be hydrophobic. As noted above, a layer with organic character can be achieved, for example, by using a precursor mixture that contains no, or substantially no, oxygen -containing reactive gas (i.e. no, or substantially no, or 0 ₂ , N2O or NO2). As discussed above, if an oxygen-containing gas is present a significant amount in the precursor mixture, the organic character and thus hydrophobicity of the resulting layer will be reduced. It is thus preferable that the final/uppermost layer of the multi-layer coating is deposited using a precursor mixture that contains no, or substantially no, O2, N2O or N0 ₂ .

The hydrophobicity of a layer can also be increased by using a halogen-containing organosilicon compound, such as the compounds of formula VII defined above. With such a precursor, the resulting layer will contain halogen atoms and will generally be hydrophobic. Halogen atoms can also be introduced by including S1F4 or HFP as a reactive gas in the precursor mixture, which will result in the inclusion of fluorine in the resulting layer. It is thus preferable that the final/uppermost layer of the multi-layer coating is deposited using a precursor mixture that comprises a halogen-containing organosilicon compound, S1F4 and/or HFP, typically in addition to the components discussed above for achieving organic character.

It is also generally desirable for the final/uppermost layer of the multi-layer coating to be oleophobic. Generally, a layer that is hydrophobic will also be oloephobic. This is particularly the case for fluorine-containing coatings. Thus, if the water contact angle (WCA) of the final/uppermost layer of the multi-layer coating is greater than 100°, then the coating will be oleophobic. A WCA of greater than 105° is preferred for increased oleophobic properties.

It is also generally desirable for the final/uppermost layer of the multi-layer coating to have a nanohardness of at least 1.0 GPa and reduced Young's modulus of at least 3GPa.

Hardness and the Young's modulus can be measured by nanohardness tester techniques known to those skilled in the art. The hardness of a layer can be modified by adjusting the precursor mixture, for example to include a non-reactive gas such as He, Ar and/or Kr. This results in a layer which is denser and thus harder. It is thus preferably that the final/uppermost layer of the multi-layer coating is deposited using a precursor mixture that comprises He, Ar and/or Kr.

It is also possible to adjust the hardness by modifying the plasma deposition conditions. Thus, reducing the pressure at which deposition occurs generally results in a layer which is denser and thus harder. Increasing the RF power generally results in a layer which is denser and thus harder. These conditions and/or the precursor mixture can be readily adjusted to achieve a desired hardness as set out above.

Moisture barrier properties

It is desirable for the multi-layer coating to act as a moisture barrier, so that fluids (for example those that will come into contact with the medical device when it is inserted or implanted into a patient) cannot breach the coating and damage the underlying medical device. The moisture barrier properties of the multi-layer coating can be assessed by measuring the water vapour transmission rate (WVTR) using standard techniques, such as a MOCON test. Typically, the WVTR of the multi-layer coating is from 10 g/m ² /day down to 0.001 g/m ² /day.

Typically, the moisture barrier properties of the multi-layer coating may be enhanced by inclusion of at least one layer which has a WVTR of from 0.5 g/m ² /day down to 0.1 g/m ² /day. This moisture barrier layer is typically not the first/lowest or final/uppermost layer of the multilayer coating. Several moisture barrier layers may be present in the multi-layer coating, each of which may have the same or different composition.

Generally, layers which are substantially inorganic in character and contain very little carbon are the most effective moisture barriers. Such layers can be obtained by, for example, plasma deposition of a precursor mixture that comprises an organosilicon compound and an oxygen-containing reactive gas (ie. 0 ₂ , N2O or NO2). Addition of a non-reactive gases such as He, Ar or Kr, use of a high RF power density and/or reducing the plasma pressure will also assist in forming a layer with good moisture barrier properties.

It is therefore preferred that at least one layer of the multi-layer coating is obtainable by plasma deposition of a precursor mixture comprising an organosilicon compound and O2, N2O and/or NO2, and preferably also He, Ar and/or Kr. Preferably the precursor mixture consists, or consists essentially, of these components. A layer containing nitrogen atoms will also typically have desirable moisture barrier properties. Such a layer can be obtained by using a nitrogen-containing organosilicon compound, typically a silazane or aminosilane precursor, such as the compounds of formula (IV) to (VI) defined above. Nitrogen atoms can also be introduced by including N ₂ , NO2, N2O or NH3 as a reactive gas in the precursor mixture. Preferably the precursor mixture consists, or consists essentially, of these components.

It is therefore also preferred that at least one layer of the multi-layer coating is obtainable by plasma deposition of a precursor mixture comprising a nitrogen-containing organosilicon compound, N ₂ , NO2, N2O and/or NH3. Preferably the precursor mixture consists, or consists essentially, of these components.

Other properties

The thickness of the multi-layer coating is typically from 20 nm to 2000 nm, for example from 100 nm to 500 nm, or from 200 nm to 400 nm.

The thickness of each layer within the multi-layer coating of the present invention will depend upon the number of layers that are deposited, and overall thickness of the multi-layer coating. Each layer with the multilayer coating may have the same, or approximately the same, thickness. Alternatively, it may desirable under some circumstances for one or more of the layer to be thicker than one or more of the other layers.

The thickness of each layer can be easily controlled by a skilled person. Plasma processes deposit a material at a uniform rate for a given set of conditions, and thus the thickness of a layer is proportional to the deposition time. Accordingly, once the rate of deposition has been determined, a layer with a specific thickness can be deposited by controlling the duration of deposition.

The thickness of the multi-layer coating and each constituent layer may be substantially uniform or may vary from point to point, but is preferably substantially uniform.

Thickness may be measured using techniques known to those skilled in the art, such as a profilometry, reflectometry or spectroscopic ellipsometry.

Adhesion between layers of the multi-layer coating can be improved, where necessary, by introducing a graded boundary between layers, as discussed above. Graded boundaries are particularly preferred for layers which contain fluorine, since these tend to exhibit poor adhesion. Thus, if a given layer contains fluorine, it preferably has a graded boundary with the adjacent layer(s).

Alternatively, where necessary, discrete layers within the multi-layer coating can be chosen such that they adhere well to the adjacent layers within the coating.

The properties of the multi-layer coatings of the invention

The multi-layer coatings of the invention inhibit the formation of biofilms, and are thus able to prevent or reduce the formation of biofilms on medical devices. The ability of the multilayer coatings of the invention to inhibit the formation of biofilms can easily be assessed using in vitro techniques well known to those of skill in the art. Staphylococcus epidermidis is generally used in these techniques, because it is generally considered representative of the bacteria involve in formation of biofilms. The biofilm inhibiting nature of the coatings of the invention is preferably studied in vitro via both static and chemostat (continuous flow) biofilm formation systems. Static biofilm formation system is particularly useful for examination of the early stages of biofilm formation, including initial adherence to the surface and microcolony formation. The chemostat system is useful to simulate in-vivo like situations.

The multi-layer coatings of the invention are biocompatible. This means that they are non-toxic and do not cause adverse or injurious effects when the come into contact with a patient during implantation of insertion, or subsequently during indwelling. The nature of the required biocompatibility for the coating will depend on the device. For example, devices coming in direct contact with the blood are tested for blood compatibility, eg., for hemolysis, haemolytic toxicity, etc. Other tests to assess to assess biocompatibility include genotoxilcology, irritation and cytotoxicity. The tests are generally performed following the relevant device standards.

Detailed Description of the Figures

Aspects of the invention will now be described with reference to the embodiment shown in Figures 1 to 3, in which like reference numerals refer to the same or similar components.

Figure 1 shows a cross section through a preferred example of the multi-layer coating 2 of the invention. The multi-layer coating 2 has a first/lowest layer 3 which is in contact with surface of medical device 1, and a final/uppermost layer 4. This multi-layer coating 2 has two layers 3 and 4, and the boundary between the layers 3 and 4 is discrete.

Figure 2 shows a cross section through another preferred example of the multi-layer coating 2. The multi-layer coating 2 has a first/lowest layer 3 which is in contact with surface of medical device 1, and a final/uppermost layer 4. Between layers 3 and 4 are two further layers 5 and 6. This multi-layer coating 2 has four layers 3, 4, 5, and 6, and the boundary between the layers 3, 4, 5, and 6 is discrete.

Figure 3 shows a cross section through another preferred example of the multi-layer coating 2. The multi-layer coating 2 has a first/lowest layer 3 which is in contact with the surface of medical device 1, and a final/uppermost layer 4. This multi-layer coating 2 has two layers 3 and 4, and the boundary 7 between layers 3 and 4 is graded.

Examples

Aspects of the invention will now be described with reference to the Examples below.

Example 1 - deposition of a single SiO _x C _y H _z layer with He as co-precursor

A substrate was placed into a plasma-enhanced chemical vapour deposition (PECVD) chamber, and the pressure was then brought to < 10 ^"3 mbar. He gas was injected at a flow rate resulting in a chamber pressure of 0.480 mbar, then it was increased (by means of a throttle valve) to 0.50 mbar. Plasma was ignited at RF power density of 0.573W cm ^"2 for 3-5 seconds. Next, HMDSO was injected into the chamber at a flow rate of 6 seem and RF power density was at 0.225, 0.382, 0.573 or 0.637 Wcm ^"2 for 20 minutes. Pressure was kept (through a throttle valve) at 0.5 mbar during the deposition process. Polymeric organosilicon SiO _x C _y H _z layers were obtained on the substrate. The FT-IR transmission spectra for the layer obtained using an RF power density of 0.637 Wcm ^"2 is shown in Figure 4.

The SiOxCyHz layers showed hydrophobic character with a WCA (water contact angle) of

~ 100°.

Layers deposited at 0.637 Wcm ^"2 as described were tested for chemical resistance against organic solvents [namely isopropyl alcohol (IPA) and acetone] and aqueous acid and basic solutions. The acid solutions were aqueous HC1 solutions with the following pHs: 6; 5; 4; 3; 2; and 1. The basic solutions were aqueous NaOH with the following pHs: 8; 9; 10; 11; 12; and 13.

The layers were wiped first with the above-mentioned solvents and solutions by rubbing a cotton bud (wet with the solvents/solutions) on the surface of the layer. The layers were secondly immersed in the above-mentioned solvents and solutions. In both tests, the layers did not show any signs of delamination, scratching or damage.

Example 2 - deposition of single SiO _x C _y H _z layer with Ar as co-precursor

A substrate was placed into a plasma-enhanced chemical vapour deposition (PECVD) chamber, and the pressure was then brought to ~ 10 ^"2 mbar. Ar and HMDSO were injected at flow rate of 20 seem each, and pressure was let stabilize. RF plasma (with a RF power density of 0.057 W · cm ^"2 ) was then ignited resulting in a process pressure of ~ 0.14 mbar. After 5 min of coating process, by keeping plasma on, and without breaking vacuum, HMDSO flow rate was stopped and the deposited coating was exposed to an Ar plasma for 30 sec (at a flow rate of 15 seem in this step). After these 30 sec, always without breaking the vacuum, the Ar flow rate was brought to 20 seem and HMDSO injected at a flow rate of 20 seem. This procedure was repeated for 5 time, except for the last 5 min coating step which didn't end to be exposed to Ar plasma. The total deposition process time was of 32.5 min.

The SiOxCyHz layer showed hydrophobic character with a WCA of - 104°. The

SiOxCyHz layer was tested for chemical resistance (IPA and Acetone) as described in Example 1, and again passed both tests. The SiO _x C _y H _z layer mechanical properties were also tested by means of pencil hardness test, showing a scratch hardness of HB-F and a gouge hardness of 2H measured with a Mitsubishi UM Pressure Proofed Hi-Density Lead pencil according to D 3363 - 00 standard.

Example 3 - deposition of single SiO _x H _z layer

A substrate was placed into a PECVD deposition chamber, and the pressure was then brought to < 10 ^"3 mbar. Against this base pressure, 0 ₂ was inject up to 0.250 mbar of chamber pressure. After that, He was injected in order to reach a chamber pressure of 0.280 mbar. Finally, HMDSO was injected at a flow rate of 2.5 seem and pressure was increased (by means of throttle valve) to 0.300 mbar. Plasma was then ignited with a power density of 0.892 Wcm ^"2 and the process was continued until the desired thickness of approximate 750 nm was achieved.

A SiOxHz layer was obtained with FT-IR transmission spectrum as shown in Figure 5. The SiOxHz layer showed hydrophilic character with a WCA ~ 50°.

The SiOxHz layers were tested for chemical resistance as described in Example 1, and again passed both tests.

Example 4 - deposition of SiO _x C _y H _z / SiO _x H _z multilayer

The experimental conditions leading to the PECVD deposition of the SiO _x C _y H _z / SiO _x H _z multilayers on substrates were basically the same as described in Examples 1 and 3. Briefly, SiOxCyHz was deposited with the same procedure explained in Example 1 (RF power density used for this experiment was 0.637 Wcm ^"2 ), then chamber was brought to vacuum (< 10 ^"3 mbar) and the deposition of SiO _x H _z , on top of the SiO _x C _y H _z layer, was performed according to the procedure explained in Example 3. Then, a second SiO _x C _y H _z layer was deposited on top of the SiOxHz layer. The thickness of the second SiO _x C _y H _z layer was half that of the first SiO _x C _y H _z layer. This was achieved by halving the deposition time. These steps resulted in multilayer coating with the structure: SiO _x C _y Hz/ SiO _x H _z /SiO _x C _y H _z .

The process was then repeated on some substrates in order to add a second pair of SiOxCyHz/SiOxHz layer, thereby giving the structure: SiO _x C _y Hz/ SiO _x H _z /SiOxC _y Hz/SiOxH _z

/SiOxCyHz.

Both multilayers were tested for chemical resistance as described in Example 1, and again passed both tests. Example 5 - assessment of properties of coatings

Coatings were deposited onto combs (a type of electrical component) under the conditions set out below.

1. Deposition conditions for SiO _x coating

Against a base pressure of 10 ^"3 mbar, 0 ₂ was inject up to 0.250 mbar of chamber pressure. After that, He was injected in order to reach a chamber pressure of 0.280 mbar.

HMDSO was added at flow rate of 2.5 seem. Pressure was set to 0.280 mbar. Plasma was ignited at a power density of 0.892 Wcm ^"2 .

2. Deposition conditions for SiOx yHz coating

Against a base pressure of 10 ^"3 mbar, He was injected at a flow rate resulting in a chamber pressure of 0.480 mbar, then the pressure was increased (by means of a throttle valve) to 0.50 mbar. Plasma was ignited at RF power density of 0.573 Wcm ^"2 for 3-5 seconds. Next, HMDSO was injected into the chamber at a flow rate of 6 seem together and RF power density of 0.637 Wcm ^"2 .

3. Deposition conditions for SiOJ _y H _z / SiO _x coating

An SiOxCyHz layer was deposited as described in paragraph 2 above. Then the deposition chamber was evacuated and the SiO _x layer was deposited on top of the SiO _x C _y H _z layer as described in paragraph 1 above.

4. Deposition conditions for SiOxC _y H _z / SiO _x / SiO _x C _y H _z coating

An SiOxCyHz layer was deposited as described in paragraph 2 above. Then the deposition chamber was evacuated and the SiO _x coating was deposited on top of the SiO _x C _y H _z layer with the same conditions as described in paragraph 1 above (except for the fact that HMDSO and He mixture was injected and RF plasma was ignited directly at a power density of 0.637 Wcm ^"2 ). Finally, the deposition chamber was evacuated and a second SiO _x C _y H _z layer was deposited on top of the SiOx layer with the conditions described in paragraph 2 above. 5. Deposition ofSiOxCyH. /SiOMyCM / SiOj yH,/ SiOJiyCM / SiO _x C _y H _z coating

The SiOxCyHz layers were deposited by mixing 17.5 seem of HMDSO with 20 seem of Ar at a RF power density of 0.057 Wcm ^"2 , while the SiOxHyCzNb layers were deposited by mixing 17.5 seem of HMDSO with 15 seem of N ₂ 0 at a RF power density of 0.057 Wcm ^"2 .

6. Deposition conditions for SiOxHyCzFa layer

A SiOx yHzFa layer was deposited by mixing 17.5 seem of HMDSO with 20 seem of HPF at a RF power density of 0.057 Wcm ^"2 .

The coated combs were then tested as follows. Water was placed on the coated combs and power was then applied across the poles of the coated combs. Electrical resistance was measured over time, with a high resistance indicating that the coating was intact and that no current was following. As soon as the coating started leaking water, current started to pass between the poles of the component and resistance decreased. Coating failure was deemed to have occurred when resistance fell below 10 ⁸ Ω. The results provide an indication as to the performance of the coatings when in contact with tissues or fluids (which contain a high content of water) in a patient.

The results of this test are depicted in Figure 6. The SiO _x C _y H _z / SiO _x / SiO _x C _y H _z coating performed well (see the black circles), with a high resistance throughout the duration of the test. The SiOxCyHz / SiO _x H _y CzN / SiO _x C _y H _z / SiO _x H _y CzN / SiO _x C _y H _z also performed well (see the black stars), with an even higher resistance throughout the duration of the test. The three single layer coatings (SiO _x [black squares], SiO _x C _y H _z [unshaded triangles] and SiO _x H _y CzF _a [diamonds]) failed, with resistance either starting below 10 ⁸ Ω (for the SiO _x layer) or decreasing to under 10 ⁸ Ω during the duration of the test (for the SiO _x C _y H _z and layers).

The SiO _x C _y H _z / SiO _x two layers coating (unshaded squares) also failed in this test, performing less well than the SiO _x C _y H _z single layer coating. It was notable that addition of a further SiO _x C _y H _z layer on top of the SiO _x C _y H _z / SiO _x coating greatly improved its performance as discussed above. It is believed that whilst a SiO _x layer as the top layer of the coating may result in reduced performance under some conditions for coatings with low numbers of layers (such as SiOxCyHz / SiO _x ), such a reduction in performance is unlikely to be observed when there are higher number of layers in the coating.