Note: Descriptions are shown in the official language in which they were submitted.
CA 02243869 1998-07-22
NON-FOUI,~G~ WETTARI ~ COATED DEVICES
The US Government has certain rights in the present invention
pursuant to the National Tn.ititlltes of Health under Grant R01 AR43186-
5 01 and by the State of Texas through the Texas Higher F.duc~tion
Coolrli~ g Board ATP Program under Grant 003656-137.
This application claims the benefit of U. S. Provisional Application
Serial No. 60/055,260 filed on August 8, 1997, and entitled "NON-
FOULl~G WETTABLE COATED DEVICES7" commonly ~igned with
10 the present invention and incorporated herein by reference.
This is a continuation-in-part application of prior U.S. Patent
Application Serial No. 08/632,935, filed April 16, 1996, the entire
content of which is hereby incorporated by reference.
15 TECHNICAL FIELD
This invention relates to devices having gas-phase deposited
coatings and their methods of production. More specifically, this
invention relates to devices, and their method of production, having gas-
phase deposited coatings which are non-fouling and wettable.
BACKGROUND
The chemical composition of surfaces plays a pivotal role in
dictating the overall efficacy of many devices. Some devices require non-
fouling, and wettable surfaces in order for the devices to be useful for
25 their inten-led purposes. For example, many biomedical devices such as
catheters, stents, implants, interocular lenses and contact lenses require
surfaces which are biologically non-fouling, which means that proteins,
lipids, and cells will not adhere to the surfaces of the devices. In some
cases materials for devices are developed which have all the necess~ry
30 attributes for their intended purposes, such as, strength, optimal
CA 02243869 1998-07-22
tr~n~mi~ion, flexibility, stability, and gas transport except that the
surfaces of the materials will foul when in use. In these cases either new
materials for the devices are developed or an attempt to change the
surface characteristics of the materials is made.
In the specific case of contact or interocular lenses, particularly
contact lenses, although many polymeric materials possess the necessary
mechanical, oxygen permeation and optical pl Op~l lies required for lens
m~nllf~r,ture, many potential contact lens materials are subject to rapid
biological fouling due to the adhesion of proteins, lipids, and other
10 molecules present in the tear fluid surrounding the lens, and/or the surface
energies of the materials are too low making the contact lenses too
hydrophobic, and therefore not wettable by the tear fluid.
In light of the above considerations, a common approach utilized
by various leseal ~;h~l ~ is to attempt to improve the biocompatibility of the
15 potential contact lens materials by application of a thin coating to these
substrates. In theory such a coating would take advantage of the inherent
favorable bulk mechanical, gas transport and optical properties of the
polymer with the applied coating providing the required hydrophilicity and
non-fouling properties. However, despite the plethora of such studies, it
20 is significant to note that, at present, not a single contact lens
m~n~lf~lrer offers commercial products having coatings applied for this
express purpose. Obviously, although the concept of simply applying a
surface coating to remedy physical property deficiencies of a given
polymer substrate has theoretical appeal, this has proven to be a totally
25 illusive goal in actual practice. The previous failures reflect the fact that,
to be commercially viable, a c~lccessfill contact lens coating procedure
must satisfy a myriad of rather stringent requirements. These
requirements, as a minim~lm, include the following criteria: the coatings
must be uniform and, ideally, pin-hole free; the coatings must be both
30 wettable and non-biologically fouling; the coatings should be e~nti~lly
CA 02243869 1998-07-22
devoid of extractables and they must exhibit long-term chemical stability
in aqueous saline solution, the coatings must exhibit excellent optical
transparency in the visible region of the electromagnetic spectrum; the
coatings must not co~ roll~ise the oxygen permeability (i.e., the so-called
5 DK value) ofthe po~mer substrate; and, in the case of reusable lenses, the
coatings must exhibit sufficient abrasion reci.~t~n~e and chemical stability
to with.~t~n-l repeated cle~ning~. In the latter case, cleaning procedures
would include both exposure to harsh chemical cle~n~in~ agents and to
mechanical rubbing actions.
European Patent Application 93810399.1, filed June 2, 19937
describes a complicated multi-step process to alter the surface of a contact
lens material. The process requires a plasma treatment of the surface to
generate surface free radicals, which are reacted with oxygen to form
hydroperoxy groups, to which are graft polymerized an ethylenically
15 unsaturated monomer plus cross-linking agent, followed by a solution
extraction period to remove unreacted monomers. This complex process
requires the presence of inhibition agents during the monomer coupling
reactions to prevent the homopolymerization of the ethylene monomers
by free radicals generated during the thermal decomposition of the
20 hydroperoxy groups.
The plasma deposition of triethylene glycol monoallyl ether is
reported in the German patent application DE19548152.6. Although it
did not deal with contact lenses, it centered on surface modifications to
reduce the adsorption of biological compounds. Coatings of such type
25 would be useful in re(l~lcing non-specific protein adsorption on certain
biosensor surfaces. In this work, substrates for coating were located
CA 02243869 1998-07-22
outside the plasma discharge zone and exceptionally low RF power
densities were employed in an attempt to ..,il~i,..i,ç fragmentation ofthe
polyethylene oxide units present in this monomer. Not unexpectedly,
coatings deposited in the relatively non-energetic region upstream of the
5 plasma discharge and outside the luminous discharge zone were only
weakly attache~ to the underlying substrates. Another problem
encountered in this work was the low volatility of the monomer. This
resulted in a req~ e~cnl for monomer heating to provide sufficient vapor
for the plasma deposition process. However, even with heating, the vapor
10 pressures obtainable without initiating thermal decomposition of the
monomer were too low to provide any sort of flow rate and/or reactor
pressure controllability. Additionally~ the llnll.sll~lly low vapor pressure
resulted in exceptionally low film depo~ition rates with accompanying film
non-ul. r~ y. The co~tin~c obtained were not tested for adhesion under
15 flow conditions, nor were they subjected to any abrasive cleaning or
rubbing actions. Simple soaking of the coating substrates in distilled
water for relatively short periods (e.g., less than 48 hours) resulted in
measurable changes in the chemical compositions of the coatings as
revealed by XPS surface analysis of these coatings before and after the
20 simple water immersion test.
US Patents 3,008,920 and 3,070,573 reveal the use of plasma
surface treatments to generate free radicals for subsequent peroxy group
formation followed by the grafting of vinylic monomers to the polymer
substrate. The control of the depth unlrol Illily and density of the grafted
25 coatings is a difficult problem encountered in these grafting experiments.
CA 02243869 1998-07-22
PCT/US90/05032 (Int. Publication #W091/04283) discloses
increasing the wettability of polymeric contact lens materials synthesized
from specific hydroxy acrylic units and vinylic siloxane monomers by
grafting other molecules to the surface. The only examples of the
5 proposed grafting procedure described in this patent involve attachment
of specific polyols by wet chemical procedures, but this patent does
suggest that hydroxy acrylic units may be grafted to the specific hydroxy
acrylic/siloxane polymeric materials by radiation methods. Additionally,
radiation induced atta~hment by gaseous hydroxyl acrylic units was
described in US Patent 4,143,949 as a means of improving surface
hydrophilic character.
US Patent 4,143,949 discloses a process for putting a hydrophilic
coating on a hydrophoic contact lens. The polymerization is achieved by
subjecting a monomer, in gaseous state, to the influence of
15 electromagnetic energy, of a frequency and power sufficient to cause an
electrodeless glow discharge of the monomer vapor.
US Patent 4,693,799 describes a process for producing a plasma
polymerized film by pulse discharging. The process comprises forming a
plasma pol~ e--~ed film on the surface of a substrate placed in a reaction
20 zone by subjecting an organic compound co..la~ -g gas to plasma
polymerization utili~ing low temperature plasma formed by pulse
discharging, in which the time of non-discharging condition is at least 1
msec, and the voltage rise time for gas breakdown is not longer than 100
msec. Specifically, the patent disclosed a process employing an
25 alternating current ("AC") electrical discharge operated in a pulsed mode
to provide films having small coefficients of friction and high lubricity for
CA 02243869 1998-07-22
use on m~gnetic tapes and discs. Althol1gh various c ,~l~elil,lental sets were
carried out at di~lenl AC frequencies (from 2 to 2 Khz), all experiments
within a given set were reportedly conducted at fixed plasma on to plasma
off times. However, it provides no mention of the film compositional
5 control available via changes in the ratio of plasma on to plasma offtimes
during pulsed plasma polymerization of an organic monomer; nor is any
mention made of the adhesion of the deposited films with respect to
soaking or abrasive cleaning actions.
US Patents 3,854,982 and 3,916,033 describe the use of liquid
10 coating techniques to improve the wettability of contact lens polymers.
In these procedures free radical polymerizable precursors, including
hydroxy alkyl methacrylates, are attached to contact lenses by exposure
to high energy radiation. However, these solution attachment processes
provide poor control of the film thickness and these films exhibit poor~5 abrasion resistance, particularly when attached to polysilicone substrates.
The direct plasma treatment to improve the wettability of contact
lenses is described in US Patent 3,925,178 in which an electrical or radio
frequency discharge in water vapor is employed for that purpose. This
non-coating treatment results in a relatively unstable hydrophilic surface
20 in which the wettability of the contact lens substrate decreases rapidly in
time.
US Patent 57153,072 describes a method of controlling the
chemical structure of polymeric films by plasma deposition and films
produced thereby. The focus of this invention involves controlling the
25 telllpel~lure ofthe substrate and the reactor so as to create a temperature
differential between the substrate and reactor such that the precursor
CA 02243869 l998-07-22
molecules are plere~e~ ally adsorbed or condensed on the substrate
either during plasma deposition or between plasma deposition steps.
Yasuda et al., "Some Aspects of Plasma Polymerization
Investig~ted by Pulsed R.F. Discharge," Journal of Polymer Science:
Polymer Chemistry Edition, Vol. 15, pp. 81-97 (1977), discloses the
polymerization of organic compounds in glow discharge (plasma
polymerization) by using pulsed RF discharge ( 100 microsec. on, and 900
microsec. of ~. The effect of pulsed d;s~ ,e on polymer deposition rate,
pressure change in plasma, ESR signals of free spins in both plasma
polymer and substrate, and the contact angle of water on the plasma
polymer surface were investaged for various organic compounds.
N~ etal., "PlasmaPolyrnerization of Tetrafluoroethylene,"
Journal of Applied Polymer Science, Vol. 23,pp. 2627-2637(1979),
describes the plasma polymerization of tetrafluoroethylene in both
continuous wave and pulsed radio frequency ("RF") discharges They
reported that both polymer deposition rates and polymer structures were
e~nti~lly identical when using continuous wave and pulsed RF discharge.
Lopez et al., "Glow discharge plasma deposition of tertraethylene
glycol dimethyl ether for fouling-res;31alll biomaterial surfaces," Jozlrnal
of BiomeG~calMaterialsResearch, Vo].26,pp 415-439(1992), discloses
the glow discharge plasma deposition of tetraethylene glycol dimethyl
ether onto glass, polytetrafluoroethylene and polyethylene. The monomer
required heating, and low power to retain the ethylene oxide content of
the plasma deposited coatings. As a result, no monomer flow rate
controllability was available, and the films deposited at the lower RF
powers exhibited low stability to even simple overnight soaking in water.
CA 02243869 1998-07-22
The film adhesion to the polymeric substrate could be improved by
carrying out the plasma deposition at higher power but this improved
adhesion was achieved at the ~,Apense of loss of ethylene oxide fflm
content and thus poorer non-fouling properties.
The need still remains for a composition which can be applied to
the surface of a substrate to provide a film of coating that is uniform in
thickness, pin-hole free7 optically ~l~nspa.cllL in the visible region of the
magnetic spectrum7 perrneable to oxygen7 biologically non-fouling,
relatively abrasive resict~nt, and wettable (hydrophilic).
SUM:MARY
The present invention provides a device Col~ g a substrate and
a coating composition7 the coating composition being formed by the gas
phase or plasma polymerization of a gas comprising at least one organic
15 compound or monomer7 the organic compound having the following
structure:
Rl F13 R4 R6
C_~Y ) 0--C--C ~8
m l I
R2 ~ R5 R7 Jn
m = 0-1; n = 0-67
25 where Y represents C=0;
Rl7 R27 R3, R4, R5, R6 and R' each independently represents:
CA 02243869 1998-07-22
OH,
halogen,
Cl- C4 alkyl,
Cl - C4 alkene,
Cl- C4 diene,
Cl- C4 alkyne,
C,- C4 alkoxy,
or
0 C,- C4 alkyl halide;
and
R8 represents:
H,
halogen,
C, - C4 alkyl,
Cl- C4 alkene,
C,- C4 diene,
C,- C4 alkyne,
Cl- C4 alkyl halide,
Cl - C4 aldehyde,
Cl- C4 ketone,
Cl- C4 epoxide,
Cl- C4 carboxylic acid,
C,- C4 ester,
-CH = CHR9, where R9 is H, halogen7 C, - C4 alkyl, C, -
C4 alkyl halide, C, - C4 aldehyde, C, - C4 ketone,
CA 02243869 1998-07-22
Cl-C4 alkoxyl, Cl - C4 epoxide, Cl - C4 carboxylic
acid, or C, - C4 ester,
or
-ORI~, where Rl~ is H, halogen, C~ - C4 alkyl, Cl - C4
alkene, Cl - C4 diene, C, - C4 alkyne, C~ - C4 alkyl
halide, Cl - C4 aldehyde, C~ - C4 ketone, Cl - C4
epoxide, Cl - C4 carboxylic acid, or C~ - C4 ester.
The polymerization of the present invention can be carried out
using a pulsed discharge having a duty cycle of less than about 1/5, in
10 which the pulse-offtime is less than about 2000 msec and the pulse-on
time is less than about 100 msec. The duty cycle can also be varied, thus
the coating composition can be gradient layered accordingly.
The compound generally has low molecular weight, one or more
ether link~es and at least one unsaturated carbon-carbon bond.
The devices of this invention have coating compositions which are
uniform in thickness, pin-hole free, optically transparent in the visible
region ofthe m~n.-.tic spectrum, permeable to oxygen, abrasive resi~t~nt,
wettable and biologically non-fouling; therefore, making it possible to use
substrates which, except for their surface characteristics, are well suited
for their intended uses. In the specific case of contact or interocular
lenses, particularly contact lenses, substrates which are not wettable by the
tear fluid, which are subject to rapid biological fouling7 and/or have
surface energies which are too low can be made useful when coated with
the coating compositions of this invention.
The co~ting.C of the present invention are deposited on the surface
of a solid substrate via plasma polymerization of at least one selected
CA 02243869 1998-07-22
monomer. The plasma deposition of the present invention is achieved by
either continuous wave ("CW") or pulsed plasmas. In the pulsed mode,
the deposition is carried out of a fixed plasma duty cycle or, alternately,
using a variable duty cycle pulsed plasma deposition.
BRI~,F DF.SCRIPTION OF THE DRAWINGS
Fig. 1 is an illustration of the variation in coating wettability with
changes in RF duty cycles employed during deposition, while all other
plasma reaction variables were being held constant.
Figs. 2 (a-d) are illustrations of the variation in coating
composition with changes in RF duty cycles employed during deposition
of plasma polymerized EO2V film at 200 watts, while all other plasma
reaction variables were being held constant. The numerator given below
denotes the plasma-on time, and the denominator given below denotes the
plasma-off time, both in the unit of msec. High resolution C (1s) XPS
spectra are shown for films deposited at RF on/off ratio (in msec) of: (a)
1/20; (b) 1/50; (c) 1/100; and (d) 1/200.
Fig. 3 is an illustration of the variation in coating wettability with
changes in RF peak power employed during deposition, at a constant
plasma on/off ratio of 10/200 msec, all other plasma reaction variables
were held constant.
Figs. 4 (a-b) are illustrations of the stability of EO2V plasma films
to prolonged exposure to air. The EO2V plasma film was deposited at a
plasma-on time of 10 msec and a plasma-offtime of 200 msec at 50 watts.
The spectra shown are C (1s) XPS results of these films: (a) after
exposure to air for 10 months; and (b) fresh film.
CA 02243869 1998-07-22
Figs. 5 (a-e) are illustrations of XPS high resolution C ( 1 s) spectra
of plasma polymerized EO2V films obtained from a series of runs carried
out at a fixed plasma-on to plasma-offratio of 1 to 20 at 50W but with
varying actual plasma-on and plasma-offpulse width: (a) 100 msec on
and 2000 msec off; (b) 10 msec on and 200 msec off; (c) 1 msec on and
20 msec off; (d) 0.1 msec on and 2 msec off; and (e) 0.01 msec on and
0.2 msec off.
DET~l,F.n DESCRIPTION
The devices of this invention comprise non-fouling coating
compositions. The coating compositions provide surfaces which are
uniform, pin-hole free, wettable, devoid of extractables, and chemically
stable. Further, the coatings exhibit excellent optical transparency in the
visible region ofthe electromagnetic spectrum, are oxygen permeable, and
15 are abrasion resistant. These are desirable characteristics particularly for
biomedical devices, such as stents, implants, catheters, etc., and
particularly for contact or interoccular lenses. The coating of the present
invention is also suitable for surface coating of magnetic recording media,
m~gn~.tic tapes, m~n~ic discs, cell cultivation bed, carriers for diagnostic
20 reagents, biosensors, and artificial organs, such as artificial blood vessels,
artificial bones, and others.
The substrates for the devices of this invention can comprise
polymers, plastic, ceramics, glass, ~ilpni7ed glass, fabrics, paper, metals7
sil~ni7ed metals, silicon, carbon, silicones and hydogels. Some of the
25 more prere-l~d materials include those that are likely to be used for
biomedical devices, such as silicone and silicone cont~ining compositions,
CA 02243869 1998-07-22
(mixed blends and copolymers), polyurethanes, and hydrogels, and
mixtures ofthese materials. The most plerer~ed substrate materials are
those polymers used to make contact lenses, which do not support a stable
tear film on the surface, such as silicones? silicone mixed blends,
5 alkoxylated methyl glucosides, silicone hydrogels, polyurethane-silicone
hydrogels, and polysulfones. Illustrative silicones are polydimethylsiloxane
polydimethyl-co-vinylmethylsiloxane, silicone rubbers described in US
Patent No. 3,228,741, silicone blends such as those described in US
Patent 3,341,490, and silicone compositions such as described in US
Patent 3,518,324. Useful silicone materials are the cross linked
polysiloxanes obtained by cross linking siloxane prepolymers by means of
hydrosilylation, cocondensation and by free radical mech~ni~m~.
Particularly suitable substrate materials are organopolysilioxane polymer
mixtures which readily undergo hydrosilylation. Such prepolymers will
15 comprise vinyl radicals and hydride radicals which serve as cros~linking
sites during chain extension and crosslinking reaction and are of the
general formulation comprising polydihydrocarbyl-co-
vinylhydrocarbylsiloxane and polydihydrocarbyl-co-
hydrocarbylhydrogensiloxanes wherein the hydrocarbyl radicals are
20 monovalent hydrocarbon radicals such as alkyl radicals having 1-7 carbon
atoms, such as, methyl, ethyl, propyl, butyl, pentyl, hexyl and heptyl; aryl
radicals, such as phenyl, tolyl, xylyl, biphenyl; haloaryl, such as
chlorophenyl and cycloalkyl radicals such as cyclopentyl, cyclohexyl, etc.
The more preferred materials are silicone hydrogels, particularly silicone-
25 hydrogels formed from monomer mixtures comprising an acrylic-capped
polysiloxane prepolymer, a bulky polysiloxanylalkyl (meth)acrylate
CA 02243869 1998-07-22
14
monomer and hydrophilic monomers as described in US Patents
5,387,632; 5,358,995; 4,954,586; 5,023,305; 5,034,461; 4,343,927; and
4,780,515. Other p.~r~ d substrate materials comprise cyclic polyols of
alkoxylated glucose or sucrose like those described in 5,196,458 and
5,304,584, and US Patent Application Serial No. 08/712,657, filed
September 13, 1996. All of the patents cited above are incorporated
herein by reference.
The pl~r~--ed coating compositions comprise gas phase deposited
low molecular weight, high volatility organic compounds cont~inin~ one
10 or more ether linkages. Preferably, the molecules contain at least one
unsaturated carbon-carbon bond in the molecule to assist in achieving
polymerization, particularly under low energy gas-phase deposition
methods. The groups having unsaturated carbon-carbon bonds are
preferably vinyl compounds. The coating compositions are stable, and
15 adherent to a wide range of substrates while m~int~ining maximum
integrity of the ether linkages present in these monomers. The weight
average molec ll~r weights ofthe compounds are preferably less than 400,
more preferably less than 300, and most preferably less than 200.
CA 02243869 1998-07-22
The p- ere - ed coating compositions are formed by the gas phase
deposition and polymerization of a linear or branched organic compound
or monomer having the following structure:
R1 R3 R4 R~
C G~Y ) O--C--C R~
m
F ~2 ~ R5 R~ Jn
~0
m = 0-1; n = 0-6,
where Y represents C=0;
Rl, R2, R3, R4, R5, R6 and R' each independently represents:
H,
OH,
halogen,
Cl- C4 alkyl,
Ct- C4 alkene,
Cl- C4 diene,
Cl - c4alkyne~
Cl- C4 alkoxy,
or
C,- C4~kyl halide;
and
R8 represents:
H,
CA 02243869 1998-07-22
16
halogen,
Cl- C4 alkyl,
Cl- C4 alkene,
Cl- C4 diene,
S C,- C4 alkyne,
C,- C4 alkyl halide,
C,- C4 aldehyde,
C,- C4 ketone,
Cl- C4 epoxide,
0 C,- C4 carboxylic acid,
Cl- C4 ester,
-CH = CHR9, where R9 is H, halogen, Cl - C4 alkyl, Cl -
C4 alkyl halide, C, - C4 aldehyde, C, - C4ketone1
C,-C4 alkoxyl, C, - C4 epoxide, Cl - C4 carboxylic
acid, or C, - C4 ester,
or
-ORI~, where R'~ is H, halogen, C, - C4 alkyl, C, - C4
alkene, C, - C4 diene,
C,- C4 alkyne, C, - C4 alkyl halide, Cl - C4
aldehyde, C, - C4 ketone, C, - C4 epoxide, Cl - C4
carboxylic acid, or C, - C4 ester.
Examples of usable organic compounds include the following
structures:
R'C(R")=C(R" ')-(OCH2CH2)n-OR
R'C(R'')=C(R''')-(OcH2cH2)n-R
R'C(R")=C(R" ')-C(O)-(OcH2cH2)n-oR~ " '
CA 02243869 1998-07-22
and R'C(R")=C(R"')-C(O)-(OCH2CH2)n-R""
where R', R", R"', and R"" independently represent H, a linear or
branched alkyl having I to 4 carbons; preferably methyl or H; more
preferably H; and n is 1 to 6; preferably 1 to 5; more preferably 2 or 3
5 For specifically ~l~r~lled monomers having the above structural formulas
R', R", R"'~ and R"" are H; or R', R", R"' are H, and R"" is CH3; and
n is 2 or 3, more preferably 2.
Example of more specific usable organic compounds include:
1 0 CH2=CH-(OCH2CH2)n-OH
CH2=CH-(OCH2CH2)n-OCH3
CH2=CH-(OCH2CH2)n-OCH=CH2
Other examples of usable organic compounds in the coating
composition of this invention include:
di(ethylene glycol) divinyl ether (H2C=CHOcH2CH2)2O
di(ethylene glycol) vinyl ether H2C=CH(OCH2CH2)2OH
di(ethylene glycol) methyl vinyl ether H2C=CH(OCH2CH2)2OCH3
di(ethylene glycol) diacrylate (H2C=CHcO2cH2CH2)2O
di(ethylene glycol) ethyl ether acrylate
H2C=CHC(O)(OCH2CH2)20c2H5
trimethylolpropane diallyl ether
C2H5c(cH2ocH2cH=cH2)2cH2oH
tetra(ethylene glycol) propyl ether methacrylate
CA 02243869 1998-07-22
18
H2C=C(CH3)CO2(0CH2CH2)4CH2CH2CH3
hexa(ethylene glycol) methyl ether methacrylate
H2C=C(CH3)C02(0CH2CH2)6CH3
The more plerelled organic compounds include di(ethylene
5 glycol) divinyl ether, di(ethylene glycol) methyl vinyl ether, di(ethylene
glycol) ethyl ether acrylate, and trimethylolpropane diallyl ether. The
most plt;re.led compound is di(ethylene glycol) vinyl ether.
The coating compositions can comprise the polymerization of
substantially a single organic compound or of a mixture of organic
10 compounds with or without the addition of cross-linking agents. The
single and the mixture of organic compounds p~ere,~ly are selected from
the organic compounds described above.
The selection of compounds and method of application of the
compounds to the surface of the substrate preferably provide a coating
15 composition in which the outermost layer of the coating has a ratio of
carbon-oxygen bonds to carbon-carbon bonds of greater than 1:1, more
p.er~.~bly greater than 1.5:1, and most preferably greater than 2:1, even
more prer~;--ed is greater than 2.5:1. The coating compositions having
a higher ratio of carbon-oxygen bonds to carbon-carbon bonds are
20 prere~ed, because of improved non-fouling and higher wettability
characteristics.
One method for depositing the coating compositions on the
substrates is by gas phase deposition, because it provides uniform coating
compositions. Gas phase deposition means by any method the gaseous
25 monomers are attached to the solid substrate as a surface coating. Gas
phase depositions include plasma and photochemical induced
CA 02243869 l998-07-22
~ 19
polymerizations. Plasma induced polymerizations or plasma depositions
are polymerizations due to the generations of free radicals caused by
passing an electrical discharge through a gas. The electrical discharge
can be caused by high voltage methods, either alternating current ("AC")
5 or direct current ("DC"), or by electromagnetic methods, such as, radio
frequency ("RF") and microwave. Alternatively, the coating process can
be carried out using photochemical inlluced polymerizations as provided
by direct absorption of photons of sufficient energy to create free radicals
and/or electronically excited species capable of initiation of the
10 polymerization process.
One preferred method of one-step gas phase deposition is by
plasma polymerization, particularly radio frequency plasma
polymerization, in which the coating is deposited on the surface of the
substrate via direct monomer polymerization. This process will be
15 described herein. It is more fully described in U. S. Patent Application
Serial No. 08/632,935, incorporated herein by reference. Additional
descriptions can be found in PanchPling~m et al., "Molecular Surface
Tailoring of Biomaterials Via Pulsed RF Plasma Discharges,"
J.Biomater. Sci. Polymer Edn., Vol. 5, pp. 131-145 (1993), and
20 Panr.h~ling~nn et al, "Molecular Tailoring of Surfaces Via Pulsed RF
Plasma Depositions," Journal of Applied Science: Applied Polymer
Symposium, 54, 123-141 (1994), incorporated herein by reference. In
this method, coatings are deposited on solid substrates via plasma
poly~ ion of selected monomers under controlled conditions. The
25 plasma is driven by RF radiation using coaxial external RF electrodes
located around the exterior of a cylindrical reactor. Substrates to be
CA 02243869 1998-07-22
coated are preferably located in the reactor between the RF electrodes;
however, substrates can be located either before or after the electrodes.
The reactor is evac~l~ted to background pressure using a rotary vacuum
pump. A fine metering valve is opened to permit vapor of the monomer
5 (or monomer mixtures) to enter the reactor. The pressure and flow rate
of the monomer through the reactor is controlled by adjustments of the
metering valve and a butterfly control valve (connected to a pressure
controller) located dowl~lJ eam of the reactor. In general, the monomer
reactor pressures employed range from applox~,.a~ely 50 to 200 mili-
10 torr, although values outside this range can also be utilized. It isplere..ed that the compounds have sufficiently high vapor pressures so
that the compounds do not have to be heated above room temperature
(from about 20 to about 25~C) to vaporize the compounds. Although
the electrodes are located exterior to the reactor, the process of the
15 invention works equally well for electrodes located inside the reactor (i.e.
a capacitively coupled system).
The chemical composition of a film obtained during plasma
deposition is a strong function of the plasma variables employed,
particularly the RF power used to initiate the polymerization processes.
20 It is pr~re~ed to operate the plasma process under pulsed conditions,
coml)ared to continuous wave ("CW") operation, because it is possible
to employ reasonably large peak powers during the plasma on initiation
step while m~int~ining a low average power over the course of the
coating process. Pulsing means that the power to produce the plasma is
25 turned on and off. The average power under pulsing is defined as:
CA 02243869 1998-07-22
..
21
AveragePower = pl~m~-ontime X PeakPower
plasma-on time + plasma-off time
For example, a plasma deposition carried out at a RF duty
cycle of 10 msec on and 200 msec offand a peak power of 25 watts
corresponds to an average power of 1.2 watts. The Peak Power is
preferably between about 10 and about 300 watts.
The formal definition of duty cycle is defined as the ratio of the
plasma on time (i.e. discharge time) to a sum of the plasma-on time and
the plasma-offtime (i.e. non-discharge time), as represented below:
plasma-on time
Duty cycle
plasma-ontime + plasma-offtime
However, for convenience, the plasma on to plasma off times are
frequently cited herein as a simple ratio of on to off time, both times
employing the same scale (i.e. milli~econds or microseconds).
The workable range of duty cycle is less than about 1/5, the preferred
range is between about 1/10 and about 1/1000, and the more plere--ed
range is between about 1/10 and about 1/30. The plasma-on time should
be larger than about 1 ,usec, preferably in the range of between about 10
,(lsec and about 100 msec, and more preferably in the range of between
about 100 ,~sec and about 10 msec. The plasma offtime, i.e. the non-
discharge time, should be larger than about 4 ,usec, preferably in the
range of between about 100 ,usec and 2000 msec, and more preferably
CA 02243869 1998-07-22
in the range of between about 200 ,~sec and about 100 msec. The total
deposition time varies depending on the monomer and the conditions
used. Typically, the deposition time can vary from about 0.5 min to
about 3 hours.
Pulsed plasma deposition permits use of relatively high peak
powers while simlllt~neously I~lAil~l~ining relatively low average powers
which provides for the retention of monomer functional groups. Coating
compositions deposited under low average power pulsed conditions tend
to be more adhesive to a given substrate when compared to films
10 deposited at the same average power but under CW operation. For a
given average power7 the momentary high peak power available under
pulsed conditions appal e,.~ly assists in obtaining a stronger grafting of the
film to the substrate than that obtained under the same average power
CW conditions.
For a given RF peak power, an increased retention of the ether
content (C-O functionality) of the plasma generated coating is observed
as the plasma duty cycle is reduced when working with a given
monomer. Alternatively, the chemistry of the coating composition can
be varied under pulsed conditions by working at a single plasma duty
cycle but varying peak powers. There is an increased incorporation of
C-O functionality in coating compositions as the peak power is
decreased. Surprisingly, the plasma generated film composition can be
varied by ch~nging the plasma on to plasma offpulse widths, at a fixed
ratio of plasma on to plasma off times and at a fixed RF peak power.
Although the film deposition mode described is one of RF plasma
polymerization, those familiar in the art will recognize that other
CA 02243869 1998-07-22
poly~ fi~lion methods (e.g., microwave plo~m~ photo-polymerization,
ionizing radiation, electrical discharges, etc.) could also be adapted for
this purpose.
The chemical composition of the films of this invention can be
varied during pulsed plasma deposition, by varying the peak power
and/or the duration ofthe plasma on and plasma offpulse widths. This
excellent film chemistry controllability is achieved without recourse to
mod~ tin~ the temperature of the substrate during the actual coating
process. To produce a coating composition with the prerel I ed ratio of
10 C-O functionality to C-C functionality, it is prere.-ed that the average
power of the pulsed plasma deposition is less than 100 watts, more
prere- ably less than 40 watts, most preferably less than 10 watts. The
highest ratios of C-O functionality to C-C functionality can be obtained
when the average power is 1 watt and less which provides the most non-
15 fouling and wettable coating compositions.
However, as those skilled in the art will recognize, the actual
effect of peak power input on film composition is dependent on the
reactor volume (i.e. power density). In the present invention, the reactor
volume is approximately 2 liters. Obviously, if a smaller reactor were
20 employed, the same film compositioned changes reported herein would
be achieved at lower peak power inputs. Other reaction variables which
would infll~ence peak power inputs are reactor pressure and monomer(s)
flow rates. If larger reactor volumes were employed, the same film
compositional variations could be achieved using higher power input.
The use of lower average power conditions increases the
presence of functional groups, e.g. ether units, in the coatings, but the
CA 02243869 1998-07-22
24
less energetic deposition conditions at lower average power may result
in poorer adhesion of the polymer film to the underlying substrate. Thus,
the plasma coating process involves somewhat of a compromise between
retention of monomer integrity in the plasma generated film and the
5 strength ofthe adhesion between the coating and the solid substrate. In
the case of biomedical devices and contact lenses, the adhesion and
overall stability of the coating composition to the lens substrate is an
extremely important consideration.
One method of applying the coating compositions to the substrate
10 of the present invention is by pulsed plasma coupled with gradient
layering. The duty cycle can be varied? thus creating variable duty cycle.
The method can be used to maximize the adhesion of the coating
composition and the functionalities present in the coating composition.
Films deposited under low average power pulsed conditions tend to be
15 more adhesive to a given substrate when compared to films deposited at
the same average power but under CW operation. For a given average
power, the momentary high peak power available under pulsed
conditions assists in obtaining a stronger grafting of the film to the
substrate than that obtained under the same average power CW
20 condition. This stronger grafting under pulsed conditions is repeated
with each plasma on cycle. The better grafting of the film to the
substrate ~l~ ed under pulsed conditions can be even further enhanced
by combining the pulsed deposition with a gradient layering technique.
This method is described further in U. S. Patent Application 08/632,93 5,
25 which is incorporated herein by reference. In this process, an initial high
power, high plasma duty cycle is employed to graft the plasma generated
CA 02243869 1998-07-22
coating composition tightly to the underlying substrate. The plasma duty
cycle is subsequently progressively decreased in a systematic manner,
with each decrease reslllting in an increased retention of the C-O
functionality in the coating. In this way, the successive plasma deposited
S films are tightly bonded to each other. The process is tern in~ted when
the exterior film layer has reached the desired composition. The
succession of thin layers, each differing slightly in composition in a
progressive fashion from the p,c;cedin~ one, results in a significantly more
adhesive composite coating composition bonded to the substrate than
10 coatings deposited without adjusting the deposition conditions under a
relatively lower plasma duty cycle
Gas-phase deposition, particularly plasma depositions, provide
coating compositions of s~ tially uniform thickness. The thicknesses
of the coating composition could be between 5 A and 5 ,L~m, more
pl~rt;l~bly between 50 A and 1 ,~m, and most preferably between 100 A
and 0.1 ,~lm. The uniform film thickness and controllability of the
deposition method can be contrasted with thickness controllability
problems encountered using previously disclosed methods. Using the RF
pulsed plasma deposition provides linearity of the thickness of the
20 coating composition with deposition time for a given plasma duty cycle
and fixed monomer pressure and flow rate.
The coatings of this invention increase the hydrophilic character
ofthe surface ofthe substrates, particularly with substrates that are more
hydrophobic (e.g., polysiloxanes). The extent of hydrophilicity
25 introduced during the plasma process was observed to increase as the
oxygen content of the plasma generated coating compositions increased.
CA 02243869 1998-07-22
26
The wettabilities of the substrates employed were measured
before and after plasma coating using both static and dynamic water
contact angle measurements. In general, the coatings applied serves to
increase the hydrophilic character of the surface, particularly with
5substrates that are more hydrophobic (e.g., polysiloxanes). The extent
of hydrophilicity introduced during the plasma process was observed to
increase as the oxygen content of the plasma generated films increased.
The stability of the surface wettability was examined in several
ways, including exposure to aqueous solution flow and to abrasive
10r~le~n:ng and rubbing tests. Additional s~lcces~fill stability testing of the
coated substrates involved autoclaving for five cycles at 121~ C for 30
minutes each cycle. The examples below include the results of these
tests.
The non-fouling character of the coating compositions were
15measured using adsorption studies with radioactively labeled proteins, as
well as by total protein assay. In general, decreases in protein adsorption
were observed for coated polymer substrates as compared to uncoated
polymer substrate as shown in the examples which follow.
The optical transparency of the coating compositions was
20measured spectrophotometrically at wavelengths ranging from 800 to
200 nm. The plasma coating compositions of the invention exhibited
consistent excellent transparency over the entire region of the visible
spectrum (i.e., from 780 to 380 nm) with photon absorption be~inning
to occur around 370 nm in the near W region. The absorption increases
25sharply over the interval from 370 to 200 nm, as revealed by samples
deposited on quartz plates.
CA 02243869 1998-07-22
The oxygen permeability was measured using the Fatt Method
(Patt, I. et al, International Contact Lens Clinic, 9(2), pp. 76-88 1992).
In general, the oxygen permeabilities (reported as DK values) of the
polymeric substrates were not measurably decreased by the presence of
5 the plasma film on the surface.
The substrates with coating compositions of this invention are
suited for contact lenses and other biomedical devices. The coating
compositions exhibit good adhesion, high wettability, high oxygen
permeability, and excellent transparency in the visible region of the
10 electromagnetic spectrum when deposited on polymer substrates. The
adhesion ofthe coating compositions to these substrates are sufficiently
strong to resist del~min~tion.
Thus the coating composition applied by a one-step and all-dry
process of this invention satisfies the stringent criteria listed above to
15 improve the biocon-phlibility of contact lenses. The emphasis in this
invention has been placed on the contact lenses; however, those skilled
in the art will recognize that the highly wettable, biologically non-fouling,
transparent coatings of this invention are useful for various other
applications (e.g., biomedical devices, biosensors, detectors deployed in
20 marine en~ nel.Ls, membranes, tissue culture growth, implants, etc.).
A particularly surprising result obtained in the present study is the
lt;lll~uk~bly stable and good biologically non-fouling properties ofthese
coatings despite the very low molecular weights of the monomers
employed to form the coating compositions. This observation is contrary
25 to many previous studies which conclude that relatively large polymeric
CA 02243869 1998-07-22
molecules cont~ining ether linkages are required in order to observe the
non-fouling effect.
The approach of the present invention represents an ~Imlsll~lly
simple, one-step coating process which could be conveniently coupled
5 with a plasma based sterilization procedure to provide large scale
fabrication polyethyleneglycol ("PEG") modified surfaces. Additional
il~he~ L advantages of a plasma based approach would include successful
surface modifications being less dependent on the composition and
geometry of the solid substrates. Tetraethylene glycol dimethyl ether,
CH3O(CH2CH2O)4CH3, and tri(ethylene glycol) monoallyl ether, CH2 =
CHCH2(OCH2CH2)3OH, were studied as potential monomers for plasma
polymerized PEG surfaces. For example, tetraethylene glycol dimethyl
ether was plasma deposited to yield surfaces with high short-term
rÇc~ n~e to biomolecular absorption, as demonstrated with both plasma
15 protein and cellular adsorption studies. However, simple overnight
soaking of plasma coated substrates in water resulted in major chemical
compositional changes as revealed by XPS analysis of surfaces before
and after soaking. Similarly, plasrna polymerization of tri(ethylene
glycol) monoallyl ether produced coatings having good short term
20 resi~t~nce to biofouling but poor stability towards soaking or exposure
to flowing aqueous solutions. Adhesion of the plasma films to the
polymeric substrates could theoretically be improved by carrying out the
plasma deposition at higher power but this improved adhesion was
achieved at the expense of loss of ethylene oxide film content and thus
25 poorer non-fouling properties.
CA 02243869 1998-07-22
29
Although not wishing to be bound by any particular postulate, it
is speculated that the gas phase deposition process, particularly the
pulsed plasma deposition process of the present invention results in an
lmllsl~lly efficient stacking of ether 1 ~'-~ec on the substrate surface thus
5 providing a high surface density of such groups. This high surface
density is, in turn, extremely effective in preventing the adsorption of
biological molecules onto the surface while simultaneously creating a
relatively polar environment to adsorb water molecules, thus providing
high surface wettability. When the coating process is used for contact
10 lenses, the coating composition on the contact lens substrate should
provide a low water contact angle. For contact lenses, it is preferred that
the coating compositions have an advancing sessile drop water contact
angle of less than 85 ~, more pl~rela~ly less than 65 ~, most preferably less
than 45~.
15 Example 1
Di(ethylene glycol) vinyl ether (EO2V) was plasma deposited on
a DacronTM polyester substrate under pulsed plasma deposition
conditions using an RF on/off cycle of 10 msec on and 200 msec off at
100 W peak power. A 1000 A thick film was deposited during the 20
20 minute run. X-ray photoelectron spectroscopy (XPS) analysis of this
film revealed significantly more carbon atoms bonded to oxygen than to
other carbon atoms. A sample prepared in this manner was then
subjected to 65 hours of a constant 40 ml/min flow of phosphate buffer
solution (PBS) at pH of 7.4. The sample was subsequently vacuum dried
25 and re-analyzed by XPS. The relative concentration of C-O to C-C
groups present on the surface had actually increased slightly revealing
CA 02243869 1998-07-22
negligible surface modification during the buffer flow7 indicating the
durability of the coating composition.
Example 2
A sample prepared as described in Example 1 was deposited on
5 a silicone contact lens substrate. The advancing water contact angle was
measured on the polysiloxane before and after plasma treatment. The
advancing sessile drop water contact angle of 98~ observed on the
untreated surface had decreased to 58~ a~[er surface coating by the
plasma, indicating an increased wettability due to the coating
10 composition. Subsequent soaking of the coated sample in PBS buffer
solution for several days resulted in essent~ y negligible change in the
advancing water contact angles, indicating the durability of the coating
composition. See, TABLE I. The ratio 10/200 in TABLE I indicates 10
msec plasma-on time and 200 msec plasma-offtime.
TABLE I
Contact Angle Vari~tion for EO2V Films on Silicone Contact Lenses
as a Function of Soakin~ T;me in PBS Ruffer Solution
20Coating Condition Fresh 5 hrs 10 hrs 48 hrs 96 hrs 240 hrs
Film
10/200, lOOw, 15 min 58 60 66 63 60 60
10/200, lOOw, 30min 58 62 58 62 60 60
CA 02243869 1998-07-22
Example 3
Samples were prepared as described in Example 1 on a
polyethylene substrate, but at various plasma on/off cycles of on-time in
msec/off-time in msec of 1/20, 1/50, 1/100, and 1/200 at a peak power
5 of 200 watts. Analysis ofthese films by water contact angle goniometry
revealed progressively lower advancing water contact angles
corresponding to lower RF plasma duty cycles employed during the
coating procedure. (Fig. 1) The increased wettability observed with
decreasing average power during film formation is correlated with high
10 resolution C (1s) XPS spectra ofthese films which show increasing C-O
versus C-C film content with decreasing RF duty cycle employed during
film formation. (Figs. 2 (a-d)).
Another set of samples were prepared as described in Example I
on a DacronTM substrate but at various plasma peak power of 100 watts,
50 watts, 25 watts and 10 watts and at a cycle of 10 msec on and 200
msec off. Analysis of these films by water contact angle goniometry
revealed progressively lower advancing water contact angles
corresponding to lower RF plasma peak power employed during the
coating procedure. (Fig. 3). The increased wettability observed with
20 decreasing average plasma energy correlated with XPS analysis of these
films which showed increasing C-O versus C-C film content with
decreasing RF peak power employed during film formation.
Example 4
The monomer CH2=CH-(OCH2CH2)2OCH3 (Methyl EO2V) was
25 plasma deposited on a polysiloxane substrate using the same RF duty
cycle and peak power employed in Example 1. The resulting film
CA 02243869 1998-07-22
32
revealed slightly higher C-O content relative to C-C bonds than obtained
in Example 1. Additionally, these films exhibited an advancing water
contact angle which was approximately 5~ less (i.e., more hydrophilic)
than that obtained in Example 2.
5 Example 5
A coating was prepared from the monomer di(ethylene glycol)
divinyl ether [(H2C=CHOCH2CH2)20] using the same plasma deposition
conditions employed in Fx~mples 1 and 4. The advancing water contact
angle for this sample was virtually identical to that obtained for the
10 methoxy compound of Example 4. Both the methoxy and divinyl
samples of Examples 4 and 5 revealed less hysteresis in terms of
advancing versus receding water contact angles than observed for the
sample of Example 2, indicating that the surface molecules are less
mobile, and therefore less likely to foul. Further, the contact angles
15 indicate that the surfaces are wettable.
Example 6
A sample was prepared in which the monomer of Example 1 was
plasma deposited onto a DacronTM sample using an RF on/offcycle of 10
msec on and 200 msec off and a peak power of 50 watts. Protein
20 adsorption using l25I-labeled albumin and fibrinogen was conducted using
uncoated and plasma coated DacronTM samples. The protein adsorption
on the coated samples was dr~ tic~lly reduced (i.e., by a factor in
excess of 20) when compared to adsorption on the uncoated DacronTM
control. The differences were particularly acute in contrasting protein
25 retained on these surfaces after gently washing with 1% sodiumdodecyl
sulfate (SDS) solution. The retained protein was barely detect~ble on the
CA 02243869 1998-07-22
plasma treated surfaces, being several orders of magnitude less than that
retained on the uncoated DacronTM controls. This example indicates
both the durability and non-fouling properties of the coating composition
of the invention
Another sample was prep~ed in which the monomer of Example
1 was plasma deposited onto a DacronTM sample using an RF duty cycle
of 10 msec on and 50 msec offand a peak power of 100 watts. The
protein adsorption on the coated samples was increased (i.e. by a factor
of about 1.2) when compared to adsorption on the uncoated DacronTM
10 control. This ~x~ le shows that the non-fouling properties of coatings
made at high RF duty cycle (1/5) are not as desirable as those coatings
made at low RF duty cycle.
Example 7
Samples were prepared as described in Example 1. These
15 samples were then subjected to abrasive cleaning processes using
standard commercial contact lens cleansers following the lens cleaning
instructions provided by the m~nllf~cturers. Negligible changes in
surface wetting were observed in comparing coated samples before and
after the abrasive cleaning processes as measured by the repeated
20 dynamic water content angle method.
Example 8
Samples were prepared as described in Example I and were
deposited on a silicone contact lens. These samples were subjected to
water vapor autoclaving at 121 ~C for 5 successive sterilizing cycles, each
25 of 30 mim~tes duration. Negligible ch~n~s in the surface wettabilities
CA 02243869 1998-07-22
34
were observed in comparing samples before and after autoclaving,
indicating the durability of the coating compositions.
Example 9
Silicone contact lens substrates were coated using a gradient
5 layering technique. In this process an initially high duty cycle plasma
deposition was carried out for 30 seconds at a power of 100 watts and
plasma on/offcycle of 10 msec on and 20 msec off. Subsequently the
plasma offtime was increased sequentially to values of 50, 100, 150 and
200 msec. At each onloffcycle, the plasma deposition was operated for
several mimltes with the final 10/200 deposition being carried out for 5
minutes. The resl lltin~ gradient layered film structure exhibited
exceptional abrasion resistance and stability towards long term (i.e., 15
days) soaking under rapid (40 ml/min) flow conditions in PBS buffer at
a pH of 7.2. XPS (X-ray Photoelectron Spectroscopy) analysis of the
surface composition of this layered structure revealed a high resolution
C(ls) spectrum having ei~ctollti~lly the same composition as that observed
from a direct 10 msec plasma on and 200 msec plasma offdeposition at
100 watts peak power.
Example 10
The increased wettability of substrates having the coating
composition of this invention are shown by this example.
Water contact angle measurements were measured using both
static (sessile drop) and dynamic (modified Wilhelmy plate) methods for
coated and uncoated substrates. Static measurements were made using
distilled water and a Rame'-Hart goniometer. Dynamic measurements
were made using substrates immersed in succession in three solutions,
CA 02243869 1998-07-22
namely: saline; protein; and then again in saline. The protein solution
contained a mixture of albumen, Iysozyme and immunoglobin.
Advancing and receding contact angles were measured under both static
and dynamic conditions. In the static 1~pel i"lents, the advancing contact
5 angles were measured at 4 ',lL volume intervals as the water droplet was
increased from 4 to 16 ~L. Receding angles were recorded as the
droplet size was reduced from 16 to 4 ',lL, again at 4 IlL intervals. The
dynamic measulemellts were each repeated four times as the sample was
cycled up and down, with the average value being recorded for these four
I0 measurements.
Hydrophobic polymeric substrates (e.g. polyethylene;
polyethylene terephth~l~te) having static water contact angles in excess
of 85~ were employed. After plasma coating with coating compositions
of this invention, the wettability of the surfaces increased, evidenced by
15 the large decreases in the water contact angles. No substrate dependence
was observed in achieving the improved wettabilities.
Table II provides results of static sessile drop water contact
angles observed after tre~tm~nt of an initially hydrophobic polymeric
substrate with plasma deposited films by plasma deposition of di(ethylene
20 glycol) vinyl ether monomer. As show in Table II, all samples revealed
a decrease in water contact angles from the uncoated substrate whose
advancing angle was in excess of 85~ Also as shown in Table II, the
exact extent of increased surface wettability is a function of the plasma
deposition conditions, with the wettability generally increasing as the
25 average power employed during coating was reduced
, . , , ~v
CA 02243869 1998-07-22
,.
36
TABLE II
STATIC CONTACT ANGLES
Plasma RF CyclePealc Average Advaslcing Receding
S Coated Du~ TimesPower Power Angle Angle
ON, msec OFF,msec (W) (W)
Yes 10 200 100 4.76 60 33
Yes 10 200 50 2.38 46 30
Yes 10 200 25 1.~9 3() 15
Yes 1 20 2009.52 60 48
1 0 Yes 1 50 200 3.92 46 33
Yes 1 100 200 1.98 33 22
Yes 1 200 200 0.995 32 23
No >85
The dynamic (i.e. modified Wilhelmy plate) contact angle
measurements are listed in Table III for samples prepared by plasma
deposition of di(ethylene glycol) vinyl ether as described above, using an
RF on/off cycle of 10 msec on and 200 msec off and 100 watts peak
power. The advancing and receding contact angles are shown for
measurements in the three separate solutions7 with these measurements
being carried out in succession. As in the static measurements, the
dynamic studies reveal con~i~tçntly lower contact angles for the coated
substrates with the surface wettability being appreciably higher for
samples immersed in the protein co~ inin~ solutions.
Overall, the water contact angle measurements illustrate the
L~ r~ ion ofthe initial hydrophobic polymer surface to a hydrophilic
wettable surface as provided by the plasma deposited coatings.
CA 02243869 1998-07-22
37
TABLE III
DYNAMIC CONTACT ANGLES
Solution Advancing Angle Receding Angle
Saline 61 43
Protein in Solution 25 2
Saline 45 43
Example 11
Static (sessile drop) water contact angles, both advancing and
receding, were measured on polymeric substrates, plasma coated with
different monomers. The monomers employed were diethylene glycol
vinyl ether (EO2V), diethylene glycol rnethyl vinyl ether (Methyl EO2V),
diethylene glycol divinyl ether (Divinyl EO2V), and diethylene glycol
15 ethyl ether acrylate (Acrylate EO2V). These four coatings are given in
the table which follows. All plasma films were deposited under the
irl~nti~l RF on/offcycle of 10 msec on and 200 msec offand 100 watts
peak power. In each case, the uncoated hydrophobic polymeric surface
(initially an advancing angle in excess of 85~) was transformed to a highly
20 wettable hydrophilic surface by the plasma deposition. As shown in
Table IV, the hydrophilicity of the res--lting surfaces were relatively
constant with each of these monomers, with the degree of hysteresis
between advancing and receding contact angles being significantly
reduced for the two monomers not terminated in -OH groups (i.e. Methyl
25 EO2V and Divinyl EO2V).
CA 02243869 1998-07-22
38
The results obtained clearly illustrate the utility of employing the
coatings ofthis invention to ll~n~roll~ the surface ofthe substrate from
hydrophobic to hydrophilic.
TABLE IV
STATIC CONTACT ANGLES
MonomerAdvancing Angle Receding Angle
EO2V 60 33
Methyl EO2V 53 47
Divinyl EO2V 55 49
Acrylate EO2V 65 47
These examples show that the coating compositions of this invention can
15 be used to provide non-fouling and hydrophilic surfaces to substrates,
which have bulk properties which are well-suited for particular
applications. These coatings are particularly suited for biomedical
applications and in particular for contact or interoccular lenses.
The invention has been described in detail with particular
20 reference to pl~rel-ed embodiments thereof, but it will be understood
that variations and modifications can be effected with the spirit and scope
of the invention.
Example 12
A sample on a silicon substrate was prepared from the monomer
25 of Example 1 using plasma deposition conditions of an RF on/off cycle
of 10 msec on and 200 msec offa peak power of 50 watts. XPS analysis
of this film revealed significantly more carbon atoms bonded to oxygen
., .. . ., . .. "", , ,.,, . . ,. . . . . . .. I ~.. ,. ~ . . .. . ......
CA 02243869 1998-07-22
39
than to other carbon atoms. A sample prepared in this manner was then
exposed to air for 10 months for a long term stability experiment. The
sample was then re-analyzed by XPS. The relative concentration of C-O
to C-C groups present on the surface had actually increased slightly
5 revealing negligible surface modification during air exposure, indicating
the durability of the coating composition. (Figs. 4 (a-b)).
Example 13
Samples were prepared as described in Example I on quartz
substrate. Analysis of these films by UV-VIS spectrometry showed
10 complete light tr~n~mi~sion over the entire visible region of the
electromagnetic spectrum, 380 to 800 nm.
Example 14
Samples were prepared as described in Example 1 on DacronTM
substrates at a fixed plasma-on to plasma-off ratio of l to 20 but with
15 actual plasma-on and plasma-off pulse widths varying from 100 msec to
10 ~lsec and 2000 msec to 200 ~Isec, respectively. All runs were carried
out at a peak power of 50 watts and at constant flow rate and reactor
pressure of the EO2V monomer. XPS high resolution C(l s) spectra
showed that a variation in the percent retention of the ether content of
20 the plasma generated films was observed in these experiments with
dilIelel-l plasma-on and plasma-offpulse widths but all runs carried out
at a constant average power of 2.4 watts. (Figs. 5 (a-e)).
Example 15
Samples are prepared as described in Example 1 using a 10 ~Isec
25 plasma-on time and a 400 ~lsec plasma-offtime. Again, highly wettable
surfaces can be obtained cont~ining high C-O bonds relative to C-C
CA 02243869 1998-07-22
bonds, thus illustrating the production of usable films under ultrashort
(i.e. microsecond) pulse times.
