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Remote microwave plasma modification of biomaterials for biomedical applications

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Microwave Remote Plasma Modification of BiomaterMn foe ftiwnedicai Applications
Melodie L. Ridge
Master of Applied Science, H M
Graduate Department of Chemical Engineering
University of Toronto
ABSTRACT
Studies were conducted using a microwave remote plasma reaa-tr for iSc modification of nure.s 2. s f 0r
biomedical applications. The work included characterization of the reactor and s jbscquem reduction of i_ -ttee
oxygen content by hydrocarbon attachment. Blood interaction with the modified biosnaierials was also exam ked
Preliminary characterization of the reactor was completed usm g PS as a test material. The majority of
the study was conducted with ethylene as the monomer gas. Additional tests were performed using butane in
combination with argon . Poly methyl methacrylate (PMMA) was used as the substrate. with com parison studies
com pleted on glass and Teflon. The effect of reactor power, monomer flow rate, reaction time, and distance
b etw een the sample and the plasm a zone were studied. Analysis of the surface was perform ed using X-ray
Photoelectron Spectroscopy and contact angle measurements.
T he surface oxygen concentration dropped from 23.6% for unmodified surfaces, to 3.4% for highly
m odified surfaces, which signified that PMMA was covered by a hydrocarbon layer.
T he modified flat surfaces were interacted with whole blood for one hour. Platelet counts of the bulk
blood and Scanning Electron Microscopy (SEM) were used to determine the platelet response. Little difference
w as seen amongst the platelet counts for modified and unmodified surfaces. SEM showed sim ilar platelet
distribution for the various modified surfaces; however, a distinct difference in platelet response between the
con tro l and modified surfaces was evident. The preliminary results from the blood- biom aterial interaction
demonstrated the feasibility o f conducting blood response tests on flat samples. The change in platelet response
for modified and unmodified surfaces illustrates the applicability o f plasm a modification for this area o f research.
i
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ACKNOWLEDGMENTS
i would like to thank both of my supervisors, Prof. Sefton and Rana Sodhi, for
their guidance throughout this endeavour. Rana provided much needed support and
encouragement He opened the doors of surface science to me and helped me develop a
thorough understanding of the scientific process.
I would also like to thank Brian Callen for his suggestions and assistance
throughout my studies at the Centre for Biomaterials. I am grateful to Laila Amer for her
assistance with the blood work and to Battista Calvieri for his help with the SEM. His
flexible schedule and creative time management skills were much appreciated.
Finally I would like to thank my family and friends for their continuous support
and optimism throughout the past two years. Both Michael and my parents have been
motivational and encouraging and their support right to the end was greatly appreciated.
iii
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TABLE OF CONTENTS
A B ST R A C T ................................................................................................................................ii
A CKNOW LEDGM ENTS......................................................................................................iii
TABLE OF CONTENTS ...................................................................................................... iv
LIST OF F IG U R E S ..............................................................................................................vii
NOMENCLATURE .................................................................................................................x
1.0
IN TR O D U C T IO N ........................................................................................
1
2.0
THEORETICAL BACKGROUND ........................................................................ 4
2.1
Blood-Material Interface ...................................................................................4
2.2
Coagulation P ro cess............................................................................................ 5
2.3
P latelets................................................................................................................7
2.4
Factors Affecting Initial Blood-Surface Interaction........................................ 8
2.4.1
Fluid D ynam ics......................................................................................9
2.4.2
Protein A d so rp tio n ...............................................................................9
2.4.3
Surface C haracteristics...................................................................... 10
2.5
Surface Modification ....................................................................................... 12
2.6
Plasma Polymerization Process.....................
2.7
Characteristics of Plasma Polymerized Surfaces .......................................... 16
2.8
Process Parameters........................................................................................... 19
13
2.8.1
Frequency - Microwave R e a c to rs .................................................... 20
2.8.2
Position ...............................................................................................20
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2.8.3
Pressure .......................................................................................... 21
2.8.4
P o w e r...............................................................................................23
2.8.5
How R a te ........................................................................................24
2.8.6
M o n o m e r........................................................................................26
2.8.7
T im e .................................................................................................27
3.0
SC O PE O F T H E T H E S IS ......................................................................................29
4.0
EX PERIM EN TA L M ETHODS ...........................................................................30
4.1
4.2
4.3
Surface Modification .................................................................................... 30
4.1.1
Argon Plasma Modification -varying flow ra te s ............................ 34
4.1.2
Factorial Design for the Ethylene Gas S y ste m .............................. 34
4.1.3
Factorial design for the Argon & Butane Gas System ................. 35
4.1.4
Reactor in-situ with the X P S ........................................................... 35
4.1.5
Determination of the Effect of Sample P osition.............................36
4.1.6
Study of the Interdependence between Height & Time ............... 36
4.1.7
Degradation of the Modified S urfaces............................................ 36
Surface Characterization................................................................................ 37
4.2.1
X-Ray Photoelectron Spectroscopy.................................................37
4.2.2
Contact Angle M easurem ents......................................................... 38
Blood Interactio n ........................................................................................... 38
4.3.1
Blood C ollection................................................................................38
4.3.2
Blood-Material Contact ...................................................................39
4.3.3
Platelet C o u n t.................................................................................. 40
v
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5.0
4.3.4
SEM Surface P reparation .................................................................40
4.3.5
Scanning Electron M icroscopy........................................................ 41
R E S U L T S .....................................................................................................................42
5.1
Argon Plasma Modification ........................................................................... 42
5.2
Ethylene Plasma M odification.........................................................................45
5.2.1
Spectra of the R e su lts....................................................................... 45
5.2.2
Factorial Design & Statistical Analysis for the
Ethylene Gas System ..........................................................................46
5.2.3
Application of Extreme Parameter C onditions................................51
5.2.4 Surface S tab ility ................................................................................. 58
5.2.5 Contact Angle M easurem ents........................................................... 62
5.2.6
5.3
6.0
Blood In te ra c tio n .............................................................................. 63
Butane and Argon Plasma Modification ....................................................... 67
D ISC U SSIO N ..............................................................................................................71
6.1
Argon Plasma Modification ...........................................................................72
6.2
Ethylene Plasma M odification.........................................................................74
6.2.1
Spectra of the Results
......................................................................74
6.2.2
Factorial Design and Statistical Analysis for the
Ethylene Gas System .......................................................................... 75
6.2.3
Application of the Extreme P aram eters........................................... 77
6.2.4 Surface S tab ility ................................................................................. 80
6.2.5
Contact Angle M easurem ents...........................................................82
vi
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6.2.6
6.3
Blood Interaction ..............................................................................83
Butane and Argon Plasma Modification ..................................................... 84
7.0
CONCLUSIONS .......................................................................................................87
8.0
R EC O M M E N D A T IO N S..........................................................................................88
9.0
REFERENCES ......................................................................................................... 89
10.0
APPENDICES
Appendix A - Figures
.................................................................................. 94
Appendix B - Calculations ..........................................................................100
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LIST OF FIGURES
Figure 2.1.1
Flow path of the multiple systems which lead to thrombus formation from
blood-biomaterial co n tact............................................................................ 4
Figure 2.2.1
Coagulation cascad e......................................................................................
6
Figure 2.3.1
Sequence of events involved in platelet activation.....................................
8
Figure 2.6.1
Comparison of disposition and surface etching processes of glow discharge
modifications .................................................................................................. 15
Figure 2.8.0.1 Relationship of plasma parameters and their influence on the modified layer
........................................................................................................................ 19
Figure 2.9.5.1 Comparison of the effect of power and flow rate on deposition rate
26
Figure 4.1.0.1 Schematic of plasma re a c to r..........................................................................32
Figure 4.1.0.2 Four heights for reaction, with the 1 cm distance described as raised and 21
cm described as remote or platform p o sition............................................... 32
Figure 4.3.2.1 Photograph of the test cell during an experim ent........................................ 40
Figure 5.1.1
Effect of flow rate on oxygen uptake - PS modified by argon plasma . . 42
Figure 5.1.2
Effect of time and w a sh in g ............................................................................43
Figure 5.1.3
Plasma reactor modified polystyrene - C Is fitted for washed and unwashed
surfaces ...........................................................................................................43
Figure 5.1.4
Unmodified C Is peak for polystyrene ........................................................ 44
Figure 5.1.5
PS and PMMA modified in-situ with the X P S .............................................44
Figure 5.2.1.1 C Is spectrum for unmodified PM M A .......................................................... 46
Figure 5.2.1.2 C Is spectrum for modified P M M A ...............................................................46
Figure 5.2.2.1 Effect of power on surface oxygen ...............................................................47
Figure 5.2.2.2 Effect of flow rate on surface oxygen concentration ..................................48
vii
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Figure 5.2.2.3 Effect of sample position................................................................................ 49
Figure 5.2.3.1 SEM of modified surface................................................................................ 50
Figure 5.2.3.2 SEM of control su rface .................................................................................. 51
Figure 5.2.3.3 F I s peak for T e f lo n .......................................................................................51
Figure 5.2.3.4C Is peak of T eflo n......................................................................................... 52
Figure 5.2.3.5 O Is peak of Teflon .......................................................................................52
Figure 5.2.3.6 0 Is peak of g la s s ........................................................................................... 53
Figure 5.2.3.7 C Is peak of g la s s ........................................................................................... 54
Figure 5.2.3.8 Si 2p peak of glass ......................................................................................... 54
Figure 5.2.3.9 Effect of height and reaction time - glass modified by ethylene ................55
Figure 5.2.3.10 Angle resolved studies for various h eig h ts................................................. 57
Figure 5.2.3.11 Spectra of angle resolved studies for a sample modified in the raised
position ...........................................................................................................57
Figure 5.2.4.1 Extent of X-ray damage to modified surfaces .............................................58
Figure 5.2.4.2 Degeneration of modified surface from long term exposure to air
........................................................................................................................ 59
Figure 5.2.4.3 C Is spectra superimposed onto one plot showing degradation of the modified
surface for the platform sam ple..................................................................... 60
Figure 5.2.4.4 C Is spectra superimposed onto one plot showing the degradation of the
modified surface for the raised sample ........................................................60
Figure 5.2.4.5 Effect of washing on modified PMMA s u rfa c e ...........................................61
Figure 5.2.5.1 Relationship between surface oxygen content and contact angle
m easurements..................................................................................................62
Figure 5.2.6.1 Relationship between surface oxygen and bulk blood platelet count
........................................................................................................................ 63
viii
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Figure 5.2.6.2 SEM of the control su rfa c e ............................................................................64
Figure 5.2.6.3 SEM of the control su rfa c e ............................................................................ 64
Figure 5.2.6.4 SEM of the modified surface with 5% o xygen............................................. 65
Figure 5.2.6.5 SEM of the modified surface with 10% o x y g en ...........................................65
Figure 5.2.6.6 Platelet that has adhered to a biom aterial......................................................67
Figure 5.3.0.1 C Is spectrum of modified P M M A ...............................................................68
Figure 5.3.0.2 Effect of butane flow r a t e .............................................................................. 69
Figure 5.3.0.3 Effect of p o w e r................................................................................................70
Figure 5.3.0.4 Comparison of ethylene and butane/argon modifications of Teflon
........................................................................................................................ 70
Figure A 1
Angle resolve spectra of the carbon Is peak for a sample modified 6 cm from
the plasma..........................................................................................................95
Figure A2
Angle resolve spectra of the carbon Is peak for a sample modified 13 cm from
the plasma..........................................................................................................96
Figure A3
Angle resolve spectra of the carbon Is peak for a sample modified 21 cm from
the plasma..........................................................................................................97
Figure A4
High magnification of the platelet spread on the control surface ..............98
Figure A5
High magnification of the platelet spread on the modifiedsurface with 5%
surface o x y g e n ................................................................................................ 98
Figure A6
High magnification of the platelet spread on the modified surface with 10%
surface o x y g e n ................................................................................................ 99
ix
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1.
INTRODUCTION
Cardiovascular disease is the number one cause of death in North America.
Changing lifestyles and eating habits will reduce the occurrence of this malady but cannot
prevent it. Much research has been undertaken to design grafts to replace the worn or
blocked vessels in the body. The first attempts to replace blood vessels took place in the
1940's, with the most significant work being first performed in the 1950's with open heart
surgery (1).
Grafts are classified in two ways, either as large diameter and/or high flow, or as
small diameter (<4mm) and/or low flow.
Research has been plentiful within both
categories with the majority of the success being realised within the large diameter high
flow scenario. Due to differences in flow dynamics, the materials and design utilised for
one scenario are not directly applicable to the other. The blood-material interface is
extremely complex and minor variations, including differences in blood flow rate, alter the
degree of interaction. This results in high and low flow situations requiring different
approaches to attain biocompatibility.
The challenges facing the development of
cardiovascular implants are best described by Williams (1).
Extraordinary engineering and medical feats that they [cardiovascular prostheses] are,
such applications are usually simple in concept and the functional requirements very
conservative....With these devices, the difficulties and constraints on progress are not
related to these biofunctional requirements but far more to the interaction between the
blood and the devices in use. Were it not for the critical nature of these interactions
and the tendency for blood to interact unfavourably with virtually all materials placed
in its way our devices would last longer with better overall survival rates, and we
could expect to see devices of far more complex functionality.
Blood compatibility is, therefore, of utmost importance in determining the
1
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2
performance of devices within the cardiovascular system and serves a special place
and indeed its own volume, in a series on biocompatibility.
Unfortunately, despite much research linking characteristics of materials to the blood
response, this relationship has not yet been defined and it is still unclear as to which features
enhance biocompatibility. Many materials have proven to be incompatible, but there is no
definitive pattern for materials which show a positive response. All biomaterials presently
being used were never originally engineered for biomedical purposes. Instead 'common'
materials became biomaterials when they succeeded in a biomedical application. Research is
now geared towards designing materials, specifically the surface of materials, for a particular
biological interaction.
Surface modification of both chemical and physical properties,
provides the opportunity of achieving biocompatibility, which typically depends upon these
properties, without impairing the mechanical performance of the material, which primarily
depends upon the bulk properties (2).
Although there are a variety of surface modification techniques available, plasma
modification or glow discharge methods have been used more recently to create specialized
coatings for cardiovascular applications. Plasma polymerization provides the opportunity of
obtaining a variety of surfaces, depending upon the gas chosen to enter the reaction zone.
Studies completed on the plasma polymerization of materials for vascular grafts have been
shown to increase surface wettability and cell attachment (2), as well as lower fibrinogen
deposits with reproducible results on 4mm I.D. Dacron grafts (3). Glow discharge produces
a thin film which strongly adheres with minimal effect on the bulk properties o f a material.
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3
It was thus chosen as the method of modification for the purpose of
m in im iz in g
thromboembolism formation on small diameter vascular grafts.
When blood encounters a foreign surface its response will be affected by many factors
including functional groups and surface energy. Previous work by Strzinar et. al. (4) showed
that chemical modification to produce butylated surfaces acted to reduce thromboembolism
formation; presumably by the thin layer of platelets which first attached to the biomatetial
passivating the surface to further activity. These findings led to research on alkyl group
attachment to surfaces to further understand this phenomena.
Due to the previous success of glow discharge modification of biomaterials, a remote
microwave plasma reactor was implemented for the attachment of hydrocarbon groups to the
surface. Reactor parameters including power, gas flow rate, type of monomer, time and
sample position, were investigated to achieve specific modifications. The extent of surface
modification was analyzed using X-Ray Photoelectron Spectroscopy (XPS) and contact
angle measurements. Blood compatibility was determined by exposing the modified surfaces
to whole blood and then analyzing the platelet morphology using Scanning Electron
Microscopy (SEM). Platelet counts of the bulk blood after surface interaction were measured
to complement the SEM work. The majority of this work was conducted on poly (methyl
methacrylate) (PMMA), with some comparative studies on glass and Teflon. This research
results in a better appreciation of the applicability of glow discharge surface modification for
studying biocompatibility.
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2.0
TH EO R ETIC A L BACKGROUND
2.1
BLOOD-M ATERIAL INTERFACE
Immediately after blood contacts a foreign surface, a rapid series of events takes
place. The initial step involves protein adsorption onto the surface, with albumin, fibrinogen
and gamma-globulin constituting the majority of the adsorbed proteins. The various proteins
have different affinities for surface properties. The composition of the protein layer formed
is therefore dependent upon the surface (5,6). This protein layer directs the reactions that
follow s and thus is a primary determinant of the thrombogenic properties of the polymer
surface (5,6,7).
B lo o d
M aterial
P ro te in a d s o rp tio n ,
(4 )
T h ro m b in 4-
F ib rin o g e n
•P la tele t 4 ------
■► Leukocyte 4 -
a d h e sio n a n d
a c tiv a tio n
a d h e s io n a n d
•C o m p le m e n t
a c tiv a tio n
a c tiv a tio n
(9)
F ib rin
( 11)
E r y th r o c y te s
P la te le ts
( 10)
L e u k o c y te s
T h ro m b u s
Figure 2.1.1: Flow path of the multiple systems which lead to thrombus formation from
blood-material contact (9)
4
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5
Following the adsorption of the plasma proteins, conformational and compositional
rearrangements of the protein layer occur as a function of time(8). Several reactions occur
sequentially, and are all interdependent. These include the initiation of the coagulation
cascade, platelet and leukocyte adhesion and activation, and complement activation (Figure
2.1.1).
The end result of these multiple systems is the formation of a thrombus.
Thrombogenesis is extremely complex due primarily to the interaction among the
components.
2.2
COAGULATION PROCESS
The coagulation process involves many substances in an intricate sequence of
chemical reactions. Two different situations can trigger the coagulation cascade. The
extrinsic pathway is followed when blood contacts an injured blood vessel, which releases
tissue factor or thromboplastin. The thromboplastin interacts with clotting factor VII to
form prothrombin activator (Xa). At this stage the extrinsic pathway converges with the
intrinsic system. The intrinsic route is triggered when blood contacts a foreign surface and
clotting factor XII is activated. (10,11)
As seen in Figure 2.2.1, the two processes, extrinsic and intrinsic, follow the same
route via three phases or reactions to form a clot. The first stage involves the conversion of
prothrombin, a protein circulating in the blood stream, to the enzyme thrombin. Thrombin
acts on fibrinogen, (a soluble protein found in blood plasma), and severs its peptide chain.
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This produces insoluble fibrin threads which form the network for a clot. The final phase
involves the release of fibrin stabilizing factor from platelets and plasma globulins which
link the adjacent fibrin threads under the influence of thrombin. The fibrin threads adhere
to the foreign surface or injured vessel wall and entrap passing red blood cells and platelets
to build up the clot.
Intrinsic Pathway
Extrinsic Pathway
Surface
XII
Xlla
/^ V
XI
VII
DC
IXa
I
Tissue Factor
Vila + Tissue Factor
VII
(X a t\fe + Ca2+ + PL)
Piutluuifccn
Thrombin
Fbrinogen
Fbrin
Hard Clot
Figure 2.2.1: Coagulation cascade (12)
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7
2.3
PLATELETS
Platelets play a key role in thrombogenesis by forming the 'foundation' for the clot.
Platelets are non-nucleated cells derived from megakaryocytes in bone marrow and are 2-3
pm in diameter (6,13,14). They are uniformly discoid in shape until activated. Stimulation
o f platelets occurs when they encounter ruptured vessels or foreign surfaces. Platelets
adhere to the collagen of the damaged area, or to the foreign surface. In adhering, platelets
lose their discoid shape and become irregularly spherical and form psuedopods (6).
Once the platelets have adhered to the surface, they undergo a release reaction where
ADP (adenosine diphosphate) and other components are released from dense granules within
their inner core (15).
The release of ADP stimulates further platelet adhesion and
aggregation with the build up of a platelet plug. Platelet activation may also be stimulated
by the release of ADP from injured cells (13), or from thrombin, as shown in Figure 2.3.1
(6).
The platelet release reaction is coincident with the activation of the coagulation
cascade and thrombin formation. This further stimulates platelet aggregation and leads to
a self-perpetuating process. Thrombin acts as a link between platelet activation and the
coagulation cascade, by causing primary platelet aggregation and in the production of fibrin
from fibrinogen (6).
This encourages the formation of an integrated platelet-fibrin
haemostatic thrombus. There is also an interaction between the two processes, as the outer
coating o f platelets acts as a catalytic surface for the coagulation cascade and provides a
stimulus for platelet activation by binding to thrombin (6).
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8
PLATELET ACTIVATION
CIRCULATING
PLATELETS
VASCULAR
I NJ URY
OR
POLYMER SURFACE
ADHESION
PRIMARY
AGGREGATION
ADP
SHT
RELEASE
REACTION
M m m
ADP
ADP
AGGREGATION
F igure 2.3.1: Sequence of events involved in platelet activation (6)
2.4
F acto rs Affecting Initial Blood-Surface Interaction
Platelet adhesion to a surface may result from a receptor mediated response to a
binding site on an adsorbed protein, or by a conformational change of a glycoprotein on the
platelets surface (5). Once the platelet adhesion, release and aggregation sequence has
begun, it is difficult to terminate, even with the aid of anti-platelet agents and anti­
coagulants.
Research has focused on preventing or delaying the initiation of platelet
activation and understanding the mechanics involved. Many factors have been cited as
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9
influencing platelet adhesion including, fluid dynamics, protein adsorption and surface
properties (5,7,10,16).
2.4.1
Fluid Dynamics
Fluid dynamics plays a key role in the failure of small diameter vascular grafts. High
flow conditions have the advantage of breaking up platelet and Fibrinogen deposits, before
much develops.
Any build up on the surface of a small diameter vessel reaches a
catastrophic effect sooner than its larger diameter counterpart. A general relationship
between vessel diameter and platelets has been cited by Anderson, with platelet deposition
increasing as axial diameter decreases (6).
Common to all vascular grafts is the problem associated with surgery. Often the
foreign graft is placed at an angle to the natural one resulting in changes in the flow path of
the blood. Sutures and the physical interface between the natural and artificial graft also
result in flow disruption. These factors can result in flow reversal, stagnation points and
changes in shear rate along the vessel wall. Areas where blood flow is limited provide an
ideal environment for the rapid development of thrombosis (17).
2.4.2
Protein Adsorption
Since proteins are the first type of cells to adhere to an injured vasculature or foreign
surface, they play a fundamental role in the extent of platelet adhesion and degree of
activation. For this reason much research has been conducted on protein adsorption and
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factors which encourage specific plasma proteins to be adsorbed as well as their effect on
platelets.
Many studies have shown that surfaces with a preference for albumin
adsorption inhibit platelet adhesion (4,16,18,19,20). Conversely, surfaces with increased
fibrinogen and/or gamma globulin promote platelet adhesion and sometimes release reaction
and aggregation (21). Based on these findings, further studies were completed and showed
that pre-exposure of the surface to particular proteins enhances these results (16).
2.4.3
Surface Characteristics
With the recognition that particular proteins influence platelet reaction, it has been
important to understand the mechanisms behind this interaction. Factors including pH,
temperature, time, and concentration of proteins all influence the type of protein adsorbed
(16). The characteristics of the surface are also important. The surface properties that
influence biological response include; (i) chemical components such as polarity, acidity, Hbonding and ionic charge, and (ii) molecular motion such as polymer chain ends and their
flexibility. Topography, including roughness, porosity and surface imperfections are also
im portant Finally, the relative distribution of these components further influence the
biological response (22).
Many types of surfaces with various functional groups have been studied for blood
response and it appears that both extremes in surface energy, hydrophobic and hydrophillic,
show good bio-compatibility (23). Hydrophillic surfaces tend to preferentially adsorb
fibrinogen and gamma-globulin, but are also prevalent to anticoagulant attachment, which
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11
is critical in delaying chronic thrombosis. Hydrophobic surfaces however, are dominated
by album in adsorption and inhibited platelet activity (24). Unfortunately, it is extremely
difficult to attach anticoagulants to hydrophobic surfaces and hence thrombogenesis
ultimately results.
Work has been conducted to increase the affinity of albumin adsorption to surfaces
by the attachment of alkyl chains (25,26,27,28,29). The binding of free fatty acids (FFA)
to albumin was used as a model for albumin binding to alkyl chains (27).
Munro
hypothesized that the binding sites on albumin for FFA can be used to bond to alkyl chains
(25). The alkyl chains make the surface more hydrophobic, thus increasing the extent of
albumin adsorbed to the surface, and diminishing the amount o f platelets (27,28). Cooper
e t al. found that C-18 alkyl chains added to the surface of polyurethanes increased the initial
rate of adsorption of human serum albumin (HSA), with diminished fibrinogen and platelet
deposition and little platelet activity (29). This resulted in decreased thrombus deposits at
the blood polymer interface (27,28,29).
Further studies have been conducted on the
influence of chain length on albumin adsorption. Eberhart concluded that "since alkyl
groups can be easily and durably attached to many polymers of biomedical interest, it
appears that this method has the potential of improving blood compatibility of medical
devices" (26).
From these studies it was believed that the long alkyl groups increased the surface’s
affinity for albumin, passivating the surface towards platelets. Studies by Strzinar et. al. (4)
in which polyvinyl alcohol (PVA) was reacted with C-18 isocyanate, showed increased
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12
albumin adsorption, with no effect on platelet reactivity. Butylation of the PVA showed less
effect on albumin adsorption, compared to C-18 experiments, but decreased platelet activity.
This suggests that the reduced platelet activity may be due to the initial layer of platelets that
first adhered to the surface, rather than the extent of albumin adsorption.
The passivation of surfaces with alkyl chains warranted further research to determine
the exact cause of the reduction in platelet activity. Carbon chains were attached to polymer
surfaces for this reason, to facilitate the study of this issue.
2.5
SURFACE MODIFICATION
An array of surface modification techniques exist including, UV/Ozone, corona
discharge, and 'wet chemistry', but of particular interest is plasma discharge, which has been
shown to produce thin, strongly adherent stable films for a range of surface chemistries.
Other surface modification processes generally result in an increased level o f damage to the
surface, are slower than plasma modifications and follow different reaction pathways (30).
Plasma discharges have been used in studies to modify biointeractions, form a barrier film
to inhibit diffusion, and provide reactive sites for molecular immobilization (22). With
regard to blood-biomaterial interaction, some plasma modified surfaces have been shown
to favourably alter the surface chemistry of biomaterials with respect to protein adsorption
and biocompatibility (20). Studies by Yeh in which poly (tetrafluorethylene) (FITE) grafts
were modified with hexafluoroethane/H2 plasma showed a reduced platelet deposition of
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13
87% (31). Kiaei found that tetra fluoroethylene (TFE) glow discharge treated Dacron grafts
resisted thrombus deposition, embolization and thrombotic occlusion and believed this
resistance to be the result of the tightly bound albumin to the plasma discharge modified
surface (24). Kiaei attributed the success of lower fibrinogen deposits on TFE treated
Dacron 4mm grafts to the uniform and reproducible coating deposited by the glow discharge
process (3).
2.6
PLASMA POLYMERIZATION PROCESS
The history of the glow discharge or plasma polymerization process can be traced
to the 1870's, although a systematic approach to investigating this process did not occur until
the 1960’s (32).
As a result, the field is still in its relative infancy with regard to
comprehension of all of the reactions involved and to the modelling and control of the
process parameters. The glow discharge process is also complicated by the fact that there
are many different reactor designs, and methodologies that are applicable for one system are
not directly transferable to another.
The glow discharge process itself consists of a plasma, which is generated by an
energy source, whether microwave, radio frequency, heat or electrical discharge. The
plasma consists of partially ionized gas containing a complex mixture of species including
free radicals, ions, atoms, molecules, photons and electrons (33,34). The energy from the
microwave or other energy source is transferred to free electrons which collide with other
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molecules and surfaces. Inelastic conditions with molecules generate further electrons, free
radicals, ions and excited molecules (32). Interaction of these excited species with the
surface induces modifications to the surface.
Several processes can occur at the surface: surface ablation, functional group
attachment and deposition. A continuous competition occurs between the processes with one
predominating, depending upon the gas/vapour entering the system, the reactor design, the
polymer substrate and the discharge conditions (22). Etching occurs if ablation prevails over
surface bonding and film deposition, and the plasma reacts directly with the polymer. There
is still modification to the surface as the chemical nature and the morphology of the surface
are affected. If deposition on the surface occurs, whether by functional group attachment
or cross linking of the functional groups which would produce a film, then a completely new
chemistry may be found on the surface, depending upon the monomer gas (22). Figure
2.6.1, from Ratner (35) depicts the difference between etching and deposition from highly
cross-linked functional groups.
The modified surface developed by the deposition process may occur by several
mechanisms. Free radicals and other excited species on the substrate surface may react and
polymerize with molecules from the reactive gas phase. A polymerization process may
occur in the plasma region whereby small molecules in the gas phase combine together to
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15
Plasma
♦
(gup)®®®®®©©©
©©©©©©©©©©
©©©©©©©©©©
©©©©©©©©©©
Deposition
v -
r
■- " .v'-r: ■
Etching
b
©©©©©©©©©©
©©©©©©©©©©
©©©©©©©©©©
©&© J f t c
Xb
©©©©©©©©©©
©©©©©©©©©©
©©©©©©©©©©
©©©©©©©©©©
• Overcoating
• erosion
• surface reaction
Figure 2.6.1: Comparison of deposition and surface
etching processes of glow discharge modifications
form high molecular weight molecules. These large molecules eventually settle onto the
surface and bond with the reactive surface sites, hence forming a new surface (35).
Initially with surface deposition, individual functional groups or chains of functional
groups are deposited on the substrate. As the reaction proceeds, free radicals undergo
further reactions leading to the generation of cross-links between the functional groups. The
extent of cross-linking and fragmentation of monomer gas can be controlled by the
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16
parameters of the reaction (32). Hence plasma modification can form new surfaces either
by individual functional groups bonding to the surface or by complete film coverage with
crosslinked groups.
Throughout this reaction, the monomer gas is fed continuously into the reaction
vessel and is partially or completely consumed by the reaction. The terms monomer and
polymer are used rather loosely in glow discharge, as in typical plasma polymerization the
chemical structure of the newly bonded chemical groups are not necessarily repeated
monomer units (32). In many instances, the reaction procedure is not completed until the
sample has been removed from the reactor and exposed to air. Reactive sites, whether from
free radicals or excited species, are given the opportunity to complete the reaction by
interacting with air molecules. Although this still creates a modified surface, it is not due
solely to the 'monomer' gas. This action further complicates understanding of the reaction
pathway and predicting the resulting modified surface.
2.7
CHARACTERISTICS OF PLASMA POLYMERIZED SURFACES
Although the diversity of reaction pathways makes the glow discharge process
difficult to model and compare, it leads to a menagerie of uniquely modified surfaces (35).
These modified polymer surfaces in general are complex, strongly adherent, and are often
highly crosslinked. The high quality adhesion is a result of the multiple reactions occurring
simultaneously, including contamination removal, surface activation and surface-plasma
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17
species interactions (36). Plasma polymerization is not limited by the type of materials used
for substrates, nor to the shape of the sample. Entire medical devices can be treated, as long
as the surfaces 'see' the plasma, since the polymerized surface bonds conformationally to the
surface.
This also provides the opportunity of avoiding further sterilization steps as
coatings from the reactor are sterile.
In the situation where films are deposited (ie: crosslinked chains), the surface can act
as a permeation barrier, since the coating is usually pinhole free. The films formed are quite
thin, on a scale of a few molecular layers thick, which keeps monomer costs to a minimum.
The thin coatings also provide another extremely important advantage in that only the
surface properties are influenced. The appearance, topography and bulk properties remain
unaffected.
Since both the surface texture and the chemistry are believed to influence
biocompatibility, maintaining the surface's physical properties provides the opportunity to
study these variables independently (31,37,38). The thin layers also provide the opportunity
o f laying down laminates on the surface, with each one fulfilling a particular role. In the
microelectronics industry, applications of 500 layers are not uncommon (36). Depending
upon the apparatus set up, the multiple layers can be deposited without interrupting the
discharge, by changing the feed gases.
Despite having multiple layers of potentially
different chemistries, the surfaces is resistant to delamination due to the adhesive character
and thinness of each layer (40,41).
As is apparent, the advantageous characteristics of plasma polymerized surfaces are
extensive and have been reviewed in detail by many researchers (3,22,31,33,34,37,41,42);
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18
however, there are some disadvantages to this technique. The most obvious are: (i) the
complexities involved in the process, (ii) the difficulty in predicting or directing the type of
modified surface to be achieved, and (iii) analyzing this complex surface. Unfortunately
limitation in analysis techniques make detailed description of the type of modified surface
difficult (43). The complex reaction is also blamed for the broad distribution of surface
chemistries and functional groups which can occur (41). This problem is often remedied
by adjustments to the plasma process parameters. A final complication with plasma
polymerization is the variety of apparatuses currently being used. With the extensive
process parameters that are an integral part of the modification process, variations in the
reactor design itself further complicate this issue. Results from one researcher cannot be
directly compared to that of another due to the difference in reactor design (power levels,
geometry etc.) This dictates the tedious process of redeveloping the process parameters for
each reactor geometry (41).
The primary difficulty with the plasma modified surfaces themselves, is their limited
durability. Although many instances of long term stability have been recorded, others have
found that the surfaces degenerate with time. This has been attributed to the exposure of the
surface to air, which causes the accumulation of oxygen on the surface (41).
Due to the variety in monomers and preparation techniques, there is a wide range of
properties attainable. As Boenig describes, the limitations of properties are not fully known
and in fact they may be limitless due to the possibility of doping, grafting, and cofeeding of
multiple monomers (39).
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19
2.8
PRO CESS PARAM ETERS
The importance of the process parameters on plasma polymerization surface
modifications is well documented (32,39,44). They control the degree of cross-linking and
fragmentation, and affect the variation in chemical and physical properties of the resulting
surface.
The parameters which can affect the process reaction include reactor design,
frequency, distance between substrate and reaction zone, pressure, power, monomer flow
rate, type of monomer used and
reaction time. To add to the multitude
of reaction parameters to control,
Gasflow
rat*
interactions among the parameters also
play a role in the control of the
H«,f©
reaction.
N. tau
(basic
Figure 2.8.1 depicts an
0OS
excellent overview of the relationship
of
process
parameters
and
their
influence on the type of modification to
the surface (32,35).
Although
geometry
each
reactor's
affects the experimental
results, most researchers complete their
research by using the same apparatus,
Figure 2.8.0.1: Relationship of plasma parameters
^ their
on Lhe modified layer (35).
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20
unique to their work . A comparison of reactor geometries is not feasible, and hence will
not be discussed.
2.8.1
FREQUENCY - MICROWAVE REACTORS
Although both radio frequency (RF) and microwave u.iW ) systems are commonly
used for energy generation for plasma modification of polymers, MW systems have many
advantages. As outlined by Wertheimer, microwave plasma has been shown to produce
chemical results which differ significantly from other plasma modification processes (45).
Microwave discharges operate at a frequency of 2.45 GHz and have deposition rates that are
an order of magnitude higher than RF systems (46). The enhanced deposition rate is
attributed to the energy distribution curve in which a large portion of the electrons are found
in the high energy portion for microwaves (32). As a result, microwaves are characterized
by a higher density of active species for the same absorbed power (46). The greater quantity
of activated species result in a more uniform distribution of the plasma deposited film.
Regardless of the monomer used or the type of surface which is being created, a uniform
distribution encourages more reproducible results.
2.8.2
POSITION
The distance between the substrate and the reaction area affects the time required to
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21
achieve a particular surface and can affect the type of functional groups deposited on the
surface. Plasma polymerization has been shown to preferentially deposit near the monomer
inlet The actual deposition process tends to be uniform laterally but varies longitudinally
from the monomer inlet. Low flow rates of the monomer deposit a more uniform layer
across a broader region (31). Addition of a carrier gas to the system will narrow the
distribution range. Depending upon the monomer, the actual deposition characteristics will
vary. Yasuda and Boenig found that acetylene plasmas had a greater tendency to deposit
near the monomer inlet whereas ethylene resulted in a more uniform coating over a larger
area further away from the inlet (49,36). This was attributed to the relative reactivities of
the two gases, since the other reaction conditions were kept the same. Ethylene was found
to be less reactive than acetylene and travelled randomly throughout the reaction tube before
depositing. This accounts for the broader and more uniform deposition of the ethylene
relative to the acetylene (31).
2.8.3
PRESSURE
The pressure of the system varies depending upon whether or not a reaction is
occurring. Before the reaction begins, the pressure is generally reduced to a base pressure
range of millitorr. This will reduce the quantity of non-monomer molecules in the system
and avoid undesirable reactions (32). When the plasma polymerization process begins, the
pressure may fluctuate from the pre-reaction pressure as molecules are being removed from
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22
the gas phase as they are depositing on the surface, hence decreasing the pressure.
Fragmentation of molecules also occurs as the surface is being etched or when the feed gas
molecules are being broken up, which increases the pressure. A comparison of the reaction
pressure to the base pressure, will indicate which process is occurring (48). Examining
specific gases, Gazicki discovered that hydrocarbons showed a positive pressure change until
the power reached saturation levels with respect to deposition rates (48).
The pressure of the reaction affects the residence time, the average electron energy
and the mean free path. Mean free path is the average distance a molecule travels before
colliding with another molecule and is described by equation 1.
kT
**
s /lO d 2P
(1>
where:
p - mean free path (m)
k = Boltzman constant (J/K)
T = temperature (K)
d = diameter of molecule (m)
P = pressure (Pa)
Clearly there is a direct relationship between the mean free path and the gas density,
which is affected by the pressure of the system. As the gas density increases, the mean free
path diminishes. A corresponding relationship also exists between pressure and residence
time, for gas molecules in the plasma space.
The average electron energy is proportional to the power and is inversely related to
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23
the pressure. Plasma effects associated with low power, may also be achieved with high
reaction pressure.
Greater interaction of the plasma with the surface is achieved at low pressures, since
the mean free path is large. High pressures tend to minimize the area of the glow region
which limits the extent of plasma polymerization. Pressure is thus coupled with the position
of the sample with respect to the plasma, since they both are related to mean free path. The
pressure of the system also effects the homogenous nature of the deposition. Low pressures
encourage a more uniform deposition of the polymer and as the pressure of the system is
increased the inhomogeneity of the modified surface increases (32).
In general, most reactions are conducted with the pressure in the range of millitorr
to centitorrs, as a balance to meet all of these constraints. This also helps maintain the costs
of the monomer since in many apparatus set-up, the pressure of the system is 'controlled' by
the monomer feed rate.
2.8.4
POW ER
Since power provides the energy for the plasma process, it is a critical factor. As the
pow er is increased, the glow region extends, which is important with respect to substrate
position. Deposition within the glow region involves a multitude of reaction pathways.
Beyond the glow region, the number of reaction pathways decrease and the deposition
process becomes more comparable to conventional polymerization techniques where the rate
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24
is quite low.
When the power is lower, the monomer structure remains more intact and the
resulting deposition layer resembles the structure of the feed gas. As the power is increased,
the feed molecules are more energized and are involved in more reactions. The plasma
polymerization layer that forms on the surface will depend upon the elements of the feed
gas. This variance in the type of species that bond to the surface for the same feed gas
demonstrates the extreme nature of what is possible with glow discharge (32).
Variation in power and the average electron energy determines the extent o f crosslinking. As the power is increased, the average electron energy also increases, thus greater
energy is available at the surface. This promotes breaking of bonds of higher energy and
crosslinking between functional groups.
2.8.5
FLOW RATE
Work by Morosoff has shown how the flow rate affects the deposition process (32).
As seen in Figure 2.9.5.1 where deposition rate is plotted against flow rate for different
reaction pressures, the relationship is complex. Initially, as the flow rate is increased, the
deposition rate also increases since the residence time is sufficient to ensure that all of the
monomer is reacted. A point is reached where the system becomes saturated with the
monomer and balance is attained between the monomer supply and the energy available for
reaction. Increase in the flow rate beyond this causes a decrease in residence time and hence
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25
a decrease in deposition rate. In this situation, there is not enough energy to activate all of
the incoming monomer. As a result, inactive monomer is pulled away from the plasma glow
region and passes over the substrate as it is pumped out of the system. This results in a
lower concentration of excited species interacting with the surface and hence a decrease in
the deposition of plasma polymerized material. The first part of the graph has been
described by Yasuda as the monomer-deficient region and the latter part as the energy
deficient region (32).
Changes in the flow rate also affect the flow pattern of the polymerization process.
Under conditions of low flow rate, much of the deposition process is concentrated near the
monomer inlet and in the glow region. As the flow rate increases to the saturation point, a
more uniform deposition of the polymer occurs.
Flow rate is also the prime controller of pressure for most reactors. As the flow rate
is increased, the pressure of the system also rises since the pumping capabilities remain
fixed.
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26
0 .3 0
P • 100 w
■ I Torr
• 2 Torr
A 4 Torr
o 0.20
0.10
20
40
60
00
100
Flow R o le (S T P c m ^ /m in )
Figure 2.9.5.1: Comparison of the effect of power and flow rate on
deposition rate (32)
2.8.6
M O N O M ER
Control of the plasma parameters will direct whether the monomer is deposited in
essentially the same form as the feed gas, or if it is fragmented, or if the monomer builds
upon itself and forms longer chains.
Hydrocarbons in general have a much lower deposition rate than other types of
m onomers (48). As a result greater time or power is needed to bond hydrocarbons to a
substrate surface. To attach hydrocarbon chains, the monomer should be of the same foim.
The choice between the saturation level of the hydrocarbons will influence the bonding and
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27
the time required to achieve particular results. The lower the molecular weight of the
monomer the greater the deposition rates are for a particular hydrocarbon family (39,49-.
The extent of saturation (with respect to bonding), also affects the rate of deposition, with
a steady escalation in plasma polymerization rates as the degree of unsaturation increases
(32). Kaplan and Dilks found that under the same operating conditions ethylene had twice
the deposition rate of ethane (43). They also compared the type of functionality formed on
the surface using C13-nuclear magnetic resonance techniques and concluded that ethane and
ethylene had similar amounts (19% and 24% respectively) of unsaturated hydrocarbons
bonded on the sample surface; however, acetylene produced much higher quantities (38%)
(43).
The input of the feed monomer may further be complicated by the addition of a
carrier gas. Carrier gases have been shown to increase the deposition rate by as much as an
order of magnitude (39). Carrier gases also tend to narrow the distribution of the depositing
polymer within the reactor. This effect becomes increasingly predominant as the mass and
size o f the molecules of the carrier gas increases (39). Depending upon the reactor design
this may be quite a lim itin g factor. On the other hand, it can be advantageous as it localizes
the plasma polymerization process.
2.8.7
TIME
Time directly affects the extent of modification to the surface. As the time frame for
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28
the plasma polymerization process is lengthened, the degree of surface modification is
correspondingly augmented. Longer times provide the opportunity for a more complete
coverage of a surface or for a greater extent of cross-linking. Time however can also have
a detrimental effect on surface coverage, depending upon the other process parameters, as
it provides the opportunity for fragmentation of functional groups that have already bonded
to the substrate.
Time also influences the costs involved in the process as longer reaction times incur
greater monomer usage and expense. Generally, experimental procedures are designed to
alter the other process parameters to keep time to a minimum.
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3.0
SCOPE OF THE THESIS
The ultimate goal was to devise a strategy to minimize thromboembolism formation
on small diameter cardiovascular devices and to gain an understanding of the mechanisms
taking place at the point of the formation. This research was in part based upon work by
Strzinar e t al. (4), in which butylated surfaces were found to have reduced platelet activity.
The modification of the surfaces was to be completed using a remote plasma microwave
reactor and the applicability and benefits of this method for biocompatibility modification
were to be determined.
To achieve the objectives of the research, an intense study was conducted on the
effect of the reactor parameters on the modification process. Initial studies for reactor
characterization were conducted using polystyrene with an argon feed to attach oxygen
groups from residual water vapour in the reactor. The bulk of the work, however, was to
study the attachment of hydrocarbon groups to substrate surfaces, which predominately
consisted of poly (methyl methacrylate), with some comparative work conducted on glass
and Teflon. Both ethylene alone and, butane/argon mixtures were used as feed gases. The
surface was characterized by extensive use of X-ray Photo-electron Spectroscopy (XPS), and
the results were correlated to contact angle measurements. The modified surfaces were
exposed to whole blood and the blood compatibility was estimated by using Scanning
Electron Microscopy (SEM) to examine the morphology of the attached platelets and by
platelet counts of the bulk blood.
29
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4.0
EXPERIMENTAL METHODS
4.1
SURFACE MODIFICATION
Materials:
The PMMA was obtained from Cadillac Plastics, Toronto in sheet form,
approximately 1/16* of an inch thick. The Teflon was also in sheet form of the same
thickness, from Warehouse Plastics. The glass samples were cut from microscope slides
from VWR Scientific.
Oases: Several gases were used from both Canox and Matheson, with purities as described
below.
argon
- prepurified - 99.998%
(0 2< 3ppm, H20 < 5ppm
helium
total maximum impurities = 20ppm)
- high purity - 99.995%
( 0 2< 3ppm, H20 < 5ppm
ethylene
- C.P. grade - 99.5%
n-butane
- C.P. grade - 99.0%
total maximum impurities = 50ppm)
MW Remote Plasma Reactor:
The reactor was custom designed and the main chamber had a volume of
approximately 5.8 litres. A 2.45 GHz glow discharge was created within a cavity powered
by an Opthos Instruments Inc. Model MPG 4 microwave power generator with 100 W
maximum power. Change in temperature during reactions was minimized by an air cooling
30
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31
line attached to the cavity. The reactor itself consisted of a quartz tube, with interior
diameter of 7.5 cm connected to a stainless steel vacuum chamber, which was pumped out
using a trivac "A" dual stage rotary vane pump, model D16A, from Leybold. The pressure
o f the system was measured using a Series 275 analog readout and convection gauge by
Granville-Phillips. Gases were fed into the reactor via flow meters (Matheson, series E300
and E406, with glass flow tubes of 602 and 4 respectively). Nupro SS48K valves were used
to control the gases entering the reactor.
The remote microwave plasma reactor is a unique design with several features which
distinguishes it from other designs. The monomer may enter the reactor via two different
feed points, as seen in Figures 4.I.O.I. The main feed point attaches to the quartz tube in
the middle of the plasma discharge region. The secondary line attaches to the main
chamber, and the gas is directed to the bottom of the quartz tube. This provides the
opportunity of feeding one feed gas to the reaction zone and another to flood the region over
the substrate. A combination of gases may also be used by employing a T-union on the gas
lines and having multiple feeds enter at one point.
The unique design of the reactor provided the opportunity of reacting the samples
at different distances from the glow region. Initially, all experiments were conducted with
the samples in the remote or platform position, at the bottom of the quartz tube. As the
research became more advanced, the sample was placed at various heights with respect to
glow discharge. These positions are shown in Figure 4.10.2.
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32
Primary Gas Feed
I
MW (
A ir Cooling
Secondary Gas Feed
A I
1 cm
6 cm
“ 13 cm
Sample Holder -
21 cm
►To Pump
F ig u re 4 .1 .0 .1 : Schematic of plasma reactor
F igure 4.1.0.2:
Four heights for
reaction, with the 1 cm distance
described as raised,
and 21 cm
described as remote or platform
position
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33
Method
Samples were cut to approximately 1 cm2 for parameter control studies and 1.5 by
4 cm2 for the blood work. All samples were labelled and then were cleaned with methanol.
The reactor chamber was pumped down to a base pressure of approximately 20
mtorr and the power generator was turned on to allow it to warm up. Gas tubes and flow
meters were checked and any air leaks were eliminated. The reaction gases were fed into
the quartz tube, with the flows set to the desired levels, and the high voltage switch from the
microwave generator applied. The plasma was ignited with a Tesla coil and fine tuned to
ensure a stable plasma with the microwave reflectance at a minimum. The plasma was run
for several minutes at the desired experimental conditions, to stabilize the system and
minimise contaminates.
After the initial stabilization, the system was brought up to atmospheric pressure and
the samples were loaded, either on the platform or the adjustable 'raised' holder. The system
was pum ped down to the base pressure of 20 mtorr, and the feed gas was fed into the
reaction chamber. For hydrocarbon modification, the system was flushed out with the feed
gas by closing the vacuum chamber, and flooding the system to near atmospheric pressures
with the monomer.
This process was repeated again to maximize the removal of
contaminants (ie: air), before the reaction was begun.
W ith the system flushed out, and the gas entering the quartz tube at the
experimentally desired rate, the high voltage of the microwave generator was turned on and
the plasma was ignited as described previously.
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34
After the reaction was completed, the microwave was turned off, but the feed gas
was allowed to continue for hydrocarbon monomers. This was to minimize the possibility
of free radicals or other reactive species remaining on the surface and reacting when exposed
to air, thus incorporating oxygen onto the surface. The vacuum pump and gas feeds were
closed off and the system was raised to atmospheric pressure to remove the samples. The
freshly reacted samples were stored in petri dishes until the surfaces could be analyzed.
Generally, the experiments were scheduled so thatXPS analysis could be completed the day
after the reactor was used.
The general procedure described above was followed for all of the plasma reactor
experiments. Specific details for the various studies are outlined below.
4.1.1
Argon Plasma Modification - varying flow rates
Flow rates were varied up to 340 seem for times of 30s, at a power of 10W to study
the effect of flow rate on surface oxygen uptake from residual water vapour.
4.1.2
Factorial Design for die Ethylene Gas System
Experiments were conducted with three variables for power and flow rate and two
variables for time. The quantities tested include 20,40 and 60W for power, 247, 589 and
879 seem for flow rate and times of 10 and 20 minutes. Each combination of these
parameters was completed and followed up with factorial design calculations.
The time and washing experiments were run under conditions of 20W power, and a flow
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35
rate of 760 seem, for times of 1, 2 ,5 ,1 0 , 20,30 and 60 minutes. The samples that under­
w ent a wash phase were placed in distilled water in the ultra-sonicator for ten minutes,
before being placed in petri dishes for storage.
4.1.3
Factorial Design for the Argon and Butane Gas System
The two gases were independently fed through the flow meters, with the argon gas
using the large flow meter, and the butane using the small flow meter. Their flows were
combined before entering the top of the reactor using a T-union system. The argon was run
at full flow, specifically 762 seem and the butane was varied between just greater than 0,20
and 40 seem. As with the ethylene tests, the power was varied over 20, 40 and 60W,
however the time was restricted to ten minutes.
4.1.4
Reactor in-situ with the XPS
The plasma reactor was attached to the back of the XPS, providing the opportunity
for direct transfer from the reactor to the XPS. Samples of PS and PMMA were modified
under an argon flow o f 879 seem, power of 20 W and at times of 0.17,1 and 10 minutes.
W ithout exposing the samples to air they were directly transferred to the XPS analysis
chamber and analyzed. These samples were then removed from the XPS and subject to 10
minutes of air exposure before being returned to the XPS for further analysis. One set of
samples was exposed to air overnight, before the second phase of XPS analysis.
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36
4.1.5
Determination of the Effect of Sample Position
A large sample, measuring approximately 3cm in diameter was placed on the sample
holder and reacted under conditions of 20 W power, ethylene flow rate of 879 seem and a
time o f 20 minutes. This test was completed with samples in both the remote and raised
sample holder position.
Another phase of this test was completed in which under similar reaction conditions,
the sample holder was rotated every 5 minutes while the sample was subject to the glow
discharge.
4.1.6
Study of the Interdependence between Height and Time
Glass was reacted under varying conditions of height, and time. Throughout the
experiments, the flow rate was maintained at 247 seem of ethylene, and the power was 40W.
Experimental conditions for time included 1, 5, 20, 30 and 60 minutes, and the heights
studied included 1, 6, 13.5 and 21.5 cm away from the plasma core, as seen in Figure
4.1.0.2. These surfaces had angle resolved analysis completed on them as outlined in section
4.2.
4.1.7
Degradation o f Modified Surface
PMMA modified under conditions of an ethylene flow rate of 879 seem, a power of
20W and a time of 60 minutes were surface analyzed on the XPS for time periods of 1,19,
28 and 35 days after the initial plasma experiment This was completed for samples both
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37
in the platform and raised position.
4.2
SURFACE CHARACTERIZATION
4.2.1
X-Ray Photoelectron Spectroscopy
A Leybold MAX 200 XPS was used to analyze the surfaces. PMMA and Teflon
were analyzed with the Mg K a x-ray source operated at 12 kV and 25 mA. Glass was run
under the A1 K a source at 15 kV and 20 mA, to separate the sodium Auger peak from the
carbon Is peak. The size of the analyzed area was 4x7 mm2, except for angle resolved work
which was conducted on a spot size of 1 mm2. All surfaces were analyzed at a take off angle
of 90°, with some surfaces characterized at take off angles of 15,45 and 60°. Survey scans
and low and high resolution scans focusing on the carbon, oxygen, and silicon peaks (for
glass) were completed on all samples. For Teflon, the high and low resolution scans
analysed the carbon and fluorine peaks. The survey and low resolution scans were run at
a pass energy of 192 eV and the high resolution at 48 eV. Data work up included satellite
subtraction for the Mg K a X-ray, and normalization of all the spectra to account for
transmission functions of the instrument. Peak positions were calibrated against the C Is
peak at 285 eV(50), to correct for energy shifts from charging or variations in the
instrument's calibration.
Ratios of the C, O, and F peaks were empirically calculated from the low resolution
spectra, using the instrument's sensitivity factors for the Mg source of 0.34,0.78, and 1.0
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38
respectively, for the C Is, O Is and F Is peaks. For the A1 source, the sensitivity factors are
0.75,0.36, and 0.32, for the O Is, Si 2p, and C Is.
High resolution spectra were curve fitted using software affiliated with the
spectrometer for comparison of functionality peaks.
4.2.2
Contact Angle Measurements
A goniometer, from Dr. Neumann's lab at the University of Toronto was used for
contact angle measurements. Drops approximately 5 mm in diameter of distilled water were
placed on the sample and direct angle measurements were completed by measuring the angle
between the drop and the interface. Both sides of the drop were measured and six separate
measurements were made for each sample for statistical analysis. A control sample was run
prior to all measurements to ensure accuracy in the results. The magnification was kept
constant throughout the series of experiments to ensure consistency in the measuring
technique between the sets of experiments.
4.3
BLOOD INTERACTION
4.3.1
Blood Collection
Whole human blood was drawn from healthy individuals into syringes preloaded
with PPACK, a selective thrombin inhibitor.
The blood was used immediately for
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39
experimentation.
4.3.2
Blood-Material Contact
The samples were placed in a test cell developed by Dr. L. Amer as shown in Figure
4.3.2.1. The samples were placed beneath a 24 well culture plate, with a well surface area
o f 1.77 cm 2. The test cell ensures that the same surface area of test material is contacted
with the blood, as shown in Figure 3.3.2.1. 0.9% NaCl solution was added to each well one
hour prior to the experiment. The NaCl solution was removed and 250 pL of the freshly
collected blood was added to each sample well. The test cell was then placed on an
American 5 Rotator R4140 shaking platform, at a rate of 130 rpm, in a room at 37°C for 1
hour. A sample of the same blood was kept resting in the warm room to act as a 'resting'
control.
After one hour the blood was withdrawn from the wells into vials containing lOOpL
o f 100 mM EDTA solution. The wells were rinsed with 150 pL o f HTB and added to the
vials.
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40
F igure 4.3.2.1: Photograph of the test cell, during an experiment
4.3.3
P latelet C ount
The
blood-HTB-EDTA solution was placed in a Sysmex E-2500 Automated
Haematology Analyzer where the quantity of platelets in the blood was counted.
4.3.4
SEM Surface P reparation
The surfaces in the test cells were rinsed repeatedly with a saline solution, and then
were then fixed in a solution of 2% v/v gluteraldehyde in PBS and left undisturbed in a
refrigerator overnight.
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41
The fixed samples had the excess gluteraldehyde and PBS solution withdrawn from
the cells and then underwent a series of ethanol dilutions (10, 30, 50 ,70 90, 100 w/w%) to
dry them. Critical point drying was completed on the samples using an Autosamdri-810
critical point dryer to minimize distortion of the cells on the surface.
4.3.5
Scanning Electron Microscopy
SEM pictures were taken of the surfaces after contacting blood, and of modified and
unmodified control surfaces. The samples were gold coated using a Polaron Sputter Coater
to a thickness of 300 nm. The samples were then viewed using a Hitachi S-570 scanning
electron microscope at 60 pA and a 10 kV accelerating voltage.
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5.0
RESULTS
5.1
ARGON PLASMA MODIFICATION
Preliminary studies completed on polystyrene showed the influence of flow rate,
time and washing on surface oxygen content. Figure 5.1.1 shows the oxygen uptake as a
function of argon flow rate for flow rates up to 340 seem at a power of 10 Watts and a time
of 30 seconds, for samples reacted in the remote position. The surface oxygen increases
until approximately 17%, when the slope diminishes and saturation of the surface is
approached.
Effect of Flow Rate on Oxygen Uptake
PS modified by argon plasma
Row Rate (seem)
Figure 5.1.1: Effect of argon flow rate on PS modification
A similar result is seen in Figure 5.1.2 where oxygen uptake is plotted against time,
for an argon flow rate of 760 seem and a power of 20W. Initially there is a
42
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43
Effect of Time and Washing
PS / Ar 760 seem / P*20W
20
-
0
10
20
30
so
40
60
Time (minutes)
\~m~ unwashed «amp>»
washed m ip ie s
]
F igure 5.1.2: Effect of time and washing
dramatic change in oxygen content with a plateau reached within the first two minutes.
Beyond this point, greater intervals of time of reaction have no influence on surface oxygen
uptake. This figure also demonstrates the influence of washing on surface oxygen. Both
Plasm a Reactor Modified Polystyrene
c- c
c-o
c-.o
c=o
o- c=o
c=o
Figure 5.1.3: C Is fitted spectra for washed and unwashed
surfaces
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washed and unwashed surfaces show a similar trend in treatment, however the washed
surfaces have a lower oxygen uptake saturation point.
Comparison of the C Is spectra for washed and unwashed surfaces depicts the
changes that occur at the surface. The spectrum for pure polystyrene, as seen in Figure
5.1.4, shows the main carbon peak at 285 eV, with a shake up peak associated with a n -n *
transition for the aromatic ring at 292 eV (50). With argon plasma modification, the shake
up peak disappears, and peaks associated with C-O, C = 0 and 0 -C = 0 functionalities at
286.5, 288 and 289.5 eV emerge (Figure
5.1.3). The unwashed sample appears to have
more ester groups (289.5 eV), than the
Reactor tn*sltu with the XPS
35 n
30 A
washed samples (50).
25 A
£ 20A
iH
Polystyrene
C 1s peak
:-c
0
2
4
e
6
to
12
Time (minutes)
PS • vacuum
O
PS • air
PMMA • vacuum
□
PM M A -air
F igure 5.1.4: Unmodified C Is peak for Figure 5.1.5: PS and PMMA modified in­
polystyrene
situ with the XPS
To determine if the oxygen uptake was a result of residual oxygen and water vapour
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45
within the reactor or whether further reactions occurred after the modified surface was
exposed to air, experiments were conducted with the reactor in-situ with the XPS. The
experiments were conducted on PS and on PMMA, with an argon flow rate of 762 seem at
a power of 20W for time periods of 0.17, 1, and 10 minutes. Comparison of the surfaces
showed that the experiments in which samples were directly transferred to the XPS had
slightly higher oxygen incorporation than those exposed to air before analysis, as seen in
Figure 5.1.5.
5.2
5.2.1
ETH Y LEN E PLASMA M ODIFICATION
S pectra of th e Results
A fitted spectrum for the standard PMMA C Is peak is shown in Figure 5.2.1.1.
Both the C-O and 0 -C = 0 complexes are proportional with a ratio of 1:3 with the main C-C
peak. In contrast, the modified surface, shown in Figure 5.2.1.2, has a much larger C-C
peak, with only a small C -0 peak remaining. The ester peak has completely disappeared.
On average, the surface oxygen content changed from 23.6% +/- 2.2% to 3.4% +/-1.6%
for highly modified surfaces.
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46
Unmodified PMMA • C Is spectrom /*
c -o
290
Figure 5.2.1.1: C Is spectrum for unmodified PMMA
M odified PMMA - C Is spectnim
C -O
Figure 5.2.1.2: C Is spectrum for modified PMMA
5.2.2
Factorial Design an d Statistical Analysis for the Ethylene G as System
The three parameters chosen were compared under high and low conditions, with
further work completed for a middle range of power and flow rate, for samples modified in
the raised position. The values chosen were as follows: power at 20W, 40W, and 60W; flow
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47
rate of 247 seem, 589 seem and 879 seem and times of 10 and 20 minutes. These values
selected were based upon preliminary experiments with ethylene as a feed gas.
Effect of Power
PMMA
19.2
&14.4
9.6
4.8
0
10
20
30
40
50
60
Power (Watts)
» - flow=247sccm/t=10m - m - flow=247sccm/t=20m
flow=589sccm/M0m
—t— llow=589sccm/t=20m - S - flow=879sccmfa10m -El- flow=879sccnVU20m
Figure 5.2.2.1: Effect of power on surface oxygen
Figure 5.2.2.1 shows a plot of the surface oxygen versus power for the two time
periods and three flow rates. Initially there was a dramatic decrease of oxygen on the
surface. Increasing the power appeared to enhance this effect for flow rates of 247 and 879
seem. This relationship can further be appreciated by examining Figure 5.2.2.2, which
shows the effect of flow rate on surface oxygen. Flow rates of 589 seem caused an increase
in surface oxygen, regardless of the other parameters. The greatest extent of surface
modification was obtained with a power of 40W, for a time of twenty minutes for a flow rate
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48
of 247 seem. These values will be designated 'extreme parameter conditions'. Under these
conditions, the oxygen content changed from an average of 23.6% +/- 2.27 for the
unmodified samples to almost complete disappearance of the oxygen with 1.4% remaining.
Factorial design statistical calculations were completed on this work, as shown in the
appendix. With the generally small variations between the different design conditions,
however, conclusive results were difficult to obtain.
Effect of Flow Rate
PMMA
19.2 ■
9.6 -
200
600
400
Ethylene Flow Rate (seem)
800
1000
i- P=20WA=10min h i - P=20W/t=20mln - i - P=40WA=10mln
- P=40WA=20min -e- P=60W/t=10min -O- P=60WA=20min
Figure S.2.2.2: Effect of flow rate on surface oxygen concentration
Determination of statistical variations and precision of results for samples placed at
different positions on the sample holder was completed, as depicted in Figure S.2.2.3. Each
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49
group of columns can be divided into three subgroups, with two columns representing
independent studies of PMMA modified in the remote position, two columns representing
independent tests for raised samples, and the final column showing the effect of rotating the
raised sample during the experiment Comparison amongst the five groups of columns leads
to no conclusive results. There is variance amongst the repeated tests for both the platform
and raised experiments, showing little precision with the work. The final experiment, where
the sample was rotated throughout the experiment showed no improvement.
Effect of Sample Position
PMMA/C2H4
top
Ml
[ W c f n nn
Figure S.2.2.3:
oonm
u m p to pottlon
*4
right
bottom
M r d MfrmtWdj
Comparison of different sample
positions
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50
5.2.3
Application of Extreme Parameter Conditions
The highly modified PMMA surface was compared to a control for changes in surface
topography. This was accomplished by examining micrographs of the two surfaces. As
figures 5.2.3.1 and 5.2.3.2 demonstrate, no change to the physical features of the surface was
evident.
The extreme parameter conditions were utilized for surface modification of Teflon
and glass. Modification of Teflon resulted in approximately a 50% decrease in fluorine.
The fluorine and carbon 1 s peaks are shown in Figures 5.2.3.3 and 5.2.3.4. For the carbon
Is peak, the unmodified surface has a large peak at 292.4 eV, representing CF2 and a small
F igure 5.2.3.1: SEM of modified surface
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51
F igure 5.2.3.2: SEM of control surface
unmodified
modified
b in d , e n e rg y
te v j
Un
F igure 5.2.3.3: F Is peak for Teflon
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52
C7,
u n m o d ifie d _ j
m o d ifie d
Figure S.2.3.4: C Is peak of Teflon
alkyl peak at 285 eV (50). With modification the peaks reverse roles, with the alkyl carbon
peak dominating and a smaller CF, peak remaining. The C Is spectrum shows that there
is minimal carbon-oxygen interaction, with further evidence seen in the O Is peak in Figure
5.2.3.5.
modified-
Figure 5.2.3.S: O l s peak for Teflon
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53
Modification of glass under the extreme conditions, showed a change in oxygen
concentration from 65.5% to 5.8%. The changes to the O Is, C Is and Si 2p regions can
iI \1modified
«“>]
unmodified
/
,
40001
Figure 5.2.3.6: O l s peak of glass
be seen in Figures 5.2.3.6 - 5.2.3.8, respectively. Glass was also modified under 'extreme
conditions', but at various distances from the plasma zone. More comprehensive tests were
completed to gain a better understanding of distance between samples and the plasma with
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54
I
• unmodified
12000'*
J00001
aooo-*
I
6000*
,
modified —
4°o<h
.
'<
»»»■
30 5
300
295
290
265
260
Figure 5.2.3.7: C Is peak for glass
respect to effect on surface modification. Four heights, specifically 1 ,6 ,1 3 and 21 cm, were
chosen as distances between the sample and the plasma.
Examination of the central
columns in Figure 5.2.3.9 shows this relationship, with surface modification increasing as
the sample is moved closer to the plasma for reaction. The x-axis represents a combined
unmodified
modified
Figure 5.2.3.8: Si 2p peak for glass
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55
description of the height and time for the reaction - hence the two values for each column.
An extension of this work was completed to compare the effect of time at the
different heights. At the same flow rate and power, samples at a distance of 1 cm from the
plasma were reacted for times of 1,2 and 5 minutes (columns on left side of Figure 5.2.3.9).
Samples in the remote position (21 cm) were run at time periods of 30 and 60 minutes
(columns on right side of Figure 5.2.3.9). It appears that both time and height have a similar
extent of effect on surface modification.
To determine the thickness
C o m p a ris o n of H e ig h t a n d T im e
Ethylene System on Glass
of ethylene modifications at the
% Oxygen
four heights, angle resolved XPS
was
performed
on
the
401"
- — 1
■
— ——
___l
glass
substrates. Take off angles of 90°,
t/l
60°, 30° and 15°, (with respect to
shows the
change in surface oxygen for the
i/8
n
1/30
4 /3 0
18/30
31/30
n
31/30
.
31/40
H elgh((cm )/Tlm e(rnlnutei)
the surface), were analyzed on the
XPS. Figure 5.2.3.10
1/3
C U M -I4 n < c& /r-4 8 W
M g t l M ie n to dU tam ce t m i p4<
Figure 5.2.3.9: Effect of both height and reaction
time on ethylene modification of glass
four heights at the different angles. In all cases there was a general trend towards a decrease
in oxygen as the angle became smaller.
Calculations based upon a single fractional overlayer were completed using equation
2 with estimated mean free paths of the parameters as given by Ashley (52). The overlayer
was assumed to be polyethylene for these estimates.
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56
( f . p c . (1 - exp ( --------- —---------) ) )
____________________p c « s i n ( a )
I ’1
( ( 1 - f ) . p al* f • P j • exp ( -----------—
) )
p alc . s i n (a)
A,
mean free path of C in C layer
pt i = 36 A,
pSiC= 44 A,
mean free path of Si in glass
mean free path of Si in C layer
w h ere: pc = 39
f represents the fractional coverage
t represents the thickness
(A)
I represents the intensity
position of sample
thickness
(A)
from plasma (cm)
1
86
6
90
13
115
164
21
T able 1- Summary of values obtained from iterative calculations for different positions
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57
Table 1 lists the results
Angle Resolved Studies
for Various Heights
from the iterative calculations to
30 -
determine overlayer thickness.
25 -
These results are higher than
c
0
reasonable,
but
a
relative
comparison between the results
1
O
e
al
•n
a
(0
15 -
10
-
was completed. For distances of 6 ,
13 and 21 cm respectively the
10
20
X
40
50
60
70
80
90
100
Take-ofl Angle (degrees)
thickness o f the surface was found
21cm
to be 70%, 55% and 52% relative
to the thickness of the modified
„
Figure 5.2.3.10:
surface at a distance of 1 cm from
va” ous heights
■
1 3cm
A
gem
dtetanco Irom plasm a
. , ,
, ,
.
Angled resolved studies for
the plasma. The fractional
coverage was found to be
very similar and was greater
than 0.96 in all cases. The
modified samples
control
angle resolved spectra for
the C Is peak at a sample
height of 1 cm is shown in
*00
no
Figures 5.2.3.11, with the
spectra for the other heights
no
B ind, • n tr g y
ar?o
|aVJ
p - g ^ g 5 .2 .3 . 11 ; Spectra of angle resolved studies for a
sample modified in the raised position
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58
included in the Appendix in figures A1-A3.
5.2.4
Surface Stability
Determination of surface damage as a result of exposure to the X-rays during
XPS analysis, was completed during the angle resolved analysis. As seen in Figure 5.2.4.1,
which compares samples with a single x-ray exposure to samples that received nine times
X-Ray Damage to the Surface
70
glass-std glass-mod PMMA-std PMMA-mod
IM single x-ray exposure
B multiple x-ray exposures
F igure 5.2.4.1: Extent of X-ray damage to the modified surfaces
as much exposure, little difference is evident Surfaces that were exposed to repeated x-ray
treatments had a loss of approximately 3% oxygen.
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______________________________
Long
studies
were
term
Degeneration of Surface Modification
stability
completed
in
which PMMA samples were re­
examined
at
various
time
after
their
initial
25 -
20
periods
59
modification, to determine if
the surfaces degraded with time
-
c
o
§
3 15 0u)
■§
5 io -
from exposure to air. Samples
were approximately 21 cm
away from the glow region
o
5
10
15
20
25
30
35
40
Time (days)
when modified at the platform
level and 1 cm away at the
A
p latfo rm s a m p l e
■
ra is e d s a m p le
raised sample holder position.
Five sets of experiments were
Figure 5.2.4.2: Degeneration of modified surface from
long term exposure to air
completed for each position, with q-tests conducted on the results.
A plot of surfaces
modified in both the platform and raised sample holder position is shown in Figure 5.2.4.2.
Similar results occurred in both instances. As time progressed there was a general increase
in oxygen on the surface of the sample, with that for the platform samples occuring at a
slightly faster rate than the raised samples. Regardless of the treatment however, after 35
days the oxygen content had increased to pre-modified values. C Is spectra of this
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60
1 day
19 days
28 days
35 days
275
F ig u re S.2.4.3: C Is spectra superimposed onto one plot showing
degradation of the modified surface for the platform sample
degeneration, for both the platform and raised samples, may be found in Figures 5.2.4.3 and
5.2.4.4.
1 day
19 days
28 days
35 days
275
270
F ig u re S.2.4.4: C Is spectra superimposed onto one plot showing the
deagradation of the modified surface for the raised sample
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61
A further test of the stability of the surface was completed to determine if the
samples were affected by washing. As with the argon treated PS, ultra-sonication in
distilled water for ten minutes was completed. As seen in Figure 5.2.4.5, no significant
changes were observed.
Effect of Time & W ashing
0.1
1.0
100
1000
log tim e (m inutes)
l—
J unw ashed
Figure 5.2.4.S:
Effect
modified PMMA surface
w ashed
of
washing
on
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62
5.2.5
C ontact Angle M easurem ents
Contact
angle
Surface Oxygen and Contact Angle
measurements were completed
on a range of modified surfaces.
90 -
For
each
surface,
6
measurements of contact angle
were
made
completed
with
Q-tests
o) 00 -
at a confidence
interval of 90%. As seen in
70 -
Figure 5.2.5.1, a strong trend
relates the XPS analysis and the
contact angle tests. Unmodified
samples had a contact angle of
Surface Oxygen (%)
F igure 5.2.5.1: Relationship between surface oxygen
content and contact angle measurements
67° , and as the extent of
modification increased so did the contact angle, with highly modified PMMA samples
(approximately 4% oxygen) having a contact angle of 91°.
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63
5.2.6
Blood Interaction
Platelet Count
r«latlv* to t h t r a ttin g sam p la
0.5 ■
3
3
o.
Ia
at
0.4
-
0.3 ■
tr
0.2
-
0.0
0
5
10
t5
20
25
30
Suilace Oxygen (%)
platelet counts lor the retting ta m p le ■ 146+ /-13
Figure 5.2.6.1: Relationship between surface
oxygen and bulk blood platelet count
PMMA samples, modified to various degrees, were interacted with whole blood in
the flat surface test cell apparatus. Figure 5.2.6.1, shows the relationship of platelet counts,
relative to the resting sample of the bulk blood, with respect to surface oxygen.
T h e
average resting blood count was measured at 148 +/-13. All of the surfaces interacted with
blood showed a large drop in platelet count compared to the resting sample, although a
definitive relationship between surface oxygen and platelet count is not clear.
The SEM photographs of unmodified, and modified surfaces after exposure to blood
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64
Figure 5.2.6.2: SEM of the control surface
Figure 5.2.6.3: SEM of the control surface
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F igure S.2.6.4: SEM of modified surface with 5% oxygen
F igure S.2.6.5: SEM of a modified surface with 10% oxygen
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66
can be seen in Figures 5.2.6.2-5.2.6.5. The unmodified PMMA showed a very unusual
response to blood interaction with distinct interfaces between areas of densely populated
platelets and regions of little platelet coverage. The magnifications at 50 and 300 times
show this unusual response quite clearly. The modified samples (figures 5.2.6.4 and 5.2.6.5)
showed a dramatically different platelet and blood response from the control. A similar
extent of platelet response is seen for both levels of modification (5% and 10% surface
oxygen) with the platelets adhering to the surface and some spreading and pseudopod
development A high magnification shows a platelet that has adhered to a modified surface
(10% surface oxygen), and has extended pseudopods (Figure 5.2.6.6). Generally even
coverage was found across the modified samples, as compared to the unmodified samples.
High magnification of these three sets of samples may be found in the appendix in figures
A4, A5 and A6.
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67
Figure S.2.6.6: Platelet that has adhered to a biomaterial
5.3
BUTANE AND ARGON PLASMA M ODIFICATION
Spectra demonstrating the change in surface chemistry for surfaces modified by
butane with argon as a carrier gas are shown in Figure 5.3.0.1. The C Is spectrum is quite
sim ilar to what was obtained with the ethylene with essentially complete coverage of the
surface as indicated by the reduction of the oxygen functionalities.
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68
M odified PM M A - C Is spectrum
The optimization
of
the
modification
process was conducted in
a similar manner as the
C -0
ethylene system however,
only one period of time
Figure 5.3.0.1: C Is spectrum of modified PMMA
(10
minutes)
was
examined. As seen in Figure 5.3.O.2. where the surface oxygen concentration was plotted
against flow rate of butane, regardless of the power input a similar extent of modification
occurs for the low flow rate. A further increase in modification is seen as the flow rate is
increased for the medium and high powers; however, the low power showed a decrease in
modification. This variation amongst the flow rates is seen more clearly in Figure 5.3.0.3
for the low power. The maximum change in oxygen content was found to be under
conditions of an argon flow rate of 762 seem, butane at 40 seem and power o f 40W, which
resulted in a surface oxygen content of 2.6%.
The modification process using the 'extreme parameters' for the argon/butane gases
was compared to that of the ethylene system, using Teflon as a substrate. As Figure 5.3.0.4
shows, although both procedures modified Teflon, the argon/butane system was far more
successful, and reduced the surface fluorine concentration from 66.7% to 1.9% as compared
to ethylene which only reduced the fluorine concentration to 33.5%.
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69
Effect of Flow Rate of Butane
PMMA/Ar=762 se e m
1 9 .2 •
5 14.4 ■
4.8 ■
0
10
20
30
40
B utane R ow R ate (seem )
■A -
p o w er = 20W
p o w er = 4 0W - t — p o w er = 60W
F igure 5.3.0.2: Effect of butane flow rate
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70
Effect of Power
PMMA/Ar=762 seem
19.2 ■
8>14.4 ■
8re 9.6 ■
m
3
CO
4.8 •
0
20
10
30
40
50
60
Power (W)
C4H10 = 2 sccm
-X - C4H10 = 20 seem - I - C4H10 = 40 seem
Figure 5.3.0.3: Effect of power
P l a s m a M o d i f i c a t i o n o f Tefl on
s td
C 2H 4
ly p « o f tro a tr n o n t
C 4H 10
Figure 5.3.0.4: Comparison of ethylene and argon/butane
modification of Teflon
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6.0
DISCUSSION
PS, Teflon, glass and PMMA were utilised as substrates for plasma modification.
PS was used in the preliminary stages of the research to characterize the reactor. The
majority of the work involved PMMA with supplementary comparison studies performed
on Teflon and glass.
PMMA was chosen as the primary substrate as it is relatively
hydrophobic, minimizing the degree of modification needed and any modification will be
easily recognizable by a reduction of carbon-oxygen functionalities.
There were two criteria for the monomers used in this study - minimal reaction time
and the attachment of long saturated carbon chains. Aliphatic hydrocarbons were selected
to fulfil the chain stipulation. The selection of a particular monomer required a compromise
between the increased deposition rates achievable with unsaturated hydrocarbons (alkynes),
low molecular weight hydrocarbons (32,39,49) and the obvious advantage of using chains
already in the desired saturated form. Ethylene represented the "best fit", combining a
relatively low molecular weight with a double bond. In addition ethylene has been shown
to deposit more uniformly than other alkene gases (31). Butane was included in the study
as although the molecular weight is higher, the saturation level (single bond) is ideal and
provides the opportunity of attaching longer chains (ie. C4, C8).
Both gases were examined independently and with carrier gases. Modification was
lim ited with butane alone, and for ethylene with a carrier gas. For this reason a plasma
parameter inter-dependence factorial design was completed on butane/ argon mixtures, and
ethylene.
71
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72
Ethylene was used to determine the stability of the modified surface, the thickness
of the modified layer, the effect of modification on contact angle, and the blood response
to the modified layer. The butane/argon mixture was used in PMMA and Teflon
modification studies to compare the effect with ethylene modification.
6.1
ARGON PLASMA M ODIFICATION
Preliminary reactor characterization was performed using argon and PS. Argon
resembles a carrier gas in that it does not bond to the substrate surface but provides the
source of energized species which can interact with the surface creating free radicals and
active or excited sites. These sites react with oxygen, (from residual water vapour or air in
the reactor), resulting in oxygen bonding to the surface.
By focusing the characterization of the reactor study on the plasma modification
process for oxygen bonding, it avoids the difficulties involved in eliminating residual air
and water vapour from the reactor system. Pure PS does not contain oxygen functionalities;
any oxygen on the surface can therefore be attributed to modifications resulting from the
plasma discharge. The combination of these factors results in an ideal system for a study of
the reactor characteristics.
Varying flow rate and reaction time produced similar results. An increase in the
either parameter corresponded to an increase in surface oxygen until saturation was reached.
In both tests (Figures 5.1.1-2) saturation was achieved rapidly at relatively low flow rates
indicating that oxygen incorporation to the surface is easy to promote. The fact that
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73
saturation occurs indicates that optimal parameter levels exist, beyond which surface oxygen
uptake is independent of the parameter value.
The effect of washing on surface modification is clearly illustrated in Figure 5.1.2.
Regardless of the length of reaction time the "saturated" surface oxygen was reduced from
20% to 16% after being subjected to ten minutes of washing in distilled water within an
ultra-sonicator. The fitted spectra for unwashed and washed modified surfaces helps provide
insight to the chemical changes which occurred at the surface. The unwashed surfaces have
a greater quantity of carboxyl and/or ester functionalities on the surfaces as compared to the
washed samples.
For pure polystyrene a shake up peak for the phenyl rings is evident at
approximately 292 eV (50). The modified unwashed surface does not exhibit this peak,
suggesting that the surface has been reacted and the aromatic nature has been lost. After
washing, the shake up peak reappeared indicating that some of the modified surface had
been remo ved.
There was concern that the reaction was not completed within the reactor but upon
exposure to air. To investigate this hypothesis, reactions were performed with the reactor
in-situ with the XPS and compared with modified surfaces that had been exposed to air
before XPS analysis. If the hypothesis were correct then the "air exposed" samples would
contain more oxygen than those reacted in-situ. Figure 5.1.5 shows that this did not occur.
The samples analyzed in-situ with the XPS had higher oxygen incorporation than those
exposed to air, thus indicating that the modification was completed within the reactor.
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
74
6.2
ETH Y LEN E PLASMA M ODIFICATION
The argon modification of polystyrene aided in the characterization of the plasma
reactor.
The knowledge gained from these tests was utilised in determining plasma
parameters for ethylene modification.
6.2.1
S pectra of the Results
A comparison of the area and shape of the modified and unmodified high resolution
fitted spectra shows the extent of PMMA modification. The unmodified PMMA matches
literature results with a 1:1:3 ratio for the 0 = C -0 , C -0 and C-C peaks respectively (Figure
5.2.1.1). The disappearance of the ester peak, with only a small C -0 peak at 286.5 eV (50)
remaining on the modified PMMA spectrum indicates that the surface oxygen content has
been greatly reduced (Figure 5.2.1.2). The spectrum does not show however, if monomeric
alkyl groups have been added to the surface or if cross-linking has occurred.
The spectra represent ethylene modification under extreme parameter conditions:
a power o f 40W, a time of 20 minutes, and a flow rate of 247 seem, for a sample in the
raised position. Under these conditions the reaction pressure was found to increase slightly
to 2.4 torr, from the pre-reaction pressure of 2.2 torr indicating that the reaction is at the
saturation point with respect to flow rate and power, and that deposition as opposed to
etching is occurring.
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
75
6.2.2
Factorial Design and Statistical Analysis for the Ethylene Gas System
The results from a 23 factorial design of the parameters (flow rate, time, and power)
for the ethylene system showed a strong interdependence between the three parameters.
Additionally, time and power were shown to have a possible interactive effect on lowering
surface oxygen.
Comparison of the two plots (Figures 5.2.2.1 and 5.2.2.2), shows the similarity in
results for the various combinations of flow rate and power on surface oxygen, independent
of time. A t low flow rates, regardless of the power input, there is enough energy to excite
all of the monomer entering the reactor. As Yasuda described, this is the monomer deficient
region (32). Essentially all of the incoming monomer is excited and available for reaction,
thus more modification occurs reducing the surface oxygen content.
In the high flow
regime, although the average electron energy is lower than for the corresponding low flow
rate at the same power level, the quantity of monomer in the system floods the surface,
ensuring that all modification involves the monomer. The increase in surface oxygen over
the mid flow rates may be due to a balance between average electron energy, which
decreases with flow rate, and the quantity of available monomer units which increases with
flow rate. To minimize monomer usage, the lowest flow rate (247 seem) was used for all
subsequent modification work. Using a low flow rate at the saturation point for the reaction
promotes a uniform modification of the surface (31).
Flow rate can also be linked to the mean free path. Low flow rates result in low
reaction pressures (for a constant pumping speed) and thus long mean free paths. Energized
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76
species can travel greater distances to reach the substrate surface. As the monomer density
is increased the mean free path decreases, with only surfaces nearer the plasma region being
modified. Further tests must be completed incorporating distance from the plasma to the
parameters of flow rate and power.
Power initially has a major influence on surface oxygen content. The magnitude of
the effect diminishes as the power increases (Figure 5.2.2.1). The average energy for the
excited species is determined by power; an increase in power would be expected to have a
direct impact on the extent of surface modification. Lower power encourages surface
bonding and deposition, which are desirable conditions for hydrocarbon attachment (48).
Power also influences the extent of cross-linking as higher powers correspond to a greater
degree of cross-linking. A mid range power was selected as the initial objective was to put
on hydrocarbon chains, as opposed to a carbon surface, at a minimum reaction time.
Although the two time periods (10 and 20 minutes) showed similar results, the longer
time was selected for subsequent modification work due to the lower surface oxygen
concentrations achieved. The extreme ethylene modification conditions were deemed to be
40W of power, and an ethylene flow rate of 247 seem for a time of 20 minutes.
Plasma deposition generally varies longitudinally from the plasma core. Variations
in the results were noted for samples at different radial locations on the sample holder. As
Figure 5.2.2.3 shows, there was no trend in these variations whether examining sample
position in the platform, or raised position. Rotating the sample holder during the reaction
did not diminish the variability. There appears to be an inherent variance within the reactor
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77
system of approximately 2%.
Figure 5.2.2.3 also showed that samples in the raised position had a greater extent
of surface modification that those in the platform position. This suggests that the mean free
path for the ethylene system is limited and samples must be near the plasma to undergo
much modification.
6.2.3
Application of Extreme Parameter Conditions
A comparison of unmodified and modified PMMA surfaces determined that plasma
modification had no effect on surface topography, as depicted by Figures 5.2.3.1 and 5.2.3.2.
This characteristic allows for the study of blood response to purely chemical modifications
of the surface. This will aid in the determination of what features are dominating the bloodbiomaterial response.
M odification of glass and Teflon, was completed to determine if the plasma
parameters could be applied to other materials. Examination of the spectra, for ethylene
m odification of Teflon, shows the change in peaks for both the fluorine and carbon Is
spectra (Figures 5.2.3.3 and 5.2.3.4). This supports the idea that the optimal parameters may
be extended beyond the initial circumstances in which they were tested and that modification
of other types of surfaces can be realised.
Teflon was chosen as a substrate to determine if the remaining oxygen on the
modified PMMA surfaces was due to residual water vapour within the reactor bonding to
the surface. Pure Teflon does not have any oxygen functionalities, therefore a change to the
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78
O Is spectrum would signal that water vapour or air within the system was interfering with
the alkyl group modification. As Figure 5.2.3.5 exhibits, where unmodified and modified
0 Is peaks of Teflon are compared, there is essentially no change to the oxygen peak with
modification. The small amount of oxygen seen on the pure or unmodified surface is a
result of adsorbed water vapour on the surface. These results confirm that flushing out the
reactor prior to ethylene reaction, reduces air and water vapour within the system.
Considering how easily PS was modified by argon, (within two minutes of reacting
the surface was saturated with oxygen), it is surprising that residual water does not play a
larger role in alkyl modification. This suggests that ethylene polymerization quickly
dominates over activation of water vapour in the reactor.
Plasma modification by ethylene-was extended to surface modification of glass.
Examination of spectra for glass modified under ethylene optimal conditions demonstrates
immediately the extent of modification (Figures 5.2.3.6,5.2.3.7 and 5.2.3.8). Essentially
all of the silicon and oxygen have disappeared, and the alkyl carbon peak dominates.
Glass was chosen as the substrate to use in experiments to determine the thickness
of the modified surface. This was accomplished by comparing a peak unique to the substrate
to one in the modified layer (preferably unique as well). Since PMMA modifications by
ethylene involved varying concentrations of oxygen and carbon, it was not an appropriate
substrate for this study. Instead, glass was chosen due to the presence of silicon. The silicon
was used as a monitor for the substrate and the carbon as a signal for the modified layer. As
only a lim ited number of mean free paths have been determined, the mean free paths for
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79
polyethylene were assumed to be similar to the actual deposited overlayer. The calculations
resulted in thicknesses greater than the analysis depth possible with the equipment,
indicating that the assumption was not valid, and that the modified layer must be denser.
Regardless of the absolute figures, a comparison of the relative thicknesses amongst
modifications at different heights could be performed. As would be expected, surfaces
closer to the plasma had a thicker overlayer. Further studies on a different substrate surface
may lead to more quantitative results of the thickness of modification.
Figure 5.2.3.10 shows that regardless of the position that the modification took place,
at the 15° take off angle all oxygen contents approach the same value (approximately 4%).
Only low oxygen contents were attained at the raised sample position for the 90° take-off
angle indicating that the surface must be thicker. This signifies that the distance between
the sample and plasma, for reactions under the same conditions, determines the thickness of
the modified layer that is formed. Ideally, modification of surfaces would be controlled to
deposit a thin modified layer.
The changes in extent of surface modification for the various heights also
demonstrates the importance of mean free paths.
Distance between the sample and the
plasma plays a key role in determining the number of reaction pathways, the type and extent
of modification that occurs, and the time required for modification. This was also seen in
the experiments of position of the sample on the holder, in which reactions conducted near
the plasma region were more successful in covering the surface with hydrocarbon
functionalities than for samples farther away.
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
80
The experiments for distances between the sample and the plasma, conducted under
extreme parameter conditions, were extended for various intervals of time in order to find
a relationship between these two variables (Figure 5,2.3.9). Although only preliminary
studies were completed and a factorial design was not conducted, it is apparent that both
time and distance between the sample and the plasma have a similar influence on surface
modification.
6.2.4
Surface Stability
XPS analysis can cause damage to polymer surfaces, particularly under conditions
of repeated X-ray exposure. The PMMA samples proved to be quite resistant to X-ray
damage, with only minor changes to surface concentrations (Figure 5.2.4.1). In fact, the Xray exposure appeared to improve the surface by removing some of the oxygen, which may
be attributed to the removal o f adsorbed water from the surface. This indicates that there
is no need for concern of XPS analysis damaging the surfaces prior to blood exposure.
This success was not seen though, for samples exposed to air over long time periods
(Figures 5.2.4.2 - 5.2.4.4). Over the 35 day period the modified samples had undergone a
change in surface oxygen content with values akin to the unmodified surface. As outlined
by Ratner, oxygen incorporation of plasma modified surfaces exposed to air is an
accumulation process with respect to time (40). Although this is not the situation for all
modified polymers it is one of the main disadvantages of plasma polymers.
Further
research should be completed to determine if this situation applies to any material modified
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81
by ethylene, and if other monomers or modification processes run into the same difficulty.
Degeneration tests of PS modified with argon would indicate if the change in oxygen seen
with the PMMA was a result of oxygen adsorption from long term exposure to air or if the
new surface degrades with time. Studies with ethylene modification of glass or Teflon
would further aid this endeavour.
To minimize the effects of oxygen accumulation from air exposure, surface
characterization and blood work were performed within three days of surface modification.
Based upon the preliminary work conducted on PS modified by argon in which
washed surfaces removed some of the modification, studies were completed on ethylene
modified PMMA to determine if washing the freshly modified surfaces had any effect on
the degree of modification. Unlike PS, a decrease in modification was not seen with PMMA
modified by ethylene (Figure 5.2.4.5). This may be a result of ethylene providing the source
for the attached surface groups, whereas the argon acts as a conveyor of energy, with surface
m odification occurring as a result of breaking surface polymer chains which react with
residual air/water vapour in the system. Further experiments would have to be conducted
to determine if washing had any influence on other materials modified by ethylene.
The fact that washing does not influence the surface chemistry indicates that the
washing of the samples with a weak saline solution (0.2% NaCl) prior to blood contact
would not alter the surface modifications and the surface that the blood interacts with is the
same as that analyzed by both XPS and contact angle measurements.
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
82
6.2.5
Contact Angle Measurements
The contact angle measurements were conducted as a secondary analysis method for
surface modification. Direct angle measurements on a goniometer has an accuracy of
approximately +/- 2° (53). Generally, the repeated measurements made for each sample
proved to be quite reproducible, and were consistent with the results from the XPS. The
increase in contact angle for more modified surfaces of PMMA showed the increase in
hydrophobicity of the surface. Whether this change in hydrophobic nature is from long
hydrocarbon chains bonding to the surface or from a highly cross-linked layer of carbon
groups could not be resolved, without further surface characterization tests such as SIMS.
It was interesting to compare the contact angle measurements for the surfaces
modified under the same 'extreme' conditions but at different heights, /although all samples
showed sim ilar oxygen content at small take off angles, the contact angle measurements
differed. Samples that were modified in the raised position had much higher contact angle
measurements than those that were modified at distances further away. To better understand
these results further characterization of the surface must be completed and related to the
contact angle study.
6.2.6
Blood Interaction
The original goal behind the plasma modification process was to create an alkylated
surface and to study the blood response. From the XPS analysis, the extent of modification
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
83
was determined and the results were confirmed by contact angle measurements. Several
types of modified surfaces were exposed to blood to determine the platelet response.
Difficulty was encountered with leaking of the blood from the sample holder during
experiments which hindered the initial progress of this phase of the work.
The platelet counts for the bulk blood after surface contact showed very ambiguous
results. No trend was found that related blood response to hydropliobicity or surface oxygen
content Both modified and unmodified surfaces appeared to induce a similar extent of blood
response. The only feature that was apparent was that all of the surfaces, including the
control and the various levels of modified surfaces, had much lower platelet counts than the
resting sample (Figure 5.2.6.1). As the modified surfaces did not have detailed functional
group characterization, it is not possible to correlate the results to specific chemical
functionalities and chain lengths.
Further tests are required to formulate a definitive
relationship.
The preliminary results for the control surface showed very unusual results with
unnatural lines or regions of platelet coverage. This may be a result of the processing of the
plastic or from surface contamination. Several controls were interacted with the blood, for
each experiment, with this unnatural platelet coverage occurring each time.
cleaning techniques must be employed for future studies.
Improved
The high magnification
micrographs of areas where platelets had adhered showed extreme spreading of the platelets,
with little interaction with other cells.
The modified surfaces showed an even response to the blood interaction, across the
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84
surface. Platelets had adhered with some pseudopod development. They did not appear to
have spread as extensively as the control surface, but further experiments with the control
must be completed before detailed or valid comparisons can be made. There was some
interaction with other blood groups and areas were found where thrombus had developed.
The density o f platelets on the micrographs for the 10% and 5% surface oxygen contents
appeared to be quite similar, with possibly more platelets on the less modified surface
(Figures 5.2.6.4 and h.2.6.5). Quantitative analysis is difficult to obtain from micrographs,
so other analysis techniques are required to confirm this observation.
Although strong conclusions cannot be drawn from the blood work on the impact of
surface modification on blood response, it is important to realize that these are preliminary
results. With extensive research completed on the surface modification by plasma discharge,
and the development of the procedure for the blood interaction with flat surfaces, a research
base has been formed for future studies.
6.3
BUTANE AND ARGON PLASMA MODIFICATION
The studies on butane/argon plasma modification were conducted as a comparison
to the ethylene system. Using different feed gases provides further insight of the plasma
process, and may lead to interesting comparative studies on blood response.
The various flow rates of butane with a constant flow of argon were chosen based
upon the colour of the plasma. Since the glow is a result of energy being released from
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85
excited species, different colours represent different combinations of excited species, and
hence different reactions occurring. The plasma changed colour from a grey-blue at low
butane flow rates to a dark purple at high butane flow rates.
Spectrum of argon/butane modification showed very similar results to the ethylene
modification system(Figure 5.3.0.1). Essentially, all of the oxygen was removed, with only
a small C -0 peak remaining. Although the end result of the two modification processes
appears to be the same, in depth surface characterization by SIMS would give further details
regarding this question. It is also not known if the same reaction pathways were followed
for the two processes.
Figures 5.3.0.2 and 5.3.0.3 show the effect of power, and flow rate of butane on
surface oxygen concentration. Similar to the ethylene system, the low flow regime had a
dramatic effect on surface modification. This can be related to the average energy of the
excited species being quite high due to the low concentration of monomer.
The diversion,
with respect to surface oxygen, amongst the low power (20W) and, medium and higher
powers (40 and 60 W), for increasing flow rates suggests that at 20W the system is energy
deficient
Since carrier gases tend to narrow the distribution range of the surface
modification by changing the mean finee path, the diverse results at 20 W might be improved
if the experiment was repeated at a different sample position.
The argon/butane system was directly compared to the ethylene system by
modification of Teflon, under the respective extreme parameter conditions. Although both
modification processes showed a decrease in fluorine concentration, it appears that the
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86
butane process was far more successful. This suggests that although PMMA modification
by either monomer system appeared to have the same results on modification. Teflon
responds differently.
For Teflon, the two gas systems must follow different reaction
pathways. Further studies on surface characterization would have to be completed to
determine if the same modified surface could be obtained regardless of the feed gas used.
Regardless of the material, similar degrees of modification may be obtained. This
demonstrates that conditions for a particular modification process may be applied to various
materials with only fine-tuning' of the plasma parameters needed. Considering the extensive
time required to determine the optimal conditions for a particular type of modification, it is
beneficial to be able to apply the work to other areas.
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7.0
CONCLUSIONS
Attachment of carbon groups by ethylene modification was optimized by factorial
design techniques and the surface oxygen content was found to change from 23.5% to 3.4%
for highly modified PMMA surfaces, and from 65.5% to 5.6% for modified glass surfaces.
Angle resolved techniques and fractional overlayer coverage calculations showed that
samples modified near the plasma zone had a much thicker surface deposited than those
modified at further distances.
W ashing of PS samples modified by argon resulted in a loss of modified surface
with the oxygen uptake dropping from 20% to 16%. A series of surface stability tests
showed that although the ethylene modified surfaces were resistant to wash treatments they
degraded with time (over 35 days) from exposure to air.
The contact angle measurements correlated to the XPS analysis, and showed that
ethylene modification made the PMMA surfaces more hydrophobic.
The blood interaction studies resulted in similar platelet counts for both modified and
control surfaces. The SEM micrographs showed a similar extent of platelet spreading for
the two types of modified surfaces examined but, the blood response to the control sample
was very unusual with distinct vacant regions between areas of dense platelet adhesion.
With the extensive research completed on surface modification by plasma discharge,
and the preliminary studies with the flat surface test cell apparatus for blood interaction, a
research base has been formed for plasma modification of biomaterials for biocompatibility
tests.
87
with permission o f the copyright owner. Further reproduction prohibited without permission.
8.0
RECOMMENDATIONS
1)
Further studies should be completed on angle resolved analysis and thickness of the
modified layer, by ethylene modification. Comparative experiments using Teflon,
might provide more practical values of overlayer thickness. Relating the thickness
of the modified layer to contact angle analysis and blood experiments might provide
further understanding on the factors that influence blood response.
2)
Since the ethylene modification of PMMA was found to degrade with time, further
experiments with Teflon or PS as the substrate would determine if oxygen
incorporation to modified surfaces is influenced by the type of substrate. This would
also provide insight as to the actual 'degradation' process and would determine if it
is a result of adsorption of oxygen to the surface or decaying o f the modified layer.
3)
Since washing o f modified surfaces had a direct impact on PS modified by argon,
but no apparent effect on PMMA modified by ethylene, additional studies on other
materials modified by various types of monomers, would indicate what conditions
promote surface stability, with respect to water.
4)
More extensive characterization of the modified surfaces needs to be completed to
study the influence of alkyl groups on blood response.
88
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9.0
REFERENCES
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■
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94
Appendix A - Figures
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95
m od ified s a m p le s
60°
30®
14
15°
12
10
control
300
290
280
b in d , energy
270
[eV]
Figure A 1 : Angle resolve spectra of the carbon Is peak for a sample modified 6 cm from the
plasma.
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
96
90"
modified sam ples
15"
control
300
290
280
270
b in d , enaray teV]
Figure A2 : Angle resolve spectra of carbon Is peak for a sample modified 13 cm from the
plasma.
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97
90°
modified sam ples
60°
■14
12
15°
10
control
300
290
290
b in d , energy
[tv ]
Figure A 3 : Angle resolve spectra of the carbon Is peak for a sample modified 2 1 cm from
the plasma
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98
Figure A 4 : High magnification of the platelet spread on the control
surface______________________________________________
Figure A S : High magnification of the platelet spread on modified
surface with 5% surface oxygen.
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99
Figure A 6 : High magnification of the platelet spread on modified
surface with 10% surface oxygen.
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100
Appendix B - Calculations
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101
Angle Resolved Technique
Estim ation of L ayer Thickness
-t
))
pc . »tn (a)
-t
-))
( U -/) * P j f * Pd • exP (
p MC . ita (a )
( f • pc • (1-exp (
where,
pc
represents mean free path of C in C layer (A)
represents mean free path of Si in glass layer (A)
represents mean fiee path of Si in C layer (A)
represents the fractional convergence
represents the thickness (A)
represents the intensity
1
Angle
90°
60°
oo
Pa
priC
f
t
I
15°
Intensity
5.35
6.18
14.84
26.35
S.E>.
70
1.04
1.01
9.71
9.63
0.39
80
9.86
9.64
9.56
9.61
0.11
85
9.66
9.49
9.51
86
9.62
9.46
9.50
9.61
0.07
87
9.59
9.43
9.49
9.60
0.07
90
9.50
9.36
9.47
9.61
0.09
S.D.
I
0.07
height = 13 cm thickness = 90 A
angle
90
60
30
15
intensity
6.347
8.278
25.04
47.10
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102
thickness
= 90
9.76
9.73
9.74
j 9.77
1
0.015
S.D.
height = 6 cm thickness=115A
angle
90
60
30
15
intensity
10.20
14.080
60.38
73.32
thickness
= 115
9.73
9.75
9.87
9.85
0.0*
S.D.
height = 1cm thickness = 1 cm
angle
90
60
30
15
intensity
37.7
71.8
267.4
52.23
thickness
= 164
9.957
9.98
9.96
0.010
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103
FACTORIAL DESIGN OF ETHYLENE SYSTEM
Flow
Power
Time
% 02
247
20
10
5.74
yi
879
20
10
4.20
y2
247
40
10
2.83
y3
879
40
10
5.70
y4
247
20
20
4.14
y5
879
20
20
3.68
y6
247
40
20
1.40
y7
879
40
20
2.00
y8
Change of flow from 247 to 879
y2-y 1=4,403-5.737=-1.534
y4-y3=5.700-2.834=2.866
y6-y5=3.680-4.141=-0.461
y8-y7=2.000-1.403=0.597
Flow= 0.367
Change o f power from 20 to 40
y3-y l=2.834-5.737=-2.903
y4-y2=5.700-4.203=1.497
y7-y5=1.403-4.141=-2.738
y8-y6=2.000-3.680=-1.680
Power= -1.456
Change o f time from 10 to 20
y5-y 1=4.141-5.737=-1.596
y6-y2=3.680-4.203=-0.523
y7-y3=1.403-2.834=-1.431
y8-y4=2.000-5.700=-3.700
Time= -1.8125
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104
FACTORIAL DESIGN OF ETHYLENE SYSTEM
Power
Time
% 02
247
20
10
5.74
yi
879
20
10
4.20
y2
247
40
10
2.83
y3
879
40
10
5.70
y4
247
20
20
4.14
y5
879
20
20
3.68
y6
247
40
20
1.40
y7
879
40
20
2.00
y8
(Flow
Change of flow from 247 to 879
y2-yl=4.403-5.737=-1.534
y4-y3=5.700-2.834=2.866
y6-y5=3.680-4.141=-0.461
y8-y7=2.000-l .403=0.597
Flow= 0.367
Change of power from 20 to 40
y3 -y1=2.834-5.737=-2.903
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105
y4-y2=5.700-4.203=l .497
y7-y5=1.403-4.141=-2.738
y8-y6=2.000-3.680=-l .680
Power= -1.456
Change of time from 10 to 20
y5-y1=4.141 -5.737=-l .596
y6-y2=3.680-4.203=-0.523
y7-y3=1.403-2.834=-1.431
y8-y4=2.000-5.700=-3.700
Time= -1.8125
Flow=(4.203+5.7+3.68+2.00)/4-(5.737+2.834+4.141+1.403)/4=0.367
Power^(2.834+5.7+l .403+2.00)/4-(5.737+4.203+4.141+3.680)/4=-l .455
Time=(4.141+3.680+1.403+2.00)/4-(5.737+4.203+2.834+5.700)/4=-1.813
Interaction Effects
Flow X Time=(yl+y3+y6+y8)/4 - (y2+y4+y5+y7)/4
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=(5.737+2.834+3.68+2.0)/4 -(4.203+5.7+4.141+1.403)/4
= -0.299
How X Power=(yl+y4+y5+y8)/4 -(y3+y4+y5+y6)/4
=(5.737+5.7+4.141+2.0)/4 -(4.203+2.834+3.68+1.403)/4
=1.3645
Power X Time=(yl+y2+y7+y8)/4 -(y3+y4+y5+y6)/4
=(5.737+4.203+1.403+2.0)/4-(2.834+5.7+4.141+3.68)/4
= -0.753
How X Power X Time =(y2+y3+y5+y8)/4 -(yl+y4+y6+y7)/4
=(4.203+2.834+4.141+2.00)/4-(5.737+5.7+3.680fl.403)/4
=-0.8355
Interpretation of Results
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107
Effect
Estimate
average
3.704
Main effect
Flow
0.367
Power
-1.455
Time
-1.813
2 Factors
Flow X Time
-0.299
Flow X Power
1.365
Time X Power
-0.753
3 Factors
Flow X Time X Power -0.835
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
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