U.S. patent application number 15/160150 was filed with the patent office on 2017-02-16 for polymer coating comprising 2-methoxyethyl acrylate units synthesized by surface-initiated atom transfer radical polymerization.
The applicant listed for this patent is Technical University of Denmark. Invention is credited to Katja Jankova Atanasova, Charlotte Juel Fristrup, Soren Hvilsted.
Application Number | 20170044392 15/160150 |
Document ID | / |
Family ID | 41269072 |
Filed Date | 2017-02-16 |
United States Patent
Application |
20170044392 |
Kind Code |
A1 |
Fristrup; Charlotte Juel ;
et al. |
February 16, 2017 |
POLYMER COATING COMPRISING 2-METHOXYETHYL ACRYLATE UNITS
SYNTHESIZED BY SURFACE-INITIATED ATOM TRANSFER RADICAL
POLYMERIZATION
Abstract
The present invention relates to preparation of a polymer
coating comprising or consisting of polymer chains comprising or
consisting of units of 2-methoxyethyl acrylate synthesized by
Surface-Initiated Atom Transfer Radical Polymerization (SIATRP)
such as ARGET SIATRP or AGET SIATRP and uses of said polymer
coating.
Inventors: |
Fristrup; Charlotte Juel;
(Virum, DK) ; Atanasova; Katja Jankova; (Lyngby,
DK) ; Hvilsted; Soren; (Horsholm, DK) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Technical University of Denmark |
Kgs. Lyngby |
|
DK |
|
|
Family ID: |
41269072 |
Appl. No.: |
15/160150 |
Filed: |
May 20, 2016 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
13384130 |
Apr 4, 2012 |
9346971 |
|
|
PCT/DK2010/050187 |
Jul 14, 2010 |
|
|
|
15160150 |
|
|
|
|
61225840 |
Jul 15, 2009 |
|
|
|
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61F 2/24 20130101; A61F
2/82 20130101; A61L 27/34 20130101; A61B 2017/00889 20130101; Y10T
428/31649 20150401; A01N 37/02 20130101; A61F 2/07 20130101; A61N
1/056 20130101; C08F 2438/01 20130101; Y10T 428/1334 20150115; A61B
10/0233 20130101; C09D 133/062 20130101; A61L 29/085 20130101; Y10T
428/1393 20150115; A61B 50/30 20160201; Y10T 428/31935 20150401;
A61B 17/06066 20130101; A61M 5/30 20130101; A61M 5/178 20130101;
C09D 133/14 20130101; A61L 31/10 20130101; C12M 23/20 20130101;
A61L 2300/606 20130101; A61B 2017/00955 20130101; A61M 25/0045
20130101; A61B 2017/00995 20130101; A61L 31/048 20130101; A61L
31/10 20130101; A61M 27/006 20130101; A61L 27/16 20130101; C08L
33/14 20130101; A61L 2300/404 20130101; Y10T 428/1352 20150115;
A61N 1/05 20130101; A61L 27/34 20130101; C08L 33/14 20130101; A61L
29/041 20130101 |
International
Class: |
C09D 133/14 20060101
C09D133/14; A61L 27/34 20060101 A61L027/34; A61L 31/04 20060101
A61L031/04; A61L 29/04 20060101 A61L029/04; A61L 29/08 20060101
A61L029/08; A61L 31/10 20060101 A61L031/10; A01N 37/02 20060101
A01N037/02; A61L 27/16 20060101 A61L027/16 |
Foreign Application Data
Date |
Code |
Application Number |
Jul 15, 2009 |
EP |
09165556.3 |
Claims
1.-15. (canceled)
16. A polymer coating comprising polymer chains consisting of
repeating units of 2-methoxyethyl acrylate (MEA), wherein said
polymer chains are straight and covalently bound to a surface of
one or more polymer substrate(s) via one or more covalent bonds at
an end of each of the straight polymer chains.
17. The polymer coating of claim 16, wherein the straight polymer
chains are bound to the surface via initiator groups covalently
bound to the polymer substrate.
18. The polymer coating of claim 17, wherein the initiator groups
are alkyl halide initiators.
19. The polymer coating according to claim 16, wherein the polymer
coating is obtained or obtainable by Surface Initiated Atom
Transfer Radical Polymerization (SI ATRP), reverse ATRP,
Simultaneous Reverse and Normal Initiation (SR and NI) ATRP,
Initiators for Continuous Activator Regeneration (ICAR) ATRP,
Activators Generated by Electron Transfer (AGET) ATRP, or Activator
Regenerated by Electron Transfer (ARGET) ATRP.
20. The polymer coating according to claim 16, wherein said
straight polymer chains comprises at least 5 MEA units.
21. The polymer according to claim 16, wherein at least 50% of the
straight polymer chains comprise at least 5 MEA units.
22. The polymer coating according to claim 16, wherein the
substrate is selected from the group consisting of Poly(ether ether
ketone) (PEEK), Polypropylene (PP), Polyethylene (PE) (including
linear low density polyethylene (LLDPE), low density polyethylene
(LDPE) high density polyethylene (HDPE), ultra high molecular
weight polyethylene (UHMWPE), and cross-linked polyethylene (PEX)),
Poly(ethylene terephthalate) (PET), poly(propylene terephthalate
(PPT), PPT/PET copolyester, Polybutylene terephthalate (PBT),
Poly(vinyl chloride) (PVC), Polyamide/nylon (PA), Polycarbonate
(PC), Cyclic olefin copolymer (COC), Filter paper, Cotton,
Cellulose, Poly(4-vinylbenzyl chloride) (PVBC), Poly(vinylidene
fluoride) (PVDF), Polystyrene (PS), Toyopearl.RTM., Hydrogels,
Polyimide (PI), 1,2-Polybutadiene (PB), Liquid silicon rubber
(LSR), poly(dimethylsiloxane) (PDMS), fluoropolymers -and
copolymers (e.g. poly(tetrafluoroethylene) (PTFE),
Perfluoroethylene propylene copolymer (FEP), Ethylene
tetrafluoroethylene copolymer (ETFE), Polyvinyl fluoride (PVF),
Polyvinylidene fluoride (PVDF), Polychlorotrifluoroethylene
(PCTFE)), poly(methyl methacrylate) (PMMA), Acrylonitrile butadiene
styrene (ABS), styrene acrylonitrile (SAN), polyacrylonitrile
(PAN), Polymethylpentene (TPX), Polyoxymethylene (POM), Polysulfone
(PSU), polyetherimide (PEI), polyphenylene oxide (PPO),
polyethersulfone (PES), Polyphenylene sulfide (PPS), Polyamideimide
(PM), Liquid crystal polymer (LCP), Epoxy, Polyurethane (PU),
Thermoplastic elastomer (TPE), natural or synthetic rubber,
polyisobutylene (PIB), polyisoprene, poly(ethylene-co-propylene),
Kraton polymers: Poly(styrene-b-butadiene-b-styrene) (SBS),
poly(styrene-b-isoprene-b-styrene) (SIS),
poly(styrene-b-(ethylene/butylene)-b-styrene) (SEBS), and
poly(styrene-b-(ethylene/propylene)-b-styrene) (SEPS).
23. The polymer coating of claim 16, wherein the substrate is
selected from the group consisting of polypropylene, and Poly(ether
ether ketone).
24. The polymer coating of claim 16, wherein bacterial growth is
inhibited by more than 50% on the surface of the one or more
polymer substrate(s) compared to a non-coated substrate.
25. A device comprising one or more polymer surface(s) to which
straight polymer chains consisting of repeating units of
2-methoxyethyl acrylate (MEA) are covalently bound via one or more
covalent bonds at an end of each of said straight polymer
chains.
26. The device according to claim 25, wherein said device is
selected from the group consisting of a container, an implantable
device, a tubing device, a membrane, a film, a medical device, cell
culture dishes or flasks, bioreactors, syringe, needle, biopsy
needle, pipette tip, test tube, slide for microscopic inspection,
medicine bottle or ampoule, bag, pouch, implantable device, stent,
blood filter, blood storage bag, a blood sample glass or tube,
blood filter, a blood circuit, infusion set, pump, a catheter, a
pump, an oxygenator, prostheses, and biosensors.
27. The device according to claim 25, wherein said device is
selected from the group consisting of a container, an implantable
device, a tube, a catheter, a film, a membrane, and a filter.
28. The device according to claim 25, wherein the polymer of said
polymer surface is selected from the group consisting of Poly(ether
ether ketone) (PEEK), Polypropylene (PP), Polyethylene (PE)
(including linear low density polyethylene (LLDPE), low density
polyethylene (LDPE) high density polyethylene (HDPE), ultra high
molecular weight polyethylene (UHMWPE), and cross-linked
polyethylene (PEX)), Poly(ethylene terephthalate) (PET),
poly(propylene terephthalate (PPT), PPT/PET copolyester,
Polybutylene terephthalate (PBT), Poly(vinyl chloride) (PVC),
Polyamide/nylon (PA), Polycarbonate (PC), Cyclic olefin copolymer
(COC), Filter paper, Cotton, Cellulose, Poly(4-vinylbenzyl
chloride) (PVBC), Poly(vinylidene fluoride) (PVDF), Polystyrene
(PS), Toyopearl.RTM., Hydrogels, Polyimide (PI), 1,2-Polybutadiene
(PB), Liquid silicon rubber (LSR), poly(dimethylsiloxane) (PDMS),
fluoropolymers -and copolymers (e.g. poly(tetrafluoroethylene)
(PTFE), Perfluoroethylene propylene copolymer (FEP), Ethylene
tetrafluoroethylene copolymer (ETFE), Polyvinyl fluoride (PVF),
Polyvinylidene fluoride (PVDF), Polychlorotrifluoroethylene
(PCTFE)), poly(methyl methacrylate) (PMMA), Acrylonitrile butadiene
styrene (ABS), styrene acrylonitrile (SAN), polyacrylonitrile
(PAN), Polymethylpentene (TPX), Polyoxymethylene (POM), Polysulfone
(PSU), polyetherimide (PEI), polyphenylene oxide (PPO),
polyethersulfone (PES), Polyphenylene sulfide (PPS), Polyamideimide
(PAI), Liquid crystal polymer (LCP), Epoxy, Polyurethane (PU),
Thermoplastic elastomer (TPE), natural or synthetic rubber,
polyisobutylene (PIB), polyisoprene, poly(ethylene-co-propylene),
Kraton polymers: Poly(styrene-b-butadiene-b-styrene) (SBS),
poly(styrene-b-isoprene-b-styrene) (SIS),
poly(styrene-b-(ethylene/butylene)-b-styrene) (SEB S), and
poly(styrene-b-(ethylene/propylene)-b-styrene) (SEPS).
Description
[0001] This application is a divisional of U.S. patent application
Ser. No. 13/384,130, filed Apr. 4, 2012, which is a 371 application
of PCT/DK2010/050187, filed Jul. 14, 2010, which claims priority to
U.S. Provisional Patent Application Ser. No. 61/225,840, filed Jul.
15, 2009 and European application No. EP09165556.3, filed Jul. 15,
2009. All patent and non-patent references cited in the present
application are hereby incorporated by reference in their
entirety.
FIELD OF THE INVENTION
[0002] Many conventional biomaterials lack the ability to properly
interact with or support biological matter coming into contact with
said biomaterials leading to undesired biological responses.
However, these undesired responses may be controlled by altering
the chemical and physical properties of the surface of said
biomaterials. In this respect, surface modification represents a
well known strategy of providing suitable biocompatible materials.
The present invention relates to preparation of a biocompatible
material comprising a polymer coating consisting of or comprising
poly(2-methoxyethyl acrylate) (PMEA) synthesized by
Surface-Initiated Atom Transfer Radical Polymerization (SI ATRP)
such as ARGET (activator regenerated by electron transfer) SI ATRP
or AGET (activators generated by electron transfer) SI ATRP and
uses of said biocompatible material.
BACKGROUND OF THE INVENTION
[0003] Polymers have previously been synthesized by the Atom
Transfer Radical Polymerization (ATRP) method. The ATRP process was
introduced by Matyjaszewski and Sawamoto [1-3] using different
catalyst systems. ATRP is a controlled method which converts
monomers to polymers by using radical polymerization. The
initiators used for ATRP are commonly simple alkyl halides. A
halogen atom X is transferred during the polymerization. Moreover,
a catalyst system is present which consist of a transition metal
complexed by one or more ligands. The catalyst provides equilibrium
between the active form and the inactive form (called the dormant
state). The equilibrium is displaced towards the dormant state;
therefore, the polymer chains will only be active for a short time,
thus allowing for a suppression of chain termination reactions and
thereby controlling the polymerization. A controlled polymerization
method like ATRP will result in controlled molar masses, controlled
polymer architecture, and narrow molecular weight distributions
(cf. schematic illustration of ATRP in FIG. 1).
[0004] PMEA coatings have previously been disclosed including
PMEA-coated cardiopulmonary bypass circuits and oxygenators [4-6].
Protein adsorption studies on PMEA have also been disclosed
[7-8].
[0005] PMEA polymers have previously been made by free radical
polymerisation. Homopolymerization of MEA by ATRP has e.g.
previously been described [9-11]. However, previously described
PMEA coating is physically adsorbed to the surface whereas the PMEA
made by SI ATRP such as ARGET SI ATRP or AGET SI ATRP according to
the present invention is covalently bound to the surface. The
covalent bonds result in a PMEA coating with improved
characteristics such as improved long-term stability.
SUMMARY OF THE INVENTION
[0006] The present invention relates to a polymer coating
consisting of one or more repeating units of 2-methoxyethyl
acrylate (MEA) covalently bound to one or more surface(s). The
invention relates to a PMEA coating obtained and/or obtainable by
SI ATRP such as ARGET SI ATRP or AGET SI ATRP.
[0007] In another embodiment the present invention relates to a
device comprising one or more surface(s) covalently bound to
repeating units of 2-methoxyethyl acrylate (MEA). Said device can
be a container (such as a bottle, flask, box, bag, or ampoule), an
implantable device (such as a stent, or pump), a tubing device, a
membrane, a film, or a medical device (such as an infusion set, a
dialysis device, a catheter or a pump).
[0008] The present invention further relates to methods for making
a PMEA coating by SI ATRP such as ARGET SI ATRP or AGET SI
ATRP.
[0009] In one embodiment said SI ATRP such as ARGET SI ATRP or AGET
SI ATRP method comprises one or more of the steps of [0010] i) use
of initiator groups covalently bound to one or more surface(s) of a
substrate [0011] ii) adding one or more catalyst(s), one or more
ligand(s), 2-methoxyethyl acrylate and optionally one or more
solvent(s) to a reaction container comprising one or more
substrate(s) with one or more surface(s) comprising said initiator
groups [0012] iii) allowing the reaction to take place; and
optionally [0013] iv) use of one or more reducing agents [0014]
thereby making a PMEA coating covalently attached to the surface of
the substrate.
[0015] The present invention also relates to use of a coating of
PMEA covalently bound to one or more surface(s). Said coating can
be used for contacting one or more subject matters selected from
the group consisting of one or more protein(s), one or more
peptide(s), one or more body liquids, one or more tissues, and
meat. The one or more body liquids can be selected from the group
consisting of blood, blood plasma, serum, amniotic fluid, aqueous
humour, cerumen, Cowper's fluid or pre-ejaculatory fluid, chyme,
female ejaculate, interstitial fluid, lymph, breast milk, mucus
(including nasal drainage and phlegm), pleural fluid, pus, saliva,
sebum (skin oil), semen, sweat, tears, urine, vaginal secretion and
vomit.
[0016] In one preferred embodiment the present invention also
relates to use of a coating of PMEA covalently bound to one or more
surface(s) for contacting such as during storage blood such as
whole blood or fractions of blood. Blood fractionation is the
process of fractionating whole blood, or separating it into its
component parts. This fractionation can in one embodiment be
performed by centrifugation of the blood.
[0017] The resulting components of blood fractionation are in one
embodiment: [0018] a clear solution of blood plasma in the upper
phase, [0019] the buffy coat, which is a thin layer of leukocytes
(white blood cells) mixed with platelets in the middle, and [0020]
erythrocytes (red blood cells) at the bottom of the centrifuge
tube.
[0021] The PMEA coating according to the present invention can be
used for storage or contacting of any of these blood fractions or
mixtures thereof.
[0022] The PMEA coating according to the present invention can be
used for storage or contacting of any of the following samples:
[0023] Plasma protein(s) or plasma protein mixtures e.g. including
albumin and/or, immunoglobulins, and/or clotting proteins such as
fibrinogen. [0024] Plasma protein(s) or plasma protein mixtures for
clinical use and/or therapeutic uses. [0025] Plasma components for
clinical use such as factor VIII, factor IX complex,
immunoglobulin, antithrombin III, alpha-1-antitrypsin [0026]
purified plasma component for injection or transfusion. [0027]
Plasma or plasma proteins or plasma components for analytical uses
[0028] Plasma containing one or more biomarkers that can play a
role in clinical diagnosis of diseases [0029] Plasma for clinical
diagnosis
[0030] The PMEA coating according to the present invention can be
used for limitation or prevention of bacterial growth. The PMEA
coating can be used for bacteria repelling.
[0031] The PMEA coating can also be used for long terms as it has
long term stability. Accordingly, the PMEA coating can e.g. be used
for coating of a device used for long term storage of a suitable
material (e.g. any of the materials mentioned in this application)
for more than 1 months, more than 3 months, more than 6 months,
more than 1 year, more than 5 years or more than 10 years with out
significant leak of the PMEA coating into said material. With out
significant leak into said material can in one embodiment mean that
less than 5% of the PMEA coating is leaking into said material,
such as less than 1% or less than 0.1%
BRIEF DESCRIPTION OF THE DRAWINGS
[0032] FIG. 1: Scheme showing the principle of Atom Transfer
Radical Polymerization (ATRP).
[0033] FIG. 2: Structure of poly(2-methoxyethyl acrylate)
(PMEA).
[0034] FIG. 3: Preparation of poly(2-methoxyethyl acrylate)
(PMEA).
[0035] FIG. 4: Scheme showing the principle of Surface-Initiated
ATRP (SI ATRP).
[0036] FIGS. 5A-5D show examples of preparation of initiating
groups attached to surfaces of PEEK and PP, which can be used for
SI ATRP.
[0037] FIGS. 6A-6H show the effect on bacteria attachment. FIGS.
6A-6B show S. aureus static adherence results based on 3 hours and
24 hours on control and PMEA coated glass slides; FIG. 6C-6D shows
Staphylococcus epidermidis bacterial attachment on control and PMEA
coated glass slides; FIGS. 6E-6F shows Staphylococcus epidermidis
attachment to 96 well plates; and FIGS. 6G-6H shows S. aureus
incubated for 24 hours at 37.degree. C. showing 90% reduction of S.
aureus biofilm formation.
[0038] FIG. 7: Attenuated Total Reflectance Fourier Transform
Infrared (ATR FT-IR) spectroscopy
[0039] FIGS. 8A-8J show water contact angle (WCA) measurements.
FIG. 8A shows LSR: WCA adv. .apprxeq.120 degrees; FIG. 8B shows LSR
coated with PMEA: WCA adv. .apprxeq.69 degrees; FIG. 8C shows LDPE:
WCA adv. .apprxeq.90 degrees; FIG. 8D shows LDPE coated with PMEA:
WCA adv. .apprxeq.50 degrees; FIG. 8E shows PMMA: WCA static
.apprxeq.82 degrees; FIG. 8F shows PMMA coated with PMEA: WCA
static .apprxeq.51 degrees; FIG. 8G shows PP: WCA adv. .apprxeq.106
degrees; FIG. 8H shows PP-g-PMEA: WCA adv. .apprxeq.78 degrees;
FIG. 8I shows PP: WCA rec. .apprxeq.90 degrees; and FIG. 8J shows
PP-g-PMEA: WCA adv. .apprxeq.41 degrees.
[0040] FIG. 9: Scheme showing the principle of ARGET SI ATRP
DEFINITIONS AND ABBREVIATIONS
[0041] ATRP is an abbreviation of Atom Transfer Radical
Polymerization
[0042] Biocompatible surface: Material that, when interacting with
biological material, does not disturb the biological material, e.g.
without provoking a natural defensive response or e.g. does not
induce an acute or chronic inflammatory response or e.g. does not
prevent a proper differentiation of implant-surrounding tissues or
e.g. does not affect the stability of proteins and/or peptides.
[0043] Biocompatibility as used herein means the quality of not
having toxic or injurious effects on biological systems. In one
embodiment biocompatibility refers to the ability of a biomaterial
to perform its desired function with respect to a medical therapy,
without eliciting any undesirable local or systemic effects in the
recipient or beneficiary of that therapy, but generating the most
appropriate beneficial cellular or tissue response in that specific
situation, and optimizing the clinically relevant performance of
that therapy.
[0044] Biological material: Any material derived from a living
entity including plants, animals and human beings or a living part
thereof, such as an organ, tissue or cell. The preferred biological
system is a mammalian system, preferably a human system. The
biological material includes e.g. proteins, peptides and
enzymes.
[0045] Bodily fluids are liquids that are inside the bodies of
animals or human beings. They include fluids that are excreted or
secreted from the body as well as fluids that normally are not
excreted or secreted from the body.
[0046] Container can be any type of a container with a void cavity
for storage (with or without a lid) such as a bottle, flask, bag,
blood bag, pot, tub, dish, tray, bowl, basin, pill bottle, medicine
bottle, ampoule, flagon, syringe, needle, tube, cell culture dish
or flask, tissue culture dish or flask.
[0047] Fouling: Fouling refers to the accumulation of unwanted
material on a surface, e.g. in an aquatic environment. The fouling
material can consist of either living organisms (biofouling) or a
non-living substance (inorganic or organic). Other terms used in
the literature to describe fouling include: deposit formation,
encrustation, crudding, deposition, scaling, scale formation, and
sludge formation. The last five terms have a more narrow meaning
than fouling within the scope of the fouling science and
technology.
[0048] HMTETA is an abbreviation of
1,1,4,7,10,10-hexamethyltriethylenetetramine
[0049] Implantable device: as used herein, an implantable device
may be any suitable medical substrate that can be implanted in a
human or veterinary patient.
[0050] MEA is an abbreviation of 2-methoxyethyl acrylate.
[0051] A medical device is a product which is used for medical
purposes in an animal or a human being in any type of diagnosis,
treatment, therapy or surgery.
[0052] Membrane: Barrier between two phases and allowing transport
via sorption/diffusion and/or through pores.
[0053] PEEK is an abbreviation of poly(ether ether ketone)
[0054] PMDETA is an abbreviation of
1,1,4,7,7-pentamethyldiethylenetriamine
[0055] PMEA is an abbreviation of poly(2-methoxyethyl
acrylate).
[0056] PP is an abbreviation of polypropylene.
[0057] Prosthesis (plural prostheses) is an artificial extension
that replaces a missing body part.
[0058] Ratio: a ratio mentioned herein is a mole by mole ratio
unless otherwise specified.
[0059] SI ATRP is an abbreviation of Surface-Initiated Atom
Transfer Radical Polymerization. In one embodiment SI ATRP can be
performed without use of a reducing agent. Normal SI ATRP refers to
SI ATRP performed without use of a reducing agent.
[0060] The term `substrate` can be any material whereto the polymer
according to the present invention can be covalently bound to the
surface of said substrate.
[0061] AGET: activators generated by electron transfer.
[0062] AIBN: azobisisobutyronitrile.
[0063] ARGET: activator regenerated by electron transfer.
[0064] ICAR: initiators for continuous activator regeneration.
[0065] L: ligand.
[0066] M: monomer.
[0067] RA: reducing agent.
[0068] RAFT: reversible addition-fragmentation chain transfer.
[0069] SR&NI: simultaneous reverse and normal initiation.
[0070] X: halogen atom.
DETAILED DESCRIPTION OF THE INVENTION
[0071] Preparation of PMEA coating by SI ATRP such as ARGET SI ATRP
or AGET SI ATRP ATRP from one or more surface(s) of a substrate is
called Surface-Initiated Atom Transfer Radical Polymerization (SI
ATRP). The present invention relates to a method for making a PMEA
coating by SI ATRP (see FIGS. 2 to 4) or ARGET SI ATRP (see FIG.
9). In the SI ATRP method 2-methoxyethyl acrylate (MEA) is
polymerized from one or more surface(s) and a polymer with the
repeating unit shown in FIG. 2 is obtained. Accordingly, MEA is
polymerized from one or more surface(s) with initiating groups for
ATRP and not in solution. Note that the reaction kinetics for SI
ATRP are different from those of ATRP. The invention relates to a
PMEA coating obtained by and/or obtainable by SI ATRP such as ARGET
SI ATRP or AGET SI ATRP.
[0072] The present invention further relates to methods for making
a PMEA coating by SI ATRP such as ARGET SI ATRP or AGET SI
ATRP.
[0073] In one embodiment said SI ATRP such as ARGET SI ATRP or AGET
SI ATRP method comprises one or more of the steps of [0074] i) use
of initiator groups covalently bound to one or more surface(s) of a
substrate [0075] ii) adding one or more catalyst(s), one or more
ligand(s), 2-methoxyethyl acrylate and optionally one or more
solvents) to a reaction container comprising one or more
substrate(s) with one or more surface(s) comprising said initiator
groups [0076] iii) allowing the reaction to take place, and
optionally [0077] iv) use of one or more reducing agents [0078]
thereby making a PMEA coating covalently attached to the surface of
the substrate.
[0079] In another embodiment said SI ATRP such as ARGET SI ATRP or
AGET SI ATRP method comprises one or more of the steps of [0080] i)
use of initiator groups covalently bound to one or more surfaces)
of a substrate [0081] ii) adding one or more catalyst(s), one or
more ligand(s) and optionally one or more solvent(s) to a first
reaction container comprising one or more substrate(s) with one or
more surface(s) comprising said initiator groups [0082] iii) adding
2-methoxyethyl acrylate and optionally one or more solvent(s) to a
second reaction container [0083] iv) optionally remove oxygen from
said first reaction container and/or said second reaction container
by degassing and/or flushing and/or one or more freeze-pump-thaw
cycles, [0084] v) transfer the content of said second container to
said first container [0085] vi) allowing the reaction to take
place, and optionally [0086] vii) use of one or more reducing
agents [0087] thereby making a PMEA coating covalently attached to
the surface of the substrate.
[0088] In another embodiment said SI ATRP such as ARGET SI ATRP or
AGET SI ATRP method comprises one or more of the steps of [0089] i)
use of initiator groups covalently bound to one or more surface(s)
of a substrate [0090] ii) adding one or more catalyst(s),
2-methoxyethyl acrylate and optionally one or more solvent(s) to a
first reaction container comprising one or more substrate(s) with
one or more surface(s) comprising said initiator groups [0091] iii)
adding one or more ligand(s) and optionally one or more solvent(s)
to a second reaction container [0092] iv) optionally remove oxygen
from said first reaction container and/or said second reaction
container by degassing and/or flushing and/or one or more
freeze-pump-thaw cycles, [0093] v) transfer the content of said
second container to said first container [0094] vi) allowing the
reaction to take place, and optionally [0095] vii) use of one or
more reducing agents [0096] thereby making a PMEA coating
covalently attached to the surface of the substrate.
[0097] In another embodiment said SI ATRP such as ARGET SI ATRP or
AGET SI ATRP method comprises one or more of the steps of [0098] i)
use of initiator groups covalently bound to one or more surface(s)
of a substrate [0099] ii) adding one or more catalyst(s), one or
more ligand(s), 2-methoxyethyl acrylate and optionally one or more
solvent(s) to a reaction container comprising one or more
substrate(s) with one or more surface(s) comprising said initiator
groups [0100] iii) optionally remove oxygen from said reaction
container by degassing and/or flushing and/or one or more
freeze-pump-thaw cycles, [0101] iv) allowing the reaction to take
place, and optionally [0102] v) use of one or more reducing agents
thereby making a PMEA coating covalently attached to the surface of
the substrate.
[0103] In another embodiment said SI ATRP such as ARGET SI ATRP or
AGET SI ATRP method comprises one or more of the steps of [0104] i)
adding one or more catalyst(s), one or more ligand(s), and
optionally one or more solvent(s) to a reaction container
comprising one or more substrate(s) [0105] ii) optionally remove
oxygen from said reaction container by degassing and/or flushing
and/or one or more freeze-pump-thaw cycles, [0106] iii) adding
2-methoxyethyl acrylate and optionally one or more solvent(s) to
said reaction container after oxygen has been removed from said
reaction container and [0107] iv) allowing the reaction to take
place, and optionally [0108] v) use of one or more reducing agents
and thereby preparing a PMEA-coated surface.
[0109] In another embodiment said SI ATRP such as ARGET SI ATRP or
AGET SI ATRP method comprises one or more of the steps of [0110] i)
adding one or more catalyst(s), 2-methoxyethyl acrylate, and
optionally one or more solvent(s) to a reaction container
comprising one or more substrate(s) [0111] ii) optionally remove
oxygen from said reaction container by degassing and/or flushing
and/or one or more freeze-pump-thaw cycles, [0112] iii) adding one
or more ligand(s) and optionally one or more solvent(s) to said
reaction container after oxygen has been removed from said reaction
container and [0113] iv) allowing the reaction to take place, and
optionally [0114] v) use of one or more reducing agents [0115] and
thereby preparing a PMEA-coated surface.
[0116] In another embodiment said SI ATRP such as ARGET SI ATRP or
AGET SI ATRP method comprises one or more of the steps of [0117] i)
adding one or more catalyst(s), 2-methoxyethyl acrylate, one or
more ligand(s) and optionally one or more solvent(s) to a reaction
container under inert atmosphere such as in a glove box [0118] ii)
optionally remove oxygen from said reaction container by degassing
and/or flushing and/or one or more freeze-pump-thaw cycles, [0119]
iii) adding one or more substrates to said reaction container under
inert atmosphere [0120] iv) allowing the reaction to take place,
and optionally [0121] v) use of one or more reducing agents [0122]
and thereby preparing a PMEA-coated surface.
[0123] In one embodiment the one or more reducing agents are added
to the reaction in excess.
[0124] The one or more freeze-pump-thaw cycles used in the
preparation of the PMEA coating can be 2, 3, 4, 5, 6, 7, 8 or more
than 8 cycles of freeze-pump-thaw cycles.
[0125] The reaction for generation of a PMEA coating by SI ATRP
such as ARGET SI ATRP or AGET SI ATRP can take place at any
temperature such as at from 20.degree. C. to 25.degree. C., for
example at from 25.degree. C. to 30.degree. C., such as at from
30.degree. C. to 35.degree. C., for example at from 35.degree. C.
to 40.degree. C., such as at from 40.degree. C. to 45.degree. C.,
for example at from 45.degree. C. to 50.degree. C., such as at from
50.degree. C. to 55.degree. C., for example at from 55.degree. C.
to 60.degree. C., such as at from 60.degree. C. to 65.degree. C.,
for example at from 65.degree. C. to 70.degree. C., such as at from
70.degree. C. to 75.degree. C., for example at from 75.degree. C.
to 80.degree. C., such as at from 80.degree. C. to 85.degree. C.,
for example at from 85.degree. C. to 90.degree. C., such as at from
90.degree. C. to 95.degree. C., for example at from 95.degree. C.
to 100.degree. C. or any combination thereof). The reaction can
e.g. be performed at 20.degree. C., 25.degree. C., 30.degree. C.,
35.degree. C., 40.degree. C., 45.degree. C., 50.degree. C.,
55.degree. C., 60.degree. C., 65.degree. C., 70.degree. C.,
75.degree. C., 80.degree. C., 90.degree. C., 95.degree. C., or
100.degree. C. or any combination thereof.
[0126] The reaction for generation of a PMEA coating by SI ATRP
such as ARGET SI ATRP or AGET SI ATRP can take place for any
duration of time such as for 1 hour to 2 hours, for example for 2
hours to 3 hours, such as for 3 hours to 4 hours, for example for 4
hours to 5 hours, such as for 5 hours to 6 hours, for example for 6
hours to 7 hours, such as for 7 hours to 8 hours, for example for 8
hours to 9 hours, such as for 9 hours to 10 hours, for example for
10 hours to 11 hours, such as for 11 hours to 12 hours, for example
for 12 hours to 13 hours, such as for 13 hours to 14 hours, for
example for 14 hours to 15 hours, such as for 15 hours to 16 hours,
for example for 16 hours to 17 hours, such as for 17 hours to 18
hours, for example for 18 hours to 19 hours, such as for 19 hours
to 20 hours, for example for 20 hours to 21 hours, such as for 21
hours to 22 hours, for example for 22 hours to 23 hours, or such as
for 23 hours to 24 hours or any combination thereof. Alternatively,
the reaction can take place for less than 24 hours, such as less
than 23 hours, for example less than 22 hours, such as less than 21
hours, for example less than 20 hours, such as less than 19 hours,
for example less than 18 hours, such as less than 17 hours, for
example less than 16 hours, such as less than 15 hours, for example
less than 14 hours, such as less than 13 hours, for example less
than 12 hours, such as less than 11 hours, for example less than 10
hours, such as less than 9 hours, for example less than 8 hours,
such as less than 7 hours, for example less than 6 hours, such as
less than 5 hours, for example less than 4 hours, such as less than
3 hours, for example less than 2 hours, such as less than 1 hour,
for example less than 50 minutes, such as less than 40 minutes, for
example less than 30 minutes, such as less than 20 minutes, for
example less than 10 minutes, such as less than 5 minutes, for
example less than 1 minute.
[0127] The reaction time for generation of a PMEA coating by SI
ATRP such as ARGET SI ATRP or AGET SI ATRP determines the length
and molecular weight of the polymer chains.
[0128] In one embodiment the PMEA coating obtained by the SI ATRP
method such as ARGET SI ATRP or AGET SI ATRP comprises chains of
PMEA consisting of at least 5 MEA units, such as at least 10 MEA
units, for example at least 15 MEA units, such as at least 20 MEA
units, for example at least 25 MEA units, such as at least 30 MEA
units, for example at least 35 MEA units, such as at least 40 MEA
units, for example at least 45 MEA units, such as at least 50 MEA
units, for example at least 55 MEA units, such as at least 60 MEA
units, for example at least 65 MEA units, such as at least 70 MEA
units, for example at least 75 MEA units, such as at least 80 MEA
units, for example at least 85 MEA units, such as at least 90 MEA
units, for example at least 95 MEA units, such as at least 100 MEA
units, for example at least 200 MEA units, such as at least 300 MEA
units, for example at least 400 MEA units, such as at least 500 MEA
units, for example at least 600 MEA units, such as at least 700 MEA
units, for example at least 800 MEA units, such as at least 900 MEA
units, for example at least 1000 MEA units.
[0129] In another embodiment the PMEA coating obtained by the SI
ATRP method such as ARGET SI ATRP or AGET SI ATRP comprises chains
of PMEA, wherein at least 50% such as at least 60%, for example at
least 70%, such as at least 80%, for example at least 85%, such as
at least 90%, for example at least 95%, such as at least 99% of the
MEA chains consisting of at least 5 MEA units, such as at least 10
MEA units, for example at least 15 MEA units, such as at least 20
MEA units, for example at least 25 MEA units, such as at least 30
MEA units, for example at least 35 MEA units, such as at least 40
MEA units, for example at least 45 MEA units, such as at least 50
MEA units, for example at least 55 MEA units, such as at least 60
MEA units, for example at least 65 MEA units, such as at least 70
MEA units, for example at least 75 MEA units, such as at least 80
MEA units, for example at least 85 MEA units, such as at least 90
MEA units, for example at least 95 MEA units, such as at least 100
MEA units, for example at least 200 MEA units, such as at least 300
MEA units, for example at least 400 MEA units, such as at least 500
MEA units, for example at least 600 MEA units, such as at least 700
MEA units, for example at least 800 MEA units, such as at least 900
MEA units, for example at least 1000 MEA units.
[0130] The PMEA coating can be polymerized from the surface of
various substrates which means it will be covalently bound to the
surface of said substrate [15].
[0131] The one or more catalyst(s) can be selected from the group
consisting of CuBr and CuCl. In one preferred embodiment the metal
ion in the catalyst is copper. In another embodiment the metal ion
can be selected from the group consisting of ruthenium, iron,
nickel, palladium, cobalt, rhodium, rhenium, osmium, titanium,
lithium, molybdenum, and chromium. Accordingly, ruthenium, iron,
nickel, palladium, cobalt, rhodium, rhenium, osmium, titanium,
lithium, molybdenum, chromium and copper can work as catalyst in
various complexes. In addition, other catalysts in combination with
various ligands can be used.
[0132] The one or more ligand(s) can be selected from the group
consisting of 2,2'-bipyridine, 4,4'-dimethyl-2,2'-bipyridine,
5,5'-dimethyl-2,2'-bipyridine, 5,5'-isopropyl-2,2'-bipyridine,
5,5'-diheptyl-2,2'-bipyridine, 4,4'-di(5-nonyl)-2,2'-bipyridine
(dNbpy), 1,10-Phenanthroline (1,10-Phen),
4,7-Diphenyl-1,10-phenanthroline,
N,N,N',N'-tetramethylethylenediamine (TMEDA),
2,2':6',2''-terpyridine (tpy),
4,4',4''-tris(5-nonyl)-2,2':6',2''-terpyridine (tNtpy),
N,N-bis(2-pyridylmethyl)amine (BPMA),
N,N-bis(2-pyridylmethyl)octylamine (BPMOA),
N,N-bis(2-pyridylmethyl)propylamine (BPMPrA),
N,N-bis(2-pyridylmethyl)octadecylamine (BPMODA),
tris[2-aminoethyl]amine (TREN), tris(2-(dimethylamino)ethyeamine
(Me.sub.6TREN), tris(2-(diethylarnino)ethypamine (Et.sub.6TREN),
tris(2-aminoethyl)-amine-tris[di(2-butoxycarbonylethypaminoethyl]amine
(BuA.sub.6TREN), tris(2-di(methylacrylate)aminoethyl)amine
(MA.sub.6TREN), tris(2-di(buthyl acrylate)aminoethyl)amine
(BA.sub.6TREN), tris[(2-pyridyl)methyl]amine (TPMA),
1,4,8,11-tetraazacyclotetradecane (CYCLAM),
1,4,8,11-tetraaza-1,4,8,11-tetramethylcyclotetradecane
(Me.sub.4CYCLAM),
4,11-dimethyl-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane referred to
as dimethyl cross bridged cyclam (DMCBCy),
N,N,N',N'-tetrakis(2-pyridylmethypethylenediamine (TPEN),
diethylenetriamine (DETA), triethylenetetramine (TETA),
1,1,4,7,10,10-hexamethyltriethylenetetramine (HMTETA),
1,1,4,7,7-Pentamethyldiethylenetriamine (PMDETA),
1,1,4,7,7-Penta(methyl acrylate)diethylenetriamine (MA.sub.6DETA),
Glyoxal diimine-type (Gllm-R) ligands, Haddletons ligands (U.S.
Pat. No. 6,310,149): N-(n-Pentyl)-2-pyridylmethanimine (n-Pen-1),
N-Ethyl-2-pyridylmethanimine (Et-1),
N-(n-Propyl)-2-pyridylmethanimine (n-Pr-1),
N-(Cyclopropyl)-2-pyridylmethanimine (cyclo-Pr-1),
N-(iso-Propyl)-2-pyridylmethanimine (iso-Pr-1),
N-(n-Propyl)-2-pyridylmethanimine (n-Pr-3),
N-(n-Hexyl)-2-pyridylmethanimine (n-Hex-1),
N-(n-Heptyl)-2-pyridylmethanimine (n-Hep-1),
N-(n-Octyl)-2-pyridylmethanimine (n-Oct-1),
N-(n-Nonyl)-2-pyridylmethanimine (n-Non-1),
N-(n-Octadecyl)-2-pyridylmethanimine (n-Octadec-1),
n-Propyldiazabutadiene (n-Pr-2), Isopropyldiazabutadiene
(iso-Pr-2), Cyclopropyldiazabutadiene (cyclo-Pr-2),
1,4-Dihexyl-2,3-diphenylmethyl-1,4-diaza-1,3-butadiene, and
N-(n-Hexyl)-2-pyridylphenylmethanimine.
[0133] The one or more solvents can be selected from the group
consisting of water, ethanol, methanol, ethanol/water,
methanol/water, toluene, propanol, isopropanol, butanol,
1,1,1,3,3,3-hexafluoro-2-propanol or anisole. The ethanol/water or
methanol/water can in one embodiment be mixed in the following
ratios (volume by volume) 1:1, 1:2, 1:3, 1:4, 1:5, 2:1, 3:1, 4:1,
5:1, (0.1-1):1, 1:(0.1-1) or any other ratio.
[0134] The ratio of solvent:MEA can be any ratio (volume by volume)
such as (0.1-3):1, for example (0.1-0.2):1, such as (0.2-0.3):1,
for example (0.3-0.4):1, such as (0.4-0.5):1, for example
(0.5-0.6):1, such as (0.6-0.7):1, for example (0.7-0.8):1, such as
(0.8-0.9):1, for example (0.9-1.0):1, such as (1.0-1.1):1, for
example (1.1-1.2):1, such as (1.2-1.3):1, for example (1.3-1.4):1,
such as (1.4-1.5):1, for example (1.5-1.6):1, such as (1.6-1.7):1,
for example (1.7-1.8):1, such as (1.8-1.9):1, for example
(1.9-2.0):1, such as (2.0-2.1):1, for example (2.1-2.2):1, such as
(2.2-2.3):1, for example (2.3-2.4):1, such as (2.4-2.5):1, for
example (2.5-2.6):1, such as (2.6-2.7):1, for example (2.7-2.8):1,
such as (2.8-2.9):1, or any combination thereof.
[0135] The ratio of MEA:solvent can be any ratio (volume by volume)
such as (0.1-3):1, for example (0.1-0.2):1, such as (0.2-0.3):1,
for example (0.3-0.4):1, such as (0.4-0.5):1, for example
(0.5-0.6):1, such as (0.6-0.7):1, for example (0.7-0.8):1, such as
(0.8-0.9):1, for example (0.9-1.0):1, such as (1.0-1.1):1, for
example (1.1-1.2):1, such as (1.2-1.3):1, for example (1.3-1.4):1,
such as (1.4-1.5):1, for example (1.5-1.6):1, such as (1.6-1.7):1,
for example (1.7-1.8):1, such as (1.8-1.9):1, for example
(1.9-2.0):1, such as (2.0-2.1):1, for example (2.1-2.2):1, such as
(2.2-2.3):1, for example (2.3-2.4):1, such as (2.4-2.5):1, for
example (2.5-2.6):1, such as (2.6-2.7):1, for example (2.7-2.8):1,
such as (2.8-2.9):1, or any combination thereof.
[0136] In another embodiment the ratio of solvent:MEA is 1:1
(volume by volume).
[0137] The ratio of MEA:catalyst:ligand can be any ratio (mole by
mole) such as (30-1000):1:(1-3), for example (30-50):1:(1-3), such
as (50-100):1:(1-3), for example (100-150):1:(1-3), such as
(150-200):1:(1-3), for example (200-250):1:(1-3), such as
(250-300):1:(1-3), for example (300-350):1:(1-3), such as
(350-400):1:(1-3), for example (400-450):1:(1-3), such as
(450-500):1:(1-3), for example (500-550):1:(1-3), such as
(550-600):1:(1-3), for example (600-650):1:(1-3), such as
(650-700):1:(1-3), for example (700-750):1:(1-3), such as
(750-800):1:(1-3), for example (800-850):1:(1-3), such as
(850-900): I :(1-3), for example (900-950):1:(1-3), such as
(950-1000):1:(1-3), for example (30-50):1:(1-2), such as
(50-100):1:(1-2), for example (100-150):1:(1-2), such as
(150-200):1:(1-2), for example (200-250):1:(1-2), such as
(250-300):1:(1-2), for example (300-350):1:(1-2), such as
(350-400):1:(1-2), for example (400-450):1:(1-2), such as
(450-500):1:(1-2), for example (500-550):1:(1-2), such as
(550-600):1:(1-2), for example (600-650):1:(1-2), such as
(650-700):1:(1-2), for example (700-750):1:(1-2), such as
(750-800):1:(1-2), for example (800-850):1:(1-2), such as
(850-900):1:(1-2), for example (900-950):1:(1-2), such as
(950-1000):1:(1-2), for example (30-50):1:(2-3), such as
(50-100):1:(2-3), for example (100-150):1:(2-3), such as
(150-200):1:(2-3), for example (200-250): I :(2-3), such as
(250-300):1:(2-3), for example (300-350):1:(2-3), such as
(350-400):1:(2-3), for example (400-450):1:(2-3), such as
(450-500):1:(2-3), for example (500-550):1:(2-3), such as
(550-600):1:(2-3), for example (600-650):1:(2-3), such as
(650-700):1:(2-3), for example (700-750):1:(2-3), such as
(750-800):1:(2-3), for example (800-850):1:(2-3), such as
(850-900):1:(2-3), for example (900-950):1:(2-3), such as
(950-1000):1:(2-3), or any combination thereof.
[0138] In another embodiment the ratio of MEA:catalyst:ligand
(equivalents; mole by mole) is (1-2000):1:(0.1-50).
[0139] None limiting examples of substrates are listed herein
below.
[0140] Polymeric or organic substrates: Poly(ether ether ketone)
(PEEK), Polypropylene (PP), Polyethylene (PE) (including linear low
density polyethylene (LLDPE), low density polyethylene (LOPE) high
density polyethylene (HDPE), ultra high molecular weight
polyethylene (UHMWPE), and crass-linked polyethylene (PEX)),
Polyethylene terephthalate) (PET), poly(propylene terephthalate
(PPT), PPT/PET copolyester, Polybutylene terephthalate (PBT),
Poly(vinyl chloride) (PVC), Polyamide/nylon (PA), Polycarbonate
(PC), Cyclic olefin copolymer (COC), Filter paper, Cotton,
Cellulose, Poly(4-vinylbenzyl chloride) (PVBC), Poly(vinylidene
fluoride) (PVDF), Polystyrene (PS), Toyopearl.RTM., Hydrogels,
Polyimide (PI), 1,2-Polybutadiene (PB), Liquid silicon rubber
(LSR), poly(dimethylsiloxane) (PDMS), fluoropolymers- and
copolymers (e.g. poly(tetrafluoroethylene) (PTFE),
Perfluoroethylene propylene copolymer (FEP), Ethylene
tetrafluoroethylene copolymer (ETFE), Polyvinyl fluoride (PVF),
Polyvinylidene fluoride (PVDF), Polychlorotrifluoroethylene
(PCTFE)), poly(methyl methacrylate) (PMMA), Acrylonitrile butadiene
styrene (ABS), styrene acrylonitrile (SAN), polyacrylonitrile
(PAN), Polymethylpentene (TPX), Polyoxymethylene (POM), Polysulfone
(PSU), polyetherimide (PEI), polyphenylene oxide (PPO),
polyethersulfone (PES), Polyphenylene sulfide (PPS), Polyamideimide
(PA1), Liquid crystal polymer (LCP), Epoxy, Polyurethane (PU),
Thermoplastic elastomer (TPE), natural or synthetic rubber,
polybutadiene (PB) etc. Natural synthetic rubber comprises
polyisobutylene (PIB), polyisoprene, poly(ethylene-co-propylene),
Kraton polymers: Poly(styrene-b-butadiene-b-styrene) (SBS),
poly(styrene-b-isoprene-b-styrene) (SIS),
poly(styrene-b-(ethylene/butylene)-b-styrene) (SEBS),
poly(styrene-b-(ethylene/propylene)-b-styrene) (SEPS).
[0141] Metallic or inorganic substrates: Titanium, gold, glass,
silicon, geranium, quartz, silicon oxide, silica, stainless steel,
diamond, magnetic nanoparticles (e.g. Fe.sub.3O.sub.4) etc.
[0142] Other: Nanoporous materials, Membranes, Mesostructured
cellular foam (MCF), and singlewall or multiwall Carbon Nanotubes
(SWCNT, MWCNT).
[0143] In principle Surface-Initiated Atom Transfer Radical
Polymerization (SI-ATRP) can be performed on all materials provided
that they can be coupled to an initiator for ATRP [15]. Some
materials have functional groups which can be used directly for the
coupling whereas others will need to be activated before the
coupling reaction to the initiator can take place [14, 15, 16,
17].
Initiation Systems
[0144] A standard ATRP initiating system is described in the
background for the invention. Reverse ATRP involves in one
embodiment in situ formation of Cu.sup.I from standard free radical
initiators (e.g. AIBN) and Cu.sup.II salt which makes it less prone
to oxidation problems and more useful for commercial applications.
The transferable halogen atom is part of the copper salt in reverse
ATRP i.e. ATRP initiator is not added; therefore, the catalyst
concentration must be comparable to the concentration of the
initiator. For the technique SR&NI ATRP a dual initiating
system is present consisting of standard free radical initiators
and initiators with a transferable atom or group. The radicals
formed by AIBN are deactivated by an oxidatively stable Cu.sup.II
salt in that way Cu.sup.I and some halogenated chains are
generated. Thus Cu.sup.I can reactivate the alkyl halide initiators
and mediate normal ATRP. The ICAR ATRP method differs from
SR&NI by use of a large excess of free radical initiator to
catalyst. The radicals are slowly formed during the reaction and
mechanistic studies have shown resemblance between the kinetics of
ICAR and RAFT. AGET ATRP utilizes reducing agents which are unable
to initiate new chains. The reducing agent reacts in one embodiment
with the Cu.sup.II complex and forms the Cu.sup.I ATRP activator.
Cu.sup.0, tin.sup.II 2-ethylhexanoate, ascorbic acid, and
triethylamine have been reported as reducing agents for AGET ATRP.
In ARGET ATRP the Cu.sup.II is continuously reduced to Cu.sup.I as
a large enough excess of reducing agent to copper is applied. This
makes it possible to lower the concentration of catalyst to
initiator significantly. Good control was obtained with 50 ppm of
copper for ARGET ATRP of acrylate and 10 ppm of copper for styrene
polymerization. In addition to the reducing agents for AGET ATRP a
number of organic derivatives of hydrazine, phenol, sugar, and
ascorbic acid as well as inorganic species such as Sn.sup.II and
Cu.sup.0 can be used for ARGET ATRP[18]. Table A herein below gives
an overview of the ratios and reagents which can be applied in the
techniques.
TABLE-US-00001 TABLE A Examples of typical ratios used for the
different ATRP initiation systems [18]. M/R- RA (reducing ATRP
method X/Cu.sup.IX/Cu.sup.IIX L (ligand) agent) AIBN Normal
200/1/1/-- 1 -- -- Reverse 200/--/--/1 1 -- 0.5 SR&NI
200/1/--/0.2 0.2 -- 0.1 ICAR 200/1/--/<0.01 0.01 -- <0.1 AGET
200/1/--/0.2 0.2 0.18 -- ARGET 200/1/--/<0.01 0.1 <0.1 --
[0145] In one embodiment the present invention relates to ARGET
ATRP wherein low concentration of catalyst to initiator is
used.
The PMEA Coating
[0146] The coating of the present invention is a biocompatible
coating e.g. compatible with biological material such as protein,
peptide, body liquids such as blood, skin, tissue such as fatty
tissue.
[0147] Advantages of the covalently linked PMEA coating of the
present invention compared to a traditional physically adhered PMEA
coating are e.g. the following characteristics of the present
coating: [0148] prevention or inhibition of bacterial growth [0149]
bacteria repellent activity [0150] Improved long-term stability
[0151] Change of friction and wear
[0152] The above mentioned inhibition of bacterial growth can be an
inhibition of the bacterial growth with more than 50%, such as more
than 60%, for example more than 70%, such as more than 80%, for
example more than 90%, such as more than 95% or such as more than
99% compared to a surfaced that is not coated with PMEA.
[0153] Another advantage is that there will be less leakage of the
PMEA from a covalently bound PMEA coating than from a physically
adhered PMEA coating. This can be an advantage e.g. for coatings on
an implantable device. In one embodiment e.g. under moderate
conditions there will be no leakage from the covalently bound PMEA
coating. In another embodiment there will be less than 10% leakage,
such as less than 9%, for example less than 8%, such as less than
7%, for example less than 6%, such as less than 5%, for example
less than 4%, such as less than 3%, for example less than 2%, such
as less than 1%, for example less than 0.5%, such as less than
0.1%, for example less than 0.01% leakage.
[0154] Importantly, a PMEA coating which is covalently bound to one
or more surface(s) has an improved stability compared to a
physically adhered PMEA coating. This improvement is of crucial
importance for applications within the field of medical devices.
Furthermore, the SI ATRP such as ARGET SI ATRP or AGET SI ATRP
methods are more specific and effective compared to the ATRP method
for generation of a PMEA coating.
[0155] In one embodiment the PMEA coating prepared by SI ATRP such
as ARGET SI ATRP or AGET SI ATRP will lower the water contact angle
of the substrate.
Use of the PMEA Coating
[0156] The PMEA coating can be used in the area of biocompatible
surface, i. e. those materials that are used in contact with living
or dead tissue and biological fluids for prosthetic, therapeutic,
diagnostics, storage or other applications. Many conventional
biocompatible surfaces lack the ability to properly interact with
or support biological matter coming into contact with said
biocompatible surface leading to undesired biological
responses.
[0157] The PMEA coating can be used to produce a biocompatible
surface e.g. for contact with e.g. one or more subject matters
selected from the group consisting of one or more protein(s), one
or more peptide(s), one or more liquid(s) comprising one or more
protein(s), one or more liquid(s) comprising one or more
peptide(s), one or more pharmaceuticals, one or more body liquids,
one or more tissues, and meat. The body liquids can in one
embodiment be selected from the group consisting of blood, serum,
blood plasma, amniotic fluid, aqueous humour, cerumen, Cowper's
fluid or pre-ejaculatory fluid, chyme, female ejaculate,
interstitial fluid, lymph, breast milk, mucus (including nasal
drainage and phlegm), pleural fluid, pus, saliva, sebum (skin oil),
semen, sweat, tears, urine, vaginal secretion and vomit. In one
preferred embodiment the PMEA coating can be used as a
blood-contacting surface e.g. for a medical device.
[0158] The PMEA coated biocompatible surfaces of substrates may
thus be used as containers, cell-culture dishes, bioreactors,
implants, biohybrid organs such as pacemakers, bioartificial
pancreas, liver or kidney, and the like.
[0159] The invention also pertains to the use of the PMEA coating
in a method of controlling cellular growth and/or cellular
proliferation and/or cellular differentiation in vivo, or use of
the material in a method of separating and/or isolating biological
material in vivo, or use of the material in a method of controlling
cellular growth and/or cellular proliferation and/or cellular
differentiation ex vivo, or use of the material in a method of
separating and/or isolating biological material ex vivo, or use of
the material in a method of producing a biohybrid organ ex vivo,
and the use of the material in the manufacture of an implantable
organ or part thereof.
[0160] The PMEA coating according to the invention may also be used
as a carrier for a pharmaceutically active ingredient or a
pharmaceutical formulation or composition.
[0161] The invention also pertains to the following methods: [0162]
Method of therapy carried out on the human or animal body, said
method comprising the step of contacting said body with the PMEA
coating according to the present invention. [0163] Method of
surgery carried out on the human or animal body, said method
comprising the step of contacting said body with the PMEA coating
according to the invention. [0164] Method of diagnosis carried out
on the human or animal body, said method comprising the steps of
contacting said body with the PMEA coating according to the present
invention, and detecting a signal generated directly or indirectly
by said PMEA coating.
A Container
[0165] In one embodiment the PMEA coating according to the present
invention can be used for coating of a container. Said container
can be used for storage of e.g. one or more subject matters
selected from the group consisting of one or more protein(s), one
or more peptide(s), one or more liquid(s) comprising one or more
protein(s), one or more liquid(s) comprising one or more
peptide(s), one or more enzymes, one or more pharmaceuticals, one
or more body liquids, one or more tissues, meat, cells including
bacteria and mammalian cells such as human cells.
[0166] The container coated with the covalently bound PMEA coating
can in one embodiment be used for storage of one or more body
liquids. The body liquids can in one embodiment be selected from
the group consisting of blood, serum, blood plasma, amniotic fluid,
aqueous humour, cerumen, Cowper's fluid or pre-ejaculatory fluid,
chyme, female ejaculate, interstitial fluid, lymph, breast milk,
mucus (including nasal drainage and phlegm), pleural fluid, pus,
saliva, sebum (skin oil), semen, sweat, tears, urine, vaginal
secretion and vomit.
[0167] In one embodiment the container coated with the PMEA coating
of the present invention can be used for storage to prevent or
limit bacterial growth inside said container. Accordingly, the
coating can be used to inhibit and/or prevent non-specific
fouling.
[0168] The PMEA coating disclosed by the present invention can be
used for coating of a container such as any container (with or
without a lid) with a void cavity suitable for storage such as a
bottle, flask, bag, blood bag, pot, tub, dish, tray, bowl, basin,
pill bottle, medicine bottle, ampoule, flagon, syringe, needle,
tube, cell culture dish or flask or tissue culture dish or flask,
bioreactor, pipette tip, or Pasteur pipette. The lid can also be
coated if needed.
[0169] In one embodiment the invention relates to use of the PMEA
coating for coating of a container that can e.g. be used for
sampling in a laboratory during diagnostics such as a test tube,
PCR tube, an eppendorf tube, a blood sample glass, or a conical
test tube, tissue culture dish or flask, cell culture dish or
flask, slides for microscopic inspection, chamber slide, biopsy
needle.
A Medical Device Including Implantable Devices
[0170] The PMEA coating disclosed by the present invention can be
used for coating of a medical device such as an implantable device
such as a hip replacement or a stent. The medical device can be
selected from the group consisting of a blood filter, a blood
storage bag, a blood circuit, an indwelling needle, a catheter, a
pump, an infusion set, a guide wire, a stent, an oxygenator, a
dialyzer and an adhesive for tissues.
[0171] The medical device can further be an apparatus used for
blood collection such as a blood collection equipment consisting of
a plastic hub, a hypodermic needle, and a vacuum tube. In one
embodiment the blood collection equipment is an evacuated tube
system, such as the RD Vacutainer system. Alternatively, the blood
collection equipment comprises a syringe with a butterfly needle,
which is a plastic catheter attached to a short needle. In another
embodiment the blood collection equipment comprises one or more
Vacuum tubes.
[0172] The medical device can further be selected from the group
consisting of, blood collection tubes, vacuum blood collection
tubes, vacuum tubes, negative pressure blood taking tube, capillary
blood collection tube, blood transfusion equipment, blood sample
equipment, blood transfusion set, infusion set, blood collection
needle, serum tube, plasma tube, blood tube, bidirectional blood
needle, cardiopulmonary bypass circuits and oxygenators.
[0173] The medical device can further be a drug delivery device.
Drug delivery devices are specialized tools for the delivery of a
drug or therapeutic agent via a specific route of administration.
Such devices are used as part of one or more medical
treatments.
[0174] Drug delivery devices include, but are not limited to, the
following: [0175] An autoinjector such as a dual-chamber
autoinjector which is a medical device designed to deliver a single
dose of a particular (e.g. life-saving) drug. Most autoinjectors
are spring-loaded syringes. [0176] A drug-eluting stent (DES) which
is a coronary stent (a scaffold) placed into narrowed, diseased
coronary arteries that slowly releases a drug e.g. to block cell
proliferation. [0177] A Dry powder inhaler (DPI) which is a device
that delivers medication to the lungs in the form of a dry powder.
DPIs can be used to treat respiratory diseases such as asthma,
bronchitis, emphysema, COPD and diabetes mellitus. [0178] Inhaler,
Metered-dose inhaler or Respimat [0179] a needle-based injector,
e.g. computer-controlled, battery-powered medical drug delivery
device e.g. for delivery of the recombinant human growth hormone
somatropin. [0180] a needle-free injector drug delivery device
which, instead of accelerating a liquid jet across the skin like
other needle-free injectors, uses a solid dose. The dose itself is
the delivery vehicle. [0181] a pen injector using short needles to
deliver precise doses of e.g. insulin. [0182] An infusion pump
infuses fluids, medication or nutrients into a patient's
circulatory system. It is generally used intravenously, although
subcutaneous, arterial and epidural infusions are occasionally
used. [0183] Intraject is a needle-free injector medical device
(drug delivery device) which accelerates a liquid jet across the
skin to deliver the dose. It is a needle-free, prefilled,
single-use, disposable, subcutaneous drug injection system. [0184]
A jet injector is a type of medical injecting syringe that uses a
high-pressure narrow jet of the injection liquid instead of a
hypodermic needle to penetrate the epidermis, the purpose being to
reduce the pain associated with needle injection.
[0185] The implantable device can be implanted in a patient to
treat or prevent a disorder such as atherosclerosis, thrombosis,
restenosis, hemorrhage, vascular dissection or perforation,
vascular aneurysm, vulnerable plaque, chronic total occlusion,
claudication, anastomotic proliferation for vein and artificial
grafts, bile duct obstruction, ureter obstruction, tumor
obstruction, or combinations thereof.
[0186] Examples of such implantable devices include self-expandable
stents, balloon-expandable stents, stent-grafts, grafts (e.g.,
aortic grafts), artificial heart valves, cerebrospinal fluid
shunts, pacemaker electrodes, and endocardial leads (e.g., FINELINE
and ENDOTAK, available from Guidant Corporation, Santa Clara,
Calif.). The underlying structure of the device can be of virtually
any design. The device can be made of a metallic material or an
alloy such as, but not limited to, cobalt chromium alloy (ELGILOY),
stainless steel (316L), high nitrogen stainless steel, e.g., BIODUR
108, cobalt chrome alloy L-605, "MP35N," "MP20N," ELASTINITE
(Nitinol), tantalum, nickel-titanium alloy, platinum-iridium alloy,
gold, magnesium, or combinations thereof. "MP35N" and "MP20N" are
trade names for alloys of cobalt, nickel, chromium and molybdenum
available from Standard Press Steel Co., Jenkintown, Pa. "MP35N"
consists of 35% cobalt, 35% nickel, 20% chromium, and 10%
molybdenum. "MP20N" consists of 50% cobalt, 20% nickel, 20%
chromium, and 10% molybdenum. Devices made from bioabsorbable or
biostable polymers could also be used with the embodiments of the
present invention. The device itself, such as a stent, can also be
made from the described inventive PMEA coating.
[0187] Other examples of implantable devices include pacemaker, hip
replacement, stent, brain implant, breast implant, buttock implant,
cochlear implant, dental implant, extraocular implant, Harrington
implant, Microchip implant, Retinal implant, Subdermal implant, and
transdermal implant.
[0188] The medical device can also be one or more prostheses.
Prostheses can be used to replace body parts lost by injury
(traumatic) or missing from birth (congenital) or to supplement
defective body parts. Inside the body, artificial heart valves are
in common use with artificial hearts and lungs seeing less common
use but under active technology development. Other medical devices
and aids that can be considered prosthetics include artificial
eyes, palatal obturator, gastric bands, dentures, artificial limbs,
artificial organs, artificial knee, Lower Extremity Prosthetics,
Hip disarticulations prosthetics, Knee disarticulations
prosthetics, Symes prosthetics.
[0189] The PMEA coating according to the invention can also be used
for coating of neuromotor prostheses or neurocognitive prostheses
such as implantable neurocognitive brain-computer interfaces for
treat of a condition and/or disease such as stroke, traumatic brain
injury, cerebral palsy, autism, and Alzheimer's disease.
[0190] The PMEA coating can also be used for coating of biosensors.
Biosensors detect signals from the users nervous or muscular
systems. Examples of biosensors include wires that detect
electrical activity on the skin, needle electrodes implanted in
muscle, or solid-state electrode arrays with nerves growing through
them. One type of these biosensors are employed in Myoelectric
prosthesis.
[0191] In one embodiment the PMEA coating can be used for
prevention and/or inhibition of infection associated with a medical
device and/or implant.
A Tubing Device
[0192] The PMEA coating according to the present invention can be
used for coating of a tube. The tubes can be any type of tube such
as a tube made of glass or plastic. The tube can be used for
transport of one or more subject matters selected from the group
consisting of one or more protein(s), one or more peptide(s), one
or more liquid(s) comprising one or more protein(s), one or more
liquid(s) comprising one or more peptide(s), one or more enzymes,
one or more pharmaceuticals, one or more body liquids such as
blood, blood plasma or serum, one or more tissues, meat, cells
including bacteria and mammalian cells such as human cells.
[0193] The tube can e.g. be a tube of an infusion set or blood
transfusion equipment. The tube can also be part of laboratory
equipment such as a device for chromatographic separation.
[0194] The PMEA coating according to the present invention can be
used for coating of a catheter.
[0195] The catheter is in one embodiment a tube that can be
inserted into a body cavity, duct, or vessel. The catheter thereby
allow drainage, injection of fluids, or access by surgical
instruments. In most uses, the catheter is a thin, flexible tube
("soft" catheter), though in some uses, it is a larger, solid
("hard") catheter. The catheter can be left inside the body, either
temporarily or permanently (referred to as an indwelling catheter).
A permanently inserted catheter may be referred to as a
permcath.
[0196] Placement of the PMEA coated catheter into a particular part
of the body can e.g. allow: [0197] draining urine from the urinary
bladder as in urinary catheterization, e.g., the Foley catheter or
even when the urethra is damaged as in suprapubic catheterisation.
[0198] drainage of urine from the kidney by percutaneous
nephrostomy [0199] drainage of fluid collections, e.g. an abdominal
abscess [0200] administration of intravenous fluids, medication or
parenteral nutrition with a peripheral venous catheter [0201]
angioplasty, angiography, balloon septostomy, balloon sinuplasty,
catheter ablation [0202] direct measurement of blood pressure in an
artery or vein [0203] direct measurement of intracranial pressure
[0204] administration of anaesthetic medication into the epidural
space, the subarachnoid space, or around a major nerve bundle such
as the brachial plexus [0205] subcutaneous administration of
insulin or other medications e.g. with the use of an infusion set
and/or insulin pump [0206] A central venous catheter is a conduit
for giving drugs or fluids into a large-bore catheter positioned
either in a vein near the heart or just inside the atrium. [0207] A
Swan-Ganz catheter is a special type of catheter placed into the
pulmonary artery for measuring pressures in the heart. [0208] An
umbilical line is a catheter used in Neonatal Intensive Care Units
(NICU) providing quick access to the central circulation of
premature infants. [0209] A Touhy burst adapter is a medical device
used for attaching catheters to various other devices. [0210] A
Quinton catheter is a double or triple lumen, external catheter
used for hemodialysis.
A Separation Media
[0211] The PMEA coating according to the present invention can be
used for preparation of separation media such as a membrane or
filter for selective separation or purification of specific
biological components like proteins, peptides and cells from
biological fluids. Such separation media can be any which is suited
for immobilisation, separation etc. such as filters, membranes,
ultrafiltration membranes, nanoporous membranes, anti-fouling
membranes, Silicone-Based Membrane, nanofiltration membranes, blood
purification membrane, Membranes for Reverse Osmosis
Desalinization, Reverse osmosis membrane, Hollow Fiber Membranes,
Ion-exchange membrane, beads, fibres, webs, sinters or sieves
[0212] The separation media can be a filter medium for selectively
removing components from biological fluids e.g. leucocytes from
blood and blood products.
[0213] The invention will e.g. enable the use of improved membranes
for ensuring spatial separation of e.g. xenogenic and/or allogenic
cells from the host immune system.
[0214] Modifying membranes with the PMEA coating according to the
present invention can reduce the amount of adsorption of biological
material such as proteins, peptides or cells on the plane of the
membrane and at the same time improve the conformational/functional
state/form of adsorbed proteins, peptides or cells.
[0215] The coating according to the present invention can further
be used on anti-fouling membranes e.g. in sensors, pumps,
bioreactors, desalination, dialyses, blood purification etc.
A Film
[0216] The PMEA coating according to the present invention can also
be used for coating of one or more films such as polymer film(s),
single or multiple layer films, e.g. for food and/or feed
packaging, pharmaceutical packaging, blood bags etc.
[0217] The present invention is in one embodiment characterised by
the items herein below.
Items:
[0218] 1. A polymer coating comprising or consisting of polymer
chains comprising or consisting of repeating units of
2-methoxyethyl acrylate, wherein said polymer chains are covalently
bound to one or more surface(s) of one or more substrate(s).
[0219] 2. The polymer coating according to item 1, wherein the
polymer coating is obtained or obtainable by SI ATRP, reverse ATRP,
SR and NI ATRP, ICAR ATRP, AGET ATRP and/or ARGET ATRP.
[0220] 3. The polymer coating according to item 1, wherein said
polymer chains comprises chains of PMEA consisting of at least 5
MEA units, such as at least 10 MEA units, for example at least 15
MEA units, such as at least 20 MEA units, for example at least 25
MEA units, such as at least 30 MEA units, for example at least 35
MEA units, such as at least 40 MEA units, for example at least 45
MEA units, such as at least 50 MEA units, for example at least 55
MEA units, such as at least 60 MEA units, for example at least 65
MEA units, such as at least 70 MEA units, for example at least 75
MEA units, such as at least 80 MEA units, for example at least 85
MEA units, such as at least 90 MEA units, for example at least 95
MEA units, such as at least 100 MEA units, for example at least 200
MEA units, such as at least 300 MEA units, for example at least 400
MEA units, such as at least 500 MEA units, for example at least 600
MEA units, such as at least 700 MEA units, for example at least 800
MEA units, such as at least 900 MEA units, for example at least
1000 MEA units.
[0221] 4. The polymer coating according to item 1, wherein said
polymer chains comprises chains of PMEA, wherein at least 50% such
as at least 60%, for example at least 70%, such as at least 80%,
for example at least 85%, such as at least 90%, for example at
least 95%, such as at least 99% of the MEA chains consisting of at
least 5 MEA units, such as at least 10 MEA units, for example at
least 15 MEA units, such as at least 20 MEA units, for example at
least 25 MEA units, such as at least 30 MEA units, for example at
least 35 MEA units, such as at least 40 MEA units, for example at
least 45 MEA units, such as at least 50 MEA units, for example at
least 55 MEA units, such as at least 60 MEA units, for example at
least 65 MEA units, such as at least 70 MEA units, for example at
least 75 MEA units, such as at least 80 MEA units, for example at
least 85 MEA units, such as at least 90 MEA units, for example at
least 95 MEA units, such as at least 100 MEA units, for example at
least 200 MEA units, such as at least 300 MEA units, for example at
least 400 MEA units, such as at least 500 MEA units, for example at
least 600 MEA units, such as at least 700 MEA units, for example at
least 800 MEA units, such as at least 900 MEA units, for example at
least 1000 MEA units.
[0222] 5. A device comprising one or more surface(s) covalently
bound to the polymer coating according any of to items 1 to 4.
[0223] 6. The device according to item 5, wherein said device is a
container.
[0224] 7. The device according to item 5, wherein said device is an
implantable device.
[0225] 8. The device according to item 5, wherein said device is a
tubing device.
[0226] 9. The device according to item 5, wherein said device is a
membrane.
[0227] 10. The device according to item 5, wherein said device is a
film.
[0228] 11. The device according to item 5, wherein said device is a
medical device.
[0229] 12. The device according to item 5, wherein said device can
be selected from the group consisting of cell culture dishes or
flasks, bioreactors, syringe, needle, biopsy needle, pipette tip,
test tube, slide for microscopic inspection, medicine bottle or
ampoule, bag, pouch, implantable device, stent, blood filter, blood
storage bag, a blood sample glass or tube, blood filter, a blood
circuit, infusion set, pump, a catheter, a pump, an oxygenator,
prostheses, and biosensors.
[0230] 13. A method for making the polymer coating according any of
to items 1 to 4.
[0231] 14. The method according to item 13, wherein the method
comprises SI ATRP such as ARGET SI ATRP or AGET SI ATRP.
[0232] 15. The method according to item 13, wherein MEA is
polymerized from one or more surface(s) of one or more
substrate(s).
[0233] 16. The method according to item 13, wherein the method
comprises one or more of the steps of [0234] i) use of initiator
groups covalently bound to one or more surface(s) of a substrate
[0235] ii) adding one or more catalyst(s), one or more ligand(s),
2-methoxyethyl acrylate and optionally one or more solvent(s) to a
reaction container comprising one or more substrate(s) with one or
more surface(s) comprising said initiator groups [0236] iii)
allowing the reaction to take place, and optionally [0237] iv) use
of one or more reducing agents [0238] thereby making the polymer
coating according to item 1.
[0239] 17. The method according to item 13, wherein the method
comprises one or more of the steps of [0240] i) use of initiator
groups covalently bound to one or more surface(s) of a substrate
[0241] ii) adding one or more catalyst(s), one or more ligand(s)
and optionally one or more solvent(s) to a first reaction container
comprising one or more substrate(s) with one or more surface(s)
comprising said initiator groups [0242] iii) adding 2-methoxyethyl
acrylate and optionally one or more solvent(s) to a second reaction
container [0243] iv) optionally remove oxygen from said first
reaction container and/or said second reaction container by
degassing and/or flushing and/or one or more freeze-pump-thaw
cycles, [0244] v) transfer the content of said second container to
said first container [0245] vi) allowing the reaction to take
place, and optionally [0246] vii) use of one or more reducing
agents [0247] thereby making a PMEA coating covalently attached to
the surface of the substrate.
[0248] 18. The method according to item 13, wherein the method
comprises one or more of the steps of [0249] i) use of initiator
groups covalently bound to one or more surface(s) of a substrate
[0250] ii) adding one or more catalyst(s), 2-methoxyethyl acrylate
and optionally one or more solvent(s) to a first reaction container
comprising one or more substrate(s) with one or more surface(s)
comprising said initiator groups [0251] iii) adding one or more
ligand(s) and optionally one or more solvent(s) to a second
reaction container [0252] iv) optionally remove oxygen from said
first reaction container and/or said second reaction container by
degassing and/or flushing and/or one or more freeze-pump-thaw
cycles, [0253] v) transfer the content of said second container to
said first container [0254] vi) allowing the reaction to take
place, and optionally [0255] vii) use of one or more reducing
agents [0256] thereby making a PMEA coating covalently attached to
the surface of the substrate.
[0257] 19. The method according to item 13, wherein the method
comprises one or more of the steps of [0258] i) use of initiator
groups covalently bound to one or more surface(s) of a substrate
[0259] ii) adding one or more catalyst(s), one or more ligand(s),
2-methoxyethyl acrylate and optionally one or more solvent(s) to a
reaction container comprising one or more substrate(s) with one or
more surface(s) comprising said initiator groups [0260] iii)
optionally remove oxygen from said reaction container by degassing
and/or flushing and/or one or more freeze-pump-thaw cycles, [0261]
iv) allowing the reaction to take place, and optionally [0262] v)
use of one or more reducing agents [0263] thereby making a PMEA
coating covalently attached to the surface of the substrate.
[0264] 20. The method according to item 13, wherein the method
comprises one or more of the steps of [0265] i) adding one or more
catalyst(s), one or more ligand(s), and optionally one or more
solvent(s) to a reaction container comprising one or more
substrate(s) [0266] ii) optionally remove oxygen from said reaction
container by degassing and/or flushing and/or one or more
freeze-pump-thaw cycles, [0267] iii) adding 2-methoxyethyl acrylate
and optionally one or more solvent(s) to said reaction container
after oxygen has been removed from said reaction container and
[0268] iv) allowing the reaction to take place, and optionally
[0269] v) use of one or more reducing agents and thereby preparing
a PMEA-coated surface.
[0270] 21. The method according to item 13, wherein the method
comprises one or more of the steps of [0271] i) adding one or more
catalyst(s), 2-methoxyethyl acrylate, and optionally one or more
solvent(s) to a reaction container comprising one or more
substrate(s) [0272] ii) optionally remove oxygen from said reaction
container by degassing and/or flushing and/or one or more
freeze-pump-thaw cycles, [0273] iii) adding one or more ligand(s)
and optionally one or more solvent(s) to said reaction container
after oxygen has been removed from said reaction container and
[0274] iv) allowing the reaction to take place, and optionally
[0275] v) use of one or more reducing agents [0276] and thereby
preparing a PMEA-coated surface.
[0277] 22. The method according to item 13, wherein the method
comprises one or more of the steps of [0278] i) adding one or more
catalyst(s), 2-methoxyethyl acrylate, one or more ligand(s) and
optionally one or more solvent(s) to a reaction container under
inert atmosphere such as in a glove box [0279] ii) optionally
remove oxygen from said reaction container by degassing and/or
flushing and/or one or more freeze-pump-thaw cycles, [0280] iii)
adding one or more substrates to said reaction container under
inert atmosphere [0281] iv) allowing the reaction to take place,
and optionally [0282] v) use of one or more reducing agents [0283]
and thereby preparing a PMEA-coated surface.
[0284] 23. The method according to any of items 13 to 22, wherein
the reaction is allowed to take place at a temperature between
20.degree. C. and 100.degree. C.
[0285] 24. The method according to any of items 13 to 23, wherein
the reaction is allowed to take place at a temperature interval
between 20.degree. C. and 100.degree. C. such as at from 20.degree.
C. to 25.degree. C., for example at from 25.degree. C. to
30.degree. C., such as at from 30.degree. C. to 35.degree. C., for
example at from 35.degree. C. to 40.degree. C., such as at from
40.degree. C. to 45.degree. C., for example at from 45.degree. C.
to 50.degree. C., such as at from 50.degree. C. to 55.degree. C.,
for example at from 55.degree. C. to 60.degree. C., such as at from
60.degree. C. to 65.degree. C., for example at from 65.degree. C.
to 70.degree. C., such as at from 70.degree. C. to 75.degree. C.,
for example at from 75.degree. C. to 80.degree. C., such as at from
80.degree. C. to 85.degree. C., for example at from 85.degree. C.
to 90.degree. C., such as at from 90.degree. C. to 95.degree. C.,
for example at from 95.degree. C. to 100.degree. C. or any
combination thereof). The reaction can e.g. be performed at
20.degree. C., 25.degree. C., 30.degree. C., 35.degree. C.,
40.degree. C., 45.degree. C., 50.degree. C., 55.degree. C.,
60.degree. C., 65.degree. C., 70.degree. C., 75.degree. C.,
80.degree. C., 90.degree. C., 95.degree. C., or 100.degree. C., or
any combination thereof.
[0286] 25. The method according to any of items 13 to 24, wherein
the reaction is allowed to take place for any duration of time
between 1 hour and 24 hours such as for 1 hour to 2 hours, for
example for 2 hours to 3 hours, such as for 3 hours to 4 hours, for
example for 4 hours to 5 hours, such as for 5 hours to 6 hours, for
example for 6 hours to 7 hours, such as for 7 hours to 8 hours, for
example for 8 hours to 9 hours, such as for 9 hours to 10 hours,
for example for 10 hours to 11 hours, such as for 11 hours to 12
hours, for example for 12 hours to 13 hours, such as for 13 hours
to 14 hours, for example for 14 hours to 15 hours, such as for 15
hours to 16 hours, for example for 16 hours to 17 hours, such as
for 17 hours to 18 hours, for example for 18 hours to 19 hours,
such as for 19 hours to 20 hours, for example for 20 hours to 21
hours, such as for 21 hours to 22 hours, for example for 22 hours
to 23 hours, or such as for 23 hours to 24 hours or any combination
thereof.
[0287] 26. The method according to any of items 13 to 25, wherein
the reaction is allowed to take place for any duration of time for
example less than 24 hours, such as less than 23 hours, for example
less than 22 hours, such as less than 21 hours, for example less
than 20 hours, such as less than 19 hours, for example less than 18
hours, such as less than 17 hours, for example less than 16 hours,
such as less than 15 hours, for example less than 14 hours, such as
less than 13 hours, for example less than 12 hours, such as less
than 11 hours, for example less than 10 hours, such as less than 9
hours, for example less than 8 hours, such as less than 7 hours,
for example less than 6 hours, such as less than 5 hours, for
example less than 4 hours, such as less than 3 hours, for example
less than 2 hours, such as less than 1 hour, for example less than
50 minutes, such as less than 40 minutes, for example less than 30
minutes, such as less than 20 minutes, for example less than 10
minutes, such as less than 5 minutes, for example less than 1
minute.
[0288] 27. The method according to any of items 13 to 26, wherein
the one or more catalyst(s) is CuBr.
[0289] 28. The method according to any of items 13 to 27, wherein
the one or more catalyst(s) is CuCl.
[0290] 29. The method according to any of items 13 to 28, wherein
the one or more catalyst(s) is a catalyst wherein the metal ion is
copper.
[0291] 30. The method according to any of items 13 to 29, wherein
the one or more catalyst(s) is a catalyst wherein the metal ion is
selected from the group consisting of ruthenium, iron, nickel,
palladium, cobalt, rhodium, rhenium, osmium, titanium, lithium,
molybdenum, and chromium.
[0292] 31. The method according to any of items 13 to 30, wherein
the one or more catalyst(s) is CuBr.sub.2 and/or CuCl.sub.2.
[0293] 32. The method according to any of items 13 to 31, wherein
the one or more catalyst(s) is CuBr.sub.2 and/or CuCl.sub.2 and
wherein one or more reducing agents are used.
[0294] 33. The method according to items 32, wherein the one or
more reducing agents can be selected from the group consisting of
tin.sup.II 2-ethylhexanoate, ascorbic acid, triethylamine, a number
of organic derivatives of hydrazine, phenol, sugar as well as
inorganic species such as Sn.sup.II and Cu.sup.0.
[0295] 34. The method according to any of items 13 to 33, wherein
the one or more ligand(s) can be selected from the group consisting
of 2,2'-bipyridine, 4,4'-dimethyl-2,2'-bipyridine,
5,5'-dimethyl-2,2'-bipyridine, 5,5'-isopropyl-2,2'-bipyridine,
5,5'-diheptyl-2,2'-bipyridine, 5,5'-ditridecyl-2,2'-bipyridine,
4,4'-di(5-nonyl)-2,2'-bipyridine (dNbpy), 1,10-Phenanthroline
(1,10-Phen), 4,7-Diphenyl-1,10-phenanthroline,
N,N,N',N'-tetramethylethylenediamine (TMEDA),
2,2':6',2''-terpyridine (tpy),
4,4',4''-tris(5-nonyl)-2,2':6',2''-terpyridine (tNtpy),
N,N-bis(2-pyridylmethyl)amine (BPMA),
N,N-bis(2-pyridylmethyl)octylamine (BPMOA),
N,N-bis(2-pyridylmethyl)propylamine (BPMPrA),
N,N-bis(2-pyridylmethyl)octadecylamine (BPMODA),
tris[2-aminoethyl]amine (TREN), tris(2-(dimethylamino)ethyl)amine
(Me.sub.6TREN), tris(2-(diethylamino)ethyl)amine (Et.sub.6TREN),
tris(2-aminoethyl)-amine-tris[di
(2-butoxycarbonylethypaminoethyl]amine (BuA.sub.6TREN),
tris(2-di(methylacrylate)aminoethyl)amine (MA.sub.6TREN),
tris(2-di(buthylacrylate)aminoethyl)amine(BA.sub.6TREN),
tris[(2-pyridyl)methyl]amine (TPMA),
1,4,8,11-tetraazacyclotetradecane (CYCLAM),
1,4,8,11-tetraaza-1,4,8,11-tetramethylcyclotetradecane
(Me.sub.4CYCLAM),
4,11-dimethyl-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane referred to
as dimethyl cross bridged cyclam (DMCBCy),
N,N,N',N'-tetrakis(2-pyridylmethypethylenediamine (TPEN),
diethylenetriamine (DETA), triethylenetetramine (TETA),
1,1,4,7,10,10-hexamethyltriethylenetetramine (HMTETA),
1,1,4,7,7-Pentamethyldiethylenetriamine (PMDETA),
1,1,4,7,7-Penta(methyl acrylate)diethylenetriamine (MA.sub.5DETA),
Glyoxal diimine-type (Gllm-R) ligands, Haddletons ligands (U.S.
Pat. No. 6,310,149): N-(n-Pentyl)-2-pyridylmethanimine (n-Pen-1),
N-Ethyl-2-pyridylmethanimine (Et-1),
N-(n-Propyl)-2-pyridylmethanimine (n-Pr-1),
N-(Cyclopropyl)-2-pyridylmethanimine (cyclo-Pr-1),
N-(iso-Propyl)-2-pyridylmethanimine (iso-Pr-1),
N-(n-Propyl)-2-pyridylmethanimine (n-Pr-3),
N-(n-Hexyl)-2-pyridylmethanimine (n-Hex-1),
N-(n-Heptyl)-2-pyridylmethanimine (n-Hep-1),
N-(n-Octyl)-2-pyridylmethanimine (n-Oct-1),
N-(n-Nonyl)-2-pyridylmethanimine (n-Non-1),
N-(n-Octadecyl)-2-pyridylmethanimine (n-Octadec-1),
n-Propyldiazabutadiene (n-Pr-2), Isopropyldiazabutadiene
(iso-Pr-2), Cyclopropyldiazabutadiene (cyclo-Pr-2),
1,4-Dihexyl-2,3-diphenylmethyl-1,4-diaza-1,3-butadiene, and
N-(n-Hexyl)-2-pyridylphenylmethanimine or any combination
thereof.
[0296] 35. The method according to any of items 13 to 34, wherein
the one or more solvent(s) is selected from the group consisting of
water, ethanol, methanol, ethanol/water, toluene, propanol,
isopropanol, butanol, 1,1,1,3,3,3-hexafluoro-2-propanol.
[0297] 36. The method according to any of items 13 to 35, wherein
the one or more solvent(s) is ethanol/water or methanol/water mixed
in the following ratios (volume by volume) 1:1, 1:2, 1:3, 1:4, 1:5,
2:1, 3:1, 4:1, 5:1, (0.1-1):1, 1:(0.1-1) or any other ratio.
[0298] 37. The method according to any of items 13 to 36, wherein
the ratio of solvent:MEA can be any ratio (volume by volume) such
as (0.1-3):1, for example (0.1-0.2):1, such as (0.2-0.3):1, for
example (0.3-0.4):1, such as (0.4-0.5):1, for example (0.5-0.6):1,
such as (0.6-0.7):1, for example (0.7-0.8):1, such as (0.8-0.9):1,
for example (0.9-1.0):1, such as (1.0-1.1):1, for example
(1.1-1.2):1, such as (12-1.3):1, far example (1.3-1.4):1, such as
(1.4-1.5):1, for example (1.5-1.6):1, such as (1.6-1.7):1, for
example (1.7-1.8):1, such as (1.8-1.9):1, for example (1.9-2.0):1,
such as (2.0-2.1):1, for example (2.1-2.2):1, such as (2.2-2.3):1,
for example (2.3-2.4):1, such as (2.4-2.5):1, for example
(2.5-2.6):1, such as (2.6-2.7):1, for example (2.7-2.8):1, such as
(2.8-2.9):1, or any combination thereof.
[0299] 38. The method according to any of items 13 to 37, wherein
the ratio of MEA:solvent can be any ratio (volume by volume) such
as (0.1-3):1, for example (0.1-0.2):1, such as (0.2-0.3):1, for
example (0.3-0.4):1, such as (0.4-0.5):1, for example (0.5-0.6):1,
such as (0.6-0.7):1, for example (0.7-0.8):1, such as (0.8-0.9):1,
for example (0.9-1.0):1, such as (1.0-1.1):1, for example
(1.1-1.2):1, such as (1.2-1.3):1, for example (1.3-1.4):1, such as
(1.4-L5):1, for example (1.5-1.6):1, such as (1.6-1.7):1, for
example (1.7-1.8):1, such as (1.8-1.9):1, for example (1.9-2.0):1,
such as (2.0-2.1):1, for example (2.1-2.2):1, such as (2.2-2.3):1,
for example (2.3-2.4):1, such as (2.4-2.5):1, for example
(2.5-2.6):1, such as (2.6-2.7):1, for example (2.7-2.8):1, such as
(2.8-2.9):1, or any combination thereof.
[0300] 39. The method according to any of items 13 to 38, wherein
the ratio of solvent:MEA is 1:1 (volume by volume).
[0301] 40. The method according to any of items 13 to 39, wherein
the ratio of MEA:catalyst:ligand can be any ratio (mole by mole)
such as (30-1000):1:(1-3), for example (30-50):1:(1-3), such as
(50-100):1:(1-3), for example (100-150):1:(1-3), such as
(150-200):1:(1-3), for example (200-250):1:(1-3), such as
(250-300):1:(1-3), for example (300-350):1:(1-3), such as
(350-400):1:(1-3), for example (400-450):1:(1-3), such as
(450-500):1:(1-3), for example (500-550):1:(1-3), such as
(550-600):1:(1-3), for example (600-650):1:(1-3), such as
(650-700):1:(1-3), for example (700-750):1:(1-3), such as
(750-800):1:(1-3), for example (800-850):1:(1 -3), such as
(850-900):1:(1 -3), for example (900-950):1:(1-3), such as
(950-1000):1:(1-3), for example (30-50):1:(1-2), such as
(50-100):1:(1-2), for example (100-150):1:(1-2), such as
(150-200):1:(1-2), for example (200-250):1:(1-2), such as
(250-300):1:(1-2), for example (300-350):1:(1-2), such as
(350-400):1:(1-2), for example (400-450):1:(1-2), such as
(450-500):1:(1-2), for example (500-550):1:(1-2), such as
(550-600):1:(1-2), for example (600-650):1:(1-2), such as
(650-700):1:(1-2), for example (700-750):1:(1-2), such as
(750-800):1:(1-2), for example (800-850):1:(1-2), such as
(850-900):1:(1-2), for example (900-950):1:(1-2), such as
(950-1000):1:(1-2), for example (30-50):1:(2-3), such as
(50-100):1:(2-3), for example (100-150):1:(2-3), such as
(150-200):1:(2-3), for example (200-250):1:(2-3), such as
(250-300):1:(2-3), for example (300-350):1:(2-3), such as
(350-400):1:(2-3), for example (400-450):1:(2-3), such as
(450-500):1:(2-3), for example (500-550):1:(2-3), such as
(550-600):1:(2-3), for example (600-650):1:(2-3), such as
(650-700):1:(2-3), for example (700-750):1:(2-3), such as
(750-800):1:(2-3), for example (800-850):1:(2-3), such as
(850-900):1:(2-3), for example (900-950):1:(2-3), such as
(950-1000):1:(2-3), or any combination thereof.
[0302] 41. The method according to any of items 13 to 40, wherein
the ratio of MEA:catalystligand:reducing agent can be any ratio
(mole by mole) such as
1:(0.000001-0.01):(0.000001-0.01):(0.000001-0.01), such as
1:(0.00001-0.01):(0.000001-0.01):(0.000001-0.01), for example
1:(0.0001-0.01):(0.000001-0.01):(0.000001-0.01), such as
1:(0.001-0.01):(0.000001-0.01):(0.000001-0.01), for example
1:(0.000001-0.001):(0.000001-0.01):(0.000001-0.01), such as
1:(0.000001-0.0001):(0.000001-0.01):(0.000001-0.01), for example
1:(0.000001-0.0001):(0.000001-0.01):(0.000001-0.01), such as
1:(0.000001-0.01):(0.00001-0.01):(0.000001-0.01), for example
1:(0.000001-0.01):(0.0001-0.01):(0.000001-0.01), such as
1:(0.000001-0.01):(0.001-0.01):(0.000001-0.01), for example
1:(0.000001-0.01):(0.000001-0.001):(0.000001-0.01), such as
1:(0.000001-0.01):(0.000001-0.0001):(0.000001-0.01), for example
1:(0.000001-0.01):(0.000001-0.00001):(0.000001-0.01), such as
1:(0.000001-0.01):(0.000001-0.01):(0.00001-0.01), for example
1:(0.000001-0.01):(0.000001-0.01):(0.0001-0.01), such as
1:(0.000001-0.01):(0.000001-0.01):(0.001-0.01), for example
1:(0.000001-0.01):(0.000001-0.01):(0.000001-0.001), such as
1:(0.000001-0.01):(0.000001-0.01):(0.000001-0.0001), for example
1:(0.000001-0.01):(0.000001-0.01):(0.000001-0.0001), such as
1:(0.000001-0.00001):(0.000001-0.01):(0.000001-0.01), for example
1:(0.00001-0.0001):(0.000001-0.01):(0.000001-0.01), such as
1:(0.0001-0.001):(0.000001-0.01):(0.000001-0.01), for example
1:(0.001-0.01):(0.000001-0.01):(0.000001-0.01), such as
1:(0.000001-0.01):(0.000001-0.00001):(0.000001-0.01), for example
1:(0.000001-0.01):(0.00001-0.0001):(0.000001-0.01), such as
1:(0.000001-0.01):(0.0001-0.001):(0.000001-0.01), for example
1:(0.000001-0.01):(0.001-0.01):(0.000001-0.01), such as
1:(0.000001-0.001):(0.000001-0.01):(0.000001-0.00001), for example
1:(0.000001-0.001):(0.000001-0.01):(0.00001-0.0001), such as 1
:(0.000001-0.001):(0.000001-0.01):(0.0001-0.001), for example
1:(0.000001-0.001):(0.000001-0.01):(0.001-0.01) or any combinations
thereof.
[0303] 42. The method according to any of items 13 to 41, wherein
the ratio of catalyst:ligand:reducing agent can be any ratio (mole
by mole) such as 1:(1-500):(1-500), for example 1425-500):(1-500),
such as 1:(50-500):(1-500), for example 1:(75-500):(1-500), such as
1:(100-500):(1-500), for example 1:(150-500):(1-500), such as
1:(200-500):(1-500), for example 1:(250-500):(1-500), such as
1:(300-500):(1-500), for example 1:(350-500):(1-500), such as
1:(400-500):(1-500), for example 1:(1-50):(1-500), such as
1:(1-100):(1-500), for example 1:(1-150):(1-500), such as
1:(1-200):(1-500), for example 1:(1-250):(1-500), such as
1:(1-300):(1-500), for example 1:(1-350):(1-500), such as
1:(1-400):(1-500), for example 1:(1-450):(1-500), such as
1:(50-500):(1-500), such as 1:(1-50):(1-500), for example
1:(50-100):(1-500), such as 1:(100-150):(1-500), for example
14150-200):(1-500), such as 1:(200-250):(1-500), for example
1:(250-300):(1-500), such as 1:(300-350):(1-500), for example
1:(350-400):(1-500), such as 1:(400-450):(1-500), for example
14450-500):(1-500) or any combinations thereof.
[0304] 43. The method according to any of items 13 to 42, wherein
the ratio of catalyst:reducing agent:ligand can be any ratio (mole
by mole) such as 1:(1-500):(1-500), for example 1425-500):(1-500),
such as 1:(50-500):(1-500), for example 1:(75-500):(1-500), such as
1:(100-500):(1-500), for example 1:(150-500):(1-500), such as
1:(200-500):(1-500), for example 1:(250-500):(1-500), such as
1:(300-500):(1-500), for example 1:(350-500):(1-500), such as
1:(400-500):(1-500), for example 1:(1-50):(1-500), such as
1:(1-100):(1-500), for example 1:(1-150):(1-500), such as
1:(1-200):(1-500), for example 1:(1-250):(1-500), such as
1:(1-300):(1-500), for example 1:(1-350);(1-500), such as
1:(1-400):(1-500), for example 1:(1-450):(1-500), such as
1:(50-500):(1-500), such as 1:(1-50):(1-500), for example
1:(50-100):(1-500), such as 1:(100-150):(1-500), for example
1:(150-200):(1-500), such as 1:(200-250):(1-500), for example
1:(250-300);(1-500), such as 1:(300-350):(1-500), for example
1:(350-400):(1-500), such as 1:(400-450):(1-500), for example
1:(450-500):(1-500) or any combinations thereof.
[0305] 44. The method according to any of items 13 to 43, wherein
the ratio of MEA:catalyst:ligand (equivalents; mole by mole) is
(1-2000):1:(0.1-50).
[0306] 45. The method according to any of items 13 to 44, wherein
the one or more substrate(s) is Polymeric or organic
substrates.
[0307] 46. The method according to any of items 13 to 45, wherein
the one or more substrate(s) is selected from the group consisting
of Poly(ether ether ketone) (PEEK), Polypropylene (PP),
Polyethylene (PE) (including linear low density polyethylene
(LLDPE), low density polyethylene (LOPE) high density polyethylene
(HDPE), ultra high molecular weight polyethylene (UHMWPE), and
cross-linked polyethylene (PEX)), Poly(ethylene terephthalate)
(PET), poly(propylene terephthalate (PPT), PPT/PET copolyester,
Polybutylene terephthalate (PBT), Poly(vinyl chloride) (PVC),
Polyamide/nylon (PA), Polycarbonate (PC), Cyclic olefin copolymer
(COC), Filter paper, Cotton, Cellulose, Poly(4-vinylbenzyl
chloride) (PVBC), Poly(vinylidene fluoride) (PVDF), Polystyrene
(PS), Toyopearl.RTM., Hydrogels, Polyimide (PI), 1,2-Polybutadiene
(PB), Liquid silicon rubber (LSR), poly(dimethylsiloxane) (PDMS),
fluoropolymers -and copolymers (e.g. poly(tetrafluoroethylene)
(PTFE), Perfluoroethylene propylene copolymer (FEP), Ethylene
tetrafluoroethylene copolymer (ETFE), Polyvinyl fluoride (PVF),
Polyvinylidene fluoride (PVDF), Polychlorotrifluoroethylene
(PCTFE)), poly(methyl methacrylate) (PMMA), Acrylonitrile butadiene
styrene (ABS), styrene acrylonitrile (SAN), polyacrylonitrile
(PAN), Polymethylpentene (TPX), Polyoxymethylene (POM), Polysulfone
(PSU), polyetherimide (PEI), polyphenylene oxide (PPO),
polyethersulfone (PES), Polyphenylene sulfide (PPS), Polyamideimide
(PAI), Liquid crystal polymer (LCP), Epoxy, Polyurethane (PU),
Thermoplastic elastomer (TPE), natural or synthetic rubber,
polyisobutylene (PIB), polyisoprene, polyethylene-co-propylene),
Kraton polymers: Poly(styrene-b-butadiene-b-styrene) (SBS),
poly(styrene-b-isoprene-b-styrene) (SIS),
poly(styrene-b-(ethylene/butylene)-b-styrene) (SEBS), and
poly(styrene-b-(ethylene/propylene)-b-styrene) (SEPS).
[0308] 47. The method according to any of items 13 to 46, wherein
the one or more substrate(s) is one or more Metallic or inorganic
substrates.
[0309] 48. The method according to any of items 13 to 47, wherein
the one or more substrate(s) is selected from the group consisting
of titanium, gold, glass, silicon, geranium, quartz, silicon oxide,
silica, stainless steel, diamond, and magnetic nanoparticles (e.g.
Fe.sub.3O.sub.4).
[0310] 49. The method according to any of items 13 to 48, wherein
the one or more substrate(s) is one or more Nanoporous
materials.
[0311] 50. The method according to any of items 13 to 49, wherein
the one or more substrate(s) is one or more membranes.
[0312] 51. The method according to any of items 13 to 50, wherein
the one or more substrate(s) is one or more Mesostructured cellular
foam (MCF).
[0313] 52. The method according to any of items 13 to 51, wherein
the one or more substrate(s) is one or more singlewall or multiwall
Carbon Nanotubes (SWCNT, MWCNT).
[0314] 53. The method according to any of items 13 to 52, wherein
the one or more substrate(s) is one or more materials with
functional groups which can be used directly for attaching the
initiating groups.
[0315] 54. The method according to any of items 13 to 53, wherein
the one or more substrate(s) is one or more materials that need to
be activated before the coupling reaction of the initiator can take
place.
[0316] 55. A polymer coating comprising or consisting of polymer
chains comprising or consisting of repeating units of
2-methoxyethyl acrylate, wherein said polymer chains are covalently
bound to one or more surface(s) of one or more substrate(s) and
wherein said polymer coating is obtained or obtainable by the
method according to any of items 13 to 54.
[0317] 56. Use of the coating according to any of items 1 to 4 and
55 for contacting one or more subject matters selected from the
group consisting of one or more protein(s), one or more peptide(s),
one or more pharmaceutical(s), one or more body liquids, one or
more living or dead tissues, skin, fatty tissue and meat
[0318] 57. The use according to item 56, wherein the one or more
body liquids can be one or more body liquids selected from the
group consisting of blood, blood plasma, serum, amniotic fluid,
aqueous humour, cerumen, Cowper's fluid or pre-ejaculatory fluid,
chyme, female ejaculate, interstitial fluid, lymph, breast milk,
mucus (including nasal drainage and phlegm), pleural fluid, pus,
saliva, sebum (skin oil), semen, sweat, tears, urine, vaginal
secretion and vomit.
[0319] 58. The use according to item 56 and 57, wherein the use
results in limitation or prevention of bacterial growth.
[0320] 59. The use according to item 56 and 57, wherein the use
results in bacteria repellent activity.
[0321] 60. Use of the device according to any of items 5 to 12.
[0322] 61. The use according to any of item 56 to 60, wherein the
use is for medical treatment of an individual in need thereof.
[0323] 62. The use according to any of item 56 to 61, wherein the
use is for medical surgery of an individual in need thereof.
[0324] 63. The use according to any of item 56 to 62, wherein the
use is for diagnostic analysis of an individual in need
thereof.
DETAILED DESCRIPTION OF THE DRAWINGS
[0325] FIG. 1: Scheme showing the principle of Atom Transfer
Radical Polymerization (ATRP). It is a controlled method which
converts monomers (M) to polymers (P) by using radical
polymerization. The initiators used for ATRP are commonly simple
alkyl halides. A halogen atom X is transferred during the
polymerization. Moreover, a catalyst system is present which
consist of a transition metal (M.sub.t.sup.x) complexed by one or
more ligands (X-M.sub.t.sup.x+1/Ligand). The catalyst provides
equilibrium between the active form, P.sub.m* and the inactive
form, P.sub.n-X (called the dormant state). The equilibrium is
displaced towards the dormant state; therefore, the polymer chains
will only be active for a short time, thus allowing for a
suppression of chain termination reactions and thereby controlling
the polymerization. A controlled polymerization method like ATRP
will result in controlled molar masses, controlled polymer
architecture, and narrow molecular weight distributions. The rate
constants for the activation, deactivation, propagation and
termination are: k.sub.act, k.sub.deact, k.sub.p, and k.sub.t.
[0326] FIG. 2: Structure of poly(2-methoxyethyl acrylate) (PMEA).
The letter n indicates the number of repeating units.
[0327] FIG. 3: Preparation of poly(2-methoxyethyl acrylate) (PMEA).
Some possible conditions for the polymerization of 2-methoxyethyl
acrylate (MEA) are shown. R-X is the initiator for ATRP and it
consists of an alkyl halide; R is the alkyl and X is the halide
(chlorine or bromine). The catalyst system for the polymerization
reaction is e.g. CuBr or CuCl and one or more ligands e.g.
2,2'-bipyridine (Bipy),
1,1,4,7,10,10-hexamethyltriethylenetetramine (HMTETA), or
1,1,4,7,7-pentamethyldiethylenetriamine (PMDETA). Examples of
solvents are listed water (H.sub.2O) or ethanol (EtOH) or a mixture
of ethanol and water (EtOH:H.sub.2O) or toluene. The polymerization
takes place at a temperature between 20 and 95.degree. C. The
polymerization time is between 1 and 24 hours. n is the number of
repeating units in PMEA.
[0328] FIG. 4: Explanation of the technique Surface-Initiated Atom
Transfer Radical Polymerization (SI ATRP). If hydroxyl groups are
present they can be used for coupling the initiating groups for
ATRP. Otherwise the surface of the substrate(s) needs to be
activated in order to form functional groups which can be used for
the coupling reaction. After anchoring of the initiating groups SI
ATRP can take place. The polymerization reaction is an equilibrium
between an active form and an inactive form and the inactive form
is the favourable state. M.sub.t.sup.x/Ligand or
X-M.sub.t.sup.x+1/Ligand is the catalyst system on either side of
the equilibrium. When the polymer chains are active the atom X
(chlorine or bromine) will bound to the catalyst. The last step is
rinsing the substrate(s) to remove the catalyst system and residual
monomer.
[0329] FIG. 5: Example of preparation of initiating groups on
poly(ether ether ketone) (PEEK). [0330] A) Some of the ketone
groups in PEEK will be reduced to hydroxyl groups by reaction with
sodium borohydride (NaBH.sub.4) in dimethyl sulfoxide (DMSO) for 3
hours at 120.degree. C. n is the number of repeating units in PEEK.
[0331] B) The hydroxyl groups on PEEK are transformed into
initiating groups for SI ATRP by using 2-bromoisobutyryl bromide
(Br-iBuBr) in the presence of 4-dimethylaminopyridine (DMAP) and
triethylamine (TEA) in tetrahydrofurane (THF). The reaction takes
place within 18 hours. When Br-iBuBr is added the temperature
should be kept at 0.degree. C. When Br-iBuBr is added the
temperature in the reaction mixture will increase. The reaction
mixture is left without cooling and the temperature will reach room
temperature (rt.).
[0332] FIG. 6: Effect on bacteria attachment [0333] S. aureus
static adherence results based on 3 hours and 24 hours on control
and PMEA coated glass slides (6A Left picture control plate; 6B
right picture PMEA coated plate, the green dots are bacteria).
[0334] Staphylococcus epidermidis bacterial attachment on control
and PMEA coated glass slides (6C Left picture control plate; 6D
right picture PMEA coated plate, the green dots are bacteria).
[0335] Staphylococcus epidermidis (down pictures) attachment (24
hours biofilm formation) to 96 well plates (6E Left picture control
plate; 6F right picture PMEA coated plate). [0336] S. aureus
incubated for 24 hours at 37.degree. C. shows 90% reduction of S.
aureus biofilm formation (6G Right picture is control plate; 6H
Left picture is PMEA coated plate).
[0337] FIG. 7: Attenuated Total Reflectance Fourier Transform
Infrared (ATR FT-IR) spectroscopy is used to confirm that the
modification of the substrate(s) has taken place. Green represents
unmodified polypropylene (PP), red represents PMEA grafted from PP
using CuBr/BiPy in methanol/water 1:1, blue represents PMEA grafted
from PP using CuBr/HMTETA in bulk and black represents PMEA grafted
from PP using CuBr/PMDETA in bulk). The PMEA coating contains e.g.
ester groups and ether groups which the substrate PP does not. The
carbonyl (C.dbd.O) absorption band from ester groups of PMEA is at
1736 cm.sup.-1. Whereas the C--O stretching band from the ether
groups of PMEA is at 1131 cm.sup.-1).
[0338] FIG. 8: A-F) Water contact angle (WCA) measurements on
substrates coated with PMEA prepared by ATRP. The advancing WCA of
unmodified Liquid Silicon Rubber (LSR) is 120.degree. and it is
lowered to 69.degree. when coated with PMEA. For low density
polyethylene (LDPE) the advancing WCA is 90.degree. and coated with
PMEA it is 50.degree. . The static WCA of poly(methyl methacrylate)
(PMMA) is changed from 82.degree. to 51.degree. when coated with
PMEA. G-J) Water contact angle (WCA) measurements on substrates
coated with PMEA prepared by SI ATRP. [0339] G-J) Water contact
angle (WCA) measurements on PMEA grafted from polypropylene (PP),
PP-g-PMEA by SI ATRP and unmodified PP. The measurements are made
with a dynamic method which gives the advancing (adv.) and receding
(rec.) contact angles. The advancing angles will be sensitive to
the hydrophobic domains and receding angles will characterize the
hydrophilic domains on the surface. The difference between the
advancing and receding WCA can be used to help characterize surface
heterogeneity and roughness. The catalyst system CuBr/HMTETA has
been used to prepare this PMEA coating. The advancing WCA decreases
from 106.degree. to 78.degree. whereas the receding WCA is reduced
from 90.degree. to 41.degree. when MEA is polymerized from PP. In
the figure advancing and receding are abbreviated adv. and rec.
respectively.
[0340] FIG. 9: Activator regenerated by electron transfer (ARGET)
SI ATRP differs from SI ATRP in lower amount of catalyst and ligand
and presence of reducing agent. Moreover, Cu.sup.II is applied
instead of Cu.sup.I. The polymerization reaction is an equilibrium
between the dormant state (surface-X) and the active form
(surface-*). When the chains are active another monomer is added
(+M). Cu.sup.II is continuously reduced by the reducing agent to
Cu.sup.I. The copper catalyst contains X (chlorine or bromine) and
is complexed by a ligand. The rate constants for the activation,
deactivation, and propagation are: k.sub.a, k.sub.d, and
k.sub.p.
REFERENCES
[0341] [1] Wang, J. S.; Matyjaszewski, K. J. Am. Chem. Soc. 1995,
117, 5614-5615 [0342] [2] Kato, M.; Kamigaito, M.; Sawamoto, M.;
Higashimura, T. Macromolecules 1995, 28, 1721-1723 [0343] [3] WO
9630421 A1 (MATYJASZEWSKI) 3 Oct. 1996 [0344] [4] Saito, N.;
Motoyama, S.; Sawamoto, J. Artif. Organs 2000, 24, 547-554 [0345]
[5] Suhara, H.; Sawa, Y.; Nishimura, M.; Oshiyama, H.; Yokoyama,
K.; Saito, N.; Matsuda, H. Ann. Thorac. Surg. 2001, 71, 1603-1608
[0346] [6] Gunaydin, S.; Farsak, B.; Kocakulak, M.; Sari, T.;
Yorgancioglu, C.; Zorlutuna, Y. Aim. Thorac. Surg. 2002, 71,
1819-1824 [0347] [7] Tanaka, M.; Mochizuki, A.; Motomura, T.;
Shimura, K.; Onishi, M.; Okahata, Y. Colloid. Surface. A 2001, 193,
145-152 [0348] [8] Tanaka, M.; Mochizuki, A.; Shiroya, T.;
Motomura, T.; Shimura, K.; Onishi, M.; Okahata, Y. Colloid.
Surface. A 2002, 203, 195-204 [0349] [9] Bednarek, M.; Jankova, K.;
Hvilsted, S. J. Polym. Sci. Pol. Chem. 2007, 45, 333-340 [0350]
[10] Hansen, N. M. L.; Haddleton, D. M.; Hvilsted, S. J. Polym.
Sci. Pol. Chem. 2007, 45, 5770-5780 [0351] [11] Brar, A. S.; Saini,
T. Eur. Polym. J. 2007, 43, 1046-1054 [0352] [12] O. Noiset, C.
Henneuse, Y.-J. Schneider, C. Marchand-Brynaert Macromolecules 30,
1997, 540-548. [0353] [13] J. Huang, H. Murata, R. R. Koepsel, A.
J. Rusell, K. Matyjaszewski Biomacromolecules 8, 2007, 1396-1399.
[0354] [14] F. J Xu, K. G. Neoh, E. T. Kang; Prog. Polym. Sc.,
2009, 34, 719-761. [0355] [15] C. J. Fristrup, K. Jankova, S.
Hvilsted "Surface-Initiated Atom Transfer Radical Polymerization--a
Technique to Develop Biofunctional Coatings" Soft Matter, 2009, 5,
4623-4634. [0356] [16] R. Barbey, L. Lavanant, D. Paripovic, N.
Schtiwer, C. Sugnaux, S. Tugulu and H.-A. Klok, Chem. Rev., 2009,
109, 5437-5527. [0357] [17] D. Roy, M. Semsarilar, J. T. Guthrie
and S. Perrier, Chem. Soc. Rev., 2009, 38, 1825-2148. [0358] [18]
W. A. Braunecker and K. Matyjaszewski, Prog. Polym. Sci., 2007, 32,
93-146.
EXAMPLES
Example 1
Preparation of the PMEA Coating
[0359] A reactor was charged with catalyst, ligand and substrates
as well as half of the solvent if the polymerization was not done
in bulk. The monomer, 2-methoxyethyl acrylate (MEA) and the other
half of the solvent, if any, were added to a (Schlenk) tube. After
degassing 2-3 times or flushing both reactor and (Schlenk) tube
with argon or nitrogen for 15 to 60 minutes, the content of the
Schlenk tube (MEA or MEA and solvent) was transferred to the
reactor with the substrates and catalyst system. Subsequently, the
polymerization took place at an elevated temperature under inert
atmosphere (e.g. nitrogen or argon gas).
[0360] The solvent could also be added to one of the tubes instead
of dividing it into the two tubes. In case the ligand is not a
liquid; some solvent or monomer should be used to wet the catalyst
system in order to avoid removal of the catalyst system during
degassing. If monomer is used for the wetting; catalyst and ligand
should not be in the same reactor/tube.
TABLE-US-00002 TABLE 1 Polymerization of MEA, solvent:monomer
(monomer is M or MEA) ratio is by volume M:CuX:L Temperature,
Solvent Solvent:monomer Ligand Monomer:catalyst:ligand .degree. C.
Time, h Ethanol/water 1:1 (0.1-2):1 Bipy (30-1000):1:(1-3) 35
0.3-22 Methanol/water 1:1 (0.1-2):1 Bipy (30-1000):1:(1-3) 35
0.3-22 Ethanol/water 3:1 (0.1-2):1 Bipy (30-1000):1:(1-3) 35
0.3-3.3 Ethanol (0.1-2):1 Bipy (30-1000):1:(1-3) 70 5-28 -- --
PMDETA (30-1000):1:(1-2) 90 1-3 -- -- HMTETA (30-1000):1:(1-2)
90-95 1-4 Toluene (0.1-1):1 HMTETA (30-1000):1:(1-2) 90 1-4 -- --
HMTETA (30-1000):1:(1-2) 50 2-26 -- -- PMDETA (30-1000):1:(1-2) 50
2-19 Monomer = MEA M:CuX:L = Monomer:catalyst:L (equivalents), X =
Br or Cl Bipy: 2,2'-Bipyridine PMDETA:
1,1,4,7,7-Pentamethyldiethylenetriamine HMTETA:
1,1,4,7,10,10-Hexamethyltriethylenetetramine
[0361] Examples of catalyst systems comprise catalysts, wherein the
metal in the catalyst is copper. However, the metal in the catalyst
does not necessarily have to be copper. Other catalysts in
combination with various ligands can be used.
Example 2
SI ATRP of MEA
[0362] Three polypropylene (PP) plates (approximately 1.times.1 cm
each) with initiating groups (see modification step of PP in
Example 3) for ATRP, CuBr (0.0299 g), PMDETA (43.16 .mu.L), and a
stirring bar were added to one Schlenk tube. MEA (4 mL) was added
to another Schlenk tube. After three freeze-pump-thaw cycles of
each tube; MEA was transferred to the other tube. The charged
Schlenk tube was immersed in an oil bath and heated to 50.degree.
C. Different polymerization times have been used (see Table 2).
TABLE-US-00003 TABLE 2 Examples of ATRP of MEA Solvent
Solvent:monomer Ligand M:CuBr:lig. Temperature, .degree. C. Time
Ethanol/water 1:1 1:1 Bipy 139:1:2 35 22 h and 20 min.
Methanol/water 1:1 1:1 Bipy 152:1:2 35 22 h Ethanol/water 3:1 1:1
Bipy 150:1:1 35 200 min. Ethanol 1:1 Bipy 150:1:1 70 1700 min. --
-- PMDETA 150:1:1 90 60-120 min. -- -- HMTETA 150:1:1 90-95 220
min. Toluene 1:1 HMTETA 150:1:1 90 220 min. -- -- HMTETA 152:1:1 50
2-26 h -- -- PMDETA 152:1:1 50 2-19 h Monomer = MEA M:CuX:L =
Monomer:catalyst:ligand (equivalents), X = Br or Cl Bipy:
2,2'-Bipyridine PMDETA: 1,1,4,7,7-Pentamethyldiethylenetriamine
HMTETA: 1,1,4,7,10,10-Hexamethyltriethylenetetramine
Example 3
SI ATRP
[0363] A none limiting example of SI ATRP is disclosed herein
below. PEEK contains ketones which can be reduced to hydroxyl
groups by NaBH.sub.4 in dimethyl sulfoxide (DMSO) [10] (see FIG.
5A).
[0364] Subsequently, initiating groups can be formed by modifying
the hydroxyl groups with 2-bromoisobutyryl bromide (Br-iBuBr) in
the presence of 4-dimethylaminopyridine (DMAP) and triethylamine
(TEA) in tetrahydrofurane (THF) (see FIG. 5B).
[0365] PP is on the other hand a very inert material which can be
activated by e.g. irradiation, plasma treatment etc. One procedure
is immersion of PP in a solution of toluene and 4-hydroxy
benzophenone (BP-iBuBr) followed by UV irradiation at 365 nm. C--C
bonds will be formed between PP and the carbon marked with a star
(*) [11] (see FIG. 5C).
[0366] Then SI-ATRP can be performed with e.g. MEA using the
conditions described above (see FIG. 5D). For other none limiting
examples see [12-13].
Example 4
Effect on Bacteria Attachment
[0367] Bacteria test with Staphylococcus aureus (S. aureus),
Staphylococcus epidermidis and Pseudomonas aeruginosa, have shown
that the bacterial attachment is substantially reduced by the PMEA
coating disclosed in the present invention. Moreover Staphylococcus
epidermidis biofilm formation is reduced by 95% (see FIGS.
6A-6H).
[0368] FIGS. 6A-6B show the S. aureus static adherence results
based on 3 hours and 24 hours on control and PMEA coated glass
slides, respectively. This demonstrates less adherence of S. aureus
to the PMEA coated glass slide.
[0369] FIGS. 6C-6D show Staphylococcus epidermidis bacterial
attachment on control and PMEA coated glass slides, respectively.
The PMEA coated plate has less bacteria attachment.
[0370] FIGS. 6E-6F show Staphylococcus epidermidis (down pictures)
attachment (24 hours biofilm formation) to 96 well plates. The PMEA
coating has less attachment of Staphylococcus epideimidis.
[0371] FIGS. 6G-6H: S. aureus incubated for 24 hours at 37.degree.
C. shows 90% reduction of S. aureus biofilm fonnation for the PMEA
coated plate compared to the control plate.
Example 5
Attenuated Total Reflectance Fourier Transform Infrared (ATR FT-IR)
Spectroscopy
[0372] Attenuated Total Reflectance Fourier Transform Infrared (ATR
FT-IR) spectroscopy of the PMEA coating according to the present
invention (see result in FIG. 7; Green represents Unmodified PP,
Red represents PMEA grafted from PP using CuBr/BiPy in
Methanol/water 1:1, Blue represents PMEA grafted from PP using
CuBr/HMTETA in bulk and Black represents PMEA grafted from PP using
CuBr/PMDETA in bulk) and FIG. 8A).
[0373] Attenuated Total Reflectance (ATR) Fourier Transform
Infrared (FTIR) spectra were obtained using a Spectrum One
spectrometer from Perkin Elmer which was equipped with a universal
ATR sample accessory.
[0374] Grafting of PMEA from PP by SI-ATRP was continued with ATR
FT-IR. The carbonyl (C.dbd.O) absorption band at 1736 cm.sup.-1
indicated the presence of ester groups from PMEA. Moreover, a C--O
stretching band was seen from the ether group (1131 cm.sup.-1) of
PMEA (see FIG. 7). When the substrate and the coating do not
contain the same functional groups ATR FTIR spectroscopy can be
used. The absorption bands in the spectra will give information
about the functional groups which are present. The technique will
measure about 2-3 .mu.m into the sample; therefore, the spectra
will contain absorption bands from both the coating and the
substrate.
Example 6
Results From Water Contact Angle (WCA) Measurements
[0375] The water contact angle (WCA) measurements on PMEA prepared
by ATRP and coated on different substrates are shown in FIGS.
8A-8F. The method can be used to determine the hydrophilicity of
PMEA coated substrate. The measurements shown are made with either
a dynamic method which gives advancing and receding angles or a
static method which only gives one value. When testing with water,
advancing angles will be sensitive to the hydrophobic domains and
receding angles will characterize the hydrophilic domains on the
surface. The difference between the advancing and receding CA can
be used to help characterize surface heterogeneity and
roughness.
[0376] The measurements in FIGS. 8G-8J were made on. OCA20 Contact
Angle System from Dataphysics with a temperature controller. The
temperature was set to 25.degree. C. A dynamic method called
"sessile drop (needle in)" was used and the WCAs were computed
using "Ellipse Fitting". PMEA has been grafted from polypropylene
(PP) using SI-ATRP. Different catalyst systems have been used which
have resulted in different water contact angles (see table below).
The PMEA coated PP (PP-g-PMEA) in italic is used for the pictures
in FIGS. 8G-8J.
TABLE-US-00004 Material Catalyst system WCA advancing, .degree. WCA
receding, .degree. PP -- 106 .+-. 1 90 .+-. 1 unmodified PP-g-PMEA
CuBr/Bipy 103 .+-. 1 66 .+-. 3 PP-g-PMEA CuBr/HMTETA 78 .+-. 1 41
.+-. 2 PP-g-PMEA CuBr/PMDETA 75 .+-. 1 36 .+-. 3 Bipy:
2,2'-Bipyridine PMDETA: 1,1,4,7,7-Pentamethyldiethylenetriamine
HMTETA: 1,1,4,7,10,10-Hexamethyltriethylenetetramine
[0377] The WCAs are lowered when PMEA is grafted from the surface
of PP substrates. Especially the receding WCAs are lower for the
modified PP compared with the unmodified PP due to changes in the
hydrophilicity. It is shown in the table that the polymerization
conditions e.g. the catalyst systems have an influence on the WCAs
of PP-g-PMEA as they can affect the grafting densities and chain
lengths.
Example 7
ARGET SI ATRP of MEA With Low Catalyst Concentration
[0378] ARGET SI ATRP of MEA was performed from 188 PP plates
(3.5.times.0.6.times.0.1 cm each). The PP plates were
functionalized with initiating groups for ATRP (see example 3)
prior to the grafting of PMEA. The plates, CuBr.sub.2 (21.1 mg),
Me.sub.6TREN (213.6 mg), L-ascorbic acid (164.0 mg), 120 mL
anisole, and a stirring bar were added to a round-bottom flask. MEA
(180 mL) was added to another round-bottom flask. Two
freeze-pump-thaw cycles were carried out for each flask and MEA was
transferred to the other flask. After one freeze-pump-thaw cycle
for the charged round-bottom flask; the polymerization was started
by immersion into a 60.degree. C. oil bath. The polymerization time
was 20 hours. Washing of the modified plates consisted of three
steps each for one hour 1) hexane, 2) 1:1 water/methanol, and 3)
5:1 water/ethanol.
* * * * *