Note: Descriptions are shown in the official language in which they were submitted.
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Photosolubilizable Layers
Field of the Invention
This invention relates to a photosensitive and photosoluble polymeric material
capable of forming a liquid-impermeable membrane, and to compositions for
producing the material.
Background of the Invention
It is often desirable to produce a layer of material that, when either placed
on a solid
support (i.e., porous or dialysis membrane, well plate, biological material
such as
skin) or as a self supporting film can keep two aqueous solutions and/or media
(i.e.,
solid/liquid, liquid/gas, solid/gas, liquid/vapour phase) separate for a given
period of
time, and be photosolubilized, preferably in aqueous media to allow
mixing/contact of
the two solutions/media.
Polymeric membranes are used in a variety of applications. Membranes can be
used to
prevent the mixing of components that are located on either side.
Permselective
membranes, those which allow selective transport of a molecular species, are
found in
both man-made (e.g. desalination units) and biological systems (e.g. cell
membranes).
Many of the latter systems are also selectively turned on and off by some sort
of
external stimuli (e.g. swelling). There are few examples of membranes which
completely disappear allowing both sides to mix completely. Normally such
mixing is
achieved via mechanical means.
Since Walter Littke's first protein crystallization experiment was launched in
1982 in
Spacelab, scientists have been searching for better experimental designs with
which to
carry out such experiments. One way to accomplish this is to insert a membrane
between a protein and salt solution and then remove it under carefully
controlled
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conditions allowing the two aqueous solutions to contact each other.
Mechanical
means are often clumsy and prone to malfunction. A polymeric membrane that
initially prevents intermixing and which becomes completely soluble in the
aqueous
media under the influence of a controlled external input (energy) could
function in
such a manner. The protein crystallization example is just one where such a
device
can be beneficial.
US Patent 5,071,731 describes a photosensitive element adapted for the
preparation of
colored images, the element having a photosolubilizable layer that comprises
an acid-
labile polymer and a photoacid generator (PAG) substance. However, there is no
crosslinking step involved in the preparation of the photosolubilizable layer
and there
is no decrosslinking step involved in the solubilization of the photosensitive
element.
Summary of the Invention
A polymer membrane/coating that can be photosolubilized in aqueous media has
been
developed in order to have the following properties. The polymer
membrane/coating
should be able to keep two aqueous solutions/media separate for the specified
time in
a given application. As well, the polymer membrane/coating should be
compatible
with the various solutes in the aqueous media such as biological materials
(e.g.
proteins), chemical reagents, labeled materials, and pharmaceutical drugs.
Upon
irradiation, the polymer membrane/coating must dissolve in the aqueous media
thus
allowing the two solutions/media to be in contact and/or mix. The photoinduced
solubilization does not require heat or any mechanical means to be achieved.
Photoinduced dissolution should be achieved at wavelengths where the various
solutes are transparent or photostable. The use of an aqueous
photosolubilizable
membrane/coating will thus eliminate any movable parts that could otherwise
break
down or get stuck reducing reliability of instrumentation.
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In accordance with one aspect of the invention, there is provided a
photosoluble
composition comprising:
a polymer that is soluble upon de-crosslinking, preferably soluble in
water or an aqueous solution,
a multifunctional crosslinking compound, and
a compound generating an acid upon irradiation.
Preferably, the polymer comprises protic functional groups e.g. carboxylic
acid and/or
hydroxyl functional groups, and the crosslinking compound is a mufti-
functional vinyl
ether.
In accordance with another aspect of the invention, there is provided a method
of
manufacturing a photosoluble material comprising the steps of:
a) mixing a polymer soluble upon de-crosslinking with a
multifunctional crosslinking compound and a compound
generating an acid upon irradiation,
b) providing a layer of the mixture of step a), and
c) simultaneously or subsequently, heating said layer at a
temperature and for a time effective to produce a liquid-
impermeable barner.
Optionally, the composition may comprise a sensitizing compound in
order to promote decrosslinking of the polymer at longer wavelengths
with said crosslinking compound.
In accordance with yet another aspect of the invention, there is provided a
method of
solubilizing the photosoluble material, the method comprising irradiating the
material
with a radiation in the visible or ultraviolet range for a time sufficient to
effect
decrosslinking of the constituent polymer and solubilization of the material.
3
~.~r~nted 16:10 2Q01 ~ DESC ~ ~ 0092502 CA~001~'74
"..~~.a...;a;d....x.:_...~a s_,......_..,s;t~;,~.,...: r . 'k ,
- s...u.m..5~i~'Is,....u.,;,~:,..._. ~a"",::r,2~F s "cs.:~~kt
ka_"iv,.lu°:'~.a'.
CA 02388920 2002-04-24
In another aspect, the invention provides use of a photosoluble composition in
the
manufacture of a non-patterned photoactivatable barrier layer, the compositioa
comprising: a polymer that is soluble upon de-crosslinking, a multifunctional
crosslinkiag compound, and a compound generating an acid upon irradiation. Nan-
patterned radiation refers to radiation that dots not require use of a mask,
stencil, or
other means to lay down a specific pattern of radiation to define a structure.
In one
aspect, the invention also provides use of such a composition for the
manufacture of a
radiation sensor device. Further examples of uses of the composition are
described
herein. . .
In oae aspect, the photosoluble composition comprises a polymer with basic
groups that
is soluble upon de-crosslinking, a multifunctio~aal crosslinlcing compound,
and a
compound generating as acid upon in~diation.
In a further aspect, the photosoluble composition comprises a polymer that is
soluble
upon do-crosslinking, a multifunctional crosslinking polymer, and a compound
generating an acid upon irradiation.
r
3a
AMENDED SHEET
:~'~ ; ,'
GAAPGdIUf;C7GTT 11 ltllT 1a~?9 enenl?IirIfC7~TT 11 nKT 1o~~~
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Brief Description of the Drawings
Fig. 1 illustrates various examples of use of the photosensitive material of
the
invention.
Detailed Description of the Invention
Various materials have been tested as possible separators of aqueous
solutions/media
that can be dissolved by photochemical means only. For example, polymers with
carboxylic acid groups (-COZH) or hydroxyls (-OH) can be rendered insoluble in
water by crosslinking with multifunctional vinyl ethers (Scheme 1). The
polymer may
be a homopolymer, a random or block co-polymer, terpolymer or higher polymer
of
various monomers containing pendent carboxylic acid and/or hydroxyl functional
groups. The co-polymers and higher polymers may also contain monomers without
carboxylic acid or hydroxyl functionalities (e.g. vinyl carboxylic acid esters
such as
vinyl acetate) or may contain monomers with pendent vinyl ether units,
photoacid
generating units (such as ester of strong acids) or sensitizing units.
It should be noted that where the term "layer" is used, no shape or thickness
limitation is implied.
In a preferred embodiment of the invention, the material is provided in a form
of a
membrane or coating and consists of a base polymer with carboxylic acid and/or
hydroxyl functionalities [such as poly(acrylic acid), polyvinyl alcohol),
water-soluble
cellulosic derivatives] that have been crosslinked with multifunctional vinyl
ethers to
give acid labile acetal ester and/or acetal linkages. The membrane/coating is
stable to
ordinary water as well as various aqueous buffered salt solutions in the dark
in a pH
range of approx. 4 to 9. A photoacid generator is included in the
membrane/coating
that can release a strong acid upon irradiation, either by direct excitation
or by
sensitization in which case a sensitizer is also included in the
membrane/coating), in
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order to reverse the acetal linkages. Dissolution of the polymer
membrane/coating is
thus achieved by photochemical means only.
Polymers
The polymer may be a homopolymer, a random or block co-polymer, terpolymer or
higher polymer of various monomers containing pendent erotic functional groups
such as carboxylic acid, sulfonic acids, amines and/or hydroxyl functional
groups.
The erotic groups may be attached directly to the polymer backbone or be
present as
substituents in the side chains. Examples of polymers containing carboxylic
acid
groups include poly(acrylic acid), poly(methacrylic acid), poly(itanconic
acid),
poly(citraconic acid), poly(benzoic acid), polymeric derivatives of half
carboxylic
esters of malonates, and salts and copolymers thereof. Also, polymers and
copolymers containing sulfonic acid groups, e.g. poly(styrenesulfonic acid)
and salts
and copolymers thereof, can be used.
Hydroxyl containing polymers include polyvinyl alcohol) and its various
derivatives,
cellulose esters and ethers, poly(hydroxyalkylmethacrylates),
poly(hydroxyalkylacrylates), polysaccharides) and copolymers thereof.
Crosslinkers
Suitable crosslinkers are mufti (i.e., di, tri, poly) functional molecules
capable of
reacting with polymers containing erotic groups, such as vinyl ethers, blocked
isocyanates, or aldehydes. Multivinyl ethers such as tri(ethylene glycol)
divinyl ether
(3), tetra(ethylene glycol) divinyl ether (4), trimethylolpropane trivinyl
ether (5), and
tris[4-(vinyloxy)butyl] trimellitate (6) (Chart 1), or erotic polymers
modified with
vinyl ether derivatives such as 2-chloroethyl vinyl ether (7-9) (Chart 1).
S
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The crosslinking process is achieved by heating a mixture of base polymer
(e.g.
poly(acrylic acid) [PAA] and/or polyvinyl alcohol) [PVA]) and crosslinker
(vinyl
ether derivative) resulting in the formation of acetal ester linkages in the
case of
carboxylic acid functionalities (Scheme la) and acetal linkages for alcohol
functionalities (Scheme 1b). Alternatively, the base polymer already
containing
pendent vinyl ether units is crosslinked by heating with no additional
crosslinker
being necessary (Scheme lc).
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Scheme 1: Crosslinking Step
c=o
0
n
+ ~ O ~ > C_O
O O
COzH n ~~ ~ O
1 ~ O n
base polymer ~O J O
g n O
crosslinker 1a ~O-C
polymer network with O
acetal ester linkages
n 0 O
+ >
OH ~J
n ~ ~ ~O O
C
base polymer J O
~O
n
crosslinker 2a n
polymer network with
acetal linkages
O
>
O
base polymer with 2b
vinyl ether units polymer network with
acetal linkages
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Chart 1: Multifunctional Vinyl Ether Crosslinkers
~O O ~ ~O O /
3 4
3 4
O O/
J ''~-~o ,o
o ~o o r v
0
J
O
0
O
O ~ n
O / ~O O
n
O
7
O
8 ~ 9
Photoacid ~,,enerators (PAGsI
In order to achieve aqueous photosolubilization, a thermally stable photoacid
generator (PAG), or a PAG and a sensitizer, or a PAG with a sensitizing moiety
covalently tethered to it are added to the mixture of base polymer and
crosslinker or to
the base polymer with vinyl ether units prior to heating. Alternatively, the
PAG
and/or sensitizer may be covalently tethered to the base polymer. The PAG
produces a
catalyst (acid) upon irradiation only, either by direct excitation or by
sensitization at
other wavelengths where the PAG does not absorb (Scheme 2).
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Examples of PAGs include opium salts (i.e., sulfonium, iodonium, phosphonium,
selenonium salts) of complex metal halides or sulfonates (such as triflate),
iminosulfonates, esters of strong acids (e.g. nitrobenzyl sulfonate esters, N-
S hydroxyimide or N-hydroxyamides sulfonate esters), sulfones, disulfones and
halogen
compounds particularly, but not exclusively vicinal dibromides and
trichlorotriazines.
Such PAGs may need to be suitably derivatized (with suitable substitution) for
incorporation into membrane/coating formulation and for subsequent
solubilization in
media when complete dissolution of coating/membrane is required for the
intended
application (i.e., protein crystallization device).
Sensitizers
When required in order to promote and aid in the solubilization of the
polymeric
material, sensitizers such as dyes, phenothiazine, ketones (such as
benzophenone,
xanthone, thioxanthone, fluorenone, anthraquinone, benzanthrone), polycyclic
aromatic hydrocarbons (such as pyrene, anthracene, naphthalene, perylene,
rubrene,
coronene) with suitable substitution for incorporation may be added to
membrane/coating formulation and for subsequent solubilization in media when
complete dissolution of coating/membrane is required for the intended
application
(i.e., protein crystallization device). These sensitizing moieties may be
added to the
formulation or covalently tethered to the PAG and/or base polymer.
For example, di(t-butylphenyl)iodonium triflate (10, where n = 1), an opium
salt,
produces triflic acid either by direct excitation (~, < 300 nm in the general
case of
opium salts) (Scheme 2a) or by sensitization at longer wavelengths (~, > 300
nm in
the general case of opium salts) using a photosensitizer such as phenothiazine
(11) or
any of its derivatives (Scheme 2b).
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Scheme 2: Irradiation Step
a
Cn F2n+1 S03
hu
/ ' CnF2n+1S03H
~,<300 nm
PAG 10 acid
b
H
Cn F2n+1 SOg i
_ _ N
\ / + i \ / + ~ \ I ~ hu ' CnF2n+1 SO3H,.
g ~ ~.=300-350 nm
PAG 10 11 acid
The acetal ester and acetal linkages are thus hydrolyzed under acid catalysis
and the
crosslinking process is reversed (Scheme 3) leading to the dissolution of the
membrane/coating. Complete dissolution of the membrane/coating can also be
achieved (i.e. when PAA and/or PVA are used as base polymers) which may be
necessary in a given application such as protein crystallization where no
residual
nucleation centers should be present.
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Scheme 3: De-crosslinking Step
a
C~--O H ~H
~~'ln
C-O ~ ~0 O
p ~ n H''/H20 n O II
"'"~ + ~C~ + CH3CH
n O~ ~ COZH J O
1
nH
n
1a
b
H OH
O O n
O
O
H+/Hz0 ~ + n ~ r O
Y off C O + CHsCH
J ~ )
1 'O n H
2a
These materials have been tested in the form of thin (abt. 1.3 pm) and thicker
9abt.
S 30 p,m) films or coatings casted on solid support as well as capillary
plugs. The
polymer materials can be coated on various substrates using different
approaches, i.e.,
spin-coating, dip-coating, spraying, draw-down coating technique, slot
coating,
lamination or calendering technique. The films/coatings can be prepared as
single or
multiple coatings of the same or of different polymer materials using
conventional
multilayer coating techniques. Free standing films/membranes can be prepared
using
various approaches, i.e., extrusion process, calendering technique,
lamination, or by
isolating/stripping the film from a support after casting.
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In preparing the films/coatings/membranes, a baking step is preferable. The
baking is
effected at sufficiently high temperatures and for a time effective to allow
solvent
evaporation as well as crosslinking leading to aqueous insolubilization of the
polymer
material. The baking temperature must be such that the degree of crosslinking
achieved can be sufficiently reversed in order for solubilization of the
membrane/coating to occur when so desired. As well, polymer formulations and
films/coatings/membranes must be protected from the specific wavelength range
of
light they are sensitive to (once prepared and incorporated into device as
well as
during their preparation and incorporation into device) until dissolution is
desired for
the given application. A small amount of base (such as amines) may be
incorporated
in polymer formulations in order to neutralize any traces of acid formed by
stray
radiation, thus avoiding early dissolution of polymer material.
POTENTIAL APPLICATIONS
The polymeric materials of the invention in the form of
films/coatings/membranes, as
illustrated in Fig. 1, may have numerous applications such as separation,
i.e., acting to
divide materials/media/solutions for containment and/or prevention of mixing,
the
films/coatings/membranes being photoremovable when containment/prevention of
mixing is no longer necessary. For example, a photosensitive membrane could be
incorporated in a device that would allow protein crystallization to be carned
out in
space. Thus, the membrane would allow two aqueous solutions to be separated
until
the proper microgravity conditions have been achieved (this may typically
require
between 2 and 10 days from the time of sample preparation). As well, the
membrane
would have to be stable to the test solutions, which typically are buffered
salt
solutions in a pH range of 4 to 9 and may contain long hydrophilic polymers.
Finally,
irradiation of the membrane would be done at wavelengths in the UVA region
(320
400 nm) in order to avoid protein structural damage but allow complete
dissolution of
the membrane (no residual nucleation centers), leading to the mixing of the
two
solutions (liquid-liquid diffusion technique).
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These polymer materials could also be coated on permeable/semi-
permeable/porous
substrates (e.g. dialysis membrane) leading to photoactivated (dialysis)
membranes.
Alternatively, these membranes could be used in surface protection
applications. As
protective barriers, these coatings/membranes can serve to prevent
exposure/damage
from unwanted media such as moisture or water. They could also be used to
protect
from light or filtered light in a given wavelength range with the use of
appropriate
sunscreen agents incorporated into the protective coating, whilst still being
photoremovable when activated in a different region of the light spectrum.
This could
include windows and biological surfaces such as skin (i.e., treating burns),
that could
then be deprotected on demand. The protection and/or sealing of images as well
as art
and archeological pieces are also envisaged.
1 S Similarly, photosensitive membranes could be used for light and radiation
sensor
devices. For example, one could monitor and control UVA/UVB light exposure or
monitor changes in light conditions, thus acting as "smart" materials, i.e.,
responding
to light in a defined engineering or scientific goal. Applications in
gathering, storage
and usage of solar energy may also be envisioned.
Other potential applications include encapsulation of materials (biological
materials,
chemical reagents, specialty chemicals, labeled materials, radioisotopes,
fluorescent
dyes, drugs, assay-specific reagents) for the purpose of packaging, temporary
storage
and/or controlled-release of these materials for therapeutic, diagnostic,
analytical,
chemical detection, as well as monitoring and control applications. For
example,
various materials could be temporarily contained in wells using a
photoremovable
coating (i.e., well caps).
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Possible ways of incorporating a photosensitive membrane into a practical
device
include (but are not limited to) fihns/membranes, coatings, plugs and capsules
as
illustrated in Figure 1.
Preparation of thin films (single and multiple-coatedl:
Example 1
This example illustrates the preparation of single-coated thin films using PAA
as a
base polymer, the crosslinking with both di- and trifunctional vinyl ethers,
and the
comparison of light (254 nm) versus dark dissolution rates in water.
A methanol solution was prepared with the following three components:
25% (w/v) of PAA in methanol
to 50% (w/w) of crosslinker (XL 3, 4 or 5) with respect to PAA
5 to 20 % (w/w) of PAG 10 (n=1) with respect to PAA
The solution was spin-coated (3000 rpm for 20 s) onto a substrate (for example
quartz
20 disk) to give a thin film (~ 2.5 pm). The disk was then placed into an oven
at 115 °C
for 3 minutes in order to remove any excess solvent (methanol) as well as to
achieve
crosslinking of PAA with the vinyl ether.
Aqueous insolubilization of such films was tested by submerging the disks in
distilled
25 water in the dark. The amount of time necessary for the films to solubilize
(in the
dark) was then determined. As well, aqueous photosolubilization was
investigated by
irradiating the films (whilst submerged in distilled water) at 254 nm and
determining
the irradiation time necessary for their complete solubilization. Results
obtained for
films prepared with various XLs and 20% (w/w) of PAG 10 (n=1) are presented in
Table 1.
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Table 1
Time in hours for darkTime in hours for aqueous
aqueous solubilizationphotosolubilizationa
50/ b of 10 4
3
50/b of 20 9
4
25/b of 30 9
50/ b of >30 16
5
5 a) irradiation at 254 nm using 8 rayonet lamps at a power of 1.9 mW/cmz
b) amount of XL with respect to PAA (w/w)
Example 2
This example compares the light (350 nm; by sensitization) versus dark
solubilization
rates of crosslinked PAA/XL4 single-coated thin films using a mixture of PAG
10
(n=1) and sensitizer 11.
A methanol solution was prepared as follows:
25% (w/v) of PAA in methanol
50% (w/w) of crosslinker (XL 4) with respect to PAA
10 % (w/w) of PAG 10 (n=1) with respect to PAA
1 molar equivalent of phenothiazine (11) to PAG 10
The films were prepared as described in example 1 except that they were baked
for 8
minutes. When such a film was exposed to 350 nm radiation (8 rayonet lamps at
a
power of 0.9 mW/cm') for 1.5 hrs and then was submerged in water, complete and
instantaneous dissolution of the film was observed. The amount of time
necessary for
CA 02388920 2002-04-24
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these films to solubilize when submerged in water was determined to be 9 hours
in the
dark compared to 1 hour when exposed to 350 nm radiation.
Example 3
This example illustrates the light versus dark dissolution rates of
crosslinked
PAA/XL4 single-coated thin films using iodonium PAGs that generate different
acids
(Chart 2).
Chart 2: PAGs generating different acids
CF3S~ C4FgS03 HgC ~ / S03
\ / y' \ / \ / ;' \ / \ / y I \ /
PAG 12 PAG 13 PAG 14
A methanol solution was prepared as follows:
25% (w/v) of PAA in methanol
50% (w/w) of crosslinker (XL 4) with respect to PAA
10 % (w/w) of PAG (12, 13 or 14) with respect to PAA
The films were prepared as described in example 1 except that the temperature
of the
oven varied between 100 - 110 °C during the baking step. Table 2
compares the
aqueous dark and photoinduced solubilization times for these films.
Table 2
PAG Time in hours for darkTime in hours for aqueous
aqueous solubilizationphotosolubilizationa
12 1 13
13 1 10
14 1 13
a) irradiation at 254 nm using 8 rayonet lamps at a power of 2.0 mW/cmz
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Example 4
This example illustrates the preparation of single-coated and multiple-coated
thin
films using PVA as a base polymer, the crosslinking with a difunctional vinyl
ether,
and the comparison of light (254 nm) versus dark dissolution rates in water.
A 2:1 (v/v) methanol:water solution was prepared with the following three
components:
10% (w/v) of PVA in solution
25 to 50% (w/w) of XL 4 with respect to PVA
5 to 20 % (w/w) of PAG 10 (n=1) with respect to PVA
A single-coated thin film (~ 1.5 p,m) was prepared as described in example 1
except
that a temperature of 170 °C was used for the crosslinking step.
Another coat was
prepared by spin-coating more solution (of the same composition) on top of the
film
(already crosslinked) followed by another baking period to achieve
crosslinking of the
top layer. A multiple-coated film was thus obtained. Table 3 compares the
aqueous
dark and photoinduced solubilization times for single and multiple-coated PVA
films
crosslinked with 50% (w/w) of XL 4 in the presence of 20% (w/w) of PAG 10 (n=1
).
Table 3
Number of Time in hours for darkTime in hours for aqueous
coats aqueous solubilizationphotosolubilizationa
1 Film still present 19
after 40 days
3 Film still present 44
after 40 days
a) irradiation at 254 nm using 8 rayonet lamps at a power of 1.9 mW/cmZ
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Example 5
This example illustrates the preparation of a multiple-coated thin film using
PAA as a
base polymer for the first coat and PVA as a base polymer for the second coat,
the
crosslinking of each coat with a difunctional vinyl ether, and the comparison
of light
(254 nm) versus dark dissolution rates in water.
A single-coated thin film was prepared as described in example 1 using the
same PAA
solution [with 50% XL 4 and 20% of PAG 10 (n=1)). A second PVA coat was
applied
on top as described in example 4 using the same PVA solution [with 50% XL 4
and
20% of PAG 10 (n=1)] and a temperature of 180 °C for the crosslinking
step.
The amount of time necessary for the PAA-PVA film to solubilize in water was
determined to be over 33 hours in the dark compared to 3 hours when exposed to
254
nm radiation.
Example 6
This example illustrates the derivatization of a trifunctional alcohol
(trimethylolpropane) with vinyl ether units to give crosslinker 15, its
crosslinking with
PAA polymer and the comparison of light (254 nm) versus dark dissolution rates
in
water.
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Preparation of crosslinker 15
J
0
O
O
O
OH
A three-neck round bottom flask fitted with a reflux condenser and an addition
funnel
5 was flushed with N2. A 1.0 g (7.5 mmol) portion of trimethylolpropane was
added
along with 10 mL of dimethyl sulfoxide (DMSO). Once everything had dissolved,
1.3
g (33 mmol) of sodium hydroxide (NaOH) pellets were added. The mixture was
stirred and warmed up to 70 °C for 1 hr resulting into a slightly
turbid solution. Then,
0.16 g (0.50 mmol) of tetrabutylammonium bromide dissolved in 3.4 mL (33 mmol)
10 of 2-chloroethyl vinyl ether was added dropwise to the DMSO mixture
resulting into a
brown slurry. The mixture was vigorously stirred at 85 °C for 3 hrs.
Once cooled, the
mixture was diluted with distilled water. The aqueous solution was extracted
three
times with ether. The organic extracts were combined, dried with magnesium
sulfate
(MgS04) and concentrated to give a dark orange liquid. A vacuum distillation
of the
15 orange liquid afforded 0.95 g of a viscous clear liquid: by 85-95
°C/0.04 mm; IR a
(crri'): 3250-3550, 3118, 2964, 2928, 2880, 1634, 1621, 1462, 1322, 1202,
1124,
1042, 977, 821; 'H NMR (200 MHz, in CDC13), 8 (ppm): 6.36-6.50 (dd, 2H), 4.11-
4.22 (dd, 2H), 3.95-4.03 (dd, 2H), 3.43-3.84 (m, 12H), 2.84-3.01 (m, 2H), 1.22-
1.38
(q, 2H), 0.75-0.88 (t, 3H).
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Preparation of film and crosslinking
A methanol solution was prepared as follows:
25% (w/v) of PAA in methanol
50% (w/w) of crosslinker (XL 15) with respect to PAA
% (w/w) of PAG 10 (n=1) with respect to PAA
The films were prepared as described in example 1 except that the temperature
of the
10 oven varied between 100 - 110 °C during the baking step.
Light versus dark solubilization of films
The amount of time necessary for these films to solubilize when submerged in
water
was determined to be 2 hours when exposed to 254 nm radiation (8 rayonet lamps
at a
power of 0.9 mW/cm2). When left in the dark whilst submerged in water, the
films
were still present after more than 6 days.
Example 7
This example illustrates the derivatization of a preformed polymer (PVA) with
vinyl
ether units, its crosslinking and subsequent insolubility in water.
Derivatization of polymer
A three-neck round bottom flask fitted with a reflux condenser and an addition
funnel
was flushed with NZ. A 1.0 g portion of polyvinyl alcohol) [80% hydrolyzed,
average
MW 9,000 - 10,000] was dissolved in 10 mL of DMSO. To this clear solution was
added 0.3 g (7.5 mmol) of NaOH pellets. The mixture was stirred and warmed up
to
65 - 70 °C with vigorous stirring for 3 hrs during which time it went
from clear to dark
CA 02388920 2002-04-24
WO 01/32720 PCT/CA00/01274
yellow in color. Then, a solution of 0.3 g (1.0 mmol) of tetrabutylammonium
bromide
dissolved in 0.76 mL (7.5 mmol) of 2-chloroethyl vinyl ether was added
dropwise to
the DMSO solution. The mixture was vigorously stirred at 65 - 70 °C for
36 hrs. The
reaction mixture was cooled to room temperature and methanol was added thereby
precipitating the polymer, which was recovered by filtration and dried.
A 25% (w/v) solution of the modified polymer in water was then spin-coated
(3000
rpm for 20 s) onto a silicon wafer and analyzed by IR spectroscopy. The IR
spectrum
revealed a broad band at 3370 cm' for the OH functional groups and a band at
1650
cm' for the C=C of the vinyl ether groups. After baking the film at 180
°C for 3
minutes, another IR spectrum was recorded. This revealed that the band at 1650
cm'
was not longer present indicating that crosslinking had occurred. The film was
then
submerged in water and remained intact for more than one week.
Preparation of capillar~plu~s:
Example 8
This example illustrates the preparation of capillary plugs using PAA as a
base
polymer, the crosslinking with a difunctional vinyl ether, and their dark
stability in
buffered salt solutions.
A methanol solution is prepared as follows:
PAA in a 1:1 (w/v) proportion with methanol (e.g. 1.0 g of PAA in 1 mL of
methanol)
25 to 50% (w/w) of crosslinker (XL 4) with respect to PAA
About 5 ~L of the viscous solution was introduced into a pyrex capillary tube
of 1.5 -
1.8 mm in internal diameter. The crosslinking of PAA with the vinyl ether was
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achieved by baking the capillary in an oven at 105 °C for one hour,
then at 140 °C
for 16 hrs. The resulting plug is about 1 mm thick.
Aqueous insolubilization of such plugs were tested by introducing a buffered
salt
solution on both sides of the plug. Blue food coloring was added to the
buffered
solution on one side of the plug only. The time necessary for the blue dye to
migrate
to the other side of the plug (in the dark) was then determined.
The buffered salt solutions are prepared in water with the following
components:
Solution PS
1 M ammonium sulfate
4% (w/v) polyethylene glycol ( average M.W. 900)
0.5 M phosphate buffer at pH of 5.0
Solution P6
1 M ammonium sulfate
5% (w/v) polyethylene glycol ( average M.W. 900)
0.5 M phosphate buffer at pH of 6.0
Solution P8
1 M ammonium sulfate
3% (w/v) polyethylene glycol ( average M.W. 900)
0.5 M phosphate buffer at pH of 8.0
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Solution T8
3 M ammonium sulfate
0.1 M Tris buffer at pH of 8.0
Results obtained for plugs prepared using 50% w/w of XL 4 are given in Table
4.
Table 4
Buffer SolutionNumber of days for dark
aqueous solubilization
P5 Plug still intact after
3 months
P6 Plug still intact after
3 months
P8 <3*
T8 Plug still intact after
3 months
* as determined by the permeability to the blue dye
Example 9
This example illustrates the preparation of PVA-PAA-PVA capillary plugs using
a
sandwich approach and the comparison of light (254 nm) versus dark
solubilization in
a phosphate buffer salt solution (pH = 6; solution P6).
A methanol solution was prepared as follows:
PAA in a 1:1 (w/v) proportion with methanol (e.g. 1.0 g of PAA in 1 mL of
methanol)
25% (w/w) of crosslinker (XL 4) with respect to PAA
10% (w/w) PAG 10 (n=1 ) with respect to PAA
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A 2:1 (v/v) methanol:water solution was prepared with the following three
components:
10% (w/v) of PVA in solution
SO% (w/w) of XL 4 with respect to PVA
10% (w/w) of PAG 10 (n=1) with respect to PVA
These PVA-PAA-PVA plugs were prepared by introducing the PAA/XL4/PAG 10
solution in a quartz capillary (1 mm in internal diameter, 3mm in length). An
initial
baking of the capillary was done on a hot plate (~ 100 °C) for one hour
(with
occasional rolling of the capillary) in order to evaporate some methanol.
Then, the
PVA/XL4/PAG10 solution was syringed into the capillary on either side of the
PAA
plug. Care must be taken not to introduce any air bubbles which expand upon
heating
leading the viscous solution to splatter all over the walls of the capillary.
The capillary
1 S was baked once again on the hot plate at 100 °C (gradually
increased to 125 °C) over
2.5 hrs. The average size of the plug after baking was ~ 1.5 mm in length and
1 mm in
internal diameter.
Dark versus light solubilization of such plugs was examined. A buffer salt
solution
(P6) was syringed into two such capillaries on both sides of the plugs. One
capillary
was kept in the dark (plug A) while the other (plug B) was irradiated at 254
nm (2.25
mW/cmz). Swelling of both plugs on the edges was observed. However, polymer
swelling was much faster for plug B. After 3.5 hrs of irradiation, the polymer
plug
was swollen throughout and was now about 3 mm in thickness. As for plug A, it
took
5.5 hrs to reach the same status. Irradiation of plug B was pursued for a
total of 22 hrs
after which time the plug became a polymer gel. In comparison, plug A turned
into a
polymer gel over a period of 5 days.
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