CA2388920A1 - Photosolubilizable layers - Google Patents

Abstract

Photosoluble polymeric barriers or membranes are produced by reacting a selected polymer with protic functional groups, e.g. poly(acrylic acid) or poly(vinyl alcohol), with a multifunctional vinyl ether and a PAG. Optionall y, a sensitizer may be added. The mixture is baked to effect crosslinking of th e polymer. The resulting water-impermeable material can be decrosslinked and solubilized by irradiation with a visible or UV light.

Description

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 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.

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.

~.~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'.

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~~~

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 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

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).

Scheme 1: Crosslinking Step c=o 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 Chart 1: Multifunctional Vinyl Ether Crosslinkers ~O O ~ ~O O /

O O/
J ''~-~o ,o o ~o o r v J
O

O
O ~ n O / ~O O
n O

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).

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).

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.

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

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.

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).

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).

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.

Table 1 Time in hours for darkTime in hours for aqueous aqueous solubilizationphotosolubilizationa 50/ b of 10 4 50/b of 20 9 25/b of 30 9 50/ b of >30 16 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

(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 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 \ /

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 a) irradiation at 254 nm using 8 rayonet lamps at a power of 2.0 mW/cmz 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

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 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.

Preparation of crosslinker 15 J

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).

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 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 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 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 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

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.

Claims (64)

Claims:

1. Use of a photosoluble composition in the manufacture of a non patterned photoactivatable barrier layer, said composition comprising:
a polymer that is soluble upon de-crosslinking, a multifunctional crosslinking compound, and a compound generating an acid upon irradiation.

2. The use of clam 1, wherein the barrier layer is for the containment and/or prevention of mixing of media until photoactivation.

3. The use of claim 2, wherein the barrier layer is soluble in the media after photoactivation.

4. The use of claim 2 or 3, for interfacial protein crystallization.

5. The use of claim 1, wherein the barrier layer is part of a dialysis membrane.

6. The use of claim 1, wherein the barrier layer is for protecting a surface.

7. The use of claim 1, wherein the barrier layer is for coating a biological surface.

8. The use of claim 1, wherein the barrier layer is for use as an encapsulation material.

9. Use of a photosoluble composition for the manufacture of a radiation sensor device, said composition comprising:
a polymer that is soluble upon do-crosslinking, a multifunctional crosslinking compound, and a compound generating an acid upon irradiation.

10. The use of any one of claims 1 to 9, wherein the polymer comprises protic functional groups.

11. The use of claim 10, wherein the polymer comprises carboxylic acid, sulfonic acid, amine, or hydroxyl functional groups.

12. The use of claim 10 or 11, wherein the functional groups are attached directly to the backbone of the polymer.

13. The use of claim 10 or 11, wherein the functional groups are present in side chains of the polymer.

14. The use of claim 10 or 11, wherein said polymer comprises carboxylic acid groups and is one or more selected from the group consisting of polyacrylic acid, polymethacrylic acid, polyitanconic acid, polycitraconic acid, polybenzoic acid, polymeric derivatives of half carboxylic esters of malonates, and salts and copolymers thereof.

15. The use of claim 10 or 11, wherein said polymer comprises sulfonic acid groups and is selected from the group consisting of poly(styrenesulfonic acid), its salts, and copolymers thereof.

16. The use of claim 10 or 11, wherein said polymer comprises hydroxyl groups and is one or more selected from the group consisting of poly(vinyl alcohol) and its derivatives, cellulose esters, cellulose others, poly(hydroxyalkylmethacrylates), poly(hydroxyalkylacrylates), poly(saccharidcs), and copolymers thereof.

17. The use of any one of claims 1 to 16, wherein the crosslinking compound is a multifunctional vinyl ether having at least two functional groups.

18. The use of claim 17, wherein the crosslinking compound is one or more selected from the group consisting of tri(ethylene glycol) divinyl ether, tetra(ethylene glycol) divinyl ether, trimethylol propane trivinyl ether, and tris[4-(vinyloxy)butyl)trimellitate.

19. The use of claim 18, wherein the crosslinking compound is synthesized by modifying multifunctional alcohols with vinyl ether derivatives.

20. The use of any one of claims 1 to 19, wherein said acid generating compound is selected from the group consisting of onion salts including sulfonium, iodonium, phosphonium, selcnonium salts of complex metal halides or sulfonates, iminosulfonates, esters of strong acids, sulfones, disulfones and mono-, di- and polyhalogenated compounds.

21. The use of any one of claims 1 to 20, wherein the composition further comprises a sensitizing compound in as amount effective, upon irradiation, to promote a reversal of crosslinking between said polymer and said crosslinking compound.

22. The use of claim 21, wherein said sensitizing compound is selected from the group consisting of dyes and compounds having moieties selected from the group consisting of phenothiazine, ketones including benzophenone, xanthone, thioxanthone, fluorenone, anthraquinone, benzanthrone, polycyclic aromatic hydrocarbons including pyrene, anthracene, naphthalene, perylone, rubrene, and coronene.

23. The use of any one of claims 1 to 22, wherein said polymer is a water-soluble polymer.

24. The use of claim 23, wherein said polymer is poly(acrylic acid) and said crosslinking compound is a difunctional vinyl ether.

25. The use of claim 23, wherein said polymer is poly(vinyl alcohol) and said crosslinking compound is a difunctional vinyl ether.

26. The use of claim 23, wherein said polymer is poly(acrylic acid) and said crosslinking compound is a trifunctional vinyl ether.

27. The use of claim 23, wherein said polymer is poly(vinyl alcohol) derivatized with vinyl ether units.

28. A photosoluble composition comprising:
a polymer with basic groups that is soluble upon de-crosslinking, a multifunctional crosslinking compound, and a compound generating as acid upon irradiation.

29. The composition according to claim 28, wherein the polymer comprises protic functional groups.

30. The composition according to claim 28, wherein the polymer comprises amine or hydroxyl functional groups.

31. The composition according to claim 29 or 30, wherein the functional groups are attached directly to the backbone of the polymer.

32. The composition according to claim 29 or 30, wherein the functional groups are present in side chains of the polymer.

33. The composition according to claim 29 or 30, wherein said polymer comprises hydroxyl groups and is one or more selected from the group consisting of poly(vinyl alcohol) and its derivatives, cellulose esters, cellulose ethers, poly(hydroxyalkylmethacrylates), poly(hydroxyalkylacrylates), poly(saccharides), and copolymers thereof.

34. The composition according to any one of claims 28 to 33, wherein the crosslinking compound is a multifunctional vinyl ether having at least two functional groups.

35. The composition according to claim 34, wherein the crosslinking compound is one or more selected from the group consisting of tri(ethylene glycol) divinyl ether, tetra(ethylene glycol) divinyl ether, trimethylol propane trivinyl ether, and tris[4-(vinyloxy)butyl]trimellitate.

36. The composition of claim 35, wherein the crosslinking compound is synthesized by modifying multifunctional alcohols with vinyl ether derivatives.

37. The composition of any one of claims 28 to 36, wherein said acid generating compound is selected from the group consisting of onium salts including sulfonium, iodonium, phosphonium, selenonium salts of complex metal halides or.
sulfonates.
iminosulfonates, esters of strong acids, sulfones, disulfones, and mono-, di-and, polyhalogenated compounds.

38. The composition of any one of claims 28 to 37, further comprising a sensitizing compound in an amount effective, upon irradiation, to promote a reversal of crosslinking between said polymer and said crosslinking compound.

39. The composition of claim 38, wherein said sensitizing compound is selected from the group consisting of dyes and compounds having moieties selected from the group consisting of phenothiazine, ketones including benzophenone, xanthone, thioxanthone, fluorenone, anthraquinone, benzanthrone, polycyclic aromatic hydrocarbons including pyrene, anthracene, naphthalene, perylene, rubrene, and coronene.

40. The composition of any one of claims 28 to 39, wherein said polymer is a water-soluble polymer.

41. The composition of claim 40, wherein said polymer is poly(vinyl alcohol) and to said crosslinking compound is a difunctional vinyl ether.

42. The composition of claim 40, wherein said polymer is poly(vinyl alcohol) and said crosslinking compound is a trifunctional vinyl ether.

43. The composition of claim 40, wherein said polymer is poly(vinyl alcohol) derivatized with vinyl ether units.

44. A method of manufacturing a photosoluble material comprising:
a) mixing a polymer with basic groups that is soluble upon de-crosslinking, with a multifunctional crosslinking compound and with 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 photosoluble material.

45. The method of claim 44, wherein step a) further comprises. mixing a sensitizing compound with said polymer, said crosslinking compound and said acid generating compound.

46. A photosoluble material produced by the method of claim 44 or 45.

47. A method of solubilizing the material of claim 46, comprising: irradiating said material with radiation in the visible or ultraviolet range for a time period sufficient to effect de-crosslinking between the polymer and the crosslinking compound, and consequently solubilizing said material.

48. A photosoluble composition comprising:
a polymer that is soluble upon de-crosslinking, a multifunctional crosslinking polymer, and a compound generating an acid upon irradiation.

49. The composition according to claim 48, wherein the soluble polymer comprises protic functional groups.

50. The composition according to claim 48, wherein the soluble polymer comprises carboxylic acid, sulfonic acid, amino, or hydroxyl functional groups.

51. The composition according to claim 49 or 50, wherein the functional groups are attached directly to the backbone of the soluble polymer.

52. The composition according to claim 49 or 50, wherein the functional groups are present in side chains of the soluble polymer.

53. The composition of claim 49 or 50, wherein said soluble polymer comprises carboxylic acid groups and is one or more selected from the group,consisting of polyacrylic acid, polymethacrylic acid, polyitanconic acid, polycitraconic acid, polybenzoic acid, polymeric derivatives of half carboxylic esters of malonates, and salts and copolymers thereof.

54. The composition of claim 49 or 50, wherein said soluble polymer comprises sulfonic acid groups and is selected from the group consisting of poly(styrenesulfonic acid), its salts and copolymers thereof.

55. The composition according to claim 49 or 50, wherein said soluble polymer comprises hydroxyl groups and is one or more selected from the group consisting of poly(vinyl alcohol) and its derivatives, cellulose esters, cellulose ethers, poly(hydroxyalkylmethacrylates), poly(hydroxyalkylacrylates), poly(saccharides), and copolymers thereof.

56. The composition according to any one of claims 48 to 55, wherein the crosslinking polymer is a profit polymer modified with a vinyl ether.

57. The composition of any one of claims 48 to 56, wherein said acid generating compound is selected from the group consisting of opium salts including sulfonium, iodonium, phosphonium, selenonium salts of complex metal halides or sulfonates, iminosulfonates, esters of strong acids, sulfones, disulfones and mono-, di-and polyhalogenated compounds.

58. The composition of anyone of claims 48 to,57, further comprising a sensitizing compound in an amount effective, open irradiation, to promote a reversal of crosslinking between said soluble polymer and said crosslinking polymer.

59. The composition of claim 58 wherein said sensitizing compound is selected from the group consisting of dyes and compounds having moieties selected from the group consisting of phenothiazine, ketones including benzophenone, xanthone, thioxanthone, fluorenone, aathraquinone, benzanthrone, polycyclic aromatic hydrocarbons including pyrene, anthracene, naphthalene, perylene, rubrene and coronene.

60. The composition of any one of claims 48 to 59, wherein said soluble polymer is a water-soluble polymer.

61. A method of manufacturing a photosoluble material comprising:
a) mixing a polymer soluble upon do-crosslinking with a multifunctional crosslinking polymer 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 photosoluble material.

62. The method of claim 61 wherein step a) further comprises mixing a sensitizing compound with said soluble polymer, said crosslinking polymer, and said acid generating compound.

63. A photosoluble material produced by the method of claim 61 or 62.

64. A method of solubilizing the material of claim 63, comprising the step of irradiating said material with radiation in the visible or ultraviolet range for a time period sufficient to effect de-crosslinking between the soluble polymer and the crosslinking polymer, and consequently solubilizing said material.