MXPA96005326A

MXPA96005326A - Polymerizable composition and use of the mi

Info

Publication number: MXPA96005326A
Application number: MXPA/A/1996/005326A
Authority: MX
Inventors: Barnard Steven; Rouilly Marizel
Original assignee: Barnard Steven; Cibageigy Ag; Rouilly Marizel
Priority date: 1994-05-02
Filing date: 1996-11-01
Publication date: 1998-02-01

Abstract

A composition comprising: (a) at least one olefinic monomer, (A), (b) at least one polymer of at least one olefinic monomer, (c) an indicator dye for the basic structure, with which it is bonded covalently an olefin polymerizable group directly by means of a bridging group, (d) at least one at least diolefinic cross-linking agent, and (e) an effective amount of a polymerization initiator. The polymers of the composition are suitable as membranes in optical sensors, for the detection of ions and gas

Description

POLYIZABLE COMPOSITION AND USE OF THE SAME The present invention relates to a composition that comprises: (a) at least one olefinic monomer (A), (b) a polymer of an olefinic monomer, (c) an indicator dye for the basic structure, with which an olefin polymerizable group is covalently linked directly or by means of a ^ bridge group, (d) at least one crosslinking agent at least diolefinic, and (e) at least one polymerization initiator; to polymers from that composition: to a material coated with the polymer; and to the use of them. The International Patent number WO 88/05533 describes sensor membranes that can be copolymerized of indicators of vinyl substituted dyes and acrylic amides or methacrylic amides. The copolymers are produced directly on an optical carrier material, for example, a glass fiber, for example, by immersing a glass fiber in the monomer mixture, removing the glass fiber, and then polymerization of the layer. The surface of the glass fiber SP makes it functional in advance with acrylic amides, in such a way that the polymer is bonded in the same way covalently to the surface. Membranes are obtained on which a dye indicator has been immobilized, from which it is It is virtually impossible for the polymer-bound dye to wash off. A drawback of the membranes described is especially that their layer thicknesses depend rlp on the selected composition / viscosity thereof, and can not be controlled in an objective manner, which has a direct adverse effect on response times and sensitivities . Accordingly, usable membranes can only be obtained depending in a timely manner on the consistency of the selected monomers. International Patent No. WO 93/07483 discloses sensors for indicating the pH value, wherein the indicator dye is covalently bound to the hydrophilic polymeric membrane, in order to prevent it from being washed out through use. The immobilization is carried out by the subsequent treatment of the membrane with a dissolved dye indicator, which contains functional groups that are capable of reacting with the functional groups of the polymeric membrane. In addition, only certain polymers previously prepared for a membrane can be used, whose mechanical and physical properties can not be selectively adapted to the intended use. The manufacturing process, by its nature, is associated with a high degree of variation in the quality of the product (for example, in the dye indicator content) that makes continuous production and application difficult or impossible in conventional systems. "Apalytica Chimica Acta", 276 (1993), 3U7-352 discloses an electrochemical sensor containing, on a measuring electrode, an ion-sensitive membrane consisting of a cross-linked methacrylate polymer obtained in the presence of polyvinyl pyrrolidone. The properties for an optical ion sensor are not mentioned and for this measuring method, immobilization with a dye indicator is not required and described. It has now been discovered, in a surprising manner, that polymers of hydrophilic olefinic monomers (A) containing a homo- or co-polymer of the same monomer (A) or of hydrophilic monomers (B) different from (A), and a olefinically substituted dye indicator, they are excellently suitable as membranes for optical sensors for the determination of ions or gases, for example, oxygen or carbon dioxide. The membranes have excellent mechanical strength, and the dye indicator is covalently bonded to the central structure of the polymer and, therefore, can not be washed out with the measuring solution, which in total ensures a long service life. The membranes exhibit the necessary optical transparency as a result of an unexpected homogeneous consistency. The desired degree of hydrophilicity can be adjusted in an objective way, so that, especially for the optical detection of the pH, the scale of pH measurement can be determined previously by the selection and the amount of hydrophilic monomers and polymers. A further great advantage is that economical production processes can be employed, for example, centrifugal emptying processes. for coating the carrier materials, since the viscosity of the polymerizable composition can be established and adapted to the process technology, by selection and quantity of the hydrophilic polymer. In addition, manufacturing processes ecologically favorable for mass production are possible, since coating solutions can be used aqueous, and the polymerization can be carried out directly on the carrier material. Therefore, a high degree is obtained of production conformance, especially with respect to layer thicknesses, even in the case of very thin layers, such that a conventional calibration is generally adequate, and no further calibration is necessary if the sensors are to be replaced. In addition, it is possible to produce very thin, but at the same time uniform. The polymerizable compositions have adequate storage stability, and can be marketed as such. The polymers from the compositions surprisingly form a network, where the polymer molecules of the monomers (A) are embedded. or penetrate the network. It is surprising that no segregation is observed, but, on the contrary, there is a uniform distribution of the polymer molecules. in such a way that the polymerized material is homogeneous. The invention relates to a composition that comorende: (a) at least one olepipic mopomer (A). (b) at least one polymer, of at least one olefinic monomer, (c) an indicator dye for the basic structure, with which an olefin polymerizable group is covalently bonded directly or by means of a bridging group , (d) at least one crosslinking agent. at least diolefinic, and (e) an effective amount of a polymerization initiator. The desired properties of the membrane can be varied and established within a wide range by selecting the monomers (A) and the polymers of the component (b), and the combination thereof. For optical detection of ions or for pH measurements in an aqueous medium, hydrophobic membranes are generally preferred. The hydrophilic character can be established by the selection and quantity of the hydrophilic monomers (A), optionally mixed with hydrophobic monomers. and the amount proportions thereof, and by the selection and quantity of the polymer of component (b) and the hydrophilicity thereof, which is determined by the content of hydrophobic and / or hydrophobic monomers. In the optical detection of gases in the medium that can be liquid, for example blood, in general preference is given to the hydrophobic membranes that can be obtained and adjusted as above, but using hydrophobic monomers (A) and polymers of the component (b) ). The hydrophilic and hydrophobic monomers and the polymers can be combined according to the above as desired, with other hydrophilic and / or hydrophobic monomers and polymers in order to obtain the desired properties. "Hydrophilic" may indicate a solubility in water of at least 1 percent by weight, preferably at least 10 percent by weight, especially at least 20 percent by weight, most especially at least 40 percent by weight , and most especially at least 50 percent by weight, based on the percentages in the solution. The polymer of component (b) may comprise at least one monomer identical to (A), at least one monomer (B) that is different from (A), or a mixture of those monomers. In a preferred form, the polymer of component (b) is composed predominantly, and especially exclusively of monomer (A). The hydrophilic olefinic monomers (A) and / or (B) may be present in an amount of 5 to 95 weight percent, preferably 10 to 90 weight percent, especially 10 to 80 weight percent, and more especially from 20 to 70 weight percent, based on the composition. The same applies to hydrophobic monomers or mixtures of hydrophobic and hydrophilic monomers. The homo-6 co-polymers of the hydrophilic component (b) can be present in an amount of 95 to 5 percent by weight, preferably 90 to 10 percent by weight, especially 90 to 20 percent by weight, and more especially from 80 to 30 percent by weight, based on the composition. The same applies to hydrophobic polymers or to polymers composed of mixtures of hydrophobic and hydrophilic monomers. The indicator dye may be present in an amount of 0.01 to 10 percent by weight, preferably 0.1 to 5 percent by weight, and especially 0.5 to 3 percent by weight. The polymerization initiator may be present in an amount of 0.1 to 20 percent by weight, preferably 0.5 to 10 percent by weight, and especially 1 to 8 percent by weight. The composition according to the invention comprises a crosslinking agent, for example, in an amount of 0.1 to 30 percent by weight, preferably 0.5 to 20 percent by weight, especially 0.5 to 10 percent by weight, and more especially from 0.5 to 5 percent by weight. The numerical values of the percentages by weight always add 100 percent by weight. The monomers (A) or (B) are preferably selected from the group of olefins substituted by at least one hydrophilic radical. The hydrophilic radicals are especially selected, for example, from the group consisting of pyrrolidonyl, amino, primary amino, secondary amino, corresponding ammonium groups and hydroxy, each bonding directly or by means of a bridge group with the olefin group. The bridge groups can be -C (0) -. -C (0) -0-alkylene-, -C (0) -NH-alkylene-, -C (0) -0- (alkylene of 2 to 6 carbon atoms-O) ^ a ^ -alkylene of 2 to 6 carbon atoms-, -C (0) -NH- (alkylene of 2 to 6 carbon atoms-0) j ^ -alkylene of 2 to 6 carbon atoms- or -O-alkylene. There may also be acidic hydrophilic groups, for example, -C (0) 0H, present in the form of salts, for example, in the form of alkali metal or alkaline earth metal salts. The hydrophilic monomers (A) or (B) may correspond, for example, to Formula I: Kt? ? LJ- * G? -T '(i) where R., Rn and R-? are, each independently of the others, hydrogen or a hydrophobic substituent, and Z is a hydrophilic radical. A hydrophobic substituent may be, for example, alkyl of 1 to 12 carbon atoms, preferably alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 12 carbon atoms, preferably alkoxy of 1 to 6 carbon atoms, haloalkyl from 1 to 12 carbon atoms, preferably haloalkyl of 1 to 6 carbon atoms, phenyl, halophenyl, for example, chlorophenyl, alkyl of 1 to 4 carbon atoms-phenyl, alkoxy of 1 to 4 carbon atoms-phenyl, a carboxylic acid ester group having a total of 2 to 20 carbon atoms, -CN, F or Cl. In a preferred form, in Formula I, Rj and R2 are hydrogen, and R3 is hydrogen or methyl. The hydrophilic radical can be, for example, -OH, -0- (alkylene of 2 to 12 carbon atoms) -OH and preferably -O- (alkylene of 2 to 6 carbon atoms) -OH, -C (0) ) -NH2, -C (OJNH- (alkylene of 2 to 12 carbon atoms) -OH, and preferably -C (0) -NH- (alkylene of 2 to 6 carbon atoms) -OH, -C (0) ) -N- (alkylene of 2 to 12 carbon atoms) 2-0H, and preferably -C (0) -N- (alkylene of 2 to 6 carbon atoms) 2-0H, -C (0) -NH -Alkyl of 1 to 12 carbon atoms, and preferably -C (O) -NH-alkyl of 1 to 6 carbon atoms, -C (O) -N- (alkyl of 1 to 12 carbon atoms) 2, and preferably -C (0) -N- (alkyl of 1 to 6 carbon atoms) 2, pyrrolidonyl, -C (0) -NH-alkylene of 1 to 12 carbon atoms-NH2, and preferably -C ( 0) -NH-alkylene of 1 to 6 carbon atoms-NH2, -C (0) -NH-alkylene of 1 to 12 carbon atoms-NH-alkyl of 1 to 6 carbon atoms, and preferably -C ( 0) -NH-alkylene of 2 to 6 carbon atoms-NH-alkyl of 1 to 4 carbon atoms, -C ( O) -NH-alkylene of 1 to 12 carbon atoms-N- (alkyl of 1 to 6 carbon atoms) 2, and preferably -C (0) -NH-alkylene of 2 to 6 carbon atoms-N- (alkyl of 1 to 4 carbon atoms) 2, or -C (O) -O (alkylene of 2 to 12 carbon atoms) -OH, and of r '"preference -C (O) -0- (alkylene of 2 to 6 carbon atoms) -OH, or -C (0) -0- (C 2-6 -alkylene-OJi to 12-alkylene of 2 to 6 carbon atoms-OH, or -C (O) -NH- (alkylene of 2 to 6 carbon atoms) carbon-0)! to 12-alkylene of 2 to 6 carbon atoms-OH having the same alkylene-O- or different radicals, which are preferably present in 1 to 6, especially 1 to 4 times, and alkylene is preferably ethylene, 1,2- or 1,3-propylene or 1,4-butylene. Examples of such monomers A are vinyl alcohol, ethers hydroxy- 2 to 6 carbon atoms vinyl, acrylic amide, methacrylic amide metilacrílica, metilmetacrílica amide, amide etilacrílica, etilmetacrílica amide, amide propyl or isopropyl acrylic normally amide propyl or isopropyl normally methacrylic, butyl amide normally, isobutilo-, or tertiary-butyl acrylic, butyl amide normally, isobutilo-, or tertiary-butyl methacrylic amide dimetilacrílica, etacrílica dimethyl amide, amide dietilacrílica, amide dietilmetacrílica , dipropyl amide or acrylic normally diisopropyl amide dipropyl or diisopropyl normally methacrylic amide dibutyl normally, diisobutilo-, or tertiary-dibutyl acrylic amide normally dibutyl, diisobutyl, dibutyl or tertiary-methacrylic pyrrolidone acrylate and hydroxyethyl methacrylate, acrylate and methacrylate of hydroxy-1,2-propyl, acrylate and methacrylate of hydroxy-1,3-propyl, acrylate and methacrylate ato hydroxy 1,2-butyl acrylate and methacrylate, 1,3-hydroxy butyl acrylate and methacrylate, hydroxy l, a-butyl acrylate and methacrylate, hydroxy-1, 2-pentyl acrylate and methacrylate hydroxy-1 , 3-pentyl acrylate and methacrylate, hydroxy-1, 4-peptilo acrylate and methacrylate hydroxy-1,5-pentyl acrylate and methacrylate hydroxy-1, 2-hexyl acrylate and methacrylate, hydroxy-1, 3-Hexyl, Acrylate and Methacrylate of Hydroxy-1,4-Hexyl, Acrylate and Hydroxy-1-Methacrylate, 5-hexy lo, acrylic amide and methacrylic amide of hydroxyethyl, acrylic amide and methacrylic amide of hydroxy-1,2-proyl, acrylic amide and methacrylic amide of hydroxy-1,3-propyl, acrylic amide and methacrylic amide hydroxy-1,2-butyl, acrylic amide and methacrylic amide of hydroxy-1,3-butyl, acrylic amide and methacrylic amide of hydroxy-1,4-butyl, acrylic amide and methacrylic amide of hydroxy-1,2-penti or , acrylic amide and methacrylic amide of hydroxy-1,3-pentyl, acrylic amide and methacrylic amide of hydroxy-1,4-pentyl, acrylic amide and methacrylic amide of hydroxy-1,5-pentyl, acrylic amide and hydroxy methacrylic amide -1, 2-hexyl, acrylic amide and methacrylic amide of hydroxy-1,3-hexyl, acrylic amide and methacrylic amide of hydroxy-1,4-hexyl, acrylic amide and methacrylic amide of hydroxy-1,5-hexyl, amide acrylic and methacrylic amide of hydroxy-1, 6-hexy lo. dialkyl ethers of hydroxypolyoxyalkylene, acrylate or hydroxypolyoxyalkylene methacrylate.

The polymer of component (b) preferably comprises at least one identical monomer (A) of component (a), or a monomer (B) different from monomer (A), or a mixture of these monomers. In the case of a copolymer, the polymer comprises different monomers (A), or monomers (A) and monomers (B). The homopolymers are composed of the monomers (A) or the monomers (B). In a preferred form of the composition according to the invention, the polymer of component (b) is ~ consists of a monomer (A) selected from the same group of monomers (A) and is the same or different, the group being, for example, acrylates and / or methacrylates, acrylic amides and / or methacrylic amides, vinyl alcohols and / or hydroxyalkylvinyl ethers, pyrrolidone and styrene. In an especially preferred form of the composition according to the invention, the polymer of component (b) is composed of the same monomer (A) as that used as the monomer (A). Some especially preferred combinations of hydrophilic monomers and polymers are vinyl pyrrolidone / pyrrolidone, acrylic amide / polyacrylic amide, acrylic amide / polymethacrylic amide, methacrylic amide / polyacrylic amide, ethylacrylic amide / polyethylacrylic amide, propyl acrylamide / polypropyl amide, tertiary butyl amide- acrylic / tertiary-acrylic polybutyl amide, tertiary-acrylic butyl amide / polyacrylic amide, tertiary-acrylic butyl amide / polymethacrylic amide, hydroxyalkyl vinyl ether / polyhydroxyalkylvinyl ether, hydroxyethyl methacrylate / polyhydroxyethyl methacrylate, hydroxyethyl methacrylate / acrylate polyhydroxyethyl, normal hydroxypropyl methacrylate / normal polyhydroxypropyl methacrylate, hydroxyisopropyl methacrylate / polyhydmixy isopropyl methacrylate, normal hydroxybutyl methacrylate / normal polyhydroxybutyl methacrylate, normal hydroxypenthacrylate / polyhydroxyl methacrylate ipentyl normal, normal hydroxyhexyl methacrylate / normal polyhydroxyhexyl methacrylate. The hydrophobic monomers (A) or (B) may correspond, for example, to Formula III: R6R7C = CR8-Y (III) wherein: R1 and R7 and Rg are each independently of the others, hydrogen or a hydrophobic substituent, and Y is a hydrophobic radical. The hydrophobic substituents can be, for example, alkyl of 1 to 12 carbon atoms, preferably alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 12 carbon atoms, preferably alkoxy of 1 to 6 carbon atoms, haloalkyl of the 12 carbon atoms, preferably haloalkyl of 1 to 6 carbon atoms, phenyl, halophenyl, for example, odophenyl. alkyl of 1 to 4 carbon atoms-phenyl, alkoxy of 1 to 4 carbon atoms-phenyl, an ester group of carboxylic acid having a total of 2 to 20 carbon atoms, -CN. F or Cl. The hydrophobic radical Y can be a radical as mentioned for R, to Rg. Preferred radicals Y are alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, phenyl, chlorophenyl, alkyl of 1 to 4 carbon atoms-phenyl, alkoxy of 1 to 4 carbon atoms-phenyl, groups carboxylic acid ester having a total of 2 to 10 carbon atoms, -Chi and Cl. In a preferred form, in the ITI Formula. Rfe and R7 are hydrogen, and Rg is hydrogen or methyl. Some preferred combinations of hydrophobic monomers and polymers are styrene / polystyrene, methyl acrylate / polymethyl acrylate, methyl methacrylate / polymethyl methacrylate, vinylethyl ether / polyvinylethyl ether, acrylonitrile / polyacrylonitrile and acrylonitrile / polystyrene. The polymer of component (b) can have an average molecular weight of 1,000 to 1,000,000 daltons, preferably 10,000 to 500,000 daltons, determined according to the gel permeation method using conventional polymers of known molecular weight. The preferred indicator dye is a fluorophore for the detection of changes in emissions, for example, in fluorescence.

The indicator dye can be a dye of Formula II: R4HC = CR5- (X) q-dye (II) wherein: R4 is methyl and R5 is hydrogen, or R5 is methyl and R is hydrogen, q is 0 or 1, X is a bridging group, and dye is the monovalent radical of a dye indicator. In a preferred form, R4 is hydrogen and R5 is hydrogen or methyl. In a different preferred form, q is 1. The bridge group X can be, for example, -O-, -NH, -NH-alkyl of 1 to 4 carbon atoms, -C (0) -0-, -C (0) -NH-, -C (0) -NH-alkyl of 1 to 4 carbon atoms-, -NH - (CO) -O-, -0-C (0) -NH-, -C (O) -O-alkylene of 2 to 12 carbon atoms-OC (O) -, -C (0) -NH- alkylene of 2 to 12 carbon atoms-OC (O) -, -C (O) -O-alkylene of 2 to 12 carbon atoms-NH-C (O) -, -C (O) -NH-alkylene 2 to 12 carbon atoms-NH-C (O) -, -C (O) -NH-alkylene of 2 to 12 carbon atoms-C (O) -NH-, -NH-C (O) -O- alkylene of 2 to 12 carbon atoms-OC (O) -, -C (O) -O- (alkylene of 2 to 6 carbon atoms-O)! a 12-, -C (0) -0- (alkylene of 2 to 6 carbopo-O atoms) ^ to 12-alkylene of 2 to 6 carbon atoms-NH-, -C (0) -NH- (alkylene) of 2 to 6 carbon atoms-0) 1 to ^ -alkylene of 2 to 6 carbon atoms-NH-, -C (0) -NH- (alkylene of 2 to 6 carbon atoms -O), to 12- CH2-C (0) -NH- The preferred bridging groups are -C (0) -NH-, -C (0) -0 (CH2CH2-0) l a6-, -C? Q -NH-CCHjCHj-O)! at 6"CH2C (O) -NH-, -C (0) -NH- (alkylene of 2 to 6 carbon atoms-0) ^ ^ -alkylene of 2 to 6 carbon atoms-NH- and -C (0) ) -NH-alkylene of 2 to 12 carbon atoms-C (0) -NH- The dye indicator can be a dye indicator that changes its absorption or emission under the action of a test sample and, therefore, Particularly preferred are fluorescent dyes (fluorophores), for example, those of the xanthine and benzoxaphene group (eg, 1-chloroscein, halogenated luoresceins, semi-naphofluoresce-1, semi-naphro-1-fluor, 2, 3-benzofluorescein, 3-benzofluorescein, the isomers of benzorhodamine and substituted derivatives, the isomers of bepzochromogen and substituted derivatives); acridines (for example, acridine, 9-amino-6-chloroacridine): acridones (for example, 7-hydroxyacridone) , 7-hydroxybepzacridone); pyrenes (for example, 8-hydroxypyren-1, 3,6-trisulfonic acid): coumarins (eg, 7-hid roxycoumarin, 4-chloromethyl-7-hydroxycoumarin): cyanine dyes and conjugated metal complexes, for example, platinum porphyrins. Fluorescent dyes are made olefinically functional to bind to a polymer. The especially preferred fluorophores are 3- or 4-acryloylaminofluorescein and 3- or 4-methacryloylaminofluorescein. A wide variety of absorption dyes for sensors are known. Examples are methyl violet, crystal violet, malachite green oxalate, methyl green, red quinaldine, 4-phenylazodifenlline amine, thymol blue (thiolsulfonephthalein), metacresol purple, orange IV, benzopurpurine 4B, p- (m-tolylazo) N, N-dimethyl amine. broccoli blue, Congo red, methyl orange, bromocresol green, resazurin, 4-phenylazo-l-naphthyl amine, ethyl red, lacmoide, red alizarin S, purple bromocresol, red ! ' chlorophenol, alizarin, bro otimol blue, bright yellow, phenol red, neutral red, cresol red, metacresol purple, thymol blue, o-cresolphthalein, p-naphtholbenzene, phenolphthalein, thymolphthalein, alizarin yellow R, curcumin, alizarin. The absorption dyes are made olefinically functional to bind to a polymer. Suitable functional groups for linking to a carbon atom of the olefinic group (directly or by means of a bridging group) are, for example, -OH, -NH2, -NH-alkyl 1 to 4 carbon atoms, -C (0) 0H, -C (0) C1.

-S02C1, -C (0) -NH2, -C (0) -NH-CH2CH2-OH, -C (O) -0-CH2CH2-OH, -C (0) -NH-CH2CH2-NH2, -C ( O) -0-CH2CH2-NH2, -NH-C (O) -CH2CH2, -CH2I, -CH2Br, -CH2C1, -NCS, NCO, -N3 and succinyl esters. Vinyl or methylvinyl is suitable for a direct bond. The indicator dye can also be linked directly or by means of a bridge group to the nitrogen atom of an unsubstituted or substituted maleinimidyl group. Suitable crosslinking agents are, for example, esters of acrylic or methacrylic acid or polyol amides, preferably diols to tetroles, or polyamines, preferably diamines to tetramines. Aliphatic and cycloaliphatic diols and diamines are preferred. These crosslinking agents are known and many are described in the literature. Some examples of polyols are alkylene diols, such as ethylene glycol, 1,3-propanediol, 1,4-butanediol, 1,6-hexanediol, diethylene glycol, polyalkylene diols, preferably 2 to 6 alkylene diols. carbon atoms having especially from 3 to 100 units of alkylene diol, for example, polyethylene glycols, polypropylene glycols, polybutylene glycols, and polyethylene-propylene glycols, 1, 1, l-trihydroxy-methyl-ethane or -propane, pentaerythritol and dipentaerythritol. Some examples of polyamines are ethylenic diamine, 1,3-propanediamine, 1,4-butanediamine, 1,6-hexanediamine, diethylene triamine and triethyl tetramine. Other known crosslinking agents are, for example, divinyl benzene and bis (dimethylmaleinimidyl) alkylenes, for example, methylene or 1,2-ethylene-bis (dimethylmaleimidyl). Some examples are N, N * -methylene-bis-acrylic acid amide, N, N'-ethylene-bis-acrylic acid amide, acid amide N, N'-propylene-bis-acrylic, ethylene glycol bis-acrylate, propylene glycol bis-methacrylate, butylene glycol bismethacrylate, hexylene glycol bis-methacrylate, and "Polyethylene glycol bismetacrylates having average molecular weights of 200 to 3000. The composition according to the invention comprises polymerization initiators, which can be activated either thermally or by the action of radiation. Examples of thermal initiators are radical formers, for example, organic azo compounds, peroxo compounds and peroxodisulfates. Some examples are a, a-azo-bisisobutyronitrile or ammonium peroxodisulfate. Examples of photo-activators that can be activated by radiation, for example ultraviolet light, which can optionally be used together with sensitizers, are benzophenones, xanthones, thioxanthones, a-amino secondary acetophenones and a-hydroxy acetophenones. The components of the composition according to the invention are known or can be prepared according to known or analogous processes. Indicator dyes that become functional are known or can be prepared and derived with reagents that form groups of bridges according to known or analogous processes. The acrylic aminofluorescein amide is commercially available. Rhoxes derived from carboxyalkyl groups are described, for example, by T. Werner et al in Journal of Fluorescence, Volume 2, No. 2, pages 93 to 98 (1992). If desired, the carboxy groups can be functionally derivatized in a known manner (amides, amines, etc.). The composition according to the invention may comprise additives to improve processability, for example, flow agents, viscosity increasing agents or viscosity reducers and solvents. However, in general it is convenient to add a solvent diluent or a mixture of solvents. Polar, and optionally protic, solvents are preferred. Examples of these solvents and diluents that may be mentioned are: water; esters, such as ethyl acetate; ethers, such as diethyl ether, dipropyl ether, di-isopropyl ether, dibutyl ether, tertiary butyl methyl ether, ethylene glycol onomethyl ether, ethylene glycol monoethyl ether, ethylene glycol dimethyl ether, dimethoxydiethyl ether, tetrahydrofuran or dioxane; ketones, such as acetone, methylethyl ketone, or methyl isobutyl ketone: alcohols, such as methanol, ethanol, propanol, isopropanol, butanol, ethylene glycol or glycerol; amides, such as formamide N, N-di methyl, formamide, N-diethyl, acetamide N, N-dimethyl, pyrrole idone N-methyl, or triamide hexamethylphosphoric acid; nitriles, such as acetonitrile or propionitrile; and sulfoxides, such as dimethyl sulfoxide. Preferred solvents are water, alkanols, and N-dialkylated carboxylic acid amides. The composition according to the invention is excellently suited for the coating of carrier materials, especially carriers which can be transparent, according to customary surface coating methods, the layer being polymerized in a manner known per se after coating, and where appropriate, after removing a cosolvent used. The coated material is especially suitable for the manufacture of sensors. The composition according to the invention is excellently suited for the manufacture of membranes for optical sensors. The invention also relates to a method for coating coating carrier materials, wherein the composition according to the invention is applied to at least one surface of the carrier material, where it is appropriate to remove a solvent, and the layer is polymerized. For the purpose of improving adhesion, the carrier materials can be treated in advance with adhesion promoters. For the same purpose, it is also possible to carry out plasma treatment of the carrier material, in order to generate functional groups on the surface. The surface can also be provided with copolymerizable groups in order to achieve an especially high degree of adhesion. The known adhesion promoters for glass are, for example, triethoxy-glycidyloxy-silane, 3-azidopropyl triethoxysilane. or 3-aminopropyl-triethoxy-silane. The surfaces thus treated can be further modified, for example, with O- (N-succipimidyl) 6- (4'-azido-2'-nitrophenylamino) -hexanoate. It has been found to be especially advantageous to treat the surfaces with ethylenically unsaturated carboxylic acid ester silanes, for example 3-trimethoxysilylpropyl methacrylic acid ester, because, in the polymerization, the layer can be anchored covalently to the surface. Known coating techniques are, for example, spreading, immersion, knife application, spraying, pouring, draining or, especially, pouring by centrifugation or spin coating, respectively. It is especially convenient that the coating itself can be made with aqueous solutions, and in this case, spin coating processes can also be employed. The invention also relates to a carrier material wherein a layer of the composition according to the invention has been applied, at least to a surface. The invention also relates to a carrier material wherein a polymeric layer of the composition according to the invention has been applied, at least to a surface. The polymeric layers are optically transparent and, therefore, are especially suitable for optical detection methods. The invention also relates to an optical sensor wherein a polymeric layer of the composition according to the invention has been applied, at least to a surface. In this form of the invention, preferably there is no fluorophore sensitive to the protons for the detection of the pH present in a hydrophilic polymeric layer. The invention also relates to the use of the sensors according to the invention for the optical determination of ions and gases (for example, 0 or C02 in the blood). In this form of the invention, preferably there is no fluorophore sensitive to the protons for the detection of the pH present in the hydrophilic polymeric layer. The invention also relates to a polymer from a composition according to the invention, preferably in the form of an unsupported film, which can be used directly as an optical sensor. The polymers can be obtained, for example, by stripping off the layers of the carrier material, or by means of polymerization in molds. The geometric shape of the carrier material can vary to a very large degree; for example, it may be in the form of fibers, cylinders, spheres, cuboids or cubes. Transverse flow systems are also possible, where continuous measurements or successive measurements can be made. Flat sensors are preferred. The carrier material is preferably transparent. It can be, for example, inorganic glass or transparent plastic, such as polycarbonate, polyesters, polyamides, or polyacrylates or polymethacrylates. In another preferred form, the carrier material of the optical sensors is transparent, and preferably consists of glass or a transparent polymer. The flat sensor can have any desired external shape, for example, it can be square, rectangular or round. It can have a surface area of 0.01 to about 50 cm2, conveniently 0.02 to 10 cm2. The measurement region of the sensor can have an area of, for example, less than 5 mm2, preferably less than or equal to 2 mm2. The measurement region can be identical to the fully coated surface of the sensor. Conveniently, a coating provided on both sides, but locally separated, can be used. The thickness of the polymer layer (b) can be, for example, from 0.01 to 50 microns, preferably from 0.1 to 25 microns, and especially from 0.1 to 10 microns. The forms of the invention mentioned above are subject to the same preferences as those indicated for the composition according to the invention. The polymerization of the composition according to the invention can be carried out using thermal initiators at an elevated temperature, for example, from 40 to 200 ° C, and preferably from 50 to 150 ° C. The photopolymerization can be carried out at room temperature . In that case, an increase in temperature, as mentioned above, can be used to accelerate the reaction. The polymers can also be prepared by plasma polymerization. For the determination of cations and anions, in general ionophores are also incorporated, which, upon contact with the analysis solution, produce, as a result of the interaction with the indicator dye, a change in the absorption or emission in the form of a measurable signal, thus allowing optical determination. As a rule in these systems, salts, such as tetraphenyl borate, and optionally pH regulators are also used. If the indicator dye is sensitive to protons, this sensitivity can be used directly for the determination of the pH value, or indirectly in pH-altering reactions for the determination of ions (anions or metal cations). The determination of potassium is described, for example, by T. Werner 0 et al in "Journal of Fluorescepce", Volume 2, No. 2, pages 93 to 98 (1992), and can be performed in a manner analogous to that process . The determination of the pH using two sensors having different dependencies in the ionic concentration of the measuring solution, is described in German Patent DE-A-5 3,430,935, and can be performed in an analogous manner using the sensors according to the invention. The radiation used for the measurement can be selected from the ultraviolet scale, by means of the visible scale up to the near infrared scale (NIR scale); the selection depends substantially on the nature of the dye indicator. The hydrophilic polymer membranes prepared according to the invention are especially suitable for the optical detection of the pH value in aqueous electrolyte solutions on the physiological scale, for example in blood or in blood serum, if a sensitive fluorophore is present to the protons in the membrane. The method for the independent and reversible optical determination of the pH value and the ionic concentration of an aqueous sample (electrolyte solution) with the help of two different sensors, according to the fluorescence method can be performed, for example, as follows: two optical sensors, which are each composed of polymers of different structure, but each containing the same fluorescent dye, and each consisting of a coated material according to the invention, are contact with an aqueous test sample, and irradiate with exciting light, fluorescence is measured. and the pH values and ionic concentrations are calculated from the fluorescence intensities measured with reference to calibration curves. In detail, a procedure can be performed where. after calibration with samples of a known ionic concentration and a known pH, the fluorescence intensity in contact with an electrolyte solution of an unknown composition is measured, and the separate contributions of the ionic concentration and the pH for the intensity are determined of fluorescence measured by a calculation. The measurement data obtained from the calibrations are evaluated by a calculation, for example, using a pattern recognition algorithm. Using the calculation method. then the pH and the ionic concentration can be determined from the measurement data obtained. Both pre-calibration and direct calibration can be performed. The sensors are put in contact with the calibration solutions or with the test samples. This can be done manually (for example, using pipettes) or with an appropriate automatic transverse flow system, rigidly mounting the sensors in a flow cell. These cross flow cells are known to the person skilled in the art, and can simply be adapted to the particular intended use. As the light sources to excite the fluorescence, it is possible to use ultraviolet lamps (for example, mercury vapor lamps, halogen lamps), laser devices, diode laser devices, and light emitting diodes. It may be convenient to use filters to filter the light from the wavelength at which the fluorescent dye has maximum absorption. The fluorescent light emitted by the sensors can be collected, for example, using a lens system, and then guided to a detector, for example, a secondary electron multiplier or a photodiode. The lens system can be configured in such a way that the fluorescence radiation is measured through the transparent carrier, over the edges of the carrier or through the test sample. Conveniently, the radiation is guided in a manner known per se, by means of a dichroic mirror. The fluorescence of the sensors is preferably measured while in contact with the calibration or sample solutions. An example of the procedure for the measurement method is described in the Examples.

The following Examples illustrate the invention.

A) Preparation Examples Examples Al a A9: Preparation of coated carriers (sensors) Example Al: First the glass substrates are cleaned (sheets of 18 millimeters in diameter) with a 30 percent sodium hydroxide solution, and then activated in 65 percent nitric acid. The activated sheets are then silanized with 3-trimethoxysilylpropyl ester of methacrylic acid. 150 microliters of hydroxyethyl methacrylate, 5 milligrams of N, N-methylenebisacrylic acid amide, 2 milligrams of 4-acryloyl inofluorescein, and 20 milligrams of ammonium peroxodisulfate are added to 4 milliliters of a solution taken from a solution of 4. grams of polyhydroxyethyl methacrylate, in 60 milliliters of dimethyl formamide. 50 microliters of the resulting mixture are transferred by pipette to a sheet that remains on the head of a centrifugal coater, and the sheet is centrifuged for 30 seconds at a rate of 5,000 revolutions per minute. For the polymerization, the coated sheets are then kept in an oven at 64 ° C for? 3 hours. Transparent substrates are obtained which have a polymer layer of about 1 micron thick. The polymeric layer has a good mechanical stability.

Example A2: First, glass substrates (sheet 18 millimeters in diameter) are cleaned with a solution of sodium hydroxide al. 30 percent, and then activated in 65 percent nitric acid. The activated plates are then silanelated with 3-tri- methoxysilylpropyl ester of methacrylic acid. 150 microliters of hydroxyethyl methacrylate, 5 milligrams of acid amide, N-methylenebisacrylate, 2 milligrams of 4-acryloylaminofluorescein, and 10 milligrams of "Irgacure 651" (photoinitiator, Ciba-Geigy AG) are added to 4 milliliters of a solution taken from a solution of 4 grams of polyhydroxyethyl ethacrylate in 60 milliliters of dimethyl formamide. 50 microliters of the resulting mixture are transferred by pipette to a sheet that remains on the head of a centrifugal coater, and the sheet is centrifuged for 30 seconds at a rate of 5,000 revolutions per minute. For polymerization, the coated sheets are then irradiated with ultraviolet light (365 nanometers, 1330 μW / cm) for 10 to 20 minutes at room temperature. Transparent substrates are obtained which have a polymer layer of about 1 micron thick. The polymeric layer has a good mechanical stability.

Examples A3 to A7: In a manner analogous to that described in Examples Al and A2, it is also possible to prepare the other membranes mentioned in Table 1. polyhydroxyethyl methacrylate, PHPMA: polyhydroxypropyl methacrylate, PHBA: polyhydroxybutyl acrylate. 2 VP: pyrrolidonavillin, AA: acrylic amide, HEMA: hydroxyethyl methacrylate. HPMA: hydroxypropyl methacrylate. HBA: hydroxybutyl acrylate. 4-acryloylaminofluoresceypa. amide of N, N-methyl enbisacrylic acid ammonium peroxodisulfate. Irgacure 651 sol = solvent DMF = dimethyl formamide, B) Application Examples Examples Bl to B8: Two sensors are mounted, one behind the other, in two flow cells. Calibration solutions or sample solutions are introduced and transported through the cells using pumps. The configuration of the measurement is controlled thermostatically. The light of a halogen lamp (white light, 480 nanometer excitation wavelength) is passed through an excitation filter, reflected on a dichroic mirror, and focused on the flat sensors using lenses. The fluorescent light (at 520 nanometers) emitted by the sensors is collected using the same lens system, and is guided by the dichroic mirror by means of an emission filter to a photodiode. The fluorescence of the sensors is recorded while the calibration or sample solutions are acting on them. The measurement data obtained from the calibrations are evaluated with a partial least squares pattern recognition algorithm; then the calculation method is able to determine the pH and the ion concentration from the measurement data obtained from the sample. The following Table gives the effects of the different membrane compositions on the properties of embedded fluorescent dyes. Since the variation in ionic concentration alters not only the pKa of the dye, but also the pH of the measuring solution, and the latter in turn has an influence on the maximum fluorescence intensity of the dye, in order to measure the pH using the ssor system described, it is necessary to know the dependence on the ionic concentration of both the pKa of the dye and the pH of the calibration buffer solution. Table 2 shows examples of fluorescent dyes, their pKa, and the dependence on ionic concentration of pKa and pH with different membrane compositions of the sensor. The sensors of the following Table that have different dependencies in the ionic concentration, can be selected for the determination of the pH. Table 2 1 for the abbreviations, see Table I 2 A: 4-acryloylaminofluorescein, B: 4-acryloylamino-4 ', 5'-dimethylfuorescein. 3 at an ionic concentration of 0.1M 4 displacement of the pKa between the calibration curves in the regulatory solutions of an ionic concentration of 0.1M and 0.3M. 5 displacement of the pH between the calibration curves in the regulatory solutions of an ionic concentration of 0.1M and 0.3M.

Claims

1. A composition comprising: (a) at least one olefinic monomer (A), (b) at least one polymer of at least one olefinic monomer, (c) an indicator dye for the basic structure, with which it is bonded to a covalently an olefinic polymerizable group, directly or by means of a bridging group, (d) at least one at least one diolefinic crosslinking agent, and (e) an effective amount of a polymerization initiator.

2. A composition according to claim 1. wherein the monomers and polymers are hydrophilic, and have a solubility in water of at least 1 weight percent.

3. A composition according to the claim

1, wherein the polymer of component (b) comprises at least one monomer identical to (A), at least one monomer (B) that is different from (A), or a mixture of these monomers.

4. A composition according to claim 3, wherein the polymer of component (b) is composed predominantly or exclusively of. monomer (A).

A composition according to claim 3, wherein the olefinic monomers (A) and / or (B) are present in an amount of 5 to 95 weight percent, based on the composition.

6. A composition according to claim 1, wherein the polymers of component (b) are present in an amount of 95 to 5 weight percent, based on the composition.

7. A composition according to the claim

1, wherein the indicator dye is present in an amount of 0.01 to 10 weight percent.

8. A composition according to claim 1, wherein the polymerization initiator is present in an amount of 0.1 to 20 weight percent.

9. A composition according to claim 1, wherein the crosslinking agent is present in an amount of 0.1 to 30 weight percent.

10. A composition according to claim 3, wherein the monomers (A) or (B) are selected from the group of olefipas substituted by at least one hydrophilic radical.

11. A composition according to claim 10, wherein the hydrophilic radicals are selected from the group of pyrrolidonyl, amino, primary amino, secondary amino, ammonium and hydroxy groups, each bonding directly or by means of a bridge group. , with the olefipa group.

12. A composition according to claim 11, wherein the bridging group is -C (0) -, -C (0) -0-alkynedio-, -C (0) -NH-alkylene-, -C (0) -0- (alkylene of 2 to 6 carbon atoms-0) j. ^ -alkylene of 2 to 6 carbon atoms-, -C (0) -NH- (alkylene of 2 to 6 carbon atoms -O) ^. j 2 -alkylene of 2 to 6 carbon atoms- or -O-alkylene.

13. A composition according to the claim

10, wherein the monomers (A) or (B) correspond to Formula I:

R1R2C = CR3-Z (I)

wherein Rj, R2 and R3 are each independently of the others, hydrogen or a hydrophobic substituent, and Z is a hydrophilic radical.

14. A composition according to claim 13, wherein the hydrophobic substituents are selected from alkyl of 1 to 12 carbon atoms, alkoxy. from 1 to 1.2 carbon atoms, haloalkyl of 1 to 12 carbon atoms, phenyl, halophenyl, alkyl of 1 to 4 carbon atoms-phenyl, alkoxy of 1 to 4 carbon atoms-phenyl, carboxylic acid ester groups have a total of 2 to 20 carbon atoms, -CN, F and Cl.

15. A composition according to claim 13, wherein, in Formula I, | and Rj snn hydrogen, and R-, is hydrogen or methyl.

16. A composition according to claim 13, wherein the hydrophilic radical is -OH, -0- (alkylene of 2 to 12 carbon atoms) -OH, -C (0) -NH2, -C (0) - NH- (alkylene of 2 to 12 carbon atoms) -OH, -C (0) -N- (alkylene of 2 to 12 carbon atoms) 2-OH, -C (0) -NH-alkyl of 1 to 12 carbon atoms, -C (0) -N- (alkyl of 12 carbon atoms) 2, pyrrolidonyl, -C (0) -NH-alkylene of 1 to 12 carbon atoms-NH 2,

-C (0) -NH-alkylene of 1 to 12 carbon atoms-NH-alk of 1 to

6 carbon atoms, -C (0) -NH-alkylene of 1 to 12 carbon atoms-N- (alkyl of 1 to 6 carbon atoms) 2, -C (0) -0- (alkylene of 2 to 12 carbon atoms) -OH, or -C (0) -0- (alkylene of 2 to 6 carbon atoms-0) j. I2-alkylene from

2 to 6 carbon atoms-OH, or -C (0) -NH- (alkylene of 2 to 6 carbon atoms-0) ^ a [~ a ^ i ui l > 2 to 6 carbon atoms-OH, which have the same or different alkylene-0- radicals.

17. A composition according to claim 1, wherein the polymer of component (b) is monopone pi same monomer (A), which was used as the monomer (A).

18. A composition according to claim 1, wherein the polymer of component (b) has an average molecular weight of 1,000 to 1,000,000.

19. A composition according to claim 1, wherein the indicator dye is a dye of Formula II:

R1HC = CR5- (X) a-dye (II) where Rq is methyl and R ^ is hydrogen, or Rj is methyl and R ^ is hydrogen, q is 0 or 1, X is a bridging group, and dye is the monovalent radical of a dye indicator.

20. A composition according to claim 19, wherein Rj is hydrogen and Rcj is hydrogen or methyl.

21. A composition according to claim 19, wherein q is 1.

22. A composition according to claim 19, wherein the bridge group X is -0-. -NH, -NH-alauyl of 1 to 4 carbon atoms, -C (0) -0-, -C (0) -NH-, -C (0) -NH-alkyl of 1 to 4 carbon atoms- , -NH- (C0) -0-, -0-C (0) -NH-, -C (0) -0-alkylene of 2 to 12 carbon atoms-OC (O) -, -C (0) -NH-alkylene of 2 to 12 carbon atoms-0-C (0) -, -C (0) -0-alkylene of 2 to 12 carbon atoms-NH-C (O) -, -C (0) -NH- L alkylene having 2 to 12 carbon atoms-NH-C (O) -, -C (0) -NH-alkylene of 2 to 12 carbon atoms-C (O) -NH-, -NH-C ( O) -O-alkylene of 2 to 12 carbon atoms-OC (0) -, -C (O) -O- (alkylene of 2 to 6 carbon atoms-O)? to 12-, -C (0) -0- (alkylene of 2 to 6 carbon atoms -O) x to 12-alkylene of 2 to 6 carbon atoms-NH-, -C (0) -NH- (alkylene of 2 to 6 carbon atoms-O)! to 12-alkylene of 2 to 6 carbon atoms-NH-, or -C (0) -NH- (alkylene of 2 to 6 carbon atoms-O)? to 12-CH2-C (OJNH- 23.

A composition according to claim 1, wherein the cross-linking agent is selected from the group consisting of esters of acrylic and methacrylic acid and amides of polyols and polyamines, divinyl benzene. and alkyl bis (dimethylmalein idyl) 24.

A composition according to claim 1, wherein the polymerization initiator is an organic azo compound, a peroxo compound, peroxodisulfate or a photoinitiator that can be activated by radiation. according to the claim

1, which comprises a solvent.

26. A composition according to the claim

3, wherein the hydrophobic monomers (A) or (B) correspond to Formula I:

wherein R R and R are each independently of the others, hydrogen or a hydrophobic substituent, and Y is a hydrophobic radical.

27. A composition according to claim 26, wherein the hydrophobic substituents are selected from alkyl of 1 to 12 carbon atoms, alkoxy of 1 to 12 carbon atoms, haloalkyl of 1 to 12 carbon-phenyl atoms, halophenyl, alkyl of 1 to 4 carbopo-fepyl atoms, alkoxy of 1 to 4 carbon atoms-phenyl, carboxylic acid ester groups having a total of 2 to 20 carbon atoms, -C, F and Cl.

A composition according to claim 26, wherein, in Formula III, Rj and R2 are hydrogen, and R3 is hydrogen or methyl.

29. A composition according to claim 26, wherein, in Formula III, Y is alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, phenyl, chlorophenyl, alkyl of 1 to 4 carbon atoms. carbon-phenyl, alkoxy of 1 to 4 carbon atoms-phenyl, a carboxylic acid ester group having a total of 2 to 10 carbon atoms, -CN or -Cl.

30. A carrier material, in which a layer of the composition according to claim 1 has been applied, at least to a surface.

31. A carrier material in which a polymeric layer of the composition according to claim 1 has been applied, at least to a surface.

32. A carrier material according to claim 31, which is planar.

33. A carrier material according to claim 31, which is transparent.

34. A carrier material according to claim 31, which consists of a glass or a transparent polymer.

35. A carrier material according to claim 31, wherein the polymeric layer has a thickness of 0.01 to 50 microns.

36. An optical sensor in which a polymeric layer of the composition according to claim 1 has been applied, at least to a surface.

37. The use of a sensor according to claim 36, for the optical determination of ions or gases.

38. A polymer from a composition according to claim 1, preferably in the form of an unsupported film.

SUMMARY

A composition comprising: (a) at least one olefinic monomer (A), (b) at least one polymer of at least one olefinic monomer, (c) an indicator dye for the basic structure, with which it is bonded to a covalently an olefin polymerizable group directly or by means of a bridge group, (d) at least one crosslinking agent. at least, diolefinic, and (e) an effective amount of a polymerization initiator. The polymers of the composition are suitable as membranes in optical sensors, for the detection of ions and gases.

* *

I, ANA ELENA FERRER RAMÍREZ, translator member of the Mexican Organization of Translators, A.C., with address at Av. Clavería 224-205, Col. Clavería, México, D.F. 02080, Tels. 396 2669 and 396 5201, I certify that the foregoing document is, to the best of my knowledge, a faithful and accurate translation of the original document in English that I had in view.

Mexico, D.F., September 30, 1996.