DE2838877A1 - ANALYTICAL ELEMENT WITH IMPROVED REAGENT STABILITY - Google Patents

Description

PATENT LAWYERS I

2 ß? R ft 7 7 '

J. RBITSTÖTTER W. KINZEBACH 'j

I'KOR I) H. DH. IJIl'L. IN O. OH. PIIII ,. I) IPI.,. CHUM. !

W. BUNTE (1058-1U70) K. P. HOLLER j

DR. ING. DH. IUCH. ΝΛΤ. DIPL .. CIIBM. I. TiiiiKfONt (OKO): ι7ιώκι I TIOLIIX: n ^ IBüOe lfaAU D! BAUKHSTHASSIi: 22, SOOO MÜNCIÜSN 40 I.

Munich, September 6th 7Ö M / 19 162 "· USSN 831 204 ί

EASTMAN KODAK COMPANY
343 State Street

Rochester, New York 14650
United States

Analytical element with enhanced
Reagent stability

POSTANBCIlHIITl! »OWfl'AClI 7HO, R-BOOO MONCIIICN 4! I

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Performing quantitative or semi-quantitative analyzes an aqueous liquid by contacting the liquid with an analytical element which is a combination of reagents that are proportional to the concentration of a given analyte in the aqueous liquid can lead to a detectable product is known. The term "reagent" as used herein is intended to mean a material that: that with the given analyte, with a precursor of the analyte, or with any materials used during the Analysis of the analyte formed reacts. Such a reaction or interaction includes chemical reactivity, catalytic activity or some other form of chemical or physical interaction that ultimately results in a change in the element, which by suitable measurement of radiant energy, usually in the visible light range can be measured in the spectrum. The term "given analyte" relates to the substance, its concentration in the course the analysis is to be measured. .

One group of particularly useful analytical elements makes use of an enzymatic global test in which the given analyte reacts with oxygen in contact with the analytical element in the presence of a suitable enzyme which is contained in the element. A peroxide liquid ^formed: This is proportional to the Konzentr.a · tion of the predetermined analyte in the aqueous analyzed. Then by reaction _; this peroxide generates a detectable product with an indicator means in the presence of peroxidase, both of which are present in the analytical element. The detectable product is formed in the element directly proportional to the peroxide present and thus also proportional to the concentration of the given analyte in the aqueous liquid. Elements and analyzes of this type are, for example, in the US patent

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writing 3 992 158 and in DE-OS 2 735 690 described. Such elements usually include those described above Reagents including peroxidase in a carrier. This is for aqueous liquids and for the chosen one given analyte permeable. With the wearer it can be or be the main material of the element a layer in a multilayer element. Because of its permeability it is ensured that the aqueous liquid and the given analyte comes into contact with each of the test reagents contained in the carrier when the aqueous liquid is brought into contact with the wearer.

One of the advantages of such analytical elements lies in the fact that analyzes can be carried out quickly and reliably is made possible by people who have little technical training and no access to a chemical Have a laboratory for "wet" analyzes. These analytical elements are used as diagnostic tools, for example, for ' Doctors are an extremely useful addition, because you can use various elements of this type for immediate analysis of the body * have fluids, such as urine or blood serum, ready.

Due to the required permeability of the carrier for However, aqueous liquids can regrettably reagents contained in the carrier are damaged or spoiled during a prolonged storage period, thereby reducing the accuracy and reliability of the analysis is adversely affected. For example, exposure to air and damp! the ability of the peroxide contained in a test element used to catalyze the oxidation of an indicatural agent a peroxide can be adversely affected. This has the consequence that an exact and repeatable formation of detectable pro, duct proportional to the concentration of the given analyte; is prevented.

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In order to improve the stability of the reagents during storage times, it was found desirable to use the carrier to be built up entirely from a hydrophobic material to prevent moisture and air from becoming the test reagents to penetrate. This is for example in the US patent 3 630 957. Such carriers are unfortunate however, not sufficiently permeable to aqueous liquids and therefore not usable for analyzes where the prerequisites are met is that aqueous liquids penetrate to the reagents can.

U.S. Patents 3,212,855 and 3,598,704 suggest water-soluble polymers or hydrophilic colloids to an absorbent carrier to keep the reagents physically separated and to help provide a Prevent damage to these reagents due to the action of moisture. Such polymers like the Penetration speed of moisture and air to the Lower test reagents. However, since they are water-soluble When it comes to polymers, it is obvious that moisture gradually penetrates them. Hence they deliver limited protection only. '

U.S. Patent 3,616,251 suggests the reagents embedded in the surface of a carrier made of a hydrophobic polymer, using an organic solvent j used. The purpose stated is that washing out of the reagents should be prevented when they are mixed with aqueous Liquids are brought into contact. It's on the Hand that the reagents are nonetheless the damaging are exposed to the chemical influence of moisture and air.

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, When an analytical element comprises a support suitable for Aqueous liquid is permeable and with a hydrophobic

; If the carrier material has been coated, an additional one can also be used Problem arise. This is the unwanted throwing or waves of the element. This throwing is

; sorption and evaporation of moisture caused in the carrier, resulting in swelling and shrinking of the carrier relative

j to the carrier material that neither absorbs nor verj steams, leads. This problem is in the photographic industry

: well known. There, materials like gelatin are hydro-. phobic substrates applied to photographic films

! to manufacture. In US Patent 3,459,790 is proposed ^1, certain hydrophobic polymers in the gelatin layers

: of photographic films to include around this problem I decrease.

From the foregoing discussion it can be seen that it would be desirable to provide an analytical element that is one for aqueous liquids permeable carrier, the reagents, such as ; Contains peroxidase, but that during storage

■ is free from the above drawbacks, i.e. free from undesirable ones

■ Throwing and instability of reagents, such as peroxidase. ;

j It was found that certain copolymers after the ' ! Dispersing in carriers which are permeable to aqueous liquids

as very desirable effects, a reduction in the problem! the physical throwing or corrugation and at the same time an ι: improved stability of the reagents, such as the Peroxi-: dase, result. The skilled person could not predict that the; '■ the stability of the peroxidase would be improved because - although the'

I ι

selected copolymers largely of hydrophobic, addi- j

; tion-polymerizable monomers are derived - they are single-I borrowed in a carrier which is permeable to aqueous liquids, disper-j-I are greedy. Mind you, this carrier remains for aqueous liquids

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and extremely permeable to oxygen. Because moisture and oxygen could still permeate the carrier and come into contact with the reagents would be expected have reagents such as peroxidase, their Damage during storage is known in the elements of the prior art, including the elements according to the invention Were damaged. However, surprisingly, this is not the case. Although currently the cause of this result is not can be explained, the addition of the polymers described below does indeed lead to a substantial improvement the stability of the reagents and, in addition, a reduction of the problems associated with throwing, although the wearer's permeability to moisture and oxygen is not is affected.

The invention thus provides an improved element for analyzing a given analyte in an aqueous liquid. The element comprises a carrier which is permeable to the given analyte and to aqueous liquids. Alternatively, the carrier can be a layer of a multilayer element. Dispersed in the carrier are reagents (one of which is peroxidase) which can react or facilitate the reaction with the given analyte or its reaction products. Also dispersed in the carrier is a copolymer composed of from about 80 to about 98% by weight of recurring units derived from _: one or more hydrophobic addition-polymerizable monomers, from about 1 to about 20% by weight of recurring units Units derived from one or more anionic monomers and from 0 to about 15 weight percent repeating units derived from one or more crosslinkable, active methylene group-containing monomers _; consists. ^:

The copolymer should normally be about 80 to about 50 percent . of the total weight of carrier and hydrophobic polymer! do. j

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Preferred classes of these polymers are: about 80 to about 98% by weight of repeating units, the ! of one or more hydrophobic, addition-polymerizable Monomers such as alkyl acrylates, alkyl methacrylates, styrene and substituted styrenes derived from about 1 to about 20% by weight of repeating units composed of one or more anionic monomers such as acrylic acid, methacrylic acid, sulfonic acid group-containing Monomers containing sulfonate groups Monomers, sulfate group-containing monomers, phosphate group-containing Monomers and phosphonate groups-contain-! the monomers, including the salts of the above acid, preferably the ammonium or alkali metal salts derived 'Monomers, with preferred monomers being suIfoalkylacryl ate, sulfo-

alkyl methacrylates, suIfoalkylacrylamides, and suIfoalkyl methacrylamides, such as those described in US Pat. Nos. 2,923,734 and 3,506,707; as well as from 0 to 15,; preferably 2 to 10 wt .-% of repeating units derived from one or more cross-linkable active methylene groups 'are derived containing monomers, such as, for example,' ■ in U.S. Patents 3,459,790, 3,929,482 and 3,939,130:; are described, a preferred monomer being 2-acetoacetoxyethyl methacrylate.

! The preferred classes include the following! ; constricting specific copolymers, which have proved to be particularly useful in the inventions, • to the invention analytical elements:

Poly (methyl acrylate-co-3-acryloylοxypropanesulfonic acid sodium salt-co-2-acetoacetoxyethyl
ratio 88.75: 4.75: 6.5);

j sodium salt-co-2-acetoacetoxyethyl methacrylate) (weight

Poly (methy1acrylate-co-2-acrylamido-2-methylpropanesulfonic acid-co-2-acetoacetoxyethyl methacrylate) (Weight ratio 88.75: 4.75: 6.5);

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Poly (methyl acrylate-co-2-acrylamido-2-methylpropanesulfonic acid-co-2-acetoacetoxyethyl methacrylate) (weight ratio
35: 10: 5);

Poly (n-buty1 acryl at-co-3-acryloyloxy propanesulfonic acid sodium salt-co-2-acetoacetoxyethyl methacrylate) (Weight ratio 91: 25: 4.75: 4.0); and

Poly (n-buty1 acrylate-co-2-aery! Amido-2-methy! Propanesulfonic acid-co -2- acetoacetoxyethyl methacrylate) (ratio
85: 10: 5).

The procedures for preparing the copolymers are the
Known to those skilled in the art. The monomers are either straightforward
available or the methods for their synthesis are known.

As stated previously, the useful copolymers described above are dispersed in a carrier which seiner- \ can make hand, the main part of the analytical element.
Alternatively, it may be, the wearer only one layer of a multilayer element ^l. In both cases, the: carrier consists of a material that is suitable for aqueous liquids and! the given analyte is permeable. The choice of material can
will of course vary and depend on the intended use of the element. One can be naturally occurring
hydrophilic substances such as gelatin, gelatin derivatives, hydrophilic cellulose derivatives, polysaccharides such as dextran, gum arabic, agarose, and the like, but also synthetic ones
hydrophilic substances, such as water-soluble polyvinyl compounds, for example polyvinyl alcohol and polyvinylpyrrolidone, water-soluble acrylic amide polymers, and the like, use. ! The choice also depends in part on the optical properties of the carrier obtained, if one wants to undertake a photometric determination of the analytical result.

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If the carrier is a layer of a multilayer element other layers can also be present, for example spreading layers, reflective layers, blocking layers, intermediate layers, carrier layers, filter layers or recording layers such as those in US patents 3,992,158 and 4,042,335. These documents also describe those for the production of such multilayer elements widely used methods. A substrate made of a hydrophobic material is particularly useful, such as polyethylene terephthalate to which the carrier is applied, the carrier in turn having a propagating reflective layer is coated, which is a "blush" polymer (blushed polymer) and a pigment such as cellulose acetate and titanium dioxide, includes. In addition, the element can contain several carrier layers.

In addition to the selected copolymer, there are or are in the carrier several reagents distributed, which are used to react with the given analyte or its reaction products or for relief the reaction are required to produce a detectable product '

to surrender. In the analytical elements according to the invention ^; Peroxidase is one of these reagents. The choice of the other reagents depends on the analysis to be performed. Other reagents include, for example an enzyme for geeigntes catalogs \ lysis of the oxidation of the predetermined analyte to form a j peroxide, an indicator agent capable of reacting with peroxide '. is capable in the presence of peroxidase to give a detectable product, a compound for adjusting the pH,! and the same. A number of useful indicator means are described in DE-OS 2,735,690. Specific examples include an element for the analysis of glucose which comprises reagents such as glucose oxidase, peroxidase, 7-hydroxy-1-naphthol, 4-amino-; antipyrin'HCl and a phosphate buffer system for pH 6. j Further can to call an element for the analysis of uric acid, j

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the reagents such as bis (vinylsulfonylmethyl) ether, uricase, Peroxidase, a leuco dye in a suitable solvent, such as a dispersion of 2- (3,5-dimethoxy-4-hydroxyphenyl) -4,5-bis- (4-dimethyl aminophenyl) imidazole in 2,4-di-npentylphenol , and a borate buffer for pH 9.

The carrier is usually produced by applying a solution or dispersion of carrier material, copolymer and reagents to a surface from which the dried film or the dried layer of the carrier can be physically removed. If the element is to have multiple layers, multiple coatings can be applied directly to one another, as described in US Pat. No. 3,992,158. The respective reagents are added in the proportions already known from the prior art. ^:

. , usually

The particular selected copolymer! Sat is / in such proportions added so that it makes up about 20 to about 50% by weight of the total weight of the carrier and copolymer.

As previously described, the elements of the present invention are ^: used by contacting them with the aqueous liquid to be analyzed and calculating the concentration of the given analyte in the aqueous liquid from a spectrophotometric measurement of the density of the detectable product formed in the element. According to the invention, a wide variety of elements can be produced and used with ^; a variety of chemical analyzes not only in the field; clinical chemistry, but also in chemical research and in applications for controlling chemical processes! adjust. _;

The following examples serve for further explanation specific embodiments of the invention, as well as to demonstrate their advantageous properties compared to the analyti

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see elements of the prior art. In these examples
the term "Copolymer! sat Nr. 1" means:

Poly (methy! Acrylate-co-3-acryloyloxypropanesulfonic acid sodium salt-co-2-acetoacetoxyethyl methacrylate) (Weight ratio 88.75: 4.75: 6.5)

and "Copolymer No. 2":

Poly (methyl acrylate-co-2-acrylamido-2-methylpropanesulfonic acid-co-2-acetoacetoxyethyl methacrylate)
(Weight ratio 88.75: 4.75: 6.5).

Example 1_

Improved stability of reagents in elements for the analysis of glucose

As described below, various multilayer elements were produced for the analysis of glucose in aqueous liquids ¹ , which differ in their formulations:

Element A - control (does not contain any Mr. 1 copolymer)

A polyethylene terephthalate film base is coated with

I 2 ^!

j a carrier made of deionized gelatin (21.5 g / m 2),;

I glycerine (2.15 g / m ² ), glucose oxidase (10,000 U / m ² ), peroxidase \

(10,000 U / m ² ), 7-hydroxy-l-naphthol (0.66 g / m ² ), 4-amino,

^! 2

; antipyrine HCl (0.86 g / m) and a phosphate buffer system (pH ι

j I

■ 6.0) exists. An intermediate layer and a spreading layer made of a "blush" polymer of cellulose acetate (6.6 g / m ² ) and TiO ₂ (46.0 g / m ² ) are then applied.

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Element B - (contains copolymer no.1)

This element is the same as element A with the exception that

Polymer No. 1 (21.5 g / m) is added instead of glycerine.

Element C - (contains less gelatin and more copolymer No. 1 than element B)

This element is the same as element B with the exception that

2 the amount of deionized gelatin in the carrier is 16 g / m 2 and the copolymer No. 1 is used in an amount of 24.2 g / m 2.

The elements are at room temperature (26 ⁰ C) and 50 % more relative

Humidity (RH) stored. Then be at a wave end Density.

length of 540 nm readings / of the background (ie of the dry element) and of the elements spotted with standard solutions of 800 mg% glucose. The results shown in Table 1 show that with the elements containing the copolymer no. 1, a considerably smaller decrease in density in the dry element (substrate) and in an element spotted with glucose solution after 16 and 24 weeks of storage than with elements which did not contain any copolymer no. This indicates the substantially improved reagent stability for the elements containing copolymer # 1.

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TABLE 1

Influence of Copolymer No. 1 on the Elements for glucose test

percentage deterioration (percentage change in density, related on the Frisian element)

element Ie) A. Storage time
(Weeks) dry element loaded with glucose
stippled element (Control B. 16 46 20th C. 16 11 δ Ie) A. 16 0 4th (Control B. 24 70 19th C. 24 26th 0 24 9 2

example Comparison of two copolymers

Two elements (D and E) were made as described in Example 1 with the exception that the carrier of the element

2 2

D 16.0 g / m deionized gelatin and 16.0 g / m copolymer

No. 1 and element E contained 16 g / m of deionized gelatin

ρ
and 16.0 g / m 2 of copolymer no. As a buffer system j

2 for the elements 3,3-dimethylglutaric acid (1.96 g / m)

used for pH 5.0. J

The density readings were taken with the dry ground and _ · the mg with a standard solution to 600% glucose-spotted j elements after for 24 weeks at Raumtemperaf structure (26 ⁰ C and 50% relative humidity) under cooling j (6 ⁰ C , 50 % relative humidity) and had stored in the frozen state (-23 ⁰ C, 50% relative humidity).

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As shown in Table 2, the copolymers behaved in terms of stability and sensitivity to Glucose standard essentially the same. (Note that the Background density readings have been made in millivolts, which are inversely proportional to density units.)

TABLE 2

Comparison of the copolymers No. 1 and 2

Underground R

Element Temp. ° C /% RH mV Gl ucose-spotted element

D. 26/50 727 1.406 6/50 750 1.368 -23/50 776 1.393 E. 26/50 713 1.407 6/50 737 1.377 -23/50 776 1.341

Example 3

Improved stability for elements used to determine uric acid

Various multilayer elements were made using the following procedure for the analysis of uric acid in aqueous liquids:

A polyethylene terephthalate film carrier is coated with

2 a carrier consisting of deionized gelatin (10.8 g / m),

2 bis (vinylsulfonyl methyl ether) (0.129 g / m), peroxidase

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(6500 U / m ² ), Uricase (215 U / m ² ), a dispersion of 2- (3,5-dimethoxy-4-hydroxyphenyl) -4,5-bis- (4-dimethylaminophenyl) -

2 2

imidazole (0.14 g / m) in 2,4-di-n-amylphenol (1.35 g / m) and Borate buffer for pH 9.

In addition, the carrier layers of the elements G contained

2 2

and H 5.4 g / m and 10.8 g / m copolymer did not contain any such copolymer.

2 2

and H 5.4 g / m and 10.8 g / m Copolymer No. 1, Element F, respectively

A gelatin layer was applied to the carrier layer, ι

2 consisting of deionized gelatin (5.4 g / m and bis- (vinyl-

2
sulfonylmethyl) ether (0.065 g / m) in borate buffer for pH 9,

2 an intermediate layer of poly (n-isopropyl acryl amide) (0.3 g / m)

2 and a spreading layer made of TiO ₉ (46.0 g / m) and cellulose

2 ^

acetate (6.6 g / m).

Then the elements were tested for changes in the density of the dry substrate and the density after spotting with a 15.0 mg% uric acid solution after an incubation period of 0, 8 and 24 weeks at 26 ° C / 50 % relative air humidity, examined.

As can be seen in Table 3, the use of the Copolymer No. 1 in the carrier layer of the element for Determination of uric acid results in a significantly smaller change in the dry subsurface and the response behavior in relation to ί the passage of time, which increases the shelf life of the item ch will be increased;

Essentially the same results were obtained when using the uric acid determination element instead of the copolymer No. 1 used the copolymer No. 2.

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TABLE 3

Effect of the No. 1 copolymer on elements for the uric acid test

percentage deterioration

(percentage change in density, based on the fresh element )

iiüTT

element Ie) F. storage time
(Weeks) dry element in it Ha
dab uric acid
th element (Control G 8th 14th * H 8th 7th Ie) F. 8th 4th * (Control G 24 16 59 H 24 11 32 24 8th 30th

no information available

e i s ρ i e 1

The following procedure was used to produce multilayer analytical elements for the determination of triglycerides in body fluids:

A reaction layer of deionized gelatin (5.4 g / m ² ), Dimedon (0.33 g / m 2), Triton X-100 (0.39 g / m ² ), 2- (3.5 -Dimethoxy-4-hydroxyphenyl) -4,5-bis- (4-dimethylamino phenyl) imidazole (0.4 g / m)

2
in 2, 4-di-n-amylphenol (4.0 g / m), bis- (vinylsulfonylmethyl) -

ether (BVSME) (0.03 g / m ² ), MgCl ₉ (0.01 g / m ² ), ATP (1.35 g / m ² ), peroxidase (6997 U / m), glycerine kinase (323 U / m), of-glycero-

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phosphate oxidase (2831 U / m ² ), copolymer no. 1 (5.38 g / m ² ) and 0.05 M phosphate buffer for pH 7.0; then it is coated with a gel pad made of deionized gelatin (5.4 g / m ² ), Triton X-100 (0.06 g / m ² ), BVSME (0.03 g / m ² ), copolymer no 1 (5.4 g / m) and 0.05M phosphate buffer for pH 7.0; this is followed by coating with an enzyme layer of lipase

2
M (3.24 g / m), poly-ZU-isopropylacrylamide-co-2- (methacryloyloxy) äthyltrimethylammoni um-methosulfat-co-2-hydroxyäthylacry-

Iat7 (weight ratio 70:20:10) (1.08 g / m ² ) and Triton X-100

2
(0.08 g / m); then an intermediate layer of poly-n-iso-

2 propyl acryl amide and a spreading layer made of TiU2 (50.0 g / m),

Cellulose acetate (7.0 g / m ² ) and Triton X-100 (5.5 g / m ² ).

A second element was prepared in the same way, with the exception that neither the reaction layer nor the gel pad contained copolymer No. 1. The freshly prepared elements were each tested with solutions containing 0 to 300 mg / dl triglyceride. FIG. 1 shows that higher densities can be achieved with this dye system if a copolymer such as copolymer no. 1 is included. ^;

example

It was incubated as prepared as described in Example 4 _; Elements for 4 weeks relative at 26 ⁰ C and 50% Luf tfeuchti gjkeit, and for 8 weeks at 6 ⁰ C and 50% relative humidity. The elements were then examined with j (1) Cordis, a commercially available triglyceride preparation (approximately 3.52 mM or 340 mg / dl), (2) glycerol (approximately 3.52 mM in 7 % albumin and 0.155 M NaCl), (3) <* -Glycerophosphate (7.04 mM in 7% albumin / saline) and (4) H ₂ O ₂ (3.52 mM in water).

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The results shown in FIGS. 2 (a, b, c and d) show that the addition of copolymer no. 1 leads to a substantial improvement in the stability of the peroxidase for this element. As shown in curve B, however, the glycerol kinase stability is not improved ^{by the copolymer no. 1 at 26 °} C. and 50 % relative atmospheric humidity.

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Claims (1)

USSN 831 204 Patent a η s ρ rü che Element for the analysis of a given analyte in an aqueous liquid, with ι a) a carrier for the aqueous liquid and the I given analyte is permeable, and '. b) reagents dispersed in the carrier which react to form a detectable product with the given analyte or its reaction products or which react enter ti on,
¹ wherein the reagents comprise peroxidase, characterized in that in addition to the reagents a copolymer 1) about 80 to about 98 weight percent recurring Units derived from one or more hydrophobic, addition-polymerizable monomers, ; 2) about 1 to about 20 percent by weight of recurring a '-. units derived from one or more anionic monomers, and 3) 0 to about 15 percent by weight of repeating units, those of one or more crosslinkable, active Methy-I are derived from containing monomers, is dispersed in the carrier. : 2. Element according to claim 1, characterized in that it is at I in which or the hydrophobic addition monomers polymerisierj cash to a alkylacrylic, alkyl _{methacrylate;} is styrene or a substituted styrene and that 909813/0776 ORIGINAL M / 19 162
USSN 831 204 the anionic monomer or monomers are acrylic acid, an acrylic acid salt, methacrylic acid, a methacrylic acid salt, a monomer containing a sulfonic acid group, a salt of a monomer having a sulfonic acid group contains, a monomer that contains a sulfate group, a monomer that contains a sulfate group, a monomer, containing a phosphate group and a monomer containing a phosphonate group. Element according to one of Claims 1 or 2, characterized in that that the reagents also include an enzyme that catalyzes the oxidation of the given analyte to a peroxide is capable, and an indicator means that in the presence of peroxidase to form a detectable product by which peroxide is oxidizable. Element according to any one of claims 1 to 3, characterized in that the reagents also contain a compound for adjustment of pH. Element according to one of Claims 1 to 4, characterized in that that the carrier comprises a hydrophilic colloid which is gelatin, a gelatin derivative Cellulose derivative, a polysaccharide, an acrylamide, polyvinyl alcohol and / or polyvinylpyrrolidone. Element according to any one of Claims 1 to 5, characterized in that it comprises more than one layer and the Carrier represents one of the layers. Element according to one of Claims 1 to 6, characterized in that the carrier is a layer on a carrier material is upset. 909813/077 $ USSN 831 204 η _ «τ υ u υ υ / / 8. Element according to any one of claims 1 to 7, characterized in that that an intermediate layer is applied to the carrier and a spreading reflective layer is applied to this in turn is. 9. Element according to any one of claims 1 to 8, characterized in that that the copolymer is about 20 to about 50 percent by weight of the total weight of carrier and copolymer! sat. 10. Element according to one of claims 1 to 9, characterized in that that the copolymer consists of the following substances: Poly (methy1 acrylate-co-3-acryloyl oxypropanesulfon acid sodium salt-co-2-acetoacetoxyethyl methacrylate) (Weight ratio 88.75: 4.75: 6.5); Poly (methyl acrylate-co-2-acrylanido-2-methylpropanesulfonic acid-co-2-acetoacetoxyethyl methacrylate) "(Weight ratio 88.75: 4.75: 6.5); Poly (methyl acrylate-co-2-acrylamido-2-methy1propanesulfonic acid -co-2-acetoacetoxyethyimethacrylate) (weight ratio 85: 10: 5); Poly (n-buty1 acrylate-co-3-acryloyloxypropanesulfonic acid sodium salt-co-2-acetoacetoxyethyl methacrylate) (weight ratio 91.25: 4.75: 4.0); and Poly (n-butyl acrylate-co-2-acrylamido-2-methylpropanesulfonic acid-co-2-acetoacetoxyethyl methacrylic at) (weight ratio 85: 10: 5). 11. Element for the analysis of glucose in aqueous liquids, with 90981 3/0776 USSN 831 204 -ψ- "°°°" a) a carrier which is permeable to the aqueous liquid and to glucose, and b) in the carrier dispersing reagents to which glucose oxidase, Peroxidase, 7-hydroxy-1-naphthol, 4-aminoantipyrine · HCl and a phosphate buffer (pH 6), characterized in that in addition to the reagents a co-polymer Poly (methy1 acrylate-co-3-acryloy1 oxypropanesulfonic acid sodium salt-co-2-acetoacetoxyethyl methacrylate) (Weight ratio 88.75: 4.75: 6.5); Poly (methyl acrylate-co-2-acrylami do-2-methylpropanesulfon acid-co-2-acetoacetoxyethyl methacrylate) (Weight ratio 88.75: 4.75: 6.5); Poly (methyl acrylate-co-2-acrylamido-2-methylpropanesulfonic acid -co-2-acetoacetoxyethy 1 methacrylate) (weight ratio 85: 10: 5); Polyin-butyl acrylate-co-S-acryloyloxypropanesulfonic acid sodium salt-co-2-acetoacetoxyethyl methacrylate) (Weight ratio 91.25: 4.75: 4.0); and Poly (η-butyl acrylate-co-2-acrylamido-2-methylpropanesulfonic acid-co-2-acetoacetoxyethyl methacrylate) (Weight ratio 85: 10: 5) is dispersed in the carrier. 12. Element according to claim 11, characterized in that the Carrier comprises a hydrophilic colloid which is gelatin, a gelatin derivative, a cellulose derivative, a polysaccharide, an acrylamide, to polyvinyl alcohol and / or polyvinylpyrrolidone. 909813/0776 USSN 831 204 13. Element according to claims 11 or 12, characterized in that that the Copol ymeri sat about 20 to about 50 wt .- '/. of the total weight of carrier and copolymer! sat. 14. Element according to any one of claims 11 to 13, characterized in that that it is the carrier is a layer consisting of de ionized gelatin and on one Polyethylene terephthalate film carrier is applied and that the support with an intermediate layer and a spreading reflective layer made of a "blush" polymer (blushed- ■ polymer) made of cellulose acetate and titanium dioxide is. j 15. Element for the analysis of uric acid in aqueous liquids, with a) a carrier which is permeable to the aqueous liquid and to uric acid, and jb) reagents dispersed in the carrier, the bis (vinyl sulfonylmethyl) ether, uricase, peroxidase, a dispersion of 2- (3 _s 5-dimethoxy-4-hydroxyphenyl) -4,5-bis (4- dimethylaminophenyl) imidazole in 2,4-di-n-pentylphenol ; and a borate buffer (pH 9), • characterized in that in addition to the reagents ^; a copolymer of: Poly (methyl acrylate-co-3-acryloyloxypropanesulfonic acid-sodium salt-co-2-acetoacetoxyethyl methacrylate) (Weight; ratio 88.75: 4.75: 6.5); ·! Poly (methyl acrylate-co-2-acrylamido-2-methyIpropansulfon- j acid-co-2-acetoacetoxyethyl methacrylate) (weight loss; ratio 88.75: 4.75: 6.5); ! 909813/0776 M / 19 162 - USSN 831 204 "G" Polyimethyl acrylate-co ^ -acrylamido ^ -methylpropanesulfonic acid-co-2-acetoacetoxyethyl methacrylate) (Weight ratio 85: 10: 5); ^: Poly (n-buty1 acrylate-co-3-acryloyloxypropane u1 hair dryer acid re sodium salt-co-2-acetoacetoxyethyl methacrylate) (weight ratio 91.25: 4.75: 4.0); and Poly (n-buty Iac ry lat-co-2-acryl ami do-2-methylpropanesulfonic acid-co-2-acetoacetoxyethyl methacrylate) (weight ratio 85: 10: 5) is dispersed in the carrier. ! 16. Element according to claim 15, characterized in that the Carrier comprises a hydrophilic colloid which is gelatin, a gelatin derivative, a cellulose derivative, a polysaccharide, an acrylamide, to polyvinyl alcohol and / or polyvinylpyrrolidone. 17. Element according to one of claims 15 or 16, characterized in that that the copolymer is about 20 to about 50% by weight of the total weight of carrier and copolymer matters. ! 18. Element according to one of claims 15 to 17, characterized in that the carrier is a layer which consists of deionized gelatin and is applied to a polyethylene enterephthalate film and that the carrier is provided with a layer of deionized gelatin ^m / 15is- (vinyl sulfonylmethyl) ether ^U / ⁿ borate buffer (pH 9), an intermediate layer made of poly (n-isopropyl acryl amide) and a spreading reflective layer made of a "blush" poly- > ι kidneys (blushed polymer) made of cellulose acetate and titanium oxide |, is covered. ! 909813/0776