Analytical elements with improved reagent stability

Claim 2

In an element for the analysis of a predetermined analyte in an aqueous liquid, said element comprising: (a) a carrier permeable to said aqueous liquid and to said predetermined analyte and, (b) dispersed in said carrier, reagents capable of interacting with or facilitating interaction with said predetermined analyte or its reaction products to yield a detectable product, one of said reagents comprising peroxidase, the improvement comprising having dispersed in said carrier in addition to said reagents a polymer in an amount sufficient to impart stability to said peroxidase, said amount comprising from about 20 percent to about 50 percent of the total weight of said carrier material plus said polymer, said polymer comprising: (1) from about 80 to about 98 percent by weight of recurring units derived from one or more hydrophobic, addition-polymerizable monomers selected from the group consisting of an alkyl acrylate, an alkyl methacrylate, styrene and a substituted styrene, (2) from about 1 to about 20 percent by weight of recurring units derived from one or more anionic monomers selected from the group consisting of an acrylic acid, an acrylic acid salt, a methacrylic acid, a methacrylic acid salt, a sulfonic acid, a sulfonic acid salt, a sulfonate, a sulfate, a phosphate and a phosphorate, and (3) from 0 to about 15 percent by weight of recurring units derived from one or more crosslinkable, active methylene group-containing monomers.

Claim 3

An element as described in claim 1 wherein said reagents further comprise an enzyme capable of catalyzing the oxidation of said predetermined analyte to a peroxide and an indicator composition oxidizable by said peroxide in the presence of peroxidase to yield a detectable product.

Claim 4

An element as described in claim 1 wherein said reagents further comprise a compound for adjusting pH.

Claim 5

An element as described in claim 1 wherein said carrier comprises a hydrophilic colloid selected from the group consisting of gelatin, a gelatin derivative, a cellulose derivative, a polysaccharide, an acrylamide, poly(vinyl alcohol), and poly(vinyl pyrrolidone).

Claim 6

An element as described in claim 1 which comprises more than one layer, said carrier comprising one of said layers.

Claim 7

An element as described in claim 1 wherein said carrier comprises a layer coated on a support material.

Claim 8

An element as described in claim 1 wherein a subbing layer is coated on said carrier and a spreading-reflecting layer is coated on the subbing layer.

Claim 9

In an element for the analysis of a predetermined analyte in an aqueous liquid, said element comprising: (a) a carrier permeable to said aqueous liquid and to said predetermined analyte and (b) dispersed in said carrier, reagents capable of interacting with or facilitating interaction with said predetermined analyte or its reaction products to yield a detectable product, one of said reagents comprising peroxidase, the improvement comprising having dispersed in said carrier in addition to said reagents a polymer comprising: (1) from about 80 to about 98 percent by weight of recurring units derived from one or more hydrophobic, addition-polymerizable monomers selected from the group consisting of an alkyl acrylate, an alkyl methacrylate, styrene, and a substituted styrene, (2) from about 1 to about 20 percent by weight of recurring units derived from one or more anionic monomers selected from the group consisting of an acrylic acid, an acrylic acid salt, a methyacrylic acid, a methyacrylic acid salt, a sulfonic acid, a sulfonic acid salt, a sulfonate, a sulfate, a phosphate, and a phosphorate, and (3) from 0 to about 15 percent by weight of recurring units derived from one or more crosslinkable, active methylene group-containing monomers, said polymer comprising from about 20 percent to about 50 percent of the total weight of said carrier plus said polymer.

Claim 10

In an element for the analysis of a predetermined analyte in an aqueous liquid, said element comprising: (a) a carrier permeable to said aqueous liquid and to said predetermined analyte and (b) dispersed in said carrier, reagents capable of interacting with or facilitating interaction with said predetermined analyte or its reaction products to yield a detectable product, one of said reagents comprising peroxidase, the improvement comprising having dispersed in said carrier in addition to said reagents a polymer comprising: (1) from about 80 to about 98 percent by weight of recurring units derived from one or more hydrophobic, addition-polymerizable monomers selected from the group consisting of an alkyl acrylate, an alkyl methacrylate, styrene, and a substituted styrene, (2) from about 1 to about 20 percent by weight of recurring units derived from one or more anionic monomers selected from the group consisting of an acrylic acid, an acrylic acid salt, a methyacrylic acid, a methyacrylic acid salt, a sulfonic acid, a sulfonic acid salt, a sulfonate, a sulfate, a phosphate, and a phosphorate, and (3) from 0 to about 15 percent by weight of recurring units derived from one or more crosslinkable, active methylene group-containing monomers, said polymer comprising from about 20 percent to about 50 percent of the total weight of said carrier plus said polymer.

Claim 11

An element as described in claim 8 wherein said reagents further comprise an enzyme capable of catalyzing the oxidation of said predetermined analyte to a peroxide and an indicator composition oxidizable by said peroxide in the presence of peroxidase to yield a detectable product.

Claim 12

An element as described in claim 8 wherein said reagents further comprise a compound for adjusting pH.

Claim 13

An element as described in claim 8 wherein said carrier comprises a hydrophilic colloid selected from the group consisting of gelatin, a gelatin derivative, a cellulose derivative, a polysaccharide, an acrylamide, poly(vinyl alcohol), and poly(vinyl pyrrolidone).

Claim 14

An element as described in claim 8 which comprises more than one layer, said carrier comprising one of said layers.

Claim 15

An element as described in claim 8 wherein said carrier comprises a layer coated on a support material.

Claim 16

An element as described in claim 8 wherein a subbing layer is coated on said carrier and a spreading-reflecting layer is coated on the subbing layer.

Claim 17

In an element for the analysis of a predetermined analyte in an aqueous liquid, said element comprising: (a) a carrier permeable to said aqueous liquid and to said predetermined analyte and, (b) dispersed in said carrier, reagents capable of interacting with or facilitating interaction with said predetermined analyte or its reaction products to yield a detectable product, one of said reagents comprising peroxidase, the improvement comprising having dispersed in said carrier in addition to said reagents a polymer in an amount sufficient to impart stability to said peroxidase, said amount comprising from about 20 percent to about 50 percent of the total weight of said carrier material plus said polymer, said polymer being selected from the group consisting of: poly(methyl acrylate-co-3-acryloxyloxypropane.tbd.sulfonic acid, sodium salt-co-2-acetoacetoxyethyl methacrylate) (weight ratio 88.75:4.75:6.5); poly(methyl acrylate-co-2-acrylamido-2-methyl.tbd.propanesulfonic acid-co-2-acetoacetoxyethyl methacrylate) (weight ratio 88.75:4.75:6.5); poly(methyl acrylate-co-2-acrylamido-2-methyl.tbd.propanesulfonic acid-co-2-acetoacetoxyethyl methacrylate) (weight ratio 85:10:5); poly(n-butyl acrylate-co-3-acryloyloxypropane.tbd.sulfonic acid, sodium salt-co-2-acetoacetoxyethyl methacrylate) (weight ratio 91.25:4.75:4.0); and poly(n-butyl acrylate-co-2-acrylamido-2-methylpropane sulfonic acid-co-2-acetoacetoxyethyl methacrylate) (weight ratio 85:10:5).

Claim 18

In an element for the analysis of a predetermined analyte in an aqueous liquid, said element comprising: (a) a carrier permeable to said aqueous liquid and to said predetermined analyte and, (b) dispersed in said carrier, reagents capable of interacting with or facilitating interaction with said predetermined analyte or its reaction products to yield a detectable product, one of said reagents comprising peroxidase, the improvement comprising having dispersed in said carrier in addition to said reagents a polymer in an amount sufficient to impart stability to said peroxidase, said amount comprising from about 20 percent to about 50 percent of the total weight of said carrier material plus said polymer, said polymer being selected from the group consisting of: poly(methyl acrylate-co-3-acryloxyloxypropane.tbd.sulfonic acid, sodium salt-co-2-acetoacetoxyethyl methacrylate) (weight ratio 88.75:4.75:6.5); poly(methyl acrylate-co-2-acrylamido-2-methyl.tbd.propanesulfonic acid-co-2-acetoacetoxyethyl methacrylate) (weight ratio 88.75:4.75:6.5); poly(methyl acrylate-co-2-acrylamido-2-methyl.tbd.propanesulfonic acid-co-2-acetoacetoxyethyl methacrylate) (weight ratio 85:10:5); poly(n-butyl acrylate-co-3-acryloyloxypropane.tbd.sulfonic acid, sodium salt-co-2-acetoacetoxyethyl methacrylate) (weight ratio 91.25:4.75:4.0); and poly(n-butyl acrylate-co-2-acrylamido-2-methylpropane sulfonic acid-co-2-acetoacetoxyethyl methacrylate) (weight ratio 85:10:5).

Claim 19

In an element for the analysis of a predetermined analyte in an aqueous liquid, said element comprising: (a) a carrier permeable to said aqueous liquid and to said predetermined analyte and (b) dispersed in said carrier, reagents capable of interacting with or facilitating interaction with said predetermined analyte or its reaction products to yield a detectable product, one of said reagents comprising peroxidase, the improvement comprising having dispersed in said carrier in addition to said reagents a polymer selected from the group consisting of Poly(methyl acrylate-co-3-acryloyloxypropane.tbd.sulfonic acid, sodium salt-co-2-acetoacetoxyethyl methacrylate) (weight ratio 88.75:4.75:6.5); Poly(methyl acrylate-co-2-acrylamido-2-methyl.tbd.propanesulfonic acid-co-2-acetoacetoxyethyl methacrylate) (weight ratio 88.75:4.75:6.5); Poly(methyl acrylate-co-2-acrylamido-2-methyl.tbd.propanesulfonic acid-co-2-acetoacetoxyethyl methacrylate) (weight ratio=85:10:5); Poly(n-butyl acrylate-co-3-acryloyloxypropane.tbd.sulfonic acid, sodium salt-co-2-acetoacetoxyethyl methacrylate) (weight ratio 91.25:4.75:4.0); and Poly(n-butyl acrylate-co-2-acrylamido-2-methylpropane sulfonic acid-co-2-acetoacetoxyethyl methacrylate) (weight ratio 85:10:5), said polymer comprising from about 20 percent to about 50 percent of the total weight of said carrier plus said polymer.

Claim 20

In an element for the analysis of a predetermined analyte in an aqueous liquid, said element comprising: (a) a carrier permeable to said aqueous liquid and to said predetermined analyte and (b) dispersed in said carrier, reagents capable of interacting with or facilitating interaction with said predetermined analyte or its reaction products to yield a detectable product, one of said reagents comprising peroxidase, the improvement comprising having dispersed in said carrier in addition to said reagents a polymer selected from the group consisting of Poly(methyl acrylate-co-3-acryloyloxypropane.tbd.sulfonic acid, sodium salt-co-2-acetoacetoxyethyl methacrylate) (weight ratio 88.75:4.75:6.5); Poly(methyl acrylate-co-2-acrylamido-2-methyl.tbd.propanesulfonic acid-co-2-acetoacetoxyethyl methacrylate) (weight ratio 88.75:4.75:6.5); Poly(methyl acrylate-co-2-acrylamido-2-methyl.tbd.propanesulfonic acid-co-2-acetoacetoxyethyl methacrylate) (weight ratio=85:10:5); Poly(n-butyl acrylate-co-3-acryloyloxypropane.tbd.sulfonic acid, sodium salt-co-2-acetoacetoxyethyl methacrylate) (weight ratio 91.25:4.75:4.0); and Poly(n-butyl acrylate-co-2-acrylamido-2-methylpropane sulfonic acid-co-2-acetoacetoxyethyl methacrylate) (weight ratio 85:10:5), said polymer comprising from about 20 percent to about 50 percent of the total weight of said carrier plus said polymer.

Claim 21

An element as described in claim 13 wherein said reagents further comprise an enzyme capable of catalyzing the oxidation of said predetermined analyte to a peroxide and an indicator composition oxidizable by said peroxide in the presence of peroxidase to yield a detectable product.

Claim 22

An element as described in claim 13 wherein said reagents further comprise a compound for adjusting pH.

Claim 23

An element as described in claim 13 wherein said carrier comprises a hydrophilic colloid selected from the group consisting of gelatin, a gelatin derivative, a cellulose derivative, a polysaccharide, an acrylamide, poly(vinyl alcohol), and poly(vinyl pyrrolidone).

Claim 24

An element as described in claim 13 which comprises more than one layer, said carrier comprising one of said layers.

Claim 25

An element as described in claim 13 wherein said carrier comprises a layer coated on a support material.

Claim 26

An element as described in claim 13 wherein a subbing layer is coated on said carrier and a spreading-reflecting layer is coated on the subbing layer.

Claim 27

In an element for the analysis of glucose in aqueous liquids, said element comprising: (a) a carrier permeable to said aqueous liquid and to glucose and, (b) dispersed in said carrier, reagents comprising glucose oxidase, peroxidase, 7-hydroxy-1-naphthol, 4-aminoantipyrine HCL and a phosphate buffer system (pH 6), the improvement comprising having dispersed in said carrier in addition to said reagents a polymer in an amount sufficient to impart stability to said peroxidase, said amount comprising from about 20 percent to about 50 percent of the total weight of said carrier material plus said polymer, said polymer being selected from the group consisting of: poly(methyl acrylate-co-3-acryloxyloxypropane.tbd.sulfonic acid, sodium salt-co-2-acetoacetoxyethyl methacrylate) (weight ratio 88.75:4.75:6.5); poly(methyl acrylate-co-2-acrylamido-2-methyl.tbd.propanesulfonic acid-co-2-acetoacetoxyethyl methacrylate) (weight ratio 88.75:4.75:6.5); poly(methyl acrylate-co-2-acrylamido-2-methyl.tbd.propanesulfonic acid-co-2-acetoacetoxyethyl methacrylate) (weight ratio 85:10:5); poly(n-butyl acrylate-co-3-acryloyloxypropane.tbd.sulfonic acid, sodium salt-co-2-acetoacetoxyethyl methacrylate) (weight ratio 91.25:4.75:4.0); and poly(n-butyl acrylate-co-2-acrylamido-2-methylpropane sulfonic acid-co-2-acetoacetoxyethyl methacrylate) (weight ratio 85:10:5).

Claim 28

In an element for the analysis of glucose in aqueous liquids, said element comprising: (a) a carrier permeable to said aqueous liquid and to glucose and, (b) dispersed in said carrier, reagents comprising glucose oxidase, peroxidase, 7-hydroxy-1-naphthol, 4-aminoantipyrine HCL and a phosphate buffer system (pH 6), the improvement comprising having dispersed in said carrier in addition to said reagents a polymer in an amount sufficient to impart stability to said peroxidase, said amount comprising from about 20 percent to about 50 percent of the total weight of said carrier material plus said polymer, said polymer being selected from the group consisting of: poly(methyl acrylate-co-3-acryloxyloxypropane.tbd.sulfonic acid, sodium salt-co-2-acetoacetoxyethyl methacrylate) (weight ratio 88.75:4.75:6.5); poly(methyl acrylate-co-2-acrylamido-2-methyl.tbd.propanesulfonic acid-co-2-acetoacetoxyethyl methacrylate) (weight ratio 88.75:4.75:6.5); poly(methyl acrylate-co-2-acrylamido-2-methyl.tbd.propanesulfonic acid-co-2-acetoacetoxyethyl methacrylate) (weight ratio 85:10:5); poly(n-butyl acrylate-co-3-acryloyloxypropane.tbd.sulfonic acid, sodium salt-co-2-acetoacetoxyethyl methacrylate) (weight ratio 91.25:4.75:4.0); and poly(n-butyl acrylate-co-2-acrylamido-2-methylpropane sulfonic acid-co-2-acetoacetoxyethyl methacrylate) (weight ratio 85:10:5).

Claim 29

An element as described in claim 23 wherein said carrier comprises a hydrophilic colloid selected from the group consisting of gelatin, a gelatin derivative, a cellulose derivative, a polysaccharide, an acrylamide, poly(vinyl alcohol), and poly(vinyl pyrrolidone).

Claim 30

An element as described in claim 23 wherein said polymer comprises from about 20 percent to about 50 percent of the total weight of said carrier plus said polymer.

Claim 31

An element as described in claim 23 wherein the carrier is a layer comprising deionized gelatin coated on a polyethylene terephthalate film support and said carrier is overcoated with a subbing layer and a blushed-polymer, spreading-reflecting layer comprising cellulose acetate and titanium dioxide.

Claim 32

In an element for the analysis of uric acid in aqueous liquids, said element comprising: (a) a carrier permeable to said aqueous liquid and to uric acid and, (b) dispersed in said carrier, reagents comprising bis(vinylsulfonylmethyl)ether, uricase, peroxidase, a dispersion of 2-(3,5-dimethoxy-4-hydroxyphenyl)-4,5-bis-(4-dimethylaminophenyl)imidazole in 2,4-di-n-pentylphenol, and a borate buffer (pH 9), the improvement comprising having dispersed in said carrier in addition to said reagents a polymer in an amount sufficient to impart stability to said peroxidase, said amount comprising from about 20 percent to about 50 percent of the total weight of said carrier material plus said polymer, said polymer being selected from the group consisting of: poly(methyl acrylate-co-3-acryloxyloxypropane.tbd.sulfonic acid, sodium salt-co-2-acetoacetoxyethyl methacrylate) (weight ratio 88.75:4.75:6.5); poly(methyl acrylate-co-2-acrylamido-2-methyl.tbd.propanesulfonic acid-co-2-acetoacetoxyethyl methacrylate) (weight ratio 88.75:4.75:6.5); poly(methyl acrylate-co-2-acrylamido-2-methyl.tbd.propanesulfonic acid-co-2-acetoacetoxyethyl methacrylate) (weight ratio 85:10:5); poly(n-butyl acrylate-co-3-acryloyloxypropane.tbd.sulfonic acid, sodium salt-co-2-acetoacetoxyethyl methacrylate) (weight ratio 91.25:4.75:4.0); and poly(n-butyl acrylate-co-2-acrylamido-2-methylpropane sulfonic acid-co-2-acetoacetoxyethyl methacrylate) (weight ratio 85:10:5).

Claim 33

In an element for the analysis of uric acid in aqueous liquids, said element comprising: (a) a carrier permeable to said aqueous liquid and to uric acid and, (b) dispersed in said carrier, reagents comprising bis(vinylsulfonylmethyl)ether, uricase, peroxidase, a dispersion of 2-(3,5-dimethoxy-4-hydroxyphenyl)-4,5-bis-(4-dimethylaminophenyl)imidazole in 2,4-di-n-pentylphenol, and a borate buffer (pH 9), the improvement comprising having dispersed in said carrier in addition to said reagents a polymer in an amount sufficient to impart stability to said peroxidase, said amount comprising from about 20 percent to about 50 percent of the total weight of said carrier material plus said polymer, said polymer being selected from the group consisting of: poly(methyl acrylate-co-3-acryloxyloxypropane.tbd.sulfonic acid, sodium salt-co-2-acetoacetoxyethyl methacrylate) (weight ratio 88.75:4.75:6.5); poly(methyl acrylate-co-2-acrylamido-2-methyl.tbd.propanesulfonic acid-co-2-acetoacetoxyethyl methacrylate) (weight ratio 88.75:4.75:6.5); poly(methyl acrylate-co-2-acrylamido-2-methyl.tbd.propanesulfonic acid-co-2-acetoacetoxyethyl methacrylate) (weight ratio 85:10:5); poly(n-butyl acrylate-co-3-acryloyloxypropane.tbd.sulfonic acid, sodium salt-co-2-acetoacetoxyethyl methacrylate) (weight ratio 91.25:4.75:4.0); and poly(n-butyl acrylate-co-2-acrylamido-2-methylpropane sulfonic acid-co-2-acetoacetoxyethyl methacrylate) (weight ratio 85:10:5).

Claim 34

An element as described in claim 27 wherein said carrier comprises a hydrophilic colloid selected from the group consisting of gelatin, a gelatin derivative, a cellulose derivative, a polysaccharide, an acrylamide, poly(vinyl alcohol), and poly(vinyl pyrrolidone).

Claim 35

An element as described in claim 27 wherein said polymer comprises from about 20 percent to about 50 percent of the total weight of said carrier plus said polymer.

Claim 36

An element as described in claim 27 wherein the carrier is a layer comprising deionized gelatin coated on a polyethylene terephthalate film support and said carrier is overcoated with a layer comprising deionized gelatin, bis(vinylsulfonylmethyl) ether, borate buffer (pH9), a subbing layer comprising poly(n-isopropyl acrylamide) and a blushed-polymer, spreading-reflecting layer comprising cellulose acetate and titanium dioxide.