Multilayer analytical element

Claim 2

In an integral element useful in the analysis of a fluid sample for a predetermined analyte, the element including 1. a reagent capable of interacting in the presence of said analyte to produce a decomposition product; and 2. a reagent capable of interacting with said decomposition product or an intermediate to provide a detectable change; the improvement comprising a barrier composition separating substantially all of said said reagent (1) from said reagent (2), said barrier composition being substantially uniformly permeable to said decomposition product and substantially impermeable to interferants.

Claim 3

An element as defined in claim 1, wherein said reagents are uniformly distributed in separate layers and said barrier composition is in a layer between said separate layers or in one of said separate layers.

Claim 4

An element as defined in claim 2 wherein said barrier composition is substantially impermeable to liquid water and wherein said decomposition product is a vapor.

Claim 5

An element as defined in claim 1 wherein said composition includes a member selected from the group consisting of cellulose propionate valerate, cellulose acetate butyrate, cellulose acetate, and poly(methyl methacrylate).

Claim 6

In an integral, multilayered element useful in the analysis of a fluid sample for a predetermined analyte, the element including, in superposed relationship: 1. a first layer which includes at least one reagent capable of interacting in the presence of the analyte to produce a decomposition product; and 2. a second layer which includes at least one reagent capable of interacting in the presence of said decomposition product or an intermediate to provide a detectable change; the improvement comprising a barrier composition separating substantially all of said reagents in said first and second layers from one another, said composition being substantially uniformly permeable to said decomposition product and substantially impermeable to interferants; one of said reagents being distributed within said barrier composition.

Claim 7

In an integral, multilayered element useful in the analysis of a fluid sample for a predetermined analyte, the element including, in superposed relationship: 1. a first layer which includes at least one reagent capable of interacting in the presence of the analyte to produce a decomposition product; and 2. a second layer which includes at least one reagent capable of interacting in the presence of said decomposition product or an intermediate to provide a detectable change; the improvement comprising a barrier composition separating substantially all of said reagents in said first and second layers from one another, said composition being substantially uniformly permeable to said decomposition product and substantially impermeable to interferants; one of said reagents being distributed within said barrier composition.

Claim 8

An element as defined in claim 5 wherein said first layer reagent includes at least one enzyme capable of complexing with analyte to produce a decompostion product capable of reacting with said distributed reagent to produce said detectable species; and further including a non-fibrous isotropically porous spreading layer.

Claim 9

An element as defined in claim 6 wherein said enzyme is confined to a discrete layer interposed between said spreading layer and said barrier composition.

Claim 10

An element as defined in claim 5 wherein said barrier composition is substantially impermeable to liquid water and wherein said decomposition product is a vapor.

Claim 11

An element as defined in claim 8 wherein said composition includes a member selected from the group consisting of cellulose propionate valerate, cellulose acetate butyrate, cellulose acetate, and poly(methyl methacrylate).

Claim 12

In an integral, multilayered element useful in the analysis of a fluid sample for a predetermined analyte, the element including, in superposed relationship: 1. a first layer which includes at least one reagent capable of interacting in the presence of the analyte to produce a decomposition product; and 2. a second layer which includes at least one reagent capable of interacting with said decomposition product or an intermediate to provide a detectable change; the improvement comprising a barrier composition separating substantially all of said first and second layer reagents from one another, said barrier composition being substantially permeable to said decomposition product and substantially uniformly impermeable to interferants; said barrier composition being contiguous with and between said two layers.

Claim 13

In an integral, multilayered element useful in the analysis of a fluid sample for a predetermined analyte, the element including, in superposed relationship: 1. a first layer which includes at least one reagent capable of interacting in the presence of the analyte to produce a decomposition product; and 2. a second layer which includes at least one reagent capable of interacting with said decomposition product or an intermediate to provide a detectable change; the improvement comprising a barrier composition separating substantially all of said first and second layer reagents from one another, said barrier composition being substantially permeable to said decomposition product and substantially uniformly impermeable to interferants; said barrier composition being contiguous with and between said two layers.

Claim 14

An element as defined in claim 10 wherein said first layer reagent includes at least one enzyme capable of complexing with a predetermined analyte to produce a decomposition product capable of reacting with said second layer reagent to produce said detectable change; and further including an isotropically porous spreading layer.

Claim 15

An element as defined in claim 11 wherein said enzyme is generally confined to a layer distinct from and between said spreading layer and said barrier composition.

Claim 16

An element as defined in claim 12 wherein said composition includes a member selected from the group consisting of cellulose propionate valerate, cellulose acetate butyrate, cellulose acetate, and poly(methyl methacrylate).

Claim 17

In an integral element useful in the analysis of a fluid sample for urea, the element including 1. urease; and 2. a reagent capable of interacting with ammonia to form a detectable product; the improvement comprising a barrier composition separating substantially all of said urease from said reagent, said composition being substantially uniformly permeable to ammonia vapor and substantially impermeable to liquid bases.

Claim 18

In an integral element useful in the analysis of a fluid sample for urea, the element including 1. urease; and 2. a reagent capable of interacting with ammonia to form a detectable product; the improvement comprising a barrier composition separating substantially all of said urease from said reagent, said composition being substantially uniformly permeable to ammonia vapor and substantially impermeable to liquid bases.

Claim 19

An element as defined in claim 14 wherein said reagent includes a dye precursor which, in the presence of NH 3 , produces a dye.

Claim 20

An element as defined in claim 15 wherein said dye precursor is a leuco compound which deprotonates in the presence of NH 3 .

Claim 21

An element as defined in claim 16 wherein said leuco compound is a leuco dye selected from the group consisting of leuco cyanine dyes, nitro-substituted leuco dyes, and leuco phthalein dyes.

Claim 22

An element as defined in claim 17 and for the analysis of BUN, wherein said leuco dye is present in an amount sufficient to provide deprotonation in response to all the ammonia transmitted to the leuco dye during the time of the analysis and corresponding to a range of from 0 to about 120 mg of BUN per deciliter of sample.

Claim 23

In an integral element useful in the analysis of a fluid sample for urea, the element including 1. urease; and 2. a reagent capable of interacting with ammonia to form a detectable product; the improvement comprising a barrier composition separating said urease and said reagent, said composition being substantially uniformly permeable to ammonia vapor and substantially impermeable to liquid bases, said reagent including a 1,2-substituted quinolinium salt which deprotonates in the presence of NH 3 to produce a dye.

Claim 24

In an integral element useful in the analysis of a fluid sample for urea, the element including 1. urease; and 2. a reagent capable of interacting with ammonia to form a detectable product; the improvement comprising a barrier composition separating said urease and said reagent, said composition being substantially uniformly permeable to ammonia vapor and substantially impermeable to liquid bases, said reagent including a 1,2-substituted quinolinium salt which deprotonates in the presence of NH 3 to produce a dye.

Claim 25

In an integral element useful in the analysis of a fluid sample for urea, the element including 1. urease; and 2. a reagent capable of interacting with ammonia to form a detectable product; the improvement comprising a barrier composition separating said urease and said reagent, said composition being substantially uniformly permeable to ammonia vapor and substantially impermeable to liquid bases, said reagent including a 1,4-substituted quinolinium salt which deprotonates in the presence of NH 3 to produce a dye.

Claim 26

In an integral element useful in the analysis of a fluid sample for urea, the element including 1. urease; and 2. a reagent capable of interacting with ammonia to form a detectable product; the improvement comprising a barrier composition separating said urease and said reagent, said composition being substantially uniformly permeable to ammonia vapor and substantially impermeable to liquid bases, said reagent including a 1,4-substituted quinolinium salt which deprotonates in the presence of NH 3 to produce a dye.

Claim 27

In an integral element useful in the analysis of a fluid sample for urea, the element including 1. urease; and 2. a reagent capable of interacting with ammonia to form a detectable product; the improvement comprising a barrier composition separating said urease and said reagent, said composition being substantially uniformly permeable to ammonia vapor and substantially impermeable to liquid bases, said reagent including a leuco dye that deprotonates in the presence of NH 3 and has the formula ##STR17## wherein: a. k represents 0 or 1; b. m represents 0 or 1; c. n represents 1 or 2; d. each L represents a methine group; e. A represents an electron donating moiety, selected from the group oxygen (--O--), sulfur (--S--), and ##STR18## f. E is an electron-withdrawing group selected from the class consisting of nitro, cyano, ethoxycarbonyl, and halogenated methyl; g. p represents 0 or 1; h. R 3 represents either an alkyl group having from 1 to 18 carbon atoms and preferably a lower alkyl group having from 1 to 4 carbon atoms, a sulfoalkyl group, a carboxyalkyl group, a sulfatoalkyl group, an alkoxyalkyl group, an acyloxyalkyl group, an alkoxycarbonylalkyl group, a dialkylaminoalkylene group, a cycloaminoalkylene group, an alkenyl group, or an aryl group; i. X - is an acid anion; j. Z 3 represents the atoms necessary to complete an aryl ring; and k. Z 4 represents the nonmetallic atoms necessary to complete a heterocyclic nucleus.

Claim 28

In an integral element useful in the analysis of a fluid sample for urea, the element including 1. urease; and 2. a reagent capable of interacting with ammonia to form a detectable product; the improvement comprising a barrier composition separating said urease and said reagent, said composition being substantially uniformly permeable to ammonia vapor and substantially impermeable to liquid bases, said reagent including a leuco dye that deprotonates in the presence of NH 3 and has the formula ##STR17## wherein: a. k represents 0 or 1; b. m represents 0 or 1; c. n represents 1 or 2; d. each L represents a methine group; e. A represents an electron donating moiety, selected from the group oxygen (--O--), sulfur (--S--), and ##STR18## f. E is an electron-withdrawing group selected from the class consisting of nitro, cyano, ethoxycarbonyl, and halogenated methyl; g. p represents 0 or 1; h. R 3 represents either an alkyl group having from 1 to 18 carbon atoms and preferably a lower alkyl group having from 1 to 4 carbon atoms, a sulfoalkyl group, a carboxyalkyl group, a sulfatoalkyl group, an alkoxyalkyl group, an acyloxyalkyl group, an alkoxycarbonylalkyl group, a dialkylaminoalkylene group, a cycloaminoalkylene group, an alkenyl group, or an aryl group; i. X - is an acid anion; j. Z 3 represents the atoms necessary to complete an aryl ring; and k. Z 4 represents the nonmetallic atoms necessary to complete a heterocyclic nucleus.

Claim 29

An element as defined in claim 21 wherein said leuco dye is 1-ethyl-4(2,6-dinitrophenyl)methyl quinolinium ethyl sulfonate.

Claim 30

An element as defined in claim 21 wherein said leuco dye is 1-methyl-2(2,4-dinitrophenyl)methyl quinolinium perchlorate.

Claim 31

An element as defined in claim 21 wherein said leuco dye is 1-ethyl-4(2,4-dinitro-1-naphthyl)methyl quinolinium chloride.

Claim 32

An element as defined in claim 21 wherein said leuco dye is 1-propyl-4(2,6-dinitro-4-chlorophenyl)methyl quinolinium ethane sulfonate.

Claim 33

In an integral element useful in the analysis of a fluid sample for urea, the element including 1. urease; and 2. a reagent capable of interacting with ammonia to form a detectable product; the improvement comprising a barrier composition separating said urease and said reagent, said composition being substantially uniformly permeable to ammonia vapor and substantially impermeable to liquid bases, said reagent including a dye precursor that deprotonates in the presence of NH 3 and has the formula ##STR19## wherein: n represents a positive integer of 1 to 10; X - represents an acid anion; R 1 and R 2 are the same or different and each represents either hydrogen, a substituted or unsubstituted alkyl group, an alkoxyalkyl group, a carboxyalkyl group, a sulfoalkyl group, a sulfato alkyl group, an acyloxyalkyl group, an alkoxycarbonylalkyl group, an aralkyl group, an alkenyl group, or a substituted or unsubstituted aryl group; and Z 1 and Z 2 are the same or different and each represents the nonmetallic atoms necessary to complete a heterocyclic nucleus.

Claim 34

In an integral element useful in the analysis of a fluid sample for urea, the element including 1. urease; and 2. a reagent capable of interacting with ammonia to form a detectable product; the improvement comprising a barrier composition separating said urease and said reagent, said composition being substantially uniformly permeable to ammonia vapor and substantially impermeable to liquid bases, said reagent including a dye precursor that deprotonates in the presence of NH 3 and has the formula ##STR19## wherein: n represents a positive integer of 1 to 10; X - represents an acid anion; R 1 and R 2 are the same or different and each represents either hydrogen, a substituted or unsubstituted alkyl group, an alkoxyalkyl group, a carboxyalkyl group, a sulfoalkyl group, a sulfato alkyl group, an acyloxyalkyl group, an alkoxycarbonylalkyl group, an aralkyl group, an alkenyl group, or a substituted or unsubstituted aryl group; and Z 1 and Z 2 are the same or different and each represents the nonmetallic atoms necessary to complete a heterocyclic nucleus.

Claim 35

In an integral element useful in the analysis of a fluid sample for urea, the element including 1. urease; and 2. a reagent capable of interacting with ammonia to form a detectable product; the improvement comprising a barrier composition separating said urease and said reagent, said composition being substantially uniformly permeable to ammonia vapor and substantially impermeable to liquid bases, said reagent including an ammonia-bleachable dye.

Claim 36

In an integral element useful in the analysis of a fluid sample for urea, the element including 1. urease; and 2. a reagent capable of interacting with ammonia to form a detectable product; the improvement comprising a barrier composition separating said urease and said reagent, said composition being substantially uniformly permeable to ammonia vapor and substantially impermeable to liquid bases, said reagent including an ammonia-bleachable dye.

Claim 37

An element as defined in claim 27 wherein said dye is a pyrylium dye or styryl dye.

Claim 38

An integral multilayered element useful in the analysis of a fluid sample for a predetermined analyte, the element comprising, in superposed relationship,

Claim 39

An integral multilayered element useful in the analysis of a fluid sample for a predetermined analyte, the element comprising, in superposed relationship,

Claim 40

a first layer which includes an enzyme capable of complexing with analyte to produce a decomposition product; 2. a second layer which includes a reagent capable of interacting with said decomposition product or an intermediate to form a detectable change; 3. a barrier composition separating substantially all of said enzyme from said reagent, said composition being substantially uniformly permeable to said decomposition product and substantially impermeable to interferants; and 4. a non-fibrous isotropically porous spreading layer.

Claim 41

a first layer which includes an enzyme capable of complexing with analyte to produce a decomposition product; 2. a second layer which includes a reagent capable of interacting with said decomposition product or an intermediate to form a detectable change; 3. a barrier composition separating substantially all of said enzyme from said reagent, said composition being substantially uniformly permeable to said decomposition product and substantially impermeable to interferants; and 4. a non-fibrous isotropically porous spreading layer.

Claim 42

An element as defined in claim 29 wherein said spreading layer includes means for reflecting light.

Claim 43

An element as defined in claim 30 wherein said means includes titanium dioxide.

Claim 44

An integral element useful in the analysis of a fluid sample for a predetermined analyte, the element comprising 1. an enzyme capable of complexing with said analyte to produce a decomposition product; 2. a dye precursor capable of forming a detectable change and having the formula ##STR20## wherein: n represents a positive integer of 1 to 10; X - represents an acid anion; R 1 and R 2 are the same or different and each represents either hydrogen, a substituted or unsubstituted alkyl group, an alkoxyalkyl group, a carboxyalkyl group, a sulfoalkyl group, a sulfato alkyl group, an acyloxyalkyl group, an alkoxycarbonylalkyl group, an aralkyl group, an alkenyl group, or a substituted or unsubstituted aryl group; and Z 1 and Z 2 are the same or different and each represents the nonmetallic atoms necessary to complete a heterocyclic nucleus; and

Claim 45

An integral element useful in the analysis of a fluid sample for a predetermined analyte, the element comprising 1. an enzyme capable of complexing with said analyte to produce a decomposition product; 2. a dye precursor capable of forming a detectable change and having the formula ##STR20## wherein: n represents a positive integer of 1 to 10; X - represents an acid anion; R 1 and R 2 are the same or different and each represents either hydrogen, a substituted or unsubstituted alkyl group, an alkoxyalkyl group, a carboxyalkyl group, a sulfoalkyl group, a sulfato alkyl group, an acyloxyalkyl group, an alkoxycarbonylalkyl group, an aralkyl group, an alkenyl group, or a substituted or unsubstituted aryl group; and Z 1 and Z 2 are the same or different and each represents the nonmetallic atoms necessary to complete a heterocyclic nucleus; and

Claim 46

a barrier composition separating said enzyme and said dye, said composition being substantially uniformly permeable to said decomposition product and substantially impermeable to interferants.

Claim 47

a barrier composition separating said enzyme and said dye, said composition being substantially uniformly permeable to said decomposition product and substantially impermeable to interferants.

Claim 48

A process of analyzing a liquid for the presence of a predetermined analyte, comprising the steps of a. depositing a sample of the liquid on an element comprising a first reagent capable of producing a radiant energy detectable species and having in association with it a binder, a second reagent capable of producing from the analyte a decomposition product which is interactive with said first reagent; and a barrier composition separating substantially all of said second reagent from said first reagent, said composition being substantially uniformly permeable to said decomposition product and substantially impermeable to interferants; whereby the analyte and the second reagent react to produce a decomposition product that selectively permeates through the barrier composition where it reacts with the first reagent; and b. measuring said detectable change.

Claim 49

A process of analyzing a liquid for the presence of a predetermined analyte, comprising the steps of a. depositing a sample of the liquid on an element comprising a first reagent capable of producing a radiant energy detectable species and having in association with it a binder, a second reagent capable of producing from the analyte a decomposition product which is interactive with said first reagent; and a barrier composition separating substantially all of said second reagent from said first reagent, said composition being substantially uniformly permeable to said decomposition product and substantially impermeable to interferants; whereby the analyte and the second reagent react to produce a decomposition product that selectively permeates through the barrier composition where it reacts with the first reagent; and b. measuring said detectable change.

Claim 50

In an integral, multilayered element useful in the analysis of a fluid sample for a predetermined analyte, the element including, in superposed relationship: 1. a first layer which includes a sample intercept area, and reagent in said area capable of interacting with the analyte to produce a decomposition produt; and 2. a second layer which includes at least one reagent capable of interacting with said decomposition product or an intermediate to form a detectable change; the improvement comprising a barier composition separating substantially all of said first and second layer reagent from one another and having a sample intercept area that is at least coextensive with said sample intercept area of said first layer, said composition within its sample intercept area being uniformly permeable to said decomposition product and impermeable to interferants.

Claim 51

In an integral, multilayered element useful in the analysis of a fluid sample for a predetermined analyte, the element including, in superposed relationship: 1. a first layer which includes a sample intercept area, and reagent in said area capable of interacting with the analyte to produce a decomposition produt; and 2. a second layer which includes at least one reagent capable of interacting with said decomposition product or an intermediate to form a detectable change; the improvement comprising a barier composition separating substantially all of said first and second layer reagent from one another and having a sample intercept area that is at least coextensive with said sample intercept area of said first layer, said composition within its sample intercept area being uniformly permeable to said decomposition product and impermeable to interferants.

Claim 52

An element as defined in claim 34 wherein said barrier composition is substantially impermeable to liquid water and wherein said decomposition product is a vapor.

Claim 53

In an integral, multilayered element useful in the analysis of a fluid sample for a predetermined analyte, the element including, in superposed relationship: 1. a first layer which includes a sample intercept area and a reagent in said area capable of interacting with the analyte to produce a decomposition product; and 2. a second layer which includes a reagent capable of interacting with said decomposition product or an intermediate to form a detectable change; the improvement comprising a barrier composition separating substantially all of said first and second layer reagents from one another and having a sample intercept area that is at least coextensive with said sample intercept area of said first layer, said barrier composition within said sample intercept area being uniformly impermeable to interferants; said barrier composition incorporating one of said reagents within said coextensive sample intercept area.

Claim 54

In an integral, multilayered element useful in the analysis of a fluid sample for a predetermined analyte, the element including, in superposed relationship: 1. a first layer which includes a sample intercept area and a reagent in said area capable of interacting with the analyte to produce a decomposition product; and 2. a second layer which includes a reagent capable of interacting with said decomposition product or an intermediate to form a detectable change; the improvement comprising a barrier composition separating substantially all of said first and second layer reagents from one another and having a sample intercept area that is at least coextensive with said sample intercept area of said first layer, said barrier composition within said sample intercept area being uniformly impermeable to interferants; said barrier composition incorporating one of said reagents within said coextensive sample intercept area.

Claim 55

An element as defined in claim 36 wherein said first layer reagent includes an enzyme capable of complexing with the analyte being tested to effect a decomposition product capable of reacting with said incorporated reagent to produce said detectable species, and further including a non-fibrous isotropically porous spreading layer.

Claim 56

An element as defined in claim 37 wherein said enzyme is confined to a layer separate and distinct from the spreading layer between said spreading layer and said barrier composition.

Claim 57

An element as defined in claim 36 wherein said barrier composition includes a member selected from the group consisting of cellulose propionate valerate, cellulose acetate butyrate, cellulose acetate, and poly(methyl methacrylate).

Claim 58

In an integral element useful in the analysis of a fluid sample for urea, the element including 1. a layer comprising urease in a sample intercept area; and 2. a reagent capable of interacting with ammonia to form a detectable change; the improvement comprising a barrier composition separating substantially all of said urease from said reagent and having a sample intercept area that is at least coextensive with the sample intercept area of the layer comprising said urease, said barrier composition within its sample intercept area being uniformly permeable to ammonia vapor and impermeable to liquid base.

Claim 59

In an integral element useful in the analysis of a fluid sample for urea, the element including 1. a layer comprising urease in a sample intercept area; and 2. a reagent capable of interacting with ammonia to form a detectable change; the improvement comprising a barrier composition separating substantially all of said urease from said reagent and having a sample intercept area that is at least coextensive with the sample intercept area of the layer comprising said urease, said barrier composition within its sample intercept area being uniformly permeable to ammonia vapor and impermeable to liquid base.

Claim 60

An element as defined in claim 40 wherein said barrier composition is substantially impermeable to liquid water.

Claim 61

An element as defined in claim 40 wherein said one reagent includes a leuco compound which deprotonates in the presence of NH 3 .

Claim 62

An element as defined in claim 42 wherein said compound is selected from the group consisting of leuco cyanine dyes, nitro-substituted leuco dyes, and leuco phthalein dyes.

Claim 63

In an integral element useful in the analysis of a fluid sample for urea, the element including 1. a layer comprising urease in a sample intercept area; and

Claim 64

In an integral element useful in the analysis of a fluid sample for urea, the element including 1. a layer comprising urease in a sample intercept area; and

Claim 65

a reagent capable of interacting with ammonia to form a detectable change; the improvement comprising a barrier composition separating said urease and said reagent and having a sample intercept area that is at least coextensive with the sample intercept area of the layer comprising said urease, said barrier composition within its sample intercept area being uniformly permeable to ammonia vapor and impermeable to liquid bases, said reagent including a 1,2-substituted quinolinium salt which deprotonates in the presence of NH 3 .

Claim 66

a reagent capable of interacting with ammonia to form a detectable change; the improvement comprising a barrier composition separating said urease and said reagent and having a sample intercept area that is at least coextensive with the sample intercept area of the layer comprising said urease, said barrier composition within its sample intercept area being uniformly permeable to ammonia vapor and impermeable to liquid bases, said reagent including a 1,2-substituted quinolinium salt which deprotonates in the presence of NH 3 .

Claim 67

In an integral element useful in the analysis of a fluid sample for urea, the element including 1. a layer comprising urease in a sample intercept area; and 2. a reagent capable of interacting with ammonia to form a detectable change; the improvement comprising a barrier composition separating said urease and said reagent and having a sample intercept area that is at least coextensive with the sample intercept area of the layer comprising said urease, said barrier composition within its sample intercept area being uniformly permeable to ammonia vapor and impermeable to liquid bases, said reagent including a 1,4-substituted quinolinium salt which deprotonates in the presence of NH 3 .

Claim 68

In an integral element useful in the analysis of a fluid sample for urea, the element including 1. a layer comprising urease in a sample intercept area; and 2. a reagent capable of interacting with ammonia to form a detectable change; the improvement comprising a barrier composition separating said urease and said reagent and having a sample intercept area that is at least coextensive with the sample intercept area of the layer comprising said urease, said barrier composition within its sample intercept area being uniformly permeable to ammonia vapor and impermeable to liquid bases, said reagent including a 1,4-substituted quinolinium salt which deprotonates in the presence of NH 3 .

Claim 69

In an integral element useful in the analysis of a fluid sample for urea, the element including 1. a layer comprising urease in a sample intercept area; and 2. a reagent capable of interacting with ammonia to form a detectable change; the improvement comprising a barrier composition separating said urease and said reagent and having a sample intercept area that is at least coextensive with the sample intercept area of the layer comprising said urease, said barrier composition within its sample intercept area being uniformly permeable to ammonia vapor and impermeable to liquid bases, said reagent including a leuco dye that deprotonates in the presence of NH 3 and has the formula ##STR21## wherein: a. k represents 0 or 1; b. m represents 0 or 1; c. n represents 1 or 2; d. each L represents a methine group; e. A represents an electron donating moiety, selected from the group oxygen (--O--), sulfur (--S--), and ##STR22## f. E is an electron-withdrawing group selected from the class consisting of nitro, cyano, ethoxycarbonyl, and halogenated methyl; g. p represents o or 1; h. R 3 represents either an alkyl group having from 1 to 18 carbon atoms and preferably a lower alkyl group having from 1 to 4 carbon atoms, a sulfoalkyl group, a carboxyalkyl group, a sulfatoalkyl group, an alkoxyalkyl group, an acyloxyalkyl group, an alkoxycarbonyl alkyl group, a dialkylaminoalkylene group, a cycloaminoalkylene group, an alkenyl group, or an aryl group; i. X - is an acid anion; j. Z 3 represents the atoms necessary to complete an aryl ring; and k. Z 4 represents the nonmetallic atoms necessary to complete a heterocyclic nucleus.

Claim 70

In an integral element useful in the analysis of a fluid sample for urea, the element including 1. a layer comprising urease in a sample intercept area; and 2. a reagent capable of interacting with ammonia to form a detectable change; the improvement comprising a barrier composition separating said urease and said reagent and having a sample intercept area that is at least coextensive with the sample intercept area of the layer comprising said urease, said barrier composition within its sample intercept area being uniformly permeable to ammonia vapor and impermeable to liquid bases, said reagent including a leuco dye that deprotonates in the presence of NH 3 and has the formula ##STR21## wherein: a. k represents 0 or 1; b. m represents 0 or 1; c. n represents 1 or 2; d. each L represents a methine group; e. A represents an electron donating moiety, selected from the group oxygen (--O--), sulfur (--S--), and ##STR22## f. E is an electron-withdrawing group selected from the class consisting of nitro, cyano, ethoxycarbonyl, and halogenated methyl; g. p represents o or 1; h. R 3 represents either an alkyl group having from 1 to 18 carbon atoms and preferably a lower alkyl group having from 1 to 4 carbon atoms, a sulfoalkyl group, a carboxyalkyl group, a sulfatoalkyl group, an alkoxyalkyl group, an acyloxyalkyl group, an alkoxycarbonyl alkyl group, a dialkylaminoalkylene group, a cycloaminoalkylene group, an alkenyl group, or an aryl group; i. X - is an acid anion; j. Z 3 represents the atoms necessary to complete an aryl ring; and k. Z 4 represents the nonmetallic atoms necessary to complete a heterocyclic nucleus.

Claim 71

In an integral element useful in the analysis of a fluid sample for urea, the element including 1. a layer comprising urease in a sample intercept area; and 2. a reagent capable of interacting with ammonia to form a detectable change; the improvement comprising a barrier composition separating said urease and said reagent and having a sample intercept area that is at least coextensive with the sample intercept area of the layer comprising said urease, said barrier composition within its sample intercept area being uniformly permeable to ammonia vapor and impermeable to liquid bases, said reagent including a chromogen that deprotonates in the presence of NH 3 and has the formula ##STR23## wherein: n represents a positive integer of 1 to 10; X - represents an acid anion; R 1 and R 2 are the same or different and each represents either hydrogen, an alkyl group, an alkoxyalkyl group, a carboxyalkyl group, a sulfoalkyl group, a sulfato alkyl group, an acyloxyalkyl group, an alkoxycarbonylalkyl group, an aralkyl group, an alkenyl group, or an aryl group; and Z 1 and Z 2 are the same or different and each represents the nonmetallic atoms necessary to complete a heterocyclic nucleus.

Claim 72

In an integral element useful in the analysis of a fluid sample for urea, the element including 1. a layer comprising urease in a sample intercept area; and 2. a reagent capable of interacting with ammonia to form a detectable change; the improvement comprising a barrier composition separating said urease and said reagent and having a sample intercept area that is at least coextensive with the sample intercept area of the layer comprising said urease, said barrier composition within its sample intercept area being uniformly permeable to ammonia vapor and impermeable to liquid bases, said reagent including a chromogen that deprotonates in the presence of NH 3 and has the formula ##STR23## wherein: n represents a positive integer of 1 to 10; X - represents an acid anion; R 1 and R 2 are the same or different and each represents either hydrogen, an alkyl group, an alkoxyalkyl group, a carboxyalkyl group, a sulfoalkyl group, a sulfato alkyl group, an acyloxyalkyl group, an alkoxycarbonylalkyl group, an aralkyl group, an alkenyl group, or an aryl group; and Z 1 and Z 2 are the same or different and each represents the nonmetallic atoms necessary to complete a heterocyclic nucleus.

Claim 73

In an integral element useful in the analysis of a fluid sample for urea, the element including

Claim 74

In an integral element useful in the analysis of a fluid sample for urea, the element including

Claim 75

a layer comprising urease in a sample intercept area; and 2. a reagent capable of interacting with ammonia to form a detectable change; the improvement comprising a barrier composition separating said urease and said reagent and having a sample intercept area that is at least coextensive with the sample intercept area of the layer comprising said urease, said barrier composition within its sample intercept area being uniformly permeable to ammonia vapor and impermeable to liquid bases, said reagent including an ammonia-bleachable dye.

Claim 76

a layer comprising urease in a sample intercept area; and 2. a reagent capable of interacting with ammonia to form a detectable change; the improvement comprising a barrier composition separating said urease and said reagent and having a sample intercept area that is at least coextensive with the sample intercept area of the layer comprising said urease, said barrier composition within its sample intercept area being uniformly permeable to ammonia vapor and impermeable to liquid bases, said reagent including an ammonia-bleachable dye.

Claim 77

An element as defined in claim 48 wherein said dye is a pyrylium dye or styryl dye.

Claim 78

An integral element useful in the analysis of a fluid sample for a predetermined analyte, the element comprising 1. a layer which includes an enzyme in a sample intercept area, capable of reacting with said analyte to produce a decomposition product; 2. a dye precursor having the formula ##STR24## wherein: n represents a positive integer of 1 to 10; X - represents an acid anion; R 1 and R 2 are the same or different and each represents either hydrogen, an alkyl group, an alkoxyalkyl group, a carboxyalkyl group, a sulfoalkyl group, a sulfato alkyl group, an acyloxyalkyl group, an alkenyl group, or an aryl group; and Z 1 and Z 2 are the same or different and each represents the nonmetallic atoms necessary to complete a heterocyclic nucleus; and

Claim 79

An integral element useful in the analysis of a fluid sample for a predetermined analyte, the element comprising 1. a layer which includes an enzyme in a sample intercept area, capable of reacting with said analyte to produce a decomposition product; 2. a dye precursor having the formula ##STR24## wherein: n represents a positive integer of 1 to 10; X - represents an acid anion; R 1 and R 2 are the same or different and each represents either hydrogen, an alkyl group, an alkoxyalkyl group, a carboxyalkyl group, a sulfoalkyl group, a sulfato alkyl group, an acyloxyalkyl group, an alkenyl group, or an aryl group; and Z 1 and Z 2 are the same or different and each represents the nonmetallic atoms necessary to complete a heterocyclic nucleus; and

Claim 80

a barrier composition separating said enzyme and said dye and having a sample intercept area that is at least coextensive with said enzyme sample intercept area, said composition within its sample intercept area being uniformly permeable to said decomposition product and impermeable to interferants.

Claim 81

a barrier composition separating said enzyme and said dye and having a sample intercept area that is at least coextensive with said enzyme sample intercept area, said composition within its sample intercept area being uniformly permeable to said decomposition product and impermeable to interferants.