Multilayer analytical element
First Claim
Patent Images
1. In an integral element useful in the analysis of a fluid sample for a predetermined analyte, the element includinga reagent capable of interacting in the presence of said analyte to produce a decomposition product;
- and2. a reagent capable of interacting with said decomposition product or an intermediate to provide a detectable change;
the improvement comprisinga 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.
1 Assignment
0 Petitions
Accused Products
Abstract
An analytical element for assay of complex fluids, such as blood, the element comprising two reagents and a barrier composition separating the reagents. Such an element is particularly useful in the analysis of blood for urea nitrogen and cholesterol content.
-
Citations
55 Claims
-
1. In an integral element useful in the analysis of a fluid sample for a predetermined analyte, the element includinga 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. - View Dependent Claims (2, 3, 4)
- and
-
5. 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. - View Dependent Claims (6, 7, 8, 9)
-
-
10. 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. - View Dependent Claims (11, 12, 13)
-
-
14. In an integral element useful in the analysis of a fluid sample for urea, the element includingurease;
- 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. - View Dependent Claims (15, 16, 17, 18)
- and
-
19. In an integral element useful in the analysis of a fluid sample for urea, the element includingurease;
- 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 NH3 to produce a dye.
- and
-
20. In an integral element useful in the analysis of a fluid sample for urea, the element includingurease;
- 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 NH3 to produce a dye.
- and
-
21. In an integral element useful in the analysis of a fluid sample for urea, the element includingurease;
- 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 NH3 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. R3 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. Z3 represents the atoms necessary to complete an aryl ring; and k. Z4 represents the nonmetallic atoms necessary to complete a heterocyclic nucleus. - View Dependent Claims (22, 23, 24, 25)
- and
-
26. In an integral element useful in the analysis of a fluid sample for urea, the element includingurease;
- 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 NH3 and has the formula ##STR19## wherein;
n represents a positive integer of 1 to 10;X- represents an acid anion; R1 and R2 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 Z1 and Z2 are the same or different and each represents the nonmetallic atoms necessary to complete a heterocyclic nucleus.
- and
-
27. In an integral element useful in the analysis of a fluid sample for urea, the element includingurease;
- 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. - View Dependent Claims (28)
- and
- 29. An integral multilayered element useful in the analysis of a fluid sample for a predetermined analyte, the element comprising, in superposed relationship,
-
30. 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. - View Dependent Claims (32)
-
-
33. An integral element useful in the analysis of a fluid sample for a predetermined analyte, the element comprisingan 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; R1 and R2 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 Z1 and Z2 are the same or different and each represents the nonmetallic atoms necessary to complete a heterocyclic nucleus; and
- 34. a barrier composition separating said enzyme and said dye, said composition being substantially uniformly permeable to said decomposition product and substantially impermeable to interferants.
-
35. 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.
- 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;
-
36. 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. - View Dependent Claims (39, 41)
-
-
38. 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.
-
-
42. In an integral element useful in the analysis of a fluid sample for urea, the element includinga 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. - View Dependent Claims (45)
- and
-
46. In an integral element useful in the analysis of a fluid sample for urea, the element includinga layer comprising urease in a sample intercept area;
- and
-
47. 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 NH3.
-
-
48. In an integral element useful in the analysis of a fluid sample for urea, the element includinga 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 NH3. - View Dependent Claims (53)
- and
-
49. In an integral element useful in the analysis of a fluid sample for urea, the element includinga 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 NH3 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. R3 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. Z3 represents the atoms necessary to complete an aryl ring; and k. Z4 represents the nonmetallic atoms necessary to complete a heterocyclic nucleus.
- and
-
50. In an integral element useful in the analysis of a fluid sample for urea, the element includinga 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 NH3 and has the formula ##STR23## wherein;
n represents a positive integer of 1 to 10;X- represents an acid anion; R1 and R2 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 Z1 and Z2 are the same or different and each represents the nonmetallic atoms necessary to complete a heterocyclic nucleus.
- and 2. a reagent capable of interacting with ammonia to form a detectable change;
-
51. In an integral element useful in the analysis of a fluid sample for urea, the element including
-
52. 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.
- and
-
54. An integral element useful in the analysis of a fluid sample for a predetermined analyte, the element comprisinga 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; R1 and R2 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 Z1 and Z2 are the same or different and each represents the nonmetallic atoms necessary to complete a heterocyclic nucleus; and
-
-
55. 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.
Specification