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US4528274A Expired / Lapsed US ⏱️ 0.0 years remaining

Multi-purpose blood diluent and lysing agent for differential determination of lymphoid-myeloid population of leukocytes

Assignee: Beckman Coulter Inc
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Filing: 1983-03-25
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Granted: 1985-07-09
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Expires: 2003-03-25
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Abstract

Abstract A method and reagent system is described for differential determination of more that one class of leukocyte populations, using an automatic blood cell analyzer. The reagent system includes a blood diluent and stromatolyzing reagent. The blood diluent is an osmotically balanced aqueous solution of ingredients for maintaining erythrocyte morphology, blood cell stabilizing, buffering and bacteriostatic action. The stromatolyzing reagent is a mixture of an aqueous solution of quaternary ammonium salts, a chromagen forming agent and an additive which is a non-cationic surfactant. The quaternary ammonium salts, with the additive, serve the purpose of positioning, relative to one another and a volume reference point, the lymphoid and myeloid populations. The additive also acts to prevent or to reduce the amount of protein deposit in the sensing orifices of the analyzer, which deposit tends to accumulate from the cell debris resulting from blood cell stromatolyzation.

Inventors

  • 👤 James H. Carter
  • 👤 Stephen L. Ledis
  • 👤 Harold R. Crews
  • 👤 Ted Sena
  • 👤 Fred L. Larsen

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-11-01 05:20
CPC Classifications
G; G01; G01N; G01N33/00; G01N33/48; G01N33/50; G01N33/5005; G01N33/5094; Y; Y10; Y10T; Y10T436/00; Y10T436/10; Y10T436/101666; Y10T436/107497; Y10T436/108331

Claims Analysis

Total Claims: 27
Claim 1
Independent Claim 122 words
A stromatolysing reagent for use in the determination of at least two leukocyte populations in blood, two such populations being lymphoid and myeloid, the blood being processed through a blood cell analyzer using the Coulter Principle of operation, which employs a leukocyte sensing zone, the blood having been first diluted with an electrically conductive isotonically balanced diluent, wherein said stromatolysing reagent comprises an aqueous solution of at least two quaternary ammonium salts having surface active properties and an additive which is at least one non-cationic surfactant, said salts and additive being present in sufficient amounts for positioning said leukocyte populations relative to one another and relative to a blood cell volume reference point, within the time constraints of said blood cell analyzer.
Claim 2
Dependent Claim 122 words
A stromatolysing reagent for use in the determination of at least two leukocyte populations in blood, two such populations being lymphoid and myeloid, the blood being processed through a blood cell analyzer using the Coulter Principle of operation, which employs a leukocyte sensing zone, the blood having been first diluted with an electrically conductive isotonically balanced diluent, wherein said stromatolysing reagent comprises an aqueous solution of at least two quaternary ammonium salts having surface active properties and an additive which is at least one non-cationic surfactant, said salts and additive being present in sufficient amounts for positioning said leukocyte populations relative to one another and relative to a blood cell volume reference point, within the time constraints of said blood cell analyzer.
Claim 3
Dependent Claim 16 words
The stromatolysing reagent of claim 1 wherein said non-cationic surfactant additive is a nonionic polyoxyethylated alkylphenol.
Claim 4
Dependent Claim 54 words
The stromatolysing reagent of claim 2 wherein said additive has the following product characteristics: ______________________________________ Appearance clear, almost water-white liquid 1% solution clear and colorless solubility in water readily soluble, even in cold water pH of 1% solution neutral stability stable to acids, alkalis and metallic ions cloud point clear at 212° C. ______________________________________
Claim 5
Dependent Claim 84 words
The stromatolysing reagent of claim 1 wherein the quaternary ammonium salts are those with C 12 and C 14 , alkyl radicals which have useful ranges of approximately 10 to 55 g/L and 9 to 20 g/L, respectively, with said additive having a useful range of approximately 4 to 20 mL/L; such that the selection of any two of these three components anywhere within their ranges will provide a useful reagent when the amount of the third component is properly selected within its range.
Claim 6
Dependent Claim 36 words
The stromatolysing reagent of claim 4 wherein said salts are dodecyltrimethylammonium chloride and tetradecyltrimethylammonium bromide, and said additive is selected from the group consisting of: 1. Polyoxyethylated alkylphenols, 2. Poly(oxypropylene)poly(oxyethylene)condensates, and 3. Polyethylene glycol p-isoalkylphenyl ethers.
Claim 7
Dependent Claim 98 words
The stromatolysing reagent of claim 1 wherein the quaternary ammonium salts are those with C 12 and C 14 , alkyl radicals which have useful ranges of approximately 10 to 55 g/L and 9 to 20 g/L, respectively, with said additive having a useful range of approximately 0.5 to 5 ml/L and being an alkali metal salt of a C 10 -C 18 alkyl sulfate; such that the selection of any two of these three components anywhere within their ranges will provide a useful reagent when the amount of the third component is properly selected within its range.
Claim 8
Dependent Claim 15 words
The stromatolysing reagent of claim 6 where said salts are dodecyltrimethylammonium chloride and tetradecyltrimethylammonium bromide.
Claim 9
Dependent Claim 14 words
The stromatolysing reagent of claim 1 wherein said non-cationic surfactant additive is a poly(oxypropylene)polyoxyethylene)condensate.
Claim 10
Dependent Claim 17 words
The stromatolysing reagent of claim 1 wherein said non-cationic surfactant additive is a polyethylene glycol p-isoalkylphenyl ether.
Claim 11
Dependent Claim 24 words
The stromatolysing reagent of claim 1 wherein said non-cationic surfactant additive is an alkali metal salt of a C 10 -C 18 alkyl sulfate.
Claim 12
Dependent Claim 32 words
The stromatolysing reagent of claim 1 which includes the following three ingredients in approximately the concentrations indicated: 1. Tetradecyltrimethylammonium bromide: 9 g/L 2. Dodecyltrimethylammonium chloride: 55 g/L 3. Polyoxyethylated alkylphenol: 12 mL/L.
Claim 13
Dependent Claim 32 words
The stromatolysing reagent of claim 1 which includes the following three ingredients in approximately the concentrations indicated: 1. Tetradecyltrimethylammonium bromide: 20 g/L 2. Dodecyltrimethylammonium chloride: 10 g/L 3. Polyoxyethylated alkylphenol: 8 mL/L.
Claim 14
Dependent Claim 37 words
The stromatolysing reagent of claim 1 which includes the following three ingredients in approximately the concentrations indicated: 1. Tetradecyltrimethylammonium bromide: 13 g/L 2. Dodecyltrimethylammonium chloride: 70 g/L 3. Polyethylene glycol p-isoalkylphenyl ether or polyoxyethylated alkylphenol: 8 mL/L.
Claim 15
Dependent Claim 33 words
The stromatolysing reagent of claim 1 which includes the following three ingredients in approximately the concentrations indicated: 1. Tetradecyltrimethylammonium bromide: 13 g/L 2. Dodecyltrimethylammonium chloride: 35 g/L 3. Sodium lauryl sulfate: 1.25 g/L.
Claim 16
Dependent Claim 17 words
A stromatolysing reagent according to claim 1 for use in the measurements of two populations of leukocytes.
Claim 17
Dependent Claim 17 words
A stromatolysing reagent according to claim 1 for use in the measurements of three populations of leukocytes.
Claim 18
Dependent Claim 41 words
The stromatolysing reagent of claim 1 for the measurements of three populations of leukocytes, stromatolysing reagent including the following three ingredients in approximately the concentrations indicated: 1. Tetradecyltrimethylammonium bromide: 6.5 g/L 2. Dodecyltrimethylammonium chloride: 18.8 g/L 3. Polyoxyethylated alkylphenol: 3 mL/L.
Claim 19
Dependent Claim 128 words
In a method for determination of at least two leukocyte populations in blood which is being processed through a blood cell analyzer using the Coulter Principle of operation which includes the step of: I. diluting a blood sample with an electronically conductive isotonically balanced diluent, the improvement which comprises the step of: II. stromatolysing with a reagent comprising an aqueous solution of at least two quaternary ammonium salts having surface active properties, and an additive which contains at least one non-cationic surfactant, said salts and additive being present in sufficient amounts for affecting the normal leukocyte volume distributions during said stromatolysation so as to cause the volume distribution measurements of said blood cell analyzer to lie within predetermined limits, with reference to at least one volume reference point.
Claim 20
Dependent Claim 128 words
In a method for determination of at least two leukocyte populations in blood which is being processed through a blood cell analyzer using the Coulter Principle of operation which includes the step of: I. diluting a blood sample with an electronically conductive isotonically balanced diluent, the improvement which comprises the step of: II. stromatolysing with a reagent comprising an aqueous solution of at least two quaternary ammonium salts having surface active properties, and an additive which contains at least one non-cationic surfactant, said salts and additive being present in sufficient amounts for affecting the normal leukocyte volume distributions during said stromatolysation so as to cause the volume distribution measurements of said blood cell analyzer to lie within predetermined limits, with reference to at least one volume reference point.
Claim 21
Dependent Claim 38 words
The method of claim 18 in which the diluent comprises an aqueous solution of: 1. buffering means, 2. cell membrane stabilizing means, 3. germicidal means, and 4. means for producing an osmotically balanced and substantially neutral pH solution.
Claim 22
Dependent Claim 76 words
The method of claim 18 in which the diluent comprises an aqueous solution of: 1. Procaine hydrochloride, 2. N-(2-acetamido)iminodiacetic acid (ADA), 3. Dimethylolurea, and 4. Alkali metal sulfate and alkali metal halide, said diluent being an osmotically balanced and substantially neutral pH solution; and said stromatolysing reagent further comprises an alkali metal cyanide; and said ingredients are present in a concentration range which is effective to enable the differential determination of leukocyte populations and hemogram values.
Claim 23
Dependent Claim 27 words
The method of claim 18 wherein said quaternary ammonium salts are selected from the group consisting of: 1. Dodecyltrimethylammonium chloride, 2. Tetradecyltrimethylammonium bromide, and 3. Hexadecyltrimethylammonium bromide.
Claim 24
Dependent Claim 41 words
The method of claim 18 wherein said non-cationic surfactant additive is selected from the group consisting of: 1. Polyoxyethylated alkylphenols, 2. Poly(oxypropylene)poly(oxyethylene)condensates, 3. Polyethylene glycol p-isoalkylphenyl ethers, and 4. An alkali metal salt of a C 10 -C 18 alkyl sulfate.
Claim 25
Dependent Claim 117 words
In a method for the size differentiation of at least two populations of leukocytes in blood, the blood being processed through a blood cell analyzer using the Coulter Principle of operation which employs a leukocyte sensing zone, the blood having been first diluted with an electrically conductive isotonically balanced diluent, the improvement wherein said stromatolysing reagent comprises an aqueous solution of at least two quaternary ammonium salts having surface active properties and an additive which is at least one non-cationic surfactant, said salts and additive being present in sufficient amounts for positioning said leukocyte populations relative to one another and relative to a blood cell volume reference point, within the time constraints of said blood cell analyzer.
Claim 26
Dependent Claim 117 words
In a method for the size differentiation of at least two populations of leukocytes in blood, the blood being processed through a blood cell analyzer using the Coulter Principle of operation which employs a leukocyte sensing zone, the blood having been first diluted with an electrically conductive isotonically balanced diluent, the improvement wherein said stromatolysing reagent comprises an aqueous solution of at least two quaternary ammonium salts having surface active properties and an additive which is at least one non-cationic surfactant, said salts and additive being present in sufficient amounts for positioning said leukocyte populations relative to one another and relative to a blood cell volume reference point, within the time constraints of said blood cell analyzer.
Claim 27
Dependent Claim 76 words
In the method of claim 23 the improvement wherein said quaternary ammonium salts have the formula ##STR2## where R 1 is a long chain alkyl radical having 10 to 18 carbon atoms, R 2 , R 3 , R 4 are short chain alkyl radicals having 1 to 6 carbon atoms and X - is a salt forming radical such as Cl - , Br - , PO 4 3- and CH 3 PO 4 .

USPTO Annuity & Maintenance Windows

Annuity Stage Window Opens Payment Deadline Surcharge Period Until Estimated Fee Status
3.5 Years (Year 4) 1988-07-08 1989-01-07 1989-07-09 $2000.00 Window Closed / Lapsed
7.5 Years (Year 8) 1992-07-08 1993-01-07 1993-07-09 $3760.00 Window Closed / Lapsed
11.5 Years (Year 12) 1996-07-08 1997-01-07 1997-07-09 $7700.00 Window Closed / Lapsed

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