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US5460974A Expired / Lapsed US ⏱️ 0.0 years remaining

Method of assaying whole blood for HDL cholesterol

Assignee: Bayer Corp
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Filing: 1992-10-13
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Granted: 1995-10-24
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Expires: 2012-10-13
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Abstract

Abstract An improved device and method of a) separating the cellular components of whole blood from plasma or serum, b) separating the low density lipoprotein (LDL) fraction and the very low density lipoprotein (VLDL) fraction from the plasma or serum, then c) assaying the plasma or serum for cholesterol present in the high density lipoprotein (HDL) fraction are disclosed. The device includes a separation area that separates the cellular components of whole blood from the serum or plasma and separates the LDL and VLDL fractions from the serum or plasma, and a test area that assays the serum or plasma for the concentration of the HDL cholesterol. The method includes introducing a whole blood sample to a test device including a separation area comprising a first zone that separates the cellular components of the whole blood from the plasma or serum; and a second zone that separates the LDL and the VLDL fractions from the plasma or serum. The essentially cell-free, LDL-free and VLDL-free plasma or serum then migrates to a test area. After the plasma or serum migrates to the test area, plasma or serum is assayed for HDL cholesterol and the test area is examined for a quantitative response to HDL cholesterol present in the whole blood sample.

Inventors

  • 👤 Mary B. Kozak
  • 👤 Andrea Badke

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-11-08 14:58
CPC Classifications
G; G01; G01N; G01N33/00; G01N33/48; G01N33/483; G01N33/487; G01N33/49; G01N33/491; C; C12; C12Q; C12Q1/00; C12Q1/60; G01N33/50; G01N33/92; G01N2800/00; G01N2800/04; G01N2800/044; Y; Y10; Y10T; Y10T436/00; Y10T436/25; Y10T436/25375

Claims Analysis

Total Claims: 20
Claim 1
Independent Claim 276 words
A method of separating cellular components, low density lipoprotein fraction and very low density lipoprotein fraction from an undiluted whole blood sample consisting essentially of: (a) first directly contacting the undiluted whole blood sample with a first carrier matrix to separate the cellular components of the whole blood sample and provide a plasma or serum, wherein said first carrier matrix has incorporated therein about 25 to about 250 units of an agglutinin, about 50 to about 150 NIH units of a coagulant or a mixture thereof to agglutinize or coagulate the cellular components of the undiluted whole blood sample in the first carrier matrix; (b) then allowing the plasma or serum to migrate by gravity to a second carrier matrix that has the same dimensions and is in fluid communication with the first carrier matrix to separate the low density lipoprotein fraction and the very low density lipoprotein fraction from the plasma or serum, said second carrier matrix having a pore size of at least 1 to about 50 microns and having incorporated therein a precipitating reagent composition comprising a sufficient amount of a polyvalent metal ion and a sufficient amount of a precipitating compound to separate the low density lipoprotein fraction and the very low density lipoprotein fraction from the plasma or serum and to provide a serum or plasma including a high density lipoprotein fraction, wherein the precipitating compound is selected from the group consisting of dextran sulfate, heparin sodium, phosphotungstic acid, polyvinyl sulfate, sodium tungstate, ammonium molybdate, and mixtures thereof; and (c) then allowing the serum or plasma including the high density lipoprotein fraction to flow by gravity through the second carrier matrix.
Claim 2
Independent Claim 276 words
A method of separating cellular components, low density lipoprotein fraction and very low density lipoprotein fraction from an undiluted whole blood sample consisting essentially of: (a) first directly contacting the undiluted whole blood sample with a first carrier matrix to separate the cellular components of the whole blood sample and provide a plasma or serum, wherein said first carrier matrix has incorporated therein about 25 to about 250 units of an agglutinin, about 50 to about 150 NIH units of a coagulant or a mixture thereof to agglutinize or coagulate the cellular components of the undiluted whole blood sample in the first carrier matrix; (b) then allowing the plasma or serum to migrate by gravity to a second carrier matrix that has the same dimensions and is in fluid communication with the first carrier matrix to separate the low density lipoprotein fraction and the very low density lipoprotein fraction from the plasma or serum, said second carrier matrix having a pore size of at least 1 to about 50 microns and having incorporated therein a precipitating reagent composition comprising a sufficient amount of a polyvalent metal ion and a sufficient amount of a precipitating compound to separate the low density lipoprotein fraction and the very low density lipoprotein fraction from the plasma or serum and to provide a serum or plasma including a high density lipoprotein fraction, wherein the precipitating compound is selected from the group consisting of dextran sulfate, heparin sodium, phosphotungstic acid, polyvinyl sulfate, sodium tungstate, ammonium molybdate, and mixtures thereof; and (c) then allowing the serum or plasma including the high density lipoprotein fraction to flow by gravity through the second carrier matrix.
Claim 3
Dependent Claim 56 words
The method of claim 1 further comprising treating the plasma or serum including the high density lipoprotein fraction that exits the second carrier matrix to assay for the presence or concentration of a predetermined constituent of the high density lipoprotein fraction, wherein said assay is independent of the amount of hematocrit in the whole blood sample.
Claim 4
Dependent Claim 157 words
The method of claim 1 wherein the agglutinin is a nonblood specific lectin selected from the group consisting of Abrus precatorius (abrin, Jequirty bean), Agaricus bisporous (mushroom), Bauhinia purpurea (camels foot tree), Caragana arborescens (Siberian pea tree), Cicer arietinum (chick pea), Codium fragile (Green marine algae), Canavalia ensiformis (Con A, Concanavalin A. Jack bean), Datura stramonium (jimson weed), Glycine max (Soybean), Lathyrus odoratus (Sweet Pea), Lens culinaris (Lentil), Limulus polyphemus (Horseshoe crab, Limulin), Lycopersicon esculentum (Tomato), Maclura pomifera (Osage orange), Mycoplasma gallisepticum, Naja mocambique mocambique (cobra venom), Naja Naja kaouthia (cobra venom), Perseau americana (Avocado), Phaseolus coccineus (Scarlet runner bean), Phaseolus vulgaris (Red Kidney bean), Phytolacca americana (Pokeweed), Pisum sativum (garden pea), Pseudomonas aeruginosa, Psophocarpus tetragonolobus (winged bean), Robinia pseudoacacia (Black locust, false locust), Sambucus nigra (elder), Solanum tuberosum (Potato), Triticum vulgaris (Wheat germ), Vicia faba (fava bean, broad bean), Vicia sativa, Vigna radiata (Mung bean), Viscum album (European mistletoe), Wisteria floribunda (Japanese wisteria) and mixtures thereof.
Claim 5
Dependent Claim 39 words
The method of claim 1 wherein the coagulant is selected from the group consisting of bovine thrombin, human thrombin, horse thrombin, goat thrombin, mouse thrombin, rat thrombin, pig thrombin, sheep thrombin, agkistrodon contortrix, ancrod, atroxin, crotalase, and mixtures thereof.
Claim 6
Independent Claim 390 words
A method of separating plasma or serum that is essentially free of cellular components, low density lipoproteins and very low density lipoproteins, from an undiluted whole blood sample and assaying the plasma or serum for a predetermined constituent of high density lipoproteins present in the plasma or serum consisting essentially of: (a) first directly contacting the undiluted whole blood sample with a first carrier matrix to separate the cellular components of the whole blood sample and to provide a plasma or serum, wherein said first carrier matrix has incorporated therein a separating reagent composition comprising about 25 to about 250 units an agglutinin, about 50 to about 150 NIH units of a coagulant or a mixture thereof to agglutinize or coagulate the cellular components of the undiluted whole blood sample in the first carrier matrix; (b) then allowing the plasma or serum to migrate by gravity to a second carrier matrix that has the same dimensions and is in fluid communication with the first carrier matrix to separate the low density lipoproteins and the very low density lipoproteins from the plasma or serum, said second carrier matrix having a pore size of at least 1 to about 50 microns and having incorporated therein a precipitating reagent comprising a sufficient amount of a polyvalent metal ion and a sufficient amount of a precipitating compound to separate the low density lipoproteins and the very low density lipoproteins from the plasma or serum and to provide a serum or plasma that is essentially free of cellular components, low density lipoproteins and very low density lipoproteins and that includes high density lipoproteins, wherein the precipitating compound is selected from the group consisting of dextran sulfate, heparin sodium, phosphotungstic acid, polyvinyl sulfate, sodium tungstate, ammonium molybdate, and mixtures thereof; (c) then allowing the serum or plasma including the high density lipoproteins to flow by gravity through the second carrier matrix to contact a test area incorporating a reagent composition to assay for the predetermined constituent of the high density lipoproteins in the plasma or serum, said reagent composition capable of interacting with the predetermined constituent of the high density lipoprotein to produce a detectable change in the test area; and (d) examining the test area for a detectable change, wherein the assay is independent of the amount of hematocrit present in the whole blood sample.
Claim 7
Independent Claim 390 words
A method of separating plasma or serum that is essentially free of cellular components, low density lipoproteins and very low density lipoproteins, from an undiluted whole blood sample and assaying the plasma or serum for a predetermined constituent of high density lipoproteins present in the plasma or serum consisting essentially of: (a) first directly contacting the undiluted whole blood sample with a first carrier matrix to separate the cellular components of the whole blood sample and to provide a plasma or serum, wherein said first carrier matrix has incorporated therein a separating reagent composition comprising about 25 to about 250 units an agglutinin, about 50 to about 150 NIH units of a coagulant or a mixture thereof to agglutinize or coagulate the cellular components of the undiluted whole blood sample in the first carrier matrix; (b) then allowing the plasma or serum to migrate by gravity to a second carrier matrix that has the same dimensions and is in fluid communication with the first carrier matrix to separate the low density lipoproteins and the very low density lipoproteins from the plasma or serum, said second carrier matrix having a pore size of at least 1 to about 50 microns and having incorporated therein a precipitating reagent comprising a sufficient amount of a polyvalent metal ion and a sufficient amount of a precipitating compound to separate the low density lipoproteins and the very low density lipoproteins from the plasma or serum and to provide a serum or plasma that is essentially free of cellular components, low density lipoproteins and very low density lipoproteins and that includes high density lipoproteins, wherein the precipitating compound is selected from the group consisting of dextran sulfate, heparin sodium, phosphotungstic acid, polyvinyl sulfate, sodium tungstate, ammonium molybdate, and mixtures thereof; (c) then allowing the serum or plasma including the high density lipoproteins to flow by gravity through the second carrier matrix to contact a test area incorporating a reagent composition to assay for the predetermined constituent of the high density lipoproteins in the plasma or serum, said reagent composition capable of interacting with the predetermined constituent of the high density lipoprotein to produce a detectable change in the test area; and (d) examining the test area for a detectable change, wherein the assay is independent of the amount of hematocrit present in the whole blood sample.
Claim 8
Dependent Claim 41 words
The method of claim 5 wherein the first carrier matrix is selected from the group consisting of inorganic powders, sponge materials, argillaceous substances, cloth, hydrophilic naturally-occurring polymers, hydrophilic naturally-occurring modified polymers, hydrophilic synthetic polymers, cellulosic materials, glass fibers, and mixtures thereof.
Claim 9
Dependent Claim 49 words
The method of claim 5 wherein the first carrier matrix is selected from the group consisting of silica gel, alumina, diatomaceous earth, filter paper, chromatographic paper, glass fiber, dellulose acetate, cellulosic beads, polyvinyl chloride, polyacrylamide, polyacrylate, polyurethane, crosslinked dextran, agarose, polyethylene, polypropylene, nylon, polyvinylidene fluoride, polysulfone, and mixtures thereof.
Claim 10
Dependent Claim 26 words
The method of claim 5 wherein the first carrier matrix has a pore size in the range of from about 0.1 micron to about 50 microns.
Claim 11
Dependent Claim 157 words
The method of claim 5 wherein the agglutinin is a nonblood specific lectin selected from the group consisting of Abrus precatorius (abrin, Jequirty bean), Agaricus bisporous (mushroom), Bauhinia purpurea (camels foot tree), Caragana arborescens (Siberian pea tree), Cicer arietinum (chick pea), Codium fragile (Green marine algae), Canavalia ensiformis (Con A, Concanavalin A, Jack bean), Datura stramonium (jimson weed), Glycine max (Soybean), Lathyrus odoratus (Sweet Pea), Lens culinaris (Lentil), Limulus polyphemus (Horseshoe crab, Limulin), Lycopersicon esculentum (Tomato), Maclura pomifera (Osage orange), Mycoplasma gallisepticum, Naja mocambique mocambique (cobra venom), Naja Naja kaouthia (cobra venom), Perseau americana (Avocado), Phaseolus coccineus (Scarlet runner bean), Phaseolus vulgaris (Red Kidney bean), Phytolacca americana (Pokeweed), Pisum sativum (garden pea), Pseudomonas aeruginosa, Psophocarpus tetragonolobus (winged bean), Robinia pseudoacacia (black locust, false locust), Sambucus nigra (elder), Solanum tuberosum (Potato), Triticum vulgaris (Wheat germ), Vicia faba (fava bean, broad bean), Vicia sativa, Vigna radiata (Mung bean), Viscum album (European mistletoe), Wisteria floribunda (Japanese wisteria) and mixtures thereof.
Claim 12
Dependent Claim 39 words
The method of claim 5 wherein the coagulant is selected from the group consisting of bovine thrombin, human thrombin, horse thrombin, goat thrombin, mouse thrombin, rat thrombin, pig thrombin, sheep thrombin, agkistrodon contortrix, ancrod, atroxin, crotalase, and mixtures thereof.
Claim 13
Dependent Claim 41 words
The method of claim 5 wherein the second carrier matrix is selected from the group consisting of inorganic powders, sponge materials, argilllaceous substances, cloth, hydrophilic naturally-occurring polymers, hydrophilic naturally-occurring modified polymers, hydrophilic synthetic polymers, cellulosic materials, glass fibers, and mixtures thereof.
Claim 14
Dependent Claim 49 words
The method of claim 5 wherein the second carrier matrix is selected from the group consisting of silica gel, alumina, diatomaceous earth, filter paper, chromatographic paper, glass fiber, cellulose acetate, cellulosic beads, polyvinyl chloride, polyacrylamide, polyacrylate, polyurethane, crosslinked dextran, agarose, polyethylene, polypropylene, nylon, polyvinylidene fluoride, polysulfone, and mixtures thereof.
Claim 15
Dependent Claim 15 words
The method of claim 5 wherein the polyvalent metal ion is a divalent metal ion.
Claim 16
Dependent Claim 28 words
The method of claim 13 wherein the divalent metal ion is selected from the group consisting of magnesium, calcium, manganese, cobalt, strontium, zinc, barium, copper, and mixtures thereof.
Claim 17
Dependent Claim 31 words
The method of claim 5 wherein the polyvalent metal ion is selected from the group consisting of aluminum, iron, chromium, magnesium, calcium, manganese, cobalt, strontium, zinc, barium, copper, and mixtures thereof.
Claim 18
Dependent Claim 36 words
The method of claim 5 wherein the precipitating reagent includes about 10 to about 1000 millimoles per liter of the polyvalent metal ion and about 0.1 to about 20 grams per liter of the precipitating compound.
Claim 19
Dependent Claim 16 words
The method of claim 5 wherein the predetermined constituent of the high density lipoproteins is cholesterol.
Claim 20
Dependent Claim 30 words
The method of claim 5 further comprising allowing the serum or plasma including the high density lipoproteins to flow through a third carrier matrix prior to contacting the test area.

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