Direct measurement of HDL cholesterol via dry chemistry strips

• US 5,135,716 A
• Filed: 02/25/1991
• Issued: 08/04/1992
• Est. Priority Date: 07/12/1989
• Status: Expired due to Term

• Current Assignee: Polymer Technology Systems Incorporated (Sinocare, Inc.)
• Original Assignee: Kingston Diagnostics, L.P.
• Inventors: Thakore, Yatin B.
• Primary Examiner(s): Housel, James C.
• Assistant Examiner(s): Snay, Jeffrey R.
• Application Number:
  US07/660,429
• Time in Patent Office: 526 Days
• Field of Search: 422/56, 422/57, 422/58, 422/73, 436/17, 436/71, 435/11, 435/805
• US Class Current: 422/412
• CPC Class Codes: B01D 61/18 Apparatus therefor
• CPC Class Codes: B01L 2300/0681 Filter
• CPC Class Codes: B01L 2300/0825 Test strips
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 3/5023 with a sample being transported to, and subsequently stored in an absorbent for analysis
• CPC Class Codes: G01N 33/5002 Partitioning blood components
• CPC Class Codes: G01N 33/526 the element being adapted for a specific analyte
• CPC Class Codes: G01N 33/92 involving lipids, e.g. cholesterol , lipoproteins, or their receptors steroid hormones G01N33/743
• CPC Class Codes: Y10S 435/805 Test papers
• CPC Class Codes: Y10T 436/107497 Preparation composition [e.g., lysing or precipitation, etc.]

Abstract

A device for determining HDL cholesterol by obtaining plasma from whole blood and determining the HDL cholesterol level from the plasma. The device includes an inert substrate support or an active substrate support (e.g. one or the other layers), a physical transport medium, a microporous plasma separation membrane connected to the physical transport medium, at least one plasma collecting test membrane, a filtering membrane, LDL and VLDL reactants to form LDL and VLDL precipitates and an optional carrier precipitation membrane. The plasma collecting test membrane has reactants which will react with HDL cholesterol and indicate the HDL cholesterol level quantitatively. The filtering membrane may be located between the microporous plasma separation membrane and the transport medium or between the microporous plasma membrane and the plasma collecting test membrane and its function is to block the precipitated particles from reaching the test zone. The LDL and VLDL reactants which form precipitates of LDL and VLDL may be located anywhere upstream from the plasma collecting test membrane, i.e., within one or more of the transport medium, the microporous plasma separation membrane, the filtering membrane and the optional carrier separation membrane.

Claims

1. A device for determining HDL cholesterol by obtaining plasma from whole blood and determining HDL level from the plasma which comprises:

(a) a physical transport medium;

(b) a microporous plasma separation membrane having a first surface against said physical transport medium and having a second surface opposite and away from said physical transport medium;

(c) a filtering membrane having a first surface and a second surface and being capable of filtering LDL and VLDL precipitates from a blood or plasma flow containing these, said filtering membrane having its first surface in contact with said microporous plasma separation membrane;

(d) at least one plasma collecting test membrane in contact with a portion of said second surface of said filtering membrane and having one or more reactants therein capable of reacting with said plasma to display at least one characteristic of HDL cholesterol; and

,

(e) LDL and VLDL reactants to form LDL and VLDL precipitates, said reactants being located in one or more of said microporous plasma separation membrane, said filtering membrane and said physical transport medium.

2. The device of claim 1 wherein a portion of said physical transport medium is not in contact with the microporous plasma separation membrane and is exposed for applying a sample of blood thereto.

3. The device of claim 1 wherein said physical transport medium relies, at least in part, on capillary forces to move the blood.

4. The device of claim 3 wherein said physical transport medium is a transport membrane sheet.

5. The device of claim 3 wherein said physical transport medium is an open structured mesh with openings of at least 1 micron in size and having hydrophilic surfaces.

6. The device of claim 3 wherein said microporous plasma separation membrane has a nominal pore size of about 0.02 to about 10 microns.

7. The device of claim 1 wherein said physical transport medium is a transport membrane sheet.

8. The device of claim 7 wherein said transport membrane sheet is a sheet of fabric selected from woven fabric, non-woven fabric, gauze and monofilament yarn.

9. The device of claim 1 wherein said LDL and VLDL reactants are contained in said physical transport medium.

10. The device of claim 1 wherein said physical transport medium constitutes grooves or channels formed on an inert substrate to promote movement of blood.

11. The device of claim 10 wherein said LDL and VLDL reactants are contained within the grooves or channels formed in said inert substrate.

12. The device of claim 1 wherein said physical transport medium is an open-structured mesh with openings of at least 1 micron in size and having hydrophilic surfaces.

13. The device of claim 1 wherein said LDL and VLDL reactants are contained in said microporous plasma separation membrane.

14. The device of claim 1 wherein said microporous plasma separation membrane has a nominal pore size of about 0.02 to about 10 microns.

15. The device of claim 1 wherein said microporous plasma separation membrane is a skinned membrane.

16. The device of claim 21 wherein said microporous plasma separation membrane is cellulosic.

17. The device of claim 1 wherein said microporous plasma separation membrane is of nitrocellulose.

18. The device of claim 1 wherein said filtering membrane is a membrane having a pore size of less than about 1 micron.

19. The device of claim 18 wherein said filtering membrane has a pore size of about 0.2 to about 0.8 microns.

20. The device of claim 18 wherein said filtering membrane is an asymmetric membrane with the second surface in contact with the plasma collecting test membrane having smaller pores in the pore size range of 0.01 to 0.1 micron.

21. The device of claim 18 wherein said filtering membrane has uniform cylindrical pores.

22. The device of claim 1 further comprising:

(f) an absorbent storage medium connected to said physical transport medium wherein said physical transport medium moves excess blood to said absorbent storage medium to prevent excess blood from retarding the effectiveness of said plasma collecting test membrane.

23. The device of claim 22 further including at least one inert substrate to which at least one of said microporous plasma separation membrane, said plasma collecting test membrane and said physical transport medium is connected.

24. The device of claim 1 wherein said plasma collecting test membrane includes one or more reactants which react with HDL cholesterol in said plasma to effect colorimetric reactions of HDL cholesterol for colorimertic determination of HDL cholesterol level.

25. The device of claim 1 further including at least one inert substrate to which at least one of said microporous plasma separation membrane, said plasma collecting test membrane and said physical transport medium is connected.

26. The device of claim 25 wherein said inert substrate support contains grooves or channels to promote movement of blood.

27. The device of claim 26 wherein said LDL and VLDL reactants are located in said grooves or channels in inert substrate support.

28. The device of claim 1 which further comprises:

(g) a top sheet containing at least one orifice through which a blood sample may be applied onto the physical transport medium, and at least a portion of this top sheet overlying said plasma collecting test membranes, said portion having transparent areas to view one or more colorimetric reactions.

29. The device of claim 28 wherein portions of said transparent areas on the top sheet havwe apertures to ensure oxygen transport to the plasma collecting test membrane for reactions that utilize oxygen.

30. The device of claim 29 wherein said apertures for oxygen transport are covered by transparent oxygen permeable membranes.

31. A device for determining HDL cholesterol by obtaining plasma from whole blood and determining HDL level from the plasma which comprises:

(a) a physical transport medium;

(b) a filtering membrane having a first surface and a second surface and being capable of filtering LDL and VLDL precipitates from a blood or plasma flow containing these, said filtering membrane having its first surface in contact with physical transport medium;

(c) a microporous plasma separation membrane having a first surface against the second surface of filtering membrane and having a second surface opposite and away from said second surface of said filtering membrane;

(d) at least one plasma collecting test membrane in contact with a portion of said second surface of said microporous plasma separation membrane and having one or more reactants therein capable of reacting with said plasma to display at least one characteristic of HDL cholesterol; and

,

(e) LDL and VLDL reactants to form LDL and VLDL precipitants, said reactants being located in one or more of said filtering membrane and said physical transport medium.

32. The device of claim 31 wherein a portion of said physical transport medium is not in contact with said filtering membrane and is exposed for applying a sample of blood thereto.

33. The device of claim 31 wherein said physical transport medium relies, at least in part, on capillary forces to move the blood.

34. The device of claim 33 wherein said physical transport medium is a transport membrane sheet.

35. The device of claim 33 wherein said physical transport medium is an open structured mesh with openings of at least 1 micron in size and having hydrophilic surfaces.

36. The device of claim 33 wherein said microporous plasma separation membrane has a nominal pore size of about 0.02 to about 10 microns.

37. The device of claim 31 wherein said physical transport medium is a transport membrane sheet.

38. The device of claim 37 wherein said transport membrane sheet is a sheet of fabric selected from woven fabric, non-woven fabric, gauze and monofilament yarn.

39. The device of claim 31 wherein said LDL and VLDL reactants are contained in said physical transport medium.

40. The device of claim 31 wherein said physical transport medium constitutes grooves or channels formed on an inert substrate to promote movement of blood.

41. The device of claim 40 wherein said LDL and VLDL reactants are contained in said grooves or channels formed on said inert substrate.

42. The device of claim 31 wherein said physical transport medium is an open-structured mesh with openings of at least 1 micron in size and having hydrophilic surfaces.

43. The device of claim 31 wherein said microporous plasma separation membrane has a nominal pore size of about 0.02 to about 10 microns.

44. The device of claim 31 wherein said mocroporous plasma separation membrane is a skinned membrane.

45. The device of claim 31 wherein said microporous plasma separation membrane is cellulosic.

46. The device of claim 31 wherein said microporous plasma separation membrane is of nitrocellulose.

47. The device of claim 31 wherein said filtering membrane is a membrane having a pore size of less than about 1 micron.

48. The device of claim 47 wherein said filtering membrane has a pore size of about 0.01 to about 0.8 microns.

49. The device of claim 47 wherein said filtering membrane is an asymmetric membrane with the second surface in contact with the microporous plasma separating membrane having smaller pores in the pore size range of 0.01 to 0.1 micron.

50. The device of claim 47 wherein said filtering membrane has uniform cylindrical pores.

51. The device of claim 31 further comprising:

(f) an absorbent storage medium connected to said physical transport medium wherein said physical transport medium moves excess blood to said absorbent storage medium to prevent excess blood from retarding the effectiveness of said plasma collecting test membrane.

52. The device of claim 51 further including at least one inert substrate to which at least one of said microporous plasma separation membrane, said plasma collecting test membrane and said physical transport medium is connected.

53. The device of claim 31 wherein said plasma collecting test membrane includes one or more reactants which react with HDL cholesterol in said plasma to effect colorimetric reactions of HDL for colorimetric determination of HDL cholesterol level.

54. The device of claim 31 further including at least one inert substrate to which at least one of said microporous separation membrane, said plasma collecting test membrane and said physical transport medium is connected.

55. The device of claim 54 wherein said inert substrate support contains grooves or channels to promote movement of blood.

56. The device of claim 55 wherein said LDL and VLDL reactants are located in said grooves or channels in said inert substrate support.

57. The device of claim 31 which further comprises:

(g) a top sheet containing at least one orifice through which a blood sample may be applied onto the physical transport medium, and at least a portion of this top sheet overlying said plasma collecting test membranes, said portion having transparent areas to view one or more colorimetric reactions.

58. The device of claim 57 wherein portions of said transparent areas on the top sheet have apertures to ensure oxygen transport to the plasma collecting test membrane for reactions that utilize oxygen.

59. The device of claim 58 wherein said apertures for oxygen transport are covered by transparent oxygen permeable membranes.

60. A device for determining HDL cholesterol by obtaining plasma from whole blood and determining HDL level from the plasma which comprises:

(a) a physical transport medium;

(b) a microporous plasma separation membrane having a first surface against said physical transport medium and having a second surface opposite and away from said physical transport medium.

(c) A carrier precipitant membrane containing reactants for precipitation of LDL and VLDL from plasma having a first surface and a second surface, said first surface in contact with said microporous plasma separation membrane and said second surface opposite and away from said microporous plasma separation membrane;

(d) a filtering membrane having a first surface and a second surface and being capable of filtering LDL and VLDL precipitates from a blood or plasma flow containing these, said filtering membrane having its first surface in contact with said carrier precipitant membrane; and

,

(e) at least one plasma collecting test membrane in contact with a portion of said second surface of said microporous plasma separation membrane and having one or more reactants therein capable of reacting with said plasma to display at least one characteristic of HDL cholesterol.

61. The device of claim 60 wherein a portion of said physical transport medium is not connected to the microporous plasma separation membrane and is exposed for applying a sample of blood thereto.

62. The device of claim 60 wherein said physical transport medium relies, at least in part on capillary forces to move the blood.

63. The device of claim 62 wherein said physical transport medium is a transport membrane sheet.

64. The device of claim 62 wherein said physical transport medium is an open structured mesh with openings of at least 1 micron in size and having hydrophilic surfaces.

65. The device of claim 62 wherein said microporous plasma separation membrane has a nominal pore size of about 0.02 to about 10 microns.

66. The device of claim 60 wherein said physical transport medium is a transport membrane sheet.

67. The device of claim 66 wherein said transport membrane sheet is a sheet of fabric selected from woven fabric, non-woven fabric, gauze and monofilament yarn.

68. The device of claim 60 wherein said physical transport medium constitutes grooves or channels formed on an inert substrate to promote movement of blood.

69. The device of claim 60 wherein said physical transport medium is an open-structured mesh with openings of at least 1 micron in size and having hydrophilic surfaces.

70. The device of claim 60 wherein said microporous plasma separation membrane has a nominal pore size of about 0.02 to about 10 microns.

71. The device of claim 60 wherein said micorporous plasma separation membrane is a skinned membrane.

72. The device of claim 60 wherein said microporous plasma separation membrane is cellulosic.

73. The device of claim 60 wherein said microporous plasma separation membrane is of nitrocellulose.

74. The device of claim 60 wherein said filtering membrane is a membrane having a pore size of less than about 1 micron.

75. The device of claim 74 wherein said filtering membrane has a pore size of about 0.01 to about 0.8 microns.

76. The device of claim 74 wherein said filtering membrane has uniform cylindrical pores.

77. The device of claim 60 wherein said carrier precipitant membrane has pore sizes in the range of 0.01 to 25 microns.

78. The device of claim 60 wherein said carrier precipitant membrane is polysulfone.

79. The device of claim 60 further comprising:

(f) an absorbent storage medium connected to said physical transport medium wherein said physical transport medium moves excess blood to said absorbent storage medium to prevent excess blood from retarding the effectiveness of said plasma collecting test membrane.

80. The device of claim 79 further including at least one inert substrate to which at least one of said microporous plasma separation membrane, said carrier precipitant membrane, said plasma collecting test membrane membrane and said physical transport medium is connected.

81. The device of claim 60 wherein said plasma collecting test membrane includes one or more reactants which react with HDL cholesterol in said plasma to effect colorimetric reactions of HDL for colorimetric determination of HDL cholesterol level.

82. The device of claim 60 wherein said filtering membrane and said plasma collecting test membrane are combined into a single membrane.

83. The device of claim 82 wherein said single membrane is an asymmetric membrane with pore sizes in the range of 0.02 to 0.1 microns with the finer pores located in contact with said second surface of said carrier precipitant membrane.

84. The device of claim 83 wherein said asymmetric membrane includes one or more reactants which react with HDL cholesterol in said plasma to effect colorimetric reactions of HDL for colorimetric determination of HDL cholesterol level.

85. The device of claim 60 wherein said carrier precipitant membrane and said filtering membrane are combined into a single membrane.

86. The device of claim 85 wherein said single membrane is an asymmetric membrane with the finer pores in the pore range of 0.02 to 1.0 micron located in contact with said first surface of said plasma collecting test membrane.

87. The device of claim 85 wherein said single membrane is a membrane with ultramicroporous structure with pore size in the range of 0.01 to 0.1 microns.

88. The device of claim 60 further including at least one inert substrate to which at least one of said microporous separation membrane, said carrier precipitant membrane, said plasma collecting test membrane and said physical transport medium is connected.

89. The device of claim 60 which further comprises:

(g) a top sheet containing at least one orifice through which a blood sample may be applied onto the physical transport medium, and at least a portion of this top sheet overlying said plasma collecting test membrane, said portion having transparent areas to view one or more colorimetric reactions.

90. The device of claim 89 wherein portions of said transparent areas on the top sheet have apertures to ensure oxygen transport to the plasma collecting test membrane for reactions that utilize oxygen.

91. The device of claim 90 wherein said apertures for oxygen transport are covered by transparent oxygen permeable membranes.