Devices and compositions for preservation of cell-free nucleic acids

1. A direct blood draw tube comprising:

a composition formulated for stabilizing cell-free nucleic acids within a blood sample including:

a) one or more formaldehyde releaser preservative agents;

b) ethylenediaminetetraacetic acid (EDTA);

c) one or more solvents;

d) about 1% formaldehyde;

wherein the composition is free of separately added formaldehyde but contains the formaldehyde as a result of the one or more formaldehyde releaser preservative agents;

wherein an amount of composition within the direct blood draw tube prior to blood draw is less than, or about 1000 g/liter and is in an amount sufficiently small so that any consequential dilution of the blood sample is avoided; and

wherein the direct blood draw tube including the composition:

facilitates storage of the blood sample collected in the direct draw blood tube at room temperature for at least, or about 14 days without cell lysis and without cell-free nucleic acid degradation of the blood sample due to DNase and RNase activity after blood draw.

2. A direct blood draw tube comprising:

a composition formulated for stabilizing cell-free nucleic acids within a blood sample including:

a) one or more formaldehyde releaser preservative agents;

b) one or more protease inhibitors;

c) ethylenediaminetetraacetic acid (EDTA);

d) one or more solvents;

e) formaldehyde;

wherein the composition is free of separately added formaldehyde but contains the formaldehyde as a result of the one or more formaldehyde releaser preservative agents;

wherein an amount of composition within the direct blood draw tube prior to blood draw is less than, or about 1000 g/liter and is in an amount sufficiently small so that any consequential dilution of the blood sample is avoided; and

wherein the direct blood draw tube including the composition:

facilitates storage of a blood sample collected in the direct draw blood tube at room temperature for at least, or about 14 days without cell lysis and without cell-free nucleic acid degradation of the blood sample due to DNase and RNase activity after blood draw.

3. A direct blood draw tube comprising:

a composition formulated for stabilizing cell-free nucleic acids within a blood sample including:

a) one or more formaldehyde releaser preservative agents;

b) ethylenediaminetetraacetic acid (EDTA);

c) one or more solvents;

d) formaldehyde;

wherein the composition is free of separately added formaldehyde but contains the formaldehyde as a result of the one or more formaldehyde releaser preservative agents;

wherein an amount of the one or more formaldehyde releaser preservative agents relative to an amount of the EDTA is about 1 to about 10 parts by weight of the one or more formaldehyde releaser preservative agents to about 2 parts by weight of EDTA;

wherein an amount of composition within the direct blood draw tube prior to blood draw is less than, or about 1000 g/liter and is in an amount sufficiently small so that any consequential dilution of the blood sample is avoided; and

wherein the direct blood draw tube including the composition:

facilitates storage of the blood sample collected in the tube at room temperature for at least, or about 14 days without cell lysis and without cell-free nucleic acid degradation of the blood sample due to DNase and RNase activity after blood draw.

4. The tube of claim 1 , wherein the composition includes one or more metabolic inhibitors.

5. The tube of claim 2 , wherein the composition includes one or more metabolic inhibitors.

6. The tube of claim 3 , wherein the composition includes one or more metabolic inhibitors.

7. The tube of claim 1 , wherein the composition in the direct blood draw tube prior to the blood draw is in a form of a film, gel or other substantially solid or highly viscous layer that provides a substantially immobile coating that is re-dissolved or otherwise dispersed upon contact with the blood sample.

8. The tube of claim 2 , wherein the composition in the direct blood draw tube prior to the blood draw is in a form of a film, gel or other substantially solid or highly viscous layer that provides a substantially immobile coating that is re-dissolved or otherwise dispersed upon contact with the blood sample.

9. The tube of claim 3 , wherein the composition in the direct blood draw tube prior to the blood draw is in a form of a film, gel or other substantially solid or highly viscous layer that provides a substantially immobile coating that is re-dissolved or otherwise dispersed upon contact with the blood sample.

10. The tube of claim 4 , wherein the composition in the direct blood draw tube prior to the blood draw is in a form of a film, gel or other substantially solid or highly viscous layer that provides a substantially immobile coating that is re-dissolved or otherwise dispersed upon contact with the blood sample.

11. The tube of claim 5 , wherein the composition in the direct blood draw tube prior to the blood draw is in a form of a film, gel or other substantially solid or highly viscous layer that provides a substantially immobile coating that is re-dissolved or otherwise dispersed upon contact with the blood sample.

12. The tube of claim 6 , wherein the composition in the direct blood draw tube prior to the blood draw is in a form of a film, gel or other substantially solid or highly viscous layer that provides a substantially immobile coating that is re-dissolved or otherwise dispersed upon contact with the blood sample.

13. The tube of claim 1 , wherein, at least a portion of the blood sample upon contacting the composition will also contact an inner wall of the direct blood draw tube that is polymeric and includes a polymer selected from a silicon containing polymer, a polyolefin, polyethylene terephthalate, or any combination thereof.

14. The tube of claim 2 , wherein, at least a portion of a blood sample upon contacting the composition will also contact an inner wall of the direct blood draw tube that is polymeric and includes a polymer selected from a silicon containing polymer, a polyolefin, polyethylene terephthalate, or any combination thereof.

15. The tube of claim 3 , wherein, at least a portion of the blood sample upon contacting the composition will also contact an inner wall of the direct blood draw tube that is polymeric and includes a polymer selected from a silicon containing polymer, a polyolefin, polyethylene terephthalate, or any combination thereof.

16. The tube of claim 4 , wherein, at least a portion of the blood sample upon contacting the composition will also contact an inner wall of the direct blood draw tube that is polymeric and includes a polymer selected from a silicon containing polymer, a polyolefin, polyethylene terephthalate, or any combination thereof.

17. The tube of claim 5 , wherein, at least a portion of the blood sample upon contacting the composition will also contact an inner wall of the direct blood draw tube that is polymeric and includes a polymer selected from a silicon containing polymer, a polyolefin, polyethylene terephthalate, or any combination thereof.

18. The tube of claim 6 , wherein, at least a portion of the blood sample upon contacting the composition will also contact an inner wall of the direct blood draw tube that is polymeric and includes a polymer selected from a silicon containing polymer, a polyolefin, polyethylene terephthalate, or any combination thereof.

19. The tube of claim 7 , wherein, at least a portion of the blood sample upon contacting the composition will also contact an inner wall of the direct blood draw tube that is polymeric and includes a polymer selected from a silicon containing polymer, a polyolefin, polyethylene terephthalate, or any combination thereof.

20. The tube of claim 8 , wherein, at least a portion of the blood sample upon contacting the composition will also contact an inner wall of the direct blood draw tube that is polymeric and includes a polymer selected from a silicon containing polymer, a polyolefin, polyethylene terephthalate, or any combination thereof.

21. The tube of claim 9 , wherein, at least a portion of the blood sample upon contacting the composition will also contact an inner wall of the direct blood draw tube that is polymeric and includes a polymer selected from a silicon containing polymer, a polyolefin, polyethylene terephthalate, or any combination thereof.

22. The tube of claim 10 , wherein, at least a portion of the blood sample upon contacting the composition will also contact an inner wall of the direct blood draw tube that is polymeric and includes a polymer selected from a silicon containing polymer, a polyolefin, polyethylene terephthalate, or any combination thereof.

23. The tube of claim 11 , wherein, at least a portion of the blood sample upon contacting the composition will also contact an inner wall of the direct blood draw tube that is polymeric and includes a polymer selected from a silicon containing polymer, a polyolefin, polyethylene terephthalate, or any combination thereof.

24. The tube of claim 12 , wherein, at least a portion of the blood sample upon contacting the composition will also contact an inner wall of the direct blood draw tube that is polymeric and includes a polymer selected from a silicon containing polymer, a polyolefin, polyethylene terephthalate, or any combination thereof.

25. A method comprising isolating cell-free nucleic acids from a blood sample collected in the direct draw blood tube of claim 1 , wherein the isolating occurs six hours or more after a blood draw and following transport of the blood sample in the direct blood draw tube from a blood draw site to a remote site for the isolating, which is at least 3 kilometers from the blood draw site.

26. A method comprising isolating cell-free nucleic acids from a blood sample collected in the direct draw blood tube of claim 2 , wherein the isolating occurs six hours or more after a blood draw and following transport of the blood sample in the direct blood draw tube from a blood draw site to a remote site for the isolating, which is at least 3 kilometers from the blood draw site.

27. A method comprising isolating cell-free nucleic acids from a blood sample collected in the direct draw blood tube of claim 3 , wherein the isolating occurs at six hours or more after a blood draw and following transport of the blood sample in the direct blood draw tube from a blood draw site to a remote site for the isolating, which is at least 3 kilometers from the blood draw site.

28. A method comprising isolating cell-free nucleic acids from a blood sample collected in the direct draw blood tube of claim 4 , wherein the isolating occurs six hours or more after a blood draw and following transport of the blood sample in the direct blood draw tube from a blood draw site to a remote site for the isolating, which is at least 3 kilometers from the blood draw site.

29. A method comprising isolating cell-free nucleic acids from a blood sample collected in the direct draw blood tube of claim 5 , wherein the isolating occurs six hours or more after a blood draw and following transport of the blood sample in the direct blood draw tube from a blood draw site to a remote site for the isolating, which is at least 3 kilometers from the blood draw site.

30. A method comprising isolating cell-free nucleic acids from a blood sample collected in the direct draw blood tube of claim 6 , wherein the isolating occurs six hours or more after a blood draw and following transport of the blood sample in the direct blood draw tube from a blood draw site to a remote site for the isolating, which is at least 3 kilometers from the blood draw site.

31. A method comprising isolating cell-free nucleic acids from a blood sample collected in the direct draw blood tube of claim 7 , wherein the isolating occurs six hours or more after a blood draw and following transport of the blood sample in the direct blood draw tube from a blood draw site to a remote site for the isolating, which is at least 3 kilometers from the blood draw site.

32. A method comprising isolating cell-free nucleic acids from a blood sample collected in the direct draw blood tube of claim 8 , wherein the isolating occurs six hours or more after a blood draw and following transport of the blood sample in the direct blood draw tube from a blood draw site to a remote site for the isolating, which is at least 3 kilometers from the blood draw site.

33. A method comprising isolating cell-free nucleic acids from a blood sample collected in the direct draw blood tube of claim 9 , wherein the isolating occurs six hours or more after a blood draw and following transport of the blood sample in the direct blood draw tube from a blood draw site to a remote site for the isolating, which is at least 3 kilometers from the blood draw site.

34. A method comprising isolating cell-free nucleic acids from a blood sample collected in the direct draw blood tube of claim 10 , wherein the isolating occurs six hours or more after a blood draw and following transport of the blood sample in the direct blood draw tube from a blood draw site to a remote site for the isolating, which is at least 3 kilometers from the blood draw site.

35. A method comprising isolating cell-free nucleic acids from a blood sample collected in the direct draw blood tube of claim 11 , wherein the isolating occurs six hours or more after a blood draw and following transport of the blood sample in the direct blood draw tube from a blood draw site to a remote site for the isolating, which is at least 3 kilometers from the blood draw site.

36. A method comprising isolating cell-free nucleic acids from a blood sample collected in the direct draw blood tube of claim 12 , wherein the isolating occurs six hours or more after a blood draw and following transport of the blood sample in the direct blood draw tube from a blood draw site to a remote site for the isolating, which is at least 3 kilometers from the blood draw site.

37. A method comprising isolating cell-free nucleic acids from a blood sample collected in the direct draw blood tube of claim 13 , wherein the isolating occurs six hours or more after a blood draw and following transport of the blood sample in the direct blood draw tube from a blood draw site to a remote site for the isolating, which is at least 3 kilometers from the blood draw site.

38. A method comprising isolating cell-free nucleic acids from a blood sample collected in the direct draw blood tube of claim 14 , wherein the isolating occurs six hours or more after a blood draw and following transport of the blood sample in the direct blood draw tube from a blood draw site to a remote site for the isolating, which is at least 3 kilometers from the blood draw site.

39. A method comprising isolating cell-free nucleic acids from a blood sample collected in the direct draw blood tube of claim 15 , wherein the isolating occurs six hours or more after a blood draw and following transport of the blood sample in the direct blood draw tube from a blood draw site to a remote site for the isolating, which is at least 3 kilometers from the blood draw site.

40. A method comprising isolating cell-free nucleic acids from a blood sample collected in the direct draw blood tube of claim 16 , wherein the isolating occurs six hours or more after a blood draw and following transport of the blood sample in the direct blood draw tube from a blood draw site to a remote site for the isolating, which is at least 3 kilometers from the blood draw site.

41. A method comprising isolating cell-free nucleic acids from a blood sample collected in the direct draw blood tube of claim 17 , wherein the isolating occurs six hours or more after a blood draw and following transport of the blood sample in the direct blood draw tube from a blood draw site to a remote site for the isolating, which is at least 3 kilometers from the blood draw site.

42. A method comprising isolating cell-free nucleic acids from a blood sample collected in the direct draw blood tube of claim 18 , wherein the isolating occurs six hours or more after a blood draw and following transport of the blood sample in the direct blood draw tube from a blood draw site to a remote site for the isolating, which is at least 3 kilometers from the blood draw site.

43. A method comprising isolating cell-free nucleic acids from a blood sample collected in the direct draw blood tube of claim 19 , wherein the isolating occurs six hours or more after a blood draw and following transport of the blood sample in the direct blood draw tube from a blood draw site to a remote site for the isolating, which is at least 3 kilometers from the blood draw site.

44. A method comprising isolating cell-free nucleic acids from a blood sample collected in the direct draw blood tube of claim 20 , wherein the isolating occurs six hours or more after a blood draw and following transport of the blood sample in the direct blood draw tube from a blood draw site to a remote site for the isolating, which is at least 3 kilometers from the blood draw site.

45. A method comprising isolating cell-free nucleic acids from a blood sample collected in the direct draw blood tube of claim 21 , wherein the isolating occurs six hours or more after a blood draw and following transport of the blood sample in the direct blood draw tube from a blood draw site to a remote site for the isolating, which is at least 3 kilometers from the blood draw site.

46. A method comprising isolating cell-free nucleic acids from a blood sample collected in the direct draw blood tube of claim 22 , wherein the isolating occurs six hours or more after a blood draw and following transport of the blood sample in the direct blood draw tube from a blood draw site to a remote site for the isolating, which is at least 3 kilometers from the blood draw site.

47. A method comprising isolating cell-free nucleic acids from a blood sample collected in the direct draw blood tube of claim 23 , wherein the isolating occurs six hours or more after a blood draw and following transport of the blood sample in the direct blood draw tube from a blood draw site to a remote site for the isolating, which is at least 3 kilometers from the blood draw site.

48. A method comprising isolating cell-free nucleic acids from a blood sample collected in the direct draw blood tube of claim 24 , wherein the isolating occurs six hours or more after a blood draw and following transport of the blood sample in the direct blood draw tube from a blood draw site to a remote site for the isolating, which is at least 3 kilometers from the blood draw site.

49. A method comprising performing polymerase chain reaction on a sample obtained in the direct blood draw tube of claim 1 .

50. A method comprising performing polymerase chain reaction on a sample obtained in the direct blood draw tube of claim 2 .

51. A method comprising performing polymerase chain reaction on a sample obtained in the direct blood draw tube of claim 3 .

52. A method comprising performing polymerase chain reaction on a sample obtained in the direct blood draw tube of claim 4 .

53. A method comprising performing polymerase chain reaction on a sample obtained in the direct blood draw tube of claim 5 .

54. A method comprising performing polymerase chain reaction on a sample obtained in the direct blood draw tube of claim 6 .

55. A method for storing a blood sample at ambient temperatures for at least 24 hours where cell lysis is substantially prevented using the direct blood draw tube of claim 1 .

56. A method for storing a blood sample at ambient temperatures for at least 24 hours where cell lysis is substantially prevented using the direct blood draw tube of claim 2 .

57. A method for storing a blood sample at ambient temperatures for at least 24 hours where cell lysis is substantially prevented using the direct blood draw tube of claim 3 .

58. A method for storing a blood sample at ambient temperatures for at least 24 hours where cell lysis is substantially prevented using the direct blood draw tube of claim 4 .

59. A method for storing a blood sample at ambient temperatures for at least 24 hours where cell lysis is substantially prevented using the direct blood draw tube of claim 5 .

60. A method for storing a blood sample at ambient temperatures for at least 24 hours where cell lysis is substantially prevented using the direct blood draw tube of claim 6 .

61. The method of claim 25 , wherein the isolating includes using proteinase K.

62. The method of claim 26 , wherein the isolating includes using proteinase K.

63. The method of claim 27 , wherein the isolating includes using proteinase K.

64. The method of claim 28 , wherein the isolating includes using proteinase K.

65. The method of claim 29 , wherein the isolating includes using proteinase K.

66. The method of claim 30 , wherein the isolating includes using proteinase K.

67. The method of claim 31 , wherein the isolating includes using proteinase K.

68. The method of claim 32 , wherein the isolating includes using proteinase K.

69. The method of claim 33 , wherein the isolating includes using proteinase K.

70. The method of claim 34 , wherein the isolating includes using proteinase K.

71. The method of claim 35 , wherein the isolating includes using proteinase K.

72. The method of claim 36 , wherein the isolating includes using proteinase K.

73. The method of claim 37 , wherein the isolating includes using proteinase K.

74. The method of claim 38 , wherein the isolating includes using proteinase K.

75. The method of claim 39 , wherein the isolating includes using proteinase K.

76. The method of claim 40 , wherein the isolating includes using proteinase K.

77. The method of claim 41 , wherein the isolating includes using proteinase K.

78. The method of claim 42 , wherein the isolating includes using proteinase K.

79. The method of claim 43 , wherein the isolating includes using proteinase K.

80. The method of claim 44 , wherein the isolating includes using proteinase K.

81. The method of claim 45 , wherein the isolating includes using proteinase K.

82. The method of claim 46 , wherein the isolating includes using proteinase K.

83. The method of claim 47 , wherein the isolating includes using proteinase K.

84. The method of claim 48 , wherein the isolating includes using proteinase K.

85. The tube of claim 1 , wherein the tube includes one or more formaldehyde releaser preservative agents, and one or both of imidazolidinyl urea (IDU) and a buffered salt solution.

86. The tube of claim 2 , wherein the tube includes one or more formaldehyde releaser preservative agents, and one or both of imidazolidinyl urea (IDU) and a buffered salt solution.

87. The tube of claim 3 , wherein the tube includes one or more formaldehyde releaser preservative agents, and one or both of imidazolidinyl urea (IDU) and a buffered salt solution.

88. The tube of claim 4 , wherein the tube includes one or more formaldehyde releaser preservative agents, and one or both of imidazolidinyl urea (IDU) and a buffered salt solution.

89. The tube of claim 5 , wherein the tube includes one or more formaldehyde releaser preservative agents, and one or both of imidazolidinyl urea (IDU) and a buffered salt solution.

90. The tube of claim 6 , wherein the tube includes one or more formaldehyde releaser preservative agents, and one or both of imidazolidinyl urea (IDU) and a buffered salt solution.

91. The tube of claim 7 , wherein the tube includes one or more formaldehyde releaser preservative agents, and one or both of imidazolidinyl urea (IDU) and a buffered salt solution.

92. The tube of claim 8 , wherein the tube includes one or more formaldehyde releaser preservative agents, and one or both of imidazolidinyl urea (IDU) and a buffered salt solution.

93. The tube of claim 9 , wherein the tube includes one or more formaldehyde releaser preservative agents, and one or both of imidazolidinyl urea (IDU) and a buffered salt solution.

94. The tube of claim 10 , wherein the tube includes one or more formaldehyde releaser preservative agents, and one or both of imidazolidinyl urea (IDU) and a buffered salt solution.

95. The tube of claim 11 , wherein the tube includes one or more formaldehyde releaser preservative agents, and one or both of imidazolidinyl urea (IDU) and a buffered salt solution.

96. The tube of claim 12 , wherein the tube includes one or more formaldehyde releaser preservative agents, and one or both of imidazolidinyl urea (IDU) and a buffered salt solution.

97. The tube of claim 1 , wherein the tube includes 2-bromo-2-nitropropane-1,3-diol.

98. The tube of claim 2 , wherein the tube includes 2-bromo-2-nitropropane-1,3-diol.

99. The tube of claim 3 , wherein the tube includes 2-bromo-2-nitropropane-1,3-diol.

100. The tube of claim 4 , wherein the tube includes 2-bromo-2-nitropropane-1,3-diol.

101. The tube of claim 5 , wherein the tube includes 2-bromo-2-nitropropane-1,3-diol.

102. The tube of claim 6 , wherein the tube includes 2-bromo-2-nitropropane-1,3-diol.

103. The tube of claim 7 , wherein the tube includes 2-bromo-2-nitropropane-1,3-diol.

104. The tube of claim 8 , wherein the tube includes 2-bromo-2-nitropropane-1,3-diol.

105. The tube of claim 9 , wherein the tube includes 2-bromo-2-nitropropane-1,3-diol.

106. The tube of claim 10 , wherein the tube includes 2-bromo-2-nitropropane-1,3-diol.

107. The tube of claim 11 , wherein the tube includes 2-bromo-2-nitropropane-1,3-diol.

108. The tube of claim 12 , wherein the tube includes 2-bromo-2-nitropropane-1,3-diol.