Apparatus and methods for processing biological samples and a reservoir therefore

• US 20050281711A1
• Filed: 01/07/2005
• Published: 12/22/2005
• Est. Priority Date: 01/08/2004
• Status: Active Grant

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Dakocytomation California Incorporated
• Inventors: Matthiesen, Steen Hauge, Rasmussen, Ole Feldballe, Winther, Lars, Poulsen, Tim Svenstrup, Testa, Gregory A.
• Granted Patent: US 7,901,634 B2
• Time in Patent Office: Days
• US Class Current: 422/400
• CPC Class Codes: B01L 2200/142 Preventing evaporation
• CPC Class Codes: B01L 2300/043 Hinged closures
• CPC Class Codes: B01L 2300/069 Absorbents; Gels to retain a fluid
• CPC Class Codes: B01L 2300/0822 Slides
• CPC Class Codes: B01L 2300/10 Means to control humidity and/or other gases
• CPC Class Codes: B01L 2300/1822 using Peltier elements
• CPC Class Codes: B01L 2300/1844 using fans
• CPC Class Codes: B01L 3/508 rigid containers not provided for above
• CPC Class Codes: B01L 7/52 with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples amplification or hybridisation processes per se C12Q1/68; controlling sequential reactions for synthesis B01J19/0046
• CPC Class Codes: C12M 41/14 Incubators; Climatic chambers per se B01L1/00
• CPC Class Codes: C12M 41/36 of biomass, e.g. colony counters or by turbidity measurements electrooptical investigation of individual particles G01N15/14, flow cytometers G01N15/1404
• CPC Class Codes: C12Q 1/6841 In situ hybridisation
• CPC Class Codes: G01N 1/312 for samples mounted on planar substrates
• CPC Class Codes: Y10T 436/143333 Saccharide [e.g., DNA, etc.]

Abstract

An apparatus for processing biological samples comprising means for processing at least one biological sample accommodated on at least one carrier member (15) in a chamber, characterised in that at least one reservoir (18) able to accommodate a fluid is arranged on a surface inside the chamber adjacent to and/or facing a substantial part of the at least one biological sample. Preferably the apparatus comprises a bottom member (12) arranged to support at least one carrier member (15) carrying at least one biological sample and a lid (14) including at least one fluid reservoir (18). The reservoir filled with water provides humidity to the chamber and impedes drying out of the sample.

Claims

1. An apparatus for processing at least one biological sample on at least one carrier member in a chamber, the apparatus comprising a reservoir able to accommodate a fluid, wherein the reservoir is attached to a surface inside the chamber, the reservoir having at least one disposition chosen from the group consisting of being adjacent to a portion of the at least one biological sample and facing a portion of the at least one biological sample.

2. The apparatus of claim 1, wherein the reservoir is disposed above the sample.

3. The apparatus of claim 1, further comprising:

a bottom member supporting the at least one carrier member; and

a lid including the at least one reservoir.

4. The apparatus of claim 3, wherein the lid is provided with holding means supporting the at least one fluid reservoir such that the reservoir is disposed above the at least one biological sample when the lid is closed and covering the bottom member.

5. The apparatus of claim 1, wherein the reservoir is less than 5 cm from the carrier member.

6. The apparatus of claim 5, wherein the reservoir is less than 1.0 cm from the carrier member.

7. The apparatus of claim 5, wherein the reservoir is less than 0.5 cm from the carrier member.

8. The apparatus of claim 1, wherein a macroscopic surface area of the reservoir is greater than 10% of the total carrier member area.

9. The apparatus of claim 8, wherein the macroscopic surface area of the reservoir is greater than 30% of the total carrier member area.

10. The apparatus of claim 8, wherein the macroscopic surface area of the reservoir is greater than 60% of the total carrier member area.

11. The apparatus of claim 1, further comprising temperature controlling means controlling the temperature of the carrier member and the at least one biological sample.

12. The apparatus of claim 11, further comprising at least one temperature sensor connected to the temperature controlling means.

13. The apparatus of claim 11, wherein the temperature controlling means comprise heating wires.

14. The apparatus of claim 11, wherein the temperature controlling means comprise an inductive heater.

15. The apparatus of claim 11, wherein the temperature controlling means comprises cooling means for cooling the at least one biological sample.

16. The apparatus of claim 15, wherein the cooling means are chosen from the group consisting of a Peltier element and a fan.

17. The apparatus of claim 1, further comprising heating means for heating the reservoir.

18. The apparatus of claim 1, wherein relative humidity in the chamber is controlled by a temperature change produced by at least one member of the group consisting of means for heating the reservoir, means for cooling the reservoir, means for heating the at least one biological sample and means for cooling the at least one biological sample.

19. The apparatus of claim 1, further comprising:

first temperature controlling means for controlling the temperature of the at least one biological sample; and

second temperature controlling means for controlling the temperature of the reservoir, the first and second temperature controlling means being separately controlled so that the reservoir may be made warmer then the sample or vice versa.

20. The apparatus of claim 1, wherein the reservoir is shaped as a substantially flat sheet.

21. The apparatus of claim 20, wherein the thickness of the reservoir is less than 10% of the length of the reservoir.

22. The apparatus of claim 20, wherein the reservoir is attached to a lid and the carrier member lies upon a temperature-controlled plate, the lid, in a closed position, covering the at least one biological sample.

23. The apparatus of claim 20, wherein the reservoir is a lid, which, in a closed position, covers slides having respective temperature-controlled plates.

24. The apparatus of claim 20, wherein the reservoir is a lid, which, in a closed position, covers a plurality of slides lying upon a plurality of temperature-controlled plates.

25. The apparatus of claim 1, wherein the reservoir has a surface that is curved or uneven.

26. The apparatus of claim 1, wherein the reservoir has a corrugated surface.

27. The apparatus of claim 1, wherein the fluid is a liquid and the reservoir comprises a medium having at least one property chosen from the group consisting of adsorbing the liquid, desorbing the liquid and releasing the liquid.

28. The apparatus of claim 1, wherein the fluid is substantially pure water.

29. The apparatus of claim 1, wherein the fluid is water including at least one additive.

30. The apparatus of claim 29, wherein an additive is an anti-microbial agent.

31. The apparatus of claim 1, wherein the fluid is chosen from the group consisting of formamide, aqueous buffers, alcohols, dimethylformamide, dimethylsulfoxide, N-methyl-pyrolidone and non-aqueous buffers.

33. The apparatus of claim 1, wherein reservoir is made of a material having a high internal surface area comprising a plurality of cavities able to accommodate a fluid.

34. The apparatus of claim 1, wherein the reservoir is made of a material having a high internal surface area, and wherein at least a substantial portion of the reservoir surface or surfaces is hydrophilic.

35. The apparatus of claim 1, wherein the reservoir is made of a material from the group consisting of polymeric fiber composites, polymeric fiber blends, glass fiber materials, expanded porous polymers, porous ceramics, rockwool™

, wood pulp, cardboard, leather and cellulose-based materials.

36. The apparatus of claim 1, wherein the reservoir is made of a material comprising a composition chosen from the group consisting of polyethylene, polypropylene, polyurethanes, polysulfones, polyvinyl, polyacrylics, ethylene Vinyl Acetate, viscose rayon, polystyrene, macroreticular polystyrene, aliphatic polymers, phenol-formaldehyde condensate polymers, epoxy, cotton, polysaccharide, modified polysaccharides, wood pulp, calcium carbonate, silica gels, glass fiber, bentonite, perlite and zeolite.

37. The apparatus of claim 1, wherein the reservoir is made of a material from the group consisting of polymeric bonded fibers, non-bonded fibers, woven fibers, knitted fibers, micro fibers, textiles and tufted textiles.

38. The apparatus of claim 1, wherein the reservoir is made of a material from the group consisting of bonded polyamide fibers, polyester fibers, polyolefin fibers and cellulose acetate fibers.

39. The apparatus of claim 1, wherein the reservoir material is made of non-woven and bonded blends of hydrophilic modified polypropylene and polyethylene micro fibers.

40. The apparatus of claim 1, wherein the reservoir material is made of bundles of fibers or loose material retained by a thin wall of film.

41. The apparatus of claim 1, wherein the reservoir is impregnated with an anti microbial agent or other protective agent.

42. The apparatus of claim 1, wherein the type, shape and size of the reservoir material is selected to optimize surface properties to match with the liquid surface tension.

43. The apparatus of claim 1, wherein the reservoir material has a density from 0.050 to 1.5 gram/cm³.

44. The apparatus of claim 43, wherein the reservoir material has a density from 0.075 to 0.75 gram/cm³.

45. The apparatus claim 1, wherein the reservoir has the ability to hold at least a predefined minimum volume of liquid per carrier member.

46. The apparatus of claim 45, wherein the predefined minimum volume is 10 micro-liters.

47. The apparatus of claim 45, wherein the predefined minimum volume is 100 micro-liters.

48. The apparatus of claim 45, wherein the predefined minimum volume is 200 micro-liters.

49. The apparatus of claim 45, wherein the predefined minimum volume is 500 micro-liters.

50. The apparatus of claim 45, wherein the predefined minimum volume is 1000 micro-liters.

51. The apparatus of claim 3, further comprising a second reservoir on top of the lid and outside the chamber and in fluid communication with the reservoir inside the chamber.

32. The apparatus of claim I, wherein the fluid is a complex mixture having components chosen from the group consisting of inorganic salts, detergents, pH buffers, organic solvents, glycerol, oil and water.

52. A liquid-accommodating reservoir for an apparatus for processing at least one biological sample on at least one carrier member in a chamber, a portion of the biological sample being adjacent to the reservoir, the reservoir comprising a medium having at least one property chosen from the group consisting of adsorbing the liquid, desorbing the liquid and releasing the liquid.

53. The reservoir of claim 52, wherein the reservoir is shaped as a substantially flat sheet or plate.

54. The reservoir of claim 53, wherein the thickness of the reservoir is less than 10% of the length of the reservoir.

55. The reservoir of claim 52, wherein the reservoir has a surface that is curved or uneven.

56. The reservoir of claim 52, wherein the reservoir has a corrugated surface.

57. The reservoir of claim 52, wherein a macroscopic surface area of the reservoir is greater than 10% of the total carrier member area.

58. The reservoir of claim 57, wherein the macroscopic surface area is greater than 30% of the total carrier member area.

59. The reservoir of claim 57, wherein the macroscopic surface area is greater than 60% of the total carrier member area.

60. The reservoir of claim 52, wherein the reservoir is made of a material having a very high internal surface area comprising a plurality of cavities able to accommodate a fluid.

61. The reservoir of claim 52, wherein the reservoir is made of a material having a high internal surface area, and wherein at least a substantial portion of the reservoir surface or surfaces is hydrophilic.

62. The reservoir of claim 52, wherein the reservoir is made of a material from the group consisting of polymeric fiber composites, polymeric fiber blends, glass fiber materials, expanded porous polymers, porous ceramics, rockwool™

, wood pulp, cardboard, leather and cellulose-based materials.

63. The reservoir of claim 52, wherein the reservoir is made of a material comprising any of the compositions from the group consisting of polyethylene, polypropylene, polyurethanes, polysulfones, polyvinyl, polyacrylics, ethylene Vinyl Acetate, viscose rayon, polystyrene, macroreticular polystyrene, aliphatic polymers, phenol-formaldehyde condensate polymers, epoxy, cotton, polysaccharide, modified polysaccharides, wood pulp, calcium carbonate, silica gels, glass fiber, bentonite, perlite and zeolite.

64. The reservoir of claim 52, wherein the reservoir is made of a material from the group consisting of polymeric bonded fibers, non-bonded fibers, woven fibers, knitted fibers, micro fibers, textiles and tufted textiles.

65. The reservoir of claim 52, wherein the reservoir is made of a material from the group consisting of bonded polyamide fibers, polyester fibers, polyolefin fibers and cellulose acetate fibers.

66. The reservoir of claim 52, wherein the reservoir material is made of non-woven and bonded blends of hydrophilic modified polypropylene and polyethylene micro fibers.

67. The reservoir of claim 52, wherein the reservoir material is made of bundles of fibers or other loose material retained by a thin wall of film.

68. The reservoir of claim 52, wherein the reservoir is impregnated with an anti microbial agent or other protective agents.

69. The reservoir of claim 52, wherein the type, shape and size of the reservoir material is selected to optimize surface properties to match with the surface tension of a liquid.

70. The reservoir of claim 52, wherein the reservoir material has a density from 0.050 to 1.5 gram/cm³.

71. The reservoir of claim 70, wherein the reservoir material has a density from 0.075 to 0.75 gram/cm³.

72. The reservoir of claim 52, wherein the reservoir has the ability to hold at least a predefined minimum volume of liquid per carrier member.

73. The reservoir of claim 72, wherein the predefined minimum volume is 10 micro-liters.

74. The reservoir of claim 72, wherein the predefined minimum volume is 100 micro-liters.

75. The reservoir of claim 72, wherein the predefined minimum volume is 200 micro-liters.

76. The reservoir of claim 72, wherein the predefined minimum volume is 500 micro-liters.

77. The reservoir of claim 72, wherein the predefined minimum volume is 1000 micro-liters.

78. A method of processing biological samples, wherein at least one biological sample is arranged on a carrier member, for treatment to prepare the sample by staining, the method comprising the step of maintaining at least 80% relative humidity above the sample through the close presence of a reservoir containing water, the reservoir comprising a medium having at least one property chosen from the group consisting of adsorbing the water, desorbing the water and releasing the water.

79. The method of claim 78, wherein the thickness of the reservoir is less than 10% of the length of the reservoir.

80. The method of claim 78, wherein the reservoir has a surface that is curved or uneven.

81. The method of claim 78, wherein the reservoir has a corrugated surface.

82. The method of claim 78, wherein a macroscopic surface area of the reservoir is greater than 10% of the total carrier member area.

83. The method of claim 82, wherein the macroscopic surface area is greater than 30% of the total carrier member area.

84. The method of claim 82, wherein the macroscopic surface area is greater than 60% of the total carrier member area.

85. The method of claim 78, wherein the reservoir is made of a material having a high internal surface area comprising a plurality of cavities able to accommodate a fluid.

86. The method of claim 78, wherein the reservoir is made of a material having a high internal surface area, and wherein at least a substantial portion of the reservoir surface or surfaces is hydrophilic.

87. The method of claim 78, wherein the reservoir is made of a material from the group consisting of polymeric fiber composites, polymeric fiber blends, glass fiber materials, expanded porous polymers, porous ceramics, rockwool™

, wood pulp, cardboard, leather and cellulose-based materials.

88. The method of claim 78, wherein the reservoir is made of a material comprising any of the compositions from the group consisting of polyethylene, polypropylene, polyurethanes, polysulfones, polyvinyl, polyacrylics, ethylene Vinyl Acetate, viscose rayon, polystyrene, macroreticular polystyrene, aliphatic polymers, phenol-formaldehyde condensate polymers, epoxy, cotton, polysaccharide, modified polysaccharides, wood pulp, calcium carbonate, silica gels, glass fiber, bentonite, perlite and zeolite.

89. The method of claim 78, wherein the reservoir is made of a material from the group consisting of polymeric bonded fibers, non-bonded fibers, woven fibers, knitted fibers, micro fibers, textiles and tufted textiles.

90. The method of claim 78, wherein the reservoir is made of a material from the group consisting of bonded polyamide fibers, polyester fibers, polyolefin fibers and cellulose acetate fibers.

91. The method of claim 78, wherein the reservoir material is made of non-woven and bonded blends of hydrophilic modified polypropylene and polyethylene micro fibers.

92. The method of claim 78, wherein the reservoir material is made of bundles of fibers or other loose material retained by a thin wall of film.

93. The method of claim 78, wherein the reservoir is impregnated with an anti microbial agent or other protective agents.

94. The method of claim 78, wherein the type, shape and size of the reservoir material is selected to optimize surface properties to match with the surface tension of a liquid.

95. The method of claim 78, wherein the reservoir material has a density from 0.050 to 1.5 gram/cm³.

96. The method of claim 78, wherein the reservoir material has a density from 0.075 to 0.75 gram/cm³.

97. The method of claim 78, wherein the reservoir has the ability to hold at least a predefined minimum volume of liquid per carrier member.

98. The method of claim 97, wherein the predefined minimum volume is 10 micro-liters.

99. The method of claim 97, wherein the predefined minimum volume is 100 micro-liters.

100. The method of claim 97, wherein the predefined minimum volume is 200 micro-liters.

101. The method of claim 97, wherein the predefined minimum volume is 500 micro-liters.

102. The method of claim 97, wherein the predefined minimum volume is 1000 micro-liters.