Flexible heating cover assembly for thermal cycling of samples of biological material

• US 6,730,883 B2
• Filed: 10/02/2002
• Issued: 05/04/2004
• Est. Priority Date: 10/02/2002
• Status: Active Grant

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Stratagene California
• Inventors: Brown, Larry R., Zajac, Kenneth J., Brumley, William D.
• Primary Examiner(s): PELHAM, JOSEPH MOORE
• Application Number:
  US10/262,994
• Publication Number:
  US 20040065655A1
• Time in Patent Office: 580 Days
• Field of Search: 219/385, 219/428, 219/429, 219/430, 219/436, 219/521, 219/528, 219/530, 219/535, 219/549, 435/289.1, 435/288.4, 435/286.1, 435/305.3, 435/305.4
• US Class Current: 219/428
• CPC Class Codes: B01L 2300/046 Function or devices integrated in the closure
• CPC Class Codes: B01L 2300/0829 Multi-well plates; Microtitration plates
• CPC Class Codes: B01L 2300/1822 using Peltier elements
• CPC Class Codes: B01L 2300/1827 using resistive heater
• CPC Class Codes: B01L 2300/1844 using fans
• CPC Class Codes: B01L 3/50851 specially adapted for heating or cooling samples laboratory heating apparatus B01L7/00; incubators C12M
• CPC Class Codes: B01L 3/50853 with covers or lids
• 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: B01L 7/54 using spatial temperature gradients

Abstract

A flexible heating cover assembly for an apparatus for heating samples of biological material with substantial temperature uniformity includes a housing having a plurality of engageable enclosure components; a resistive heater having a plurality of heater element areas; a heater backing plate providing stability to the resistive heater; a force distribution system that distributes a force over the heater backing plate; and a support plate providing stiffness for the force distribution system, wherein the arrangement of the resistive heater, the heater backing plate, the force distribution system and the support plate provide substantial temperature uniformity among a plurality of sample tubes for receiving samples of biological material. The flexible heating cover assembly improves the uniformity, efficiency, quality, reliability and controllability of the thermal response during thermal cycling of the biological material.

Claims

1. A flexible heating cover assembly comprising:

a housing including a plurality of engageable enclosure components;

a resistive heater located within the housing, the resistive heater including a plurality of heater element areas;

a heater backing plate engaging the resistive heater and providing stability to the resistive heater;

a force distribution system that engages the heater backing plate and distributes a force over the heater backing plate; and

a support plate providing stiffness for the force distribution system,

wherein the arrangement of the resistive heater, the heater backing plate, the force distribution system and the support plate provide substantial temperature uniformity among a plurality of sample tubes for receiving samples of biological material.

2. The flexible heating cover assembly of claim 1 wherein the housing further comprises a pair of end caps and a pair of side bars all composed of a thermally insulating material.

3. The flexible heating cover assembly of claim 1 wherein the resistive heater is thin to allow rapid heating and cooling during thermal cycling of the plurality of sample tubes.

4. The flexible heating cover assembly of claim 1 wherein the resistive heater produces a non-uniform heat distribution along a surface exposed to the plurality of sample tubes.

5. The flexible heating cover assembly of claim 1 wherein the resistive heater further comprises a plurality of heater element areas including at least one outer heater element area and at least one central heater element area.

6. The flexible heating cover assembly of claim 5 wherein the at least one outer heater element area is C-shaped and located along an outer edge of a plurality of sample well openings.

7. The flexible heating cover assembly of claim 5 wherein the at least one outer heater element area includes a tapered portion and curved end portions.

8. The flexible heating cover assembly of claim 1 wherein the resistive heater further comprises at least one heat carrier circuit that is not electrically connected to a heater power source wherein the at least one heat carrier circuit transfers heat through the resistive heater.

9. The flexible heating cover assembly of claim 1 wherein the resistive heater further comprises a thermistor located toward a center portion of the resistive heater to provide control of the vapor and the condensation environment of the plurality of sample tubes.

10. The flexible heating cover assembly of claim 1 wherein the resistive heater can move vertically within the flexible heating cover assembly to provide a more uniform heat distribution.

11. The flexible heating cover assembly of claim 1 wherein the heater backing plate is thin to promote flexibility when the heater backing plate is connected to the resistive heater.

12. The flexible heating cover assembly of claim 1 wherein the heater backing plate is composed of a thermally conductive material.

13. The flexible heating cover assembly of claim 1 wherein the heater backing plate further comprises a plurality of narrow slots to promote the flexibility of the heater backing plate and minimize the retardation of heat transfer through the heater backing plate.

14. The flexible heating cover assembly of claim 1 wherein a top surface of the heater backing plate is treated to minimize reflecting or scattering of light from the top surface of the heater backing plate.

15. The flexible heating cover assembly of claim 1 wherein the force distribution system further comprises at least one spring strip and a spring retainer plate.

16. The flexible heating cover assembly of claim 15 wherein the at least one spring strip has an elongated body and a plurality of spring extensions.

17. The flexible heating cover assembly of claim 16 wherein the plurality of spring extensions distribute the force uniformly on the heater backing plate.

18. The flexible heating cover assembly of claim 16 wherein the spring retainer plate retains the at least one spring strip and allows the plurality of spring extensions of the at least one spring strip to pass through the spring retainer plate.

19. The flexible heating cover assembly of claim 1 wherein the support plate has sufficient stiffness to provide a reaction force for the force distribution system with minimal deflection of the support plate.

20. The flexible heating cover assembly of claim 1 wherein the support plate retains a substantially planar shape under a loading force from the force distribution system, while the loading force acts to deform the heater backing plate attached to the resistive heater.

21. The flexible heating cover assembly of claim 1 wherein the support plate has a plurality of ribs located on a top surface of the support plate to provide stiffness to the support plate while permitting the close travel of optical scanning equipment to pass between the plurality of ribs.

22. The flexible heating cover assembly of claim 1 further comprising at least one heater slide to locate and guide the heater backing plate attached to the resistive heater in the flexible heating cover assembly.

23. The flexible heating cover assembly of claim 1 wherein at least one heater slide controls a horizontal position of the heater backing plate attached to the resistive heater, while permitting some freedom of movement in a vertical direction.

24. The flexible heating cover assembly of claim 1 wherein the resistive heater, the heater backing plate, and the support plate each comprise a plurality of aligned sample well openings, each sample well opening corresponding to a respective sample tube of the plurality of sample tubes.

25. The flexible heating cover assembly of claim 1 further comprising an optical scanning equipment that collects optical data for quantitative PCR type experiments.

26. The flexible heating cover assembly of claim 1 wherein a plurality of mechanical interfaces transfer force between the flexible heating cover assembly and a thermal system base.

27. The flexible heating cover assembly of claim 1 wherein the flexible heating cover assembly surrounds the top and extends over at least a portion of a side of a thermal system base.

28. The flexible heating cover assembly of claim 1 wherein the flexible heating cover assembly holds the plurality of sample tubes in a plurality of sample wells of a thermal system base by imparting a substantially uniform compressive force on the plurality of sample tubes.

29. The flexible heating cover assembly of claim 1 wherein the flexible heating cover assembly tends to thermally insulate the plurality of sample tubes.

30. The flexible heating cover assembly of claim 1 wherein each sample tube extends for a substantial length in the flexible heating cover assembly.

31. The flexible heating cover assembly of claim 1 wherein the flexible heating cover assembly is capable of withstanding thermally cycling of the samples of biological material.

32. The flexible heating cover assembly of claim 1 wherein the flexible heating cover assembly helps to minimize the convective heat loss to an ambient environment.

33. A cover assembly for an apparatus for heating samples of biological material, comprising:

a housing including a plurality of engageable enclosure components;

a resistive heater located within the housing, the resistive heater including at least one outer heater element area and at least one central heater element area;

a heater backing plate engaging the resistive heater to provide protection and stability to the resistive heater, wherein the heater backing plate is thin and composed of a thermally conductive material;

a force distribution system comprising at least one spring strip and a spring retainer plate, the force distribution system engaging the heater backing plate to distribute a force over the heater backing plate; and

a support plate providing sufficient stiffness to provide a reaction force for the force distribution system with minimal deflection of the support plate,

wherein the arrangement of the resistive heater, the heater backing plate, the force distribution system and the support plate provide substantial temperature uniformity among a plurality of sample tubes for receiving samples of biological material.

34. The cover assembly of claim 33 wherein the housing further comprises a pair of end caps and a pair of side bars all composed of a thermally insulating material.

35. The cover assembly of claim 33 wherein the resistive heater is thin to allow rapid heating and cooling during thermal cycling of the plurality of sample tubes.

36. The cover assembly of claim 33 wherein the resistive heater produces a non-uniform heat distribution along a surface exposed to the plurality of sample tubes.

37. The cover assembly of claim 33 wherein the at least one outer heater element area is C-shaped and located along an outer edge of a plurality of sample well openings.

38. The cover assembly of claim 33 wherein the at least one outer heater element area includes a tapered portion and curved end portions.

39. The cover assembly of claim 33 wherein the resistive heater further comprises at least one heat carrier circuit that is not electrically connected to a heater power source wherein the at least one heat carrier circuit transfers heat through the resistive heater.

40. The cover assembly of claim 33 wherein the resistive heater further comprises a thermistor located toward a center portion of the resistive heater to provide control of the vapor and the condensation environment of the plurality of sample tubes.

41. The cover assembly of claim 33 wherein the resistive heater can move vertically within the flexible heating cover assembly to provide a more uniform heat distribution.

42. The cover assembly of claim 33 wherein the heater backing plate further comprises a plurality of narrow slots to promote the flexibility of the heater backing plate and minimize the retardation of heat transfer through the heater backing plate.

43. The cover assembly of claim 33 wherein a bottom surface of heater backing plate is connected to the resistive heater to provide protection and stability to the resistive heater.

44. The cover assembly of claim 33 wherein a top surface of the heater backing plate is treated to minimize reflecting or scattering of light from the top surface of the heater backing plate.

45. The cover assembly of claim 33 wherein the at least one spring strip has an elongated body and a plurality of spring extensions.

46. The cover assembly of claim 45 wherein the plurality of spring extensions distribute the force uniformly on the heater backing plate.

47. The cover assembly of claim 45 wherein the spring retainer plate retains the at least one spring strip and allows the plurality of spring extensions of the at least one spring strip to pass through the spring retainer plate.

48. The cover assembly of claim 33 wherein the support plate retains a substantially planar shape under a loading force from the force distribution system, while the loading force acts to deform the heater backing plate attached to the resistive heater.

49. The cover assembly of claim 33 wherein the support plate has a plurality of ribs located on a top surface of the support plate to provide stiffness to the support plate while permitting the close travel of optical scanning equipment to pass between the plurality of ribs.

50. The cover assembly of claim 33 further comprising at least one heater slide to locate and guide the heater backing plate attached to the resistive heater in the flexible heating cover assembly.

51. The cover assembly of claim 33 wherein at least one heater slide controls a horizontal position of the heater backing plate attached to the resistive heater, while permitting some freedom of movement in a vertical direction.

52. The cover assembly of claim 33 wherein the resistive heater, the heater backing plate, and the support plate each comprise a plurality of aligned sample well openings, each sample well opening corresponding to a respective sample tube of the plurality of sample tubes.

53. The cover assembly of claim 33 further comprising an optical scanning equipment that collects optical data for quantitative PCR type experiments.

54. The cover assembly of claim 33 wherein a plurality of mechanical interfaces transfer force between the flexible heating cover assembly and a thermal system base.

55. The cover assembly of claim 33 wherein the flexible heating cover assembly surrounds the top and extends over at least a portion of a side of a thermal system base.

56. The cover assembly of claim 33 wherein the flexible heating cover assembly holds the plurality of sample tubes in a plurality of sample wells of a thermal base system by imparting a substantially uniform compressive force on the plurality of sample tubes.

57. The cover assembly of claim 33 wherein the flexible heating cover assembly tends to thermally insulate the plurality of sample tubes.

58. The cover assembly of claim 33 wherein each sample tube extends for a substantial length in the flexible heating cover assembly.

59. The cover assembly of claim 33 wherein the flexible heating cover assembly is capable of withstanding thermally cycling of the samples of biological material.

60. The cover assembly of claim 33 wherein the flexible heating cover assembly helps to minimize the convective heat loss to an ambient environment.

61. A flexible heating cover assembly for an apparatus for heating samples of biological material with substantial temperature uniformity comprising:

a housing including a plurality of end caps and a plurality of side bars all composed of a thermally insulating material;

a resistive heater located within the housing, the resistive heater including at least one outer heater element area and at least one central heater element area to produce a non-uniform heat distribution along a surface exposed to a plurality of sample tubes;

a heater backing plate engaging the resistive heater to provide protection and stability to the resistive heater wherein the heater backing plate is thin and composed of a thermally conductive material;

at least one spring strip engaging a spring retainer plate, wherein the least one spring strip has a plurality of spring extensions to distribute a force uniformly over the heater backing plate; and

a support plate providing sufficient stiffness to provide a reaction force for the at least one spring strip engaging the spring retainer plate with minimal deflection of the support plate,

wherein the resistive heater, the heater backing plate, the spring retainer plate, and the support plate each comprise a plurality of aligned sample well openings, each sample well opening corresponding to a respective sample tube of a plurality of sample tubes.

62. The flexible heating cover assembly of claim 61 wherein the resistive heater is thin to allow rapid heating and cooling during thermal cycling of the plurality of sample tubes.

63. The flexible heating cover assembly of claim 61 wherein the at least one outer heater element area is C-shaped and located along an outer edge of a plurality of sample well openings.

64. The flexible heating cover assembly of claim 61 wherein the at least one outer heater element area includes a tapered section and curved end portions.

65. The flexible heating cover assembly of claim 61 wherein the resistive heater further comprises at least one heat carrier circuit that is not electrically connected to a heater power source wherein the at least one heat carrier circuit transfers heat through the resistive heater.

66. The flexible heating cover assembly of claim 61 wherein the resistive heater further comprises a thermistor located toward a center portion of the resistive heater to provide control of the vapor and the condensation environment of the plurality of sample tubes.

67. The flexible heating cover assembly of claim 61 wherein the resistive heater can move vertically within the flexible heating cover assembly to provide a more uniform heat distribution.

68. The flexible heating cover assembly of claim 61 wherein the heater backing plate further comprises a plurality of narrow slots to promote the flexibility of the heater backing plate and minimize the retardation of heat transfer through the heater backing plate.

69. The flexible heating cover assembly of claim 61 wherein a top surface of the heater backing plate is treated to minimize reflecting or scattering of light from the top surface of the heater backing plate.

70. The flexible heating cover assembly of claim 61 wherein the spring retainer plate retains the at least one spring strip and allows the plurality of spring extensions of the at least one spring strip to pass through the spring retainer plate.

71. The flexible heating cover assembly of claim 61 wherein the support plate retains a substantially planar shape under a loading force from the force distribution system, while the loading force acts to deform the heater backing plate attached to the resistive heater.

72. The flexible heating cover assembly of claim 61 wherein the support plate has a plurality of ribs located on a top surface of the support plate to provide stiffness to the support plate while permitting the close travel of optical scanning equipment to pass between the plurality of ribs.

73. The flexible heating cover assembly of claim 61 further comprising at least one heater slide to locate and guide the heater backing plate attached to the resistive heater in the flexible heating cover assembly.

74. The flexible heating cover assembly of claim 61 wherein at least one heater slide controls a horizontal position of the heater backing plate attached to the resistive heater, while permitting some freedom of movement in a vertical direction.

75. The flexible heating cover assembly of claim 61 further comprising an optical scanning equipment that collects optical data for quantitative PCR type experiments.

76. The flexible heating cover assembly of claim 61 wherein a plurality of mechanical interfaces transfer force between the flexible heating cover assembly and a thermal system base.

77. The flexible heating cover assembly of claim 61 wherein the flexible heating cover assembly surrounds the top and extends over at least a portion of a side of a thermal system base.

78. The flexible heating cover assembly of claim 61 wherein the flexible heating cover assembly holds the plurality of sample tubes in a plurality of sample wells of a thermal system base by imparting a substantially uniform compressive force on the plurality of sample tubes.

79. The flexible heating cover assembly of claim 61 wherein the flexible heating cover assembly tends to thermally insulate the plurality of sample tubes.

80. The flexible heating cover assembly of claim 61 wherein each sample tube extends for a substantial length in the flexible heating cover assembly.

81. The flexible heating cover assembly of claim 61 wherein the flexible heating cover assembly is capable of withstanding thermally cycling of the samples of biological material.

82. The flexible heating cover assembly of claim 61 wherein the flexible heating cover assembly helps to minimize the convective heat loss to an ambient environment.