Apparatus and reaction vessel for controlling the temperature of a sample

• US 20030152492A1
• Filed: 03/03/2003
• Published: 08/14/2003
• Est. Priority Date: 07/25/2000
• Status: Active Grant

• Current Assignee: Cepheid (Danaher Corporation)
• Original Assignee: Cepheid (Danaher Corporation)
• Inventors: Chang, Ronald, Petersen, Kurt E., Northrup, M. Allen, McMillan, William A., Pourahmadi, Farzad, Christel, Lee A., Young, Steven J., Kovacs, Gregory T.A., Dority, Douglas B., Yuan, Robert
• Granted Patent: US 7,255,833 B2
• Time in Patent Office: Days
• US Class Current: 422/99
• CPC Class Codes: B01J 19/0093 Microreactors, e.g. miniaturised or microfabricated reactors laboratory containers with capillary fluid transport in microfabricated channels or chambers B01L3/5027
• CPC Class Codes: B01J 2219/00804 Plurality of plates
• CPC Class Codes: B01J 2219/0081 Plurality of modules
• CPC Class Codes: B01J 2219/00873 Heat exchange
• CPC Class Codes: B01J 2219/0097 Optical sensors
• CPC Class Codes: B01L 2300/042 Caps; Plugs
• CPC Class Codes: B01L 2300/0809 rectangular shaped
• CPC Class Codes: B01L 2300/0858 Side walls
• CPC Class Codes: B01L 2300/168 Specific optical properties, e.g. reflective coatings
• CPC Class Codes: B01L 2300/1805 Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
• 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: F28D 2021/0077 for tempering, e.g. with cooling or heating circuits for temperature control of elements
• CPC Class Codes: F28F 21/04 of ceramic; of concrete; of natural stone
• CPC Class Codes: F28F 2280/10 Movable elements, e.g. being pivotable
• CPC Class Codes: F28F 3/12 Elements constructed in the shape of a hollow panel, e.g. with channels F28D1/02, F28D1/03 take precedence
• CPC Class Codes: G01N 2035/00326 Analysers with modular structure
• CPC Class Codes: G01N 21/0303 Optical path conditioning in cuvettes, e.g. windows; adapted optical elements or systems; path modifying or adjustment G01N21/031 - G01N21/15 take precedence
• CPC Class Codes: G01N 21/0332 with temperature control control of temperature G05D23/00; cryostats F17C3/08

Abstract

This invention provides an apparatus for rapidly heating and/or cooling a sample in a reaction vessel. In some embodiments, the apparatus includes optics for the efficient detection of a reaction product in the vessel. The invention also provides a reaction vessel having a reaction chamber designed for optimal thermal conductance and for efficient optical viewing of reaction products in the chamber.

Claims

1. An apparatus for controlling the temperature of a sample, the apparatus comprising:

a) a vessel having;

i) a reaction chamber for holding the sample, the chamber being defined by two opposing major walls and a plurality of rigid minor walls joining the major walls to each other, wherein at least one of the major walls comprises a sheet or film;

ii) a port for introducing fluid into the chamber; and

iii) a channel connecting the port to the chamber;

b) at least one heating surface for contacting the sheet or film; and

c) a plug that is insertable into the channel to increase pressure in the chamber, whereby the pressure increase in the chamber forces the sheet or film against the heating surface.

2. The apparatus of claim 1, wherein at least two of the walls are light transmissive, and wherein the apparatus further comprises optics for optically interrogating the chamber while the heating surface is in contact with the sheet or film, the optics comprising at least one light source for transmitting light to the chamber through a first one of the light transmissive walls and at least one detector for detecting light exiting the chamber through a second one of the light transmissive walls.

3. The apparatus of claim 2, wherein the at least one heating surface is provided by a thermal sleeve for receiving the vessel, the sleeve including at least one heater for heating the surface, the sleeve having at least one window or opening providing optical access to the light transmissive walls, and the optics being positioned to interrogate the chamber through the at least one window or opening in the sleeve.

4. The apparatus of claim 1, wherein the heating surface comprises a surface of a plate, the plate having at least one heating resistor coupled thereto.

5. The apparatus of claim 1, wherein each of the major walls comprises a sheet or film, the apparatus includes at least two heating surfaces defined by opposing plates positioned to receive the vessel between them such that the plates contact the major walls, and the apparatus includes means for heating the plates.

6. The apparatus of claim 5, further comprising at least one support for holding the plates in an opposing relationship to each other, the support including a slot for inserting the chamber of the vessel between the plates.

7. The apparatus of claim 5, wherein at least two of the minor walls are light transmissive to provide optical windows to the chamber, and wherein the apparatus further comprises optics for optically interrogating the chamber through at least one window or opening between the plates, the optics comprising at least one light source for transmitting light to the chamber through a first one of the light transmissive walls and at least one detector for detecting light exiting the chamber through a second one of the light transmissive walls.

8. The apparatus of claim 7, wherein the optics include:

i) a plurality of light sources and filters for transmitting different wavelengths of excitation light to the chamber; and

ii) a plurality of detectors and filters for detecting different wavelengths of light emitted from the chamber.

9. The apparatus of claim 7, wherein the plates, heating means, and optics are incorporated into a heat-exchanging unit, the apparatus further comprises a base support for receiving the heat-exchanging unit, and the base support includes at least one controller for controlling the operation of the heat-exchanging unit.

10. The apparatus of claim 9, wherein the heat-exchanging unit further comprises:

i) a housing for holding the plates, heating means, and optics; and

ii) a cooling element disposed within the housing for cooling the chamber.

11. The apparatus of claim 10, wherein the cooling element comprises a fan for blowing cooling air.

12. The apparatus of claim 1, wherein the base support is constructed to receive and independently control a plurality of such heat-exchanging units.

13. The apparatus of claim 2, wherein the light transmissive walls are angularly offset about 90°

from each other, and wherein the optics provide about a 9020 angle between optical excitation and detection paths.

14. The apparatus of claim 1, wherein the apparatus includes a heat source for heating the surface, and the apparatus further includes a cooling element for cooling the chamber.

15. The apparatus of claim 14, wherein the cooling element comprises a fan for blowing cooling air.

16. A vessel having a reaction chamber for holding a sample, the vessel comprising:

a) a rigid frame defining the minor walls of the chamber, wherein at least two of the minor walls are light transmissive to provide optical windows to the chamber;

b) at least one sheet or film attached to the rigid frame to form a major wall of the chamber; and

c) a port for introducing the sample into the chamber.

17. The vessel of claim 16, wherein the vessel includes at two sheets or films that are attached to opposite sides of the frame to form two opposing major walls of the chamber, each of the sheets or films being sufficiently flexible to conform to a respective heating-surface.

18. The vessel of claim 17, wherein each of the sheets or films comprise a polymeric material.

19. The vessel of claim 16, wherein the light transmissive walls are angularly offset from each other.

20. The vessel of claim 16, wherein the light transmissive walls are angularly offset from each other by about 90°

.

21. The vessel of claim 16, further comprising optical elements or coatings on the light transmissive walls for allowing only certain wavelengths of light to pass through the walls.

22. The vessel of claim 16, wherein each of the light transmissive walls has a lens molded into its surface.

23. The vessel of claim 16, wherein the chamber has at least four minor walls, at least two of the minor walls being the light transmissive walls, and at least two other of the minor walls being retro-reflective walls for reflecting light in the chamber.

24. The vessel of claim 16, further comprising at least one reagent in the chamber.

25. The vessel of claim 16, further comprising sealing means for sealing the port.

26. The vessel of claim 16, wherein the vessel further includes:

a channel connecting the port to the chamber; and

a plug that is insertable into the channel to increase pressure in the chamber.

27. The vessel of claim 16, wherein the at least one sheet or film is sufficiently flexible to conform to a heating or cooling surface.

28. The vessel of claim 17, wherein the ratio of the thermal conductance of the major walls to that of the minor walls is at least 2:

1.

29. A reaction vessel having a reaction chamber for holding a sample, the vessel comprising:

a) a rigid frame defining the minor walls of the chamber;

b) at least one sheet or film attached to the rigid frame to form a major wall of the chamber;

c) a port for introducing the sample into the vessel;

d) a channel connecting the port to the chamber; and

e) a plug that is insertable into the channel to increase pressure in the chamber.

30. The vessel of claim 29, wherein the vessel includes two sheets or films that are attached to opposite sides of the rigid frame to form two opposing major walls of the chamber, the major walls being connected to each other by the minor walls, and each of the sheets or films being sufficiently flexible to conform to a respective heating surface.

31. The vessel of claim 30, wherein each of the sheets or films comprise a polymeric material.

32. The vessel of claim 29, wherein at least two of the minor walls are light transmissive to provide optical windows to the chamber.

33. The vessel of claim 32, wherein the light transmissive walls are angularly offset from each other.

34. The vessel of claim 32, wherein the light transmissive walls are angularly offset from each other by about 90°

.

35. The vessel of claim 32, further comprising optical elements or coatings on the light transmissive walls for allowing only certain wavelengths of light to pass through the walls.

36. The vessel of claim 29, wherein the chamber has at least four minor walls, at least two of the minor walls being light transmissive to provide optical windows to the chamber, and at least two other of the minor walls being retro-reflective walls for reflecting light in the chamber.

37. The vessel of claim 29, wherein the at least one sheet or film is sufficiently flexible to conform to a heating or cooling surface.

38. The vessel of claim 29, further comprising at least one reagent in the chamber.

39. The vessel of claim 30, wherein the ratio of the thermal conductance of the major walls to that of the minor walls is at least 2:

1.

40. The vessel of claim 30, wherein the ratio of the total surface area of the major walls to that of the minor walls is at least 2:

1.

41. A reaction vessel comprising:

a) two opposing major walls, wherein at least one of the major walls comprises a sheet or film;

b) a plurality of rigid minor walls joining the major walls to each other to form a reaction chamber, at least two of the minor walls being light transmissive; and

c) a port for introducing fluid into the chamber;

wherein the ratio of the total surface area of the major walls to that of the minor walls is at least 2;

1.

42. The vessel of claim 41, wherein the sheet or film is sufficiently flexible to conform to a heating or cooling surface.

43. The vessel of claim 41, further comprising sealing means for sealing the port.

44. The vessel of claim 41, wherein the vessel includes a channel connecting the port to the chamber, and the vessel further comprises a plug that is insertable into the channel to increase pressure in the chamber.

45. The vessel of claim 41, wherein the vessel includes a rigid frame providing the minor walls of the chamber, and wherein the two opposing major walls comprise two sheets or films that are attached to opposite sides of the rigid frame.

46. The vessel of claim 45, wherein each of the sheets or films comprise a polymeric material.

47. The vessel of claim 41, wherein the light transmissive walls are angularly offset from each other.

48. The vessel of claim 47, wherein the light transmissive walls are offset from each other by about 90°

.

49. The vessel of claim 41, further comprising optical elements or coatings oil the light transmissive walls for allowing only certain wavelengths of light to pass through the light transmissive walls.

50. The vessel of claim 41, wherein the vessel includes at least four minor walls defining the chamber, at least two of the minor walls being the light transmissive walls, and at least two other of the minor walls being retro-reflective walls for reflecting light in the chamber.

51. The vessel of claim 41, further comprising at least one reagent in the chamber.

52. A reaction vessel comprising:

a) two opposing major walls, wherein at least one of the major walls comprises a sheet or film;

b) a plurality of rigid minor walls joining the major walls to each other to form a reaction chamber, at least two of the minor walls being light transmissive to provide optical windows to the chamber; and

c) a port for introducing fluid into the chamber;

wherein the ratio of the thermal conductance of the major walls to that of the minor walls is at least 2;

1.

53. The vessel of claim 52, wherein the sheet or film is sufficiently flexible to conform to a heating or cooling surface.

54. The vessel of claim 52, wherein-the vessel includes a channel connecting the port to the chamber, and the vessel further comprises a plug that is insertable into the channel to increase pressure in the chamber.

55. The vessel of claim 52, wherein the vessel includes a rigid frame providing the minor walls of the chamber, and wherein the two opposing major walls comprise two sheets or films that are attached to opposite sides of the rigid frame, each of the sheets or films being sufficiently flexible to conform to a respective heating surface.

56. The vessel of claim 55, wherein each of the sheets or films comprise a polymeric material.

57. The vessel of claim 52, wherein the light transmissive walls are angularly offset from each other.

58. The vessel of claim 57, wherein the light transmissive walls are offset from each other by about 90°

.

59. The vessel of claim 52, further comprising optical elements or coatings on the light transmissive walls for allowing only certain wavelengths of light to pass through the walls.

60. The vessel of claim 52, wherein the vessel includes at least four minor walls defining the chamber, at least two of the minor walls being the light transmissive walls, and at least two other of the minor walls being retro-reflective walls for reflecting light in the chamber.

61. The vessel of claim 52, further comprising sealing means for sealing the port.

62. The vessel of claim 52, further comprising at least one reagent in the chamber.

63. A reaction vessel comprising:

a) two opposing major walls, wherein at least one of the major walls comprises a sheet or film;

b) a plurality of rigid minor walls joining the major walls to each other to form a reaction chamber

c) a port for introducing fluid into the vessel;

d) a channel connecting the port to the reaction chamber; and

e) a plug that is insertable into the channel to increase pressure in the reaction chamber.

64. The vessel of claim 63, wherein each of the major walls comprises a sheet or film, and wherein each of the sheets or films is sufficiently flexible to conform to a respective heating surface.

65. The vessel of claim 64, wherein each of the sheets or films comprise a polymeric material.

66. The vessel of claim 63, wherein at least two of the minor walls are light transmissive to provide optical windows to the chamber.

67. The vessel of claim 66, wherein the light transmissive walls are angularly offset from each other.

68. The vessel of claim 66, wherein the light transmissive walls are angularly offset from each other by about 90°

.

69. The vessel of claim 66, further comprising optical elements or coatings on the light transmissive walls for allowing only certain wavelengths of light to pass through the walls.

70. The vessel of claim 63, wherein the chamber has at least four minor walls, at least two of the minor walls being light transmissive to provide optical windows to the chamber, and at least two other of the minor walls being retro-reflective walls for reflecting light in the chamber.

71. The vessel of claim 63, wherein the at least one sheet or film is sufficiently flexible to conform to a heating or cooling surface.

72. The vessel of claim 63, further comprising at least one reagent in the chamber.

73. The vessel of claim 63, wherein the ratio of the thermal conductance of the major walls to that of the minor walls is at least 2:

1.

74. The vessel of claim 63, wherein the ratio of the total surface area of the major walls to that of the minor walls is at least 2:

1.