Reaction vessel and temperature control system

• US 7,101,509 B2
• Filed: 06/11/2002
• Issued: 09/05/2006
• Est. Priority Date: 02/04/2000
• Status: Expired due to Fees

• Current Assignee: Cepheid (Danaher Corporation)
• Original Assignee: Cepheid (Danaher Corporation)
• Inventors: Chang, Ronald, Petersen, Kurt E., Christel, Lee A., Dority, Douglas B.
• Primary Examiner(s): Gordon, Brian R.
• Application Number:
  US10/167,898
• Publication Number:
  US 20020168299A1
• Time in Patent Office: 1,547 Days
• Field of Search: 422/100, 422/68.1, 422/58, 422/59, 422/102, 436/180, 436/165
• US Class Current: 422/68.1
• CPC Class Codes: B01L 2200/026 Fluid interfacing between devices or objects, e.g. connectors, inlet details
• CPC Class Codes: B01L 2200/0642 Filling fluids into wells by specific techniques
• CPC Class Codes: B01L 2200/0684 Venting, avoiding backpressure, avoid gas bubbles
• CPC Class Codes: B01L 2300/0654 Lenses; Optical fibres
• CPC Class Codes: B01L 2300/14 Means for pressure control
• CPC Class Codes: B01L 2400/049 vacuum
• CPC Class Codes: B01L 2400/0644 rotary valves
• CPC Class Codes: B01L 3/502 with fluid transport, e.g. in multi-compartment structures centrifugal-type cuvettes G01N21/07; analysis by separation into components G01N30/00; automatic analysers G01N35/00
• CPC Class Codes: B01L 3/50825 Closing or opening means, corks, bungs closures for containers B65D; means for removing stoppers B67B7/02
• 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: G01N 2035/0405 manipulating closing or opening means, e.g. stoppers, screw caps, lids or covers
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

Abstract

A reaction vessel has a reaction chamber, a loading reservoir connected to the reaction chamber via a first channel, and an aspiration port connected to the chamber via a second channel. To load the sample into the reaction chamber, the sample is dispensed into the loading reservoir and then drawn into the chamber by application of a vacuum to the aspiration port. A system for controlling the temperature of the sample in the reaction vessel includes one or more thermal elements for heating or cooling the sample and optionally optics for detecting one or more analytes in the sample.

Claims

1. A system for controlling the temperature of a sample, the system comprising:

a) a reaction vessel having;

i) a reaction chamber defined by two opposing major walls and side walls connecting the major walls to each other, at least one of the major walls comprising a sheet or film;

ii) a loading reservoir for receiving the sample prior to loading the sample into the reaction chamber, the loading reservoir being connected to the reaction chamber via a first channel; and

iii) an aspiration port connected to the reaction chamber via a second channel;

b) an aspiration device for establishing a seal with the aspiration port and for drawing the sample from the loading reservoir into the reaction chamber, wherein the vessel further includes flow control means for preventing substantial flow of the sample from the loading reservoir into the reaction chamber until the sample is drawn into the chamber by the aspiration device;

c) at least one heating or cooling surface for contacting the sheet or film, the sheet or film being sufficiently flexible to conform to the surface; and

d) at least one thermal element for heating or cooling the surface to induce a temperature change in the reaction chamber.

2. The system of claim 1, wherein the flow control means comprises at least one portion of the first channel having a sufficiently small width or diameter to prevent substantial flow of the sample from the loading reservoir to the chamber until the sample is drawn into the chamber by the aspiration device.

3. The system of claim 1, wherein the flow control means comprises at least one valve in the first channel.

4. The system of claim 1, wherein the flow control means comprises at least one membrane or screen in the first channel.

5. The system of claim 1, wherein the system includes at least two heating or cooling surfaces positioned to receive the vessel between them such that the surfaces contact the major walls, and wherein each of the major walls comprises a flexible sheet or film.

6. The system of claim 5, wherein the heating or cooling surfaces are the surfaces of opposing plates positioned to receive the vessel between them, each of the plates having a thermal mass less than 1 J/°

C.

7. The system of claim 1, wherein each of the plates comprises a ceramic material, and wherein the at least one thermal element comprises heating elements coupled to the plates.

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

9. The system of claim 8, wherein the optically transmissive walls are angularly offset from each other by about 90°

.

10. The system of claim 9, further comprising at least one controller for controlling the operation of the thermal element, light source, and detector.

11. The system of claim 1, wherein the chamber has a thickness less than the width or diameter of the aspiration device.

12. The system of claim 1, wherein the ratio of the width of the chamber to the thickness of the chamber is at least 4:

1, and wherein the thickness of the chamber is less than or equal to 3 mm.

13. The system of claim 1, further comprising means for increasing the pressure in the chamber, wherein the pressure increase in the chamber is sufficient to force the sheet or film to conform to the surface.

14. The system of claim 13, wherein the vessel further includes a seal aperture extending over an outer end of the loading reservoir and an outer end of the aspiration port, and wherein the means for increasing the pressure in the chamber comprises a plug that is insertable into the aperture to compress gas in the vessel.

15. The system of claim 14, wherein the vessel includes an inner surface defining the seal aperture, and wherein the inner surface has at least one pressure control groove formed therein, the pressure control groove extending to a predetermined depth in the aperture to allow gas to escape from the aperture until the plug reaches the predetermined depth.

16. The system of claim 15, further comprising an automated machine for inserting the plug into the aperture, wherein the machine has a machine tip for engaging the plug, and wherein the plug includes a cap having an engagement aperture for receiving and establishing a fit with the machine tip.

17. The system of claim 14, wherein the plug includes a cap having latches, and wherein the vessel further comprises catches for engaging the latches, thereby securing the plug in the aperture.

18. The system of claim 13, wherein the means for increasing the pressure in the chamber comprises first and second plugs which are inserted into the loading reservoir and the aspiration port, respectively, to compress gas in the vessel and increase pressure in the chamber.

19. The system of claim 13, wherein the means for increasing pressure in the chamber comprises:

i) a machine head for communicating with the vessel; and

ii) a pressure source for pressurizing the chamber through the machine head.

20. The system of claim 19, wherein the vessel further includes a seal aperture extending over an outer end of the loading reservoir and an outer end of the aspiration port, the system further comprises an adapter for placing the machine head in fluid communication with the chamber, and the adapter is sized to be inserted into the aperture.

21. The system of claim 20, wherein the adapter includes a valve for preventing fluid from escaping from the vessel.

22. The system of claim 13, wherein the vessel further includes a seal aperture extending over an outer end of the loading reservoir and an outer end of the aspiration port, and wherein the means for increasing pressure in the chamber comprises:

i) an elastomeric plug for sealing the aperture; and

ii) a needle for injecting fluid into the vessel through the plug.

23. The system of claim 13, wherein the vessel further includes a seal aperture extending over an outer end of the loading reservoir and an outer end of the aspiration port, and wherein the means for increasing pressure in the chamber comprises a platen for heat sealing a film or foil to the vessel to seal the aperture.

24. The system of claim 1, further comprising a pick-and-place machine having a machine tip for engaging the vessel, wherein either the loading reservoir or the aspiration port has tapered walls for establishing a fit with the machine tip, thereby enabling the machine tip to pick and place the vessel.

25. A system for controlling the temperature of a sample, the system comprising:

a) a reaction vessel having;

i) a reaction chamber;

ii) a loading reservoir for receiving the sample, wherein the loading reservoir is connected to the reaction chamber via a first channel;

iii) an aspiration port connected to the reaction chamber via a second channel; and

iv) a seal aperture extending over an outer end of the loading reservoir and an outer end of the aspiration port;

b) an aspiration device for establishing a seal with the aspiration port and for drawing the sample from the loading reservoir into the reaction chamber, wherein the vessel further includes flow control means for preventing substantial flow of the sample from the loading reservoir into the reaction chamber until the sample is drawn into the reaction chamber by the aspiration device;

c) a plug that is insertable into the aperture; and

d) at least one thermal element for heating or cooling the reaction chamber.

26. The system of claim 25, wherein the flow control means comprises at least one portion of the first channel having a sufficiently small width or diameter to prevent substantial flow of the sample from the loading reservoir to the chamber until the sample is drawn into the chamber by the aspiration device.

27. The system of claim 25, wherein the flow control means comprises at least one valve in the first channel.

28. The system of claim 25, wherein the flow control means comprises at least one membrane or screen in the first channel.

29. The system of claim 25, wherein the reaction chamber is defined by two opposing major walls and side walls connecting the major walls to each other, at least one of the major walls comprises a sheet or film, and the at least one thermal element comprises:

i) at least one heating or cooling surface for contacting the sheet or film, the sheet or film being sufficiently flexible to conform to the surface; and

ii) means for heating or cooling the surface.

30. The system of claim 25, wherein the vessel includes a rigid frame defining side walls of the chamber, the vessel includes two sheets or films attached to opposite sides of the frame to form two opposing major walls of the chamber, and the at least one thermal element comprises:

i) opposing plates positioned to receive the vessel between them such that the plates contact the major walls; and

ii) means for heating or cooling the plates.

31. The system of claim 30, wherein each of the plates comprises a ceramic material, and wherein each of the plates has a thickness less than or equal to 1 mm.

32. The system of claim 30, wherein the means for heating or cooling the plates comprises resistive heating elements coupled to the plates.

33. The system of claim 30, wherein each of the plates has a thermal mass less than or equal to 1 J/°

C.

34. The system of claim 25, wherein the reaction chamber is defined by a plurality of walls, at least two of the walls are optically transmissive, and the system further comprises optics for optically interrogating the chamber, the optics comprising at least one light source for transmitting light to the chamber through a first one of the optically transmissive walls and at least one detector for detecting light exiting the chamber through a second one of the optically transmissive walls.

35. The system of claim 34, wherein the optically transmissive walls are angularly offset from each other by about 90°

.

36. The system of claim 34, further comprising at least one controller for controlling the operation of the thermal element, light source, and detector.

37. The system of claim 25, wherein the reaction chamber has a thickness less than the width or diameter of the aspiration device.

38. The system of claim 25, wherein the ratio of the width the reaction chamber to the thickness of the reaction chamber is at least 4:

1, and wherein the thickness of the reaction chamber is less than or equal to 3 mm.

39. The system of claim 25, wherein the plug is sized to compress gas in the vessel, thereby increasing pressure in the reaction chamber to at least 2 pounds per square inch above ambient pressure.

40. The system of claim 25, further comprising an automated machine for inserting the plug into the aperture, wherein the machine has a machine tip for engaging the plug, and wherein the plug includes a cap having an engagement aperture for receiving the machine tip.

41. The system of claim 25, wherein the plug includes a cap having latches, and wherein the vessel further comprises catches for engaging the latches, thereby securing the plug in the aperture.

42. A system for loading a sample into a reaction vessel and for controlling the temperature of the sample in the vessel, wherein the vessel includes a reaction chamber, a loading reservoir connected to the reaction chamber via a first channel, an aspiration port connected to the reaction chamber via a second channel, and a seal aperture extending over an outer end of the loading reservoir and an outer end of the aspiration port, the system comprising:

a) an aspiration and dispensing device for dispensing the sample into the loading reservoir, for establishing a seal with the aspiration port, and for drawing the sample from the loading reservoir into the reaction chamber, wherein the vessel includes flow control means for preventing substantial flow of the sample from the loading reservoir into the reaction chamber until the sample is drawn into the reaction chamber by the aspiration and dispensing device;

b) an automated machine for inserting a plug into the seal aperture after loading the sample into the chamber; and

c) at least one thermal element for heating or cooling the reaction chamber.

43. The system of claim 42, wherein the flow control means comprises at least one portion of the first channel having a sufficiently small width or diameter to prevent substantial flow of the sample from the loading reservoir to the chamber until the sample is drawn into the chamber by the aspiration device.

44. The system of claim 42, wherein the flow control means comprises at least one valve in the first channel.

45. The system of claim 42, wherein the flow control means comprises at least one membrane or screen in the first channel.

46. The system of claim 42, wherein the at least one thermal element comprises:

i) opposing plates positioned to receive the vessel between them such that the plates contact major walls of the reaction chamber; and

ii) means for heating or cooling the plates.

47. The system of claim 46, wherein each of the plates comprises a ceramic material, and wherein each of the plates has a thickness less than or equal to 1 mm.

48. The system of claim 46, wherein the means for heating or cooling the plates comprises resistive heating elements coupled to the plates.

49. The system of claim 46, wherein each of the plates has a thermal mass less than or equal to 1 J/°

C.

50. The system of claim 42, wherein the reaction chamber is defined by a plurality of walls, at least two of the walls are optically transmissive, and the system further comprises optics for optically interrogating the chamber, the optics comprising at least one light source for transmitting light to the chamber through a first one of the optically transmissive walls and at least one detector for detecting light exiting the chamber through a second one of the optically transmissive walls.

51. The system of claim 50, further comprising at least one controller for controlling the operation of the thermal element, light source, and detector.

52. A reaction vessel comprising:

a) a reaction chamber defined by two opposing major walls and side walls connecting the major walls to each other, wherein at least one of the major walls comprises a sheet or film sufficiently flexible to conform to a heating or cooling surface, and wherein at least two of the side walls are optically transmissive to provide optical windows to the reaction chamber;

b) a loading reservoir for receiving the sample prior to loading the sample into the reaction chamber, wherein the loading reservoir is connected to the reaction chamber via a first channel; and

c) an aspiration port for establishing a seal with an aspiration device, the aspiration port being connected to the reaction chamber via a second channel, thereby enabling the aspiration device to draw the sample from the loading reservoir into the chamber, wherein the vessel further includes flow control means for preventing substantial flow of the sample from the loading reservoir into the reaction chamber until the sample is drawn into the reaction chamber by the aspiration device.

53. The vessel of claim 52, wherein the flow control means comprises at least one portion of the first channel having a sufficiently small width or diameter to prevent substantial flow of the sample from the loading reservoir to the reaction chamber until the sample is drawn into the reaction chamber by the aspiration device.

54. The vessel of claim 52, wherein the flow control means comprises at least one valve in the first channel.

55. The vessel of claim 52, wherein the flow control means comprises at least one membrane or screen in the first channel.

56. The vessel of claim 52, wherein the vessel includes a rigid frame defining the side walls, each of the two opposing major walls comprises a flexible sheet or film attached to the frame, and the vessel includes a loading structure extending from the frame, the loading structure defining the loading reservoir and the aspiration port.

57. The vessel of claim 52, wherein the optically transmissive walls are angularly offset from each other by about 90°

.

58. The vessel of claim 52, wherein the ratio of the width the reaction chamber to the thickness of the reaction chamber is at least 4:

1, and wherein the thickness of the reaction chamber is less than or equal to 3 mm.

59. The vessel of claim 52, further comprising:

i) a seal aperture extending over an outer end of the loading reservoir and an outer end of the aspiration port; and

ii) a plug that is insertable into the aperture.

60. The vessel of claim 59, wherein the plug is sized to compress gas in the vessel, thereby increasing pressure in the reaction chamber.

61. The vessel of claim 59, wherein the vessel includes an inner surface defining the seal aperture, and wherein the inner surface has at least one pressure control groove formed therein, the pressure control groove extending to a predetermined depth in the aperture to allow gas to escape from the aperture until the plug reaches the predetermined depth.

62. The vessel of claim 52, wherein the plug includes a cap having an engagement aperture for receiving and establishing a fit with a machine tip.

63. The vessel of claim 52, wherein the plug includes a cap having latches, and wherein the vessel further comprises catches for engaging the latches, thereby securing the plug in the aperture.

64. The vessel of claim 52, wherein either the loading reservoir or the aspiration port has tapered walls for establishing a fit with a machine tip, thereby enabling the machine tip to pick and place the vessel.

65. The vessel of claim 52, further comprising dried or lyophilized reagents in the reaction chamber.

66. A reaction vessel comprising:

a) a reaction chamber;

b) a loading reservoir for receiving the sample prior to loading the sample into the reaction chamber, the loading reservoir being connected to the chamber via a first channel;

c) an aspiration port for establishing a seal with an aspiration device, the aspiration port being connected to the reaction chamber via a second channel thereby enabling the aspiration device to draw the sample from the loading reservoir into the reaction chamber, wherein the vessel further includes flow control means for preventing substantial flow of the sample from the loading reservoir into the reaction chamber until the sample is drawn into the reaction chamber by the aspiration device; and

d) a seal aperture, extending over an outer end of the loading reservoir and an outer end of the aspiration port, for receiving a plug that is inserted into the aperture after loading the sample into the reaction chamber.

67. The vessel of claim 66, wherein the flow control means comprises at least one portion of the first channel having a sufficiently small width or diameter to prevent substantial flow of the sample from the loading reservoir to the reaction chamber until the sample is drawn into the reaction chamber by the aspiration device.

68. The vessel of claim 66, wherein the flow control means comprises at least one valve in the first channel.

69. The vessel of claim 66, wherein the flow control means comprises at least one membrane or screen in the first channel.

70. The vessel of claim 66, wherein the reaction chamber is defined by two opposing major walls and side walls connecting the major walls to each other, and wherein at least one of the major walls comprises a sheet or film sufficiently flexible to conform to a heating or cooling surface.

71. The vessel of claim 70, wherein at least two of the side walls are optically transmissive to provide optical windows to the reaction chamber.

72. The vessel of claim 70, wherein the vessel includes a rigid frame defining the side walls, each of the two opposing major walls comprises a flexible sheet or film attached to the frame, and the vessel includes a loading structure extending from the frame, the loading structure defining the loading reservoir and the aspiration port.

73. The vessel of claim 71, wherein the optically transmissive walls are angularly offset from each other by about 90°

.

74. The vessel of claim 66, wherein the ratio of the width the reaction chamber to the thickness of the reaction chamber is at least 4:

1, and wherein the thickness of the reaction chamber is less than or equal to 3 mm.

75. The vessel of claim 66, wherein the plug is sized to compress gas in the vessel, thereby increasing pressure in the reaction chamber.

76. The vessel of claim 66, wherein the pressure increase is at least 2 pounds per square inch.

77. The vessel of claim 66, wherein the pressure increase is in the range of 8 to 15 pounds per square inch.

78. The vessel of claim 66, wherein the vessel includes an inner surface defining the seal aperture, and wherein the inner surface has at least one pressure control groove formed therein, the pressure control groove extending to a predetermined depth in the aperture to allow gas to escape from the aperture until the plug reaches the predetermined depth.

79. The vessel of claim 66, wherein the plug includes a cap having an engagement aperture for receiving and establishing a fit with a machine tip.

80. The vessel of claim 66, wherein the plug includes a cap having latches, and wherein the vessel further comprises catches for engaging the latches, thereby securing the plug in the aperture.

81. The vessel of claim 66, wherein either the loading reservoir or the aspiration port has tapered walls for establishing a fit with a machine tip, thereby enabling the machine tip to pick and place the vessel.

82. The vessel of claim 66, further comprising dried or lyophilized reagents in the reaction chamber.