Fixed mounted sorting cuvette with user replaceable nozzle

• US 20040062685A1
• Filed: 09/27/2002
• Published: 04/01/2004
• Est. Priority Date: 09/27/2002
• Status: Active Grant

• Current Assignee: Becton, Dickinson & Co
• Original Assignee: Becton, Dickinson & Co
• Inventors: Javadi, Shervin, Norton, Pierce O., Vrane, David R.
• Granted Patent: US 7,201,875 B2
• Time in Patent Office: Days
• US Class Current: 422/81
• CPC Class Codes: G01N 15/14 Optical investigation techniques, e.g. flow cytometry
• CPC Class Codes: G01N 15/1404 Handling flow, e.g. hydrodynamic focusing
• CPC Class Codes: Y10T 436/101666 Particle count or volume standard or control [e.g., platelet count standards, etc.]
• CPC Class Codes: Y10T 436/117497 with a continuously flowing sample or carrier stream
• CPC Class Codes: Y10T 436/119163 with aspirator of claimed structure

Abstract

A flow cell and flow cytometer in which a nozzle at the end of a flow channel is disposed on a removable substrate held at a registered location on a flow cell. Other elements including illumination optics, light collection optics, and the flow cell may then be positioned at fixed locations and would not require subsequent periodic adjustment. The registered location for positioning the nozzle allows removal and replacement of the nozzle key with the nozzle subsequently positioned in the identical location.

Claims

1. A flow cell for use with a flow cytometer comprising:

a flow cell body;

a sample delivery tube extending into said flow cell body;

at least one sheath flow port on said flow cell body, said at least one port allowing introduction of a flow of sheath flow liquid through said flow cell body;

a cuvette joined to the flow cell body;

a channel extending through the cuvette, wherein liquid from said sample delivery tube and said at least one sheath flow port flows into said channel; and

a removable nozzle at a terminus of said channel, said nozzle held in a registered position on said flow cell, said registered position at a defined three dimensional position and at a registered rotational orientation.

2. The flow cell of claim 1, further including a droplet generator associated with said flow cell, said droplet generator allowing production of droplets as a stream exits the nozzle.

3. The flow cell of claim 2, wherein said droplet generator is located within said flow cell body such that droplet generation oscillations are imparted to flow fluid before said fluid enters the channel.

4. The flow cell of claim 3, wherein said droplet generator includes a piston.

5. The flow cell of claim 2, wherein said droplet generator is a vibrating element.

6. The flow cell of claim 5, wherein said vibrating element vibrates one of a group consisting of the nozzle, the cuvette, and the flow cell body.

7. The flow cell of claim 1, wherein said removable nozzle is positioned on a removable nozzle key.

8. The flow cell of claim 7, wherein said nozzle key includes a biasing spring on one side of said key.

9. The flow cell of claim 7, wherein said nozzle key includes an o-ring surrounding the nozzle.

10. The flow cell of claim 1, wherein said cuvette has sidewalls that extend downward from a location of said terminus of said channel.

11. The flow cell of claim 1, wherein said channel has a rectangular cross section.

12. The flow cell of claim 1, wherein said channel has a length sufficiently long so that liquid flowing through said channel has fully developed flow when said fluid reaches an illumination location on said channel.

13. The flow cell of claim 1, wherein when said nozzle is inserted into said registered location, a nozzle opening of the nozzle is off center from a centered position within the channel.

14. A flow cytometer system comprising:

a flow cell body;

a sample delivery tube extending into said flow cell body;

at least one sheath flow port on said flow cell body, said at least one port allowing introduction of a flow of sheath flow liquid through said flow cell body;

a cuvette joined to the flow cell body;

a channel extending through the cuvette, said channel joined to said flow cell body such that liquid from said sample delivery tube and said at least one sheath flow port flows into said channel;

a removable nozzle at a terminus of said channel, said nozzle held in a registered position, said registered position at a defined three-dimensional position and at a registered rotational orientation;

illumination optics which focus and direct illumination light into said flow cell at an illumination region of said flow cell; and

light collection optics which collect light produced from targets in the channel of the flow cell and transmit collected light to detection optics.

15. The system of claim 14, further including a droplet generator associated with said flow cell, said droplet generator allowing production of droplets as a stream exits the nozzle.

16. The system of claim 15, wherein said droplet generator is located within said flow cell body such that droplet generation oscillations are imparted to flow fluid before said fluid enters the channel.

17. The system of claim 16, wherein said droplet generator includes a piston.

18. The system of claim 15, wherein said droplet generator is a vibrating element.

19. The system of claim 18, wherein said vibrating element vibrates one of a group consisting of the nozzle, the cuvette, and the flow cell body.

20. The system of claim 14, wherein said removable nozzle is positioned on a removable nozzle key.

21. The system of claim 20, wherein said nozzle key includes a biasing spring on one side of said key.

22. The system of claim 20, wherein said nozzle key includes an o-ring surrounding the nozzle.

23. The system of claim 14, wherein said cuvette has sidewalls that extend downward from a location of said terminus of said channel.

24. The system of claim 14, wherein said channel has a rectangular cross section.

25. The system of claim 14, wherein said channel has a length sufficiently long so that liquid flowing through said channel has fully developed flow when said fluid reaches the illumination region.

26. The system of claim 14, wherein when said nozzle is inserted into said registered location, a nozzle opening of the nozzle is off center from a centered position within the channel.

27. The system of claim 14, further including a light transmissive coupling joining the cuvette with a light collection lens, said lens being an element of the light collection optics.

28. The system of claim 24, wherein said channel is rectangular and has a shorter cross-sectional side and a longer cross-sectional side, wherein said shorter cross-sectional side faces a first direction in which light is directed by the illumination optics and the longer cross-sectional side faces a second direction from which emitted light is collected by the light collection optics.

29. A sorting flow cytometer component including a flow cell and light collection optics comprising:

a flow cell body;

a sample delivery tube extending into said flow cell body;

at least one sheath flow port on said flow cell body, said at least one port allowing introduction of sheath flow liquid into said flow cell body;

a cuvette;

a channel extending through the cuvette, wherein liquid flowing from said sample delivery tube and said at least one sheath flow port flows into said channel as a flow stream, wherein said channel has an illumination region, wherein light from an illumination source of a flow cytometer system illuminates liquid flowing through the channel, wherein emission light produced by said illumination light passes from said channel into an optically transmissive material of the cuvette surrounding said channel;

a nozzle at a terminal end of said channel;

a droplet generator associated with said flow cell body, said droplet generator allowing production of droplets from a stream exiting said nozzle;

a light collection lens; and

a coupling material joining said light collection lens to said optically transmissive material, said coupling material allowing emission light to pass from said optically transmissive material into said light collection lens without a transition into air.

30. The component of claim 29, wherein said nozzle is a removable nozzle, said nozzle held in a registered position said registered position registered in three dimension and rotational orientation.

31. The component of claim 29, wherein said cuvette has sidewalls that extend downward from a location of said terminus of said channel.

32. The component of claim 29, wherein said channel has a rectangular cross section.

33. The component of claim 29, wherein said droplet generator is positioned within the flow cell body, said droplet generator producing an oscillating pressure wave in sheath fluid flowing through said flow cell body.

34. The component of claim 29, wherein said coupling material is a gel material.

35. The component of claim 29, wherein said channel has a length sufficiently long so that liquid flowing through said channel has fully developed flow when said fluid reaches the illumination region.

36. The component of claim 29, wherein when said nozzle is inserted into a said registered position on said flow cell, a nozzle opening of said nozzle is off center from a cross sectional center position within the channel.

37. A sorting flow cytometer system comprising:

a flow cell body;

a sample delivery tube extending into the flow cell body;

at least one sheath flow port on said flow cell body, said at least one port allowing introduction of sheath flow liquid through said flow cell body;

a droplet generator associated with said flow cell body, said droplet generator allowing production of droplets from a stream exiting said nozzle;

a cuvette;

a channel extending through said cuvette, wherein liquid flowing from said sample delivery tube and said at least one sheath flow port flows into said channel, wherein said channel has an illumination region, wherein light from an illumination source of the flow cytometer system may illuminate liquid flowing through the channel at the illumination region, wherein emission light produced by said illumination light passes from said channel into an optically transmissive material surrounding said channel;

a nozzle at a terminal end of said channel;

illumination optics that focus and direct illumination light into said channel at the illumination region;

a light collection lens; and

a coupling material joining said light collection lens to said optically transmissive material surrounding the channel, said coupling material allowing emission light to pass from said optically transmissive material into said light collection lens without a transition into air.

38. The system of claim 37, wherein said nozzle is a removable nozzle, said nozzle held in a registered position said registered position at a defined three-dimensional position and at a registered rotational orientation.

39. The system of claim 37, wherein said cuvette has sidewalls that extend downward from a location of said terminus of said channel.

40. The system of claim 37, wherein said channel has a rectangular cross section.

41. The system of claim 37, wherein said droplet generator is positioned within the flow cell body, said droplet generator producing an oscillating pressure wave in sheath fluid flowing through said flow cell body.

42. The system of claim 37, wherein said coupling material is a gel material.

43. The system of claim 37, wherein said channel has a length sufficiently long so that liquid flowing through said channel has fully developed flow when said fluid reaches the illumination region.

44. The system of claim 37, wherein when said nozzle is inserted into a said registered position on said flow cell, a nozzle opening of said nozzle is off center from a cross sectional center position within the channel.

45. A flow cell for use with a sorting flow cytometer comprising:

a flow cell body;

a sample delivery tube extending into said flow cell body;

at least one sheath flow port on said flow cell body, said at least one sheath flow port allowing introduction of a flow of sheath flow liquid through said flow cell body;

a cuvette;

a channel extending through the cuvette, wherein liquid flowing from said sample delivery tube and said at least one sheath flow port flow into said channel;

a nozzle at a terminal end of the channel; and

a droplet generator associated with said flow cell body, said droplet generator allowing production of droplets in said flow stream, said droplet generator imparting an oscillating force to fluid flowing into said flow cell body without direct vibration of the flow cell body or the nozzle.

46. The flow cell of claim 45, wherein said cuvette has sidewalls that extend downward from a location of the terminal end of the channel.

47. The flow cell of claim 45, wherein said channel has a rectangular cross section.

48. The flow cell of claim 45, wherein said channel has a length sufficiently long so that liquid flowing through said channel has fully developed flow when said fluid reaches the nozzle.

49. A flow cytometer system comprising:

a flow cell body;

a sample delivery tube extending into said flow cell body;

at least one sheath flow port on said flow cell body, said at least one port allowing introduction of a flow of sheath flow liquid through said flow cell body;

a cuvette;

a channel extending a length through the cuvette, wherein liquid flowing from said sample delivery tube and said at least one sheath flow port flow into said channel;

a nozzle at a terminal end of the channel;

a droplet generator associated with said flow cell body, said droplet generator allowing production of droplets in said flow stream, said droplet generator imparting an oscillation to fluid flowing into said flow cell body without direct vibration of the flow cell body or the nozzle;

illumination optics which focus and direct illumination light into said flow cell at an illumination region of said channel; and

a light collection optics that collect emitted light from said channel.

50. The system of claim 49, further including a light transmissive coupling joining the cuvette with a light collection lens, said lens being an element of the light collection optics.

51. The system of claim 49, wherein said cuvette has sidewalls that extend downward from a location of said terminal end of said channel.

52. The system of claim 49, wherein said channel has a rectangular cross section.

53. The system of claim 52, wherein the rectangular cross section has a shorter cross sectional side and a longer cross-sectional side, wherein said shorter cross sectional side faces a first direction in which light is directed by the illumination optics and the longer cross sectional side faces a second direction from which emitted light is collected by the light collection optics.

54. The system of claim 49, wherein said channel has a length sufficiently long so that liquid flowing through said channel has fully developed flow when said fluid reaches the nozzle.

55. A flow cell for use with a sorting flow cytometer comprising:

a flow cell body;

a sample delivery tube extending into said flow cell body;

at least one sheath flow port on said flow cell body, said at least one port allowing introduction of a flow of sheath flow liquid;

a cuvette joined to said flow cell body;

a rectangular channel extending a length through said cuvette, wherein liquid flowing from said sample delivery tube and said at least one sheath flow port flow into said channel;

a droplet generator connected to said flow cell, said droplet generator allowing production of droplets from a liquid stream exiting said nozzle; and

a nozzle at a terminus of said channel, wherein the cuvette has sidewalls that extend below said terminus of the channel, said sidewalls being optically transmissive such that light emitted from liquid in the channel may be transmitted through said sidewalls to light collection optics.

56. The flow cell of claim 55, wherein said channel has a length sufficiently long so that liquid flowing through said channel has fully developed flow when said fluid reaches the nozzle.

57. The flow cell of claim 56, wherein the nozzle is held at a registered position said registered position at a defined three-dimensional position and at a registered rotational orientation.

58. The flow cell of claim 55, wherein said nozzle is a removable nozzle, said nozzle held in a registered position, said registered position at a defined three-dimensional position and at a registered rotational orientation.

59. A sorting flow cytometer system comprising:

a flow cell body;

a sample delivery tube extending into said flow cell body;

at least one sheath flow port on said flow cell body, said at least one port allowing introduction of a flow of sheath flow liquid;

a droplet generator connected to said flow cell, said droplet generator allowing production of droplets in said flow stream;

a cuvette joined to said flow cell body, said cuvette having;

a rectangular channel extending through said cuvette to a terminus of said channel, wherein liquid flowing from said sample delivery tube and said at least one sheath flow port flow into said channel;

a nozzle at the terminus of said channel, wherein the cuvette has sidewalls that extend below said terminus of the channel, said sidewalls being optically transmissive such that light emitted from liquid in the channel may be transmitted through said sidewalls to light collection optics;

an illumination input optics which focuses and directs illumination light into said flow cell at an illumination region of said channel; and

light collections optics which collect light produced from targets in the channel of the flow cell and transmit collected light to detection optics.

60. The system of claim 59, further including a light transmissive coupling joining the cuvette with a light collection lens, said lens being an element of the light collection optics.

61. The system of claim 59, wherein said channel has a length sufficiently long so that liquid flowing through said channel has fully developed flow when said fluid reaches the nozzle.

62. The system of claim 61, wherein the nozzle is held at a registered position said registered position at a defined three-dimensional position and at a registered rotational orientation.

63. The system of claim 59, wherein said nozzle is a removable nozzle, said nozzle held in a registered position, said registered position at a defined three-dimensional position and at a registered rotational orientation.

64. A flow cell for use with a flow cytometer comprising:

a flow cell body;

a sample delivery tube extending into said flow cell body;

at least one sheath flow port on said flow cell body, said at least one port allowing introduction of a flow of sheath flow liquid;

a cuvette;

a channel extending through the cuvette and having a longitudinal axis, said channel joined to said flow cell body such that liquid from said sample delivery tube and said at least one sheath flow port flow into said channel; and

a removable nozzle at a terminus of said channel, said nozzle held in a registered position such that at said registered position a nozzle opening of said nozzle is off-center from the longitudinal axis of the channel.

65. The flow cell of claim 64, wherein said cuvette has sidewalls that extend downward from a location of a terminal end of said channel.

66. The flow cell of claim 64, wherein said channel has a rectangular cross section.

67. The flow cell of claim 64 wherein said channel has a length sufficient such that flow of fluid through the channel is fully developed at the nozzle location.

68. A flow cytometer system comprising:

a flow cell body;

a sample delivery tube extending into said flow cell body;

at least one sheath flow port on said flow cell body, said port allowing introduction of a flow of sheath flow liquid;

a cuvette joined to said flow cell body, said cuvette having;

a rectangular channel extending a length through said cuvette to a terminus of said channel, wherein liquid flowing from said sample delivery tube and said at least one sheath flow port flow into said channel;

a nozzle at the terminus of said channel, wherein the cuvette has sidewalls that extend below said terminus of the channel, said sidewalls being optically transmissive such that light emitted from liquid in the channel may be transmitted through said sidewalls to light collection optics;

an illumination input optics which focuses and directs illumination light into said flow cell at an illumination region of said channel; and

light collections optics which collect light produced from targets inn the channel of the flow cell and transmit collected light to detection optics.

69. The system of claim 68, wherein said channel has a length sufficiently long so that liquid flowing through said channel has fully developed flow when said fluid reaches the nozzle.