Automated robotic workstation and methods of operation thereof

• US 20040047765A1
• Filed: 11/27/2002
• Published: 03/11/2004
• Est. Priority Date: 10/16/1998
• Status: Abandoned Application

• Current Assignee: Parallabs Incorporated
• Original Assignee: Parallabs Incorporated
• Inventors: Grenier, Steven, Barrett, Edward, Hathaway, Kenneth, Boccuti, A. David, Gordon, Steven J., Brancazio, David
• Application Number:
  US10/306,787
• Publication Number:
  US 20040047765A1
• Time in Patent Office: Days
• US Class Current: 422/63
• CPC Class Codes: B01L 13/02 for receptacle or instruments
• CPC Class Codes: B01L 2200/025 Align devices or objects to ensure defined positions relative to each other
• CPC Class Codes: B01L 2300/0829 Multi-well plates; Microtitration plates
• CPC Class Codes: B01L 3/021 Pipettes, i.e. with only one conduit for withdrawing and redistributing liquids
• CPC Class Codes: B01L 3/022 Capillary pipettes, i.e. having very small bore B01L3/0224 - B01L3/0237 take precedence
• CPC Class Codes: G01N 2035/00237 Handling microquantities of analyte, e.g. microvalves, capillary networks
• CPC Class Codes: G01N 2035/0425 Stacks, magazines or elevators for plates
• CPC Class Codes: G01N 2035/0446 Combinations of the above
• CPC Class Codes: G01N 2035/0498 Drawers used as storage or dispensing means for vessels or cuvettes
• CPC Class Codes: G01N 35/0099 comprising robots or similar manipulators robots per se B25J
• CPC Class Codes: G01N 35/028 having reaction cells in the form of microtitration plates
• CPC Class Codes: G01N 35/1004 Cleaning sample transfer devices
• CPC Class Codes: G01N 35/1065 Multiple transfer devices

Abstract

The invention provides an automated workstation capable of continuous, non-stop processing of specimens. The workstation includes a storage area that holds multiple cassettes containing specimens compounds or other materials to be analyzed or used in conjunction therewith (collectively, “specimens”) which, preferably, are maintained on slides, microliter plates, or the like (collectively, “plates”). The workstation also includes a robotic arm for processing the specimens, e.g., by grasping the plates, moving them from the cassettes to other apparatus contained within the workstation, and placing the plates back in the cassettes. The invention also provides methods and apparatus for acquiring and processing samples in narrow, thin-walled pipettes without transferring them to wells, vials, or other reaction vessels.

Claims

1. In a robotic arm of the type having an effector that is detachably coupled to the arm via a latching mechanism that includes first portion disposed on the effector and a second portion disposed on the arm, the improvement comprising

a release at least one of (i) disposed on the effector separately from the first portion of the latching mechanism and (ii) disposed on the arm separately from the second portion of the latching mechanism,

the release effecting a torque on at least one of the first and second portions of the latching mechanism at least partially countering a torque effected on that portion of the latching mechanism by at least one of the effector and an article carried thereby.

2. In the robotic arm of claim 1, the further improvement wherein the release effects a torque tending to bring the first and second portions of the latching mechanism into alignment for disengagement.

3. In the robotic arm of claim 1, the further improvement wherein the release comprises a rod that stands proud from a surface of any of the arm and effector.

4. In the robotic arm of claim 3, the further improvement wherein the rod is spring-loaded.

5. An effector for use with a robotic arm, the effector comprising

one or more extending forks adapted for handling a specimen or vessel therefor,

a first latching member adapted for releasable engagement with a second latching member on the arm,

a release disposed separately from the first latching member, the release adapted for exerting a force on the arm when the first and second latching members are engaged, the force effecting a torque on the first latching member that at least partially counters a torque effected on that member by at least one of the forks, the specimen, and a vessel therefor.

6. The effector of claim 5, wherein the first latching member comprises an elongate element adapted for releasable engagement by an element on the arm.

7. The effector of claim 5, wherein the release comprises a spring-loaded element.

8. The effector of claim 5, wherein the release comprises a rod that stands proud from a surface of the effector.

9. The effector of claim 5, wherein the release is disposed opposite the first latching member with respect to forks.

10. The effector of claim 5, wherein the release effects a torque that brings the first and second latching members into alignment for disengagement.

11. An effector for use with a robotic arm, the effector comprising

structure adapted for handling a specimen or vessel therefor,

an elongate element adapted for releasable engagement with a latch or other actuator (collectively, “

latch”

) on the arm,

a release member disposed separately from and independent of the elongate element on an opposite side thereof with respect to the aforesaid structure,

the release member adapted for effecting a torque at least partially countering that effected on the elongate element by the structure or a specimen or vessel handled thereby and, thereby, facilitating release of any engagement therebetween.

12. The effector of claim 11, wherein the release comprises a spring-loaded member disposed on a surface of the effector.

13. The effector of claim 12, wherein the first latching member comprises a rod that stands proud from a surface of the effector.

14. The effector of claim 12, wherein the surface of the effector is one that mates with a surface of the arm.

15. In an automated workstation, the improvement comprising a robotic arm including

a moveable member,

a pneumatic latch or actuator (collectively, “

pneumatic latch”

) disposed on the moveable member,

an effector,

the effector comprising

a load-carrying structure,

a latching member adapted for releasable engagement with the pneumatic latch,

a release member disposed separately from the latching member,

the release member exerts on the latching member a torque that at least partially counters that effected on the latching member by the load-carrying structure or a load carried thereby.

16. In the automated workstation of claim 15, the further improvement wherein moveable member is coupled to an assembly capable of translating the moveable member in at least two dimensions.

17. In the automated workstation of claim 16, the further improvement wherein the load-carrying structure comprises one or more extending forks.

18. In the automated workstation of claim 16, the further improvement wherein

the latching member comprises an elongate element,

the release member exerts a torque tending to bring the elongate element into line with the pneumatic latch.

19. In the automated workstation of claim 16, the further improvement wherein the release comprises a spring-loaded member.

20. In the automated workstation of claim 19, the further improvement wherein the spring-loaded member stands proud from a surface of the effector.

21. In a robotic arm, the improvement comprising

a wash apparatus comprising one or more apertures, each arranged for receiving one or more respective tips disposed on the arm,

the wash apparatus translating from a first, carrying position in which the apertures are disposed clear of the respective one or more tips to a second, operative position in which the one or more tips are received in the one or more apertures,

such translation of the wash apparatus including rotating from the first position to a third, intermediate position and moving linearly from the third position to the second position.

22. In the robotic arm of claim 21, the further improvement wherein, when the wash apparatus is in the third position, each of the one or more apertures are aligned with one or more respective tips which are to be received therein.

23. In the robotic arm of claim 21, the further improvement wherein the tips are pipette tips and wherein the one or more apertures are arranged for receiving such pipette tips.

24. In the robotic arm of claim 23, the further improvement wherein at least one of the apertures is arranged for receiving the tip of a pipette comprising a thin-walled cylindrical chamber with a body having a wall defining a cavity, the cavity having an average diameter substantially equal to or under any of 1000 microns, 750 microns, 500 microns and 250 microns, the wall having an average thickness substantially equal to or under any of 1000 microns, 750 microns, 500 microns and 250 microns, the body holding a fluid volume substantially equal to or under any of 10 microliters, 1 microliter, 100 nanoliters, 50 nanoliters, and under 10 nanoliters.

25. In the robotic arm of claim 21, the further improvement wherein the wash apparatus comprises at least one of an ingress and egress for wash fluid.

26. In the robotic arm of claim 21, further improvement wherein the wash apparatus is disposed on an actuator for motion relative to the tips.

27. A pipetter for use with the robotic arm, comprising

a plurality of pipettes, each having a tip,

a wash apparatus disposed for motion relative to at least the tips, the wash apparatus comprising a plurality of apertures, each arranged for receiving a respective pipette tip,

the wash apparatus translating from a first, carrying position in which the wash apparatus and the apertures are disposed clear of the tips to a second, operative position in which the tips are received in the respective apertures, such translation of the wash apparatus including rotating from the first position to a third, intermediate position and moving linearly from the third position to the second position, wherein the apertures are aligned with their respective tips when the wash apparatus is in the third position,

the wash apparatus having at least one of an ingress and egress for wash fluid.

28. The pipetter of claim 27, wherein at least one of the apertures is arranged for receiving the tip of a pipette comprising a thin-walled cylindrical chamber with a body having a wall defining a cavity, the cavity having an average diameter substantially equal to or under any of 1000 microns, 750 microns, 500 microns and 250 microns, the wall having an average thickness substantially equal to or under any of 1000 microns, 750 microns, 500 microns and 250 microns, the body holding a fluid volume substantially equal to or under any of 10 microliters, 1 microliter, 100 nanoliters, 50 nanoliters, and under 10 nanoliters.

29. A pipette carrier for use in an automated workstation, comprising

a pipette having a proximal end and a distal end,

a plunger disposed for motion relative to the pipette,

a first element for at least pushing the plunger toward a distal end of the pipette,

a second element having an aperture in which the plunger is slidably disposed, the aperture being disposed between the first element and the proximal end of the pipette, the aperture being sized to prevent buckling of the plunger when the latter is pushed by the first element.

30. The pipette carrier of claim 29, wherein at least the proximal end of the pipette is disposed within a ferrule that is seated within a third element.

31. The pipette carrier of claim 30, wherein the proximal end of the pipette is disposed within a plenum within the third element.

32. The pipette carrier of claim 31, wherein the third element comprises at least one of an inlet and an outlet for wash fluid.

33. The pipette carrier of claim 29, wherein the aperture is disposed along a desired path of motion of the plunger.

34. The pipette carrier of claim 29, wherein the aperture is sized to permit motion of the plunger without such play as permits buckling of plunger or adversely impact positioning of its distal end.

35. The pipette carrier of claim 29, wherein the pipette comprises a thin-walled cylindrical chamber comprising a body having a wall defining a cavity, the cavity having an average diameter substantially equal to or under any of 1000 microns, 750 microns, 500 microns and 250 microns, the wall having an average thickness substantially equal to or under any of 1000 microns, 750 microns, 500 microns and 250 microns, the body holding a fluid volume substantially equal to or under any of 10 microliters, 1 microliter, 100 nanoliters, 50 nanoliters, and under 10 nanoliters.

36. In a pipette carrier of the type for carrying a plurality of pipettes, the improvement comprising

one or more pipettes coupled to a first member,

one or more plungers coupled to a second member,

the first and second members being coupled for motion relative to one another,

a third member disposed between the first and second members for motion relative to at least one of them,

the third member having one or more apertures in each of which one or more plungers are slidably disposed, at least one of the apertures being sized to reduce buckling of the one or more plungers disposed therein when those plungers are pushed.

37. In the pipette carrier of claim 36, the further improvement wherein at least one of plungers is sized to permit motion of the one or more plungers disposed therein without such play as permits buckling of those plungers or otherwise adversely impacts positioning of their distal ends when those plungers are pushed.

38. In the pipette carrier of claim 36, the further improvement wherein at least one of the pipettes is removably mounted to the first member.

39. In the pipette carrier of claim 38, the further improvement wherein at least one of the pipettes is disposed within a ferrule that is seated within the first member.

40. In the pipette carrier of claim 39, the further improvement wherein the proximal end is flanged of a pipette that is disposed within a ferrule.

41. In the pipette carrier claim 36, the further improvement wherein the pipettes are arranged in any of an array or matrix.

42. In the pipette carrier of claim 36, the further improvement wherein at least one of the plungers is removably mounted to the second member.

43. In the pipette carrier of claim 42, the further improvement wherein each plunger has a corresponding pipette, the proximal end into which the distal end of that plunger extends.

44. In the pipette carrier of claim 36, wherein the pipette comprises a thin-walled cylindrical chamber comprising a body having a wall defining a cavity, the cavity having an average diameter substantially equal to or under any of 1000 microns, 750 microns, 500 microns and 250 microns, the wall having an average thickness substantially equal to or under any of 1000 microns, 750 microns, 500 microns and 250 microns, the body holding a fluid volume substantially equal to or under any of 10 microliters, 1 microliter, 100 nanoliters, 50 nanoliters, and under 10 nanoliters.

45. In a pipetter for use with a robotic arm, the improvement comprising

a first plate (hereinafter termed “

lower”

plate) from which a set of pipettes extend,

a plunger assembly that includes

a second plate (hereinafter termed “

upper”

plate),

a set of plungers mounted in the upper plate, each plunger corresponding to a pipette in the set of pipettes and extending from the upper plate to the corresponding pipette,

the plunger assembly being coupled to the first plate for reciprocating motion with respect thereto,

the plunger assembly further including one or more anti-buckle plates disposed between the upper and lower plates, the one or more anti-buckle plates including apertures through which the plungers are slidably disposed, the apertures being sized to substantially prevent buckling of the plungers.

46. In the pipetter of claim 45, wherein the first plate includes a plenum in which proximal ends of the pipettes are in fluid communication.

47. In the pipetter of claim 46, comprising one or more fluid lines to any of supply wash fluid to and remove wash fluid from the plenum.

48. A pipetter, comprising

a pipette having a proximal end and a distal end,

a plunger disposed for motion relative to the pipette,

a first element for at least pushing the plunger toward a distal end of the pipette,

a second element having an aperture in which the plunger is slidably disposed, the aperture being disposed between the first element and the proximal end of the pipette, the aperture being sized to reduce buckling of the plunger when the latter is pushed by the first element,

an effector comprising a motor that is coupled to at least one of the first and second elements for moving at least one of the plunger and the pipette relative to the other.

49. A pipetter, comprising

a pipette having a proximal end and a distal end,

a plunger disposed for motion relative to the pipette,

an aperture in which the plunger is slidably disposed, the aperture being sized to reduce buckling of the plunger when the latter pushed relative to the pipette.

50. A pipetter of claim 49, comprising a motor for moving the plunger and the pipette relative to the other.

51. A pipetter of claim 50, comprising a suction member providing coupling between the motor and at least one of the plunger and the pipette.

52. A pipetter of claim 51, wherein the suction member is a suction cup.

53. A pipette carrier of claim 52, wherein the pipette comprises a thin-walled cylindrical chamber comprising a body having a wall defining a cavity, the cavity having an average diameter substantially equal to or under any of 1000 microns, 750 microns, 500 microns and 250 microns, the wall having an average thickness substantially equal to or under any of 1000 microns, 750 microns, 500 microns and 250 microns, the body holding a fluid volume substantially equal to or under any of 10 microliters, 1 microliter, 100 nanoliters, 50 nanoliters, and under 10 nanoliters.

54. A pipetter for use with a robotic arm, the pipetter comprising

a nanopipette carrier including

one or more nanopipettes coupled to a first plate-like member, at least one nanopipette comprising a thin-walled cylindrical chamber having a body with a wall defining a cavity, the cavity having an average diameter substantially equal to or under any of 1000 microns, 750 microns, 500 microns and 250 microns, the wall having an average thickness substantially equal to or under any of 1000 microns, 750 microns, 500 microns and 250 microns, the body holding a fluid volume substantially equal to or under any of 10 microliters, 1 microliter, 100 nanoliters, 50 nanoliters, and under 10 nanoliters,

one or more plungers coupled to a second plate-like member,

a third plate-like member disposed between the first and second members for motion relative to at least one of them,

the third plate-like member having one or more apertures in each of which one or more plungers are slidably disposed, at least one of the apertures being sized to reduce buckling of the one or more plungers disposed therein when those plungers are pushed,

an effector that is coupled to the carrier by way of at least a suction member, the effector for at least pushing the plungers relative to the nanopipettes.

55. The pipetter of claim 54, wherein the suction member comprises a suction cup arranged for releasable coupling to the second plate-like member.

56. The pipetter of claim 54, wherein the effector is coupled to the robotic arm.

57. The pipetter of claim 54, wherein the effector comprises a motor that is coupled with any of the first and second plate-like members.

58. The pipetter of claim 57, wherein the motor is arranged for at least one of pushing and pulling the plungers relative to the nanopipettes.

59. The pipetter of claim 58, wherein the nanopipette carrier is releasably coupled to the effector.

60. The pipetter of claim 58 comprising a fourth plate-like member that is coupled to the carrier, the fourth plate-like member providing a magnetic field for one or more of the nanopipettes.

61. The pipetter of claim 60, wherein the fourth plate-like member comprises one or more apertures arranged to receive distal tips of each of one or more nanopipettes, each aperture having an associated magnetic field source.

62. The pipetter of claim 60, wherein the fourth plate-like member is releasably attached to the carrier.

63. A processing station for use with a pipetter effector, comprising

a housing defining a cavity arranged to receive a set of nanopipettes carried by the pipetter effector,

the housing having a surface that at least one of supports and couples with effector,

the cavity having a surface including a sealing member arranged for sealing distal tips of nanopipettes received in the cavity.

64. The processing station of claim 63, wherein the cavity is sized to receive the set of nanopipettes at multiple registration positions.

65. The processing station of claim 64, wherein the housing surface includes at least one of a hole and a pin defining at least one said registration position.

66. The processing station of claim 65, wherein the at least one hole and pin is arranged to mate with structure on the pipetter effector.

67. The processing station of claim 63, wherein the first surface comprises an environmental sealing member that mates with the effector.

68. A processing station for use with a pipetter effector, comprising

a housing defining a cavity arranged to receive a set of nanopipettes carried by the pipetter effector,

the cavity having a wash member with one or more apertures arranged for receiving nanopipettes in the cavity, and

the wash member having a medium for washing one or more nanopipettes received by the wash member.

69. The processing station of claim 68, wherein the wash member comprises a reservoir for the medium.

70. The processing station of claim 68, wherein the wash member comprises a plurality of apertures, each for receiving a respective one of the nanopipettes.

71. The processing station of claim 68, wherein the wash member comprises at least one of an inlet and an outlet for the wash medium.

72. In a thermal processing station for use with a pipetter effector, the improvement comprising

a cavity arranged to receive one or more pipettes,

an airflow path that includes at least a portion of the cavity in which the pipettes are received,

the cavity being arranged with respect to the airflow path such that pipettes received in the cavity are exposed to an equi-temperature airflow.

73. In the thermal processing station of claim 72, the further improvement comprising a heater and a fan disposed, the heater and fan being arranged for generating a heated airflow along the airflow path.

74. In the thermal processing station of claim 73, the further improvement wherein the heater is positioned so as not to directly heat the pipettes by radiance.

75. In the thermal processing station of claim 74, the further improvement comprising baffles disposed between the heater and the pipettes.

76. In the thermal processing station of claim 73, the further improvement wherein the fan is a paddle wheel-style fan.

77. In the thermal processing station of claim 73, the further improvement comprising a baffle that can be set in one or more positions to permit at least one of environmental and cooling air to be drawn into the airflow path.

78. In the thermal processing station of claim 77, the further improvement wherein the baffle can be set in a position to permit recirculation of air.

79. In the thermal processing station of claim 73, the further improvement comprising a temperature-sensing device arranged for measuring a temperature of the airflow.

80. In the thermal processing station of claim 79, the further improvement wherein the temperature-sensing device is arranged for measuring a temperature of the airflow in a vicinity of the pipettes.

81. In the thermal processing station of claim 72, the further improvement wherein one or more of the pipettes comprise a thin-walled cylindrical chamber having a body with a wall defining a cavity, the cavity having an average diameter substantially equal to or under any of 1000 microns, 750 microns, 500 microns and 250 microns, the wall having an average thickness substantially equal to or under any of 1000 microns, 750 microns, 500 microns and 250 microns, the body holding a fluid volume substantially equal to or under any of 10 microliters, 1 microliter, 100 nanoliters, 50 nanoliters, and under 10 nanoliters.

82. A thermal processing station for use with a pipetter effector, comprising

a housing defining a cavity arranged to receive a set of nanopipettes carried by the pipetter effector,

an airflow path that includes at least a portion of the cavity in which the nanopipettes are received,

a heater for heating an airflow in the airflow path,

a baffle that selectively permits at least one of environmental and cooling air to be drawn into the airflow path,

a thermocouple arranged for measuring a temperature of the airflow,

the cavity being arranged with respect to the airflow path such that pipettes received in the cavity are exposed to an equi-temperature airflow.