Continuous processing automated workstation

• US 20030026732A1
• Filed: 06/24/2002
• Published: 02/06/2003
• Est. Priority Date: 10/16/1998
• Status: Abandoned Application

• Current Assignee: Brooks Automation Ltd. (United Kingdom) (Azenta, Inc.)
• Original Assignee: Brooks Automation Ltd. (United Kingdom) (Azenta, Inc.)
• Inventors: Liberman, Alex G., Prabhakar, Jayanth, Caron, Kenneth M., Keane, Richard J., Christopher, Anthony J., Gordon, Steven J., Sallum, Hani M.
• Application Number:
  US10/179,916
• Publication Number:
  US 20030026732A1
• Time in Patent Office: Days
• US Class Current: 422/63
• 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 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 35/1065 Multiple transfer devices
• CPC Class Codes: Y10T 436/11 Automated chemical analysis
• CPC Class Codes: Y10T 436/112499 with sample on test slide
• CPC Class Codes: Y10T 436/114165 with step of insertion or removal from test line
• CPC Class Codes: Y10T 436/114998 with treatment or replacement of aspirator element [e.g., cleaning, etc.]
• CPC Class Codes: Y10T 436/119163 with aspirator of claimed structure
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

Abstract

An automated workstation capable of continuous, non-stop processing of specimens includes an environmentally controlled storage area that holds multiple cassettes containing specimen plates. 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. An interlock mechanism prevents the operator and robotic arm from simultaneously accessing a cassette. Novel robotic arms, robotic arm positioning mechanisms, plate handling mechanisms, effector tip/plate washing mechanisms, thin-walled pipetters, back-flushing mechanisms and fluid level detection mechanisms, as well as methods for operating the same, facilitate continuous operation of the workstation along with compactness, high throughput and high accuracy of operation. Narrow, thin-walled capillary-like pipetters serve as both means for acquiring and processing small quantity specimens with high precision.

Claims

1. An automated workstation, comprising

A. a storage area capable of holding one or more specimens, the storage area having first and second accesses;

B. a robotic arm disposed for accessing specimens in the storage area via the first access; and

C. an interlock that prevents access to the specimens in the storage area via the second access when the robotic arm is accessing the specimens via the first access.

2. An automated workstation according to claim 1, comprising a panel for removably blocking the second access, wherein the interlock prevents the panel from being removed from blocking the second access when the robotic arm is accessing the specimens via the first access.

3. An automated workstation according to claim 1, wherein the interlock prevents the robotic arm from accessing the specimens in the storage area via the first access when the specimens are being accessed via the second access.

4. An automated workstation according to claim 1, comprising a panel for removably blocking the first access, wherein the interlock prevents the panel from being removed from blocking the first access when the specimens are being access via the second access.

5. An automated workstation, comprising

A. a storage area capable of holding a cassette containing zero, one or more specimens, the storage area having first and second accesses;

B. first and second panels for removable blocking the first and second accesses, respectively;

C. a robotic arm disposed for at least one of (i) removing specimens from and (ii) placing specimens in the cassette, via the first access; and

D. an interlock that at least one of (i) prevents the first panel from being removed from blocking the first access when the cassette is being accessed via the second access, and (ii) prevents the second panel from being removed from blocking the second access when the cassette is being accessed via the first access.

6. An automated workstation according to claim 5, wherein the interlock at least one of (i) prevents the first panel from being removed from blocking the first access when the second panel has been removed from blocking the second access, and (ii) prevents the second panel from being removed from blocking the second access when the first panel has been removed from blocking the first access.

7. An automated workstation, comprising

A. a storage area capable of holding a cassette containing zero, one or more specimens, the storage area having first and second accesses that are removably blocked by first and second panels, respectively;

B. a work area comprising at least one of (i) a transfer station and (ii) an apparatus for placing or processing a specimen;

C. a robotic arm that transfers specimens between the cassettes and the work area via the first access; and

D. an interlock that at least one of (i) prevents the first panel from being removed from blocking the first access when the cassette is being accessed via the second access, (ii) prevents the second panel from being removed from blocking the second access when the cassette is being accessed via the first access, and (iii) prevents at least selected action of the robotic arm when the storage area is being accessed by an operator through any of the first and second accesses, respectively.

8. An automated workstation according to claim 7, wherein the interlock at least one of (i) prevents the first panel from being removed from blocking the first access when the second panel has been removed from blocking the second access, (ii) prevents the second panel from being removed from blocking the second access when the first panel has been removed from blocking the first access.

9. An automated workstation according to claim 8, comprising

a third panel for removably blocking access to the work area,

wherein the interlock prevents any of (i) the third panel from being removed when the robotic arm is moving therein, and (ii) at least selected action of the robotic arm when the work area is being accessed by an operator.

10. An automated workstation according to claim 7, wherein at least one of the storage area and the work area is environmentally controlled.

11. An automated workstation according to claim 10, comprising apparatus that generates at least one of cooled, warmed, humidified, dehumidified or otherwise processed gas for transfer to at least one of the storage area and work area.

12. An automated workstation according to claim 7, comprising a carriage for moving the robotic arm, the carriage being disposed above the work area.

13. Apparatus for positioning a robotic arm, the apparatus comprising

A. a first carriage arranged for motion along a first axis;

B. a second disposed on the first carriage for motion along a second axis;

C. a first plurality of wheels disposed stationarily relative to the first and second carriages, and a second plurality of wheels disposed on the first carriage;

D. at least two of the wheels comprising drive wheels;

E. a drive belt defining a pathway about the wheels and having two ends that are coupled to the second carriage, the drive belt being so arranged that rotation of the drive wheels results in translation of the second carriage along at least one of the first and second axes.

15. Apparatus according to any of claims 13 and 14, wherein the first plurality of wheels are disposed at locations defining vertices of a first rectangle having a longitudinal axis substantially parallel to the first axis, and wherein the second plurality of wheels are disposed at locations defining vertices of a second rectangle having a longitudinal axis substantially parallel to the second axis.

16. Apparatus according to claim 15, wherein the drive belt pathway is substantially H-shaped.

17. Apparatus according to claim 15, wherein the first plurality of wheels includes the drive wheels and wherein those drive wheels are disposed at opposing vertices of the first rectangle with respect to a midline running parallel to the first axis.

18. Apparatus according to any of claims 13 and 14, wherein one or more wheels of wheels are biasedly mounted so as to affect tension in the belt.

14. An automated workstation, comprising

A. a storage area capable of holding specimens;

B. a work area comprising at least one of (i) a transfer station and (ii) an apparatus for placing or processing a specimen;

C. a robotic arm that transfers specimens between the cassettes and the work area via the first access, the robotic arm being disposed on a track that is situated above the work area and that is oriented along a first axis;

D. a first carriage arranged for motion along the track;

E. a second disposed on the first carriage for motion along a second axis, the second axis being substantially orthogonal to the first axis;

F. a first plurality of wheels disposed stationarily relative to the first and second carriages, and a second plurality of wheels disposed on the first carriage, at least two of the wheels comprising drive wheels;

G. a drive belt defining a pathway about the wheels and having two ends that are coupled to the second carriage, the drive belt being so arranged that rotation of the drive wheels results in translation of the second carriage along at least one of the first and second axes.

19. A robotic arm disposed on a mount, the arm comprising:

A. a first portion that extends along a first axis and that is finely positionable along that axis; and

B. a second portion that is coupled to the first portion and that extends between first and second positions in a direction of the first axis.

20. A robotic arm according to claim 19, wherein any of the first and second portions are coupled to a mount that moves along a plane, and wherein the first axis is substantially normal to that plane.

21. A robotic arm according to claim 20, wherein the mount moves along any of x- and y-axes and wherein the first and second sections extend along a z-axis.

22. A robotic arm disposed on a mount, the arm comprising:

A. a first extensible section comprising

i) a first frame;

ii) a finely-positionable motor-driven element that is coupled to the mount;

iii) a motor that is coupled to the frame and that is coupled to the motor-driven element, the motor driving the motor-driven element relative to the mount and, thereby, translating the first frame relative to the mount;

B. a second extensible section comprising

i) a second frame;

ii) an actuator that is coupled to the first and second frames, whereby actuation of the actuator translates the second frame relative to the first frame.

23. A robotic arm according to claim 22, comprising one or more effectors coupled to any of the first and second extensible sections.

24. A robotic arm according to claim 22, wherein the motor-driven element is a screw that is threadably coupled in the mount, and wherein the motor is mounted to the frame.

25. A robotic arm according to claim 22, wherein the actuator comprises

A. a housing that is affixed to the first frame,

B. an extensible portion that is affixed to the second frame.

31. An apparatus according to claim 22, comprising one or more effectors coupled to any of the first and second extensible sections for motion along the third axis.

32. An apparatus according to claim 31, wherein the effectors comprise any of handling apparatus, rinse apparatus, probes, pipettes and other handling and processing apparatus.

26. An apparatus comprising

A. first and second carriages, the first carriage arranged for motion along a first axis and the second carriage disposed on the first carriage for motion along a second axis;

B. first and second pluralities of wheels, the first plurality being disposed stationarily, the second plurality of wheels being disposed on the first carriage, at least two of the wheels in either of the first and second plurality of sets comprising drive wheels;

C. a drive belt defining a pathway about the wheels and having two ends that are coupled to the second carriage, the drive belt being so arranged that rotation of the drive wheels results in translation of the second carriage along at least one of the first and second axes; and

D. a robotic arm disposed on the second carriage, the robotic arm comprising

i) a first section that is affixed to the second carriage and that translates along a third axis via action of a motor;

ii) a second section that is affixed to the first section and that translates along the third axis.

27. An apparatus according to claim 26, wherein the first section comprises

A. a first frame;

B. a finely-positionable motor-driven element that is coupled to the mount; and

C. a motor that is coupled to the frame and that is coupled to the motor-driven element, the motor driving the motor-driven element relative to the mount and, thereby, translating the first frame relative to the mount;

28. An apparatus according to claim 26, wherein the second section comprises:

A. a second frame; and

B. an actuator that is coupled to the first and second frames, whereby actuation of the actuator translates the second frame relative to the first frame;

29. An apparatus according to claim 28, wherein the motor-driven element is a screw that is threadably coupled in the mount, and wherein the motor is mounted to the first frame.

30. An apparatus according to claim 28, wherein the actuator comprises

A. a housing that is affixed to the first frame,

B. an extensible portion that is affixed to the second frame.

33. A plate handling apparatus for use with a robotic arm, the plate handling apparatus comprising a first member for engaging a plate when the arm is positioned adjacent a side of the plate and a second member for engaging a plate when the arm is positioned adjacent a top of the plate.

34. A plate handling apparatus according to claim 33, wherein the first member comprises one or more elongate elements.

35. A plate handling apparatus according to claim 34, wherein a distal end of at least one of the elongate elements includes a protuberance.

36. A plate handling apparatus according to claim 35, wherein the protuberance comprises a hook-shaped end of the respective elongate element.

37. A plate handling apparatus according to claim 34, wherein at least one of the elongate elements is arranged for any of extension and retraction from the arm.

38. A plate handling apparatus according to claim 33, wherein the second member comprises one or more elements arranged for inward and outward motion relative to a central region of the effector.

39. A plate handling apparatus according to claim 33, wherein the second member comprises a plurality of elements arranged for any of pinching or grasping the plate.

40. A plate handling apparatus for use with a robotic arm, the plate handling apparatus comprising

A. a first member for engaging a plate when the arm is positioned adjacent a side of the plate, the first member comprising one or more elongate elements arranged for extension from the arm;

B. a second member for engaging a plate when the arm is positioned adjacent a top of the plate, the second member comprising a plurality of elements arranged for any of pinching or grasping the plate.

41. A plate handling apparatus according to claim 40, comprising a sensor that detects information regarding a plate.

42. A plate handling apparatus according to claim 41, wherein the sensor comprises an optical sensor.

43. A plate handling apparatus according to claim 41, wherein the optical sensor is arranged to detect information from plates disposed on multiple sides of the arm.

44. A plate handling apparatus according to claim 41, wherein the optical sensor comprises a beam splitter defining multiple optical sensing pathways.

45. A plate handling apparatus according to claim 42, wherein the optical sensor comprises a bar code reader.

46. A plate handling apparatus for use with a robotic arm, the plate handling apparatus comprising

A. a first member for engaging a plate when the arm is positioned adjacent a side of the plate, the first member comprising one or more elongate elements arranged for extension from the arm;

B. a second member for engaging a plate when the arm is positioned adjacent a top of the plate, the second member comprising a plurality of elements arranged for any of pinching or grasping the plate; and

C. an optical sensor for sensing indicia disposed on the plate, the optical sensor comprising a bar code reader and a beam splitter defining multiple optical sensing pathways.

47. A robotic arm disposed on a mount, the arm comprising:

A. a first extensible section comprising

i) a first frame;

ii) a finely-positionable, motor-driven element that is coupled to the mount;

iii) a motor that is coupled to the frame and that is coupled to the motor-driven element, the motor driving the motor-driven element relative to the mount and, thereby, translating the first frame relative to the mount;

B. a second extensible section comprising

i) a second frame;

ii) an actuator that is coupled to the first and second frames, whereby actuation of the actuator translates the second frame relative to the first frame;

C. a plate handling apparatus coupled to any of the first and second extensible section, the plate handling member comprising

i) a first member for engaging a plate when the arm is positioned adjacent a side of the plate, the first member comprising one or more elongate elements arranged for extension from the arm; and

ii) a second member for engaging a plate when the arm is positioned adjacent a top of the plate, the second member comprising a plurality of elements arranged for any of pinching or grasping the plate.

iii) an optical sensor for sensing indicia disposed on the plate, the optical sensor comprising a bar code reader and a beam splitter defining multiple optical sensing pathways.

48. In a specimen handling apparatus for use with a moveable robotic arm, the improvement comprising a wash fluid outlet disposed on the specimen handling apparatus.

49. In a specimen handling apparatus according to claim 48, the improvement wherein the wash fluid outlet comprises a cup for washing at least a portion of a specimen processing device disposed on the specimen handling apparatus.

50. In a specimen handling apparatus according to claim 49, the improvement wherein the specimen processing device comprises a tip and wherein the wash fluid outlet comprises a cup for washing that tip.

51. In a specimen handling apparatus according to claim 50, the improvement wherein the specimen processing device comprises a pipette.

52. In a specimen handling apparatus according to claim 49, the further improvement wherein the cup comprises a fluid port for washing any of a specimen or a specimen plate.

53. A robotic arm disposed on a moveable carriage, the arm comprising:

A. a first portion that is coupled to the mount and that extends via action of a motor;

B. a second portion that is coupled to the first portion and that extends therefrom;

C. a specimen handling apparatus coupled to any of the first and second portions, the specimen handling apparatus comprising a wash cup for washing at least a portion of a specimen processing device disposed on the specimen handling apparatus.

54. A robotic arm according to claim 53, wherein wash cup is arranged for translation between an inoperative position and an operative position.

55. A robotic arm according to claim 54, wherein wash cup is arranged for pivoting into an operative position.

56. A robotic arm according to claim 55, wherein the wash cup comprises a fluid port for washing any of a specimen or a specimen plate.

57. A fluid handling apparatus for use with a robotic arm, the apparatus comprising

A. a body for holding fluid, the body having a first fluid outlet;

B. a plunger slidably disposed within the body for at least one of expelling and drawing fluid via the first fluid outlet; and

C. a fluid inlet disposed for introducing fluid into the body, the fluid inlet being blocked by the plunger when the plunger is disposed in a first position, the fluid inlet not being blocked by the plunger when the plunger is disposed in a second position.

58. A fluid handling apparatus according to claim 57, wherein the body comprises a pipette and the first fluid outlet comprises a pipette tip.

59. A fluid handling apparatus according to claim 57, wherein the fluid inlet is disposed at an opposite end of the body from the first fluid outlet.

60. A fluid handling apparatus according to claim 57, wherein the plunger blocks the fluid inlet when the plunger is disposed within the body and wherein the plunger does not block the fluid inlet when the plunger is disposed outside the body.

61. A pipette apparatus for use with a robotic arm, the apparatus comprising

A. a body for holding fluid, the body having a tip;

B. a wash fluid inlet disposed at an end of the body opposite that of the tip;

C. a plunger slidably disposed within the body for at least one of expelling and drawing fluid via the tip, the plunger blocking the wash fluid inlet when the plunger is at least one of expelling and drawing fluid via the tip; and

D. the plunger being arranged for being drawn at least partially out of the body so as not to block the fluid inlet, thereby, permitting wash fluid to pass therefrom.

62. A pipette apparatus according to claim 61, comprising a fluid outlet providing an egress for the wash fluid.

63. A pipette apparatus according to claim 62, wherein the fluid outlet can be selectively opened thereby affecting a flow of wash fluid through the tip.

70. The pipette apparatus of claims 61, 68, and 69, wherein at least one body for holding fluid comprises a capillary having a wall defining a cavity for holding the fluid, 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.

64. A fluid handling apparatus for use with a robotic arm, the apparatus comprising

A. a body for holding fluid;

and

B. an optical detector for detecting at least one of a presence and a level of fluid in the body.

65. A fluid handling apparatus according to claim 64, comprising an illumination source that generates radiation for detection by the optical detector.

66. A fluid handling apparatus according to claim 65, wherein the optical detector generates an output as a function of radiation detected thereby.

67. A fluid handling apparatus according to claim 66, wherein the optical detector output at least one increases and decreases as a function of any of the presence and level of fluid in the body.

68. A pipette apparatus for use with a robotic arm, the apparatus comprising

A. a body for holding fluid;

B. an illumination source; and

C. an optical detector for detecting at least one of a presence and a level of fluid in the body.

69. A pipette apparatus for use with a robotic arm, the apparatus comprising

A. a plurality of bodies, each for holding fluid;

B. an illumination source; and

C. an optical detector for detecting at least one of a presence and a level of fluid in one or more of the bodies.

71. A method of processing biological and chemical samples, the method comprising steps of:

introducing a sample into a pipetter having a wall defining a cavity for holding the fluid, 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, and processing the sample within the pipetter.

72. The method of claim 71, comprising the steps of

introducing first and second samples into the pipetter,

mixing the first and second samples within the pipetter.

73. The method of claim 72, wherein the mixing step comprises reciprocating a plunger within the pipetter.

74. The method of claim 72, wherein the processing step comprises any of heating and cooling the pipetter.

75. The method of claim 74, wherein the processing step comprises exposing the pipetter to one or more thermally controlled environments.

76. The method of claim 72, wherein the processing step comprises exposing the pipetter to a magnetic field.

77. A method of thermally processing small volume biological and chemical samples, said method comprising steps of:

introducing a sample into a body having a wall defining a cavity for holding the fluid, 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 sample having a volume substantially equal to or under any of 10 microliters, 1 microliter, 100 nanoliters, 50 nanoliters, and under 10 nanoliters, and exposing the body to any of heating and cooling.

78. The method of claim 77, wherein the exposing step comprises exposing the body to one or more thermally controlled environments.

79. A method of isolating components of small volume biological or chemical samples, said method comprising steps of:

introducing a sample into a body having a wall defining a cavity for holding the fluid, 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 sample having a volume substantially equal to or under any of 10 microliters, 1 microliter, 100 nanoliters, 50 nanoliters, and under 10 nanoliters, the sample including any of a ferromagnetic and a paramagnetic component (collectively, “

magnetic component”

), and

placing the body in a magnetic field, thereby, at least partially separating the magnetic component from one or more other components in the sample.

80. A method of isolating components of a small volume biological or chemical sample, said method comprising steps of:

mixing the sample with magnetic beads,

introducing the sample and beads into a body having a wall defining a cavity for holding the fluid, 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 introduced sample and beads having a fluid volume substantially equal to or under any of 10 microliters, 1 microliter, 100 nanoliters, 50 nanoliters, and under 10 nanoliters,

placing the body into a magnetic field, thereby, at least partially localizing the magnetic compound and any components of the sample bound therewith,

any of separating and processing separately the bound components of the sample from any other components of the sample.

81. A nanopipetter for processing small volume fluid samples comprising:

a thin-walled cylindrical chamber for housing samples; and

a plunger slidably disposed of within the cylindrical chamber.

82. The nanopipetter of claim 81, wherein the thin-walled cylindrical chamber comprises a body having a wall defining a cavity for holding the fluid, 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.

83. An automated workstation comprising:

a robotic arm having an effector end; and

at least one thin-walled pipetter attached to the effector end of the robotic arm, the thin-walled pipetter comprising a body having a wall defining a cavity for holding the fluid, 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.

84. A robotic arm comprising:

A. first and second extensible portions that are coupled to one another,

B. the first extensible portion being extendable between first and second positions along a first axis,

C. the second extensible portion being extendable to a range of positions along the first axis and providing fine motion control therealong.

85. A robotic arm according to claim 84, wherein the first extensible portion extends pneumatically.

86. A robotic arm according to claim 85, wherein the second extensible portion extends via action of any of a motor and a screw.

87. A robotic arm according to claim 84, wherein the first extensible portion extends pneumatically and the second extensible portion extends via action of any of a motor and a screw.

88. A robotic arm according to claim 87, wherein the second extensible portion is coupled to a mount and extends therefrom, and wherein the first extensible portion is coupled to the second extensible portion is extends therefrom.

89. A robotic arm according to claim 88, wherein the mount is moveable along of any of second and third axes.

90. A robotic arm according to claim 89, wherein the first axis is a z-axis and wherein the first and second axes are x- and y-axes.