WO1999015905A1 - Systems and methods for handling and manipulating multi-well plates - Google Patents

Systems and methods for handling and manipulating multi-well plates Download PDF

Info

Publication number
WO1999015905A1
WO1999015905A1 PCT/EP1998/005994 EP9805994W WO9915905A1 WO 1999015905 A1 WO1999015905 A1 WO 1999015905A1 EP 9805994 W EP9805994 W EP 9805994W WO 9915905 A1 WO9915905 A1 WO 9915905A1
Authority
WO
WIPO (PCT)
Prior art keywords
plate
wells
frame member
robot
grasping mechanism
Prior art date
Application number
PCT/EP1998/005994
Other languages
French (fr)
Inventor
Albert William Brown, Jr.
Haim Kedar
Original Assignee
Glaxo Group Limited
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Glaxo Group Limited filed Critical Glaxo Group Limited
Priority to EP98952609A priority Critical patent/EP1018020A1/en
Priority to AU10244/99A priority patent/AU1024499A/en
Publication of WO1999015905A1 publication Critical patent/WO1999015905A1/en

Links

Classifications

    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/0099Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor comprising robots or similar manipulators
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/02Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
    • G01N35/04Details of the conveyor system
    • G01N2035/0401Sample carriers, cuvettes or reaction vessels
    • G01N2035/0418Plate elements with several rows of samples
    • G01N2035/042Plate elements with several rows of samples moved independently, e.g. by fork manipulator
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/02Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
    • G01N35/04Details of the conveyor system
    • G01N2035/0401Sample carriers, cuvettes or reaction vessels
    • G01N2035/0418Plate elements with several rows of samples
    • G01N2035/0425Stacks, magazines or elevators for plates
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/02Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
    • G01N35/028Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations having reaction cells in the form of microtitration plates
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10TTECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00Chemistry: analytical and immunological testing
    • Y10T436/11Automated chemical analysis
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10TTECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00Chemistry: analytical and immunological testing
    • Y10T436/11Automated chemical analysis
    • Y10T436/113332Automated chemical analysis with conveyance of sample along a test line in a container or rack
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10TTECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00Chemistry: analytical and immunological testing
    • Y10T436/11Automated chemical analysis
    • Y10T436/113332Automated chemical analysis with conveyance of sample along a test line in a container or rack
    • Y10T436/114998Automated chemical analysis with conveyance of sample along a test line in a container or rack with treatment or replacement of aspirator element [e.g., cleaning, etc.]

Definitions

  • the invention relates generally to the field of device handling and manipulation, and particularly to the handling and manipulation of multi-well plates.
  • the invention provides for the transport of multi-well plates to precise and known locations at various processing or evaluation stations.
  • multi-well plates to facilitate the performance of various chemical and biological procedures has become widely accepted.
  • Such multi-well plates are typically rectangular in geometry and have a two dimensional array of wells.
  • one common multi-well plate design has an 8 by 12 array of wells.
  • the wells of such plates are configured to receive various chemicals or substances.
  • One common procedure is the performance of assays where various chemicals or substances are introduced into the wells and any reactions are evaluated.
  • One type of assay evaluation may proceed by placing the plate above a camera to detect an emitted signal from the wells.
  • the plate This often requires the plate to be moved to various pieces of processing equipment for filling or removal. Further, the plates may also need to be transported to evaluation equipment for detection or other evaluation.
  • the wells When introducing or removing fluids or substances into or from the wells, and when evaluating the substances within the wells, the wells typically need to be aligned with distal tips, detection devices and the like.
  • various pieces of equipment may be needed to complete a procedure, each time the plate is moved to a different piece of equipment, the plate will need to be properly oriented according to the specifications of the given piece of equipment.
  • many types of fluid delivery equipment include a stage on which the plate is placed. Often a robot is employed to grasp the plate and move the plate to the stage.
  • such robots typically have a pair of grasping fingers which grasp the plate in an arbitrary manner and then place the plate on the stage.
  • the dispensing tips will need to be aligned with the wells in the plate.
  • Such a system is often burdensome and time consuming.
  • many types of filling equipment are provided with 96 dispensing tips. If an 864 well plate is placed on a stage which can move only in the vertical direction, it is difficult, if not impossible, for the 96 dispensing tips to fill all of the 864 wells while the plate remains fixed on the stage.
  • the invention provides exemplary systems, devices and methods for handling multi-well plates.
  • the invention provides a system for handling a plate having a plurality of wells and comprises a robot having a base member and at least one arm.
  • the arm includes a grasping mechanism which is adapted to grasp the plate.
  • the grasping mechanism is configured to receive the plate in a repeatable and known location such that the location of each well relative to the grasping mechanism is known by the robot.
  • the robot of the invention is particularly useful in combination with a plurality of stations which are positioned at known locations relative to the robot.
  • a processor that is associated with the robot may be configured to control movement of the robot to place the plate at predetermined locations at the stations.
  • some of the stations may include processing equipment having an array of delivery lines to allow fluids or substances to be introduced into the wells when the plate is at the predetermined locations. In this way, the plate may remain attached to the robot and be precisely aligned with the various delivery lines during a given procedure.
  • the plate may include 864. wells that are to be filled by a piece of equipment having 96 dispensing tips. Since the location of the wells is known to the robot relative to the dispensing tips, the robot may move the plate to nine different locations to allow all of the 864 wells to be filled. Once filling is finished, the robot may move the plate to another station where other procedures may be performed in a similar manner.
  • the arm comprises a shaft, an elbow attached to the shaft, and a linkage pivotally attached to the elbow.
  • the grasping mechanism is operably attached to the linkage.
  • the shaft is rotatable relative to the base member and is also movable in a vertical direction.
  • the linkage is pivotable relative to the elbow to move the grasping mechanism radially outward from the base member.
  • the grasping mechanism comprises a frame member having edges which are adapted to frame at least a portion of a periphery of the plate in a repeatable and predictable manner so that the location of the wells of the plate relative to the frame member is known when the plate is received into the frame member.
  • the grasping mechanism further includes a securing mechanism for securing the plate to the frame member when the plate is received within the frame member.
  • the system further includes a rack having a plurality of patterned shelves for housing a plurality of plates.
  • the frame member is provided with a patterned opening to allow the grasping mechanism to grasp a plate from the rack by positioning the frame member below one of the shelves having the desired plate and upwardly moving the frame member until the frame member lifts the plate from the shelf. During the upward movement of the frame member, the shelf passes through the patterned opening. To replace a plate, the frame member is lowered until the patterned opening passes over the patterned shelf, with the patterned shelf lifting the plate from the frame member.
  • the securing mechanism preferably comprises a clamping arm that is pivotally attached to the frame member and which is adapted to engage a portion of the periphery of the plate.
  • a clamping arm is particularly useful when the plate is generally rectangular in geometry. With such a plate geometry, the edges of the frame member are preferably configured to engage at least two sides of the plate while the clamping arm engages a corner of the plate that is located at an intersection of the other two sides of the plate. The clamping arm thus secures the plate against the edges of the frame member.
  • edges of the frame member which are adapted to engage the plate are inwardly tapered to assist in securing the plate to the frame member.
  • an edge of the clamping arm may also be tapered. Such tapering serves to prevent vertical movement of the plate when clamped to the frame member.
  • an attachment member is operably attached to the frame member to facilitate attachment to the arm of the robot.
  • a translation mechanism is provided for axially translating the frame member. In this way, the grasping mechanism may be laterally moved relative to the arm of the robot.
  • the invention further provides an exemplary method for handling a plate having a plurality of wells.
  • a robot is provided having a base member and at least one arm which includes a grasping mechanism.
  • a plate having a plurality of wells is grasped with the grasping mechanism such that the location of each well in the plate relative to the grasping mechanism is known by the robot.
  • the plate is moved with the robot to a predetermined location at a station.
  • the station may comprise a processing station which has delivery lines for introducing fluids into the wells or aspirating fluids from the wells.
  • the invention provides for introducing fluids into a first group of the wells while the plate is at a first predetermined location.
  • the plate is then moved with the robot to a second predetermined location at the processing station and fluids are introduced into a second group of the wells.
  • the plate may be moved with the robot to a predetermined location at another processing station to allow a sample to be introduced into the wells while the plate is at the predetermined location.
  • the station may comprise an evaluation station to allow the wells to be imaged with a camera while the plate is at the predetermined location.
  • the wells are aligned with pixels of the camera when the plate is at the predetermined location.
  • a plurality of plates may be stored on shelves of a rack. In this way, the robot may move the grasping mechanism to grasp one of the plates from the rack.
  • Fig. 1 is an exploded perspective view of an exemplary grasping mechanism according to the invention.
  • Fig. 2 is a top view of the grasping mechanism of Fig. 1.
  • Fig. 3 is a side view of the grasping mechanism of Fig. 1.
  • Fig. 4 is a perspective view of an exemplary plate handling system having a robot which employs the grasping mechanism of Fig. 1 according to the invention.
  • Fig. 4A is a perspective view of the robot of Fig. 4.
  • Fig. 4B is a more detailed view of the robot of Fig. 4A taken along lines B-B.
  • Figs. 4C and 4D illustrate movement of the robot of Fig. 4.
  • Fig. 4E is a perspective view of a patterned shelf of one of the racks of the system of Fig. 4.
  • Fig. 5 is a top view of the plate handling system of Fig. 4.
  • Fig. 6 is a side view of the plate handling system of Fig. 4.
  • Fig. 7 is a perspective view of an alternative grasping mechanism according to the invention.
  • Fig. 8 is an exploded view of the grasping mechanism of Fig. 7.
  • the invention provides exemplary systems, devices and methods for handling and manipulating multi-well plates.
  • the invention provides a robot having an arm with a grasping mechanism which is configured to grasp a multi- well plate in a repeatable and predictable manner such that the location of the wells relative to the robot is known each time the plate is grasped.
  • the grasping mechanism is configured such that each time a plate is grasped, it will be received at a precise location on the grasping mechanism so that the robot will know the precise location of each of the wells.
  • the robot of the invention will preferably be included in a work cell having various pieces of processing and/or evaluation equipment which are positioned at known locations relative to the robot.
  • the robot may be employed to move the plate to the various pieces of equipment and then align the wells with appropriate parts of the equipment.
  • Such a system thus eliminates, if desired, the need to place the plate on stages that are commonly incorporated into the various pieces of equipment.
  • the processing and evaluation equipment may be simplified, thereby reducing costs and simplifying the process.
  • the robot may be easily programmed to move the plate to the various pieces of equipment.
  • the invention may be used with a wide variety of multi-well plates, and will find its greatest use with multi-well plates having outer dimensions that are similar to the outer dimensions of most commercially available 96 well plates, typically having a length of about 12.8 cm and a width of about 8.6 cm.
  • the invention will be particularly useful with multi-well plates with more than 96 wells, such as 384 well plates, 864 well plates, 1536 well plates, and the like, while still having the same outer dimensions as standard 96 well plates.
  • 864 well plate which may be used with the invention is described in co- pending U.S. Application Serial No. 08/868,689, filed June 4, 1997, the disclosure of which is herein incorporated by reference.
  • the invention is particularly useful with multi-well plates having more than 96 wells because the robot is able to move the wells into alignment with pieces of equipment that are designed for 96 well plates.
  • the robot provides a way to use plates having larger numbers of wells with commercially available equipment originally designed for only 96 wells.
  • the position of each well relative to the robot will be known with precision.
  • the robot may then be employed to accurately align the wells with various pieces of equipment. Such accurate alignment is particularly important when the plate has more than 96 wells because the well sizes will be relatively small. If the wells are not precisely aligned, proper filing or processing will not be possible.
  • Grasping mechanism 10 comprises a frame member 12 which is configured to receive a multi-well plate 14.
  • Multi-well plate 14 includes a plurality of wells 16 which are arranged in a two dimensional array (for convenience of illustration, only a selected number of the wells are shown).
  • Frame member 12 includes four raised edges 18 which serve as stops when plate 14 is forced against them. Edges 18 are arranged such that they will engage two sides of plate 14 when plate 14 is grasped.
  • a clamping arm 20 is pivotally attached to frame member 12 in a manner such that it may be forced against a corner of plate 14. As clamping arm 20 pushes against the corner, it forces plate 14 against edges 18 to secure plate 14 to a precise location relative to frame member 12.
  • Edges 18 and clamping arm 20 are inwardly tapered as they approach frame member 12. In this way, when clamping arm 20 is pivoted against the corner, plate 14 will be forced downward against frame member 12. Hence, the location of plate 14 relative to frame member 12 will be secured in the X, Y and Z directions. In this manner, grasping mechanism 10 can be used with a wide variety of plates having standard sized outer dimensions and formats since the location of each well can be repeatably and precisely fixed relative to frame member 12.
  • Clamping arm 20 is pivotally attached to frame member 12 by an arm shaft 24.
  • an air actuated piston To pivot clamping arm 20 relative to frame member 12, an air actuated piston
  • Piston 26 having a rod 27 in combination with a spring 34 is employed.
  • Piston 26 is attached to frame member 12 by a mount bracket 28, and spring 34 is attached to an arm post 22 on frame member 12.
  • spring 34 (which is in tension) causes clamping arm 20 to pivot about shaft 24 to apply a force against the corner of plate 14 as previously described.
  • piston 26 is actuated to causing rod 27 to retract. In this manner, clamping arm 20 is pivoted in an opposite direction to release it from plate 14. As rod 27 of piston 26 retracts, spring 34 expands to allow clamping arm 20 to pivot.
  • frame member 12 includes a patterned opening 36.
  • patterned opening 36 is adapted to allow frame member 12 to pass over a patterned shelf when grasping plate 14.
  • Grasping mechanism 10 further includes an attachment member 38 which allows grasping mechanism 10 to be operably attached to a robot.
  • attachment member 38 Mounted to attachment member 38 is a linear translator 40 which moves frame member 12 in an axial direction.
  • linear translator 40 is able to move frame member 12 parallel to an X axis. In this way, once plate 14 is positioned at a piece of equipment, linear translator 40 may be employed to precisely move wells 16 into alignment with a set of dispensing tips or syringes as described in greater detail hereinafter.
  • an alignment extension 42 which tapers away from the inner surfaces of edges 18. In this way, when frame member 12 is moved upward to grasp a plate, alignment extensions 42 will assist in tunneling the plate into alignment with edges 18.
  • a robot 46 Central to work cell 44 is a robot 46 having a base member 48 and an arm 50. Pivotally attached to arm 50 is grasping mechanism 10. As best shown in Figs. 4A and 4B, arm 50 comprises a shaft 50a, an elbow 50b, and a linkage 50c. Robot 46 is operably attached to a table 52 having a top 54 which includes a plurality holes 56 (with only a few of holes 56 being shown for convenience of illustration). The distance between each of holes 56 is known so that various pieces of equipment may be attached to top 54, with the distance between the pieces of equipment and robot 46 being known.
  • An exemplary table top which may be used with the invention is a TMC optical table top.
  • Robot 46 is configured to move in a variety of directions to position plate 14 at various locations.
  • shaft 50a is vertically movable in an up and down motion, i.e. along a Z axis.
  • Shaft 50a is also rotatable relative to base member 48.
  • Elbow 50b is fixedly attached to shaft 50a and rotates with shaft 50a.
  • Linkage 50c is pivotable relative to elbow
  • frame member 12 is axially translatable relative to attachment member 38.
  • One such robot that may be used with the invention is a ATM-205 robot, commercially available from Equipe Technologies. However, it will be appreciated that other robots may also be used.
  • the invention employ a robot where radial motion is achieved by extension and retraction of a piston.
  • Grasping mechanism 50 is attached to turntable 51 which is configured to maintain a Y axis of plate 14 (see Figs. 4C and 4D) parallel to a line between points A and B on arm 50 during vertical or rotational movement of shaft 50a and/or during movement of linkage 50c. In this way, turntable 51 will rotate relative to linkage 50c during movement of arm 50 to maintain the Y axis of plate 14 at a constant orientation relative to the line between points A and B. With such a configuration, plate 14 will be properly oriented when moved to various locations surrounding robot 46.
  • Figs. 4-6 Selectively positioned about table 52 are various pieces of equipment which facilitate the performance of various procedures involving multi-well plate 14. It will appreciated that the particular arrangement illustrated in Figs. 4-6 is only one type of arrangement, and a variety of other pieces of equipment and/or arrangements may be used in accordance with the principles of the invention.
  • pieces of equipment such as particle dispensers or handlers, fluorimeters, cameras, and the like may be attached to top 54 for performing a variety of procedures including fluid handling, detection, mixing, incubation, depositing of particles (such as beads) in multi-wells plates, and the like.
  • Each of the racks includes a plurality of patterned shelves 68 which are configured to pass through patterned opening 36 of frame member 12 (see Fig. 1 ) and which are provided to hold multi-well plates.
  • robot 46 may be employed to grasp and remove a plate from one of the racks by positioning frame member 12 below one of the shelves 68 which holds a plate that is to be removed.
  • the robot aligns patterned opening 36 with the patterned self 68 and then lifts frame member 12 vertically upward until frame member 12 lifts the plate from the shelf.
  • alignment extensions 42 see Fig. 2 assist in positioning plate 14 onto frame member 12.
  • shelf 68 includes raised portions 69 which assist in properly positioning plate 14 on the shelf. For example, when placing a plate on shelf 68, grasping mechanism 10 is lowered until shelf 68 passes through patterned opening 36. At this point raised portions 69 guide plate 14 onto shelf 68 in a desired orientation.
  • Robot 46 may be used in performing a variety of procedures. As one example, robot 46 may be employed to move plate 14 to a dispensing station 70.
  • Dispensing station 70 includes an array of dispensing tips or syringes (not shown) for introducing fluids into well 16 of plate 14.
  • dispensing station 70 may comprise a Hydra 96 dispenser, commercially available from Robbins Scientific, which includes a two dimensional array of 96 syringes. With such an arrangement of syringes, robot 46 will move plate 14 to align 96 of its
  • the linear translator 40 (see Fig. 1 ) will linearly translate plate 14 a few millimeters along the X axis to align a group of 96 wells (which are laterally adjacent to the wells just filled) with the 96 syringes. This process is repeated for the next group of wells which are laterally adjacent to the wells just filled.
  • Arm 50 then moves plate 14 so that another set of rows of the wells which are longitudinally spaced from the filled wells are aligned with the syringes.
  • turntable 51 maintains plate 14 properly oriented along the Y axis during movement of arm 50.
  • the aligned rows are then filled as described above.
  • the above process is then repeated until all of the 864 wells are filled. Hence, by precisely locating 864 wells relative to the frame member, the wells can be accurately filled with 96 syringes.
  • Adjacent dispensing station 70 is a valve array 72, such as an 8X valve array, having valves which are commercially available from The Lee Company.
  • Robot 46 is employed to move plate 14 to valve array 72, with eight of the wells being aligned with the eight valve array.
  • Array 72 may also be moved by a linear stage to align itself with the columns of wells in plate 14.
  • robot 46 which is employed to move plate 14 to various stations within the work cell.
  • various processes and/or evaluation procedures may be performed, with robot 46 facilitating manipulation and handling of plate 14. Since both the location of the wells relative to the robot and the location of the various pieces of equipment relative to the robot are known, the robot may be employed to align the wells with the appropriate pieces of equipment as needed.
  • Grasping mechanism 80 may be employed with a robot in work cell 44 in a manner similar to that previously described.
  • Grasping mechanism 80 comprises a frame member 82 for holding a multi-well plate 84 having a plurality of wells 86.
  • Frame member 82 includes a pair of edges 88 which are perpendicular to each other.
  • a clamping arm 90 is pivotally attached to frame member 82 by a shaft 92. Further, clamping arm 90 includes leaf springs 94 and 96. In this way, when plate 84 is placed on frame member 82, clamping arm 90 is pivoted to force springs 94 and 96 against two sides of plate 84.

Abstract

The invention provides exemplary systems, devices and methods for manipulating and handling multi-well plates. In one exemplary embodiment, a system is provided which comprises a robot having a base member and at least one arm. The arm includes a grasping mechanism which is adapted to grasp the plate. Further, the grasping mechanism is configured to receive the plate in a repeatable and known location such that the location of each well relative to the grasping mechanism is known by the robot.

Description

SYSTEMS AND METHODS FOR HANDLING AND MANIPULATING MULTI- WELL PLATES
BACKGROUND OF THE INVENTION
The invention relates generally to the field of device handling and manipulation, and particularly to the handling and manipulation of multi-well plates. In one particular aspect, the invention provides for the transport of multi-well plates to precise and known locations at various processing or evaluation stations.
The use of multi-well plates to facilitate the performance of various chemical and biological procedures has become widely accepted. Such multi-well plates are typically rectangular in geometry and have a two dimensional array of wells. For example, one common multi-well plate design has an 8 by 12 array of wells.
To accommodate the performance of various procedures, the wells of such plates are configured to receive various chemicals or substances. One common procedure is the performance of assays where various chemicals or substances are introduced into the wells and any reactions are evaluated. One type of assay evaluation may proceed by placing the plate above a camera to detect an emitted signal from the wells.
Hence, when using such multi-well plates, it is often desirable to efficiently deliver and/or remove various chemicals or substances into or from the wells.
This often requires the plate to be moved to various pieces of processing equipment for filling or removal. Further, the plates may also need to be transported to evaluation equipment for detection or other evaluation.
When introducing or removing fluids or substances into or from the wells, and when evaluating the substances within the wells, the wells typically need to be aligned with distal tips, detection devices and the like. However, since various pieces of equipment may be needed to complete a procedure, each time the plate is moved to a different piece of equipment, the plate will need to be properly oriented according to the specifications of the given piece of equipment. For example, many types of fluid delivery equipment include a stage on which the plate is placed. Often a robot is employed to grasp the plate and move the plate to the stage. However, such robots typically have a pair of grasping fingers which grasp the plate in an arbitrary manner and then place the plate on the stage.
Hence, once on the stage and removed from the robot, the dispensing tips will need to be aligned with the wells in the plate. Such a system is often burdensome and time consuming. Moreover, as it becomes more desirable to increase the numbers of wells in the plate while reducing their size, it becomes more difficult to precisely align the wells with various pieces of equipment. For example, many types of filling equipment are provided with 96 dispensing tips. If an 864 well plate is placed on a stage which can move only in the vertical direction, it is difficult, if not impossible, for the 96 dispensing tips to fill all of the 864 wells while the plate remains fixed on the stage.
Hence, it would be desirable to provide systems, devices and methods to facilitate the transport of multi-well plates between various pieces of equipment in a manner such that the wells may be efficiently accessed or evaluated.
SUMMARY OF THE INVENTION
The invention provides exemplary systems, devices and methods for handling multi-well plates. In one exemplary embodiment, the invention provides a system for handling a plate having a plurality of wells and comprises a robot having a base member and at least one arm. The arm includes a grasping mechanism which is adapted to grasp the plate. Further, the grasping mechanism is configured to receive the plate in a repeatable and known location such that the location of each well relative to the grasping mechanism is known by the robot.
The robot of the invention is particularly useful in combination with a plurality of stations which are positioned at known locations relative to the robot. In this way, a processor that is associated with the robot may be configured to control movement of the robot to place the plate at predetermined locations at the stations. For instance, some of the stations may include processing equipment having an array of delivery lines to allow fluids or substances to be introduced into the wells when the plate is at the predetermined locations. In this way, the plate may remain attached to the robot and be precisely aligned with the various delivery lines during a given procedure.
As one example, the plate may include 864. wells that are to be filled by a piece of equipment having 96 dispensing tips. Since the location of the wells is known to the robot relative to the dispensing tips, the robot may move the plate to nine different locations to allow all of the 864 wells to be filled. Once filling is finished, the robot may move the plate to another station where other procedures may be performed in a similar manner.
In one particular aspect, the arm comprises a shaft, an elbow attached to the shaft, and a linkage pivotally attached to the elbow. With such a configuration, the grasping mechanism is operably attached to the linkage. In another aspect, the shaft is rotatable relative to the base member and is also movable in a vertical direction. The linkage is pivotable relative to the elbow to move the grasping mechanism radially outward from the base member.
In one particularly preferable aspect, the grasping mechanism comprises a frame member having edges which are adapted to frame at least a portion of a periphery of the plate in a repeatable and predictable manner so that the location of the wells of the plate relative to the frame member is known when the plate is received into the frame member. The grasping mechanism further includes a securing mechanism for securing the plate to the frame member when the plate is received within the frame member.
In one exemplary aspect, the system further includes a rack having a plurality of patterned shelves for housing a plurality of plates. With such a configuration, the frame member is provided with a patterned opening to allow the grasping mechanism to grasp a plate from the rack by positioning the frame member below one of the shelves having the desired plate and upwardly moving the frame member until the frame member lifts the plate from the shelf. During the upward movement of the frame member, the shelf passes through the patterned opening. To replace a plate, the frame member is lowered until the patterned opening passes over the patterned shelf, with the patterned shelf lifting the plate from the frame member.
The securing mechanism preferably comprises a clamping arm that is pivotally attached to the frame member and which is adapted to engage a portion of the periphery of the plate. Such a clamping arm is particularly useful when the plate is generally rectangular in geometry. With such a plate geometry, the edges of the frame member are preferably configured to engage at least two sides of the plate while the clamping arm engages a corner of the plate that is located at an intersection of the other two sides of the plate. The clamping arm thus secures the plate against the edges of the frame member.
In one particular aspect, at least some of the edges of the frame member which are adapted to engage the plate are inwardly tapered to assist in securing the plate to the frame member. Similarly, an edge of the clamping arm may also be tapered. Such tapering serves to prevent vertical movement of the plate when clamped to the frame member. In still another aspect, an attachment member is operably attached to the frame member to facilitate attachment to the arm of the robot. In yet another aspect, a translation mechanism is provided for axially translating the frame member. In this way, the grasping mechanism may be laterally moved relative to the arm of the robot.
The invention further provides an exemplary method for handling a plate having a plurality of wells. According to the method, a robot is provided having a base member and at least one arm which includes a grasping mechanism. A plate having a plurality of wells is grasped with the grasping mechanism such that the location of each well in the plate relative to the grasping mechanism is known by the robot.
Once grasped, the plate is moved with the robot to a predetermined location at a station. In this manner, the location of the wells of the plate relative to the station is known so that fluids or substances may be transferred into or removed from the wells. For example, the station may comprise a processing station which has delivery lines for introducing fluids into the wells or aspirating fluids from the wells. When the plate has more wells than fluid delivery lines, the invention provides for introducing fluids into a first group of the wells while the plate is at a first predetermined location. The plate is then moved with the robot to a second predetermined location at the processing station and fluids are introduced into a second group of the wells.
Further, the plate may be moved with the robot to a predetermined location at another processing station to allow a sample to be introduced into the wells while the plate is at the predetermined location. As another example, the station may comprise an evaluation station to allow the wells to be imaged with a camera while the plate is at the predetermined location. Preferably, the wells are aligned with pixels of the camera when the plate is at the predetermined location. In still another aspect, a plurality of plates may be stored on shelves of a rack. In this way, the robot may move the grasping mechanism to grasp one of the plates from the rack.
BRIEF DESCRIPTION OF THE DRAWINGS
Fig. 1 is an exploded perspective view of an exemplary grasping mechanism according to the invention.
Fig. 2 is a top view of the grasping mechanism of Fig. 1.
Fig. 3 is a side view of the grasping mechanism of Fig. 1.
Fig. 4 is a perspective view of an exemplary plate handling system having a robot which employs the grasping mechanism of Fig. 1 according to the invention.
Fig. 4A is a perspective view of the robot of Fig. 4.
Fig. 4B is a more detailed view of the robot of Fig. 4A taken along lines B-B.
Figs. 4C and 4D illustrate movement of the robot of Fig. 4.
Fig. 4E is a perspective view of a patterned shelf of one of the racks of the system of Fig. 4.
Fig. 5 is a top view of the plate handling system of Fig. 4.
Fig. 6 is a side view of the plate handling system of Fig. 4. Fig. 7 is a perspective view of an alternative grasping mechanism according to the invention.
Fig. 8 is an exploded view of the grasping mechanism of Fig. 7.
DETAILED DESCRIPTION OF THE SPECIFIC EMBODIMENTS
The invention provides exemplary systems, devices and methods for handling and manipulating multi-well plates. In particular, the invention provides a robot having an arm with a grasping mechanism which is configured to grasp a multi- well plate in a repeatable and predictable manner such that the location of the wells relative to the robot is known each time the plate is grasped. The grasping mechanism is configured such that each time a plate is grasped, it will be received at a precise location on the grasping mechanism so that the robot will know the precise location of each of the wells.
The robot of the invention will preferably be included in a work cell having various pieces of processing and/or evaluation equipment which are positioned at known locations relative to the robot. In this way, the robot may be employed to move the plate to the various pieces of equipment and then align the wells with appropriate parts of the equipment. Such a system thus eliminates, if desired, the need to place the plate on stages that are commonly incorporated into the various pieces of equipment. In this manner, the processing and evaluation equipment may be simplified, thereby reducing costs and simplifying the process. Further, by using a relatively simple robot, the robot may be easily programmed to move the plate to the various pieces of equipment.
The invention may be used with a wide variety of multi-well plates, and will find its greatest use with multi-well plates having outer dimensions that are similar to the outer dimensions of most commercially available 96 well plates, typically having a length of about 12.8 cm and a width of about 8.6 cm. The invention will be particularly useful with multi-well plates with more than 96 wells, such as 384 well plates, 864 well plates, 1536 well plates, and the like, while still having the same outer dimensions as standard 96 well plates. For instance, one type of 864 well plate which may be used with the invention is described in co- pending U.S. Application Serial No. 08/868,689, filed June 4, 1997, the disclosure of which is herein incorporated by reference. The invention is particularly useful with multi-well plates having more than 96 wells because the robot is able to move the wells into alignment with pieces of equipment that are designed for 96 well plates. In this way, the robot provides a way to use plates having larger numbers of wells with commercially available equipment originally designed for only 96 wells. Moreover, by providing a grasping mechanism which can repeatably grasp a multi-well plate in a precise location on the grasping mechanism, the position of each well relative to the robot will be known with precision. The robot may then be employed to accurately align the wells with various pieces of equipment. Such accurate alignment is particularly important when the plate has more than 96 wells because the well sizes will be relatively small. If the wells are not precisely aligned, proper filing or processing will not be possible.
Referring now to Figs. 1-3, an exemplary embodiment of a grasping mechanism 10 which is useful in connection with a robot will be described. Grasping mechanism 10 comprises a frame member 12 which is configured to receive a multi-well plate 14. Multi-well plate 14 includes a plurality of wells 16 which are arranged in a two dimensional array (for convenience of illustration, only a selected number of the wells are shown).
Frame member 12 includes four raised edges 18 which serve as stops when plate 14 is forced against them. Edges 18 are arranged such that they will engage two sides of plate 14 when plate 14 is grasped. A clamping arm 20 is pivotally attached to frame member 12 in a manner such that it may be forced against a corner of plate 14. As clamping arm 20 pushes against the corner, it forces plate 14 against edges 18 to secure plate 14 to a precise location relative to frame member 12.
Edges 18 and clamping arm 20 are inwardly tapered as they approach frame member 12. In this way, when clamping arm 20 is pivoted against the corner, plate 14 will be forced downward against frame member 12. Hence, the location of plate 14 relative to frame member 12 will be secured in the X, Y and Z directions. In this manner, grasping mechanism 10 can be used with a wide variety of plates having standard sized outer dimensions and formats since the location of each well can be repeatably and precisely fixed relative to frame member 12.
Clamping arm 20 is pivotally attached to frame member 12 by an arm shaft 24. To pivot clamping arm 20 relative to frame member 12, an air actuated piston
26 having a rod 27 in combination with a spring 34 is employed. Piston 26 is attached to frame member 12 by a mount bracket 28, and spring 34 is attached to an arm post 22 on frame member 12. Between piston 26 and clamping arm 20 is a clevis 30 and a linkage 32. With such a configuration, spring 34 (which is in tension) causes clamping arm 20 to pivot about shaft 24 to apply a force against the corner of plate 14 as previously described. To release clamping arm 20, piston 26 is actuated to causing rod 27 to retract. In this manner, clamping arm 20 is pivoted in an opposite direction to release it from plate 14. As rod 27 of piston 26 retracts, spring 34 expands to allow clamping arm 20 to pivot.
As best shown in Fig. 1 , frame member 12 includes a patterned opening 36. As described in greater detail hereinafter, patterned opening 36 is adapted to allow frame member 12 to pass over a patterned shelf when grasping plate 14. Grasping mechanism 10 further includes an attachment member 38 which allows grasping mechanism 10 to be operably attached to a robot. Mounted to attachment member 38 is a linear translator 40 which moves frame member 12 in an axial direction. For instance, as illustrated in Fig. 2, linear translator 40 is able to move frame member 12 parallel to an X axis. In this way, once plate 14 is positioned at a piece of equipment, linear translator 40 may be employed to precisely move wells 16 into alignment with a set of dispensing tips or syringes as described in greater detail hereinafter.
Attached to two of the edges 18 is an alignment extension 42 which tapers away from the inner surfaces of edges 18. In this way, when frame member 12 is moved upward to grasp a plate, alignment extensions 42 will assist in tunneling the plate into alignment with edges 18.
Referring now to Figs. 4-6, an exemplary work cell 44 will be described.
Central to work cell 44 is a robot 46 having a base member 48 and an arm 50. Pivotally attached to arm 50 is grasping mechanism 10. As best shown in Figs. 4A and 4B, arm 50 comprises a shaft 50a, an elbow 50b, and a linkage 50c. Robot 46 is operably attached to a table 52 having a top 54 which includes a plurality holes 56 (with only a few of holes 56 being shown for convenience of illustration). The distance between each of holes 56 is known so that various pieces of equipment may be attached to top 54, with the distance between the pieces of equipment and robot 46 being known. An exemplary table top which may be used with the invention is a TMC optical table top.
Robot 46 is configured to move in a variety of directions to position plate 14 at various locations. For example, as best shown in Figs. 4A and 4B, shaft 50a is vertically movable in an up and down motion, i.e. along a Z axis. Shaft 50a is also rotatable relative to base member 48. Elbow 50b is fixedly attached to shaft 50a and rotates with shaft 50a. Linkage 50c is pivotable relative to elbow
50b to allow a distal end of linkage 50c having a turntable 51 to move in a radial direction relative to base member 48. As previously described, frame member 12 is axially translatable relative to attachment member 38. One such robot that may be used with the invention is a ATM-205 robot, commercially available from Equipe Technologies. However, it will be appreciated that other robots may also be used. For example, the invention employ a robot where radial motion is achieved by extension and retraction of a piston.
Grasping mechanism 50 is attached to turntable 51 which is configured to maintain a Y axis of plate 14 (see Figs. 4C and 4D) parallel to a line between points A and B on arm 50 during vertical or rotational movement of shaft 50a and/or during movement of linkage 50c. In this way, turntable 51 will rotate relative to linkage 50c during movement of arm 50 to maintain the Y axis of plate 14 at a constant orientation relative to the line between points A and B. With such a configuration, plate 14 will be properly oriented when moved to various locations surrounding robot 46.
Selectively positioned about table 52 are various pieces of equipment which facilitate the performance of various procedures involving multi-well plate 14. It will appreciated that the particular arrangement illustrated in Figs. 4-6 is only one type of arrangement, and a variety of other pieces of equipment and/or arrangements may be used in accordance with the principles of the invention. For example, pieces of equipment such as particle dispensers or handlers, fluorimeters, cameras, and the like may be attached to top 54 for performing a variety of procedures including fluid handling, detection, mixing, incubation, depositing of particles (such as beads) in multi-wells plates, and the like.
As shown, attached to top 54 are a plurality of racks 58, 60, 62, 64, and 66. Each of the racks includes a plurality of patterned shelves 68 which are configured to pass through patterned opening 36 of frame member 12 (see Fig. 1 ) and which are provided to hold multi-well plates. In this manner, robot 46 may be employed to grasp and remove a plate from one of the racks by positioning frame member 12 below one of the shelves 68 which holds a plate that is to be removed. The robot aligns patterned opening 36 with the patterned self 68 and then lifts frame member 12 vertically upward until frame member 12 lifts the plate from the shelf. As previously described, alignment extensions 42 (see Fig. 2) assist in positioning plate 14 onto frame member 12.
When plate 14 rests upon frame member 12, air piston 26 (see Fig. 2) is de- pressurized causing spring 34 to force clamping arm 20 against the corner of plate 14 as previously described. In turn, this forces plate 14 against edges 18 to secure plate 14 to grasping mechanism 10. Robot 46 then moves plate 14 to another one of the racks or another piece of equipment for processing, evaluation, or the like.
As shown in Fig. 4E, shelf 68 includes raised portions 69 which assist in properly positioning plate 14 on the shelf. For example, when placing a plate on shelf 68, grasping mechanism 10 is lowered until shelf 68 passes through patterned opening 36. At this point raised portions 69 guide plate 14 onto shelf 68 in a desired orientation.
Robot 46 may be used in performing a variety of procedures. As one example, robot 46 may be employed to move plate 14 to a dispensing station 70.
Dispensing station 70 includes an array of dispensing tips or syringes (not shown) for introducing fluids into well 16 of plate 14. For example, dispensing station 70 may comprise a Hydra 96 dispenser, commercially available from Robbins Scientific, which includes a two dimensional array of 96 syringes. With such an arrangement of syringes, robot 46 will move plate 14 to align 96 of its
864 wells with the 96 syringes. After the fluids have been introduced to the 96 wells, the linear translator 40 (see Fig. 1 ) will linearly translate plate 14 a few millimeters along the X axis to align a group of 96 wells (which are laterally adjacent to the wells just filled) with the 96 syringes. This process is repeated for the next group of wells which are laterally adjacent to the wells just filled.
Arm 50 then moves plate 14 so that another set of rows of the wells which are longitudinally spaced from the filled wells are aligned with the syringes. As described above, turntable 51 maintains plate 14 properly oriented along the Y axis during movement of arm 50. The aligned rows are then filled as described above. The above process is then repeated until all of the 864 wells are filled. Hence, by precisely locating 864 wells relative to the frame member, the wells can be accurately filled with 96 syringes.
Adjacent dispensing station 70 is a valve array 72, such as an 8X valve array, having valves which are commercially available from The Lee Company. Robot 46 is employed to move plate 14 to valve array 72, with eight of the wells being aligned with the eight valve array. Array 72 may also be moved by a linear stage to align itself with the columns of wells in plate 14.
Hence, a variety of pieces of equipment may be disposed about robot 46 which is employed to move plate 14 to various stations within the work cell. In turn, various processes and/or evaluation procedures may be performed, with robot 46 facilitating manipulation and handling of plate 14. Since both the location of the wells relative to the robot and the location of the various pieces of equipment relative to the robot are known, the robot may be employed to align the wells with the appropriate pieces of equipment as needed.
Referring now to Figs. 7 and 8, an alternative embodiment of a grasping mechanism 80 will be described. Grasping mechanism 80 may be employed with a robot in work cell 44 in a manner similar to that previously described. Grasping mechanism 80 comprises a frame member 82 for holding a multi-well plate 84 having a plurality of wells 86. Frame member 82 includes a pair of edges 88 which are perpendicular to each other. A clamping arm 90 is pivotally attached to frame member 82 by a shaft 92. Further, clamping arm 90 includes leaf springs 94 and 96. In this way, when plate 84 is placed on frame member 82, clamping arm 90 is pivoted to force springs 94 and 96 against two sides of plate 84. In turn, the other two sides of plate 84 are forced against edges 88 to secure plate 84 to frame member 82 in a manner similar to that previously described in connection with grasping mechanism 10. An air piston 98 is employed to pivot clamping arm 90. Piston 98 is attached to an attachment member 100 which in turn is configured to attach grasping mechanism 80 to a robot. Various linkages 102 and 104 are positioned between air piston 98 and clamping arm 90 to allow clamping arm 90 to be pivoted upon actuation of air piston 98 in a manner similar to that previously described in connection with grasping mechanism 10.
The invention has now been described in detail. However, it will be appreciated that certain changes and modifications may be made. Therefore, the scope and content of this invention are not limited by the foregoing description. Rather, the scope and content are to be defined by the following claims.

Claims

CLAIMS:
1. A system for handling a plate having a plurality of wells, the system comprising: a robot having a base member and at least one arm, wherein the arm includes a grasping mechanism which is adapted to grasp the plate, and wherein the grasping mechanism is configured to receive the plate in a repeatable and known location such that the location of each well relative to the grasping mechanism is known by the robot.
2. A system as in claim 1 , further comprising a plurality of stations at known locations relative to the robot, and wherein the system further includes a processor associated with the robot, wherein the processor is configured to control movement of the robot to place the plate at predetermined locations at the stations.
3. A system as in claim 2, wherein the plate has at least 864 wells, wherein at least some of the stations include equipment operable with at least some of the wells of the plate, and wherein selective ones of the wells of the plate are aligned with the equipment when the plate is placed at the predetermined locations.
4. A system as in claim 3, wherein the equipment comprises an array of delivery lines to allow fluids, particles or substances to be introduced into the wells or removed from the wells when the plate is at the predetermined locations.
5. A system as in claim 1 , wherein the arm comprises a shaft, an elbow attached to the shaft, and a linkage pivotally attached to the elbow, and wherein the grasping mechanism is operably attached to the linkage.
6. A system as in claim 5, wherein the shaft is rotatable relative to the base member and is movable in a vertical direction, and wherein the linkage is pivotable relative to the shaft to move the grasping mechanism radially outward from the base member.
7. A system as in claim 1 , wherein the grasping mechanism comprises a frame member having edges which are adapted to frame at least a portion of a periphery of the plate in a repeatable and predictable manner so that the location of the wells of the plate relative to the frame member is known when the plate is received into the frame member; and a securing mechanism adapted to secure the plate to the frame member when the plate is received within the frame member.
8. A system as in claim 7, further comprising a rack having a plurality of patterned shelves for housing a plurality of plates, wherein the frame member has a patterned opening to allow the grasping mechanism to pass over one of the patterned shelves to grasp the plate.
9. A device for handling a plate having a plurality of wells, the device comprising: a frame member having edges which are adapted to frame at least a portion of a periphery of the plate in a repeatable and predictable manner so that the location of the wells of the plate relative to the frame member is known when the plate is received into the frame member; 5 a securing mechanism adapted to secure the plate to the frame member when the plate is received within the frame member.
10. A device as in claim 9, wherein the securing mechanism comprises a clamping arm that is pivotally attached to the frame member and which is o adapted to engage a portion of the periphery of the plate.
11. A device as in claim 10, wherein the plate is generally rectangular in geometry and includes four sides, wherein the edges of the frame member are adapted to engage at least two sides of the plate, and wherein the clamping arm is adapted to engage a corner of the plate that is at an intersection of the other two sides of the plate.
12. A device as in claim 10, further comprising a piston to pivotally move the clamping arm.
13. A device as in claim 10, wherein at least some of the edges of the frame member which are adapted to engage the plate are tapered to assist in securing the plate to the frame member.
14. A device as in claim 13, wherein an edge of the clamping arm is tapered to assist in securing the plate to the frame member.
15. A device as in claim 10, further comprising an attachment member operably attached to the frame member, the attachment member being configured to be attached to an arm of a robot.
16. A device as in claim 10, further comprising a translation mechanism for axially translating the frame member.
17. A device as in claim 10, wherein the frame member has a patterned opening which is adapted to allow the grasping mechanism to pass over a patterned shelf holding a plate that is to be grasped.
18. A method for handling a plate having a plurality of wells, the method comprising: providing a robot having a base member and at least one arm, wherein the arm includes a grasping mechanism; grasping a plate having a plurality of wells with the grasping mechanism such that the location of each well in the plate relative to the grasping mechanism is known by the robot.
19. A method as in claim 18, further comprising moving the plate with the robot to a predetermined location at a station such that the location of the wells of the plate relative to the station is known.
20. A method as in claim 19, wherein the station comprises a processing station, and further comprising introducing fluids into or aspirating fluids from a first group of the wells while the plate is at a first predetermined location.
21. A method as in claim 20, further comprising moving the plate with the robot to a second predetermined location at the processing station and introducing fluids into or aspirating fluids from a second group of the wells.
22. A method as in claim 20, further comprising moving the plate with the robot to a predetermined location at another processing station, and further comprising introducing a biological substance into the wells while the plate is at the predetermined location.
23. A method as in claim 19, wherein the station comprises an evaluation station, and further comprising imaging the wells with a camera while the plate is at the predetermined location.
24. A method as in claim 23, wherein the wells are aligned with pixels of the camera when the plate is at the predetermined location.
25. A method as in claim 18, wherein the grasping step further comprises grasping the plate from a rack.
26. A method as in claim 20, wherein the plate has at least 864 wells, and wherein the first group of wells comprises a two dimensional array of 96 wells.
27. A device for grasping a plate having a plurality of wells, the device comprising: a frame member having edges which are adapted to frame at least a portion of a periphery of the plate when the plate is received in the frame member; and a clamping arm which is adapted to force the plate against the edges; wherein at least some of the edges and the clamping arm having inwardly angled sides which are adapted to force the plate downward against the frame member when the clamping arm is forced against the plate to allow the plate to be secured to the frame member in a repeatable and predictable manner so that the location of the wells of the plate relative to the frame member is known.
PCT/EP1998/005994 1997-09-24 1998-09-22 Systems and methods for handling and manipulating multi-well plates WO1999015905A1 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
EP98952609A EP1018020A1 (en) 1997-09-24 1998-09-22 Systems and methods for handling and manipulating multi-well plates
AU10244/99A AU1024499A (en) 1997-09-24 1998-09-22 Systems and methods for handling and manipulating multi-well plates

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US08/937,139 US6323035B1 (en) 1997-09-24 1997-09-24 Systems and methods for handling and manipulating multi-well plates
US08/937,139 1997-09-24

Publications (1)

Publication Number Publication Date
WO1999015905A1 true WO1999015905A1 (en) 1999-04-01

Family

ID=25469557

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1998/005994 WO1999015905A1 (en) 1997-09-24 1998-09-22 Systems and methods for handling and manipulating multi-well plates

Country Status (4)

Country Link
US (1) US6323035B1 (en)
EP (1) EP1018020A1 (en)
AU (1) AU1024499A (en)
WO (1) WO1999015905A1 (en)

Cited By (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1018020A1 (en) 1997-09-24 2000-07-12 Glaxo Group Limited Systems and methods for handling and manipulating multi-well plates
WO2001010554A2 (en) * 1999-08-09 2001-02-15 Bilatec Ag Laboratory robot and method and reagent kit for isolating nucleic acids
DE10009555A1 (en) * 1999-09-02 2001-03-08 Liconic Ag Nendeln Storage facility and climate box with integrated storage facility
DE19949005A1 (en) * 1999-10-11 2001-05-10 Leica Microsystems Device and method for introducing various transparent substrates into a high-precision measuring device
WO2001034291A2 (en) * 1999-11-09 2001-05-17 Sri International High-throughput synthesis, screening and characterization of combinatorial libraries
WO2001057539A1 (en) * 2000-02-01 2001-08-09 Incyte Genomics, Inc. Pipetting station apparatus
WO2001057538A1 (en) * 2000-02-01 2001-08-09 Incyte Genomics, Inc. Method and apparatus for shuttling microtitre plates
DE20006549U1 (en) * 2000-04-08 2001-08-16 Mwg Biotech Ag Device for carrying out chemical or biological processes
DE20006548U1 (en) * 2000-04-08 2001-08-23 Mwg Biotech Ag Device for carrying out chemical or biological processes
EP1186891A1 (en) * 2000-09-05 2002-03-13 Tecan Schweiz AG Holder for microtiterplate
EP1214568A1 (en) * 2000-07-07 2002-06-19 TransTech Pharma Inc. Automated systems for weighing and/or liquid delivery
WO2003070874A1 (en) 2002-02-22 2003-08-28 Sanyo Electric Co., Ltd. Culture device and storage container
DE19949008C2 (en) * 1999-10-11 2003-12-11 Leica Microsystems Device and method for loading substrates of different sizes in substrate holders
DE10232680A1 (en) * 2002-07-18 2004-02-12 Siemens Ag Automatic optical analysis of contrast agents at living cell cultures/medication effects on small animals, uses robot arm which moves samples in and out of chamber where light from samples is detected for evaluation
EP1582874A1 (en) * 2004-03-31 2005-10-05 Roche Diagnostics GmbH Modular analysing apparatus
WO2008152204A1 (en) * 2007-06-12 2008-12-18 Wallac Oy Automated instrumentation and method for measurements of samples
US7510362B2 (en) 2002-12-18 2009-03-31 Liconic Ag Climate controlled cabinet with movable carrier
US7544329B2 (en) 2001-01-26 2009-06-09 Liconic Ag Air-conditioned storage cupboard
WO2011113858A1 (en) * 2010-03-18 2011-09-22 Quantifoil Instruments Gmbh Positioning unit for a functional unit
CH704399A1 (en) * 2011-01-29 2012-07-31 Liconic Ag System for handling or operating laboratory objects, has storage device provided with storage for multiple laboratory objects, where transition device is arranged in storage device to transport laboratory objects
US9126200B2 (en) 2009-03-18 2015-09-08 Quantifoil Instruments Gmbh Positioning device for a sample carrier
EP2310129A4 (en) * 2008-07-18 2015-12-09 Accuri Cytometers Inc Wellplate handler system for a flow cytometer
US10031064B2 (en) 2010-10-25 2018-07-24 Accuri Cytometers, Inc. Systems and user interface for collecting a data set in a flow cytometer

Families Citing this family (41)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6838051B2 (en) * 1999-05-03 2005-01-04 Ljl Biosystems, Inc. Integrated sample-processing system
US6331437B1 (en) * 1998-07-14 2001-12-18 Bayer Corporation Automatic handler for feeding containers into and out of an analytical instrument
US6485692B1 (en) * 1998-12-04 2002-11-26 Symyx Technologies, Inc. Continuous feed parallel reactor
ATE341003T1 (en) * 1999-02-16 2006-10-15 Applera Corp DEVICE FOR HANDLING BEADS
ATE334397T1 (en) * 1999-12-21 2006-08-15 Tecan Trading Ag CLAMPING DEVICE FOR RECEIVING AND PRECISELY POSITIONING AN OBJECT, PREFERABLY A MICROTITER PLATE, AND METHOD FOR OPERATING IT
US6746648B1 (en) * 2000-06-15 2004-06-08 Beckman Coulter, Inc. Method and system for transporting and storing multiple reagent packs and reagent packs used therein
EP1307749A4 (en) * 2000-06-15 2005-04-20 Irm Llc Automated precision object holder
US6719949B1 (en) * 2000-06-29 2004-04-13 Applera Corporation Apparatus and method for transporting sample well trays
US20040072225A1 (en) * 2000-08-15 2004-04-15 Incyte Corporation Microarray retrieval unit
US6852291B1 (en) * 2000-10-11 2005-02-08 Innovadyne Technologies, Inc. Hybrid valve apparatus and method for fluid handling
US7135146B2 (en) * 2000-10-11 2006-11-14 Innovadyne Technologies, Inc. Universal non-contact dispense peripheral apparatus and method for a primary liquid handling device
JP2004511788A (en) * 2000-10-13 2004-04-15 アイアールエム エルエルシー High throughput processing system and method of use
EP1390147A4 (en) * 2001-05-03 2006-06-07 Affymetrix Inc High throughput microarray spotting system and method
CA2473860A1 (en) * 2002-01-25 2003-08-07 Innovadyne Technologies, Inc. Low volume, non-contact liquid dispensing method
DE10207847A1 (en) * 2002-02-15 2003-08-28 Zeiss Carl Jena Gmbh Ejection device for a climate chamber, in particular for holding microtiter plates (MTP)
AU2002319160A1 (en) * 2002-04-26 2003-11-10 Strobbe Graphics N.V. Positioning device, especially for offset plates
US20030215357A1 (en) * 2002-05-13 2003-11-20 Nigel Malterer Automated processing system and method of using same
US7452712B2 (en) 2002-07-30 2008-11-18 Applied Biosystems Inc. Sample block apparatus and method of maintaining a microcard on a sample block
EP1403644A1 (en) * 2002-09-25 2004-03-31 Agilent Technologies Inc. a Delaware Corporation Fluid analyzer
AU2002953384A0 (en) * 2002-12-16 2003-01-09 Canon Kabushiki Kaisha Method and apparatus for image metadata entry
US7314341B2 (en) * 2003-01-10 2008-01-01 Liconic Ag Automatic storage device and climate controlled cabinet with such a device
US6970240B2 (en) * 2003-03-10 2005-11-29 Applera Corporation Combination reader
AU2004245123A1 (en) * 2003-06-05 2004-12-16 Bioprocessors Corp. System and method for process automation
US20050226779A1 (en) * 2003-09-19 2005-10-13 Oldham Mark F Vacuum assist for a microplate
US20070015289A1 (en) * 2003-09-19 2007-01-18 Kao H P Dispenser array spotting
US20050221358A1 (en) * 2003-09-19 2005-10-06 Carrillo Albert L Pressure chamber clamp mechanism
US7666362B2 (en) * 2004-03-31 2010-02-23 Becton, Dickinson And Company Micro-plate and lid for robotic handling
JP4737976B2 (en) * 2004-03-31 2011-08-03 ベクトン・ディキンソン・アンド・カンパニー Microplate and lid for robot handling
WO2006078714A2 (en) * 2005-01-19 2006-07-27 Irm Llc Multi-well container positioning devices, systems, computer program products, and methods
US7622079B2 (en) * 2005-03-22 2009-11-24 Applied Biosystems, Llc Dual nest microplate spotter
EP1715348B2 (en) * 2005-07-15 2019-05-08 Agilent Technologies, Inc. Handling unit for microfluidic devices with clamping means
DE602007006687D1 (en) * 2006-11-22 2010-07-01 Health Robotics Srl METHOD AND MACHINE FOR HANDLING TOXIC SUBSTANCES
EP1972874B1 (en) * 2007-03-20 2019-02-13 Liconic Ag Automated substance warehouse
US20100248981A1 (en) * 2009-03-27 2010-09-30 Affymetrix, Inc. System and methods for processing microarrays
DE102012016830B4 (en) * 2012-08-24 2021-08-26 Bruker Daltonics GmbH & Co. KG Preparation device for mass spectrometric samples
KR102610239B1 (en) * 2015-05-28 2023-12-04 비디 키에스트라 비.브이. Automated methods and systems for obtaining and preparing microbial samples for identification and antibiotic susceptibility testing
CN106483312B (en) * 2015-08-26 2018-03-13 广明光电股份有限公司 The tumbler of biological detection
WO2017178890A1 (en) * 2016-04-15 2017-10-19 Andrew Alliance S.A. Consumable manipulation for the purpose of liquid handling
IT201600069410A1 (en) * 2016-07-04 2018-01-04 Alifax Srl INTEGRATED SYSTEM FOR DIAGNOSTIC ANALYSIS
GB2559365A (en) * 2017-02-02 2018-08-08 Peak Analysis And Automation Ltd Robotic positioning system
EP3454064B1 (en) * 2017-09-08 2020-11-11 F. Hoffmann-La Roche AG Rack positioning system

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4971514A (en) * 1988-11-14 1990-11-20 Prolic Sa Stacking device for plate-like objects, in particular titer plates or the like
US4981801A (en) * 1984-05-15 1991-01-01 University Of Tokyo Automatic cycling reaction apparatus and automatic analyzing apparatus using the same
WO1992022800A1 (en) * 1991-06-13 1992-12-23 Abbott Laboratories Liquid dispensing mechanism
US5416329A (en) * 1990-05-08 1995-05-16 Wallac Oy Apparatus for counting liquid scintillation samples
WO1997011352A1 (en) * 1995-09-22 1997-03-27 Labsystems Oy Plate holder
US5645800A (en) * 1991-10-31 1997-07-08 Dade Microscan Inc. Specimen processing and analyzing systems with associated fluid dispensing apparatus

Family Cites Families (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3650306A (en) * 1970-09-18 1972-03-21 Cooke Eng Co Laboratory dispensing apparatus
US4396579A (en) * 1981-08-06 1983-08-02 Miles Laboratories, Inc. Luminescence detection device
US4526690A (en) * 1983-02-04 1985-07-02 Millipore Corporation Apparatus for nucleic acid quantification
US4493815A (en) * 1983-07-28 1985-01-15 Bio-Rad Laboratories, Inc. Supporting and filtering biochemical test plate assembly
WO1988000704A1 (en) * 1986-07-11 1988-01-28 Beckman Instruments, Inc. Analyzer operating method
US5108704A (en) * 1988-09-16 1992-04-28 W. R. Grace & Co.-Conn. Microfiltration apparatus with radially spaced nozzles
US5219528A (en) * 1989-07-28 1993-06-15 Pierce Chemical Company Apparatus for rapid immunoassays
US5167922A (en) * 1990-04-27 1992-12-01 Pb Diagnostic Systems Inc. Assay cartridge
FR2672126B1 (en) * 1990-11-16 1994-04-08 Alcyon Analyser Sa REACTIONAL SEGMENT FOR AUTOMATIC SAMPLE ANALYZER AND ANALYZER EQUIPPED WITH A SEGMENT.
JP2787963B2 (en) * 1991-08-24 1998-08-20 株式会社島津製作所 Reaction tank
US5332549A (en) * 1992-07-01 1994-07-26 Pb Diagnostic Systems, Inc. Assay module transport apparatus for use in an automated analytical instrument
US5324483B1 (en) * 1992-10-08 1996-09-24 Warner Lambert Co Apparatus for multiple simultaneous synthesis
WO1994008759A1 (en) * 1992-10-16 1994-04-28 Thomas Jefferson University Method and apparatus for robotically performing sanger dideoxynucleotide dna sequencing reactions
US5470744A (en) * 1994-04-14 1995-11-28 Astle; Thomas W. Bioassay incubator for use with robotic arms
US5460783A (en) * 1994-06-14 1995-10-24 Synbiotics Corporation Apparatus for automatically removing microtiter well-strips from well-strip holders
DE4425439A1 (en) * 1994-07-19 1996-01-25 Boehringer Mannheim Gmbh Test strip evaluation device with a transport unit for test strips
AU4770296A (en) * 1995-03-27 1996-10-16 Warner-Lambert Company Method and apparatus for simultaneously testing a plurality of compounds to detect their activity
US5609826A (en) * 1995-04-17 1997-03-11 Ontogen Corporation Methods and apparatus for the generation of chemical libraries
US5620894A (en) * 1995-06-16 1997-04-15 Glaxo Wellcome Inc. Apparatus for automated biological cell harvesting
US5738827A (en) * 1995-08-23 1998-04-14 Ljl Biosystems, Inc. Apparatus for holding reagent and sample vessels
US6323035B1 (en) 1997-09-24 2001-11-27 Glaxo Wellcome, Inc. Systems and methods for handling and manipulating multi-well plates

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4981801A (en) * 1984-05-15 1991-01-01 University Of Tokyo Automatic cycling reaction apparatus and automatic analyzing apparatus using the same
US4971514A (en) * 1988-11-14 1990-11-20 Prolic Sa Stacking device for plate-like objects, in particular titer plates or the like
US5416329A (en) * 1990-05-08 1995-05-16 Wallac Oy Apparatus for counting liquid scintillation samples
WO1992022800A1 (en) * 1991-06-13 1992-12-23 Abbott Laboratories Liquid dispensing mechanism
US5645800A (en) * 1991-10-31 1997-07-08 Dade Microscan Inc. Specimen processing and analyzing systems with associated fluid dispensing apparatus
WO1997011352A1 (en) * 1995-09-22 1997-03-27 Labsystems Oy Plate holder

Cited By (42)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1018020A1 (en) 1997-09-24 2000-07-12 Glaxo Group Limited Systems and methods for handling and manipulating multi-well plates
WO2001010554A2 (en) * 1999-08-09 2001-02-15 Bilatec Ag Laboratory robot and method and reagent kit for isolating nucleic acids
WO2001010554A3 (en) * 1999-08-09 2001-08-23 Bilatec Ges Zur Entwicklung Bi Laboratory robot and method and reagent kit for isolating nucleic acids
EP1074488B1 (en) * 1999-09-02 2002-09-25 Liconic Ag Air conditioned cabinet with storage device
DE10009555A1 (en) * 1999-09-02 2001-03-08 Liconic Ag Nendeln Storage facility and climate box with integrated storage facility
EP1211197B1 (en) * 1999-09-02 2003-02-26 Liconic Ag Air-conditioned cabinet
US6478524B1 (en) 1999-09-02 2002-11-12 Liconic Ag Storage arrangement and storage receptacle with storage arrangement
DE19949005A1 (en) * 1999-10-11 2001-05-10 Leica Microsystems Device and method for introducing various transparent substrates into a high-precision measuring device
DE19949008C2 (en) * 1999-10-11 2003-12-11 Leica Microsystems Device and method for loading substrates of different sizes in substrate holders
WO2001034291A2 (en) * 1999-11-09 2001-05-17 Sri International High-throughput synthesis, screening and characterization of combinatorial libraries
US6602714B1 (en) 1999-11-09 2003-08-05 Sri International Viscosity and mass sensor for the high-throughput synthesis, screening and characterization of combinatorial libraries
WO2001034291A3 (en) * 1999-11-09 2001-12-06 Stanford Res Inst Int High-throughput synthesis, screening and characterization of combinatorial libraries
US6325114B1 (en) 2000-02-01 2001-12-04 Incyte Genomics, Inc. Pipetting station apparatus
WO2001057538A1 (en) * 2000-02-01 2001-08-09 Incyte Genomics, Inc. Method and apparatus for shuttling microtitre plates
US6739448B1 (en) 2000-02-01 2004-05-25 Incyte Corporation Method and apparatus for shuttling microtitre plates
WO2001057539A1 (en) * 2000-02-01 2001-08-09 Incyte Genomics, Inc. Pipetting station apparatus
DE20006548U1 (en) * 2000-04-08 2001-08-23 Mwg Biotech Ag Device for carrying out chemical or biological processes
DE20006549U1 (en) * 2000-04-08 2001-08-16 Mwg Biotech Ag Device for carrying out chemical or biological processes
EP1214568A1 (en) * 2000-07-07 2002-06-19 TransTech Pharma Inc. Automated systems for weighing and/or liquid delivery
US6898549B1 (en) 2000-07-07 2005-05-24 Transtech Pharma, Inc. Automated systems for weighing and/or liquid delivery
WO2002021145A1 (en) * 2000-09-05 2002-03-14 Tecan Trading Ag Support for a microtiter plate
EP1186891A1 (en) * 2000-09-05 2002-03-13 Tecan Schweiz AG Holder for microtiterplate
US7544329B2 (en) 2001-01-26 2009-06-09 Liconic Ag Air-conditioned storage cupboard
WO2003070874A1 (en) 2002-02-22 2003-08-28 Sanyo Electric Co., Ltd. Culture device and storage container
US7785867B2 (en) 2002-02-22 2010-08-31 Sanyo Electric Co., Ltd. Culture device and storage container
EP1477554A1 (en) * 2002-02-22 2004-11-17 Sanyo Electric Co., Ltd. Culture device and storage container
EP1477554A4 (en) * 2002-02-22 2007-06-27 Sanyo Electric Co Culture device and storage container
DE10232680A1 (en) * 2002-07-18 2004-02-12 Siemens Ag Automatic optical analysis of contrast agents at living cell cultures/medication effects on small animals, uses robot arm which moves samples in and out of chamber where light from samples is detected for evaluation
US7510362B2 (en) 2002-12-18 2009-03-31 Liconic Ag Climate controlled cabinet with movable carrier
US8192133B2 (en) 2002-12-18 2012-06-05 Liconic Ag Climate controlled cabinet with movable carrier
EP1582874A1 (en) * 2004-03-31 2005-10-05 Roche Diagnostics GmbH Modular analysing apparatus
WO2008152204A1 (en) * 2007-06-12 2008-12-18 Wallac Oy Automated instrumentation and method for measurements of samples
US8669112B2 (en) 2007-06-12 2014-03-11 Wallac Oy Automated instrumentation and method for measurements of samples
EP2310129A4 (en) * 2008-07-18 2015-12-09 Accuri Cytometers Inc Wellplate handler system for a flow cytometer
US9126200B2 (en) 2009-03-18 2015-09-08 Quantifoil Instruments Gmbh Positioning device for a sample carrier
US9132428B2 (en) 2009-03-18 2015-09-15 Quantifoil Instruments Gmbh Positioning device for a sample carrier
WO2011113858A1 (en) * 2010-03-18 2011-09-22 Quantifoil Instruments Gmbh Positioning unit for a functional unit
US9126162B2 (en) 2010-03-18 2015-09-08 Quantifoil Instruments Gmbh Positioning unit for a functional unit
US10031064B2 (en) 2010-10-25 2018-07-24 Accuri Cytometers, Inc. Systems and user interface for collecting a data set in a flow cytometer
US10481074B2 (en) 2010-10-25 2019-11-19 Becton, Dickinson And Company Systems and user interface for collecting a data set in a flow cytometer
US11125674B2 (en) 2010-10-25 2021-09-21 Becton, Dickinson And Company Systems and user interface for collecting a data set in a flow cytometer
CH704399A1 (en) * 2011-01-29 2012-07-31 Liconic Ag System for handling or operating laboratory objects, has storage device provided with storage for multiple laboratory objects, where transition device is arranged in storage device to transport laboratory objects

Also Published As

Publication number Publication date
AU1024499A (en) 1999-04-12
EP1018020A1 (en) 2000-07-12
US6323035B1 (en) 2001-11-27

Similar Documents

Publication Publication Date Title
US6323035B1 (en) Systems and methods for handling and manipulating multi-well plates
EP1353796B1 (en) Plate locator for precision liquid handler
EP1366822B1 (en) Liquid handling robot for well plates
US6592324B2 (en) Gripper mechanism
US6159425A (en) Sample transporter
US7105132B2 (en) Liquid chemical distribution method and apparatus
EP1171230B1 (en) Matrix storage and dispensing system
EP1355766B1 (en) Method and system for picking and placing vessels
US7361309B2 (en) Matrix storage and dispensing system
US6732598B2 (en) Automatic pipettor with a single-row, multi-channel pipetting head
AU2009200967B2 (en) Dispensing apparatus
US20020037237A1 (en) Automated precision object holder and method of using same
US20040136868A1 (en) Microarray placer unit
US7264432B2 (en) Device and method for transferring objects
WO2002013968A2 (en) Microarray placer unit
NZ533143A (en) Tissue array instrument with moving and releasing of punches automatically
JPH0751559A (en) Distributing and weighing apparatus for liquid specimen
US20210220833A1 (en) Labware aligning systems and liquid handling systems and methods including same
EP1477813A1 (en) Vial transfer apparatus
US20040072225A1 (en) Microarray retrieval unit
DE19853184A1 (en) Device for conveying a carrier element
JP3459475B2 (en) Storage device
US20030165409A1 (en) Device and method for manipulating or dispensing multiple filaments
JP2023536138A (en) Autosampler system with automated sample vessel cover removal and sample probe positioning

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AL AM AT AU AZ BA BB BG BR BY CA CH CN CU CZ DE DK EE ES FI GB GE GH GM HR HU ID IL IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT UA UG US UZ VN YU ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW SD SZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
WWE Wipo information: entry into national phase

Ref document number: 1998952609

Country of ref document: EP

NENP Non-entry into the national phase

Ref country code: KR

WWE Wipo information: entry into national phase

Ref document number: 09508612

Country of ref document: US

WWP Wipo information: published in national office

Ref document number: 1998952609

Country of ref document: EP

REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

NENP Non-entry into the national phase

Ref country code: CA

WWW Wipo information: withdrawn in national office

Ref document number: 1998952609

Country of ref document: EP