Liquid handling apparatus

Abstract

A liquid handler system includes a probe transport system that has a plurality of carriages movable along a support. Each of the carriages carries a second support, which in turn carries a third support. A plurality of probes are linked to a movable holder on the third supports. Through operation of a liquid handler system of the invention, liquid may be selectively delivered to one or more of a plurality of liquid receptacles.

Description

FIELD OF THE INVENTION

[0001] The present invention relates to liquid handlers for pharmaceutical, drug development and similar laboratory applications.

DESCRIPTION OF THE PRIOR ART

[0002] In pharmaceutical, genomic and proteomic research and drug development laboratories, as well as similar applications, automated liquid handlers are used for handling laboratory samples in a variety of laboratory procedures. For example, liquid handlers are used for biotechnological and pharmaceutical liquid assay procedures, sample preparation, compound distribution, microarray manufacturing and the like. An automated liquid handler has a work surface that supports an array of sample receptacles. One-piece sample containing plates having an integral array of many sample containing receptacles or wells are widely used.

[0003] A typical liquid handler has a probe or an array of multiple probes that are moved into alignment with one or more wells to carry out liquid handling operations such as removing liquid from and adding liquid to the wells. The probe or probe array is generally carried on a support that may be movable in X, Y and Z directions. An X-direction track may be provided along with a first carriage movable along the track to facilitate movement in the X-direction. A Y-axis track is mounted on the first carriage, with a second carriage movable along this Y-axis track. A Z-axis track is in turn carried by the second carriage, with the probe support movable along the Z-axis track. One or more motors and controllers may be provided to control the carriages to position the probes to deliver liquid to or from selected receptacles on the table below the probe support. Examples of known liquid handlers generally consistent with this description can be found, for example, in U.S. Pat. No. 4,422,151 to Gilson (“the Gilson patent”), and U.S. Pat. Nos. 6,240,984 and 5,988,236 to Fawcett et al.(“the Fawcett patents”), each of which is incorporated herein by reference.

[0004] It is desirable to increase the throughput capacity of liquid handlers in order to process more samples in less time. One limit to throughput capacity is the ability of a probe support to be positioned in only one place at one time. A solution to this limit has been proposed whereby two carriages movable in an X direction are provided, with each carrying a Y-axis track, a Z-axis track, and a probe support. To date, however, this proposed solution has left problems unresolved.

[0005] For example, in many systems having two X direction carriages that have been proposed to date, two X-axis tracks are provided and separated from one another. The X-axis tracks may be spaced horizontally and/or vertically from one another. As a result, differently sized Y-axis tracks and/or Z-axis tracks are required for the two X direction carriages in order for all locations on the table below to be accessible. For example, if the two X-axis tracks are at different elevations, the uppermost track will require a longer Z-axis track than the lower X-axis track. In addition, plural X-axis tracks add additional expense. This results in higher system costs and increased complexity in that more parts and differently sized parts are required.

[0006] These and other problems remain unresolved in the art.

SUMMARY OF THE INVENTION

[0007] A principal object of the present invention is to provide an improved liquid handler that has a plurality of carriages independently movable along a single support. Another object of the invention is to provide an improved probe transport system, an improved carriage system, and an improved drive assembly for use with a liquid handler. Other objects are to provide a liquid handler system, a probe transport system, a carriage system, and a drive system that achieve increased throughput capacity and exploit a cost effective design.

[0008] In brief, in accordance with the invention there is provided an automated liquid handler having a table including a work surface for receiving liquid containers. A probe transport system is supported above the work surface. The probe transport system includes a first elongated support extending in a first direction and a plurality of first carriages independently movable along the first support. A plurality of second elongated supports extend in a second direction, each of the second supports being mounted upon one of the first carriages. A plurality of second carriages are each movable along one of the second supports. The handler includes a plurality of liquid transfer probes. A pump assembly communicates with the liquid transfer probes. Each of the second carriages supports at least one of the liquid transfer probes. At least one motor is linked to each of the first and second carriages.

BRIEF DESCRIPTION OF THE DRAWING

[0009] The present invention together with the above and other objects and advantages may best be understood from the following detailed description of the preferred embodiment of the invention illustrated in the drawings, wherein:

[0010] FIG. 1 is a perspective view of an exemplary automated liquid handler of the invention including a probe transport system;

[0011] FIG. 2 is a perspective view of the automated liquid handler of FIG. 1 with portions removed to reveal the probe transport system;

[0012] FIG. 3 is a perspective view of a portion of the liquid handler of FIG. 1 showing a carriage on the X direction track of the liquid handler;

[0013] FIG. 4 is a perspective view of one of the Y direction supports of the liquid handler of FIG. 1;

[0014] FIG. 5 is a perspective view, partly cutaway, of a portion of one of the Y direction supports of the liquid handler of FIG. 1;

[0015] FIG. 6 is a perspective view of a portion of one of the Y direction supports of the liquid handler of FIG. 1;

[0016] FIG. 7 is a front view of one of the Z direction supports of the liquid handler of FIG. 1;

[0017] FIG. 8 is a view like FIG. 7 with structure removed;

[0018] FIG. 9 is a perspective view of the Z direction support of FIG. 7 with a portion removed; and

[0019] FIG. 10 is a schematic illustrating one exemplary control configuration useful for controlling the liquid handler of FIG. 1.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0020] Having reference now to the drawings, and initially to FIGS. 1 and 2, there is shown an example of an automated precision liquid handler generally designated as 20. It will be appreciated when considering the liquid handier 20 that some elements of liquid handlers of the present invention may be generally consistent with elements of prior art liquid handling systems. For these generally known elements, detailed description need not be provided herein. Teaching regarding these elements may instead be obtained through reference to one or more of the Gilson and Fawcett patents that have been incorporated herein.

[0021] The liquid handler 20 includes a table or work bed 22 below a probe transport system shown generally at 24 that carries two probe holders 26. The probe transport system 24 independently moves the probe holders 26 above the work bed 22 and positions them with great precision in predetermined positions relative to the work bed 22. When liquid receptacles are arranged on the work bed 22, the probe transport system 24 is thus operative to position probes held by the probe holders 26 above one or more selected receptacles.

[0022] The probe transport system 24 utilizes a carriage system that includes an X direction support shown generally at 28, with two carriages generally shown at 30 that are independently and simultaneously movable along it. A Y direction support shown generally at 32 is mounted on each of the carriages 30, with a carriage 34 movably held on each of the Y-direction supports 32. Each of the carriages 34 has a Z direction support shown generally at 36 mounted on it, with the probe holders 26 movable in a vertical direction along the Z direction supports 36. It will be appreciated that although two carriages 30 have been illustrated as movable along the X direction support 28, other invention embodiments may include carriage systems having other numbers of carriages, with three or four carriage systems being examples. Additionally, it will be appreciated that although a single Z direction support 36 has been illustrated for moving along each of the Y direction supports 32, other invention embodiments may have more than one Z direction support 36 on each of the Y-direction supports 32.

[0023] The liquid handler 20 includes a plurality of bays 38 arranged generally above the X direction support 28. The bays 38 may be useful to hold fluid handling and other components such as liquid supplies, pumps, diluters, valves, heaters, chillers, analysis components, computers, and the like. A power supply linkage is preferably provided suitable to supply required power to the components held in the bays 38. The rack of bays 38 is supported on a frame 40 that rises from the liquid handler base 42. The work bed 22 is defined on the base 42.

[0024] The view of the liquid handler of FIG. 2 shows additional details of the probe transport system 24. The support 28 has a track 44 and a fixedly held threaded rod 46 that is generally parallel to the track 44. As best shown by FIG. 3, the track 44 generally includes two lengthwise channels 48 that the carriages 30 ride along. A bearing 50 is provided, with the carriages 30 having a base 52 adapted to sit in the bearing 50 as best shown by FIGS. 4-5. The bearing 50 may include rotational members such as rollers, wheels, or the like. The track 44 and bearings 50 may be a Type HRW-CR linear motion system available from THK Co., Ltd. of Tokyo, Japan and disclosed at pages 192 and 193 of THK Catalog No. 200-1AE dated April, 1996, filed herewith and incorporated herein by reference.

[0025] To drive the carriages 30 along the track 44, each of the carriages 30 has a threaded collar 54 that engages the fixed threaded rod 46. As best shown by the cutaway view of FIG. 5, each of the carriages 30 has a body 56 that contains a driving motor 58 operable to rotate the threaded collar 54. Rotation of the threaded collar 54 causes the carriage 30 to move along the rod 46. The carriages 30 may accordingly be considered to be self-propelled. Direction of movement along the rod 46 can be controlled by the selected direction of rotation: clockwise rotation will drive the carriage in one direction and counterclockwise in the opposite. A rotating motor 60 is also contained in the body 56 of each of the first carriages 30, as can be seen in the cutaway of FIG. 5.

[0026] FIG. 6 illustrates a Y direction support 32 in detail. The support 32 includes a body 62, a mounting base 64, a track 66 and a rotating threaded rod 68 contained in the body 62. As best shown by FIGS. 3-4, the mounting base 64 is attached to the carriage body 56 using fasteners such as bolts or the like. The mounting base 64 includes a passage 69 for allowing a coupler 70 to link the rotating motor 60 to the rotating threaded member 68. The rotating motor 60 is operative to rotate the threaded rod 68 in either a clockwise or counterclockwise direction. The Y support carriage 34 has a fixed threaded collar 72 that engages the rod 68 to drive the carriage 34 along the track 66 when the rod 68 rotates. When the driving motor 60 (FIG. 5) rotates the rod 68 in a clockwise direction, interaction with the non-rotating collar 72 will drive the carriage in a first direction along the track 66, while rotation of the rod 68 in the opposite direction will cause the carriage 34 to move in the opposite direction. The track 66 and mating bearing may be a Type SHS flange type linear motion system available from THK Co., Ltd. of Tokyo, Japan and disclosed at pages 13 and 14 of THK Catalog No. 235-1E dated May, 1998, filed herewith and incorporated herein by reference.

[0027] Referring once again to FIGS. 1-2, the elongated and generally vertical Z direction support 36 is connected to each of the Y direction support carriages 34. FIGS. 7-8 offer more detailed views of a Z direction support 36. The support 36 includes a screw motor 74, a pair of guide rods 76, a plurality of probes 78 supported on the probe holder 26, a foot 80, a base 82, and a housing 84. Each support 36 and probe holder 26 can have one (FIGS. 1 and 2) or eight (FIG. 7) or some other number of probes 78. FIG. 8 shows the Z direction support 36 with a portion of the housing 84, the probe holder 26 and the probes 78 removed. In this view, the Z support carriage 86 is visible, as well as a threaded rod 88. The carriage 86 is provided with four connectors 90 for attaching to the probe holder 26. The housing 84 has two slots 92 (both shown in FIG. 7) for receiving and permitting vertical, Z-direction movement of the connectors 90.

[0028] FIG. 9 shows a portion of the Z direction support 36 with all of the housing 84 (FIGS. 7-8) removed. In this view, the vertical track 92 is more clearly shown. The carriage 86 moves along the track 92 in a generally vertical direction through operation of the screw motor 74 and the threaded rod 88. In particular, a threaded collar 94 is fixedly held on the carriage 86 and engages the threaded rod 88. When the screw motor 74 causes the threaded rod 88 to rotate in a clockwise direction, its interaction with the collar 94 will cause the carriage 86 to move in a first vertical direction along the track 92. Rotation of the rod 88 in the opposite direction will similarly cause the carriage 86 to move in the opposite direction. FIG. 9 also shows an opening 96 that is provided in the base 82 for passing the probes 78 (FIG. 7). The track 92 and mating bearing may be a Type RSR stainless steel type linear motion system available from THK Co., Ltd. of Tokyo, Japan and disclosed at pages 234 and 235 of THK Catalog No. 200-1AE dated April, 1996, filed herewith and incorporated herein by reference.

[0029] When considering the probe transport system 24, it will be appreciated that a drive system is utilized that includes rotating threaded rods 68 and 88 cooperating with fixed mating collars to cause movement of the carriages 34 and 86 along the Y and Z direction supports 32 and 36, respectively. This configuration of a rotating rod cooperating with fixed collars are advantageous for reasons of strength, cost and simplicity, among others. The drive system of the probe transport system 24 further includes an X direction support that does not use a rotating threaded rod, but instead the fixed rod 46 that mates with independently rotatable collars 54 on each of the carriages 30.

[0030] It will also be appreciated that many other drive systems are available for facilitating movement of the respective carriages 30, 34, and 86 along their respective supports. By way of example and not limitation, one or more of a drive chain or a belt could be used in an endless loop along the support, with one or more carriages either permanently or selectively linked to the drive belt or chain. Also, it will be appreciated that through use of gearing or other power transmission means, motors used to cause movement of the carriages along the various supports could be separate from those supports. Further, a single motor could be used that provided several independent outputs to drive independent movement of each of the several carriages on each of the several supports.

[0031] In operation, one or more controllers may be provided to control the operation of the probe transport system 24 and its individual components that are illustrated in FIGS. 1-9. FIG. 10 is a schematic diagram useful for illustrating one exemplary configuration for control of the probe transport system 24 using a controller 98. The controller 98 is linked to the probe transport system 24 (represented in dashed line block) for controlling movement of the probes 78, and is also connected to a pumping system 100 to cause communication of liquid between it and the plurality of probes 78. For example, the controller 98 may cause one or more of the probes 78 to be aligned with one or more selected fluid receptacles 102 that are arranged in an array on the work bed 22. The receptacles 102 may be plates, tubes, containers, or the like, and may be supported by a rack or otherwise arranged in a particular manner to achieve a known spatial arrangement. Additional detail regarding the receptacles 102, arrays, racks, and the like is available in the Fawcett patents that have been incorporated herein by reference.

[0032] The controller 98 directs movement of the probes 78 through control of a drive system that includes the motors 58, 60 and 74 that drive movement of each of the carriages 30 and 34, and the probe holder 26, respectively. In particular, the schematic of FIG. 10 shows the controller 98 connected by a linkage 104 to the probe transport system 24, and in turn to each of the driving motors 58, the rotating motors 60, and the screw motors 74 to selectively operate one or more of the motors to cause the probes 78 to be positioned as desired. Preferably, the controller is operable to cause the probe holders 26 (FIG. 1) to independently and simultaneously be positioned as desired over the work bed 22. It will be understood that in accomplishing this, the controller 98 may cause each of the carriages 30 (FIG. 1) to simultaneously and independently move along the X direction support 28.

[0033] Once the controller 98 has caused the probes 78 to be positioned over one or more of the receptacles 102, it may additionally cause fluid to be delivered to or from the selected receptacles 102 through operation of the pumping system 100. The pumping system 100 may be any suitable fluid delivery system, which may include, by way of example, one or more positive displacement metering piston pumps. The pumping system 100 is connected to each of the probes 78 using fluid conduits 106 such as plastic flexible tubing or the like. Although not illustrated in the schematic of FIG. 10, the controller 98 may additionally be connected to one or more of the components such as diluters, valves, heaters, analysis components, and the like that are held in the bays 38 shown in FIG. 1. The pumping system 100 may be contained within the liquid handler 20 in a cabinet 110. The pumping system 100 may also be separate from the liquid handler 20.

[0034] Referring once again to FIG. 10, the controller 98 in practice may be a personal computer, a processor, circuitry embedded on a card or microchip, or the like. The controller 98 may also be a multi-purpose processor-based device such as a computer that is useful to execute program instructions that cause it to control the probe transport system 24 and the pumping system 100. With reference to FIG. 1 in addition to FIG. 10, the controller 98 may be contained within the fluid handling system 20 or in one or more of the cabinets 110. The controller 98 could also be an element or otherwise be contained within the probe transport system 24. The controller 98 may additionally be physically separate from the liquid handler 20, in which case the linkage 104 may be connected through an electronic communications port or the like on the liquid handler 20.

[0035] By way of example, the controller 98 may be a computer connected to a network, with the network linked to the fluid handler 20. In this circumstance, the linkage 104 may be considered to include a network. By way of still additional example, a single controller 98 may be connected over a network to a plurality of liquid handlers 20 for independent control of each of the handlers 20.

[0036] The linkage 104 may in practice include a plurality of individual linkages or connections, and may be any device practical for communicating instructions from the controller 98 to the probe transport system 24 and to the pumping system 100. By way of example, the linkage 104 may be cabling, circuitry, or a wireless communications link. When wiring or cabling is used for the linkage 104, it should be operative to communicate with the carriages 30 as they move along the X direction support 28. One exemplary linkage 104 useful for such operation is flat ribbon cable held within the X direction support 28. AC or other suitable power supplies may likewise be connected to the motors 58, 60 and 74 in a similar manner, and may even be combined with the linkage 104.

[0037] Automated liquid handlers and probe transport systems of the invention thereby solve many problems and offer many advantages over the prior art. For example, by providing multiple carriages and Y direction supports that are held on a single X direction support, the throughput capacity of liquid handlers and positioners of the invention are increased over single carriage systems of the prior art. Additionally, because the multiple carriages of systems of the invention can move along a single X direction support, each of the Y direction supports and Z direction supports can be of the same length and height, respectively. Indeed, the Y direction supports and Z direction supports may be substantially identical and interchangeable with one another. This provides cost and efficiency advantages over prior art systems that required multiple supports of different dimensions.

[0038] While the present invention has been described with reference to the details of the embodiments of the invention shown in the drawing, these details are not intended to limit the scope of the invention as claimed in the appended claims.

Claims

1. An automated liquid handler comprising: a table including a work surface for receiving liquid containers; a probe transport system supported above said work surface; said probe transport system including a first elongated support extending in a first direction; a plurality of first carriages independently movable along said first support; a plurality of second elongated supports extending in a second direction, each of said second supports being mounted upon one of said first carriages; a plurality of second carriages, each of said second carriages movable along one of said second supports; a plurality of liquid transfer probes; a pump assembly communicating with said liquid transfer probes; each of said second carriages supporting at least one of said liquid transfer probes; and at least one motor linked to each of said first and second carriages.

2. An automated liquid handler as defined by claim 1 wherein said first and second supports each include a track, respective of said first and second carriages riding on said tracks.

3. An automated liquid handler as defined by claim 1 and further comprising a plurality of third elongated supports extending in a third direction, each of said third supports being mounted on one of said second carriages, a plurality of third carriages, each of said plurality of third carriages movable along one of said third supports, said at least one motor being linked to said third carriages.

4. An automated liquid handler as defined by claim 3 wherein said first direction, said second direction and said third direction being generally perpendicular to one another to define a generally orthogonal X-Y-Z probe transport system.

5. An automated liquid handler as defined by claim 3 wherein each of said plurality of third carriages moves generally vertically.

6. An automated liquid handier as defined by claim 3 wherein each of said plurality of second supports is of substantially the same length, and wherein each of said plurality of third supports is of substantially the same length.

7. An automated liquid handler as defined by claim 1 and further including at least one controller linked to said at least one motor

8. An automated liquid handler as defined by claim 7 wherein said at least one controller is operative to cause each of said plurality of first carriages and said plurality of second carriages to move independently of one another.

9. An automated liquid handler as defined by claim 1 wherein said at least one motor includes a drive motor on each of said first carriages operative to cause said first carriage to move along said first support.

10. An automated liquid handler as defined by claim 9 wherein said at least one motor further includes a second motor on each of said first carriages operative to cause one of said second carriages to move along one of said second supports.

11. An automated liquid handler as defined by claim 1 wherein said first and second directions are generally perpendicular to one another.

12. An automated liquid handler as defined by claim 1 wherein said first support includes a first threaded member and each of said plurality of first carriages has at least one threaded coupler engaging a segment of said first threaded member.

13. An automated liquid handler as defined by claim 12 wherein said first threaded member being non-rotating, said threaded couplers being rotatable, and wherein each of said plurality of first carriages has a drive motor linked to said rotating threaded couplers

14. An automated liquid handler as defined by claim 12 wherein said first support further includes a track, said plurality of first carriages being independently movable along said track, said track and said first threaded member being substantially parallel to one another.

15. An automated liquid handler as defined by claim 1 wherein each of said second supports includes a threaded member and a track that are generally parallel to one another, and wherein each of said second carriages has a mating threaded coupler engaging said threaded member.

16. An automated liquid handler as defined by claim 15 wherein said second threaded member being rotatable, said mating threaded coupler on each of said second carriages being non-rotatable, and wherein each of said first carriages has a rotating motor linked to one of said second threaded members.

17. An automated liquid handler as defined by claim 1 wherein said work surface has a rear side edge, wherein said first support extends generally parallel to said rear side edge, and wherein said plurality of second supports are substantially perpendicular to said first support to extend over said work surface.

18. An automated liquid handler as defined by claim 1 wherein each of said plurality of first carriages being self-propelled.

19. A carriage system for use with a liquid handler system, the carriage system comprising: a first and a second elongated support; a first carriage movable along said first elongated support and a second carriage movable along said second elongated support, said first carriage including a first carriage driving motor linked to said first elongated support, and said first carriage including a second carriage driving motor linked to said second support.

20. A carriage system as defined by claim 19, wherein said first support includes a first threaded member, said first threaded member being non-rotatable, wherein said second support includes a second threaded member, said second threaded member being rotatable, said first carriage driving motor linked to a mating coupler operable to rotatably engage said first threaded member, said second carriage driving motor linked to said second threaded member.

21. A drive system for use in a liquid handler system, the drive assembly including: a non-rotating threaded rod extending in a first direction; and a plurality of carriages independently movable along said nonrotating threaded rod, each of said carriages including a drive motor linked to a rotating threaded coupler, said rotating threaded coupler engaging said non-rotating threaded rod.

22. A drive system as defined by claim 21 and further comprising a plurality of rotating threaded rods extending in a second direction, each of said rotating threaded rods being linked to a rotating motor carried on one of said plurality of carriages.

23. An automated precision liquid handler comprising: a table including a work surface for supporting a plurality of liquid receptacles arranged in an array; a probe transport system supported above said work surface; said probe transport system including a first track extending in a first direction; a plurality of first carriages independently and simultaneously movable along said first track; a plurality of supports extending in a second direction generally perpendicular to said first direction, each of said supports mounted upon one of said first carriages, each of said supports including a second track; a plurality of second carriages, each of said plurality of second carriages movable along one of said second tracks; a plurality of generally vertical elongated supports, each of said generally vertical supports including a third track, each of said plurality of generally vertical supports mounted upon one of said second carriages; a plurality of third carriages, each of said plurality of third carriages movable along one of said third tracks; a probe holder connected to each of said third carriages; a plurality of liquid transfer probes carried on each of said third carriages; a pumping system communicating with said liquid transfer probes; at least one motor linked to said first, second, and third carriages; and a controller linked to said pumping system and said at least one motor.

24. A probe transport system for use with an automated liquid handler, the probe transport system for positioning at least one liquid probe over at least one liquid receptacle supported by the liquid handler, the probe transport system comprising: a first support extending in a first direction, said first support including a first track and a generally parallel first threaded rod; a plurality of first carriages independently movable along said first track in said first direction, each of said first carriages having a threaded mating coupler engaging spaced apart portions of said first threaded rod; a plurality of second elongated supports extending in a second direction generally perpendicular to said first direction, each of said second supports being mounted upon one of said first carriages, each of said second supports including a second track and a generally parallel second threaded rod; a plurality of second carriages, each of said plurality of second carriages movable along one of said second tracks and including a threaded mating coupler engaging one of said second threaded rods; a plurality of third elongated supports extending in a generally vertical direction, each of said plurality of third supports including a third track and a generally parallel third threaded rod, each of said plurality of third elongated supports mounted upon one of said second carriages; a plurality of third carriages, each of said plurality of third carriages movable along one of said third tracks and having a threaded mating coupler engaging one of said third threaded rods; a probe holder connected to each of said third carriages, said probe holder holding at least one of the at least one liquid probes; at least one motor linked to said first, second, and third carriages; and a controller linked to said at least one motor.