WO2015067180A1 - 全自动移液仪和其用途 - Google Patents

全自动移液仪和其用途 Download PDF

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Publication number
WO2015067180A1
WO2015067180A1 PCT/CN2014/090402 CN2014090402W WO2015067180A1 WO 2015067180 A1 WO2015067180 A1 WO 2015067180A1 CN 2014090402 W CN2014090402 W CN 2014090402W WO 2015067180 A1 WO2015067180 A1 WO 2015067180A1
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WO
WIPO (PCT)
Prior art keywords
pipetting
linear guide
moving
moving rod
rod
Prior art date
Application number
PCT/CN2014/090402
Other languages
English (en)
French (fr)
Inventor
刘丹
赵海峰
Original Assignee
北京自由度科学机器有限公司
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
Priority claimed from CN201310544596.7A external-priority patent/CN103551217A/zh
Priority claimed from CN201310544587.8A external-priority patent/CN103551216A/zh
Priority to US15/034,373 priority Critical patent/US20160266162A1/en
Application filed by 北京自由度科学机器有限公司 filed Critical 北京自由度科学机器有限公司
Publication of WO2015067180A1 publication Critical patent/WO2015067180A1/zh

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1065—Multiple transfer devices
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/02—Burettes; Pipettes
    • B01L3/021—Pipettes, i.e. with only one conduit for withdrawing and redistributing liquids
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1081—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices characterised by the means for relatively moving the transfer device and the containers in an horizontal plane
    • G01N35/1083—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices characterised by the means for relatively moving the transfer device and the containers in an horizontal plane with one horizontal degree of freedom
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1009—Characterised by arrangements for controlling the aspiration or dispense of liquids
    • G01N2035/1025—Fluid level sensing
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N2035/1027—General features of the devices
    • G01N2035/103—General features of the devices using disposable tips
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1065—Multiple transfer devices
    • G01N2035/1076—Multiple transfer devices plurality or independently movable heads

Definitions

  • the present invention relates to automated liquid handling equipment. More specifically, the present invention relates to a fully automatic pipetting device and a pipetting mechanism therefor, and their use in performing liquid loading, liquid transfer, and the like.
  • the fully automatic liquid handling workstation is a biomedical laboratory automation operation platform that combines automation and liquid processing. It can realize automatic sample loading, reagent dispensing, ultra-micro pipetting and vibration, incubation, etc. related to liquid processing. operating. Can be widely used in nucleic acid purification, gene protein sequencing, rapid screening of clones, cell culture, biochip sample preparation and other fields.
  • the pipetting mechanism is one of the core mechanisms of the fully automatic liquid handling workstation, which is used to realize the transportation, extraction and transfer of liquid between standard liquid containers.
  • the most common standard liquid containers are standard liquid containers such as 8-well plates, 96-well plates, and the like.
  • the standard liquid containers such as 96-well plates commonly used in laboratories have a minimum spacing of 9 mm, a volume of about 0.5 ml, and a single column of 8 holes. Therefore, automatic liquid handling workstations, especially the pipetting mechanisms therein, need to achieve multiple, high precision and high repeatability in a small space, such as eight Simultaneous or separate pipetting of the pipetting channels.
  • the prior art automatic liquid processing workstation and the pipetting mechanism have the advantages of large mechanism wear, high noise, low motion stability, high processing precision of the moving base chute, complicated debugging of the assembly process, and large workload, and Daily operation and maintenance are cumbersome, and it is easy to cause pollution and corrosion inside the instrument.
  • the invention provides a novel automatic workstation, which overcomes the problems of large wear of the pipetting mechanism, complicated assembly and debugging, and poor smoothness of the overall operation of the mechanism in the prior art, and provides an internal environment with simple maintenance and no pollution. .
  • the invention provides a pipetting workstation comprising:
  • a moving rod driving mechanism comprising: a screw rod disposed in parallel with the moving rod; and a driving mechanism of the screw rod, wherein the screw rod is fixedly connected to the moving rod through a driving connection;
  • the linear guide fixing seat can be connected and fixed to the slider of the linear guide.
  • the linear guide can be disposed in a horizontal direction with the aforementioned rack parallel.
  • the slider of the linear guide is connected and fixed to the linear guide fixing seat, whereby the linear guide fixing seat and the moving base connected and fixed with the linear guide fixing seat can be carried along the track of the sliding guide along the slider of the linear guide Movement in the horizontal direction.
  • the gear and the rack of the pipetting station, and the position of the linear guide holder and the linear guide are arranged such that when the gear rotates, a movable base that drives the slider of the linear guide can be realized.
  • the seat moves horizontally along the direction of the rails of the rack and the linear guide.
  • the gear and the linear guide fixing seat are disposed on the same side of the frame, and the corresponding rack and the linear guide are juxtaposed in parallel.
  • the linear guide mount has a square surface that is the same or similar in shape and size to the surface of the slider of the linear guide.
  • the height H1 of the linear guide mount is greater than 25 mm, preferably greater than 30 mm.
  • the linear guide rail to which the linear guide fixing seat can be fitted or used is a linear guide rail having a slider width w of more than 25 mm, preferably more than 30 mm.
  • the linear guide mount of the pipetting mechanism is coupled to the moving base by a linear guide fixing block.
  • the linear guide fixing block and the moving base may be integrally cast or fixed on the moving base by threads or the like.
  • the linear guide fixing block is used to fix two of the linear guide fixing seats.
  • the linear guide fixing block has the same or similar width (generally referred to as the length in the horizontal direction) and not less than twice the height (usually the length in the vertical direction) of the linear guide fixing seat.
  • the height H2 of the linear guide fixing block is greater than or equal to 50 mm, preferably greater than or equal to 60 mm.
  • the moving base of the pipetting mechanism has a quadrangular outer frame having four sides, an upper beam, a lower beam, and two frames.
  • the moving rod of the pipetting mechanism of the pipetting station is movably fitted to a side frame of the moving base.
  • the frame for assembling the moving rod in the pipetting mechanism of the pipetting station has a groove opening toward the inner side of the moving base, the moving rod being movably Fitted in the groove, a part of the moving rod is outside the groove, that is, the inner side surface of the left frame is protruded, and the protruding portion of the moving rod can be used for fixed connection with the driving connection of the moving rod driving mechanism.
  • the moving rod in the pipetting mechanism of the pipetting station is movably mounted in a frame on the moving base by a moving rod sliding sleeve disposed on the frame, wherein the moving rod sliding sleeve is fixedly coupled to the frame, and the moving rod is movable within the moving rod sliding sleeve.
  • the moving rod sliding sleeve of the pipetting mechanism of the pipetting station is a sliding sleeve prepared from a polymer material.
  • a polymer material such as Igus's Series, such as G, W300, J, X and M250 and so on.
  • the parts made of these polymer materials have the characteristics of no lubrication (self-lubricating), excellent acid-base resistance, good shock absorption performance, no need for sealing or oil scraping ring, and easy installation and replacement.
  • the moving rod sliding sleeve is not a metal material component.
  • the moving rod in the pipetting mechanism of the pipetting station is a hollow tube groove.
  • the hollow tube slot can be used to install wires or pipettes.
  • the driving mechanism of the screw in the pipetting mechanism of the pipetting station is a driving motor of the screw.
  • the lead screw is driven by a drive motor.
  • the drive motor is a servo motor.
  • the lead screw is fixedly coupled to the travel bar by a spindle nut and a drive link.
  • the screw nut is screwed onto the screw, and one end of the drive coupling is fixedly connected to the moving rod, and the other end is fixed to the outside of the screw nut.
  • the screw nut is prepared from a polymer.
  • the screw nut in the pipetting mechanism of the present invention is not a metal material component.
  • the pipetting mechanism of the pipetting station of the pipetting station has a limiting block, and a pipette holder connected to the catheter below the pipette holder, the catheter being connectable Replace the pipette tip.
  • the pipette is provided with a pipe sleeve on the pipe.
  • the pipetting head has a liquid level detector.
  • the pipetting station further includes a rack disposed in a horizontal direction to form a gear pair with the gear, and the gear base is driven to move horizontally along the rack when the gear rotates.
  • the pipetting station further includes a linear guide disposed in a horizontal direction parallel to the rack, the slider of the linear guide being coupled and fixed to the linear guide mount, thereby
  • the moving base can move horizontally along the track of the linear guide along with the slider of the linear guide.
  • the moving base is through a linear guide mount (It can also include the linear guide fixing position) to connect and fix the slider of the linear guide.
  • the gear and the linear guide mount are positioned such that when the gear rotates, the drive moving base is horizontally moved in the direction of the rail of the rack and the linear guide.
  • the moving base is connected and fixed to the slider of the linear guide by a linear guide fixing seat (which may also include a linear guide fixing position).
  • a linear guide fixing seat which may also include a linear guide fixing position.
  • the gear and the linear guide mount are disposed on the same side of one of the frames, and the corresponding rack and the linear guide are juxtaposed in parallel.
  • the pipetting head of the pipetting mechanism has a limiting block, and a pipette holder connected to the catheter below the pipette holder, the catheter being connectable to the replaceable pipette head.
  • the catheter is provided with a tube sleeve.
  • the pipetting head has a liquid level detector. The level detector can be placed below the pipette holder.
  • the pipetting station has a plurality (eg, four or eight) of the aforementioned pipetting mechanisms, wherein two or more of the plurality of pipetting mechanisms are juxtaposed,
  • the moving rods of the two or more pipetting mechanisms assembled side by side are arranged in a straight line, and the gears of the two or more pipetting mechanisms arranged side by side and the same rack form a gear pair.
  • the linear guide mounts of the moving bases of the two pipetting mechanisms of the two or more pipetting mechanisms arranged side by side are connected to the two sliders of the same linear guide.
  • the linear guide fixing seats on the adjacent two moving bases are respectively fixed to the upper half or the lower half of the linear guide fixing block of the moving base, thereby the plurality of pipetting mechanisms assembled in parallel
  • the two moving bases in the two can be connected to the two sliders of the same linear guide.
  • the gear and the rack, and the position of the linear guide fixing seat and the linear guide are arranged such that when the gear rotates, the moving base fixed by the slider of the linear guide can be horizontally oriented along the rail of the rack and the linear guide. mobile.
  • the pipetting station comprises four or eight of the pipetting mechanisms.
  • the eight pipetting mechanisms are divided into two groups arranged in parallel, each group of four pipetting mechanisms being juxtaposed, and the gears of each group of four pipetting mechanisms are the same A rack forms a gear pair.
  • the linear guide mounts of the moving bases of the two pipetting mechanisms of each of the four pipetting mechanisms are coupled to the two sliders of the same linear guide.
  • linear guide rails on two adjacent moving bases fixed on the mobile
  • the linear guide rail of the base fixes the upper half or the lower half of the block, whereby two of the four pipetting mechanisms arranged side by side can be respectively connected to the two sliders of the same linear guide .
  • the gear and the rack, and the position of the linear guide fixing seat and the linear guide are arranged such that when the gear rotates, the moving base fixed by the slider of the linear guide can be horizontally oriented along the rail of the rack and the linear guide. mobile.
  • the moving rods of each of the four pipetting mechanisms are arranged in a straight line, and are alternately arranged with the moving rods of another group of four pipetting mechanisms, so that the eight pipetting mechanisms are arranged.
  • the pipette tips can be arranged in a straight line.
  • the pipetting station further includes other detection devices or containers, such as syringe pumps, heating plates, oscillators, microplate readers, PCR machines, grip mechanisms, and various samples or reagents.
  • Containers such as microcentrifuge tubes, centrifuge tubes, PCR microplates, deep well plates, microporous filter plates, tube racks, and the like.
  • a pipetting mechanism as previously described is also provided.
  • the method includes: a moving base; a moving rod movably mounted to the moving base, the moving rod can move relative to the moving base in a vertical direction;
  • the mechanism includes a screw rod disposed in parallel with the moving rod and a driving mechanism of the screw rod, the screw rod is fixedly connected to the moving rod through a driving connection member; and is mounted on a moving base frame (for example, inside the frame or a gear of the outer side, preferably the outer side, and a drive mechanism of the gear, the gear being rotatable in a vertical direction; a linear guide mount fixed to the frame of the moving base (for example, inside or outside of the frame, preferably outside); Move the pipette tip at the lower end of the rod.
  • a multi-channel pipetting device employing the aforementioned pipetting mechanism, the multi-channel pipetting device being equipped with two, four or eight of the pipetting mechanisms.
  • the pipetting mechanism, device and instrument of the invention can realize vertical or horizontal movement of each pipetting mechanism independently in operation, and the layout of the overall structure is more reasonable, the movement space is more clear, and the difficulty and complexity of assembly and debugging are assembled. It has also been greatly reduced.
  • the pipetting mechanism of the present invention uses a self-lubricating, maintenance-free polymer material to prepare a sliding sleeve for fixing and sliding the moving rod therein, and the hollow square tube is in the polymer polymer sliding sleeve.
  • the sliding is smooth, soft, and the noise is small, and the operation of lubricating the same is avoided or reduced, and the contamination of the grease-like lubricant on the pipetting operation is avoided.
  • the screw pair used in the pipetting mechanism of the present invention for realizing the vertical movement of the pipetting head drives the screw with a servo motor, which can overcome the mechanical vibration in the prior art. Unstable defects.
  • the screw nut adopts a backlash structure, which can eliminate most of the mechanical clearance between the screw nut and the screw, and can further realize a more precise transmission, thereby realizing a finer pipetting operation of the pipetting head.
  • the screw nut can also be prepared as a polymer material, whereby the mechanism for driving the vertical movement of the pipetting head can avoid or reduce the lubrication operation, and avoid the possibility that the grease lubricant can be used for pipetting operation. The pollution caused.
  • Figure 1 is a partial internal view of a pipetting station in accordance with a preferred embodiment of the present invention
  • FIG. 2 is a perspective view of a pipetting mechanism of a pipetting station in accordance with a preferred embodiment of the present invention
  • Figure 3 is a cross-sectional view of a pipetting mechanism of a pipetting station in accordance with a preferred embodiment of the present invention
  • FIG. 4 is a partial assembly view of a pipetting mechanism of a pipetting station according to a preferred embodiment of the present invention.
  • Fig. 5 is a perspective view showing another embodiment of a pipetting station according to a preferred embodiment of the present invention.
  • FIG. 1 is a partial internal device of a pipetting station in accordance with a preferred embodiment of the present invention Figure.
  • the pipetting station of the present invention typically has eight pipetting mechanisms 38 for performing liquid loading, liquid transfer.
  • the eight pipetting mechanisms are divided into two groups arranged in parallel, and each group of four pipetting mechanisms are assembled side by side.
  • Figure 1 is a schematic view of the internal portion of a pipetting station of the present invention including the above-described set of four pipetting mechanisms arranged side by side.
  • the pipetting mechanism has a moving base 1 having a quadrangular outer frame.
  • the pipetting mechanism further has a moving rod 7 movably mounted vertically on a side frame of the moving base and a pipetting head 30 mounted at a lower end of the moving rod.
  • the moving rod can move up and down relative to the moving base in the frame in a vertical direction.
  • a drive mechanism that drives the moving rod to move up and down relative to the moving base includes a lead screw 4 mounted on the moving base parallel to the moving rod.
  • the pipetting head is a mechanism for liquid sensing, conveying, suctioning, etc., and can move up and down with the up and down movement of the moving rod, and realize the function of processing the liquid sample in the container provided under the pipetting head.
  • the pipetting mechanism further has a gear wheel 16 that is mounted on the outer side of the frame of the moving base and rotatable in a vertical direction.
  • the gear wheel can form a gear pair with the horizontally disposed rack 43.
  • the pipetting mechanism further has a linear guide fixing base fixed to the moving base for connecting and fixing with the slider 42 of the linear guide, whereby the moving base can be slid along the horizontally disposed linear guide 40 to realize horizontal movement.
  • the gear 16 and the rack 43 and the linear guide fixing seat 34 and the linear guide 40 are disposed in such a manner that when the gear 16 rotates, the sliding of the moving base fixed to the slider of the linear guide along the rack and the linear guide can be achieved.
  • the rail direction moves horizontally.
  • the moving rods of each group of four pipetting mechanisms of the pipetting station of the present invention are arranged in a straight line, and are alternately arranged with the moving rods of another group of four pipetting mechanisms, so that the pipetting guns of the eight pipetting mechanisms are provided.
  • the heads can be arranged in a straight line.
  • the gears of each of the four pipetting mechanisms of the pipetting station of the present invention form a gear pair with the same rack, wherein the linear guide mounts on the adjacent two moving bases 34 are respectively connected to the two sliders of the same linear guide, whereby each set of four pipetting mechanisms is connected to the two linear guides.
  • the one rack and the two linear guide rails are arranged in parallel up and down.
  • the pipetting station of the present invention may further have a casing (not shown) and a bracket supporting the aforementioned pipetting mechanism.
  • the bracket may include a strut, a beam and a backing plate, etc. for supporting and/or erecting the pipetting mechanism.
  • the one rack 43 and the two linear guides 40 are arranged in parallel above and below, and are fixed to the backboard 9.
  • the back plate 9 can be fixed to the side wall of the casing or to a beam mounted on the inside of the machine body.
  • FIG. 2 is a perspective view of a pipetting mechanism in accordance with a preferred embodiment of the present invention.
  • Figure 3 is an internal cross-sectional view of a pipetting mechanism in accordance with a preferred embodiment of the present invention.
  • the pipetting mechanism has a moving base, and the moving base has a quadrangular outer frame; the pipetting mechanism further has a side frame movably vertically mounted on the moving base. a moving rod on the upper side (such as the left border 23) and a pipetting head mounted on the lower end of the moving rod, wherein the moving rod can move up and down relative to the moving base in the frame in a vertical direction,
  • the pipetting head is a mechanism for liquid sensing, conveying, suctioning, etc., and can move up and down with the up and down movement of the moving rod to realize the function of processing the liquid sample disposed in the container under the pipetting head;
  • the pipetting mechanism further has a driving mechanism for driving the moving rod to move up and down relative to the moving base, including a screw rod and the lead rod mounted on the moving base, parallel to the moving rod a driving motor, the lead screw is fixedly connected to the moving rod through a driving connection;
  • the pipetting mechanism further has a gear that is rotatable in a
  • the moving base is a rectangular parallelepiped member having a quadrangular outer frame, the four sides of which are the upper beam 21, the lower beam 22, and the left frame 23 and Right border 24.
  • the base is typically made of a material such as aluminum or stainless steel that reduces the weight of the device and reduces liquid adhesion.
  • the bezel has a thickness to provide support for a motor, a circuit board box for housing a device for controlling a motor, and the like, and for accommodating and supporting the aforementioned moving rod.
  • the bezel may have a thickness similar to the width of the motor (eg, the diameter of a cylindrical motor or the width of a rectangular motor, etc.) or may be greater than the width of the moving rod (eg, the diameter or square of a cylindrical moving rod) The thickness of the moving rod, etc.).
  • the bezel has a thickness greater than 0.5 cm.
  • the moving base may also be a rectangular parallelepiped component that does not have a hollow portion. At this time, the part of the four sides is also equivalent to the outer frame of the aforementioned quadrilateral, that is, "upper beam, lower Beam, left border and right border".
  • the left bezel 23 is used to provide the aforementioned moving bar 7 for moving up and down relative to the moving base within the bezel.
  • the left bezel 23 is a hollow structure, and the travel bar 7 is movably fitted within the left bezel.
  • the left bezel 23 has a recess that opens toward the inside of the moving base (ie, the side facing the right bezel) that is movably fitted in the recess In the groove, a part of the moving rod is outside the groove, that is, the inner side surface of the left side frame is protruded, and the protruding portion of the moving rod can be used for fixed connection with the driving mechanism for driving the moving rod to move up and down.
  • a driving mechanism for driving the moving rod to move up and down relative to the moving base in the left frame includes being mounted on the moving base, parallel to the moving rod.
  • the drive motor 13 is a servo motor.
  • the drive motor 13 is connected and driven to the lead screw 4 via a coupling 3.
  • the upper and lower ends of the lead screw are constrained between the upper beam and the lower beam of the moving base by bearings.
  • a drive motor 13 can be disposed above the lead screw.
  • the upper beam of the moving base has a recess in which the coupling 3 can be accommodated, and in addition a top plate 18 is disposed above the upper beam, the drive motor 13 being vertically mounted Above the top plate 18.
  • the top panel may have the same or similar length and width as the upper beam.
  • the top plate may also have a larger length than the upper beam.
  • a device such as a circuit board case (such as the circuit board case 29 in FIG. 1) for accommodating a control motor or the like.
  • the screw shaft 4 is fixedly connected to the moving rod 7 via a spindle nut 6 and a drive connection 17 .
  • the screw nut 6 is screwed onto the screw rod, and one end of the driving connector 17 is fixedly connected to the moving rod 7 by screws or the like, and the other end is fixed to the outside of the screw nut 6 by screwing.
  • the driving connecting member 17 can move up and down within the height range of the upper and lower beams of the moving base, thereby causing the moving rod to move up and down.
  • the spindle nut can take a backlash structure that eliminates most of the mechanical play of movement between the spindle nut and the lead screw.
  • the lead screw nut is made of a high molecular polymer material.
  • a high molecular polymer material such as Igus's Series, such as G, W300, J, X and M250 and so on.
  • the parts made of these polymer materials have the characteristics of no lubrication (self-lubricating), excellent acid-base resistance, good shock absorption performance, no need for sealing or oil scraping rings, and easy installation and replacement.
  • the illustrated moving rod of the pipetting mechanism of the present invention is movably fixed to the moving base in a vertical direction (i.e., a direction parallel to the frame, which is a gravity direction in the art).
  • the illustrated moving rod is movably secured within one of the frames of the mobile base.
  • the moving rod sliding sleeve disposed at the upper and lower ends of the frame is movably mounted in the frame on the moving base, wherein the moving rod sliding sleeve is fixedly connected with the frame, and the moving rod can be sleeved on the moving rod Move inside.
  • the moving rod is a square rod 7 that is movably fixed by the square tube sliding sleeve 2 and the left frame 23 at the upper and lower ends of the moving base.
  • 4 is a schematic view showing the connection relationship between the square rod 7, the square tube sliding sleeve 2 and the left frame 23.
  • the square tube sliding sleeve is fixed inside the one end of the left frame 23 (for example, the upper end of the figure, which also has the same structure at the lower end) (for example, the protrusion 201 and the left border on the square tube sliding sleeve).
  • the groove 231 of the edge is fitted, and the square rod 7 is slidably fitted in the square tube sleeve 2.
  • the square tube sleeve is made from a self-lubricating polymeric material.
  • a self-lubricating polymeric material such as Igus's Series, such as G, W300, J, X and M250 and so on. These polymer materials have excellent acid-base resistance and good shock absorption performance, eliminating the need for a seal or scraper ring for easy installation and replacement.
  • the illustrated moving rod is a hollow square rod 7.
  • the moving rod adopts a hollow tube groove and can be used for installing a wire or a pipette.
  • it can be used for wiring, including a catheter connected to a catheter, a liquid for conveying and extracting liquid, and wires used for various components and mechanisms, such as a cable of a liquid level detector, a wire of a motor, and the like.
  • a routing pipe joint 33 can be provided at the top of the square rod 7, a routing pipe joint 33 can be provided.
  • the pipetting mechanism of the present invention also has a gear 16 (i.e., rotating on a horizontal plane) that is rotatable in a vertical direction on a moving base (e.g., inside or outside the frame).
  • the gear is disposed outside the other side frame of the bezel in which the moving rod 7 is assembled.
  • the gear wheel may form a gear pair with the horizontally disposed rack, thereby driving the moving base to move horizontally along the rack when the gear rotates.
  • the rotation of the gear is driven by the gear drive motor 12.
  • the gear drive motor 12 may be disposed above the gear, for example, vertically disposed on the motor mount 11 fixed to the outside of the frame of the moving base.
  • the gear drive motor 12 is driven to the gear 16 through the coupling 8.
  • the gear drive motor is a servo motor.
  • the pipetting mechanism of the present invention further has a linear guide fixing seat 34 fixed to the moving base for fixing the slider of the linear guide.
  • the linear guide mount 34 is secured to the outside of the moving base bezel (eg, the right bezel 24 of the illustration).
  • the linear guide mount has a square surface of the same or similar size as the surface of the slider of the linear guide.
  • the height H1 of the linear guide mount is not less than 25 mm, preferably not less than 30 mm.
  • the linear guide rail of the pipetting mechanism of the present invention or the automatic pipetting instrument adopting the pipetting mechanism can have a slider width w (ie, the slider of the linear rail is in a direction perpendicular to the sliding rail of the linear guide rail)
  • the length is not less than 25 mm, preferably not less than 30 mm.
  • the use of a linear guide having the above-described slider width and/or a linear guide holder of the above-described height greatly unexpectedly improves the stability of the operation of the pipetting mechanism of the present invention.
  • the linear guide fixing seat of the pipetting mechanism of the present invention and the slider of the linear guide can be fixed by screws or the like, whereby the moving base can be slidably moved along the linear guide.
  • the linear guides are horizontally disposed, thereby realizing horizontal movement of the moving base in the direction of the linear guide.
  • the pipetting mechanism of the present invention has a linear guide fixing block 35 that can be coupled to the moving base by being fixed to the linear guide fixing block 35.
  • the linear guide fixing block 35 and the moving base can be integrally cast or fixed on the moving base by screws or the like.
  • the linear guide fixing block 35 may be a part of the bezel.
  • the height of the linear guide fixing block is greater than or equal to twice the height H2 of the linear guide mount.
  • the height of the linear guide fixing block is not less than 50 mm, preferably not less than 60 mm.
  • the linear guide fixing seat 34 can be fixed to the upper half or the lower half of the linear guide fixing block 35.
  • the gear 16 rotatable about the vertical axis and the linear guide fixing seat 34 are disposed on the same outer side of the frame of the moving base, as shown in the figure. Outside the right border.
  • the rack 43 which forms the gear pair with the gear 16 and the linear guide 40 which is connected to the linear guide mount 34 can be disposed in parallel.
  • the gear 16 and the linear guide fixing seat 34 are disposed in such a manner that when the gear 16 is rotated, the movable base that drives the slider fixed to the linear guide can be horizontally moved in the direction of the rail of the rack and the linear guide.
  • the gear 16 and the linear guide fixing seat 34 are disposed on the same side of the frame, and the corresponding rack 43 and the linear guide 40 are juxtaposed in parallel.
  • the pipetting mechanism using the present invention can be greatly saved.
  • the gear 16 and the linear guide holder 34 may also be disposed at other suitable positions of the moving base, and the sliding base of the moving base along the rack and the linear guide that is fixed to the slider of the linear guide can be realized. The direction moves horizontally.
  • the pipetting mechanism of the preferred embodiment of the present invention also has a pipetting head fixedly mounted at the lower end of the moving rod 7.
  • the pipetting head is a mechanism for functions such as liquid sensing, extraction, etc., and includes components for realizing these functions.
  • the pipetting head includes a pipette holder 27, a tube sleeve 28, a conduit 26, a stop block 31, a pipette tip 30, and a level detector 25.
  • the pipette holder 27 is used for erecting the liquid level detector 25 and the conduit 26 for connecting the pipette tip and the limiting block 31.
  • the tube sleeve 28 is used to achieve separation of the pipette tip from the catheter for automatic replacement.
  • the tube sleeve requires separation of the pipette tip from the catheter over a small distance.
  • the design of the pipetting head of the pipetting mechanism of the present invention enables the tube sleeve to achieve this purpose.
  • the level detector can be used to sense the distance between the liquid and the pipette tip in a standard liquid container (eg 8-well plate, 96-well plate) below the pipetting head, feed the signal back to the automated station, and program as needed The signal is fed back to the instrument that controls the pipetting mechanism under control.
  • the fully automatic pipetting station of the present invention can be equipped with four or eight of the pipetting mechanisms.
  • the four or eight of the pipetting mechanisms can move independently in a horizontal or vertical (vertical) direction, or can move horizontally or vertically (vertical) simultaneously, and two adjacent pipetting mechanisms occur. The same horizontal distance changes such that adjacent pipette tips undergo the same horizontal distance change.
  • Fig. 5 is a perspective view showing another embodiment of a fully automatic pipetting station according to a preferred embodiment of the present invention.
  • the fully automatic pipetting station of the present invention is usually equipped with four or eight of the pipetting mechanisms, and the eight pipetting mechanisms are divided into two parallel groups, each group of four pipetting mechanisms being assembled side by side, each group of four pipetting
  • the moving rods of the mechanism are arranged in a straight line, and the linear rail fixing seats 34 on the moving bases of the two adjacent pipetting mechanisms are respectively fixed to the upper half or the lower half of the linear rail fixing block 35, thereby being the same
  • the moving bases of two of the four pipetting mechanisms can be respectively connected to the two sliders of the same linear guide (fixed by the linear guide fixing seat and the linear guide), thereby greatly saving the pipetting mechanism using the present invention.
  • the internal space of the automated pipetting instrument is usually equipped with four or eight of the pipetting mechanisms, and the eight pipetting mechanisms are divided into two parallel groups, each group of four pipetting mechanisms being assembled side by side, each group of four pipetting
  • the moving rods of the mechanism are arranged in a straight line, and the linear rail fixing seats 34 on the moving bases of
  • the moving rods of each group of four pipetting mechanisms are arranged in a straight line, and are alternately arranged with the moving rods of another group of four pipetting mechanisms, so that the movement of the eight pipetting mechanisms is shifted.
  • the liquid gun head can be arranged in a straight line on.
  • the multi-channel pipetting device formed by the eight pipetting mechanisms can conveniently handle standard liquid containers such as 8-well plates, 24-well plates, and 96-well plates. Each of the pipetting mechanisms can move up and down independently.
  • the pipetting station of the present invention described above can be used for sensing, detecting, sucking, and discharging liquids to achieve liquid transfer.
  • the invention also provides the above-described pipetting mechanism, multi-channel pipetting device or fully automatic pipetting station of the invention for sensing, detecting, sucking and discharging liquid, thereby realizing the transfer of liquid.
  • the pipetting mechanism When a liquid suction or discharge operation is required on a standard liquid container (for example, an 8-well plate or a 96-well plate) under the pipetting head, the pipetting mechanism is moved under the program control to the upper of the standard liquid container.
  • the liquid level detector senses the distance between the liquid in the standard liquid container below the pipetting head and the pipetting tip, feeds the signal back to the control system, and the screw is driven by the moving rod driving motor 13, and the screw is driven.
  • the connecting member 17 vertically moves the moving rod 7 up and down in the vertical hole of the left frame of the moving base, thereby realizing the up and down movement of the liquid suction head.
  • the gear drive motor 12 drives the gear 16 to rotate in the horizontal direction, thereby driving the moving base to be horizontally moved along the linear guide by being fixed to the slider of the linear guide.
  • the design of the pipetting mechanism of the present invention enables the respective pipetting mechanisms in the pipetting station adopting them to perform vertical or horizontal movement completely independently, without any connection relationship with each other.
  • Such a structural arrangement makes the overall structure layout more Reasonable, the movement space is more clear, and the difficulty and complexity of assembly and debugging are greatly reduced.
  • the components in the mechanism for controlling the movement of the pipetting head are mostly prepared by self-lubricating and maintenance-free polymer, which avoids or greatly reduces the lubrication operation and avoids grease lubrication. There is a possibility of contamination of the pipetting operation.

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Abstract

一种移液工作站包括移液机构支架、数个移液机构(38)、齿条(43)和与齿条(43)平行的直线导轨(40)。该移液机构(38)包括移动基座(1)、可移动地装配于该移动基座(1)的移动杆(7)、移动杆驱动机构、可绕竖直方向转动的齿轮(16)；直线导轨固定座(34)以及安装在移动杆(7)下端的移液头。该移液工作站可用于实施液体加样、液体转移。该移液工作站的各移液机构(38)可独立地进行竖直或水平的移动，避免或大大减少了对其进行润滑的操作，并且避免了污染。

Description

全自动移液仪和其用途
本申请要求了2013年11月6日提交的、申请号为201310544596.7、发明名称为“用于全自动移液仪的移液机构和其用途”；2013年11月6日提交的、申请号为201310544587.8、发明名称为“全自动移液仪和其用途”；2014年3月20日提交的、申请号为201410104387.5、发明名称为“全自动移液仪和其用途”的中国专利申请的优先权，其全部内容通过引用结合在本申请中。
技术领域
本发明涉及自动化液体处理设备。更具体的，本发明涉及一种全自动移液仪和其中的移液机构，及其在实施液体加样、液体转移等方面的用途。
背景技术
随着生命科学技术的飞速发展，生化实验室的研究工作面对的是更为复杂的研究对象和不断增多的样品数量，传统的手工操作方式已经不能满足高通量样品处理过程中所要求的高效性、准确性和安全性，实验操作流程中部分或整体过程的自动化运行已成为必然趋势。
全自动液体处理工作站是将自动化操作与液体处理巧妙融合在一起的生物医药实验室自动化操作平台，可实现样品的自动加样、试剂分配、超微量移液以及与液体处理相关的振动、孵育等操作。可广泛应用于核酸纯化、基因蛋白质测序、克隆快速筛选、细胞培养、生物芯片样品制备等领域。
移液机构是全自动液体处理工作站的核心机构之一，用于实现液体在标准液体容器之间输送、抽提、转移等动作。在现代全自动液体处理工作站的使用中，最常用的标准液体容器是例如8孔板、96孔板等标准液体容器。其中，实验室常用的96孔板等标准液体容器相邻孔间距最小为9mm，容积约0.5ml，单列分布8个孔。因此，自动液体处理工作站，特别是其中的移液机构，需要在很小的空间范围内，高精度和高重复性地实现多个，例如八 个移液通道的同时或分别的移液动作。
现有技术的自动液体处理工作站以及移液机构存在机构磨损大、噪音大、运动平稳性不高，移动基座滑槽的加工精度要求较高，装配过程调试繁杂，工作量大的缺陷，以及日常运作和维护繁琐，且容易在仪器内部产生污染和腐蚀的问题。
发明内容
本发明提供了一种新型的全自动工作站，克服了现有技术中移液机构磨损大、装配调试繁杂且机构整体运行平滑性较差的问题，并且提供了维护简单，不产生污染的内部环境。
本发明提供了一种移液工作站，包括：
(a)移液机构支架；
(b)数个移液机构，其中，所述移液机构具有：
移动基座；
(a)可移动地装配于所述移动基座的移动杆，所述移动杆可在竖直方向做相对所述移动基座的移动；
移动杆驱动机构，包括与所述移动杆平行设置的丝杆以及所述丝杆的驱动机构，所述丝杆通过驱动连接件与所述移动杆固定连接；
i.装配于移动基座上的齿轮以及所述齿轮的驱动机构，所述齿轮可绕竖直方向转动；
固定在移动基座上的直线导轨固定座；以及安装在移动杆下端的移液头；
(c)沿水平方向设置，与所述移液机构的齿轮形成齿轮副的齿条，齿轮转动时，驱动移动基座沿齿条水平移动；以及
(d)沿水平方向设置，与所述齿条平行的直线导轨，所述直线导轨的滑块与所述移液机构的直线导轨固定座连接和固定，由此移动基座可随直线导轨的滑块沿直线导轨的轨道进行水平方向的移动。
在本发明的上述移液工作站的移液机构中，所述直线导轨固定座可与直线导轨的滑块连接和固定。所述直线导轨可沿水平方向设置，与前述齿条 平行。所述直线导轨的滑块与所述直线导轨固定座连接和固定，由此直线导轨固定座以及与直线导轨固定座连接和固定的移动基座可随直线导轨的滑块沿滑动导管的轨道进行水平方向的移动。
在本发明的其中一个方面，所述移液工作站的齿轮和齿条，以及直线导轨固定座和直线导轨的位置设置方式使得当齿轮转动时，可实现驱动与直线导轨的滑块固定的移动基座沿齿条和直线导轨的滑轨方向水平移动。例如，齿轮以及直线导轨固定座设置在边框的同一侧，对应的齿条和直线导轨上下平行并置。
在本发明的其中一个方面，所述直线导轨固定座具有与直线导轨的滑块的表面相同或类似形状和大小的四方形表面。例如，所述直线导轨固定座的高度H1大于25mm，优选大于30mm。所述直线导轨固定座可配合或使用的直线导轨为具有滑块宽度w大于25mm，优选大于30mm的直线导轨。
在本发明的其中一个方面，所述移液机构中所述直线导轨固定座通过直线导轨固定块与移动基座连接。所述直线导轨固定块与上述移动基座可一体铸造或通过螺纹等方式固定在移动基座上。所述直线导轨固定块用于固定两个所述直线导轨固定座。通常，所述直线导轨固定块具有直线导轨固定座相同或相似的宽度(通常指水平方向的长度)以及不低于两倍的高度(通常指竖直方向的长度)。例如，所述直线导轨固定块的高度H2大于或等于50mm，优选大于或等于60mm。
在本发明的其中一个方面，所述移液机构的移动基座具有四边形的外框，其四个边分别为上梁、下梁和两个边框。
在本发明的其中一个方面，所述移液工作站的移液机构中所述移动杆可移动地装配于所述移动基座一侧边框。
在本发明的其中一个方面，所述移液工作站的移液机构中所述用于装配移动杆的边框具有凹槽，所述凹槽开口向移动基座的内侧，所述移动杆可移动地装配在所述凹槽内，移动杆的一部分处于凹槽外，即突出左边框内侧表面，该移动杆的突出部分可用于与移动杆驱动机构的驱动连接件进行固定连接。
在本发明的其中一个方面，所述移液工作站的移液机构中所述移动杆 通过设置在边框的移动杆滑套可移动地装配在所述移动基座上的边框内，其中所述移动杆滑套与边框固定连接，所述移动杆可在移动杆滑套内移动。
在本发明的其中一个方面，所述移液工作站的移液机构中所述移动杆滑套为高分子聚合物材料制备的滑套。例如易格斯(Igus)公司的
Figure PCTCN2014090402-appb-000001
系列，如
Figure PCTCN2014090402-appb-000002
G、
Figure PCTCN2014090402-appb-000003
W300、
Figure PCTCN2014090402-appb-000004
J、
Figure PCTCN2014090402-appb-000005
X和
Figure PCTCN2014090402-appb-000006
M250等。这些聚合物材料制备的零件具有免润滑(自润滑)的特性，以及具有优良的酸碱抗性，吸震性能好，无需密封或刮油环，方便安装和替换。优选的，本发明的移液机构中所述移动杆滑套不为金属材料部件。
在本发明的其中一个方面，所述移液工作站的移液机构中所述移动杆为空心管槽。空心管槽内可用于安装电线或移液导管。
在本发明的其中一个方面，所述移液工作站的移液机构中所述丝杆的驱动机构为所述丝杆的驱动电机。所述丝杆通过驱动电机进行驱动。优选的，所述驱动电机为伺服电机。
在本发明的其中一个方面，所述丝杆通过丝杆螺母和驱动连接件与移动杆固定连接。例如，丝杆螺母旋装在丝杆上，驱动连接件的一端与移动杆固定连接，另一端固定在所述丝杆螺母外侧。优选的，其中所述丝杆螺母为高分子聚合物制备。选的，本发明的移液机构中所述丝杆螺母不为金属材料部件。
在本发明的其中一个方面，所述移液工作站的移液机构中所述移液头具有限位块，以及移液管架，连接在移液管架下方的导管，所述导管可连接可更换的移液枪头。在本发明的其中又一个方面，所述移液机构中所述导管上设置有脱管套筒。在本发明的其中又一个方面，所述移液头具有液面探测器。
在本发明的其中一个方面，所述移液工作站还包括沿水平方向设置，与所述齿轮形成齿轮副的齿条，齿轮转动时，驱动移动基座沿齿条水平移动。
在本发明的其中一个方面，所述移液工作站还包括沿水平方向设置，与所述齿条平行的直线导轨，所述直线导轨的滑块与所述直线导轨固定座连接和固定，由此移动基座可随直线导轨的滑块沿直线导轨的轨道进行水平方向的移动。在本发明的其中一个方面，所述移动基座是通过直线导轨固定座 (还可包括直线导轨固定位)与直线导轨的滑块连接和固定。
在本发明的其中一个方面，其中所述齿轮以及直线导轨固定座的位置设置方式使得当齿轮转动时，驱动移动基座沿齿条和直线导轨的滑轨方向水平移动。移动基座是通过直线导轨固定座(还可包括直线导轨固定位)与直线导轨的滑块连接和固定。例如，齿轮以及直线导轨固定座设置在其中一个边框的同一侧，对应的齿条和直线导轨上下平行并置。
在本发明的其中一个方面，所述移液机构中所述移液头具有限位块，以及移液管架，连接在移液管架下方的导管，所述导管可连接可更换移液枪头。在本发明的其中又一个方面，所述导管上设置有脱管套筒。在本发明的其中又一个方面，其中所述移液头具有液面探测器。所述液面探测器可设置在移液管架下方。
在本发明的其中一个方面，所述移液工作站具有数个(例如四个或八个)前述移液机构，其中所述数个移液机构中的两个或两个以上并列装配，所述并列装配的两个或两个以上移液机构的移动杆排列在一条直线上，并且所述并列装配的两个或两个以上移液机构的齿轮与同一条齿条形成齿轮副。在本发明的其中又一个方面，所述并列装配的两个或两个以上移液机构中两个移液机构的移动基座的直线导轨固定座与同一个直线导轨的两个滑块连接。例如，通过相邻两个移动基座上的直线导轨固定座分别固定在移动基座的直线导轨固定块上的上半部分或是下半部分，由此所述并列装配的数个移液机构中的两个移动基座可分别与同一个直线导轨的两个滑块连接。所述齿轮和齿条，以及直线导轨固定座和直线导轨的位置设置方式使得当齿轮转动时，可实现驱动与直线导轨的滑块固定的移动基座沿齿条和直线导轨的滑轨方向水平移动。
在本发明的其中一个方面，所述移液工作站包括四个或八个所述移液机构。在包括八个所述移液机构的移液工作站中，所述八个移液机构分成平行设置的两组，每组四个移液机构并列装配，每组四个移液机构的齿轮与同一条齿条形成齿轮副。在本发明的其中又一个方面，所述每组四个移液机构中两个移液机构的移动基座的直线导轨固定座与同一个直线导轨的两个滑块连接。例如，通过相邻两个移动基座上的直线导轨固定座分别固定在移动 基座的直线导轨固定块上的上半部分或是下半部分，由此所述并列装配的四个移液机构中的两个移动基座可分别与同一个直线导轨的两个滑块连接。所述齿轮和齿条，以及直线导轨固定座和直线导轨的位置设置方式使得当齿轮转动时，可实现驱动与直线导轨的滑块固定的移动基座沿齿条和直线导轨的滑轨方向水平移动。在本发明的移液工作站中，所述每组四个移液机构的移动杆排列在一条直线上，与另一组四个移液机构的移动杆交错设置，使得八个所述移液机构的移液枪头可排列在一条直线上。
在本发明的其中一个方面，所述移液工作站还包括其它检测装置或容器，例如注射泵、加热板、振荡器、酶标仪、PCR仪、抓手机构，以及各种容纳样品或试剂的容器，如微量离心管、离心管，PCR微孔板、深孔板、微孔过滤板、管架等。
在本发明的其中一个方面，还提供了一种如前描述的移液机构。在本发明的其中一个方面，其包括：移动基座；可移动地装配于所述移动基座的移动杆，所述移动杆可在垂直方向做相对所述移动基座的移动；移动杆驱动机构，包括与所述移动杆平行设置的丝杆以及所述丝杆的驱动机构，所述丝杆通过驱动连接件与所述移动杆固定连接；装配于移动基座边框上(例如边框内侧或外侧，优选外侧)的齿轮以及所述齿轮的驱动机构，所述齿轮可绕垂直方向转动；固定在移动基座边框上(例如边框内侧或外侧，优选外侧)的直线导轨固定座；以及安装在移动杆下端的移液头。
在本发明的其中一个方面，还提供了一种采用前述移液机构的多通道移液装置，所述多通道移液装置装配有二个、四个或八个所述移液机构。
本发明的移液机构、装置和仪器可实现在运作中各移液机构独立地进行竖直或水平的移动，以及整体结构的布局更加合理，运动空间更加明确，其装配调试的难度以及复杂性也得以大大的降低。另外，本发明的移液机构采用自润滑、免维护的高分子聚合物材料来制备用于固定和使其在其中滑动的移动杆的滑套，空心方管在高分子聚合物滑套内的滑动平顺、柔和、噪音小，并且避免或减少了对其进行润滑的操作，避免了油脂类润滑物对移液操作有可能造成的污染。另外，本发明的移液机构使用的用于实现移液头竖直方向运动的丝杠副，以伺服电机驱动丝杠，能克服现有技术中机械振动大， 不稳定的缺陷。并且其中丝杠螺母采取消隙结构，可消除丝杠螺母与丝杠之间运动的大部分机械间隙，可进一步实现更精密的传动，从而实现移液头更精细的移液操作。其中，丝杠螺母也可为聚合物材料制备，由此，驱动移液头竖直方向移动的机构可避免或减少了对其进行润滑的操作，避免了油脂类润滑物对移液操作有可能造成的污染。
附图说明
图1为本发明优选实施例的移液工作站的局部内部装置图；
图2为本发明优选实施例的移液工作站的移液机构的立体图；
图3为本发明优选实施例的移液工作站的移液机构的剖视图；
图4为本发明优选实施例的移液工作站的移液机构的局部装配示意图；
图5为本发明优选实施例的移液工作站的部分结构另一个角度的立体示意图。
附图中各标记分别为：
1 移动基座
2 方管滑套
201 方管滑套凸起
3 丝杆联轴器
4 丝杆
6 丝杆螺母
7 中空方杆
8 齿轮联轴器
9 机架背板
11 电机座
12 齿轮驱动电机
13 移动杆驱动电机
14 齿轮轴承
15 齿轮轴
16 齿轮
17 驱动连接件
18 顶板
19 底板
21 上梁
22 下梁
23 左边框
231 左边框凹槽
24 右边框
25 移液管架
26 导管
27 移液管架
28 脱管套筒
30 移液枪头
31 限位块
33 走线走管接头
34 直线导轨固定座
35 直线导轨固定块
36 电路板盒
40 直线导轨
41 直线导轨滑轨
42 直线导轨滑块
43 齿条
具体实施方式
为了更好地理解和阐释本发明，下面将参照附图对本发明作进一步的详细描述。
图1是根据本发明的一个优选实施例的移液工作站的局部内部装置 图。
本发明的移液工作站一般具有八个用于实施液体加样、液体转移的移液机构38。所述八个移液机构分成平行设置的两组，每组四个移液机构并列装配。图1示出本发明的移液工作站的内部部分装置示意图，其包括上述一组并列装配的四个移液机构的装置。所述移液机构具有移动基座1，所述移动基座具有四边形的外框。所述移液机构还具有可移动地竖直装配于移动基座的一侧边框上的移动杆7和安装在该移动杆下端的移液头30。所述移动杆可在竖直方向上在所述边框内做相对所述移动基座的上下移动。驱动所述移动杆做相对所述移动基座的上下移动的驱动机构包括装配于所述移动基座上，与所述移动杆平行的丝杆4。移液头是用于液体感应、输送、吸取等功能的机构，可随所述移动杆的上下移动发生上下移动，实现处理设置在移液头下方的盛器皿中的液体样品的功能。
所述移液机构还具有装配于移动基座边框外侧的可绕竖直方向转动的齿轮16，所述齿轮可与水平设置的齿条43形成齿轮副，齿轮转动时，驱动移动基座沿齿条水平移动。所述移液机构还具有固定在移动基座上，用于与直线导轨的滑块42进行连接和固定的直线导轨固定座，由此移动基座可沿水平设置的直线导轨40滑动实现水平移动。齿轮16和齿条43，以及直线导轨固定座34和直线导轨40的位置设置方式使得当齿轮16转动时，可实现驱动与直线导轨的滑块固定的移动基座沿齿条和直线导轨的滑轨方向水平移动。
本发明的移液工作站的每组四个移液机构的移动杆排列在一条直线上，与另一组四个移液机构的移动杆交错设置，使得八个所述移液机构的移液枪头可排列在一条直线上。
在如图所述的优选实施例中，本发明的移液工作站的每组四个移液机构的齿轮与同一条齿条形成齿轮副，其中相邻两个移动基座上的直线导轨固定座34分别与同一个直线导轨的两个滑块连接，由此每组四个移液机构与两条直线导轨连接。所述一条齿条和所述两条直线导轨上下平行设置。
本发明的移液工作站还可具有机壳(未示出)和支撑前述移液机构的支架。支架可包括用于支撑和/或架设移液机构的支柱、横梁和背板等。如图 1所示，所述一条齿条43和所述两条直线导轨40上下平行设置，固定在背板9上。背板9可固定在机壳侧壁或是固定在架设在机体内部的横梁上。
图2是根据本发明的一个优选实施例的移液机构的立体示意图。图3为本发明的一个优选实施例的移液机构的内部剖视图。
如图2和图3所示，该移液机构具有移动基座，所述移动基座具有四边形的外框；所述移液机构还具有可移动地竖直装配于移动基座的一侧边框上(如图示左边框23)的移动杆和安装在该移动杆下端的移液头，所述移动杆可在竖直方向上在所述边框内做相对所述移动基座的上下移动，移液头是用于液体感应、输送、吸取等功能的机构，可随所述移动杆的上下移动发生上下移动，实现处理设置在移液头下方的盛器皿中的液体样品的功能；所述移液机构还具有用于驱动所述移动杆做相对所述移动基座的上下移动的驱动机构，包括装配于所述移动基座上，与所述移动杆平行的丝杆以及所述丝杆的驱动电机，所述丝杆通过驱动连接件与所述移动杆固定连接；所述移液机构还具有装配于移动基座边框外侧的可绕竖直方向转动的齿轮以及所述齿轮的驱动机构，所述齿轮可与水平设置的齿条形成齿轮副，齿轮转动时，驱动移动基座沿齿条水平移动；所述移液机构还具有固定在移动基座上，用于与直线导轨的滑块进行连接和固定的直线导轨固定座，由此移动基座可沿水平设置的直线导轨滑动实现水平移动。
在图2所示的本发明优选实施例的移液机构中，所述移动基座为长方体部件，具有四边形的外框，其四个边分别为上梁21、下梁22，左边框23和右边框24。所述基座通常由可减轻装置重量并减少液体附着的金属材料如铝材或不锈钢等材料制成。所述边框具有一定厚度，以对电机、用于容纳控制电机等设备的电路板盒等装置提供支持作用，以及可以用于容纳和支撑前述移动杆。例如，所述边框可具有与电机宽度(例如圆柱型电机的直径或长方体型电机的宽度等)相似的厚度，或是具有大于所述移动杆的宽度(例如圆柱形移动杆的直径或方型移动杆的宽度等)的厚度。在本发明的其中一个方面，所述边框具有大于0.5cm的厚度。采用具有边框的设计，可以减小部件重量等优点。在其它实施方式中，移动基座也可以为不具有中空部分的长方体部件。此时，其四个边的部分也等同于前述四边形的外框，即“上梁、下 梁，左边框和右边框”。
在图示本发明优选实施例中，左边框23用于设置前述在所述边框内做相对所述移动基座的上下移动的移动杆7。在图示优选的实施例中，左边框23为中空结构，所述移动杆7可移动地装配在所述左边框内。在图示优选的实施例中，左边框23具有凹槽，所述凹槽开口向移动基座的内侧(即面对右边框的一侧)，所述移动杆可移动地装配在所述凹槽内，移动杆的一部分处于凹槽外，即突出左边框内侧表面，该移动杆的突出部分可用于与驱动移动杆上下运动的驱动机构进行固定连接。
如图2和图3所示，用于驱动所述移动杆在左边框内做相对所述移动基座的上下移动的驱动机构包括装配于所述移动基座上，与所述移动杆平行的丝杆4以及所述丝杆的驱动电机13。优选的，所述驱动电机13为伺服电机。所述驱动电机13通过联轴器3与丝杆4连接和传动。所述丝杆的上下两端通过轴承限制在移动基座的上梁和下梁之间。驱动电机13可设置在所述丝杆的上方。在图示本发明的优选实施例中，所述移动基座的上梁具有凹槽，在其中可容纳联轴器3，另外在上梁上方设置顶板18，所述驱动电机13垂直架设在所述顶板18上方。所述顶板可具有与上梁相同或相似的长度和宽度。所述顶板还可具有较上梁大的长度，除了可用于架设所述驱动电机13，还可用于架设容纳控制电机等设备的电路板盒(如图1中的电路板盒29)等装置。这种设计可大大节省采用本发明的移液机构的自动化移液仪器的内部空间，便于电线、移液导管的架设。
所述丝杆4通过丝杆螺母6和驱动连接件17与移动杆7固定连接。其中，丝杆螺母6旋装在丝杆上，驱动连接件17的一端通过螺丝等方式与移动杆7固定连接，另一端可通过旋装方式固定在丝杆螺母6外侧。当丝杆在驱动电机13驱动下发生转动时，驱动连接件17可在移动基座的上下梁高度范围内上下移动，从而带动移动杆发生上下移动。在本发明的其中一个方面，所述丝杠螺母可采取消隙结构，消除丝杠螺母与丝杠之间运动的大部分机械间隙。在本发明的其中一个方面，所述丝杠螺母采用高分子聚合物材料制备。例如易格斯(Igus)公司的
Figure PCTCN2014090402-appb-000007
系列，如
Figure PCTCN2014090402-appb-000008
G、
Figure PCTCN2014090402-appb-000009
W300、
Figure PCTCN2014090402-appb-000010
J、
Figure PCTCN2014090402-appb-000011
X和
Figure PCTCN2014090402-appb-000012
M250等。这些聚合物材料制备的零件具有 免润滑(自润滑)的特性，以及具有优良的酸碱抗性，吸震性能好，无需密封或刮油环，方便安装和替换。
本发明的移液机构的所示移动杆可移动地沿竖直方向(即与边框平行的方向，在本领域中，该竖直方向为重力方向)固定在移动基座上。优选的，所示移动杆可移动地固定在移动基座的其中一个边框内。例如，通过设置在边框上下两端的移动杆滑套可移动地装配在所述移动基座上的边框内，其中所述移动杆滑套与边框固定连接，所述移动杆可在移动杆滑套内移动。在图示实施例中，所述移动杆为方形杆7，通过方管滑套2与左边框23在移动基座的上下两端可移动地固定。图4为所述方形杆7，方管滑套2与左边框23的连接关系示意图。如图4所示，方管滑套固定在左边框23其中一端(例如图示的上端，其在下端也具有同样的结构)的内部(例如通过方管滑套上的凸起201与左边框边缘的凹槽231配合)，方形杆7可滑动地装配在方管滑套2内。在本发明的其中一个方面，所述方管滑套采用自润滑的聚合物材料制备。例如易格斯(Igus)公司的
Figure PCTCN2014090402-appb-000013
系列，如
Figure PCTCN2014090402-appb-000014
G、
Figure PCTCN2014090402-appb-000015
W300、
Figure PCTCN2014090402-appb-000016
J、
Figure PCTCN2014090402-appb-000017
X和
Figure PCTCN2014090402-appb-000018
M250等。这些聚合物材料具有优良的酸碱抗性，吸震性能好，无需密封或刮油环，方便安装和替换。
在图示实施例中，所示移动杆为中空的方形杆7。所述移动杆采用空心管槽，可用于安装电线或移液导管等。例如，可用于走线，包括与导管相连，用于液体的输送和抽提的导液管，以及各个部件和机构使用的电线，例如液面探测器的线缆，电机的电线等。在方形杆7的顶端，可设置走线走管接头33。
本发明的移液机构还具有设置在移动基座上(例如边框内侧或外侧)的可绕竖直方向转动的齿轮16(即在水平面上转动)。在图示实施例中，所述齿轮设置在于装配所述移动杆7的边框的另一侧边框的外侧。所述齿轮可与水平设置的齿条形成齿轮副，由此实现齿轮转动时，驱动移动基座沿齿条水平移动。齿轮的转动由齿轮驱动电机12驱动。齿轮驱动电机12可设置在齿轮上方，例如垂直设置在固定在移动基座的边框外侧的电机座11上。齿轮驱动电机12通过联轴器8向齿轮16传动。优选的，所述齿轮驱动电机为伺服电机。
本发明的移液机构还具有固定在移动基座上，用于与直线导轨的滑块进行固定的直线导轨固定座34。在本发明的其中一个方面，所述直线导轨固定座34固定在移动基座边框(例如图示的右边框24)外侧。直线导轨固定座具有与直线导轨的滑块的表面相同或类似的尺寸的四方形表面。在本发明的其中一个方面，所述直线导轨固定座的高度H1不小于25mm，优选不小于30mm。本发明的移液机构或采用所述移液机构的自动化移液仪器可配合或使用的直线导轨为具有滑块宽度w(即直线导轨的滑块在与直线导轨的滑轨垂直的方向上的长度)不小于25mm，优选不小于30mm的直线导轨。采用具有上述滑块宽度的直线导轨和/或上述高度的直线导轨固定座，出乎意料地大大提高了本发明移液机构运行的稳定性。本发明的移液机构的所述直线导轨固定座与直线导轨的滑块可通过螺钉等方式进行固定，由此移动基座可沿直线导轨滑动移动。在本发明的移液机构或采用本发明的移液机构的移液仪器中，直线导轨水平设置，由此实现移动基座沿直线导轨方向水平移动。
在本发明的其中一个方面，本发明的移液机构具有直线导轨固定块35，所述直线导轨固定座34可通过固定在所述直线导轨固定块35上而与移动基座连接。所述直线导轨固定块35与移动基座可一体铸造，或是通过螺钉等方式固定在移动基座上。在其中一种实施方式中，直线导轨固定块35可以是边框的一部分。在本发明的其中一个方面，所述直线导轨固定块的高度大于或等于两倍的直线导轨固定座的高度H2。优选的，所述直线导轨固定块的高度不小于50mm，优选不小于60mm。直线导轨固定座34可固定在直线导轨固定块35的上半部分或是下半部分。
本发明优选实施例的移液机构中，例如附图所示的优选实施例中，可绕竖直轴转动的齿轮16以及直线导轨固定座34设置在移动基座的边框同一外侧，如图示的右边框外侧。如图1或图5所示，与齿轮16形成齿轮副的齿条43和与直线导轨固定座34连接的直线导轨40可平行设置。齿轮16以及直线导轨固定座34的位置设置方式使得当齿轮16转动时，可实现驱动与直线导轨的滑块固定的移动基座沿齿条和直线导轨的滑轨方向水平移动。优选的，齿轮16以及直线导轨固定座34设置在边框的同一侧，对应的齿条43和直线导轨40上下平行并置。由此，可大大节省采用本发明的移液机构的 自动化移液仪器的内部空间。在其它实施方式中，齿轮16以及直线导轨固定座34也可以设置在移动基座的其它合适的位置，可实现驱动与直线导轨的滑块固定的移动基座沿齿条和直线导轨的滑轨方向水平移动。
所述本发明优选实施例的移液机构还具有固定安装在移动杆7下端的移液头。移液头是用于液体感应、抽提等功能的机构，包括了实现这些功能的部件。在图示实施例中，该移液头包括移液管架27、脱管套筒28、导管26、限位块31、移液枪头30和液面检测器25。其中，移液管架27用于架设液面检测器25和导管26，导管26用于连接移液枪头，限位块31。脱管套筒28用于实现移液枪头与导管的分离从而达到自动更换的目的。由于移液枪头与导管的结合非常紧密，脱管套筒需要在很小的距离范围内实现移液枪头与导管的分离。本发明的移液机构移液头的设计使得脱管套筒能够达到这个目的。液面检测器可用于感测移液头下方的标准液体容器(例如8孔板、96孔板)中液体与移液枪头之间的距离，将信号反馈到自动工作站，并按照需要在程序控制下把信号反馈给操控移液机构的仪器。
本发明的全自动移液工作站可装配四个或八个所述移液机构。所述四个或八个所述移液机构可独立水平或竖直(垂直)方向的移动，也可同步发生水平或竖直(垂直)方向的移动，且相邻的两个移液机构发生相同的水平距离变化，使得相邻的移液枪头发生相同的水平距离变化。
图5为本发明优选实施例的全自动移液工作站的部分结构另一个角度的立体示意图。
本发明的全自动移液工作站通常装配四个或八个所述移液机构，所述八个移液机构分成平行的两组，每组四个移液机构并列装配，每组四个移液机构的移动杆排列在一条直线上，相邻两个移液机构的移动基座上的直线导轨固定座34分别固定在直线导轨固定块35上的上半部分或是下半部分，由此同一组四个移液机构中的两个的移动基座可分别与同一个直线导轨的两个滑块连接(通过直线导轨固定座和直线导轨固定位)，从而大大节省采用本发明的移液机构的自动化移液仪器的内部空间。本发明的全自动移液工作站中每组四个移液机构的移动杆排列在一条直线上，与另一组四个移液机构的移动杆交错设置，使得八个所述移液机构的移液枪头可排列在一条直线 上。
八个移液机构形成的多通道移液装置可以方便地处理8孔板、24孔板、96孔板等标准液体容器。其中每个移液机构可以独立地上下移动。
上述本发明移液工作站可用于对液体进行感应、探测、吸取和排出等操作，从而实现液体的转移。
本发明还提供了上述本发明的移液机构、多通道移液装置或全自动移液工作站用于对液体进行感应、探测、吸取和排出，从而实现液体的转移的用途。
在操作中，上述本发明优选实施例的移液工作站的整个工作流程如下：
在需要对移液头下方的标准液体容器(例如8孔板、96孔板)进行液体的吸取或放出动作时，在程序控制下使移液机构移动到标准液体容器上方。液面检测器感测移液头下方的标准液体容器中液体与移液枪头之间的距离，将信号反馈到控制系统，可通过移动杆驱动电机13令丝杆发生转动，丝杆通过驱动连接件17使移动杆7在移动基座左边框的竖直孔内做竖直上下移动，从而实现吸液头的上下移动。当移液基座需要进行水平方向上的移动时，齿轮驱动电机12驱动齿轮16发生水平方向的转动，由此驱动移动基座通过与直线导轨的滑块固定，可沿直线导轨水平移动。
本发明的移液机构的设计使得在采用其的移液工作站中各个移液机构可完全独立地进行竖直或水平的移动，互相之间没有连接关系.这样的结构设置使得整体结构的布局更加合理，运动空间更加明确，其装配调试的难度以及复杂性也得以大大的降低。在进行移液机构的维护时，只需对其中某个损坏的移液通道维修更换即可，无需涉及其他通道的拆卸。
另外，本发明的移液工作站中控制移液头移动的机构中的部件多采用自润滑、免维护的高分子聚合物制备，避免或大大减少了对其进行润滑的操作，避免了油脂类润滑物对移液操作有可能造成的污染。
虽然关于本发明的示例实施例及其优点已经详细说明，应当理解在不脱离本发明的精神和所附权利要求限定的保护范围的情况下，可以对这些实施例进行各种变化、替换和修改。对于其他例子，本领域的普通技术人员应 当容易理解在保持本发明保护范围内的同时，工艺步骤的次序可以变化。
此外，本发明的应用范围不局限于说明书中描述的特定实施例的工艺、机构、制造、物质组成、手段、方法及步骤。从本发明的公开内容，作为本领域的普通技术人员将容易地理解，对于目前已存在或者以后即将开发出的工艺、机构、制造、物质组成、手段、方法或步骤，其中它们执行与本发明描述的对应实施例大体相同的功能或者获得大体相同的结果，依照本发明可以对它们进行应用。因此，本发明所附权利要求旨在将这些工艺、机构、制造、物质组成、手段、方法或步骤包含在其保护范围内。

Claims (21)

  1. 一种移液工作站，包括：
    (a)移液机构支架；
    (b)数个移液机构，其中，所述移液机构具有：
    移动基座(1)，
    可移动地装配于所述移动基座(1)的移动杆(7)，所述移动杆可在垂直方向做相对所述移动基座的移动；
    移动杆驱动机构，包括与所述移动杆(7)平行设置的丝杆(4)以及所述丝杆的驱动机构，所述丝杆(4)通过驱动连接件(17)与所述移动杆(7)固定连接；
    装配于移动基座(1)上的齿轮(16)以及所述齿轮的驱动机构，所述齿轮(16)可绕垂直方向转动；
    固定在移动基座(1)上的直线导轨固定座(34)；以及
    安装在移动杆(7)下端的移液头；
    (c)沿水平方向设置，与所述移液机构的齿轮(16)形成齿轮副的齿条(43)，齿轮转动时，驱动移动基座沿齿条水平移动；以及
    (d)沿水平方向设置，与所述齿条平行的直线导轨，所述直线导轨的滑块与所述移液机构的直线导轨固定座(34)连接和固定，由此移动基座可随直线导轨的滑块沿直线导轨的轨道进行水平方向的移动。
  2. 权利要求1所述的移液工作站，其中所述移动基座具有四边形的外框，所述移动杆(7)可移动地装配于所述移动基座(1)一侧边框。
  3. 权利要求2所述的移液工作站，其中所述用于装配移动杆(7)的边框具有凹槽，所述凹槽开口向移动基座的内侧，所述移动杆可移动地装配在所述凹槽内，移动杆的一部分处于凹槽外，即突出左边框内侧表面，该移动杆的突出部分可用于与移动杆驱动机构的驱动连接件(17)进行固定连接。
  4. 权利要求3所述的移液工作站，其中所述移动杆通过设置在边框的移动杆滑套可移动地装配在所述移动基座上的边框内，其中所述移动杆滑套与边框固定连接，所述移动杆可在移动杆滑套内移动。
  5. 权利要求4所述的移液工作站，其中所述移动杆滑套为高分子聚合物滑套。
  6. 权利要求1所述的移液工作站，其中所述丝杆的驱动机构包括所述丝杆的驱动电机。
  7. 权利要求6所述的移液工作站，其中所述驱动电机为伺服电机。
  8. 权利要求1所述的移液工作站，其中所述丝杆(4)通过丝杆螺母(6)和驱动连接件(17)与移动杆(7)固定连接，其中，丝杆螺母(6)旋装在丝杆上，驱动连接件(17)的一端与移动杆7固定连接，另一端固定在所述丝杆螺母(6)外侧。
  9. 权利要求1所述的移液工作站，其中所述直线导轨固定座(34)通过直线导轨固定块(35)与移动基座连接。
  10. 权利要求1所述的移液工作站，其中所述直线导轨固定座(34)的高度H1大于或等于30mm。
  11. 权利要求9所述的移液工作站，其中所述直线导轨固定块的高度H2大于或等于60mm。
  12. 权利要求1的移液工作站，其中所述移液头具有限位块，以及移液管架(25)，连接在移液管架下方的导管(26)，所述导管可连接可更换的移液枪头(30)。
  13. 权利要求1所述的移液工作站，其中所述数个移液机构中的两个或两个以上并列装配，所述并列装配的两个或两个以上移液机构的移动杆排列在一条直线上，并且所述并列装配的两个或两个以上移液机构的齿轮与同一条齿条形成齿轮副。
  14. 权利要求13所述的移液工作站，其中所述并列装配的两个或两个以 上移液机构中两个移液机构的移动基座的直线导轨固定座34与同一个直线导轨的两个滑块连接。
  15. 权利要求13所述的移液工作站，其中所述并列装配的两个或两个以上移液机构中相邻两个移液机构的移动基座的直线导轨固定座34分别固定在其直线导轨固定块上的上半部分或是下半部分。
  16. 权利要求1所述的移液工作站，其包括八个所述移液机构，所述八个移液机构分成平行设置的两组，每组四个移液机构并列装配，每组四个移液机构的齿轮与同一条齿条形成齿轮副，以及所述每组四个移液机构中两个移液机构的移动基座的直线导轨固定座与同一个直线导轨的两个滑块连接。
  17. 权利要求16所述的移液工作站，其中相邻两个移动基座上的直线导轨固定座34分别固定在直线导轨固定块35上的上半部分或是下半部分。
  18. 权利要求16所述的移液工作站，其中每组四个移液机构的移动杆排列在一条直线上，与另一组四个移液机构的移动杆交错设置，使得八个所述移液机构的移液枪头可排列在一条直线上。
  19. 一种移液机构，其结构如权利要求1中所描述，所述移液机构包括：
    移动基座(1)，
    可移动地装配于所述移动基座(1)的移动杆(7)，所述移动杆可在垂直方向做相对所述移动基座的移动；
    移动杆驱动机构，包括与所述移动杆(7)平行设置的丝杆(4)以及所述丝杆的驱动机构，所述丝杆(4)通过驱动连接件(17)与所述移动杆(7)固定连接；
    装配于移动基座(1)上的齿轮(16)以及所述齿轮的驱动机构，所述齿轮(16)可绕垂直方向转动；
    固定在移动基座(1)上的直线导轨固定座(34)；以及
    安装在移动杆(7)下端的移液头。
  20. 权利要求19所述的移液机构，其特征在于，其中所述移动基座具有 四边形的外框，所述移动杆(7)可移动地装配于所述移动基座(1)一侧边框，，其中所述用于装配移动杆(7)的边框具有凹槽，所述凹槽开口向移动基座的内侧，所述移动杆可移动地装配在所述凹槽内，移动杆的一部分处于凹槽外，即突出左边框内侧表面，该移动杆的突出部分可用于与移动杆驱动机构的驱动连接件(17)进行固定连接，
    其中所述丝杆的驱动机构包括所述丝杆的驱动电机，其中所述丝杆(4)通过丝杆螺母(6)和驱动连接件(17)与移动杆(7)固定连接，其中，丝杆螺母(6)旋装在丝杆上，驱动连接件(17)的一端与移动杆7固定连接，另一端固定在所述丝杆螺母(6)外侧，
    其中所述直线导轨固定座(34)通过直线导轨固定块(35)与移动基座连接，所述直线导轨固定座(34)的高度H1大于30mm，所述直线导轨固定块的高度H2大于或等于60mm。
  21. 权利要求20的移液机构，其特征在于，其还包括沿水平方向设置，与所述齿轮形成齿轮副的齿条，齿轮转动时，驱动移动基座沿齿条水平移动以及沿水平方向设置，与所述齿条平行的直线导轨，所述直线导轨的滑块与所述直线导轨固定座(34)连接和固定，由此移动基座可随直线导轨的滑块沿直线导轨的轨道进行水平方向的移动，其中所述齿轮(16)以及直线导轨固定座(34)的位置设置方式使得当齿轮转动时，驱动移动基座沿齿条和直线导轨的滑轨移动。
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