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EP3666379A1 - Tête de pipettage, dispositif de pipettage comprenant une tête de pipettage et procédé de pipettage à l'aide d'une tête de pipettage - Google Patents

Tête de pipettage, dispositif de pipettage comprenant une tête de pipettage et procédé de pipettage à l'aide d'une tête de pipettage Download PDF

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Publication number
EP3666379A1
EP3666379A1 EP18212800.9A EP18212800A EP3666379A1 EP 3666379 A1 EP3666379 A1 EP 3666379A1 EP 18212800 A EP18212800 A EP 18212800A EP 3666379 A1 EP3666379 A1 EP 3666379A1
Authority
EP
European Patent Office
Prior art keywords
pipetting
pipetting head
pipette tips
ring
rings
Prior art date
Legal status (The legal status 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 status listed.)
Withdrawn
Application number
EP18212800.9A
Other languages
German (de)
English (en)
Inventor
Jens Wilmer
Dominik Schneider
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Eppendorf SE
Original Assignee
Eppendorf SE
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 Eppendorf SE filed Critical Eppendorf SE
Priority to EP18212800.9A priority Critical patent/EP3666379A1/fr
Priority to US17/413,730 priority patent/US20220097038A1/en
Priority to PCT/EP2019/084908 priority patent/WO2020120683A1/fr
Priority to CA3123348A priority patent/CA3123348A1/fr
Priority to CN201980089606.8A priority patent/CN113396017A/zh
Priority to AU2019398420A priority patent/AU2019398420A1/en
Priority to JP2021533627A priority patent/JP7621255B2/ja
Priority to EP19816770.2A priority patent/EP3793738A1/fr
Publication of EP3666379A1 publication Critical patent/EP3666379A1/fr
Withdrawn legal-status Critical Current

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Classifications

    • 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
    • B01L3/0275—Interchangeable or disposable dispensing tips
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/02—Adapting objects or devices to another
    • B01L2200/021—Adjust spacings in an array of wells, pipettes or holders, format transfer between arrays of different size or geometry
    • B01L2200/022—Variable spacings
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/02—Adapting objects or devices to another
    • B01L2200/025—Align devices or objects to ensure defined positions relative to each other
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/02—Adapting objects or devices to another
    • B01L2200/026—Fluid interfacing between devices or objects, e.g. connectors, inlet details
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0689—Sealing
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0609—Holders integrated in container to position an object
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0829—Multi-well plates; Microtitration plates
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/12—Specific details about materials
    • B01L2300/123—Flexible; Elastomeric

Definitions

  • the invention relates to a pipetting head for receiving pipette tips, to a pipetting device comprising a pipetting head and to a method for pipetting liquids by means of a pipetting head.
  • Pipetting devices with a pipetting head for holding a single or for simultaneously holding a plurality of pipette tips are used in particular in medical, biological, biochemical and chemical laboratories for metering liquids.
  • Pipetting heads have at least one attachment that can be inserted into a push-on opening at the top of a pipette tip. Through a tip opening at the lower end of the pipette tip, liquid is absorbed into and released from the pipette tip.
  • the pipette tip can be detached from the attachment and exchanged for a fresh pipette tip. This avoids contamination during subsequent dosing. Plastic pipette tips for single use are available at low cost.
  • At least one displacement device for air is integrated into the pipetting device and communicatingly connected to a pipette tip clamped thereon in a communicating manner in each attachment.
  • An air cushion can be displaced by means of the displacement device, so that liquid is sucked into the pipette tip and ejected therefrom.
  • the displacement device is usually a cylinder with a piston which is displaceable therein.
  • displacement devices are also known with a displacement chamber and at least one deformable wall, wherein a deformation of the wall causes the displacement of the air cushion.
  • a small piston is arranged in the pipette tip, which is coupled to a piston drive of the pipetting device when the pipette tip is plugged onto the shoulder.
  • the liquid is preferably taken up in a single step or in several small steps.
  • the liquid is dispensed in a single step when pipetting and in several small steps when dispensing.
  • the pipetting devices can be designed as manually or electromotively driven, manageable multi-channel pipettes which are held in the hand by the user during pipetting (“hand pipettes”).
  • Pipetting stations In the case of metering stations (“pipetting stations”) or automatic metering devices (“pipetting machines”), the pipetting head can be displaced on a robot arm or another transmission system for moving the pipetting head above a work surface. Dosing stations or automatic dosing devices can use the pipetting head to take up fresh pipette tips from a holder, take up liquids from vessels with the pipette tips and dispense them into vessels and throw used pipette tips into a waste container.
  • Pipetting heads can be part of laboratory machines (“workstations”), which can perform other liquid treatments in addition to the dosing of liquids. This includes in particular mixing, tempering and other physical treatments, chemical or biochemical conversion and the analysis of samples.
  • Pipette tips can be clamped onto a shoulder with a sealing seat next to a push-on opening at their upper end.
  • at least one attachment is pressed into the plug-in opening of at least one pipette tip which is provided in a holder, so that the pipette tip widens somewhat and is stuck on the attachment under pretension.
  • the force to be applied for the clamping increases with the number of pipette tips.
  • the pipetting devices In order to release the clamped pipette tip from the attachment, the pipetting devices have a discharge device with a drive device and a discharge device. By actuating the drive device, the ejector is displaced in such a way that it detaches the pipette tip from the attachment.
  • the drive device is driven either manually or by an electric motor. The ejection force for releasing pinched pipette tips from the base increases with the number of pipette tips.
  • the DE 10 2004 003 433 B4 describes a multi-channel pipette in which the force required to clamp the pipette tips on the tips and to detach the pipette tips from the tips is reduced in that the tips are spring-loaded and project in the axial direction beyond a stop formed by the ejector. If the clamping force exceeds a certain value when clamping pipette tips, the tips deflect until the pipette tips are in contact with the ejector. This limits the clamping force to a value in which the pipette tips are held sealingly on the approaches. Accordingly, the ejection force is limited.
  • the EP 2 735 369 A1 describes a multi-channel pipette in which the ejector serves as a stop element when pushing the pipette tips onto the tips.
  • the ejection forces are further reduced in that the ejector has a plurality of contact elements which meet the pipette tips one after the other in order to push them off the attachments.
  • the WO 01/56695 A1 describes a pipetting head with 96 channels, the lugs at the lower end have a larger cone angle than above, in order to reduce the force for attaching pipette tips with a collar of greater wall thickness at the upper end and a smaller wall thickness below the collar.
  • the pipetting head comprises a stop plate for ejecting the pipette tips from the attachments.
  • the stop plate is stepped to successively push the pipette tips away from the tips and to reduce the ejection force.
  • Posts with pretensioning devices protrude from the stop plate.
  • a plunger plate which displaces pistons in cylinders connected to the lugs, strikes the pretensioners when retracted to trigger dropping of the pipette tips from the lugs through the stop plate.
  • the construction with pretensioners for ejecting pipette tips is complex.
  • the WO 2005/113149 A1 describes a device for receiving and dispensing liquids with a pipetting head, which has 96 approaches for pipette tips.
  • 96 piston-cylinder units are connected to the lugs and can be operated manually using a drive mechanism.
  • the pipetting head can be displaced along a vertical guide, around pipette tips from a pipette tip holder absorb and aspirate and dispense liquid.
  • the pipetting head can be pressed down by means of a transmission lever with increased force in order to apply the force required to hold 96 pipette tips.
  • the lugs are passed through holes in a perforated plate which can be displaced vertically in order to strip the pipette tips from the lugs.
  • the DE 20 2008 013 533 U1 describes a pipetting device with a base plate and an elastic sealing plate that laterally covers the outside thereof, wherein a multiplicity of pipetting channels arranged in a predetermined grid are passed through the base plate and the sealing plate.
  • a magazine equipped in the same grid with pipette tips, each of which has a collar, is connected to the base plate in a lying manner in a magazine holder indirectly via the collars and the sealing plate.
  • the magazine holder is formed by a magazine frame which can be raised and lowered by a drive motor via an eccentric gear in order to bring the pipette tips into sealing contact with the sealing plate or to detach them from the sealing plate.
  • the EP 0 337 726 A2 describes a device for simultaneously picking up several pipette tips by means of parallel approaches in a straight row, each have an elastomeric O-ring in an annular groove with an adjustable groove width.
  • the extent of the O-rings in the circumferential direction can be changed by adjusting the groove widths in order to tightly clamp the pipette tips onto the attachments and to detach the pipette tips from the attachments.
  • the grooves are each limited by a threaded sleeve screwed onto the shoulder, which can be rotated on the shoulder by means of a coupled gear mechanism. Each threaded sleeve is firmly connected to a gear.
  • each individual threaded sleeve is individually driven by an electric motor and the electric motors are connected to a common voltage supply for synchronous operation.
  • the drive for clamping the pipette tips on the approaches is structurally complex.
  • the DE 199 17 375 C2 describes a pipetting unit with a pipette tip and an attachment, which has a pipetting tube with a coupling sleeve at the lower end, an O-ring made of elastically deformable material which is pushed onto the pipetting tube, and a sleeve which is pushed onto the pipetting tube.
  • the sleeve serves to axially pinch the O-ring, so that it deforms radially and engages in a sealing manner in an annular groove on the inner circumference of the pipette tip.
  • the O-ring can be relieved to release the pipette tip.
  • the attachment and the pipette tip have cooperating axial positioning means.
  • a movable ejector is provided to eject the pipette tip and is designed as an ejector tube enclosing the sleeve.
  • the ejector can be actuated hydraulically or by an electric motor or by means of a pretensioning spring which is tensioned when the pipette tip is placed on the pipetting unit becomes.
  • the actuating means for clamping and releasing the pipette tip at the base are complex and take up a lot of space.
  • the attachment of the pipette tips in the defined coupling position can easily be prevented by manufacturing tolerances or an inaccurate positioning of the pipette tip on the attachment.
  • the annular groove and the axial positioning means restrict the use of different pipette tips.
  • the WO 2018/002254 A1 describes a dosing head for a dosing device with a carrier, on which a plurality of parallel approaches for receiving pipette tips is arranged side by side.
  • Each approach has a tube with an at least partially circumferential support projection projecting outward at the lower end from the outer circumference, at least one sleeve which surrounds the tube and is axially displaceable on the tube, and at least one elastomeric O-ring which surrounds the tube and is located next to the lower end of the sleeve.
  • a pressure plate with a plurality of first holes through which the tubes extend, the pressure plate along the tubes between a release position at a first distance from the support projections and a clamping position at a second distance below the first distance the support projections is displaceable, the pressure plate in the clamped position presses against the upper edge of the adjacent sleeves of all the lugs so that the sleeves are pressed with the lower ends onto the adjacent O-rings and the O-rings are widened to expose pipette tips pushed onto the lugs to clamp.
  • a first displacement device is connected to the pressure plate and is designed to shift the pressure plate between the release position and the clamping position.
  • Simultaneous clamping and loosening of a large number of pipette tips is achieved by evenly pressing the pressure plate against all sleeves and through enables even relieving of all sleeves.
  • the transmission of force from the first adjustment device via the pressure plate to the sleeves favors a relatively simple, compact and lightweight construction. Clamping by widening the O-rings favors the use of pipette tips with different shapes and dimensions.
  • the DE 10 2006 036 764 writes a pipetting system with a pipetting device with at least one push-on shaft, which has a circumferential locking bead on the outer circumference and underneath it two circumferential annular grooves which are spaced apart from one another and each accommodate a sealing ring.
  • the pipetting system comprises a pipette tip which can be clamped onto the latching bead with a latching groove and has a sealing area beneath it, against which the sealing rings bear in a sealing manner. Due to the latching, a defined fit of the pipette tip on the plug-on shaft is achieved and the sealing rings seal the pipette tip against the plug-on shaft. Relatively high attachment forces are required to lock the locking bead and locking groove.
  • the object of the invention is to provide a pipetting head with at least one approach for receiving at least one pipette tip, which enables a safe picking up and loosening of pipette tips with reduced effort and reduced construction effort.
  • Pipette tips are elongated tubes which have a tip opening at their lower end and a sealing seat at their upper end next to a push-on opening, with which they can be clamped onto the attachment.
  • the inside diameter and outside diameter of the pipette tips generally increases from the tip opening to the push-on opening. If a pipette tip is picked up on a neck of a pipetting head that has no O-ring, only one O-ring or a locking bead and two O-rings, high absorption forces arise (push-on forces, clamping forces) because the pipette tip, which is made of polypropylene, polyethylene or another hard elastic plastic, comes into direct contact with the attachment when pushed onto the attachment and deforms in the process.
  • the two O-rings and the neck are designed in the pipetting head according to the invention in such a way that a pipette tip can be clamped onto the neck solely by deformation of the two O-rings, direct contact of the pipette tip with the neck can be avoided and occurs in If the pipette tips are picked up by the pipetting head, a deformation takes place only on the two O-rings.
  • the inner diameter of the sealing seat of the pipette tip is smaller than the outer diameter of the respective O-ring at the point that contacts an O-ring, so that it is deformed when pushed on and the pipette tip clamps on the shoulder.
  • the O-rings are made of an elastomer, they can be deformed more easily than that Pipette tip. This reduces the absorption force required to hold the pipette tips. By reducing the clamping forces on a hand-held pipette, the load on the user during manual pipetting can be reduced. In the case of a pipetting station, an automatic pipetting machine or a laboratory machine, this reduces the requirements for the transmission system, in particular for its strength and the performance of the drives.
  • the two O-rings ensure that the pipette tips are precisely aligned with the attachment. This is advantageous for the insertion of pipette tips into the openings of vessels without colliding with the vessels. In this way, in particular a tilting of the pipette tip can be avoided if it contacts the wall of the vessel with the lower end during hand pipetting. This is recommended by the pipette manufacturers so that the liquid flows out of the tip opening under uniform conditions.
  • Another advantage of the two O-rings on each attachment is that all tips can be pushed onto the attachment in such a way that they can subsequently be pushed up further on the attachment and later pushed up into a position for pipetting. Alternatively, all tips can be pushed up to the ejector or stop on the attachment, so that the clamped pipette tips always have the same height.
  • the pipette tips can be tightly clamped onto the attachment, so that the pipetting head can be used to absorb and dispense liquid by means of at least one clamped-on pipette tip.
  • the pipetting head has at least one displacement device which communicates with one via at least one line Connection hole is connected at the end of the approach to displace an air cushion and to receive liquid through the tip opening in a clamped pipette tip and to dispense from it. Due to the radial deformability of the two O-rings, it is possible to hold pipette tips with different dimensions on the same attachment and to pipette with the different sized pipette tips. As a result, the effort for performing various pipetting tasks can be reduced.
  • the O-rings and the attachment can be designed such that pipette tips with a nominal volume of 10 ⁇ l and 50 ⁇ l or with a nominal volume of 300 ⁇ l and 1,000 ⁇ l can be clamped on the same attachment.
  • Commercial pipette tips from different manufacturers can be used for this, since these have matching dimensions in the sealing area.
  • the pipetting head can, if necessary, be used to transfer pipette tips of different sizes, e.g. from one pipette tip holder to another pipette tip holder, since the pipette tips are not tightly clamped on the tips, but so firmly on the tips Approaches sit that they are transferable by means of the pipetting head.
  • This can be used in particular for the automatic transfer of pipette tips in a laboratory machine.
  • the O-rings and the attachment can be designed in such a way that commercially available pipette tips with a nominal volume of 10, 50, 300 and 1,000 ⁇ l can be picked up and transferred using the same attachment.
  • the invention includes pipetting heads that can be used for the transfer of pipette tips, but not for the absorption and dispensing of liquids.
  • a pipetting head for transferring pipette tips can without Displacement device are formed and is also referred to below as a transfer head.
  • the O-rings are made from a soft elastomer.
  • the O-rings are made of rubber, silicone rubber, fluororubber (FEPM - for example Viton® from DuPont Performance Elastomers), hydrogenated nitrile rubber (HNBR), ethylene-propylene-diene rubber (EPDM) or a thermoplastic Made of elastomer.
  • FEPM fluororubber
  • HNBR hydrogenated nitrile rubber
  • EPDM ethylene-propylene-diene rubber
  • thermoplastic Made of elastomer O-rings made of a soft elastomer (silicone rubber) are marketed in particular by C. Otto Gerckens GmbH & Co. KG Dichtungstechnik, Pinneberg, Germany under the name VMQ.
  • the attachment has devices for the axial securing of position, which are designed to support each of the two O-rings in a certain upper and in a certain lower position and to allow deformation of the two O-rings in the radial direction.
  • the two O-rings can be held on the shoulder in defined positions or areas. These can be matched to the pipette tips that are to be held on the attachment.
  • the devices for securing the axial position are annular grooves.
  • Each ring groove can partially accommodate at least one O-ring, the O-ring being guided on the base of the ring groove on the shoulder and prevented by the two flanks of the ring groove from being displaced upwards and downwards.
  • the ring grooves can be dimensioned such that each O-ring is held in the respective ring groove with a precise fit, or with an axial play or in a slightly compressed manner in the axial direction. It is also possible to keep both O-rings in the same ring groove.
  • both O-rings are supported in same annular groove from each other and the upper O-ring is supported on the upper flank and the lower O-ring on the lower flank of the annular groove.
  • the devices for the axial securing of position are formed by one or more projections which are arranged on both sides of at least one O-ring on the circumference of the extension. A displacement in the axial direction is prevented or limited by the at least one projection on both sides of at least one O-ring.
  • each approach has only two O-rings. According to another embodiment, each approach has more than two O-rings. For each O-ring there can be a separate ring groove or other devices for axial securing of the position or several O-rings can be arranged together in the same ring groove or held on the shoulder by the same devices for axial securing of the position.
  • the devices for the axial securing of position are formed in one piece with the attachment.
  • the devices for axially securing the position are sleeves and / or rings which are pushed onto the neck and receive the O-rings between them, which are guided on the inside of the neck.
  • the sleeves and / or rings are either fixed on the neck or loosely guided on the neck and prevented from being stripped from the neck by additional means for securing the position axially.
  • These can be formed, for example, at the top by the carrier and at the bottom by a securing ring which is held in an additional annular groove on the circumference of the attachment.
  • the two O-rings are arranged on the shoulder at a distance from one another. This is particularly advantageous for the precise alignment of the pipette tips on the approach. This also enables a particularly gentle increase in the clamping forces when clamping a pipette tip.
  • the approach has at least one conical section. This is advantageous for clamping pipette tips onto the attachment with a gradual increase in the clamping forces.
  • the extension has at least one cylindrical section.
  • the guidance and sealing of a pipette tip at the base can be improved by the cylindrical section.
  • the projection has an upper cylindrical section at the top, a lower cylindrical section at the bottom, a conical section tapering from top to bottom between them, and between the upper cylindrical section and the conical section, upper devices for securing the axial position and between the conical section and the lower cylindrical section lower devices for axial position securing.
  • the upper O-ring has a larger inner diameter and / or a cross section with a larger diameter than the lower O-ring. This is advantageous for a gradual increase in the push-on forces when a pipette tip is clamped onto the attachment.
  • the diameter of the cross section of the upper O-ring is larger than the depth of the upper ring groove and / or the width of the upper ring groove is equal to or larger than the diameter of the cross section of the upper O-ring and / or the diameter of the Cross section of the lower O-ring is greater than the height of the lower ring groove and / or the width of the lower ring groove is equal to or greater than the diameter of the cross section of the lower O-ring.
  • the depth of the respective annular groove ensures that the respective O-ring can be deformed in the radial direction by clamping a pipette tip onto the attachment, and / or the length of the respective annular groove results in a long deformation path with low clamping forces.
  • the pipetting head has approaches which are arranged next to one another in parallel in one or more rows.
  • the pipetting head can be used for the simultaneous clamping of a large number of pipette tips, for which it is particularly well suited due to the low clamping forces.
  • the approaches are firmly connected to the carrier.
  • the clamping forces can be kept low by the two O-rings, so that it is in particular not necessary to support the attachments via springs on the carrier.
  • the lugs are supported on the carrier via springs in order to thereby additionally limit the attachment forces.
  • the carrier is a housing or part of a housing or a chassis or part of a chassis of the pipetting head.
  • the carrier is a lower housing wall of the housing or a lower part of a chassis of the pipetting head.
  • the approach can be held in particular by screwing in a lower housing wall or in a lower part of a chassis. If the extension is held in a lower part of a chassis, the housing in a lower housing wall can have a through hole for each extension or the lower housing wall can be missing.
  • the invention relates to a pipetting device or a transfer device comprising a pipetting head according to one of claims 1 to 10 or one of the above embodiments.
  • the pipetting device or transfer device can in particular be designed as a manually or electromotively driven, manageable pipetting device or transfer device with one or more channels, which can be held in the hand by the user when pipetting or transferring pipette tips (hand pipette).
  • the invention relates to a pipetting station or an automatic pipetting device or an automatic laboratory device comprising a pipetting device and / or a transfer device according to claim 11.
  • the pipetting station or the automatic pipetting device or the automatic laboratory device can be used for (automatic) pipetting or transferring pipette tips.
  • the laboratory machine can be used for automatic pipetting, for transferring pipette tips and also for other treatments of liquids, for example for tempering, mixing, carrying out chemical or biochemical reactions and other physical, chemical or biochemical treatments.
  • the pipetting head In a pipetting station, a pipetting machine or a laboratory machine, the pipetting head can be designed such that it can be attached to and detached from the pipetting station, the pipetting machine or the laboratory machine by means of a quick-change device in order to attach another one Attach pipetting head (e.g. for other pipette tip sizes ), a gripper tool for transporting laboratory items ( labware ) or another tool.
  • a pipetting tool is also referred to as a pipetting tool.
  • the pipette tips are first picked up by means of a pipetting head with only one or more channels, until pipette tips are clamped onto all the approaches.
  • the pipette tips are not pushed completely onto the attachments, ie not up to an ejector or a stop, so that they can be pushed even further up onto the attachments.
  • the pipetting head is then moved and the lower ends of all clamped pipette tips are placed on the vessel from which liquid is to be removed or released into the liquid.
  • the pipetting head is shifted until all clamped pipette tips with the lower ends simultaneously come into contact with the Have bottom of a vessel and then the pipetting head is moved until the lower ends of all pipette tips are a certain distance from the bottom of the vessel.
  • a particularly small gap can be achieved between the lower ends of the pipette tips clamped in each case and the bottom of the vessels.
  • the pipetting head is moved until the lower ends of all clamped pipette tips are in contact with a part of the surface of the vessel other than the bottom. In this way, at least an exact alignment of the pipette tips to the vessels is achieved, only tolerances between the position of the contacted surface and the bottom of the vessel not being compensated for.
  • the pipetting head is a multi-channel pipetting head and the vessel is a multiple vessel, in particular a microtest plate (microtiter plate).
  • the invention is particularly suitable for the simultaneous compensation of a large number of tolerances between clamped pipette tips and a micro test plate.
  • each pipette tip is first brought into contact with a surface of the multiple vessel or with the bottom of a well ( well ) or other cavity of the multiple vessel and then at a short distance from the bottom of the cavity.
  • each clamped pipette tip has its lower end in contact with a vessel that is provided on a work surface, for example because the vessel is filled with a liquid that is not in contact with the pipette tip
  • the pipetting head can also be used in such a way that all pipette tips are pushed up to an ejector or stop on the shoulder, so that all clamped pipette tips have the same height. This reduces the errors due to tolerances, although not in the same extent as when moving the pipetting head so that the clamped pipette tips are in contact with the vessel at their lower end.
  • the information “above” and “below”, “horizontally” and “vertically” relates to an alignment of the pipetting head with the lugs in the vertical direction, the lugs being arranged below and the remaining parts of the pipetting head above.
  • the pipetting head 1 has a housing 2 which is formed from a front and a rear housing shell 3, 4 which are joined together in a vertical plane.
  • a strip-shaped carrier plate 7 is arranged on the top of the housing 2.
  • a mounting pin 8 projects upward from the carrier plate 7.
  • Each piston-cylinder unit 9 has a cylinder 10 in which a piston 11 is slidably arranged.
  • Each cylinder 10 has an external thread 12 with which it is screwed into a corresponding internal thread 13 in a through hole 14 in a horizontal lower housing wall 15.
  • the screwing in of the cylinders 10 into the lower housing wall 15 is limited by shoulders 16 on the outer circumference of the cylinders 10, with which they rest on the upper side of the lower housing wall 15.
  • Housing 2 is thus a carrier for the lugs 5.
  • each projection 5 has an upper cylindrical section 17 at the top, a lower cylindrical section 18 at the bottom and a conical section 19 tapering from top to bottom therebetween.
  • Each O-ring 24, 25 is guided at the bottom of the annular groove 21, 23 and has a cross section with a diameter which is greater than the depth of the annular groove 21, 23 and which is smaller than the width of the annular groove 21, 23 in which he is arranged.
  • each cylinder 10 into which the piston 11 dips from above, extends down to a connecting hole 27 in the lower end face of the extension 5.
  • each cylinder 10 there is a bushing 28, through which a piston 11 is sealingly inserted into the cylinder 10.
  • Each piston 11 is designed as a cylindrical rod which is inserted at the top into a central bore 29 of a cylindrical piston head 30 and fastened therein (e.g. glued or pressed in).
  • Each piston head 30 has a circumferential annular ring groove 31 on the outer circumference.
  • a strip-shaped piston plate 33 parallel to this is arranged below a horizontal upper housing wall 32.
  • the piston plate 33 has eight downwardly open channels 34, which are aligned parallel to one another. Each channel is delimited by two strip-shaped channel walls 35 and by two channel shoulders 36 projecting inwards from the lower ends of the channel walls.
  • the channel walls 35 on the two outer edges of the piston plate 33 each delimit an adjacent channel 34 on only one side. The remaining channel walls 35 each delimit two adjacent channels 34 on one side. Between the channel shoulders 36, each channel has a slot opening 37 on the underside of the piston plate 33.
  • the channels 34 have end openings 38.
  • the piston heads 30 are inserted with upper sections into the channels 34, so that the channel shoulders 36 form-fit engage the piston head ring grooves 31.
  • the pistons 11 can be moved together in the cylinders by vertically displacing the piston plate 33.
  • An axially displaceable threaded nut 39 is arranged centrally in the fastening pin 8, the lower end of which is firmly connected to the piston plate 33 in order to displace the piston plate 33 in the axial direction of the cylinder 10.
  • the fastening pin 8 has a cylindrical upper pin section 40 at the top.
  • the upper pin section 40 carries on the outer circumference two connecting elements 41 which are offset by 180 ° and project radially outwards, in each case partially circumferentially, with which a bayonet connection can be formed.
  • the connecting elements 41 have a slight thread pitch on the underside for bracing with a matching connecting element in a pin receptacle of a bayonet connection.
  • the fastening section 8 Adjacent to the upper pin section 40, the fastening section 8 has a cylindrical central pin section 42 with a larger outer diameter than the upper pin section 40.
  • the fastening pin 8 has a lower pin section 43 that widens conically downward.
  • the lower pin section 43 is firmly connected at its base to the carrier plate 7.
  • a central bore 44 extends in the longitudinal direction of the fastening pin 8. This has two diametrically opposed longitudinal grooves 45.
  • the sleeve-shaped threaded nut 39 is inserted, which is guided with two radially projecting wings 46 at its upper end in the longitudinal grooves 45.
  • a spindle 47 is screwed into the threaded nut 39.
  • This has a protruding bearing pin 49 above its thread 48, on which it is mounted in a ball bearing 50.
  • the ball bearing 50 is held in a bearing bush 51 of a bearing bracket 52 which protrudes two diametrically from the sides Has tabs that rest on the upper edge of the upper pin section 40 and are fixed there by means of screws.
  • a driver 54 is fixed in a rotationally fixed manner by means of a radial threaded pin 53 and has a radially and axially extending slot 55 on its upper end face for inserting a pawl-shaped drive element.
  • the spindle 47 is supported on the lower end face of the ball bearing 50.
  • the driver 54 is supported on the upper end face of the ball bearing 50. As a result, the spindle 47 is not axially displaceably held in the fastening pin 8.
  • a cylindrical pin 56 is fixed, which, parallel to the central axis of the threaded nut 39, is guided through a groove of the bearing bracket 52 and protrudes from the fastening pin 8 at the top.
  • the driver 54 By turning the driver 54, the spindle 47, which is held axially in the fastening pin 8, moves the threaded nut 39, which is non-rotatably guided in the fastening pin 8, in the axial direction. As a result, the piston plate 33 is displaced and the pistons 11 are displaced in the cylinders 10. By rotating the driver 54 in different directions, the pistons 11 can be displaced in the cylinders 10 in different directions. By scanning the position of the cylinder pin 56, it is possible to determine the respective position of the pistons 11 in the cylinders 10.
  • the fastening pin 8 and the drive integrated therein with a threaded nut 39 and a spindle 47 correspond to the designs from 1 to 4 and 6 according to EP 1 407 861 B1 .
  • EP 1 407 861 B1 the content of which is hereby incorporated into this application.
  • a laboratory machine is provided with a complementary pin receptacle of a bayonet connection, which can be connected to the fastening pin.
  • the complementary connecting part of the laboratory machine preferably corresponds to the tool holder 7 to 10 the EP 1 407 861 B1 .
  • a stripper plate 57 is arranged below the lower housing wall 15 and has further through holes 58 through which the pins 5 project downwards.
  • the stripping plate 57 is connected on one long side to a linkage 59 which is guided upwards in a bulge 60 of the rear housing shell 4, which has an opening at the top through which the linkage 59 protrudes from the housing 2.
  • a driver 61 projects laterally from the upper end of the linkage 59. In the idle state, the linkage 59 is pressed upwards by means of a spring device, not shown, until the stripping plate 57 rests on the underside of the lower housing wall 15.
  • the automatic laboratory machine has a drive with a drive element with which the driver 61 can be pressed down, as a result of which the stripping plate 57 is carried downwards in order to strip pipette tips 6 from the projections 5.
  • Fig. 3 and 4th are pipette tips 6 clamped on the approaches 5.
  • the pipette tips 6 are tubes with a tip opening 62 at the lower end 63 and a push-on opening 64 at the upper end 65.
  • the inner diameter and the outer diameter of the pipette tip 6 generally increase from the tip opening 62 to the push-on opening 64.
  • Pipette tips 6 have a plurality of conical regions 64, 65, 66 and a cylindrical extension 67 in the vicinity of the upper end 65. In the region of the cylindrical extension 67 and in the region below, the pipette tip has a sealing seat 68 on the inside.
  • the shoulders 5 of the pipetting head 1 are inserted into the pipette tips 6 through the plug-on openings 64.
  • the O-rings 24, 25 are arranged at the level of the sealing seat 68.
  • the O-rings 24, 25 are compressed somewhat in the radial direction, so that the pipette tips 6 clamp on the shoulders 5 and are sealed off from the shoulders 5. Since the O-rings 24, 25 consist of soft elastic material and the pipette tips 6 are otherwise not in contact with the projections 5, the push-on forces for attaching the pipette tips 6 to the projections 5 are relatively small.
  • Fig. 5 are the measured attachment forces when attaching pipette tips as a function of the path of the pipetting head for an inventive pipetting head 1 with eight channels and two O-rings 24, 25 on each attachment 5 and a conventional pipetting head with eight channels without O-rings 24, 25 on the Approaches shown side by side.
  • the push-on forces increase sharply until they are seated on the attachments with sufficient firmness and sealing. This is the case with an attachment force of 120 Newtons and a displacement of the pipetting head of 2.2 mm.
  • the curves on the right in the diagram an adequately firm and sealing connection is established even with attachment forces of approx. 30 Newton and a displacement of the pipetting head of 2 mm.
  • the O-rings 24, 25 are elastically deformed. Above this value, the push-on forces rise steeply, since this also requires the pipette tips 6 to be deformed.
  • the reduced plug-on forces also reduce the forces for throwing off the pipette tips 6 from the projections 5.
  • an automatic laboratory machine 70 has a large number of tolerances which influence the positioning of the tip opening 64 of pipette tips 6 in the vertical direction. These tolerances include the tolerances of the positioning of a multi-axis transmitter 71 (robot arm or other transmission system). In addition, there are the tolerances of the fixation of a pipetting head 1 (pipetting tool) in the tool holder 72 held on the multi-axis transmitter 71. Furthermore, manufacturing tolerances of the pipetting head 1 must be taken into account. In addition, the approaches 5 for receiving the pipette tips 6 and the pipette tips 6 themselves have tolerances. Microtiter plates 73 and adapters 74 for positioning the microtiter plates 73 on a work surface 75 (deck) of the laboratory automat 70 have further tolerances. Finally, the work surface 75 itself also has tolerances.
  • next-generation sequencing NGS
  • contaminations are carried over, for example if a sample is to be aspirated under another phase (e.g. oil-covered samples) and parts of the overlay are carried over.
  • the "surface teaching” addresses certain tolerances on the system (e.g. positioning offset and tool tolerance), but is very labor intensive for the user and requires a lot of effort. Furthermore, a large number of tolerances are not covered by surface teaching (e.g. well (well) geometry, microtiter plate seat on adapter, pipette tip geometry, pipette tip seat, tool holder etc.), as this does not take place during the dosing process, but in advance of the application.
  • surface teaching e.g. well (well) geometry, microtiter plate seat on adapter, pipette tip geometry, pipette tip seat, tool holder etc.

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  • Health & Medical Sciences (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Devices For Use In Laboratory Experiments (AREA)
  • Sampling And Sample Adjustment (AREA)
EP18212800.9A 2018-12-14 2018-12-14 Tête de pipettage, dispositif de pipettage comprenant une tête de pipettage et procédé de pipettage à l'aide d'une tête de pipettage Withdrawn EP3666379A1 (fr)

Priority Applications (8)

Application Number Priority Date Filing Date Title
EP18212800.9A EP3666379A1 (fr) 2018-12-14 2018-12-14 Tête de pipettage, dispositif de pipettage comprenant une tête de pipettage et procédé de pipettage à l'aide d'une tête de pipettage
US17/413,730 US20220097038A1 (en) 2018-12-14 2019-12-12 Pipetting head, pipetting device comprising a pipetting head, and method for pipetting using a pipetting head
PCT/EP2019/084908 WO2020120683A1 (fr) 2018-12-14 2019-12-12 Tête de pipetage, dispositif de pipetage comprenant une tête de pipetage et procédé de pipetage au moyen d'une tête de pipetage
CA3123348A CA3123348A1 (fr) 2018-12-14 2019-12-12 Tete de pipetage, dispositif de pipetage comprenant une tete de pipetage et procede de pipetage au moyen d'une tete de pipetage
CN201980089606.8A CN113396017A (zh) 2018-12-14 2019-12-12 移液头、包括移液头的移液装置和通过移液头进行移液的方法
AU2019398420A AU2019398420A1 (en) 2018-12-14 2019-12-12 Pipetting head, pipetting device comprising a pipetting head, and method for pipetting using a pipetting head
JP2021533627A JP7621255B2 (ja) 2018-12-14 2019-12-12 ピペット・ヘッド、ピペット・ヘッドを備えたピペット装置、およびピペット・ヘッドを使用したピペット操作方法
EP19816770.2A EP3793738A1 (fr) 2018-12-14 2019-12-12 Tête de pipetage, dispositif de pipetage comprenant une tête de pipetage et procédé de pipetage au moyen d'une tête de pipetage

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
EP18212800.9A EP3666379A1 (fr) 2018-12-14 2018-12-14 Tête de pipettage, dispositif de pipettage comprenant une tête de pipettage et procédé de pipettage à l'aide d'une tête de pipettage

Publications (1)

Publication Number Publication Date
EP3666379A1 true EP3666379A1 (fr) 2020-06-17

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EP18212800.9A Withdrawn EP3666379A1 (fr) 2018-12-14 2018-12-14 Tête de pipettage, dispositif de pipettage comprenant une tête de pipettage et procédé de pipettage à l'aide d'une tête de pipettage
EP19816770.2A Pending EP3793738A1 (fr) 2018-12-14 2019-12-12 Tête de pipetage, dispositif de pipetage comprenant une tête de pipetage et procédé de pipetage au moyen d'une tête de pipetage

Family Applications After (1)

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EP19816770.2A Pending EP3793738A1 (fr) 2018-12-14 2019-12-12 Tête de pipetage, dispositif de pipetage comprenant une tête de pipetage et procédé de pipetage au moyen d'une tête de pipetage

Country Status (7)

Country Link
US (1) US20220097038A1 (fr)
EP (2) EP3666379A1 (fr)
JP (1) JP7621255B2 (fr)
CN (1) CN113396017A (fr)
AU (1) AU2019398420A1 (fr)
CA (1) CA3123348A1 (fr)
WO (1) WO2020120683A1 (fr)

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EP4202444A1 (fr) * 2021-12-23 2023-06-28 TECAN Trading AG Tête de pipetage multicanaux
EP4206679A1 (fr) * 2021-12-29 2023-07-05 TECAN Trading AG Lecteure optique pour embout de pipette

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US9415386B2 (en) * 2013-03-15 2016-08-16 Douglas Scientific, LLC Wash through pipettor
CN114199631B (zh) * 2021-12-13 2022-08-12 杭州莱和生物技术有限公司 一种用于免疫层析监测信号的扩增方法
DE102022115438A1 (de) 2022-06-21 2023-12-21 Analytik Jena Gmbh+Co. Kg Funktionsmodul für eine Pipettier- oder Dosiervorrichtung, Dosiervorrichtung und Pipettiervorrichtung
CN115090344A (zh) * 2022-07-30 2022-09-23 上海汇像信息技术有限公司 注液排枪
CN115283035B (zh) * 2022-08-29 2024-04-30 香港中文大学深港创新研究院(福田) 一种手持自动备液枪的取样滴液方法
CN116116477A (zh) * 2023-02-16 2023-05-16 北京青元开物技术有限公司 一种兼容式移液模块和液体工作站

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EP0337726A2 (fr) 1988-04-12 1989-10-18 Flow Laboratories Limited Dispositif de préhension d'embouts de pipettes
DE19917375C2 (de) 1999-04-16 2001-09-27 Hamilton Bonaduz Ag Bonaduz Pipettiereinheit
WO2001056695A1 (fr) 2000-02-01 2001-08-09 Incyte Genomics, Inc. Tete de pipette multicanaux pour appareil de prelevement a la pipette
EP1407861B1 (fr) 2002-10-12 2008-04-23 Eppendorf Ag Outil de préhension, outil de dosage et support d'outil pour automate de laboratoire
DE102004003433B4 (de) 2004-01-21 2006-03-23 Eppendorf Ag Pipettiervorrichtung mit einer Abwurfeinrichtung für Pipettenspitzen
DE202005006970U1 (de) * 2004-05-10 2005-07-14 Steinbrenner, Bernd, Dr. Vorrichtung zur Aufnahme und Abgabe von Flüssigkeiten
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EP1862219A1 (fr) * 2006-05-29 2007-12-05 Qiagen GmbH Appareil pour retenir un embout à pipette, embout pour pipette et pipette utilisant ledit embout
DE102006036764A1 (de) 2006-08-05 2008-02-07 Eppendorf Ag Pipettiersystem, Pipettiervorrichtung und Pipettenspitze
DE202008013533U1 (de) 2008-10-14 2008-12-24 Cybio Ag Pipettiervorrichtung
EP2735369A1 (fr) 2012-11-23 2014-05-28 Eppendorf Ag Pipette multi-canal
DE102016111912A1 (de) * 2016-06-29 2018-01-04 Eppendorf Ag Dosierkopf, Dosiervorrichtung umfassend einen Dosierkopf und Verfahren zum Dosieren mittels eines Dosierkopfes
WO2018002254A1 (fr) 2016-06-29 2018-01-04 Eppendorf Ag Tête de dosage, dispositif de dosage comprenant une tête de dosage et procédé de dosage au moyen d'une tête de dosage
WO2018144608A1 (fr) * 2017-01-31 2018-08-09 HighRes Biosolutions, Inc. Appareil et procédé de pipettage automatique

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP4202444A1 (fr) * 2021-12-23 2023-06-28 TECAN Trading AG Tête de pipetage multicanaux
EP4206679A1 (fr) * 2021-12-29 2023-07-05 TECAN Trading AG Lecteure optique pour embout de pipette
US12474361B2 (en) 2021-12-29 2025-11-18 Tecan Trading Ag Pipetting tip scanner

Also Published As

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JP2022514225A (ja) 2022-02-10
CN113396017A (zh) 2021-09-14
CA3123348A1 (fr) 2020-06-18
AU2019398420A1 (en) 2021-07-08
US20220097038A1 (en) 2022-03-31
WO2020120683A1 (fr) 2020-06-18
JP7621255B2 (ja) 2025-01-24
EP3793738A1 (fr) 2021-03-24

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