DE102015009695A1 - Pipetting device with a microdosing unit - Google Patents

Abstract

The invention relates to a pipetting device with a pipetting unit (1), at least one positioning device (4) with a holder (18), a micro-dosing unit (5) and a control device (6). The microdosing unit (5) can be positioned relative to the pipetting unit (1) optionally in a precisely defined relative position. The holder (18) of the positioning device (4) has a coupling device (10) and the micro-dosing unit (5) has a corresponding counter-coupling device (11). The coupling device (10) and / or the negative feedback device (11) are switchable. The microdosing unit (5) has a first detector (70) directed towards the holder (18), which switches the coupling device (10) and / or the negative feedback device (11).

Description

The invention relates to a pipetting device with a microdosing unit having the features of the preamble of claim 1.

A pipetting device of the type in question may in principle have only a single pipette tip at a coupling point. In most cases, however, such a pipetting device is a multi-channel pipetting device, in which therefore the pipetting unit has a plurality of coupling points and a corresponding number of pipette tips which can be attached to these coupling points. Frequently, such a multi-channel pipetting device is used on a pipetting or pipetting robot.

By appropriate activation of a displacer unit in the pipette unit, which is usually designed in the form of a cylinder-piston arrangement, liquid can be sucked through the mouth openings of the pipette tips into the same or expelled from these.

In a typical pipetting device of the type in question, the pipetting unit is brought into different operating positions by means of a positioning device. The positioning device may be an X / Y / Z traversing device. It can also be the arm of a robot, which can be moved largely freely in space. For this purpose, the prior art gives various suggestions.

In a pipetting device of the type in question, the pipette tips are received at a receiving position from a peak supply, that is coupled to the coupling points. Then, the pipetting unit is moved by the positioning in a liquid-receiving position. For receiving the liquid into the pipette tips, ie for aspiration, the mouth openings of the pipette tips are immersed in the liquid in corresponding vessels, for example the wells of a microtiter plate.

The liquid is absorbed by the action of the displacer unit or displacer units in the pipette unit. If the liquid intake has taken place, the pipetting unit is moved by means of the positioning device into a liquid dispensing position. There, again by means of the displacer unit or displacer units, the desired volume of liquid is dispensed from the respective pipette tip into a destination vessel. These may again be wells of a microtiter plate.

The liquid delivery can be done with larger volumes as free-flying jet. For small volumes, it may even be necessary to make contact between the target vessel and the pipette tips so that the adhesion force of the liquid drop at the pipette tip can be overcome. The aforementioned boundary conditions limit the deliverable liquid volume down to volumes in the range of a few microliters. Dispensing dosages in the nanoliter range can not be realized this way. In addition, the classical pipetting machine is at risk of carryover of substances already in the target vessel.

After dispensing the liquid in the dispensing position, a residual volume in the pipette tips is occasionally discarded. For this purpose, the pipetting unit is brought by means of the positioning device in an ejection position, in which then by means of the displacer unit, the remaining liquid is ejected in the pipette tips.

Following the discharge of the residual liquid, the pipette unit is brought into a pipette tip dropping position. There, the pipette tips are released by means of a tip ejection device from the coupling points on the pipetting unit and dropped into a collecting container.

In the prior art, from which the invention proceeds ( WO 2006/076957 A1 ), extensive prior art has been described which addresses the issue of lower minimum volumes to be dispensed in a pipetting device of the type in question. In addition, the reference describes a pipetting device according to the preamble of claim 1 which enables the dispensing of volumes down to the nanoliter range.

In the prior art discussed herein, this is accomplished by connecting a pipette tip to an elastically deformable tube as the ejection end at the pipette tip. This tube forms the mouth of the pipette tip at the lower end. This elastically deformable tube can be deformed by a movable actuating device of a microdosing unit so that a defined volume of liquid can be expelled by deformation of the tube just above the mouth opening of the pipette tip. The resulting change in volume inside the tube ejects liquid as free-flying droplets or as a free-flying jet from the mouth of the pipette tip. This makes it possible to eject smallest volumes in the nanoliter range. For this purpose, too, reference may be made to the statements in the previously mentioned prior art.

In the prior art, the microdosing unit of the pipetting device is an arrangement with clamping jaws as an abutment for the movable actuating device, which itself is driven piezoelectrically. In detail, this is also on the WO 2005/016534 A1 for such a microdosing unit, which discloses details of the structure of such a microdosing unit.

In the prior art, from which the invention proceeds, the microdosing unit of the pipetting device is stationary at the liquid dispensing position. The pipette tip must be threaded into the actuator of the microdosage unit from above. The liquid within the pipette tip is tracked into the tube by capillary forces. Purging liquid in small portions from a pipette tip into a plurality of different target vessels requires movement of the target vessels relative to the pipetting tip stationary in the liquid dispensing position.

As a result, the pipetting device described above is theoretically suitable for dispensing smallest volumes at various locations, but still has to optimize the pipetting device in practical operation.

The invention is based on the problem of specifying a practical designed pipetting device with a microdosing unit.

The above-indicated problem is solved in a pipetting device having the features of the preamble of claim by the features of the characterizing part of claim 1.

According to the invention, it is relevant that the microdosing unit is designed as a separate unit from the pipetting unit. This means that the pipetting unit in various relevant operating positions, in particular in the pipette tip receiving position, the liquid receiving position, but also preferably in the pipette tip dropping position and optionally the discharge position for residual liquid, such as a classic pipetting a pipetting without Microdosiereinheit be handled and used can. In contrast, the microdosing unit is coupled to the pipetting unit in a well-defined relative position to the pipetting unit when needed, namely in the liquid dispensing position.

However, instead of coupling the pipetting unit to the stationary in a certain liquid dispensing position microdosing, as in the prior art, the pipetting unit and the micro-dosing optionally be positioned in a well-defined relative position to the invention.

According to the invention, the microdosing unit switches by means of a detector, which is directed towards the pipetting unit, largely independently of the coupling. Switching can be done directly from the appropriately designed detector. Most switching is indirect, triggered by the detector, via a control device. Thereafter, the micro-dosing unit can be brought together with the pipetting unit by means of the positioning in different operating positions, for example, several different liquid dispensing positions.

According to the invention, optimal boundary conditions of the pipetting device for laboratory operation are created. The pipetting device has a pipetting unit without a microdosing unit where the microdosing unit is not needed. It converts to a pipetting unit with a microdosage unit where necessary, namely when dispensing liquid. For the delivery of liquid, the pipetting unit together with its microdosing unit can be moved freely, for example via different microtiter plates which are located at different locations and which in turn do not have to be moved.

The pipetting device according to the invention can thus also be used for different volumes. For larger volumes, the pipetting device can be operated without a microdosing unit, optionally also with normal pipette tips without elastically deformable ejection ends. If you want to dose in the range of very small volumes, the microdosing is coupled as needed to the pipette and can then be brought with this to the desired operating position.

Typical materials for an elastically deformable discharge end of the pipette tip are polyimide, polyamide or silicone. Typical diameters are 0.1 to 1 mm. Incidentally, the elastically deformable ejection end may be integrally formed on the pipette tip. It can also be attached by gluing, injecting, shrinking or pressing on the pipette tip by the way. The cross section of the elastically deformable ejection end may have any shape, but will be round as a rule.

Preferred embodiments and further developments of the teaching of the invention are subject matter of claims 2 to 9, which will be explained later in the course of the explanation of the preferred embodiment with reference to the drawing.

Of particular importance is claim 9. Thereafter, the pipetting unit on the one hand and the microdosing unit, on the other hand, are arranged on holders of separate positioning devices and are then positioned in their respective precisely defined relative position by the positioning devices.

• a) Die Pipettiereinheit wird mittels der Positioniereinrichtung an eine Pipettenspitzen-Aufnahmeposition verfahren und dort mit ihrem Pipettenschaft voran vertikal zu einer in einem Tragestell bevorrateten Pipettenspitze hin abgesenkt, wobei die Pipettenspitze an einer Koppelstelle am Pipettenschaft aufgesteckt wird.
• b) Die Pipettiereinheit wird mittels der Positioniereinrichtung an eine Flüssigkeits-Aufnahmeposition verfahren und dort wird die Pipettenspitze mit ihrer Mündungsöffnung in ein mit Flüssigkeit gefülltes Vorratsgefäß eingetaucht und hier durch die Wirkung einer Verdrängereinrichtung in der Pipettiereinheit, die strömungsverbunden mit der Pipettenspitze ist und einen Unter- und Überdruck erzeugen kann, Flüssigkeit in die Pipettenspitze aufgenommen.
• c) Die Pipettiereinheit wird mittels der Positioniereinrichtung an eine Ankoppelposition verfahren.
• d) In der Ankoppelposition schaltet zunächst die Mikrodosiereinheit die Ankoppeleinrichtung inaktiv, die Pipettiereinheit wird mittels der Positioniereinrichtung vollständig an die Mikrodosiereinheit heran verfahren und die Mikrodosiereinheit schaltet die Ankoppeleinrichtung zum Ankoppeln aktiv.
• e) Die Pipettiereinheit wird mitsamt der Mikrodosiereinheit mittels der Positioniereinrichtung an eine oder mehrere Flüssigkeits-Abgabepositionen verfahren, so dass die Mündungsöffnung über einem Zielgefäß angeordnet ist, und dort wird die Mikrodosiereinheit zur tröpfchenweisen Flüssigkeitsabgabe in Betrieb genommen, vorzugsweise werden mehrere Flüssigkeits-Abgabeposition angefahren und die Flüssigkeitsabgabe wiederholt.
• f) Die Pipettiereinheit wird mittels der Positioniereinrichtung wieder an die Ankoppelposition verfahren, dort inaktiviert die Mikrodosiereinheit die Ankoppeleinrichtung und die Mikrodosiereinheit wird von der Pipettiereinheit wieder abgekoppelt.
• g) Die Pipettiereinheit wird mittels der Positioniereinrichtung an eine Pipettenspitzen-Abwurfposition verfahren und dort die Pipettenspitze mittels einer Spitzenabwurfeinrichtung in einen Auffangbehälter abgeworfen.

The peculiarity of the pipetting device according to the invention is also reflected in a method for operating a pipetting device. In that regard, the following applies:
A method of transferring liquid with a pipetting device comprising a pipetting unit, a positioning device, a micro-dosing unit and a control device, comprising the following method steps:

• a) The pipetting unit is moved by means of the positioning device to a pipette tip receiving position, where it is lowered with its pipette shaft ahead vertically to a pipette tip stored in a support position, wherein the pipette tip is attached to a coupling point on the pipette shaft.
• b) the pipetting unit is moved by means of the positioning device to a liquid receiving position and there the pipette tip is immersed with its mouth opening in a liquid-filled storage vessel and here by the action of a displacing means in the pipetting unit, which is in flow communication with the pipette tip and can generate overpressure, liquid added to the pipette tip.
• c) The pipetting unit is moved by means of the positioning device to a coupling position.
• d) In the coupling position, first the microdosing unit switches the coupling device inactive, the pipetting unit is moved completely by means of the positioning device to the microdosing unit and the microdosage unit switches the coupling device for coupling actively.
• e) the pipetting unit is moved together with the microdosing unit by means of the positioning to one or more liquid dispensing positions, so that the mouth opening is disposed over a target vessel, and there the microdosing unit for droplet-like liquid dispensing is put into operation, preferably several liquid dispensing position are approached and the liquid delivery is repeated.
• f) The pipetting unit is moved back to the coupling position by means of the positioning device, where the microdosing unit deactivates the coupling device and the microdosing unit is decoupled from the pipetting unit again.
• g) The pipetting unit is moved by means of the positioning device to a pipette tip ejection position, where the pipette tip is dropped by means of a tip ejector into a receptacle.

In a preferred method step, in feature d) the pipette tip is positioned relative to an actuating device of the microdosing unit such that a lower section of the pipette tip immediately above the outlet opening always remains underneath the actuating device and does not touch it.

Between steps c) and e), the displacing means may expel liquid from the pipette tip so that the meniscus of the liquid is formed at the mouth of the pipette tip.

In a preferred variant of the method, the microdosing unit is put into operation between method steps d) and e), with its actuating device acting in a reciprocating motion on a tube located at the lower end of the pipette tip, which is arranged in front of the mouth opening, such that this is deformed radially elastic and volume reducing so that the liquid is discharged in the tube in the form of free-flying droplets or in the form of a free-flying jet.

The coupling and decoupling of the microdosing to the pipetting in the context of the preferred method may preferably be done by switched coupling devices, preferably a coupling device is a magnetic coupling, more preferably a coupling device with a current-magnet permanent magnet / electromagnet.

According to a preferred variant of the described method, a residual liquid in the pipette tip can be ejected by the displacer unit between the process steps e) and f), wherein the preferred is in a separate liquid dispensing position.

According to a further preferred variant, during the process step e) or as soon as the microdosing unit for liquid discharge is put into operation and a liquid volume is dispensed from the mouth opening of the pipette tip, the displacer unit will feed this liquid volume as an overpressure directly or discontinuously.

Due to its design, liquid of smallest volumes, volumes up to 0.1 nl, held by a pipette unit can be transferred from a storage vessel to one or more target vessels by the method according to the invention. For this purpose, the pipette tip has a tube arranged in front of its mouth opening. The coupling of the pipette tip to a pipetting unit of the pipetting device, the Picking up the liquid, possibly dispensing residual liquid and discarding the pipette tip takes place as in conventional pipetting devices. According to the invention, the dispensing of the liquid in very small volumes takes place by means of a microdosing unit, which is switchably connected to the pipetting unit after the liquid has been taken up and later decoupled again.

For this purpose, the pipetting unit is moved by means of the positioning device to a coupling position and there the pipette tip is moved with its tube between an abutment and an actuating device of the micro-dosing unit. The abutment is attached to the tube. In the coupling position, the pipetting unit with its coupling device is also coupled to the counter coupling device of the microdosing unit and, preferably, in the coupling position via a contact connection, the pipetting unit is connected to the control unit with the microdosing unit. The pipetting unit is then moved with the microdosing unit by means of the positioning device to one or more liquid dispensing positions, so that the mouth opening of the corresponding pipette tip is arranged above a destination vessel, and there the microdosing unit for droplet-like liquid dispensing is put into operation. The pipetting unit is then moved back to the coupling position by means of the positioning device and there the coupling device is uncoupled from the counter coupling device, the abutment moved away from the tube in a starting position and the microdosing off again on a base station.

In the following, the invention will now be explained in more detail with reference to a drawing showing only a preferred exemplary embodiment. In the drawing shows

1 a schematic representation of the principle of a pipetting device of the type in question,

2 schematically the pipetting device in a pipette tip receiving position,

3 in a schematic representation of the pipetting device in a liquid receiving position,

4 in a schematic representation of the pipetting 3 with a microdosing unit in a coupling position,

5 a schematic representation of a pipetting device and a microdosing in a coupling position during the adjustment of the microdosing,

6 a schematic representation of a pipetting device and a micro-dosing unit at separate positioning devices in a coupling position,

7 in a schematic representation of the pipetting 4 in the liquid delivery,

8th in a schematic representation of the pipetting 4 in a pipette tip dropping position and

9 a pipetting device with four parallel pipette tips and a quadruple Mikrodosiereinheit in a schematic representation.

1 shows a pipetting device with a pipetting unit 1 , At the pipette unit 1 is at least one pipette tip 2 replaceable attachable. In 9 It can be seen that according to a preferred embodiment of the invention, the pipetting device is a multi-channel pipetting device. Then you are at the pipetting unit 1 several pipette tips 2 ,

The pipetting device according to the invention is preferably one with a pipette tip 2 that is an elastically deformable ejection end 3 having. The elastically deformable discharge end 3 has the shape of an elastically deformable tube in the illustrated embodiment. Such a tube may have any cross section, for example, an elliptical cross section. Here are all variants possible.

Furthermore, the pipetting device has at least one positioning device 4 and a microdosing unit 5 on. The entire pipetting device is completed by an electrical or electronic, often software-controlled control device today 6 by which all processes of the pipetting device can be controlled as desired. In 1 is indicated by dashed lines where transmission means for control commands, power supply and / or data are provided between the individual components of the pipetting device.

As 1 and 2 show in context, has the pipetting unit 1 for every attachable pipette tip 2 a coupling point 7 , This is typically designed in the form of a pipette shaft. Typically, therefore, the pipette tip 2 on the coupling point formed by the pipette shaft 7 attached or the coupling point 7 into the open top of the pipette tip 2 plugged in to the in a holder or support frame 16 stockpiled pipette tip 2 to dock.

The pipetting unit 1 has one with the coupling point 7 and the attached pipette tip 2 fluidically connected displacer unit 8th on. An air cushion pipette is the displacer unit 8th typically a cylinder-piston arrangement. It is essential that the displacer unit 8th in the coupled pipette tip 2 a negative pressure for receiving liquid in the pipette tip 2 and an overpressure to expel liquid from the pipette tip 2 can generate. Also, reference may be made to the entire state of the art explained in the introduction.

By means of the positioning device 4 is the pipetting unit 1 can be brought into different operating positions. Typical operating positions are a pipette tip pickup position ( 2 ), a liquid receiving position ( 3 ), a coupling position ( 4 ), a liquid dispensing position ( 7 ) or a plurality of such liquid dispensing positions, and a pipette tip ejection position ( 8th ).

In between can also be a residual liquid ejection position, which is not shown in the drawing. In the residual liquid discharge position of the pipetting unit 1 can remove residual fluid from the pipette tips 2 be discarded before they are then dropped in the pipette tip dropping position into a container.

In the present case, in particular, the liquid dispensing position (s).

In the 5 shown microdosing unit 5 That's what's special about this is from their own control unit 15 driven. To with the elastically deformable ejection end 3 , the elastically deformable tube realized here, immediately above the mouth opening of the pipette tip 2 to interact, instructs the microdosing unit 5 a movable actuator 9 on. The microdosing unit 5 is, as already 1 can recognize, in the dispensing position of the pipette 1 relative to the pipette tip 2 arranged so that the actuator 9 at the elastically deformable ejection end 3 the pipette tip 2 is positioned.

In the in 7 shown dispensing position of the pipette 1 out 4 is by driving the microdosing 5 the expelling 3 the pipette tip 2 by means of the actuating device 9 radially elastic volume displaceable deformable. As a result, single or multiple liquid as the smallest droplets or as a free-flying beam from the discharge end 3 the pipette tip 2 ejectable. In this way, therefore, does not work for ejecting the liquid in the smallest volumes, the displacer unit 8th but the microdosing unit 5 , whose actuator 9 immediately on the expelling end 3 the pipette tip 2 so influences that the volume in the expelling end 3 reduced. The expelling 3 So is by means of the actuator 9 deforms, abruptly with a high momentum, so that the liquid is expelled in the form of minute droplets or as a short free-flying jet. Smallest amounts of liquid down to 0.1 nl can be ejected.

In 2 to 9 becomes the construction of the microdosing unit 5 relative to the pipetting unit 1 shown. In the embodiment shown in FIG 4 such as 7 and 8th is shown, it is provided that the microdosing 5 from the pipetting unit 1 carried out separately, but optionally with the pipetting unit 1 can be coupled in a well-defined relative position. For this purpose, the pipette unit 1 a coupling device 10 and the microdosing unit 5 a corresponding negative feedback device 11 on. The coupling device 10 and / or the negative feedback device 11 are switchable. By switching the coupling device 10 and / or the negative feedback device 11 is the microdosing unit 5 optionally on the pipette unit 1 can be coupled or from the pipetting unit 1 decoupled.

The microdosing unit 5 So not always with the pipetting unit 1 be coupled. It is only with the pipetting unit 1 coupled when in the liquid dispensing position with the microdosing unit 5 smallest amounts of liquid should be dispensed into target vessels.

The peculiarity of the construction lies primarily in the fact that the microdosing unit 5 if necessary, to the pipetting unit 1 coupled and then from this pipetting unit 1 by means of the positioning 4 is brought into different operating positions, is carried in the desired operating positions. This may in particular be different liquid dispensing positions.

5 shows the inventively designed pipetting, which is characterized in that the pipetting unit 1 and the microdosing unit 5 can be selectively positioned in a well-defined relative position. The positioning device 4 holding the pipetting unit 1 positioned, has a holder for this purpose 18 on with a coupling device 10 , The microdosing unit 5 has a corresponding negative feedback device 11 on.

The operation is similar to the pipetting device described above. The decisive difference is that the microdosing unit 5 even a first detector 70 for mounting 18 directed toward which the coupling device 10 and / or the negative feedback device 11 (preferably via a corresponding electronics, such as an electronic control unit) switches.

In 6 the pipetting device according to the invention is shown in another embodiment. The pipetting unit 1 is on a bracket 18 the positioning device 4 arranged. Another positioning device 4 ' , which is another bracket 18 ' is assigned to the microdosing unit 5 intended. The microdosing unit 5 can therefore be separated from the pipetting unit 1 are also brought in a well-defined relative position to different operating positions. In particular for dispensing liquid are the pipetting unit 1 with the pipette tip 2 and the microdosing unit 5 associated with each other in the well-defined relative position. To accomplish this and around the pipette tip 2 in the intended relative position to the actuator 9 to bring position the positioning 4 . 4 ' the pipetting unit 1 and the microdosing unit 5 in a coupling position. Thereafter, both positioning devices 4 . 4 ' together, ie coordinated, are moved to different operating positions, in particular different liquid dispensing positions,

In 5 recognizes that according to a particularly preferred embodiment, the pipetting a base station 12 for storing the microdosing unit 5 when not in use. The base station 12 provides a deliberately designed, defined place for storing the microdosing unit 5 when not in use. It is preferably stationarily positioned on the pipetting device.

In 5 is a stacked arrangement of the pipetting unit 1 , Microdosing unit 5 and base station 12 shown on the one hand, the coupling device 10 and negative feedback device 11 and on the other hand, the tray of the microdosing unit 5 on the base station 12 oriented in a horizontal plane. In each case another arrangement in a vertical or inclined plane are also possible.

In 5 is shown at the top of the base station 12 a positioning aid 12 ' for the microdosing unit 5 , The positioning aid 12 ' serves for exact and positionally stable positioning of the microdosing unit 5 , Repeated coupling can be done easily.

The base station 12 has a connection 12 '' for the power supply and possibly for data lines connected to the control device 6 are connected.

For the design of the coupling device 10 and the negative feedback device 11 There are, in principle, a multitude of possibilities. In principle, it would be possible for the coupling device 10 and the switched negative feedback device 11 mechanically execute, for example, as a positive connection, as a bolt connection, etc. In principle, it would also be possible to provide a merely manual operation. This is not normally done in the context of a largely automated pipetting device.

According to a preferred teaching, it is provided that the negative feedback device 11 active and from the control unit 15 off switchable and the coupling device 10 is executed passively.

Preferably, constructive in the invention in the negative feedback device 11 with at least one permanent magnet 13 and one the permanent magnet 13 associated electromagnet 14 worked. When not energized electromagnet 14 causes the holding force of the permanent magnet 13 the coupling of the microdosing unit 5 on the bracket 18 ; 18 ' , The coupling device 10 in this case has a simple counterpart 10 ' made of ferromagnetic material. electromagnet 14 are integrated elements, are very compact and have a particularly high performance.

Will the electromagnet 14 energized with current in one direction, resulting in a magnetic field of the permanent magnet 13 opposite, but about the same size magnetic field leads, so is the magnetic force of the permanent magnet 13 neutralized. With energized electromagnet 14 So is a decoupling of the negative feedback device 11 from the coupling device 10 and thus the microdosing unit 5 from the holder 18 ; 18 ' causes.

You can control the electromagnet 14 continue to optimize so that it can be energized in the opposite direction. Then the magnetic force of the energized electromagnet amplifies 14 that of the permanent magnet 13 so that the microdosing unit 5 especially strong on the bracket 18 ; 18 ' is coupled. This selective energization of the electromagnet 14 can be realized, for example, when sections high accelerations on the microdosing 5 act or otherwise the microdosing 5 exposed to special forces.

Another advantage of the present design of the preferred embodiment is that when neutralized magnetic force of the permanent magnet 13 the holder 18 ; 18 ' by means of the positioning device 4 free and easy relative to the microdosing unit 5 can be positioned. Only when the defined relative position is reached, the permanent magnets 13 unlocked in terms of their magnetic effect.

It is best to use several, as evenly as possible over the surface of the bracket 18 ; 18 ' and the microdosing unit 5 distributed counterparts 10 ' , Permanent magnets 13 and electromagnets 14 provide so that a uniform suspension of the microdosing 5 on the bracket 18 ; 18 ' results.

For control technical organization of the pipetting device according to the invention, it can be provided that the microdosing unit 5 is largely autonomous control technology, being contact-bound or wireless with the control device 6 the pipetting device communicates.

Preference is given to an electrical contact connection 60 between the bracket 18 ; 18 ' and the microdosing unit 5 set up. About this contact connection 60 In addition to communication, control signals or the power supply or charging currents for rechargeable batteries or capacitors of the microdosing unit can also be used 5 be directed. Another, similar electrical contact connection 61 is also between the pipetting unit 1 or the holder 18 ; 18 ' and the microdosing unit 5 arranged and is connected to the coupling. In the present case, the microdosing unit has 5 a separate control unit 15 which has already been mentioned above.

According to the preferred teaching of the invention, the microdosing unit 5 a first detector 70 on, the approach of the holder 18 ; 18 ' is activated. The first detector 70 So it is for mounting 18 ; 18 ' directed towards. The first detector 70 is with the control unit 15 connected and controls the negative feedback device 11 and preferably also the contact compound 60 , The negative feedback device 11 is by energizing the electromagnets 14 connected.

Preferably, another detector 71 at the bottom of the microdosing unit 5 to the base station 12 arranged and activated by her. Also the second detector 71 is with the control unit 15 Connected, switching the energizing of the electromagnets 14 for uncoupling and preferably also controls the further contact connection 61 ,

The first detector 70 in the exemplary embodiment is an optical detector which switches at a distance of 1 to 20 mm. The signal is from the control unit 15 queried and processed. The second detector 71 is in the embodiment in the simplest form in the contact connection 61 integrated. Again, the control unit 15 several contacts of the contact connection 61 interrogate and recognize the switching process with electrical contact. Alternatively, the second detector 71 a separate electrical button.

Suitable detectors are electrical buttons or proximity switch principles (magnetic, capacitive, inductive, ultrasound, optical). As an alternative, a mechanical contact interface, which operates to tolerate horizontal and vertical movement of its actuator, may also be provided.

Not shown is that the contact connections 60 . 61 each consist of at least one contact surface and a contact which is movable and advantageously springing exist. In particular, the contact connection 60 and possibly also the further contact connection 61 are controlled at the respective coupling. For this purpose, the contact is moved away from the contact surface. Only after the movement of the holder 18 ; 18 ' to the horizontal position for coupling, the contact is moved in the direction of the contact surface. When final coupling the bracket 18 ; 18 ' to the microdosing unit 5 by switching off the energizing of the electromagnets 14 becomes the contact connection 60 closed.

The following is based on 3 . 4 . 7 . 8th the operation with a pipetting device according to the invention again briefly shown.

In 3 you can see the situation in the pipette tip pickup position. The pipette tip 2 is suspended in the support frame 16 a storage container. The displacer unit 8th in the form of a cylinder-piston arrangement is located together with the associated drive 17 on the bracket 18 , It is purely schematic on the drive 17 the controller 6 the pipetting device indicated. Of course, this can also be arranged at any other location.

By arrows is indicated, as the pipette shown here 1 by means of the positioning device 4 can be moved.

At the pipette unit 1 there is a coupling point 7 in the form of a pipette shaft whose conicity is the conicity of the upper end of the pipette tip 2 equivalent. In 3 is the pipette tip 2 on the coupling point 7 been plugged. The pipetting unit 1 is by means of the positioning device 4 brought into the liquid receiving position. You can see a storage vessel below 19 in which there is liquid. This is just by means of Effect of the displacer unit 8th after the air cushion principle in the pipette tip 2 sucked. After picking up and lifting the pipette tip 2 from the liquid in the storage vessel 19 can the piston of the displacer unit 8th Move it a little further and suck in some air, so that no liquid from the mouth of the pipette tip 2 drips off when the pipette unit 1 is moved to another operating position.

4 then shows a representation of the coupling position. Here is the pipette unit 1 with the microdosing unit 5 been brought together. The coupling device 10 at the pipette unit 1 stands with the negative feedback device 11 interact so that the microdosing unit 5 firmly on the pipetting unit 1 is coupled. This happens in a defined relative position. This is required because the in 4 illustrated actuator 9 the microdosing unit 5 Of course, it has to be located exactly where the expectorant is 3 the associated pipette tip 2 located. Left in 4 at the level of the discharge end 3 the pipette tip 2 you see a jaw 20 , The arrow indicates that the jaw 20 to the expelling end 3 the pipette tip 2 is employed, so that there is an abutment for the movement of the actuator 9 results.

In the coupling position according to 4 the conditioning of the pipetting unit also takes place 1 , The piston of the displacer unit 8th is moved so far down (arrow) until at the mouth of the discharge end 3 just the meniscus of the liquid contained therein forms. Under the mouth of the pipette tip 2 is in 4 a vessel 21 arranged, in which normally no liquid is still. This should now in the vessel 21 be delivered. For this purpose, the microdosing unit 5 put into operation. With a reciprocating movement of the actuator 9 is on the designed as an elastically deformable tube ejection end 3 the pipette tip radially exerted force so that it is deformed. As a result, liquid in droplet form from the mouth of the pipette tip 2 into the vessel 21 issued.

The movement of the actuator 9 is in 7 indicated by a double arrow. It takes place back and forth against the abutment forming jaw 20 , This is first the conditioning of the pipetting device in preparation for the actual liquid delivery.

7 then shows the actual liquid delivery in the liquid dispensing position. You can see several target vessels here 21 ' , For example, the wells of a microtiter plate, and above the direction of movement of the pipette 1 together with the microdosing unit 5 , moved by the positioning 4 , Shown is a by the deformation effect of the actuator 9 the microdosing unit 5 from the expelling end 3 the pipette tip 2 blasted small liquid drop, for example, has 0.5 nl volume.

By means of the control device 6 can the displacer unit 8th the pipetter unit 1 in coordination with the delivery of liquid by means of the microdosing unit 5 be controlled so that the delivered minimum liquid volume after a number of liquid discharges discontinuous or directly into the discharge end 3 the pipette tip 2 is fed into it. So the pressure in the air cushion in the pipette tip 2 kept constant. This process at the pipetting device according to the invention is also in 7 shown. One can see the relatively small displacement movement of the piston of the displacer unit 8th understand with the arrow.

After the pipetting process, first the microdosing unit 5 again at the docking position on their base station 12 turned off, the jaw 20 from the expelling end 3 moved away to the starting position and the coupling device 10 ; 11 is solved as described above. At the base station 12 For example, those in the microdosing unit 5 indicated batteries 22 automatically reloaded.

In 8th is then the end position of the pipetting unit 1 shown after a completed pipetting process. The pipetting unit 1 is again on its own and as such by means of the positioning device 4 placed in the pipette tip discharge position. By means of the tip ejection device 23 becomes the pipette tip 2 dropped into a collection container. This collection container is not shown here.

The vertical arrows in 8th interpret the movements of the Spitzenabwurfeinrichtung 23 and in consequence of the pipette tip 2 at.

In the presentation of 4 and 7 Finally, it can be understood that a special structural design has been chosen by the pipette tip 2 relative to the actuator 9 the microdosing unit 5 at any time is arranged so that the lower portion of the discharge end 3 the pipette tip 2 always below the actuator 9 is and does not touch them. This is also true when inserting the pipette tip 2 into the microdosing unit 5 or in their actuator 9 to ensure this insertion is carried out according to the invention not from above (as in the prior art), but by a lateral insertion of the actuator 9 or on the side of the jaw 20 ,

Aspirate liquid into the pipette tip 2 always occurs only with a small immersion of the lower end of the pipette tip 2 into a liquid reservoir. Only the lower end near the mouth opening of the pipette tip 2 is wet. According to the invention, the construction is so prepared that this lower end, the lower portion of the discharge end 3 the pipette tip 2 nowhere with the microdosing unit 5 comes into contact. Carryover of liquids between different target vessels 21 ' is therefore safely avoided.

In the embodiments of 5 and 6 is different than in the embodiment of 4 the switching of the coupling device 10 and / or the negative feedback device 11 from the microdosing unit 5 triggered, namely on the first detector 70 that to the holder 18 ; 18 ' is directed.

In the embodiment of 6 is the holder 18 ' the positioning device 4 ' for the microdosing unit 5 physically completely separated from the holder 18 the positioning device 4 for the pipetting unit 1 ,

In the embodiments of 5 and 6 becomes the further contact connection 61 between the microdosing unit 5 and the base station as a contact-bound electrical connection for the charging current and / or for data exchange with the control device 6 used.

One recognizes in 9 Details of a pipetting device with a plurality of pipette tips 2 namely, four pipette tips 2 , and with a plurality of displacer units 8th , namely a cylinder-piston arrangement per coupling point 7 with pipette tip 2 , The piston rods of the cylinder-piston assemblies, which are the displacer unit 8th form, are at a common drive 17 merged. Below you can see the jaws 20 and the target vessels 21 ,

QUOTES INCLUDE IN THE DESCRIPTION

This list of the documents listed by the applicant has been generated automatically and is included solely for the better information of the reader. The list is not part of the German patent or utility model application. The DPMA assumes no liability for any errors or omissions.

Cited patent literature

• WO 2006/076957 A1 [0010]
• WO 2005/016534 A1 [0012]

Claims (10)

Pipetting device with a pipetting unit ( 1 ), at least one at the pipette unit ( 1 ) exchangeable attachable pipette tip ( 2 ) with an ejection end ( 3 ), at least one positioning device ( 4 ; 4 ' ) with a holder ( 18 ; 18 ' ), a microdosing unit ( 5 ) and a control device ( 6 ), whereby the pipetting unit ( 1 ) for the or each attachable pipette tip ( 2 ) a coupling point ( 7 ), in particular in the form of a pipette shaft, wherein the pipetting unit ( 1 ) one with the coupling point ( 7 ) and a pipette tip ( 2 ) fluidically connected displacer unit ( 8th ), in particular in the form of a cylinder-piston arrangement, wherein the pipetting unit ( 1 ) by means of the positioning device ( 4 ) is brought into different operating positions, including in particular a liquid dispensing position, wherein the microdosing ( 5 ) from the pipetting unit ( 1 ) is performed separately, wherein the microdosing ( 5 ) a movable actuator ( 9 ) and in any case in the dispensing position of the pipetting unit ( 1 ) relative to the pipette tip ( 2 ) is arranged so that the actuating device ( 9 ) at the discharge end ( 3 ) of the pipette tip ( 2 ), and wherein in the dispensing position of the pipetting unit ( 1 ) by driving the microdosing unit ( 5 ) the expelling end ( 3 ) of the pipette tip ( 2 ) by means of the actuating device ( 9 ) is influenced so that it simply or repeatedly liquid as the smallest droplets or as a free-flying beam from the discharge end ( 3 ) of the pipette tip ( 2 ) is ejected, characterized in that the pipetting unit ( 1 ) and the microdosing unit ( 5 ) are selectively positionable in a well-defined relative position that the holder ( 18 ; 18 ' ) or a positioning device ( 4 ; 4 ' ) to a coupling device ( 10 ) and the microdosing unit ( 5 ) a corresponding negative feedback device ( 11 ), that the coupling device ( 10 ) and / or the negative feedback device ( 11 ) is switchable, that by switching the coupling device ( 10 ) and / or the negative feedback device ( 11 ) the microdosing unit ( 5 ) optionally on the holder ( 18 ; 18 ' ) can be coupled or uncoupled, that the on the bracket ( 18 ; 18 ' ) coupled microdosing unit ( 5 ) together with the pipetting unit ( 1 ) can be brought into different operating positions, in particular into the liquid dispensing position, and that the microdosing unit ( 5 ) a first detector ( 70 ) for mounting ( 18 ; 18 ' ) directed towards the coupling device ( 10 ) and / or the negative feedback device ( 11 ) switches. Pipetting device according to claim 1, characterized in that the ejection end ( 3 ) of the pipette tip ( 2 ) designed as an elastically deformable tube and by means of the actuating device ( 9 ) is radially elastically volume displaceable deformable. Pipetting device according to claim 1 or 2, characterized in that the first detector ( 70 ) coupling the microdosing unit ( 5 ) on the bracket ( 18 ; 18 ' ) and that, preferably, the microdosing unit ( 5 ) a second detector ( 71 ) to a base station ( 12 ), which is a decoupling of the microdosing ( 5 ) from the bracket ( 18 ; 18 ' ) switches. Pipetting device according to one of claims 1 to 3, characterized in that the negative feedback device ( 11 ) active and switchable and the coupling device ( 10 ) is executed passively. Pipetting device according to one of claims 1 to 4, characterized in that a coupling device ( 10 ; 11 ) is designed as a switched magnetic coupling, preferably with at least one permanent magnet ( 13 ) and a permanent magnet ( 13 ), which can be energized for switching electromagnets ( 14 ), and that the other coupling device ( 10 ; 11 ) passively, preferably as a ferromagnetic counterpart ( 10 ' ) is carried out, wherein when not energized electromagnet ( 14 ) the holding force of the permanent magnet ( 13 ) the coupling of the microdosing unit ( 5 ) causes. Pipetting device according to one of claims 1 to 5, characterized in that the microdosing unit ( 5 ) own control unit ( 15 ) connected to the first detector ( 70 ), the first detector ( 70 ) via the control unit ( 15 ) preferably the energizing of the one or more electromagnets ( 14 ), wherein, preferably, the control unit ( 15 ) also with the second detector ( 71 ) and also the second detector ( 71 ) via the control unit ( 15 ) the energizing of the electromagnet or magnets ( 14 ) switches. Pipetting device according to one of claims 1 to 6, characterized in that the holder ( 18 ; 18 ' ) with the microdosing unit ( 5 ) via a contact connection ( 60 ), that, preferably, the microdosing unit ( 5 ) with the base station ( 12 ) via another contact connection ( 61 ) is electrically connected and that the contact connection ( 60 ) and possibly also the further contact connection ( 61 ) are controlled at the respective coupling. Pipetting device according to one of claims 1 to 7, characterized in that the pipetting unit ( 1 ) a plurality of coupling points ( 7 ) for attaching a plurality of pipette tips ( 2 ) (multi-channel pipetting unit), wherein, preferably, for each coupling point ( 7 ) a displacer unit ( 8th ) or, more preferably, a single displacer unit ( 8th ) for all coupling points ( 7 ) is provided jointly. Pipetting device according to one of claims 1 to 8, characterized in that the pipetting unit ( 1 ) and the microdosing unit ( 5 ) to brackets ( 18 ; 18 ' ) of separate positioning devices ( 4 ; 4 ' ) are arranged and by the positioning ( 4 ; 4 ' ) are positionable in their respective precisely defined relative position, wherein, preferably, the first holder ( 18 ) with the pipetting unit ( 1 ) and the second holder ( 18 ' ) with the microdosing unit ( 5 ) are movable in different operating positions. A method for transferring liquid with a pipetting device comprising a pipetting unit, at least one positioning device, a microdosing unit and a control device, comprising the following method steps: a) The pipetting unit is moved by means of the positioning device to a pipette tip receiving position, where it is lowered with its pipette shaft ahead vertically to a pipette tip stored in a support position, wherein the pipette tip is attached to a coupling point on the pipette shaft. b) the pipetting unit is moved by means of the positioning device to a liquid receiving position and there the pipette tip is immersed with its mouth opening in a liquid-filled storage vessel and here by the action of a displacing means in the pipetting unit, which is in flow communication with the pipette tip and can generate overpressure, liquid added to the pipette tip. c) The pipetting unit is moved by means of the positioning device to a coupling position. d) In the coupling position, first the microdosing unit switches the coupling device inactive, the pipetting unit is moved completely by means of the positioning device to the microdosing unit and the microdosage unit switches the coupling device for coupling actively. e) the pipetting unit is moved together with the microdosing unit by means of the positioning to one or more liquid dispensing positions, so that the mouth opening is disposed over a target vessel, and there the microdosing unit for droplet-wise liquid dispensing is put into operation, preferably several liquid dispensing position are approached and the liquid delivery is repeated. f) The pipetting unit is moved back to the coupling position by means of the positioning device, where the microdosing unit deactivates the coupling device and the microdosing unit is decoupled from the pipetting unit again. g) The pipetting unit is moved by means of the positioning device to a pipette tip ejection position, where the pipette tip is dropped by means of a tip ejector into a receptacle.

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