EP1699560A1 - Pipette tip, pipette device, pipette tip actuating device and pipetting method in the nanolitre range - Google Patents

Abstract

The invention relates to an interchangeable pipette tip (100) comprising a first end (106) with a fluid opening (106a) and a second end (110), which has a tube (102) that is flexible in a radial direction and a mouth (112). The mouth (112) and the fluid opening (106a) have a fluidic connection. The first end (106) is configured to be coupled to a suitable coupling device (122) of a pipetting unit (120) in such a way that liquid can be sucked through the mouth (112) into the fluid region (108) by an actuating device in the pipetting unit (120). The volume of a section of the radially flexible tube is modified to eject liquid as free-flowing drops or as a jet from the mouth of the radially elastic tube.

Description

 Pipette tip, pipetting device, pipette tip actuator and method for pipetting in the nL

Area

description

The present invention relates to an exchangeable pipette tip, a pipetting device, a pipette tip actuating device and a method for pipetting, which make it possible to take up liquid and to eject liquid volumes in the nanoliter range.

According to the prior art some microliters can with Pipetierverfahren with changeable tips only volumes in the range (10 ^-9 m ³⁾ to milliliters (ICT ⁶ m ³⁾ are dosed.

A typical hand-held pipette 10 with a replaceable pipette tip 12 is shown in FIG. 5 is shown. The hand-held pipette 10 comprises a coupling device 14, onto which the rear part of the pipette tip 12 can be plugged, so that a fluid connection of the inner fluid areas of the pipette tip to inner fluid areas of the hand-held pipette 10 takes place via the fluid opening 16. The hand-held pipette 10 includes means (not shown) for creating a negative pressure in the internal fluid areas thereof so that liquid can be drawn into or ejected from the pipette tip 12 through an orifice 18 in the pipette tip 12.

In the case of automatic pipetting devices, a moveable holder 20 (FIG. 6) is generally provided which has coupling devices 22 for receiving one or more pipette tips 24. Here, the pipette tips 24 are so connected to the pipetting device, which has the movable holder 20, that sucked by appropriate actuators in the pipetting liquid through the mouth openings of the pipette tips 24 and is ejected. As a rule, fluid regions in the pipette tip are in fluid communication with fluid regions in the pipetting device.

In pipetting machines of this type, the pipette tip 24 is picked up from a carrier and clamped in the movable holder 20. For aspiration, the mouth of the pipette tip is then dipped into a vessel. After the liquid intake, which is achieved by means of a negative pressure in the pipette, the pipette tip is moved over the target, where then by means of an overpressure in the pipette either the entire contents or a small part is discharged into the target vessel. For large volumes, this can be done in the free jet, with small volumes must if necessary. there is contact between the target and the pipette tip, since there is no drop break due to adhesion forces at the pipette tip.

The above-mentioned process limits on the one hand the minimum volume to be dispensed, on the other hand it can also lead to carryover of substances already in the target. After the dosage has been completed, the pipette tip is discharged into a waste container (waste box) by means of an automatic ejector. In the example shown in FIG. 6, as used, for example, by Eppendorf, the pipetting machine comprises coupling devices for eight pipette tips.

For the delivery of liquid volumes of less than one microliter, free jet methods are known from the prior art, as described in DE 19802367 C1 and DE 19802368 C1. There, a pressure chamber is in each case bounded on one side by a membrane, so that by deflecting the membrane liquid droplets can be ejected from a discharge opening fluidly connected to the pressure chamber. A method which makes it possible to dispense liquid quantities in the range of a few tens of nanoliters is known as the so-called "Mosquito ^xx process" from TP Labtech, in which case, however, the part to be exchanged in fluid contact is expensive to manufacture and correspondingly expensive. Other systems, such as one described in EP 1093856 Al, based on adapted pipettes in which a membrane is embedded. This allows by means of an oppressing actuator higher dynamics than air cushion pipettes, whereby small discharge quantities can be achieved.

Finally, from the non-prepublished German application 10337484.1 a method for dosing of liquids in the nanoliter range known. Such a method is shown schematically in FIGS. 7a to 7c. As shown in FIG. As shown in FIG. 7a, a flexible tube 30 includes an inlet - side end 32 for connection to a liquid reservoir, and an outlet - side end 34 at which microdrops and / or microtubes, respectively, are provided. Microbeams can be emitted. Respective walls 36 of the elastic tube 30 are shown by dashed lines. An actuator 38 in the form of a displacer is provided, which has a connecting part 40 with which the displacer 38 can be attached to an actuator for driving the displacer 38.

The elastic tube may have, for example, from its inlet end 32 to its outlet end 34 a substantially constant cross-section, which will generally be circular. An area 42 located below the displacer 38 may be referred to as a metering chamber area and is defined by the position of the displacer with respect to the elastic tube. A region 44 that begins substantially at the right end of the displacer 38 represents an outlet channel while a region 46 that begins substantially at the left end of the displacer 38 constitutes an inlet channel. The displacer 38 may be angled toward the wall 36 of the flexible Hose 30 extending Verdrängeroberfläche 50, which allows the operation of the microdosing device, the generation of a preferred direction toward the outlet opening 34.

Let it be assumed that in the case of FIG. 7a, the flexible tube 30 is filled with a liquid, such filling being able to take place, for example, by capillary forces. Starting from this state, the displacer 38 is rapidly moved downwards in the direction of the arrows 52, thereby reducing the line volume between the inlet opening and the outlet opening. This results in a fluid flow 54 towards the outlet end 34 and a fluid flow 56 towards the inlet end 32. By the forward flow 54 takes place at the outlet opening 34, a liquid ejection in the form of a micro-droplet 60 or micro-beam instead. What proportion of the liquid through the outlet opening 34 as a jet or. Drops depends on the position, nature and dynamics of the volume change. Furthermore, the amount of liquid dispensed as drops depends on the size of the displacer as well as on the stroke of the displacer 38, d. H. How hard the hose is compressed.

After the ejection operation, a refill phase occurs, in which the displacer 38 is moved away from the hose in the direction of the arrow 61, so that the volume of the inlet opening 32 and outlet opening 34 is increased again, and thus liquid flows in through the inlet channel 46, see arrow 64 in FIG 7c.

The details regarding this dosing method are, as stated above, described in the German application 10337484, the relevant disclosure of which is hereby incorporated by reference. US 5 032 343 deals with a micropipette tip for hard to reach places. For this purpose, the front section of the micropipette tip is elongated and ultrathin. This provides flexibility that allows placement of the pipette tip in hard-to-reach locations. The opposite end of the pipette tip is rigid and allows attachment of the pipette tip to conventional tools.

US 6,180,061 is concerned with a cartridge pump and dispenser assembly for applications in which cartridges containing liquid reagents are frequently changed. The cassette pump comprises a reservoir in which a movable piston is arranged. A lower open end of the reservoir empties directly into a metering chamber in the form of a flexible pipe. An actuator in the form of a rubber hammer is provided, by which the volume of the metering chamber can be reduced, thereby causing a discharge of liquid through a nozzle which is connected to an ejection-side end of the metering chamber. In the metering chamber two valves are further arranged, which allow only a unidirectional flow from the reservoir-side end to the nozzle-side end of the metering chamber.

WO 02/092228 A2 is concerned with a dispensing device which uses a conventional syringe pump to expel liquid volumes of less than 5 μl. According to this document, a syringe pump is provided, which is connected via a hose with a ■ dispenser 2. The dispenser includes a system fluid reservoir that is separated from a sample fluid reservoir by an elastomeric membrane. With the sample liquid reservoir, a nozzle having a nozzle bore is connected. The system fluid reservoir is connected to the syringe pump via the tubing so that by actuating the syringe pump via the system fluid, the diaphragm can be deflected to thereby Eject sample liquid through the nozzle. Sample liquid can also be sucked in through the nozzle, wherein in order to separate a droplet suspended from the nozzle after aspirating the sample liquid, an electric field is applied between the nozzle and a suitably arranged counter electrode. In one embodiment, an actuator is alternatively provided to cause axial expansion or compression of the nozzle thereby to separate droplets adhering to the tip after aspiration.

EP 0028478 B1 is concerned with a pipetting device in which an elastic pipe is housed in a block such that a tubular recess in the block has a larger diameter than the outside diameter of the elastic pipe. An ejection-side end of the elastic tubing is connected to a connector which in turn is connected to a pipette tip. Aspiration and expulsion of liquid through the pipette tip now occurs by applying an overpressure or depression to the internal bore of the block to cause corresponding volume changes of the elastic tubing. In one embodiment, an end of the described squish tube means spaced from the pipette tip is connectable to a syringe via a three-way valve such that sample liquid and a diluent previously drawn into the syringe are actuated by actuating the syringe and pressurizing the syringe Hole of the block can be ejected through the pipette tip into a discharge vessel.

The object of the present invention is to provide a pipette tip, a micropipetting device, a pipette tip actuating device and a method for petting, which enable the dispensing of small amounts of liquid.

This object is achieved by a pipette tip according to claim 1, a pipetting device according to claim 10, a pipette tip. tenspitzen actuator according to claim 18 and a method according to claim 22 solved.

The present invention provides a replaceable pipette tip having the following features:

a first end having a fluid port; and

a second end having a radially elastic tube with an orifice, the resilient tube being configured to be substantially rigid to deflections along the tube axis but flexible and resilient to radial deformations,

wherein the mouth and the fluid port are in fluid communication, and

wherein the first end is adapted to be coupled to a mating coupling device of a pipetting device, such that liquid can be sucked through the muzzle into the fluid region by an actuating device in the pipetting device.

The present invention further provides a pipetting device having the following features:

a coupling device for coupling with such a pipette tip;

a first actuator for generating a negative pressure at the fluid port at the first end of the pipette tip to aspirate fluid through the mouth of the radially elastic tube; and a second actuator for temporally varying the volume of a portion of the radially elastic tube to thereby expel liquid as a droplet or as a free-flying jet from the mouth of the radially elastic tube.

The present invention further provides a pipette tip actuator for a pipetting device comprising a pipette tip having a first end with a fluid opening and a second end, the second end having a radially elastic tube with an orifice, the fluid port and the mouth are in fluid communication, with the following features:

a fixing device having a first state in which the tube elastic in the radial direction is fixed at a predetermined position and a second state in which the tube elastic in the radial direction is not fixed;

fixing means driving means for changing the state of the fixing means; and

an actuator for temporally varying the volume of a portion of the radially elastic tube to thereby expel liquid as a droplet or as a free-flying jet from the mouth of the radially elastic tube when the fixing device is in the first state.

The present invention further provides a method of pipetting liquid using a pipette tip having a first end with a fluid port and a second end, the second end having a radially elastic tube with an orifice, the fluid port and the orifice in fluid communication, with the following steps: Filling the pipette tip by dipping the mouth of the radially elastic tube into a liquid and creating a negative pressure at the fluid opening of the first end of the pipette tip; and

Causing a volume change of a portion of the radially elastic tube to expel liquid as free-flying droplets or as a jet from the mouth of the radially elastic tube by the volume change.

The present invention is based on the recognition that a pipette tip, which is both a low cost replacement member and allows metering of very small volumes of liquid, can be implemented by providing it with a flexible hose having a mouth end for fluid discharge and fluid intake serves, has.

A radially elastic tube is to be understood as one which is flexible and elastic with respect to radial deformations. For example, the radially elastic tube may be formed by an elastic tube, i. H. a fluid conduit which also has deflections along the tube axis, i. H. in the axial direction, can be flexible. However, such elastic hoses tend to behave more like a tube, in the case of lengths typically used in a microdosing device, i. H. substantially rigid with respect to deflections along the tube axis, but flexible and elastic with respect to radial deformations.

Typical materials for the radially elastic tube include the polyimide, polyamide or silicone. Typical diameters can be from 0.1 to 1 mm. The tube, which is elastic in the radial direction, can be attached to the pipette tip body, for example by gluing, injecting, shrinking or by press-fitting. be satisfied. The elastic in the radial direction tube may further arbitrarily shaped, for. B. have round or angular, constant or changing cross sections.

The present invention includes devices and a method that can be integrated into conventional automatic pipetting machines and provide the ability to deliver volumes in the range of 0.1 nL to several μL. Preferably, the present invention also allows for intermediate storage of the fluid in the pipette tip.

Instead of conventional pipette tips, a composite of a rigid part, which may have the structure of a conventional pipette tip, and an elastic tube is used according to the invention. The rigid part allows the picking up of the pipette tip in the automatic pipetting machines and allows the ejection by means of conventional devices built into the machine. Alternatively, the rigid part may allow for inclusion in a handheld pipette. The tube attached to the underside of the pipette serves to deliver the fluid in the pipette tip by the method as described above with reference to Figs. 7a to 7c and as set forth in German application 10337484. The dosing volume dispensed without contact may be in the range from 0.1 nL to 10OnL per individual dosing operation. Multiple dosing allows a higher dosing volume to be achieved with flow rates of up to 20 μL / s.

The micropipette of the present invention can be used with conventional automatic pipetting machines, such as bubble pads or syringe pumps, which are capable of utilizing conventional disposable pipette tips. Instead of the conventional disposable pipette tips, the pipette tips according to the invention are used. Through this, liquid can be taken up into the pipette tip according to the invention with the conventional pipetting mechanism. The absorbed liquid can then be in different ways be delivered again. Dosing can be done with the conventional pipetting mechanism to eject large volumes. Such a conventional pipetting mechanism is typically a pressure generating device capable of generating a negative pressure in a pressure chamber in fluid communication with the interior of the pipette tip for sucking or discharging liquid to effect into or on the pipette tip.

However, in preferred embodiments of the present invention, metering is by the method described above in FIGS. 7a to 7c. In preferred embodiments, the dosing tube is fixed using a fixing device, whereupon a volume displacement in the hose is brought about and thereby the dosing process is triggered.

The exchangeable pipette tip or disposable pipette tip according to the invention can be handled automatically like conventional pipette tips by a pipetting device, i. H . be recorded and filed.

Using the pipette tip according to the invention, a liquid can be sucked in at a first position, in which case the pipette tip is moved by the automatic pipetting device to a second position at which the metering takes place. Alternatively, the pipette tip can also be removed after the liquid has been sucked in by the automatic pipetting device, with the dosage being able to be taken after removal at another point using a suitable squeezing device for the hose.

The present invention thus provides a novel pipette tip consisting of a composite of a rigid pipette tip part and a flexible tube. Such a pipette tip can automatically be inserted into an actuating Device for squeezing the elastic tube, thereby causing a liquid ejection, are recorded. Preferably, a fixing device is provided to automatically clamp the hose in the actuator, whereupon the actuator is moved up in the actuator to squeeze the hose to reduce the volume thereof to effect liquid ejection. Such an actuator may be used in combination with a conventional automatic pipetting device so that liquid can be dispensed from a pipette tip using the squeeze method, which can also be used for conventional pipetting, for example air bubble.

The dimensions of the elastic tube may be such that a liquid can be stored in the pipette tip. In this regard, the dimensions of the hose and the mouth thereof may be such that liquid is held in the hose by capillary forces and surface forces.

The present invention also allows the use of different drive units for aspiration and dosing. The aspirating can be done, for example, by a conventional automatic pipetting device which generates a vacuum at the first end of the pipette tip. However, aspiration can also be driven only by capillary forces. A capillary-driven aspiration is described, for example, in GB 2353093A. The dispensing can be done by an actuator for generating a volume change of a tube elastic in the radial direction, or by overpressure or inertial forces, such as. As disclosed in GB 2353093 A or DE 19913076 A, be brought about. Preferred embodiments of the present invention will be explained in more detail below with reference to the accompanying drawings. Show it :

1a and 1b schematically show a cross section and a full view of a pipette tip according to the invention;

FIG. 2 shows a schematic representation of an exemplary embodiment of a pipetting device according to the invention; FIG.

3a and 3b are schematic representations of a pipette tip with an actuating device for dosing;

Fig. 4a to 4c are schematic cross-sectional views for explaining different operating phases of the actuator shown in Figs. 3a and 3b;

Fig. 5 schematically shows a conventional hand pipette;

6 shows schematically a movable holder of a conventional automatic pipetting device; and

Fig. 7a to 7c are schematic representations for explaining a preferred dosing method used according to the invention.

Schematic representations of an embodiment of a pipette tip 100 according to the invention are shown in FIGS. Ia and Ib shown. The pipette tip 100 includes a rigid pipette tip body 101 and an elastic tube 102 attached to a portion 104 on the pipette tip body 101. The pipette tip 100 includes a first end 106 formed by the rigid pipette tip body 101 and adapted to be removably attached to a pipetting machine or a hand-held pipette. te to be attached. The first end 106 includes a fluid port 106a fluidly connected to a fluid chamber 108 in the micropipette. The interior of the tube 102 is also fluidly connected to the fluid chamber 108. The elastic tube is disposed at a second end 110 of the pipette tip and has a mouth or fluid opening 112 through which liquid can enter and exit.

The pipette tip body 101 may be made of the same material as conventional pipette tips, while the elastic tube 102 is preferably formed of an elastically deformable polymer material. Under elastic hose or pipe is understood to mean a fluid line, which after a deformation, for. B. by squeezing, due to the elasticity of their material returns to its original form. The dimensions of the tube are preferably such that liquid in the pipette tip can be held by the capillary action therein and the surface tensions at the orifice 112 so that the liquid can be stored in the pipette tip.

A schematic representation of an embodiment of a pipetting device according to the invention is shown in FIG. 2. The pipetting device comprises a pipetting unit 120, which has a coupling device 122 on which a pipette tip 100, for example such as was explained above with reference to FIGS. 1 a and 1 b, can be interchangeably attached. The pipetting unit can be constructed, for example, comparable to the movable holder of a conventional automatic pipetting device. A positioning device 126 is provided, by means of which the pipetting unit 120 with the pipette tip 100 mounted thereon can be moved between different operating positions. The pipetting unit further has a pressure generating device 128 in order to generate a negative pressure in the fluid chamber of the pipette tip 100. to thereby draw liquid through the orifice 112 into the pipette tip 100. In addition, the pressure-generating device can also be designed such that the pipette tip can be acted upon if necessary with an overpressure to z. B. To expel fluid in the conventional method of air cushion pipettes pressure driven. A controller 130 is provided and connected to the positioning means 126 and the pressure generating means 128 to control the operation thereof.

Furthermore, the pipetting device according to the invention has, in addition to the pressure-generating device, an actuating device or actuator. Drive means 132 to eject liquid from the elastic tube of the pipette tip 100. The controller 130 is also connected to the actuator 132 to control the operation thereof.

A complete pipetting cycle using a pipetting device as described above with reference to FIG. 2, for example, may look like this.

First, the pipette tip 100 is received from a carrier (carrier) using the pipetting unit 120 and in particular the coupling device 122. Such a recording can proceed in accordance with conventional recording methods provided by conventional pipetting automata. After receiving the pipette tip, the pipetting unit 120 is moved by use of the positioning device 126 to immerse the elastic tube of the pipette tip in the liquid. By means of a negative pressure, which is provided by the pressure generating device 128 as in conventional automatic pipetting, the liquid is drawn through the tube into the pipette tip. After completion of the Aspirier process, the dosing unit is moved together with the pipette tip by the positioning device 126 to the delivery point, d. H . to the position where the elastic tube can be actuated by the actuator 132. To- Subsequently, the actuator 132 is actuated to squeeze the elastic tube to expel one or more liquid as a droplet or as a free-flying jet from the mouth of the elastic tube. In this case, the hose and actuating device are preferably designed to discharge a metering of liquid volumes in the nanoliter range, for example between 0.1 and 100 nL per metering operation. In this case, several dosing operations to different destinations or. take place in different vessels from the same pipette tip. After completion of the dosing processes in the nanoliter range, a volume of liquid possibly remaining in the pipette tip can be ejected in pressure-driven manner by air-cushion pipettes in order to completely empty the pipette tip and, if necessary, recover valuable liquid.

After completion of the metering or metering operations, the metering unit can be moved using the positioning device 126 to a storage container where the pipette tip can be detached from the pipetting unit and coupler 122 and into the storage container using an ejection mechanism that may correspond to that of conventional automatic pipetting machines is given.

The positioning device, as will be apparent to one skilled in the art, may suitably include drive mechanisms, which may include motors and gears, to effectuate the desired movements of the dosing unit 120. The controller 130 may in any suitable manner, for example by using a microprocessor, be adapted to the positioning means 126 to control the pressure-generating device 128 and the ^'actuator 132nd An exemplary embodiment of the actuator 132 will be described below with reference to FIGS. 3 and 4 explained in more detail.

For the sake of clarity, only the pipette tip 100 and the sections of the actuating device 132 required for explanation are shown in FIGS. 3a and 3b. Furthermore, in FIGS. 3a and 3b, respective elements are shown at least partially transparent in order to simplify the explanation.

As can be seen from FIGS. 3 a, 3 b and 4 a to 4 c, the actuating device comprises a first clamping jaw 134, a second clamping jaw 136 and an actuating member 138. The clamping jaws 134 and 136 are mounted via slide rails 140, 142, wherein a suitable drive mechanism 143 (shown schematically in FIG. 4b) to move the jaws 134, 136 relative to one another along the rails 140, 142. For the actuator 138, which may also be referred to as a plunger or actuator, a suitable drive mechanism 144 (Figure 4b) is also provided by which the actuator 138 can be moved substantially parallel to the tracks 140 and 142. Furthermore, in the exemplary embodiment shown, a centering aid device 145 is provided which simplifies centering of the pipette tip 100 relative to the actuating device 132. The centering aid device 145 in this case comprises a block in which a recess 146 is formed whose shape is adapted to the outer contour of the pipette tip body 101. By inserting the pipette tip, as shown in FIG. 3a, the tube 102 thereof is thus automatically centered with respect to the actuator 132. This condition is shown in FIG. 3b and the enlarged view of Fig. 4a.

After this centering of the pipette tip, and thus of the elastic tube 102 thereof, the jaws 134 and 136 are rotated using the drive mechanism 143 closed, so that the elastic tube 102 is fixed between them. For this purpose, as best seen in Figs. 3b and 4a, the jaws 134 and 136 preferably have recesses 150 which conform to the shape of the flexible tube 102 to assist in secure fixation of the flexible tube. As further best seen in FIG. 3b, the jaw 136 includes a through opening through which the actuator 138 extends. The recesses 150 may preferably be formed such that they rest flat against the tube and surround it, so that the tube is securely fixed in the areas surrounding the actuator 138.

Figures 4a to 4c illustrate cross-sectional views with a section axis passing centrally through the recesses 150 in the jaws 134 and 136.

Fig. Figure 4b shows the actuator after the jaws 134 and 136 are automatically closed. After closing the jaws, the actuator 138 is driven up by the drive mechanism 144 through the opening of the jaw 136 provided therefor to reduce the volume of the elastic tube 102 thereby To eject liquid as a free-flowing droplet or as a free-flowing jet from the mouth 112 of the elastic tube 102. The jaw 134 acts as a counter holding element. The phase in which the volume of the tube is reduced is shown in Fig. 4c. In the position shown in FIG. 4b, the jaw 136 and actuator 138 are preferably moved together, whereupon the actuator is actuated to the position shown in FIG. 4c.

It should be noted at this point that FIGS. 3a to 4c are purely schematic in this respect, wherein the actuating member and the counter-holding element may be shaped in a suitable manner so as to cause only a partial squeezing of the sleeve. ches or even a complete squeezing of the hose to allow. In this regard, it should further be noted that the stroke of the drive means 144 of the actuator 138 may be adjustable so that by adjusting the stroke, different drop volumes may be expelled from the mouth 112 of the flexible tube 102. With regard to the ejection method, reference is again made to the above description of FIGS. 7a to 1c and also to the German application 10337484.1.

In the described embodiment, a centering auxiliary device 145 is provided to center the pipette tip in the actuator 132. It will be apparent to those skilled in the art that such a centering aid is optional, for example if a sufficiently accurate positioning device is provided for the pipetting unit. For example, the jaws may be closed using an electromagnetic drive to fix the flexible hose. The actuator may be electromagnetically or piezoelectrically driven to provide the desired nanoliter dosage. Optionally, multiple dosing may optionally be done to different targets or into different vessels. After the dosing process, the jaws can be opened and the pipette tip can be removed by a conventional automatic pipetting machine with a corresponding mechanism. The pipette tips may be dispensed in a waste box or in a storage carrier by means of an ejector mechanism (not shown) located in the pipetting machine. When stored in a bearing carrier, the dosing cycle can be resumed with the movement of the pipette tip to the dispensing position later. As an alternative to the method described above, the pipette tip can also be deposited in a bearing carrier immediately after aspiration and can only be removed again at a later time in order to carry out a dispensing of a volume of the aspirated liquid. In preferred embodiments of the pipetting device according to the invention, during centering, closing, dosing and opening, the nozzle opening has no contact whatsoever with the actuating device (drive unit) so that carry-over of the liquid is prevented. The pipette tips may also be dispensed by the pipetting unit (eg, 120 in Fig. 2) to the actuator that includes the fixation device so that fluid delivery may occur at a location other than the receptacle, with the pipette tip not communicating with the pipette unit for fluid delivery or the automatic vending machine must be coupled. As a result, the automatic petting machine or the pipetting unit can be used elsewhere during dosing by the actuating device for ejecting a liquid from the hose. By juxtaposing several drive units, which are driven either by individual or by a common actuator, a parallelization is very easy to achieve. In this regard, an actuator driven by a corresponding drive mechanism may be configured to simultaneously actuate a plurality of flexible hoses. On the other hand, a plurality of separate actuators may be provided, which can be actuated by a common drive unit or separately controllable drive units.

As explained above, the present invention provides a novel pipetting device or components for a pipetting device. In this regard, a conventional Pipetierautomat be used together with inventive pipette tips and an actuator according to the invention for such pipette tips.

Alternatively, it is also possible to use the pipette tips according to the invention without the actuating device according to the invention. In this case, the dispensing can by conventional methods, such. B. air-pressure pipettes are pressure-driven.

Claims

claims 1. Changeable pipette tip (100) with the following features: a first end (106) having a fluid port (106a); and a second end (110) having a radially elastic tube (102) with an orifice (112), the resilient tube being configured to be substantially rigid with respect to deflections along the tube axis but flexible and flexible; behaves radially with respect to radial deformations, wherein the mouth (112) and the fluid port (106a) are in fluid communication, and wherein the first end (106) is adapted to be coupled to a mating coupling device (122) of a pipetting device (120), such that liquid flows through the orifice (112) through an actuator in the pipetting device (120). in the fluid region (108) is sucked. The replaceable pipette tip (100) of claim 1, wherein the first end (106) is adapted to be coupled to a mating coupling device (122) of a potting device (120) such that the fluid region (108) in the Pipette tip (100) is fluidly coupled to a fluid region in the pipetting device (120). 3. An exchangeable pipette tip according to claim 1 or 2, wherein the first end (106) is adapted to be coupled to a coupling device (122) of a pipetting machine. 4. changeable pipette tip according to one of claims 1 to 3, wherein the elastic in the radial direction of the tube has an inner diameter, which allows an autonomous capillary filling thereof. 5. An exchangeable pipette tip according to any one of claims 1 to 4, wherein the pipette tip has a rigid portion (101) surrounding the first end (106), the radially elastic tube (102) being at a first end opposite end of the rigid portion (101) is attached thereto. 6. changeable pipette tip according to one of claims 1 to 5, wherein the elastic in the radial direction tube has a substantially constant cross-section. 7. changeable pipette tip according to one of claims 1 to 5, wherein the elastic in the radial direction tube has a substantially non-constant cross-section. 8. changeable pipette tip according to one of claims 1 to 7, wherein the elastic in the radial direction tube has a circular cross-section. 9. changeable pipette tip according to one of claims 1 to 7, wherein the elastic in the radial direction tube has a non-circular cross-section. 10. Pipetting device with the following features: a coupling device (122) for coupling to a pipette tip (100) having a first end (106) with a fluid port (106a) and a second end (110) having a radially elastic tube (102) with an orifice (112 ), wherein the The mouth (112) and the fluid port (106a) are in fluid communication, and wherein the first end (106) is adapted to be coupled to the coupler (122); a first actuator (128) for generating a negative pressure at the fluid port (106a) at the first end (106) of the pipette tip (100) to draw fluid through the mouth (112) of the radially elastic tube (102); and a second actuator (132) for temporally varying the volume of a portion of the radially elastic tube (102) to thereby expel liquid as a droplet or free-flying jet from the mouth (112) of the radially elastic tube (102). 11. The pipetting device of claim 10, wherein the second actuator (132) comprises an actuator (138) and a counter-holding member (134), the actuator (138) being operable to move, by movement toward the counter-holding member (134), the volume the portion of the radially elastic tube (102) to change. The pipetting device of claim 11, further comprising a controller (130) configured to control the distance that the actuator (138) moves, thereby to increase the volume of liquid flowing out of the mouth (112 ) is set. 13. The pipetting device according to claim 11 or 12, wherein the counter-holding element (134) is a first jaw of a fixing device, wherein the fixing device further comprises a second clamping jaw (136), wherein the first and the second clamping jaw (134, 136) are adapted to fix the radially elastic tube (102). 14. The pipetting device of claim 13, wherein the first and second jaws (134, 136) have concave surface portions (134, 136) that conform to the convex outer shape of the radially elastic tube to be radially elastic Pick up and fix tube. The pipetting device of any one of claims 10 to 14, further comprising positioning means (126) adapted to position the pipette tip (100) for aspiration of liquid at a first position and to eject liquid at a second position position. 16. A pipetting device according to claim 15, wherein the pipette tip (100) has a rigid portion (101) on which the radially elastic tube (102) is mounted, wherein the positioning means further comprises a guide means (145) having a Contour adapted to the contour of the rigid portion (101) of the pipette tip (100) to assist in positioning the pipette tip with respect to the second actuator. The pipetting device of any one of claims 10 to 16, wherein the radially elastic tube (102) and the second actuator (132) are arranged to change a volume of liquid in the range between 0.1 nL and 100 nL by varying the volume eject. 18. A pipette tip actuator (132) for a pipetting device comprising a pipette tip (100) having a first end (106) with a fluid port (106a) and a second end (110), said second end (110) having a radially elastic tube (102) with an orifice (112), said fluid orifice (106a) and said orifice (112) being in fluid communication - binding, with the following characteristics: a fixing device (134, 136) having a first state in which the radially elastic tube (102) is fixed at a predetermined position and a second state in which the radially elastic tube (102) is not fixed; fixing means driving means (143) for changing the state of the fixing means; and an actuator for temporally varying the volume of a portion of the radially elastic tube (102) to thereby expel liquid as a droplet or free-flying jet from the mouth (112) of the radially elastic tube (102) when the fixing means in the first condition is. The pipette tip actuator of claim 18, further comprising guide means (145) having a contour conforming to the contour of a rigid portion (101) of the pipette tip (100) to allow engagement of the rigid portion (101). the pipette tip (100) to assist in positioning the pipette tip (100) at the predetermined position. 20. A pipette tip actuator according to claim 18 or 19, wherein the fixing means comprises two jaws (134, 136) for clamping the radially elastic tube (102), the fixation device driving means (143) being extended. is set to move the jaws (134, 136) relative to each other. 21. pipette tip actuator according to claim 20, wherein a jaw serves as a counter-holding element (134) for the actuating device. A method of pipetting liquid using a pipette tip (100) having a first end (106) with a fluid port (106a) and a second end (110), the second end (110) being a radially elastic tube (102) having an orifice (112), said fluid orifice (106a) and said orifice (112) being in fluid communication, comprising the steps of: Filling the pipette tip (100) by immersing the mouth (112) of the radially elastic tube (102) in a liquid and creating a negative pressure at the fluid opening (106a) of the first end (106) of the pipette tip (100); and Effecting a volume change of a portion of the radially elastic tube (102) to expel liquid as free-flying droplets or as a jet from the mouth (112) of the radially elastic tube (102) by the volume change. The method of claim 22, further comprising a step of fixing the radially elastic tube (102) using a fixing means (134, 136) while effecting the volume change. 24. The method of claim 22 or 23, further comprising a step of moving the pipette tip (100) from a filling position to an ejection position prior to the step of effecting the volume change.