AUTOMATIC PIPETTERING DEVICE FOR SAMPLE AND / OR REAGENT TRANSFER AND METHOD FOR TRANSFERRING LIQUID SAMPLES AND / OR REAGENTS

Description

[0001] The invention relates to an automatic pipetting device suitable for transferring samples and / or reagents from sample and / or reagent containers into at least one receiving vessel, for example, of an analyzer intended for the analysis of liquid samples. The pipetting device has a movable pipette gate that is travelable along an x-direction and comprises at least one first pipetting needle that is travelable along a horizontal arm of the pipette gate along a y-direction that is essentially perpendicular to the x-direction and that can be lowered into the individual containers in the z-direction. The invention further relates to a method for transferring liquid samples and / or reagents from sample and / or reagent containers into at least one receiving vessel of an automatic pipetting device.

[0002] Pipetting machines or pipetting devices for transferring defined quantities of liquid between different liquid containers arranged in a grid pattern on a surface are known from the prior art. For example, physical, chemical, or biological liquid samples can be treated with specific reagents or diluents as part of sample preparation for the measurement of chemical-physical parameters in an analytical instrument. These machines have one or more pipetting units with an associated pipetting needle for dispensing and receiving liquid. These needles are movable in one or more horizontal directions relative to the surface on which the liquid containers are located and can be lowered into the liquid containers. Additionally, needle washing devices are required to prevent the carryover of residual liquid substances adhering to the needles into other containers.In addition to precise liquid dosing, the design of pipetting machines always aims to achieve the largest possible number of pipetting operations per unit of time (high throughput).

[0003] For a better understanding of the invention, some essential technical terms used in the present application are defined in more detail: Pipetting unit:

[0004] Refers to the complete system of an automatic pipetting device for transferring liquids between different vessels, which includes one or more movable pipettes along with all mobile and stationary components necessary for their function, including supply fluids (hose connections, pumps, valves, containers, etc.), sensors, control and power supply. Pipettor:

[0005] Describes a component of the pipetting unit that is horizontally movable or pivotable in at least one direction relative to the receiving vessels (sample vessels, reagent vessels, reaction vessels, or cuvettes). The pipettor includes a suspension component with at least one pipetting needle, which is designed to be lowered into the aforementioned vessels, either alone or together with the pipettor. Pipette needle:

[0006] Refers to a cannula or hollow needle attached to the pipette, including its holder with connection elements for fluidics, for aspirating samples from the sample containers and / or for aspirating reagents from the reagent containers, as well as for metered dispensing of the aspirated liquids into the receiving containers or cuvettes. Reagent tube:

[0007] Vessel or container for holding reagents required for carrying out the analysis. Sample container:

[0008] A vessel or container that holds the analytical sample in the analyzer, from which multiple smaller sample volumes (aliquots) can be taken for the analysis of individual analytes or parameters. The analysis itself does not take place in the vessel containing the analytical sample, but rather in the cuvette after the reagents have been added; in this sense, the cuvette serves as the reaction vessel.

[0009] From EP 1 230 553 B1 (MAXMAT), a chemical or biological analyzer is known in this context, comprising a storage module for sample tubes and tubes for reagents. Furthermore, an analysis module with a reaction vessel in the form of a microtiter plate is provided, as well as a rail-mounted sampling module (pipette gate) with two pipetting needles arranged at a fixed distance from each other. These needles operate independently of each other in the z-direction for automated sample extraction and are each equipped with a retractable suction pipette for transferring predetermined quantities of samples and reagents from the storage module to the analysis module. In the horizontal x / y plane, the two pipetting needles can only be moved together.

[0010] The analysis module features a heating plate for the microtiter plate, positioned near the lower part of the wells to heat the contents by convection. The sampling unit also includes a mixing device controlled by an electromagnet to cause the pipetting needle to move back and forth when lowered into a well of the microtiter plate, thus mixing the sample and reagent mixture.

[0011] Furthermore, EP 2 410 342 A2 (HOFFMANN-LA ROCHE) discloses a pipetting device comprising a pipettor with several flat, adjacent frame elements, whose pipetting needles are movable together on a main frame body in a horizontal x-direction perpendicular to the main frame body. The pipetting device serves to transfer samples or reagents from a first row of vessels to a second row of vessels offset in the x-direction. The pipetting needles are first adjusted in the y-direction to the spacing of the vessels in the first row to receive sample or reagent liquid, and then adjusted to the spacing of the second row of vessels to dispense the sample or reagent liquid. However, independent movement of two pipetting needles in the x- and y-directions is not provided.Traverse modules for the y-direction and the z-direction (raising and lowering the pipetting needles) are arranged in flat, adjacent frame elements with gaps between them to minimize the distance between the individual pipetting needles. However, independent movement of the pipetting needles in the y-direction is limited. For example, the frame elements cannot pass each other on the transfer arm, resulting in a mutual restriction of the y-direction movement of the pipetting needles. Such pipetting devices are particularly useful in conjunction with microtiter plates.

[0012] Finally, US 5,897,837 A (TOA MEDICAL) describes an automatic pipetting device or pipetting robot for sample pretreatment in an immunoassay analyzer. As in Fig. 1As shown in the present application, the pipetting machine 10 has a first pipetting gate 20, which is horizontally movable in the x and y directions and is equipped with two pipetting needles 11 and 12 that can be lowered or raised vertically independently of each other. Reagents can be assigned to one of the two needles 11, while samples arranged in different sections 14 to 19 of a table plane 23 can be assigned to the other needle 12. Additionally, a second pipetting gate 21, movable in the xy direction, with a lowerable pipetting needle 13 is also provided.

[0013] The first, horizontally movable pipettor 20 carries a needle washing unit 22, which can be moved horizontally back and forth between the vertical lowering paths of the two pipetting needles 11, 12. This allows one of the two needles to be cleaned alternately while the other needle performs a pipetting operation. The two pipetting needles 11, 12 of the first pipettor 20 can only be moved together in the x or y direction.

[0014] This has the disadvantage that the masses of the robotic components of the pipettor 20 cannot be distributed across the two horizontal axes x and y, meaning that the mass of the second pipetting unit must always be accelerated when moving to positions in the y-direction. Similarly, the mass of the needle washing unit 22, including the needle washing vessel, must also be accelerated in both horizontal directions. Furthermore, due to the shared horizontal movement, it is not possible, for example, to use both needles 11 and 12 simultaneously for pipetting on different rows of vessels that are not adjacent in the x-direction.

[0015] From WO 2011 / 119441 A1 (BIONEX SOLUTIONS) a transfer and testing device for materials is known, which is equipped with independently movable carrier and receiver devices. The carrier devices, which are movable in the X and Z directions and have hollow needles, are suspended from the underside of a stationary beam structure, which is supported at both ends of the device. The receiver devices are movable in the Y direction and rotatable in the X / Y plane and are equipped, for example, with microplates into whose wells sample materials can be transferred. The combined translational and rotational movement of the carrier and receiver devices allows the travel distances to be minimized.

[0016] German patent DE 10 2005 049 920 A1 (MANZ AUTOMATION) discloses a robot arrangement for the life sciences sector, comprising at least a first robot module with an X-axis arm on which at least one horizontally oriented Y-axis arm is arranged to be movable in the x-direction. A coupling device for attaching a pipetting module, movable in the y-direction, is provided on the Y-axis arm. According to one variant, shown in Fig. 3 , several identical robot modules can be arranged in the x-direction, wherein a first arm movable in the x-direction is equipped with a pipetting module movable in the y-direction and a second such arm has a gripping device.

[0017] EP 0 601 213 A1 (HAMILTON BONADUZ) presents an alternative concept for achieving x, y, z mobility of two pipettes. The pipettes are suspended by three magnetic elements from the underside of a support plate projecting over an arrangement of sample and reagent vessels and are supported on the support plate by three spherical bearings. The x / y movement is achieved via an electrically driven central sphere of each pipette.

[0018] The object of the invention is to significantly reduce the average duration of pipetting operations in a pipetting machine or a pipetting device, and thus to achieve the greatest possible throughput, especially in pipetting tasks where the type and quantity of dispensed reagents and samples constantly changes between individual pipetting operations.

[0019] This problem is solved according to the invention by attaching the horizontal arm of the movable pipettor to a vertical tower, which is movable by means of a movable mount on a rail extending in the x-direction, wherein the horizontal arm has at least a second pipetting needle which is movable past each other and lowerable into the individual vessels independently of the current position of the first pipetting needle, and wherein the two independently movable pipetting needles are arranged on opposite longitudinal sides or side surfaces of the arm of the pipettor.

[0020] The travel distance available on the arm of the pipettor for each pipetting needle can therefore be fully utilized – regardless of the position of the other pipettor.

[0021] The inventive method for transferring liquid samples and / or reagents from sample and / or reagent containers into at least one receiving container of an automatic pipetting device, with a pipette that can be moved horizontally along a first direction, is characterized by the following steps: Procedure of a first pipetting needle of the pipettor along a horizontal second direction, substantially perpendicular to the first direction, for transferring a predetermined quantity of a liquid sample or reagent from a sample or reagent vessel into the receiving vessel; lowering the first pipetting needle into the sample or reagent vessel, aspirating a predetermined quantity of sample or reagent liquid, and proceeding the first pipetting needle to the position of the receiving vessel; dispensing the predetermined quantity of sample or reagent liquid into the receiving vessel; and proceeding a second pipetting needle of the same pipettor in the second direction, irrespective of the current position of the first pipetting needle, for the simultaneous performance of additional pipetting tasks.

[0022] This results in increased throughput because the two pipetting needles can pass each other unimpeded. For example, the first pipetting needle can pipette samples while the second pipetting needle simultaneously and independently pipettes reagents, or a second type of sample or reagent can be pipetted. Furthermore, a sample can be divided between the two pipetting needles and then simultaneously pipetted into two different, non-adjacent vessels, freely selectable in the y-direction.

[0023] One embodiment of the invention provides that the pipettor of the pipetting device has different pipetting needles, wherein the pipetting needles each have hollow needles or cannulas that differ in the type of materials used, the internal volumes and / or the geometry of the hollow needles or cannulas.

[0024] For certain pipetting tasks requiring the use of two different types of pipetting needles, it can be advantageous to use two different pipetting needles on the same pipette. For example, one of the pipetting needles attached to the pipette can have a particularly small internal volume of the hollow needle in the microliter range to increase precision, while the second hollow needle has a correspondingly larger internal volume for dispensing larger volumes. In a further embodiment of the invention, one of the hollow needles can be made at least partially of a different material (for example, a corrosion-resistant alloy, plastic, or steel), or, for example, coated with hydrophobic or hydrophilic substances on the inside and / or outside of the hollow needle to control the wetting.The needles can also differ in other modifications, not necessarily limited to surfaces in contact with the medium, such as conductive needle components, sensors, heating or cooling devices that are part of the hollow needle or in contact with it. The second needle can also differ in its geometry; for example, it may have a different tip angle to facilitate droplet detachment, or a different length or diameter to better suit specific pipetting tasks.

[0025] Thus, by using different pipetting needles that can be moved independently in the y-direction on one and the same pipetting device, a wide variety of pipetting tasks can be performed without the need for an additional pipetting device or a needle exchange station. Furthermore, unlike when using a second pipetting device, a collision between two pipetting needles during operation is not possible, which simplifies the travel paths and control of the pipetting device.

[0026] Regardless of the type of pipetting task, a further increase in throughput is achieved if the pipetting device's pipettor includes at least one needle washing unit that moves with the pipettor for the first and second pipetting needles. For example, one pipetting operation can be performed while the second pipetting needle is being cleaned simultaneously. The pipettor's configuration is characterized by the fact that the y-movement of each pipetting needle is possible without the mass of the needle washing unit being moved along with the pipettor, allowing both pipetting needles to be accelerated and decelerated much more quickly in the y-direction.

[0027] It is particularly advantageous to carry a separate needle washing unit for each of the two pipetting needles.

[0028] According to another preferred embodiment of the pipettor, the first and second pipetting needles are designed to be movable essentially parallel to each other, at least in certain sections of the pipettor arm. This configuration offers the advantage of greater precision when approaching a horizontally located stopping point (e.g., a liquid container), as the guide rails for the pipetting needles, which are attached to the lateral surface of the pipettor arm (e.g., made of sheet metal or metal profiles), can be better aligned and supported. Furthermore, the guide rails act as bracing elements and, by increasing the stiffness of the pipettor arm, have a beneficial effect on the pipettor's acceleration capability in the x-direction.

[0029] Since the two independently movable pipetting needles are arranged on opposite longitudinal sides or lateral surfaces of the pipettor arm, unimpeded movement of the pipetting needles is possible along the entire length of the arm and the working surface. Furthermore, the rigidity of the arm is increased, allowing it to be made thinner and lighter.

[0030] Further advantages of lateral mounting of the two pipetting needles include the ability to design a more compact automatic pipetting device, with a width that does not exceed the overall length of the horizontal arm. Additionally, the energy chains required to supply the pipetting needles can be easily routed along the top of the arm, providing more space for the fluidic tubing, particularly if it allows for unimpeded upward loops during the pipetting needle's stroke.

[0031] According to one embodiment of the invention, at least one side of the arm of the pipettor has two pipetting needles that can be moved together connected via a lifting mechanism such that the two pipetting needles can be moved in opposite directions or antiparallel in the z-direction.

[0032] Since the horizontal arm of the pipettor is attached to a vertical tower, which is mounted on a rail extending in the x-direction and thus movable, the x-direction rail can, for example, be attached to the transverse supports of a work surface of the pipetting device. This allows for smaller tolerances of the pipettor suspension compared to a conventional gantry suspension. Furthermore, this configuration enables short hose and supply lines to the x-direction pipettor, which has a beneficial effect on pipetting accuracy and the overall mass of the pipettor that needs to be moved.

[0033] According to another advantageous embodiment of the pipetting device, the pipettor with its vertical tower and horizontal arm has an essentially L-shaped basic structure, whereby on the one hand the working surface is not interrupted by the width of the x-direction running rail of the pipettor, and on the other hand a part of the travel paths in the y-direction is considerably shortened.

[0034] The acceleration capability of the pipettor in the x-direction can be significantly increased by a further design variant in which the pipettor, with its vertical tower and horizontal arm, has an essentially T-shaped basic structure. This adds another plane of symmetry to the pipettor's basic structure and allows for a further increase in its rigidity. The tower and arm of the pipettor can be made with a further reduced material thickness, resulting in a lower mass and thus improved acceleration and deceleration.

[0035] The invention is explained in more detail below with reference to partially schematic embodiments. The figures show: Fig. 1 shows an automatic pipetting device for sample and reagent transfer according to the prior art in a three-dimensional view, Fig. 2 shows an automatic pipetting device according to the invention for sample and reagent transfer in a three-dimensional view, Fig. 3 shows a variant of the automatic pipetting device according to the invention. Fig. 2 , Fig. 4 a needle washing unit of the automatic pipetting device according to Fig. 2 and 3 In an enlarged sectional view, Fig. 5, fluidic elements of a pipetting needle of a pipettor according to Fig. 2 or 3 In a schematic representation, Fig. 6, fluidic elements of the needle washing unit according to Fig. 4 in a schematic representation, as well as Fig. 7 a detail of an embodiment of the automatic pipetting device according to the invention. Fig. 2 .

[0036] Functionally identical parts are provided with the same reference numerals in the different versions.

[0037] The in Fig. 1 The automatic pipetting device shown is already described in detail in the introductory description (see US 5,897,837 A).

[0038] The in Fig. 2 The illustrated pipetting device according to the invention serves for the sample transfer from sample vessels 921, which are located in a sample holder 920 on a table surface 114, and for the reagent transfer from different reagent vessels 951a, 951b, which are located in reagent holders 950a, 950b, into at least one receiving vessel 201, for example a reaction vessel or a cuvette of an analyzer for the analysis of liquid samples or a microtiter plate. Several receiving vessels 201 can be arranged in a row as a linear array, or also as a 2D array, for example in the form of a microtiter plate.

[0039] A movable pipette 300a of the pipetting device is horizontally movable along a first direction (x-direction) and has a first pipetting needle 301a1 with a cannula or hollow needle 307, which is horizontally movable along an arm 304a of the pipette 300a along a second direction (y-direction) that is essentially perpendicular to the x-direction and can be lowered vertically into the individual vessels in the z-direction. According to the invention, the arm 304a of the movable pipette 300a has a second pipetting needle 301a2 with a cannula or hollow needle 307, which is movable in the y-direction independently of the current position of the first pipetting needle 301a1 and can be lowered into the individual vessels 921, 951a, 951b and 201. The second pipetting needle 301a2 can pass the first pipetting needle 301a1 unhindered, so that both pipetting needles have the entire travel distance along the arm 304a available at all times.

[0040] To simplify the presentation in Fig. 2 Only those components of the automatic pipetting device that are essential for the invention are shown, while further components of the pipetting device, such as pumps, valves, control and drive units, which are preferably arranged below the table surface 114 aligned parallel to the x / y plane, are not discussed in detail here.

[0041] In the illustrated example, the pipettor 300a of the pipetting device has two needle washing units 700a1, 700a2 which can be moved with the pipettor 300a, one each for the hollow needle 307 of the first pipetting needle 301a1 and the second pipetting needle 301a2.

[0042] The first and second pipetting needles 301a1, 301a2 are designed to be movable essentially parallel to each other, at least in partial areas, preferably in all areas, of the arm 304a of the pipettor 300a, wherein the two pipetting needles are preferably arranged on opposite longitudinal sides of the arm 304a of the pipettor 300a.

[0043] In the version according to Fig. 2 The pipettor 300a, with its vertical tower 303a and horizontal arm 304a, has an essentially L-shaped basic structure, wherein the pipettor is movable laterally along the arrangement of the individual vessels 921, 951a, 951b, 201 of the sample storage 920, the two reagent storages 950a, 950b and the arrangement of the receiving vessels 201.

[0044] For guiding fluid lines and any electrical supply and signal lines in the y-direction, the two pipetting needles 301a1, 301a2 have retractable energy chains 311a1, 311a2. For guiding in the x-direction, a retractable energy chain 310a is provided for this purpose.

[0045] In Fig. 3 As an embodiment of the pipetting device according to the invention, a movable pipetting device 300b is shown, which, with its vertical tower 303b and horizontal arm 304b, has a substantially T-shaped basic structure, so that vessels 921, 951a, 951b, 201 can be arranged on both sides of the tower 303b. This pipetting device 300b also has two pipetting needles 301b1, 301b2 that are independently movable in the y-direction, as well as needle washing units 700b1, 700b2 that are movable with the pipetting device 300b.

[0046] In both versions, the horizontal arm 304a or 304b of the pipettor 300a or 300b is attached to a vertical tower 303a or 303b, which is fixed to a rail 111a or 111b running in the x-direction by means of a movable mount (not shown).

[0047] The two pipetting needles 301a1, 301a2 and 301b1, 301b2 are attached to the left and right of the arm 304a and 304b, respectively, by means of the y-direction movable mounts 305, allowing them to pass each other unimpeded. Each mount 305 has a downwardly projecting rail section 306, along which the needle can be lowered in the z-direction into the individual vessels 921, 951a, 951b, 201.

[0048] The rollable energy chains in the y-direction are designated here as 311b1, 311b2 and those in the x-direction as 310b.

[0049] The two pipettes 300a and 300b can also be used side by side on parallel rails 111a, 111b.

[0050] According to a Fig. 7 In the illustrated embodiment, instead of a single pipetting needle, a double pipetting needle can be arranged on at least one side of the arm 304a of the pipettor 300a on the y-direction movable receptacle 305, such that two pipetting needles 330, 331, which can be moved together, are connected via a lifting mechanism 332 that moves both pipetting needles 330, 331 in opposite directions or antiparallel in the z-direction. The two hollow needles 307 can be made of different materials and have different internal volumes, and are thus available for different tasks that can be performed without large travel distances of the pipettor 300a.

[0051] The downward-projecting rail section 306 has parallel rails for the two pipetting needles 330, 331, wherein the lifting mechanism 332 can essentially consist of a toothed belt 335 guided over deflection pulleys 333, 334, which engages the two pipetting needles 330, 331 and is driven by a toothed belt wheel 336.

[0052] Fig. 4 The enlarged sectional view shows the structure of a needle washing unit marked with the general reference number 700, which is essentially identical in construction to the one located at different positions in the Fig. 2 and 3 The needle washing units shown (700a1, 700a2, 700b1, 700b2) correspond to a pipetting needle marked with the general reference numeral 301, which is essentially identical in construction to the ones located at different positions in the Fig. 2 and 3The illustrated pipetting needles (301a1, 301a2, 301b1, 301b2) correspond to the hollow needle 307 of the pipetting needle 301. The hollow needle 307 of the pipetting needle 301 is inserted through a receiving opening 711 in the housing 710 of the needle washing unit 700. Simultaneously, the lumen of the needle is cleaned with a washing solution or the system fluid from the pressure transmission channel 712, and the outside of the needle is cleaned with a rinsing fluid 714 supplied via lateral cleaning nozzles 713 from an annular chamber 715. For internal and external cleaning of the hollow needle 307 by repeatedly aspirating and expelling washing solution from the lower part of the needle washing unit, washing solution can be supplied via a radial inlet 716 and subsequently emptied via a suction opening 717.

[0053] Fig. 5Figure 1 shows the fluidic circuit diagram of a pipetting needle 301, whose hollow needle 307 is connected via a pressure transmission channel 712 filled with a degassed liquid to a precision piston pump 325, preferably a positive displacement pump (dilutor) driven by a stepper motor. The positive displacement pump has an additional liquid connection on the side, which is connected via a solenoid valve 326 to a supply unit 320 for a system fluid. This supply unit delivers, for example, degassed, deionized water from a reservoir 322 via a flushing pump 321. The reservoir can be refilled or pressurized via a solenoid valve 323.

[0054] For the detection of disturbances, the pressure transmission channel 712 near the pipetting needle 301 has a further connection to a pressure sensor 324, which is connected to an evaluation and control unit not shown here, for example for the detection of blockages of the hollow needle 307. Description of a pipetting process

[0055] For the transfer of a defined quantity of liquid, for example with the pipetting needle 301a2 according to Fig. 2 The device is first moved horizontally towards a first vessel, 5 µL of air (spacer) is drawn into the tip of the hollow needle 307, and the pipetting needle 301a2 is lowered towards the liquid surface of the first vessel. To ensure a sufficient, but not excessive, immersion depth of the pipetting needle 301a2, the downward movement of the hollow needle 307 is stopped at a defined immersion depth by a signal from a liquid surface detection device (not shown), for example, with a capacitive detection principle. To aspirate a defined quantity of liquid with high accuracy in the µL range, the working piston is then moved downwards. Fig. 5The displacement pump (dilutor) shown creates a vacuum in the hollow needle 307 of the pipetting needle 301a2, which causes the aspiration of a corresponding volume of liquid from a first vessel. The pipetting needle 301a2, along with the aspirated liquid, which is separated from the system liquid by an air spacer, is then moved to a second vessel. The process then reverses, and the aspirated liquid is dispensed into the second vessel through the tip of the hollow needle 307. At least between two pipetting operations with different liquids, the pipetting needle 301a2 is always cleaned internally and externally in its needle washing unit 700a2. During the pipetting operation with the pipetting needle 301a2, the pipetting needle 301a1 can be cleaned and dried in its needle washing unit 700a1.

[0056] Fig. 6 The fluidic circuit diagram of a needle washing unit 700 is shown according to Fig. 4 , with the hollow needle 307 of the pipetting needle 301 lowered therein. The housing 710 of the needle washing unit has in the upper area a concentrically circumferential annular chamber 715, which serves as a media supply for several internal, concentrically aligned cleaning nozzles 713, and which are each connected via solenoid valves to a supply unit 719 for a rinsing liquid (for example, deionized water), and a supply unit 727 for dry air.

[0057] An inlet 716 arranged radially in the middle of the height of the housing 710 of the needle washing unit 700 is also connected to a solenoid valve and serves exclusively for the supply of surfactant-containing washing solution from a supply unit 723.

[0058] The supply units 719 for a rinsing fluid and 723 for a washing solution each have a pump 720, 724, which pumps the rinsing fluid or a surfactant-containing washing solution from the respective reservoirs 721, 725, which can each be refilled or pressurized via a solenoid valve 722, 726. The supply unit 727 for air has an air pump 728 for supplying compressed air and, if necessary, a drying tray (not shown).

[0059] The suction opening 717 located at the bottom of the needle washing unit 700 is connected via a solenoid valve 718 to the wastewater collection unit 729, which operates under negative pressure. The wastewater collection unit essentially consists of a collection tank 730, which has a connection in the gas space above the liquid to a vacuum pump 731. The vacuum pump is connected to the collection tank 730 via a solenoid valve. The collected wastewater can be discharged via a solenoid valve 732 at the bottom of the collection tank 730 and transferred to further wastewater treatment. Description of a needle washing process

[0060] In a typical washing process for the pipetting needle 301 (the same applies to all pipetting needles 301a1, 301a2, 301b1, 301b2), it is first moved horizontally to the needle washing unit 700 and lowered into the lower holding position of the washing chamber. All wastewater generated during the cleaning of the pipetting needle 301 is extracted via the suction opening 717 located at the bottom, collected, and, if necessary, further treated. Subsequently, via the in Fig. 5 The precision piston pump 325 shown in the illustration first empties and aspirates the residual amounts of the last pipetted liquid from the pipetting needle 301, which are located in and around the needle tip. Finally, the lowered pipetting needle 301 is pumped from behind by means of the Fig. 5 The depicted provision unit 320 for system fluid was flushed.

[0061] In the next step (with the solenoid valve 718 at the suction port 717 closed), a defined volume of surfactant-containing washing solution is introduced through the inlet 716 in the housing 710 of the needle washing unit 700, causing the chamber in the lower part to fill with a defined level of washing solution. The hollow needle 307 of the pipetting needle 301 is lowered until immersion in the washing solution allows for external wetting of the needle, and the suction of the washing solution into the needle results in internal wetting of the hollow needle 307. The aspirated washing solution is then expelled. This process of aspiration and expulsion can be repeated several times to improve the cleaning effect.

[0062] In a final step, the contaminated washing solution is extracted and the interior of the hollow needle 307 is rinsed with system water (e.g., degassed, deionized water), while the exterior of the hollow needle 307 is simultaneously rinsed with rinsing fluid from the supply unit 719 through the top, concentrically arranged cleaning nozzles 713, with the tip of the hollow needle 307 being moved from bottom to top to improve the cleaning effect.

[0063] After completion of the simultaneous internal and external rinsing, the hollow needle 307 is moved back to the lower holding position, the media supply of the cleaning nozzles 713 is switched to the compressed air supply unit 727, and the tip of the hollow needle 307 is moved again from bottom to top, allowing any adhering water droplets to be quickly removed from the needle surface. The pipetting needle 301 can now be moved out of the needle washing unit 700 and, after aspiration of a separation air spacer (5 µL), is ready for pipetting again. Examples:

[0064] The automatic pipetting device according to Fig. 2For example, it works as follows: In advance of a pipetting task, the control unit (not shown) of the pipetting device compiles all the data required for the transfer of the samples and reagents from known or previously entered information (transfer protocol, positions of vessels 921, 951a, 951b with the analytical samples and with the reagents required (e.g. for a subsequent analysis), positions of free receiving vessels 201, etc.).

[0065] The Pipettor 300a is first moved in the horizontal x-direction to the height of a sample or reagent vessel 921, 951a, 951b selected by the control unit.

[0066] Subsequently, the first pipetting needle 301a1 of the pipettor 300a moves along a horizontal y-direction, essentially perpendicular to the x-direction, to the selected sample or reagent vessel 921, 951a, 951b in order to transfer a predetermined amount of a liquid sample or reagent from a sample or reagent vessel into the receiving vessel 201 of the pipetting device.

[0067] The first pipetting needle 301a1 is now lowered in the z-direction into the sample or reagent vessel 921, 951a, 951b, whereby a quantity of sample or reagent liquid specified by the control device is drawn into the hollow needle 307 of the pipetting needle 301a1.

[0068] The first pipetting needle 301a1 is then moved to the position of the receiving vessel 201, with the pipettor 300a moving in the x-direction and the pipetting needle - guided on the horizontal arm 304a of the pipettor - simultaneously moving in the y-direction.

[0069] After reaching the position of the receiving vessel 201 and lowering the pipetting needle 301a1, the predetermined amount of sample or reagent fluid is dispensed into the receiving vessel 201.

[0070] During all the above-described actions of the first pipetting needle 301a1, the second pipetting needle 301a2 of the same pipettor 300a can be moved in the y-direction independently of the current position of the first pipetting needle 301a1 and used to perform additional pipetting tasks simultaneously.

[0071] The second pipetting needle 301a2 can pipette samples or reagents independently of the first pipetting needle, or it can be washed in the needle washing unit 700a2.

Claims

1. Automatic pipetting device, suitable for transferring samples and / or reagents from sample vessels (921) and / or reagent vessels (951a, 951b) into at least one receiving vessel (201), for example of an analyzer designed for analyzing liquid samples, wherein a pipettor (300a; 300b) of the pipetting device is designed to be movable along a first direction (x) and has at least one first pipetting needle (301a1, 301b1) which is designed to be movable along an arm (304a, 304b) of the pipettor (300a; 300b) along a y-direction, substantially normal to the x-direction, and is designed to be lowerable into the individual vessels along a z-direction, characterised in that the horizontal arm (304a; 304b) of the movable pipettor (300a; 300b) is attached to a vertical tower (303a; 303b) which is fastened by means of a movable mount to a rail (111a; 111b) extending in the x-direction, wherein the horizontal arm (304a; 304b) has at least one second pipetting needle (301a2; 301b2) which, regardless of the current position of the first pipetting needle (301a1, 301b1), is movable past the first pipetting needle and is lowerable into the individual vessels (921, 951a, 951b, 201), and wherein the two independently movable pipetting needles (301a1, 301a2, 301b1, 301b2) are arranged on opposite longitudinal sides or side faces of the arm (304a; 304b) of the pipettor (300a; 300b).

2. Pipetting device according to claim 1, characterised in that the pipettor (300a; 300b) of the pipetting device has different pipetting needles (301a1, 301a2, 301b1, 301b2), wherein the pipetting needles (301a1, 301a2, 301b1, 301b2) each have hollow needles (307) which differ in the type of materials used, the internal volumes and / or the geometry of the hollow needles (307).

3. Pipetting device according to claim 1 or 2, characterised in that the pipettor (300a; 300b) of the pipetting device comprises at least one needle washing unit (700a1, 700a2, 700b1, 700b2) for the first and the second pipetting needles (301a1, 301a2, 301b1, 301b2), which needle washing unit is movable with the pipettor (300a; 300b).

4. Pipetting device according to any one of claims 1 to 3, characterised in that the first and the second pipetting needles (301a1, 301a2, 301b1, 301b2) are designed to be movable substantially parallel to one another at least in partial regions of the arm (304a; 304b) of the pipettor (300a; 300b).

5. Pipetting device according to any one of claims 1 to 4, characterised in that, on at least one side of the arm (304a, 304b) of the pipettor (300a; 300b), two jointly movable pipetting needles (330, 331) are connected via a lifting mechanism (332) such that the two pipetting needles (330, 331) can be moved in opposite directions (in an antiparallel manner) in the z-direction.

6. Pipetting device according to any one of claims 1 to 5, characterised in that the pipettor (300a) with its vertical tower (303a) and the horizontal arm (304a) has a substantially L-shaped basic structure.

7. Pipetting device according to any one of claims 1 to 5, characterised in that the pipettor (300b) with its vertical tower (303b) and the horizontal arm (304b) has a substantially T-shaped basic structure.

8. Method for transferring liquid samples and / or reagents from sample vessels (921) and / or reagent vessels (951a, 951b) into at least one receiving vessel (201) of an automatic pipetting device, using a pipettor (300a, 300b) which is movable horizontally along a first direction (x), utilizing the device of claim 1, characterised by the following steps: a) moving a first pipetting needle (301a1, 301b1) of the pipettor (300a, 300b) along a horizontal second direction (y), substantially normal to the first direction (x), in order to transfer a predetermined quantity of a liquid sample or reagent from a sample vessel (921) or reagent vessel (951a, 951b) into the receiving vessel (201); b) lowering the first pipetting needle (301a1, 301b1) into the sample vessel (921) or reagent vessel (951a, 951b), c) taking up a predetermined quantity of sample liquid or reagent liquid and moving the first pipetting needle (301a1, 301b1) to the position of the receiving vessel (201); d) dispensing the predetermined quantity of sample liquid or reagent liquid into the receiving vessel (201); and e) moving a second pipetting needle (301a2, 301b2) of the same pipettor (300a, 300b) in the second direction (y), regardless of the current position of the first pipetting needle (301a1, 301a2), in order to simultaneously carry out additional pipetting tasks.