PIPETTING DEVICE AND METHOD FOR THE TRANSFER OF FLUIDS

Abstract

Various embodiments of the present disclosure are directed to an automatic pipetting system for transferring liquid from dispensing vessels into at least one receiving vessel. In one example embodiment, the system includes a movable pipettor moveable along an x-direction. The pipettor including an arm including two beams and a base structure, and at least one pipetting module. The base structure is movable in the x-direction, and is coupled to the two beams. The two beams oriented parallel to one another and project horizontally in the y-direction. The at least one pipetting module is moveable along each of the two beams in a y-direction and includes at least one hollow needle lowerable in to the dispensing vessels and the receiving vessels. Wherein the at least one pipetting modules move independently past one another on mutually facing longitudinal sides of said beams.

Claims

1. An automatic pipetting system for transferring liquids from dispensing vessels, into at least one receiving vessel, wherein the system comprises: a movable pipettor configured and arranged to be movable along an x-direction, and the movable pipettor includes an arm including two beams and a base structure, the base structure configured and arranged to be movable in the x-direction, the base structure coupled to the two beams, and the two beams are oriented parallel to one another and project horizontally in the y-direction, at least one pipetting module configured and arranged to be movable along each of the two beams in a y-direction, substantially normal to the x-direction, and the at least one pipetting module includes at least one hollow needle configured and arranged lowerable into the dispensing vessels and the receiving vessels, wherein the arm each of the at least one pipetting module are configured and arranged to move independently past one another, and are arranged on mutually facing longitudinal sides of said beams.

2. The pipetting system according to claim 1, wherein the two beams of the arm are connected at an end remote from the base structure thereby forming a frame structure.

3. The pipetting system according to claim 1, wherein the at least one hollow needles includes at least two hollow needles configured and arranged to move past one another with a minimal spacing from one another in the x-direction of 2 mm to 16 mm as said pipetting modules pass each other.

4. The pipetting system according to claim 1, wherein the pipettor includes, on an outer side of at least one of the beams, a mount configured and arranged to be movable in the y-direction and attaches to a working module.

5. The pipetting system according to claim 1, further including a sample and reagent deck having a work surface, and wherein the dispensing vessels are receiving vessels arranged preferably in predetermined areas on the work surface.

6. The pipetting system according to claim 1, further including a sample and reagent deck having a work surface, and wherein the dispensing vessels are sample vessels and/or reagent vessels held in interchangeable racks and/or cassettes and arranged below the work surface of the sample and reagent deck, wherein the work surface has through-openings for the hollow needles of the two pipetting modules, said through-openings corresponding to the positions of the sample vessels and/or reagent vessels.

7. The pipetting system according to claim 6, further including openable covers arranged in the work surface in proximity to at least one of the interchangeable racks and/or cassettes.

8. The pipetting system according to claim 6, further including at least one needle washing unit arranged below the work surface, and wherein the work surface of the sample and reagent deck has a slot-shaped opening along a row of receiving vessels, through which the at least one hollow needles is configured and arranged to be lowered into the at least one needle washing unit.

9. The pipetting system according to claim 1, wherein the movable pipetter comprises at least one pipetting module with different hollow needles which differ in the type of material used, the internal volumes and/or the geometry of the hollow needles.

10. The pipetting system according to claim 1, wherein the moveable pipettor further includes at least one needle washing unit configured and arranged to move synchronously with the pipettor.

11. The pipetting system according to claim 10, wherein the movable needle washing unit is arranged on a support structure which is attached to the movable base structure or to at least one of the beams of the arm.

12. The pipetting system according to claim 10, wherein characterized in that the needle washing unit includes a receiving opening configured and arranged to receive the hollow needle of a first one of the at least one pipetting module at the same time as the hollow needle of a second one of the at least one pipetting module.

13. The pipetting system according to claim 10, wherein the needle washing unit is configured and arranged to be movable or pivotable between a washing position for the hollow needle of one of the at least one pipetting modules and a washing position for the hollow needle of a second one of the at least one pipetting module.

14. The pipetting system according to claim 1, wherein the at least one a pipetting module having two jointly movable hollow needles arranged on at least one beam of the pipettor, said hollow needles being connected via a lifting mechanism such that the two hollow needles are configured and arranged to be movable antiparallel to a z-direction, substantially normal to the x-direction and the y-direction.

15. A method for transferring liquids from dispensing vessels into receiving vessels of an automatic pipetting system, the method including the following steps: moving a hollow needle of the pipetting module of the first beam of the pipettor in a travel position across a horizontal work surface to the predetermined x/y-position of the extraction opening of a dispensing vessel; lowering the hollow needle into the dispensing vessel, taking up a predetermined quantity of liquid, and raising the hollow needle into the travel position; moving the hollow needle across the horizontal work surface to the predetermined x/y-position of the filling opening of a receiving vessel; lowering the hollow needle into the receiving vessel, dispensing a predetermined quantity of liquid, and raising the hollow needle into the travel position; and simultaneously with the above steps, moving a hollow needle of the pipetting module of the second beam of the pipettor in the y-direction to the receiving opening of a needle washing unit, which is moveable synchronously with the pipettor in the x-direction, regardless of the current position of the hollow needle of the pipetting module of the first beam, or keeping it in the travel position.

16. A method for transferring liquids from dispensing vessels, into receiving vessels of an automatic pipetting system, including the following steps: moving a hollow needle of the pipetting module of the first beam of the pipettor in a travel position across a horizontal work surface to the predetermined x/y-position of the extraction opening of a first dispensing vessel; lowering the hollow needle into the first dispensing vessel, taking up a predetermined quantity of a first liquid and raising the hollow needle into the travel position; moving a hollow needle of the pipetting module of the second beam of the pipettor in the travel position across the horizontal work surface to the predetermined x/y-position of the extraction opening of a second dispensing vessel; lowering the hollow needle into the second dispensing vessel, taking up a predetermined quantity of a second liquid, and raising the hollow needle into the travel position; simultaneously moving the hollow needle of the first pipetting module, filled with the first liquid, to the x/y-position of the filling opening of a receiving vessel and the hollow needle of the second pipetting module, filled with the second liquid, to the y-position of the filling opening of the receiving vessel; lowering the hollow needle filled with the first liquid into the receiving vessel, dispensing a predetermined quantity of first liquid, and raising the hollow needle into the travel position; moving the hollow needle of the second pipetting module, filled with the second liquid, to the x-position of the filling opening of the receiving vessel and lowering the hollow needle filled with the second liquid into the receiving vessel, dispensing a predetermined quantity of second liquid, and raising the hollow needle into the travel position; moving the hollow needle of the first pipetting module in the y-direction to the receiving opening of a needle washing unit, which can move synchronously with the pipettor in the x-direction, and cleaning the hollow needle of the first pipetting module in the needle washing unit; and moving the hollow needle of the second pipetting module in the y-direction to the receiving opening of the needle washing unit, which is moveable can move synchronously with the pipettor in the x-direction, and cleaning the hollow needle of the second pipetting module in the needle washing unit.

17. A method for transferring liquids from dispensing vessels into receiving vessels of an automatic pipetting system including the following steps: moving a hollow needle of the pipetting module of the first beam of the pipettor in a travel position across a horizontal work surface to the predetermined x/y-position of the extraction opening of a first dispensing vessel; lowering the hollow needle into the first dispensing vessel, taking up a predetermined quantity of a first liquid and raising the hollow needle into the travel position; moving a hollow needle of the pipetting module of the second beam of the pipettor in the travel position across the horizontal work surface to the predetermined x/y-position of the extraction opening of a second dispensing vessel; lowering the hollow needle into the second dispensing vessel, taking up a predetermined quantity of a second liquid and raising the hollow needle into the travel position; simultaneously moving the hollow needle of the first pipetting module, filled with the first liquid, and the hollow needle of the second pipetting module, filled with the second liquid, to the x/y-position of the filling opening of the receiving vessel; simultaneously or sequentially lowering the hollow needle of the first pipetting module, filled with the first liquid, and the hollow needle of the second pipetting module, filled with the second liquid, dispensing predetermined quantities of first and second liquid into the receiving vessel, and raising the two hollow needles into the travel position; and simultaneously or sequentially moving the hollow needles of the two pipetting modules in the y-direction to the receiving opening of a needle washing unit, which can move synchronously with the pipettor in the x-direction, and simultaneously or sequentially cleaning the hollow needles of the two pipetting modules in the needle washing unit.

18. Use of an automatic pipetting system for transferring liquids from dispensing vessels into at least one receiving vessel, according to claim 1, in an automatic analyzer for carrying out chemical, biochemical and/or immunochemical analyses of liquid samples.

Description

[0047] The invention will be explained in greater detail below on the basis of partially schematic exemplary embodiments. In the drawings:

[0048] FIG. 1 shows a first automatic pipetting device for transferring samples and reagents according to the prior art, in a three-dimensional view;

[0049] FIG. 2 shows a second automatic pipetting device for transferring samples and reagents according to the prior art, in a three-dimensional view;

[0050] FIG. 3a shows an automatic pipetting device according to the invention for transferring liquids from dispensing vessels into at least one receiving vessel, said vessels being arranged on a work surface, in a three-dimensional view;

[0051] FIG. 3b shows a variant of the automatic pipetting device according to the invention as shown in FIG. 3a, as part of an automatic analyzer, the samples and reagents being arranged below the work surface;

[0052] FIG. 3c shows an enlarged detail view of the pipetting device of FIG. 3b in the region of the needle washing unit;

[0053] FIG. 3d shows the detail view of FIG. 3c at a different viewing angle;

[0054] FIG. 3e shows a detail view of a pipetting module of the automatic pipetting device according to the invention, having a double needle;

[0055] FIG. 3f shows a variant of the pipetting module of FIG. 3e, having a single needle;

[0056] FIG. 4a shows a needle washing unit of the automatic pipetting device of FIG. 3a to FIG. 3d, in an enlarged sectional illustration;

[0057] FIG. 4b shows a variant of the needle washing unit of FIG. 4a for receiving two hollow needles simultaneously;

[0058] FIG. 5 shows fluidic elements of a pipetting module of FIG. 3a or FIG. 3b, in a schematic illustration; and

[0059] FIG. 6 shows fluidic elements of the needle washing unit of FIG. 4a, in a schematic illustration.

[0060] Parts which have the same function are provided with the same reference signs in the individual embodiment variants.

[0061] The automatic pipetting device shown in FIG. 1 has already been described in detail in the introductory part of the description (see U.S. Pat. No. 5,897,837 A).

[0062] The automatic pipetting device shown in FIG. 2 has already been described in detail in the introductory part of the description (see DE 10 2005 049 920 A1).

[0063] The pipetting device according to the invention, which is shown in FIG. 3a, serves in general for transferring liquids from dispensing vessels into receiving vessels in the context of treating or processing chemical or biological liquids, for example for transferring samples from sample vessels 921, which are present in a sample store 920 on a table surface or work surface 114, and for transferring reagents from various reagent vessels 951a, 951b, which are present in reagent stores 950a, 950b, into at least one receiving vessel 201, for example a vial or a reaction vessel (see FIG. 3a), a cuvette of an analyzer (see FIG. 3b), or a well of a microtiter plate. Multiple receiving vessels 201 may be arranged in a preparation area or measurement area 200, for example in a row as a linear array, or also as a 2D array, for example in the form of a microtiter plate.

[0064] In order to simplify the illustration in FIG. 3a and FIG. 3b, only those components of the automatic pipetting device which are essential to the invention are shown, wherein other components of the pipetting device, such as pumps, valves, control units and drive units, which are preferably arranged below the work surface 114 oriented parallel to the x/y plane, will not be discussed in detail here.

[0065] The pipetting device shown in FIG. 3a and FIG. 3b has a pipettor 300, which is movable in the x-direction, wherein two pipetting modules 3011, 3012—movable along a y-direction which is substantially normal to the x-direction—are arranged on a horizontally protruding arm 304 of the pipettor 300. The arm 304 of the movable pipettor 300 has a base structure 340, which is movable in the x-direction and to which two beams 341, 342 are attached, said beams being oriented parallel to one another and projecting horizontally in the y-direction. The two pipetting modules 3011, 3012, which are independently able to move past one another, are arranged on the mutually facing longitudinal sides of said beams, each of the pipetting modules 3011, 3012 having at least one hollow needle 307 which is lowerable into the individual vessels 921, 951a, 951b, 201. The two pipetting modules 3011, 3012 are moved in the y-direction by linear drives (for example toothed belt drives), which are not shown here.

[0066] The two beams 341, 342 of the pipettor 300 can be connected at the end face of the arm 304 by a connecting web 351 so as to form a substantially rectangular frame structure 343 in order to stiffen the pipettor against deformations in the x-direction. The resulting frame structure can be made even more rigid if stiffening elements 349 are provided on the inner side thereof in each case at the point of intersection between the beam 341 or 342 and the connecting web 351 or the base structure 340 (not shown).

[0067] Particularly suitable materials for the arm 304 and the base structure 340 are light metal alloys or fiber composite materials with high tensile strength. The pipettor 300, consisting of the structural features according to the invention, can be manufactured in one or more parts.

[0068] Via the base structure 340, which is for example of trapezoidal shape, the arm 304 is suspended on a horizontal running rail 111, which enables the pipettor 300 to move in a longitudinal side of the work surface 114 of a sample and reagent deck 930, said longitudinal side being defined as the x-direction. In the variant shown in FIG. 3a or FIG. 3b, the arm 304 can be moved by a linear drive, for example a toothed belt drive (not shown), which is connected to a servo motor 347. The running rail 111 is anchored to a solid, vertically oriented back plate 348, which is suitable both as a counterweight during the acceleration and deceleration of the pipettor 300 and also for cooling the running rail 111. In one typical embodiment according to the invention, the back plate 348 may be made of aluminum and may have a weight of 20 kg; the machine frame (not shown in detail) below the work surface 114 may have a weight of >300 kg.

[0069] For guiding fluidic lines and any electrical power supply lines and signal lines in the y-direction, the two pipetting modules 3011 and 3012, which are movable on the inner side of the beams 341, 342, have energy chains 3111, 3112 which can be unrolled on the respective beam upper side. For guiding the lines in the x-direction, an energy chain 310 which can be unrolled on the running rail 111 is provided for this purpose.

[0070] The pipettor 300 of the pipetting device has a needle washing unit 700, which is movable with the pipettor 300, for washing the respective two hollow needles 307 of the two pipetting modules 3011 and 3012.

[0071] The needle washing unit 700 is carried along on a hanging support structure 344 on the pipettor 300, wherein an actuator, for example in the form of a spindle drive acting in the x-direction together with a drive unit 346 (see FIG. 3d), makes it possible to change the position of the needle washing unit 700 on the support structure 344 so that the hollow needles 307 of both pipetting modules 3011 and 3012, which are movable in the y-direction, can be washed using a single needle washing unit 700. In addition, a possibility for changing the x-position of the needle washing unit 700 can also be provided by virtue of suspension on a horizontally pivotable boom of a rotary actuator (not shown). As shown in FIG. 3a and FIG. 3b, the support structure 344 can be rigidly connected to the arm 304 or to the base structure 340.

[0072] A separate energy chain 312 may be provided for guiding fluidic lines and any electrical power supply lines and signal lines of the needle washing unit 700 in the x-direction. However, it is also possible for these lines to be carried along in the unrollable energy chain 310 of the pipettor 300.

[0073] According to one embodiment variant, it is also possible for a separate needle washing unit 700 to be provided for each of the two pipetting modules 3011 and 3012, each of said needle washing units being fixedly assigned to one of the pipetting modules 3011 or 3012.

[0074] According to another advantageous embodiment variant, a single needle washing unit 700 may be fixedly arranged on the support structure 344 exactly in the middle between the hollow needles 307 of the two pipetting modules 3011 and 3012 that are to be washed, wherein the opening of the needle washing unit 700 may be designed for example as a slot (see FIG. 4b) so that the hollow needles 307 of the pipetting modules 3011 and 3012, which are movable opposite one another on the inner side of the beams 341, 342 at a small spacing in the x-direction, can be lowered into the opening of the needle washing unit 700 one after the other, or even simultaneously. In this variant, there is advantageously no need for an actuator for moving or pivoting the needle washing unit.

[0075] Instead of a needle washing unit 700 being carried along on the pipettor 300, said needle washing unit may also be guided behind the latter in an electronically controlled manner across the entire movement range of the arm 302 of the pipettor 300. In this case, an additional travel rail must be provided, together with a horizontal linear drive in the x-direction, such as a toothed belt drive for example. One advantage of this is that the weight of the needle washing unit 700 together with its power supply lines need not be moved on the pipettor 300.

[0076] The pipettor 300 of the pipetting device according to the invention may advantageously have, on the outer side of at least one of the beams 341, 342, a mount 305 for attaching a work module (not shown), said mount being movable in the y-direction. The work module may comprise a gripper for transferring or exchanging vessels (for example microtiter plates or cuvettes). The movement of the work module may for example be coupled, via a suitable entrainment mechanism, to the movement of a pipetting module 3011 or 3012 moving on the opposite side of the relevant beam 341, 342. The work module may optionally be fixed to the mount 305 shown in FIG. 3a or FIG. 3b, or may be moved along on a lateral extension (not shown here) of one of the pipetting modules 3011 or 3012. The power supply lines of the gripper can then be carried along very easily on one of the two energy chains 3111 or 3112 together with the power supply lines of the adjacent pipetting module 3011 or 3012.

[0077] When using the pipetting device according to the invention in an automatic analyzer for analyzing biological or chemical samples by means of optical measurements in cuvettes 201 (see FIG. 3b), the gripper of the work module can be used to transfer cuvettes from a cuvette store to an optical measurement unit 500 or to a cuvette disposal container (not shown).

[0078] FIG. 3b shows a variant of an automatic pipetting device according to the invention as shown in FIG. 3a, as part of an automatic analyzer for analyzing liquid biological/chemical samples. The device configuration shown in FIG. 3b is designed for transferring, by using the two pipetting modules 3011, 3012 which can be moved across the work surface 114, liquid samples and reagents from the sample and reagent stores 920 and 950a,b of a sample and reagent deck 930 of the analyzer into the cuvettes 201 arranged in a measurement area 200 of an optical measurement unit 500, in which the reaction mixtures containing the analytes to be determined can be analyzed using optical methods (photometry or luminometry). The work surface 114, which serves as a cover, is arranged closely above the top edges of the sample vessels 921 and reagent vessels 951a, 951b and receiving vessels 201 (cuvettes). The unhindered movement of the needle washing unit 700 on its support structure 344 along the x-axis is ensured by the slot-shaped opening 936 in the work surface 114, which is shown in FIG. 3b.

[0079] In order to make it easier to maintain and populate the aforementioned storage areas 920 and 950a,b, these are arranged on a front longitudinal side of the analyzer, the sample store 920 having strip-shaped racks 933 which can be manually inserted by the user into the respective storage slots below a cover 935 having the through-openings 931 for the hollow needles 307.

[0080] The reagent stores 950a, 950b with the reagent containers 951a, 951b held therein can be manually swapped from above for example, as shown in FIG. 3b, after folding to the side a cover 935 that has through-openings 932 for the hollow needles 307 of the pipetting modules 3111, 3112. For easy, manual removal of the reagent containers 951a, 951b, it is particularly advantageous if the reagent containers are stored in cassettes 934 which can be pulled out toward the front.

[0081] FIG. 3c shows an enlarged detail view of the pipetting device of FIG. 3b, looking toward an inner side of the beam 342, wherein, of the two movable pipetting modules 3011, 3012, the pipetting module 3012 arranged in the region of the needle washing unit 700 is visible. The illustration in FIG. 3c shows the pipetting module 3012 with a vertical toothed belt 335, to which two needle holders 330, 331 are clamped, each holding at least one hollow needle 307.

[0082] The illustrations in FIG. 3c and FIG. 3d show the needle washing unit 700 together with a hollow needle 307 lowered therein for washing, wherein the power supply lines can be routed to the needle washing unit 700 over a particularly short distance if the power supply lines are guided not by the energy chain 310 or parts of the pipettor 300, but rather by a separate energy chain 312 which unrolls in the x-direction.

[0083] The lifting mechanism 332 shown by way of example in FIG. 3e and FIG. 3f has a toothed belt 335 clamped vertically between a lower pulley 333 and an upper pulley 334 serving as a drive wheel, said toothed belt being suitable for moving a needle holder 330 or 331, clamped thereto, together with a hollow needle 307, in the z-direction on a downwardly projecting and vertically oriented rail section 306. The individual hollow needles 307 of the pipetting modules 3011, 3012 located opposite one another in the x-direction are thereby clamped at the edge in the needle holders 330 or 331 such that the hollow needles 307 can move past one another at a small spacing as the pipetting modules pass each other.

[0084] It is particularly advantageous if the hollow needles 307, which come close to one another, have a minimal spacing from one another in the x-direction of 2 mm to 16 mm, preferably 2 mm to 4 mm as they pass each other in the y-direction, so as to be able to be lowered simultaneously, and without colliding, into a receiving vessel 201 having an opening of 6 mm to 20 mm diameter.

[0085] Each hollow needle 307 is connected at the upper end, via a connecting piece 338 and by the flexible pressure transfer channel 712, to the fluidics as shown in FIG. 5, by which the pressure in the hollow needle 307 can be varied accordingly for aspirating and dispensing liquids.

[0086] According to the embodiment variant of a pipetting module 3011 and 3012 shown in FIG. 3e, two hollow needles 307 are arranged on the lifting mechanism 332 such as to be movable in opposite directions or in an antiparallel manner in the z-direction, since the needle holders 330, 331 thereof act on opposite runs of the toothed belt 335. Furthermore, instead of a revolving toothed belt, other mechanical elements can also be used, provided that these act in the same way. By way of example, racks which are oriented vertically on both sides may act on the pulley or drive wheel 334, each of said racks having a needle holder 330 or 331.

[0087] According to the embodiment variant of a pipetting module 3011 or 3012 shown in FIG. 3f, which can be attached to the beam 341 of the arm 304 on a mount 305 which is movable in the y-direction, said pipetting module carries a single hollow needle 307 which is vertically movable via a lifting mechanism 332.

[0088] A further advantageous embodiment variant of the pipetting device may have pipetting modules 3011 or 3012 which comprise a plurality of lifting mechanisms of the type shown in the exemplary embodiments in FIG. 3e and/or FIG. 3f, arranged next to one another in the y-direction, so as to be able to move a plurality of hollow needles 307 independently of one another in the z-direction on a beam 341 or 342.

[0089] By arranging two lifting mechanisms 332 next to one another (not shown), different variants of a pipetting module 3011 or 3012 can be implemented, each having a total of two, three or four hollow needles 307, it also being possible for the number of lifting mechanisms combined to form a pipetting module to be greater than two, depending on the task. In this way, a greater number of hollow needles 307 can be provided for different pipetting tasks or, if the proportion of lifting mechanisms which each have only one hollow needle 307 is increased (FIG. 3f), a greater number of hollow needles 307 which are independently movable in the z-direction can be provided.

[0090] All the hollow needles 307 of the pipettor 300 may be made of different materials and/or may have different internal volumes, and therefore are available for different tasks.

Design Example and Exemplary Key Performance Indicators of a Pipetting Device According to the Invention

[0091] The maximum travel time defined in a typical application of the pipetting device according to the invention for a complete diagonal movement of a pipetting module 3011, 3012 of the pipettor 300 across a work surface 114 measuring 1 m×0.5 m is <500 ms.

[0092] Said maximum travel time is particularly important in an automatic analyzer as shown in FIG. 3b, which has the aforementioned dimensions of the work surface and has to achieve a particularly high throughput of pipetting and gripping operations at typically randomly distributed, non-adjacent receiving and dispensing positions.

[0093] The acceleration that can be measured on the structure of the pipettor 300 during the movement in the x-direction is >17 m/s2, with an instantaneous velocity of 3.6 m/s being achieved. The weight of the arm 304, when typically made of an aluminum alloy, is approximately 5 kg, a transverse force in the x-direction of >85 N being measured on the connecting web 351 of the frame structure 343 of the arm 304 when accelerating. Despite the high transverse forces, it is necessary to prevent bending deflections >0.5 mm or vibration/bouncing of the arm 304 with its pipetting modules 3011, 3012 since this may lead to errors in pipetting, for example due to a loss of liquid when moving horizontally (or to unwanted contact with the wall of approached liquid containers when subsequently lowering the hollow needles 307). Furthermore, vibration damage may occur to the entrained electronics of the pipetting modules 3011, 3012, for example to the bond wire contacting of integrated circuits of fill level and/or pressure measuring systems.

[0094] The servo motor 347 of the pipettor 300 has an output of >0.8 kW so as to ensure the kinematic power values of the pipettor desired during operation when moving in the x-direction of the work surface.

[0095] FIG. 4a shows, in an enlarged sectional illustration, the structure of a needle washing unit which is labeled with the reference sign 700 and which is arranged on the base structure 340 or on the arm 304, said needle washing unit receiving a hollow needle 307 of the pipetting modules 3011, 3012, which are shown at different positions in FIG. 3a and FIG. 3b. The hollow needle 307 is introduced through a receiving opening 711 in the housing 710 of the needle washing unit 700, wherein simultaneously the lumen of the needle is cleaned using a washing solution or the system liquid from the pressure transfer channel 712 and the outer side of the needle is cleaned using a rinsing liquid 714 which is supplied from an annular chamber 715 via lateral cleaning nozzles 713. In order to clean the inside and the outside of the hollow needle 307 by repeatedly aspirating and discharging washing solution from the lower part of the needle washing unit, washing solution may be supplied through a radial inlet 716 and can then be emptied through an extraction opening 717.

[0096] The embodiment variant of the needle washing unit shown in FIG. 4b differs from that shown in FIG. 4a substantially by a receiving opening 711a which is designed as a slot and can receive and which is able to clean two hollow needles 307 simultaneously.

[0097] FIG. 5 shows the fluidic circuit diagram of a hollow needle 307, which is connected, via a pressure transfer channel 712 filled with a degassed liquid, to a precision piston pump 325, preferably a positive displacement pump (diluter) which is 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 liquid, which conveys for example degassed, deionized water via a rinsing pump 321 from a storage vessel 322 that can be refilled or pressurized via a solenoid valve 323.

[0098] In order to detect faults, the pressure transfer channel 712 has, in the vicinity of the pipetting needle 301, a further connection to a pressure sensor 324, which is connected to an evaluation and monitoring unit (not shown here), for example in order to detect blockages of the hollow needle 307.

Description of a Pipetting Process

[0099] In order to transfer a defined quantity of liquid, for example using a pipetting module 3011 as shown in FIG. 3a, the latter is first moved in the horizontal direction to a dispensing vessel (for example sample vessel 921), 5 μl of air (spacer) is aspirated into the tip of the hollow needle 307, and the hollow needle 307 is lowered in the direction of the liquid surface of the first vessel 921. In order to ensure a sufficient, but not excessive, depth of immersion of the hollow needle 307, the downward movement of the hollow needle 307 is stopped at a defined depth of immersion by a signal from a liquid surface detection device (not shown), for example using a capacitive detection principle. In order to aspirate a defined quantity of liquid with high accuracy in the μl range, a negative pressure is then generated in the hollow needle 307 of the pipetting module 3011 by moving the working piston of the positive displacement pump (diluter) shown in FIG. 5 in the downward direction, which causes a corresponding volume of liquid to be aspirated from a first vessel. The pipetting module 3011 is then moved together with the aspirated liquid, which is separated from the system liquid by a separating air bubble (spacer), to a second vessel (for example receiving vessel 201), wherein the process then takes place in reverse and the aspirated liquid is dispensed through the tip of the hollow needle 307 into the second vessel. At least between two pipetting processes involving different liquids to be pipetted, an internal and external cleaning of the hollow needle 307 always takes place in the needle washing unit 700. During the pipetting process using the pipetting module 3011, the hollow needle 307 of the second pipetting module 3012 can be being cleaned and dried in the needle washing unit 700.

[0100] FIG. 6 shows the fluidic circuit diagram of a needle washing unit 700 according to FIG. 4a, with the hollow needle 307 lowered therein. The housing 710 of the needle washing unit has in the upper region a concentrically extending annular chamber 715, which acts as a media supply for a plurality of inner, concentrically oriented cleaning nozzles 713 and which is connected via respective solenoid valves to a supply unit 719 for a rinsing liquid (for example deionized water) and a supply unit 727 for dry air.

[0101] An inlet 716 arranged radially at mid-height of the housing 710 of the needle washing unit 700 is likewise connected to a solenoid valve and serves solely for supplying surfactant-containing washing solution from a supply unit 723.

[0102] The supply units 719 for a rinsing liquid and 723 for a washing solution each have a pump 720, 724 which conveys rinsing liquid or a surfactant-containing washing solution from the respective storage containers 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 optionally a drying means (not shown).

[0103] The extraction 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 is under a vacuum and substantially consists of a collecting container 730 which has in the gas space above the liquid a connection to a vacuum pump 731, which is connected to the collecting container 730 via a solenoid valve. The wastewater collected can be discharged via a solenoid valve 732 at the bottom of the collecting container 730 and can be fed to a further wastewater treatment.

Description of a Needle Washing Process

[0104] In a typical process for washing a hollow needle 307 of the pipetting modules 3011, 3012, said needle is first moved horizontally to the needle washing unit 700 and is lowered into the lower holding position of the washing chamber. All the wastewater that is produced when cleaning the hollow needle 307 is sucked away via the extraction opening 717 located at the bottom, is collected, and is optionally subjected to an aftertreatment. Residual amounts of the last-pipetted liquid which are located in and on the needle tip are then emptied and sucked away via the precision piston pump 325, which is shown in FIG. 5. Finally, the lowered hollow needle 307 is rinsed from behind by means of the supply unit 320 for system liquid, which is shown in FIG. 5.

[0105] In a next step (with the solenoid valve 718 at the extraction opening 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, as a result of which the chamber in the lower part fills with a defined level of washing solution. The hollow needle 307 is lowered so far until an external wetting of the needle can take place by immersion in the washing solution and an internal wetting of the hollow needle 307 can take place as a result of the washing solution being aspirated into the needle interior. The aspirated washing solution is then discharged again, it being possible for the process of aspirating and discharging the washing solution to be repeated multiple times in order to improve the cleaning effect.

[0106] In a last step, the contaminated washing solution is sucked away and the interior of the hollow needle 307 is rinsed with system water (for example degassed, deionized water), while the outer side of the hollow needle 307 is at the same time rinsed with rinsing liquid from the supply unit 719 by the concentrically arranged cleaning nozzles 713 located at the top, the tip of the hollow needle 307 being moved upward from the bottom in order to improve the cleaning effect.

[0107] Once the simultaneous rinsing of the inside and the outside is complete, the hollow needle 307 is moved back into the lower holding position, the media supply to the cleaning nozzles 713 is switched to the supply unit 727 for compressed air, and the tip of the hollow needle 307 again moves upward from the bottom, as a result of which adhering water droplets can quickly be removed from the needle surface. The hollow needle 307 can then be moved out of the needle washing unit 700 and is again ready for pipetting.

EXAMPLES

[0108] The automatic pipetting device shown in FIG. 3a and FIG. 3b operates for example as follows:

[0109] Prior to a pipetting task, the control unit (not shown) of the pipetting device brings together, from known and previously input information, all the data required for transferring the liquids (for example samples, reagents and other liquids) in the form of a transfer protocol.

[0110] Starting from a specified analysis protocol for a particular analysis to be carried out on a sample using two reagents, the transfer protocol includes for example all the instructions for transferring a liquid sample (located in a sample vessel 921 in a sample store 920) and for transferring a first and a second liquid reagent (stored in two reagent vessels 951a, 951b in a reagent store 950a, 950b), the x/y-positions of the extraction openings of the sample vessel 921 and of the two reagent vessels 951a, 951b, the x/y-position of the filling opening of a free receiving vessel 201, and the liquids and quantities of liquid to be transferred over time.

[0111] For the sake of simplicity, it is assumed in the following examples that the first pipetting module 3011 on the first beam 341 and the second pipetting module 3012 on the second beam 342 each carry only one hollow needle 307. If they carry multiple hollow needles, the control unit will in each case select a suitable hollow needle with regard to transfer volume and needle material.

[0112] In order to move in the x- and/or y-direction of the work surface, all the hollow needles 307 must always be located in a travel position in the z-direction, or must be brought into said position. The travel position is selected such that, as the pipettor 300 moves, all the hollow needles can move across the work surface without colliding. In the lifting mechanism of the double-needle variant, this is the position in the z-direction at which both hollow needles 330, 331 are at the same height. The exception is the hollow needle immersed in a needle washing unit 700.

Example 1

[0113] The steps set out below relate to an exemplary transfer protocol for sample processing and/or analysis that is to be carried out on a liquid sample using two liquid reagents. In this case, the sample should be present in a sample vessel 921 in the sample store 920. The first reagent should be present in a first reagent vessel 951a in a first reagent store 950a. The second reagent should be present in a second reagent vessel 951b in a second reagent store 950b. Quantities of sample, first reagent and second reagent specified by the analysis protocol should be introduced in sequential order into a receiving vessel 201, which is located in a preparation or measurement area 200.

[0114] In step 1, the hollow needle 307 of the first pipetting module 3011 is brought into the x/y-position of the opening of the sample vessel 921 selected by the control unit by simultaneously moving the pipettor 300 in the horizontal x-direction and the first pipetting module 3011 in the horizontal y-direction.

[0115] In step 2, the hollow needle 307 positioned in step 1 is lowered in the z-direction into the sample vessel 921, so that the tip of said hollow needle is immersed in the sample liquid, after which a quantity of sample liquid specified by the control device is aspirated into the lowered hollow needle, and subsequently the hollow needle is raised again in the z-direction into the travel position.

[0116] In step 3, the hollow needle 307 filled with sample liquid in step 2 is brought into the x/y-position of the filling opening of the receiving vessel 201 selected by the control unit, for example a reaction vessel 201 in FIG. 3a or a cuvette 201 in FIG. 3b, by simultaneously moving the pipettor 300 in the horizontal x-direction and the first pipetting module 3011 in the horizontal y-direction.

[0117] In step 4, the hollow needle filled with sample liquid in step 2 is lowered in the z-direction into the receiving vessel 201, thereby dispensing a predetermined quantity of sample liquid, and then is raised again in the z-direction into the travel position.

[0118] During all the actions of the hollow needle 307 of the first pipetting module 3011 described above in steps 1-4, the hollow needle 307 of the second pipetting module 3012, regardless of the current position of the hollow needle of the first pipetting module 3011, either may remain in the travel position or may move in the y-direction into the y-position of the inlet opening of a needle washing unit 700 moving synchronously with the pipettor 300 in the x-direction, may be cleaned therein after lowering the needle tip, and then may be raised again into the travel position.

[0119] Further steps 5-8 are analogous to steps 1-4, with the difference that now the hollow needle 307 of the second pipetting module 3012 transfers reagent liquid from a dispensing vessel 951a into the receiving vessel 201, while the hollow needle 307 of the first pipetting module 3011 is being washed.

[0120] Subsequent steps 9-12 are analogous to steps 5-8, with the difference that now the hollow needle 307 of the first pipetting module 3011 transfers a second reagent liquid from a dispensing vessel 951b into the receiving vessel 201, while the hollow needle 307 of the second pipetting module 3012 is being washed.

[0121] In the variant according to Example 1, therefore, a pipetting needle of one of the two pipetting modules 3011, 3012 can be pipetting samples and reagents while a pipetting needle of the respective other pipetting module is being washed and/or held ready in the travel position.

Example 2

[0122] The steps set out in Example 2 relate to an exemplary transfer protocol for sample processing and/or analysis that is to be carried out on a first liquid, for example a sample liquid, using a second liquid, for example a reagent liquid. In this case, the first liquid, for example the sample liquid, should be present in a sample vessel 921 of the sample store 920. The second liquid, for example the reagent liquid, should be present in a first reagent vessel 951a of the first reagent store 950a. Quantities of first and second liquid (sample and reagent) specified by the analysis protocol should be introduced in sequential order into a receiving vessel 201, which is located in a preparation or measurement area 200.

[0123] In the following, the first liquid is a sample liquid and the second liquid is a reagent liquid. However, other constellations are also conceivable; for example, the first liquid may be a sample liquid, a reagent or an active ingredient, and the second liquid may be a dilution liquid. The first and the second liquid may also be different reagents.

[0124] In step 1, the hollow needle 307 of the first pipetting module 3011 is brought into the x/y-position of the opening of the sample vessel 921 selected by the control unit by simultaneously moving the pipettor 300 in the horizontal x-direction and the first pipetting module 3011 in the horizontal y-direction.

[0125] In step 2, the hollow needle positioned in step 1 is lowered in the z-direction into the sample vessel 921, so that the tip of said hollow needle is immersed in the sample liquid, after which a quantity of sample liquid specified by the control device is aspirated into the lowered hollow needle, and subsequently the hollow needle is raised again in the z-direction into the travel position.

[0126] In step 3, the hollow needle 307 of the second pipetting module 3012 is brought into the x/y-position of the opening of the reagent vessel 951a selected by the control unit by simultaneously moving the pipettor 300 in the horizontal x-direction and the second pipetting module 3012 in the horizontal y-direction.

[0127] In step 4, the hollow needle 307 positioned in step 3 is lowered in the z-direction into the reagent vessel 951a, so that the tip of said hollow needle is immersed in the reagent liquid, after which a quantity of reagent liquid specified by the control device is aspirated into the lowered hollow needle, and subsequently the hollow needle is raised again in the z-direction into the travel position.

[0128] In step 5, the hollow needle 307 of the first pipetting module 3011 that was filled with sample liquid in step 2 is brought into the x/y-position of the filling opening of the receiving vessel 201 by simultaneously moving the pipettor 300 in the horizontal x-direction and the first pipetting module 3011 in the horizontal y-direction, while at the same time the hollow needle 307 of the second pipetting module 3012 that was filled with the reagent liquid in step 4 need only be brought into the y-position of the receiving vessel 201 by simultaneously moving the pipetting module 3012 in the horizontal y-direction.

[0129] In step 6, the hollow needle filled with sample liquid is lowered in the z-direction into the receiving vessel 201, thereby dispensing a predetermined quantity of sample liquid, and then is raised again in the z-direction into the travel position.

[0130] In step 7, the hollow needle filled with the reagent liquid is brought into the x/y-position of the filling opening of the receiving vessel 201 by moving the pipettor 300 in the horizontal x-direction.

[0131] In step 7, therefore, it is no longer necessary to move the second pipetting module 3012 into the y-position of the receiving vessel since the corresponding hollow needle has already been brought into this position in step 5. The beam construction with the pipetting modules moving on the inner longitudinal sides makes it possible in step 5 to bring the two hollow needles toward one another in the x-direction to a spacing in the mm range, so that in step 7 the travel distance and travel time of the pipettor in the x-direction can be kept very small.

[0132] In step 8, the hollow needle 307 filled with a reagent liquid is lowered in the z-direction into the receiving vessel 201, thereby dispensing a predetermined quantity of first reagent liquid, and then is raised again in the z-direction into the travel position.

[0133] After the actions in step 6 have been carried out, the hollow needle 307 of the first pipetting module 3011 is moved into the y-position of the inlet opening of the needle washing unit 700 moving therewith, and after lowering the needle tip is cleaned therein and then is raised again into the travel position, after which, once the actions in step 8 have been carried out, the hollow needle 307 of the second pipetting module 3012 is moved into the y-position of the inlet opening of the needle washing unit 700 moving therewith, and after lowering the needle tip is cleaned therein and then is raised again into the travel position.

Example 3

[0134] The steps set out in Example 3 relate (as in Example 2) to an exemplary transfer protocol for sample processing and/or analysis that is to be carried out on a first liquid, for example a sample liquid, using a second liquid, for example a reagent liquid, it being possible for both liquids to be dispensed simultaneously.

[0135] In the following, the first liquid is a sample liquid and the second liquid is a reagent liquid. However, other constellations are also conceivable; for example, the first liquid may be a sample liquid, a reagent or an active ingredient, and the second liquid may be a dilution liquid. The first and the second liquid may also be different reagents.

[0136] Steps 1-5 are substantially analogous to steps 1-5 in Example 2.

[0137] In step 6, the hollow needle 307 of the first pipetting module 3011 that was filled with the sample liquid in step 2 and the hollow needle 307 of the second pipetting module 3012 that was filled with the reagent liquid in step 4 are simultaneously lowered in the z-direction into the dispensing vessel 201—thereby respectively dispensing a predetermined quantity of sample liquid and a predetermined quantity of reagent liquid—and then are raised again in the z-direction into the travel position.

[0138] In step 7, the hollow needle 307 of the first pipetting module 3011 and the hollow needle 307 of the second pipetting module 3012 are successively or simultaneously moved to the x/y-position of the receiving opening 711a of the needle washing unit 700 moving synchronously with the pipettor 300, so that the imaginary, common center of the two needles 307 is located above the slot-shaped receiving opening 711a of the needle washing unit 700 and, after lowering the needle tips, these are successively or simultaneously cleaned therein (see FIG. 4b) and then are raised again into the travel position.

[0139] Compared to Example 2, step 7, the step of moving the pipettor 300 in the x-direction can be omitted in Example 3.