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WO2025083017A1 - Appareil de manipulation automatisée de liquide, dont les composants ont un degré de liberté élevé - Google Patents

Appareil de manipulation automatisée de liquide, dont les composants ont un degré de liberté élevé Download PDF

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Publication number
WO2025083017A1
WO2025083017A1 PCT/EP2024/079128 EP2024079128W WO2025083017A1 WO 2025083017 A1 WO2025083017 A1 WO 2025083017A1 EP 2024079128 W EP2024079128 W EP 2024079128W WO 2025083017 A1 WO2025083017 A1 WO 2025083017A1
Authority
WO
WIPO (PCT)
Prior art keywords
container
reaction
liquid
reaction vessel
waste
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/EP2024/079128
Other languages
German (de)
English (en)
Inventor
Kai Hassler
Konstantin Lutze
Hans-Jürgen TIEDTKE
Michael KÜHNI
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Hamilton Bonaduz AG
Original Assignee
Hamilton Bonaduz AG
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Hamilton Bonaduz AG filed Critical Hamilton Bonaduz AG
Publication of WO2025083017A1 publication Critical patent/WO2025083017A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

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Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/0098—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor involving analyte bound to insoluble magnetic carrier, e.g. using magnetic separation
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
    • G01N35/04—Details of the conveyor system
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1009—Characterised by arrangements for controlling the aspiration or dispense of liquids
    • G01N35/1016—Control of the volume dispensed or introduced
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/02—Burettes; Pipettes
    • B01L3/0289—Apparatus for withdrawing or distributing predetermined quantities of fluid
    • B01L3/0293—Apparatus for withdrawing or distributing predetermined quantities of fluid for liquids
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N2035/00465—Separating and mixing arrangements
    • G01N2035/00564—Handling or washing solid phase elements, e.g. beads
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
    • G01N35/04—Details of the conveyor system
    • G01N2035/0401—Sample carriers, cuvettes or reaction vessels
    • G01N2035/0418—Plate elements with several rows of samples
    • G01N2035/0422—Plate elements with several rows of samples carried on a linear conveyor
    • G01N2035/0424—Two or more linear conveyors

Definitions

  • the present invention relates to an automated liquid handling device for handling liquids.
  • Such an automated liquid handling device comprises: i. a reaction container device with at least one reaction container arrangement with at least one reaction container, wherein the at least one reaction container has an input end with an input opening and an output end with an output opening located at a distance from the input end, ii. a useful receiving device for receiving liquid dispensed through the output opening of the at least one reaction container as a handling target, iii. a waste receiving device, different from the useful receiving device, for receiving liquid dispensed through the output opening of the at least one reaction container as handling waste, iv. a magnetic device for forming a magnetic field in the at least one reaction container, v.
  • a pressure changing device wherein the pressure changing device is designed to change a gas pressure difference between an internal gas pressure in at least one reaction container of the reaction container device and an external gas pressure outside the at least one reaction container, and vi. a dosing device with at least one dosing opening for transferring liquid into at least one reaction container of the reaction container device, wherein the dosing device is designed for transferring liquid by means of the dosing opening through the input opening of the at least one reaction container.
  • Such a liquid handling device is used in laboratories, for example, for the purification of nucleic acids.
  • a liquid handling device with the features mentioned above is essentially known in an abstract form from WO 2019/096407 A1.
  • An advantage of this known liquid handling device is that, during processing, liquid is always moved in the same direction from the input opening to the output opening of the at least one reaction container. Consequently, no reversal of direction of processed liquids occurs, as is known from other prior art liquid handling devices. Thus, a source of potential cross-contamination can be avoided.
  • the reaction container device is the device in which a liquid is "processed" in the broadest sense and in which the liquid is handled. For example, chemical reactions and/or physical processes take place here.
  • nucleic acids in particular DNA or RNA
  • contained in a starting liquid transferred at the beginning of a handling process can be bound to appropriately prepared magnetic particles.
  • the magnetic particles with the bound nucleic acids can be cleaned by transferring them, optionally waiting for a reaction time, and dispensing a cleaning liquid.
  • the bound and purified nucleic acids can be eluted, i.e., detached from the magnetic particles, by transferring them, optionally waiting for a reaction time, and dispensing an elution liquid.
  • the eluate thus obtained can be discharged from the at least one reaction container as a handling target.
  • a portion of the aforementioned starting liquid and the subsequently transferred cleaning liquid can be discharged from the at least one reaction container as handling waste.
  • the useful receiving device of the liquid handling device serves, as already described above, to receive liquid that is dispensed from the at least one reaction container as the desired handling target, usually an eluate containing purified nucleic acid.
  • the useful receiving device can advantageously serve to transport the liquid received therein to further processing locations or stations.
  • the useful receiving device preferably comprises a useful container arrangement with at least one useful liquid container, particularly preferably with a plurality of useful liquid containers.
  • the waste receiving device of the liquid handling device serves to receive liquids that arise as waste during liquid processing, for example an original carrier liquid for nucleic acid, in which impurities, such as residues of cell components of the cells originally containing the nucleic acid and the like, may be undesirably present, which, after the nucleic acids have bound to magnetic particles, are released with the carrier liquid and are to be washed out by one or more subsequent washing processes.
  • the cleaning liquid used during the washing processes therefore also forms handling waste within the meaning of the present application.
  • the waste receiving device preferably comprises a waste container arrangement with at least one waste liquid container to receive the handling waste.
  • the waste container arrangement can also have a plurality of waste liquid containers within the scope of the present invention
  • the waste container arrangement preferably comprises only one waste liquid container as a collection container for handling waste released from the reaction containers, i.e.
  • a waste liquid container is provided to receive handling waste from all reaction containers present simultaneously.
  • the magnetic device serves to temporarily immobilize the magnetic particles in the at least one reaction container. This allows It can be ensured that only the respective liquid suspending the magnetic particles in the at least one reaction container can be dispensed through the dispensing opening, while the magnetic particles, in particular with nucleic acids bound thereto, can be retained in the reaction container.
  • the pressure-changing device of the liquid handling device serves to create the aforementioned gas pressure difference between a gas inside the at least one reaction container and the gas surrounding the reaction container.
  • This specifically generated gas pressure difference allows liquid held in the at least one reaction container to be moved through the dispensing opening.
  • the pressure-changing device is designed only to create a positive pressure difference, at which the gas pressure inside the reaction container is higher than the gas pressure outside the at least one reaction container.
  • liquid is exclusively dispensed through the dispensing opening, but not drawn into the reaction container.
  • the dosing device of the liquid handling device serves for the automated introduction of liquid into the at least one reaction container. It is hygienically advantageous that the liquid is introduced into the at least one reaction container through the inlet opening located remote from the dispensing opening of the at least one reaction container.
  • Liquid handling devices are also known, for example from EP 0 691 541 A2 or EP 1 065 001 A1, whose reaction container has only one opening through which liquids are aspirated into the reaction container and subsequently dispensed again.
  • the aspiration and dispensing of different liquids in one liquid processing operation is considered to be disadvantageous in terms of process hygiene compared to the liquid processing explained above with the passage of liquids through the reaction container from the input opening to the output opening.
  • the reason for this lies to a large extent Part of this is that the inlet opening can be designed so large that it does not need to be wetted by the liquid introduced into the at least one reaction container or by a nozzle dispensing it. This is virtually impossible with aspiration and dispensing through the same opening.
  • FIG. 2010/075199 A2 Another liquid handling device is known from WO 2010/075199 A2.
  • the liquid handling device known from WO 2010/075199 A2 discloses a similar structure to that mentioned above. However, WO 2010/075199 A2 does not disclose a waste collection device.
  • the reaction containers of the known liquid handling device are connected to a common disposal line, which serves as a waste collection device. Rather, an eluate produced as a handling target in the liquid handling device known from WO 2010/075199 A2 is removed from the device together with the reaction containers containing the eluate and transported for further processing.
  • WO 2004/113874 A2 discloses another liquid handling device which, by means of a valve arrangement, allows different liquids to be fed through one and the same metering device into a plurality of reaction containers.
  • the discharge openings of the reaction containers of the liquid handling device known from WO 2004/113874 A2, which are located away from the input openings, are connected to a common disposal line, as in the liquid handling device of the aforementioned WO 2010/075199 A2.
  • the reaction containers that can be removed from the liquid handling device are therefore removed from the liquid handling device together with the handling target contained therein for further processing of the handling target once it has been achieved and transported further.
  • DE 10 2007 041 071 B4 discloses a device for applying liquid to a sample carrier as further technological background known in which the dispensing opening is a capillary. Due to its dimensions, this capillary holds a liquid up to a certain liquid height above the dispensing opening in the receiving container solely through the capillary pressure caused by a gas atmosphere surrounding the receiving container at normal pressure, i.e. around 1013 hPa.
  • a pressure head can be sealingly attached to an opening on the receiving container that is remote from the dispensing opening. This pressure head can be used to generate gas pressure pulses in the receiving container, by means of which the liquid can be dispensed as a small drop onto a sample carrier.
  • DE 10 2007 041 071 B4 states that liquids with a dosing volume of 0.1 nanoliter can be dispensed in this way.
  • DE 10 2007 041 071 B4 limits its description to droplet dispensing and in no way concerns the use of magnetic particles or the application of magnetic fields to the liquid held in the receiving container.
  • a liquid is introduced into and discharged from the at least one reaction container at least once, but usually several times, during the liquid handling.
  • Solid components contained in the at least one reaction container can be bound in the at least one reaction container by different physical principles of action, depending on the method performed and the substances used, for example by electrostatic interaction, hydrophobic interaction, or by exploiting a biospecific affinity, such as an antigen-antibody interaction or an enzyme-substrate interaction.
  • the solid components that can be bound or immobilized in a reaction container are the above-mentioned magnetic particles, which can be immobilized in the at least one reaction container due to an external magnetic field generated by the provided magnetic device.
  • the immobilizable solid components can thus come into contact with a sequence of liquids, particularly in one and the same reaction container, wherein the liquids can be the same or different liquids.
  • the immobilizable solid components can be suspended several times in a liquid contained in at least one reaction vessel.
  • Other, non-immobilized, solid components that are undesirable in the reaction vessels can be rinsed out with the handling waste.
  • the object of the present invention is to further improve the automated liquid handling device mentioned above.
  • the aim is, in particular, to reduce potential sources of error and improve process hygiene.
  • an automated liquid handling device of the type mentioned at the outset in which, in addition, each of the devices mentioned under i. to v., consisting of the reaction container device, the useful receiving device, the waste receiving device, the magnetic device, and the pressure-changing device, is accommodated in a device housing of the liquid handling device so that it can move relative to each other of the devices mentioned under i. to v., and in which each of the devices mentioned under i. to iv. and vi., consisting of the reaction container device, the useful receiving device, the waste receiving device, the magnetic device, and the dosing device, is accommodated in a device housing of the liquid handling device so that it can move relative to each other of the devices mentioned under i.
  • the device housing is a stationary reference system of the automated liquid handling device.
  • Each of the devices mentioned under i. to vi. consisting of the reaction container device, the useful receiving device, the waste receiving device, the magnetic device, the pressure-changing device, and the dosing device, is arranged so that it can move relative to the device housing.
  • the term "apparatus” generally refers to the liquid handling device. To distinguish it from the liquid handling device, its functional components, unless they already have a specific designation, are each referred to as “devices.””Devices” as a shortened collective term therefore generally refers to several or all of the devices referred to above under i. to vi.
  • the aforementioned relative mobility of the devices in pairs to each other achieves the greatest possible automated mobility of components of the liquid handling device without the need for a human operator to intervene in the automated liquid handling process.
  • each of the aforementioned devices is preferably guided by a guide device along a movement path defined by the guide device.
  • the guide device can, for example, comprise a guide rail and a guide carriage or guide slide movably arranged along the guide rail.
  • Guide rails of the guide device are generally arranged in a fixed location, for example, on at least one device housing component consisting of the side wall, housing base, housing cover, and a structure firmly connected to the device housing.
  • Each of the devices mentioned can be driven to move by a motion drive, such as a belt drive and/or a spindle drive and/or a linear motor and/or another drive familiar to those skilled in the art, usually electrically powered.
  • the motion drive can only be effective over sections of the motion range of a device. However, the motion drive is preferably effective over the entire motion range of a device. Furthermore, devices can be driven to move within their motion range by more than one motion drive. This can be advantageous, for example, if the motion path of a device has a bent or angled course, such as a horizontal and a vertical section, so that a different motion drive can be effective in one section of the motion path than in another.
  • the liquid handling device preferably comprises a control device for controlling processes within the device.
  • the control device which preferably comprises at least one data memory and at least one integrated circuit as an electronic control device, is designed to control motion drives and/or valve devices of the device according to an operating program stored in the at least one data memory, using application data stored in the at least one data memory, optionally supplemented by user inputs and/or data transmitted from additional control units.
  • the automated liquid handling device discussed here is intended as an "entry-level model" and should not exceed a size that allows the device to be placed on a laboratory bench and easily relocated as needed. This is not intended as a mobile, portable device, but rather as a device whose flexibility of placement in the laboratory is comparable to that of a printer in an office: the device can be set up and operated in almost any location. Once set up, however, it often remains at the chosen location until substantial reasons arise for changing the location. In order to keep the weight and costs of the automated liquid handling device discussed here as low as possible, it can be provided that the device that is generally moved least frequently, i.e. the waste receiving device, has no drive and is instead only moved manually by an operator. The waste receiving device is preferably accommodated in a drawer of the device.
  • the waste receiving device is preferably a collective receiving device with sufficient holding capacity, which can receive handling waste over several handling cycles until its fill level indicates emptying and thus movement. This is why the waste receiving device is moved less frequently than the other devices, which are generally moved at least once, and often even multiple times, during each handling cycle.
  • the waste receiving device can comprise a waste container carrier movably guided in the liquid handling device, to which the aforementioned waste container arrangement can be releasably connected for joint movement. To empty the waste container arrangement, it can preferably be removed from the waste container carrier.
  • the waste container carrier can surround a section of the waste container assembly.
  • a base of the drawer can preferably have at least one recess or cutout that is complementary to the shape of the section of the waste container assembly accommodated therein. This makes it possible to securely accommodate the waste container assembly in the drawer together with the drawer in a few simple steps and with as little movement play as possible.
  • the waste container assembly preferably comprises a waste liquid container as a collection container, into which, in the case of a plurality of reaction containers, all reaction containers dispense liquid as handling waste.
  • the automated liquid handling device discussed here provides a liquid as the handling target, but not its further laboratory processing.
  • the devices mentioned under i. to iii. require regular processing interventions by a device operator.
  • each of the devices mentioned under i. to iii. consisting of the reaction container device, the useful receiving device, and the waste receiving device, is movable along a respective standby movement path between a respective setup position and a respective standby position.
  • the setup positions of the reaction container device, the useful receiving device, and the waste receiving device can and usually will differ from one another.
  • the setup position of each of the devices mentioned is a functional position that differs spatially from the setup position of another of the devices mentioned, but not, or only to a lesser extent, functionally.
  • An automated liquid handling device with the smallest possible installation space can be achieved if the respective standby movement paths of the reaction container device, the useful receiving device, and the waste receiving device run parallel at least in sections.
  • the respective standby movement paths run parallel to one another not only in sections but over most of their extent, particularly preferably over their entire extent. If the standby movement paths of two devices are of different lengths, the shorter one is preferably completely parallel to the longer one. If the standby movement paths of two devices partially overlap and partially do not overlap, the movement path sections extending along a common overlap section are preferably parallel to one another.
  • the position of the respective device is preferably used to prepare the device for a future handling task and/or to complete a previous handling task.
  • the necessary measures often go hand in hand, for example, when the user Receiving device, the useful container arrangement, such as a microtiter plate, with a handling target achieved in the immediately previous handling process is removed from a useful container carrier of the useful receiving device, which carrier releasably supports the useful container arrangement for joint movement as intended, and an empty useful container arrangement is inserted into the useful container carrier to receive the handling target of the next handling process.
  • a further development of the present invention provides that the respective setup positions of the reaction container device, the useful receiving device and the waste receiving device are located outside the device housing.
  • the standby position is a position assumed by the aforementioned devices and each of their components in preparation for or during liquid handling.
  • the liquid handling device comprising the devices can be realized with a small installation space requirement if the reaction vessel device, the useful receiving device, and the waste receiving device are arranged one above or one below the other in their respective standby positions.
  • a standby position of a device is therefore also a standby position for each of its individual components.
  • the useful receiving device comprises a liquid container for each existing reaction container of the reaction container device.
  • the waste receiving device is preferably designed and configured to receive liquid from each reaction container of the reaction container device. Therefore, the base areas of the devices: reaction container device, useful receiving device and waste receiving device, with respect to the device with the largest base area, preferably differ by no more than 20%, preferably by no more than 15%. Arranged one above the other, the Reaction vessel device, the useful receiving device and the waste receiving device occupy approximately the same floor space.
  • the base area is the area depicted when a device is projected onto a projection plane orthogonal to the direction of gravity.
  • a further advantage of the stacking of the aforementioned devices in their respective standby positions is the shortest possible further movement path for arranging a device in a handling position in which the liquid handling takes place.
  • the at least one reaction container of the reaction container device is preferably arranged above at least one useful liquid container of the useful receiving device.
  • a useful liquid container of the useful receiving device is preferably arranged below each reaction container.
  • the waste container arrangement of the waste receiving device which preferably has a waste liquid container as a collecting container, is preferably also arranged such that each reaction container is arranged above a waste liquid container of the waste container arrangement of the waste receiving device.
  • the reaction container device is the uppermost of the three aforementioned devices arranged one above the other.
  • the useful receiving device is preferably arranged in the superimposed arrangement between the reaction container device and the waste receiving device.
  • the useful receiving device is arranged directly below the container device in such a way that no further devices are located between the dispensing opening of the at least one reaction container and a filling opening of at least one useful liquid container. are arranged. Since, in contrast to the utility receiving device, the waste receiving device only concerns the safe reception of handling waste to be disposed of, the waste receiving device is preferably the lowest of the devices arranged one above the other.
  • At least one part of the reaction container device comprising at least one reaction container and at least one part of the useful receiving device comprising at least one useful liquid container can be brought closer to one another and removed from one another along a handling movement path that is different from their respective standby movement paths.
  • At least one part of the reaction container device comprising at least one reaction container and at least one part of the waste receiving device comprising at least one waste liquid container can be brought closer to one another and removed from one another starting from their respective standby positions along a handling movement path that is different from their respective standby movement paths.
  • at least one reaction container arrangement, particularly preferably the at least one reaction container arrangement, as part of the reaction container device and at least the useful container arrangement as part of the useful receiving device are adapted to approach one another along a handling movement path.
  • At least one reaction container arrangement particularly preferably the at least one reaction container arrangement, as part of the reaction container device and at least the waste container arrangement as part of the waste receiving device are adapted to approach one another along a handling movement path.
  • a reaction container of the reaction container device can be immersed a certain distance into a liquid container of the respective receiving device when dispensing liquid to the useful receiving device or to the waste receiving device, so that a liquid jet emerging from the dispensing opening is always directed away from the The wall can then shield the area surrounding the liquid transfer region from radially escaping satellite droplets.
  • the other container arrangement can be fixed to the device housing.
  • the standby movement path is preferably a linear movement path.
  • the handling movement path is preferably a linear movement path.
  • the linear movement path can be curved, but is preferably a straight-line movement axis, which can be implemented particularly easily using a guide device.
  • the part of the useful receiving device comprising at least one useful liquid container and the part of the waste receiving device comprising at least one waste liquid container can each be movable from their respective standby positions along the respective handling movement paths into respective handling positions approaching the reaction container device.
  • the part of the useful receiving device comprising at least one useful liquid container and the part of the waste receiving device comprising at least one waste liquid container can be moved from their respective standby positions along the respective handling movement paths into respective handling positions approaching the reaction container device.
  • the standby position of the reaction container device can also be the handling position of the reaction container device. This means that it can be sufficient for the reaction container device to be displaceable only between its setup position and the standby/handling position.
  • At least one of the devices comprises reaction container device, useful receiving device, and waste receiving device comprise a container carrier into which a container arrangement with at least one liquid container can be removably inserted.
  • the respective liquid containers of the device can be disposed of as disposable containers after use, thus eliminating the need for an otherwise complex cleaning of areas of the liquid handling device.
  • a liquid container of the reaction container device is referred to as a "reaction container" in the present application.
  • each reaction vessel is preferably provided with exactly one useful liquid container, accommodating the respective handling target.
  • the useful liquid containers are preferably integrally connected to one another, for example, as recesses in a common useful container arrangement.
  • a microtiter plate can be a useful container arrangement.
  • Such a useful container arrangement with a plurality of integrally connected useful liquid containers can be easily manufactured using an injection molding process.
  • reaction containers are combined in one piece in a reaction container arrangement, which is also preferably manufactured from plastic using an injection molding process.
  • the reaction container arrangement preferably has a smaller number of containers than the useful container arrangement.
  • several reaction containers can be arranged in a matrix-like arrangement in rows and columns in the reaction container carrier.
  • a reaction container arrangement preferably has as many reaction containers as the matrix arrangement has containers per row or containers per column.
  • the useful container arrangement preferably has a number of useful liquid containers which corresponds to the product of rows and columns of the matrix arrangement, so that it is always ensured that when the useful container arrangement is inserted in a useful container carrier, a useful liquid container is ready to be received for every possible location of liquid dispensing by the reaction container device.
  • the respective handling movement paths run at least partially parallel or collinearly as a relative movement path of the part of the reaction container device comprising at least one reaction container and of the part of the useful receiving device comprising at least one useful liquid container, on the one hand, and as a relative movement path of the part of the reaction container device comprising at least one reaction container and of the part of the waste receiving device comprising at least one waste liquid container, on the other hand. If one relative movement path is longer than the other, the shorter one particularly preferably extends completely parallel or collinearly to the longer one.
  • the handling movement paths are preferably movement paths exclusively of the useful receiving device and the waste receiving device.
  • At least one of the devices consisting of the useful receiving device and the waste receiving device is preferably movable into an evasive position along an evasive movement path that is non-parallel to the handling movement path of another device consisting of the reaction container device, the useful receiving device, and the waste receiving device.
  • the useful receiving device which is preferably located between the reaction container device and the waste receiving device in the stacked arrangement, is movable into an evasive position along a compensating movement path that is orthogonal to the handling movement path of the waste receiving device, so that the part of the waste receiving device comprising at least one waste liquid container can be brought closer to the reaction container device without colliding with the useful receiving device.
  • the evasive movement path of the device from the useful receiving device and the waste receiving device is preferably parallel or collinear to its standby movement path. Collinearity is particularly preferred, so that the device in question
  • the same drive and the same guide device can be moved once between the standby position and the setup position and another time between the standby position and the alternative position.
  • the alternative position is preferably located between the standby position and the setup position of the device and particularly preferably within the device housing.
  • the handling movement paths of the useful receiving device and the waste receiving device are parallel to each other or collinear and orthogonal to the standby movement paths of the receiving devices.
  • the automated liquid handling device comprises a common lifting device for displacing the part of the useful receiving device comprising at least one useful liquid container and the part of the waste receiving device comprising at least one waste liquid container along their respective handling movement paths between their respective standby position and their respective handling position.
  • the handling movement paths preferably run parallel to the direction of gravity.
  • the common lifting device preferably has mobility only along the handling movement path, wherein the waste container assembly is preferably brought into driving engagement with the lifting device upon engagement into its ready position.
  • This driving engagement can be a contact engagement or a form-fitting engagement.
  • the above-described recess or recess in the waste container carrier facilitates lifting the waste container assembly out of the waste container carrier.
  • the common lifting device can lift the waste container assembly arranged in the standby position with a lifting movement of its lifting gear.
  • the common lifting device therefore either lifts and lowers only the waste container assembly, namely when the waste container assembly is not in its standby position, for example in its alternative position or in its setup position, or it raises and lowers the waste container arrangement and the useful container arrangement together when the useful container arrangement is to be moved into its handling position to receive the handling target.
  • the lifting device comprises a weighing device with which it can detect the weight of the at least one lifted component.
  • the lifting device can be used with the weighing device to qualitatively or quantitatively detect the fill level of the waste container assembly and determine the need for emptying.
  • the magnet arrangement is preferably also movable in order to be able to generate a variable magnetic field on the at least one reaction vessel depending on its position.
  • the magnet arrangement preferably comprises permanent magnets, so that the generation of a magnetic field by the magnet arrangement is independent of a power supply.
  • the magnet arrangement is preferably multi-part, in particular two-part, with each magnet-bearing part of the magnet arrangement preferably being movable parallel to the handling movement path of the receiving devices. Particularly preferably, this is the only mobility of the magnet arrangement.
  • the input openings of the plurality of reaction vessels of the reaction vessel device are arranged in a common surface, in particular in a common plane.
  • Surface is not to be understood in the strictly mathematical sense as an infinitely thin two-dimensional shape, but rather as an engineering surface with a thickness determined, among other things, by the manufacturing and arrangement tolerances of reaction vessels, reaction vessel supports, and the like.
  • the input openings, arranged ready for handling, are located in this surface.
  • the pressure-variation device and the dosing device are displaceable parallel to the common surface.
  • the direction of extension of the common surface preferably runs parallel to the standby movement path of one of the reaction vessel device, the useful receiving device, and the waste receiving device.
  • the common surface preferably extends orthogonally to the handling movement paths of the receiving devices. Further preferably, the common surface is a flat surface.
  • the pressure-changing device and the dosing device both essentially only need to serve the inlet openings of the provided reaction vessels, they can be driven for movement by a common drive. Therefore, according to a preferred development, the pressure-changing device and the dosing device can be combined to form a jointly displaceable combined feeding device with at least one gas outlet opening, different from the dosing opening, for discharging gas and with the at least one dosing opening.
  • the loading device is displaceable along a loading path in a direction orthogonal to the handling movement path. Additionally, the loading device can be moved along a working path in a direction away from and toward the reaction vessel device. The mobility along the working path allows a sealing arrangement carried by the loading device, in particular by the pressure-changing device, to be pressed sealingly against the reaction vessel and then lifted off again.
  • Fig. 1 is a roughly schematic perspective view of a liquid handling device of the present invention obliquely from the front and above
  • Fig. 2 is a schematic perspective view of the liquid handling device of Figure 1 without housing walls
  • Fig. 3 is an enlarged schematic side view according to Figure 2 with the reaction container device and the useful receiving device in positions different from the illustration in Figure 2,
  • Fig. 4 is an enlarged schematic perspective interior view of the liquid handling device of Figures 1 to 3 with partially sectioned devices,
  • Fig. 5 is an enlarged schematic perspective interior view, partially sectioned like that of Figure 4, with the useful receiving device in an alternative position,
  • Fig. 6 is a rough schematic representation of the magnet carrier arrangement of the magnet device of the liquid handling device of Figures 1 to 5 in plan view
  • Fig. 7 is an exploded bottom view of one magnet carrier of the magnet carrier arrangement of the magnet device
  • Fig. 8 is an exploded bottom view of the other magnet carrier of the magnet carrier arrangement of the magnet device.
  • Fig. 9 is a perspective view obliquely from above of a reaction container arrangement for use on the reaction container device of the liquid handling device of Figs. 1 to 5,
  • Fig. 10A is a longitudinal sectional view through the reaction vessel assembly of
  • Fig. 10B is a roughly schematic side view of the reaction vessel arrangement of Figure 10A with an exaggerated curvature for fixing the reaction vessel arrangement in the reaction vessel carrier,
  • Fig. 11 is a longitudinal section through a peripheral reaction vessel, cut along the same cutting plane as that of Figure 10A,
  • Fig. 12 is an enlarged view of the discharge end of the reaction vessel of Figure 11,
  • Fig. 13 is a roughly schematic detailed view of an input end of a reaction vessel and an adjoining vessel section with a radial projection for fixing the reaction vessel in a reaction vessel receptacle of the reaction vessel carrier,
  • Fig. 14 shows a cross-section through a reaction vessel along a sectional plane orthogonal to its virtual vessel axis
  • Fig. 15 is a plan view of the reaction vessel assembly of Figures 9 and 10A,
  • Fig. 16 is a cross-sectional view of a reaction vessel arrangement along a section plane XVI-XVI in Fig. 10A oriented orthogonally to the virtual vessel axes of the reaction vessels,
  • Fig. 17 is a perspective view of the waste liquid container of the liquid handling device of Figs. 1 to 5,
  • Fig. 18 is a perspective cross-sectional view of the waste liquid container of Fig. 17, Fig. 19 is a perspective view of the loading device of the liquid handling device of Figures 1 to 5 with its movement apparatus, viewed predominantly from below,
  • Fig. 20 is a further perspective view of the loading device with its movement apparatus of Fig. 19,
  • FIG. 21 perspective view of the switchable valve-bearing rear side of the loading device of Figures 19 and 20,
  • Fig. 22 is a perspective view of the loading device of Figs. 19 to 21 mainly from below and without switchable valves,
  • Fig. 23 a piping system in the piping body of the loading device of Figs. 19 to 22,
  • Fig. 24 is a perspective view of the rear of the loading device of Fig. 22, without switchable valves, and
  • Fig. 25 is a perspective view of the front of the loading device of Figs. 19 to 22 and 24, without switchable valves.
  • an embodiment of a liquid handling device is generally designated by 10.
  • the liquid handling device 10 comprises a device housing 12.
  • the viewer of Figure 1 looks at the front side 12a with the front wall 13a, the top side 12b with the top wall 13b and the right side 12c with the right side wall 13c of the device housing 12.
  • An operator working with the liquid handling device 10 is usually located opposite the front side 12a.
  • a display and A control panel 14 is arranged on which information about an ongoing, a prepared, and/or a completed liquid handling process of the liquid handling device 10 can be displayed.
  • the display and control panel 14, as a touchscreen serves not only as an output device but also as an input device of the liquid handling device, or "device" 10 for short. Consequently, an operator can also enter data and commands into the device 10 or its control device 40 (see Fig. 2) via the display and control panel 14.
  • an access opening 16 which is open in the operating state of Figure 1 and through which a reaction container device 18 has been moved out of the interior of the device housing 12.
  • the reaction container device 18 is located in its setup position outside the device housing 12. In the setup position, the reaction container device 18 and numerous of its components are accessible to an operator or a service robot.
  • the reaction container device 18 comprises a reaction container carrier 20, on which a plurality of reaction container assemblies 86 (see Fig. 3), explained in more detail below, as well as a sealing assembly 22, also explained below, for use in the loading device 62 of the device 10 can be arranged by the operator.
  • the reaction container carrier 20 has reaction container receptacles 24 arranged in a matrix-like manner in an orthogonal 12 x 8 matrix for receiving reaction containers 88 (see Figs. 9 to 16) or reaction container assemblies 86, and has a sealing assembly receptacle 26 designed as a recess, in which a new, unused sealing assembly 22 is located in Fig. 1 for a subsequent handling operation.
  • the reaction container device 18 is movable along the preferably rectilinear standby movement path RB starting from the illustrated setup position into a standby position located inside the device housing 12.
  • the access opening 16 is preferably assigned a flap (not shown in Figure 1) prestressed into its closed position to automatically close the access opening 16 in the absence of any devices passing through it.
  • the flap (not shown) is displaced by the reaction vessel device 18, against its prestress, into its open position, which differs from the closed position, as it approaches its setup position, and is held in the open position for the duration of the projection of the reaction vessel device 18 through the access opening 16 into the external environment U of the device 10.
  • a drawer 28 in which a waste receiving device 46 (see Fig. 2 ff.) is accommodated, explained further below.
  • the drawer 28 can be pulled out of the device housing 12 from the standby position shown in Figure 1 along a rectilinear standby movement path AB of the waste receiving device 46, parallel to the standby movement path RB of the reaction container device 18, and pushed back into the device housing 12.
  • a standby position of the drawer 28 corresponds to a standby position of the waste receiving device 46, which is movable together with the drawer 28.
  • an operating fluid compartment 32 in which, by way of example, two containers 34 and 36 containing operating fluids are provided for use during fluid handling operations in the device 10.
  • the container 34 may contain a cleaning fluid and the container 36 may contain an elution fluid.
  • Extraction lines 38a and 38b extend into the containers 34 and 36 and reach almost to the bottom of the respective container 34 and 36.
  • a pressure line 38c enables the introduction of gas into the operating fluid compartment 32 to increase the gas pressure above the respective liquid level of the operating fluid contained in the containers 34 and 36 relative to the atmospheric pressure of the environment U, so that the gas pressure in the operating fluid compartment 32 forces the operating fluids in the containers 34 and 36 into the respective extraction lines 38a and 38b.
  • An actual flow of operating fluids in a line system of the device 10, which also includes the extraction lines in 38a and 38b, is controlled in the device 10 by switching valves explained in more detail below, which can be switched between a flow position and a blocking position.
  • the operating fluid compartment 32 is sealed from the outside environment and from the rest of the interior of the device 10 in order to maintain a gas pressure level that is higher than the outside environment U.
  • Figure 2 shows a part of the interior I of the device 10.
  • the control device 40 of the device 10 is only roughly schematically indicated by the representation of some integrated circuit boards.
  • This control device 40 as an electronic data processing unit, controls processes in the device 10 and, for this purpose, controls actuators and drives, is in data transmission connection with sensors, and reads out a data memory 42 integrated in the control device 40 or writes to it.
  • the drawer 28 has a drawer base 28a, in which a waste container arrangement 44 with, in this embodiment, only a single waste liquid container 45 as a collecting container is inserted in a recess 28b in a form-fitting manner for joint movement with the drawer 28.
  • the waste container arrangement 44 and thus the waste liquid container 45 can, however, be lifted out of the recess 28b against the direction of gravity g, so that an operator or an operating robot can remove the waste liquid container 45 when the drawer 28 is moved from the position shown in Figures 1 and 2.
  • the waste container 46 which has been moved from its standby position along the standby movement path AB into its setup position located outside the device 10, can be removed from the drawer 28, emptied, cleaned, and reinserted into the recess 28b.
  • the drawer 28 with its drawer base 28a is thus a waste container carrier within the meaning of the introduction to the description.
  • a guide rail 48 can be seen as a guide device of the waste receiving device 46, which guides the drawer 28 together with the waste receiving device 46 for movement along the standby movement path AB.
  • the useful receiving device 50 is guided by a guide rail 54 fixed to the device housing as part of a guide device of the useful receiving device 50 for movement along a standby movement path NB of the useful receiving device 50.
  • the useful receiving device 50 In contrast to the waste receiving device 46, which can only be moved manually in the present embodiment, the useful receiving device 50, or more precisely its useful container carrier 52, can be driven by an electric motor via a belt drive 56.
  • the control device 40 can actuate the belt drive 56, so that the control device 40 can control the movement of the useful receiving device 50 between a setup position, also located outside the device housing 12, and the standby position shown in Figure 2.
  • the standby movement path NB of the useful receiving device 50 is parallel to the standby movement paths AB and RB of the waste receiving device 46 and the reaction container device 18, respectively.
  • Above the useful receiving device 50 is the reaction container device 18, already known from Figure 1.
  • the reaction container device 18, or more precisely the reaction container carrier 20 is guided on a guide rail 58 as part of a guide device for movement along the standby movement path RB of the reaction container device 18.
  • the reaction container device 18, or more precisely the reaction container carrier 20, can also be driven by an electric motor-operated belt drive 60 by the control device 40 for movement along the standby movement path RB.
  • the setup positions of the reaction vessel device 18 and the useful receiving device 50 are also located outside the device housing 12, one above the other and one below the other.
  • the devices 18 and 50 can be moved into their setup position through one and the same access opening 16, provided the access opening 16 is large enough. Otherwise, a separate access opening can be formed for each of the devices 18 and 50 on the front side 12a of the device housing 12.
  • a loading device 62 is arranged, which, as will be explained in more detail below, comprises a metering device 62a for transferring operating liquid into one or more reaction vessels 88 and a pressure changing device 62b for changing the pressure of a gas in one or more reaction vessels 88.
  • the metering device 62a and the pressure changing device 62b are connected or combined for joint movement in the loading device 62 along a loading path BP orthogonal to the previously explained standby movement paths AB, NB and RB.
  • the loading device 62 is also connected by a guide rail 64 for movement along the loading track BP and can be driven to move by means of an electromotive belt drive 66 controllable by the control device 40.
  • a compressor 68 and a pressure accumulator 69 can be seen as part of the pressure-changing device 62b.
  • the compressor 68 which can be controlled by the control device 40, enables the compression of gas, in particular air, which is provided as compressed gas, in particular compressed air, in the pressure accumulator 69 and can be removed through switchable valves along selected lines.
  • a pressure sensor 69a can detect the gas pressure in the pressure accumulator 69 and transmit it to the control device 40.
  • reaction container 88 Gas is always present in a reaction container 88 of the reaction container device 18. Additionally, the reaction container 88 can be filled with a liquid, which can be expelled from a discharge opening of the reaction container by increasing the gas pressure in the reaction container 88 by the charging device 62, more precisely by the pressure-changing device 62b. Depending on whether the useful receiving device 50 or the waste receiving device 46 is located below a reaction container 88 when expelling a liquid, the liquid expelled from the reaction container 88 is discharged either into the useful liquid container 90 (see Fig. 3) of the useful receiving device 50 or into the waste liquid container 45.
  • the present application fundamentally distinguishes between a liquid present in the reaction vessel 88 as a handling target, in which case the liquid present was desired as an intermediate or final product of a liquid handling, and a liquid present in the reaction vessel 88 as handling waste, in which case the liquid present is no longer required and is disposed of.
  • the transparent cover 32b of the operating fluid compartment 32 can be displaced upwards from the position shown in Figures 1 and 2 in order to change the containers 34 and 36 in the operating fluid compartment 32 and, if necessary, to carry out cleaning work in the compartment 32.
  • the cover 32b is connected to a compartment mechanism 32c is connected to a guide carriage 32d that can be displaced along the guide rail 32a. Gravity preloads the cover 32b into the position shown in Figures 1 and 2, in which the operating fluid compartment 32 is sealed gas-tight by the cover.
  • a magnetic device 70 is arranged on the device 10, by means of which a magnetic field can act inside the reaction vessels 88.
  • the magnetic device 70 is largely concealed by the reaction vessel device 18 in the view of Figure 2.
  • Figures 3 to 5 show the interior region I of the device housing 12 in further operating situations, which also reveal the magnetic device 70.
  • the magnetic field emanating from the respective magnet carrier 72a or 72b can be shifted in its spatial position relative to the reaction vessels 88 of the reaction vessel device 18.
  • the movement drives 74a and 74b can also be controlled by the control device 40 such that the two magnet carriers 72a and 72b are moved synchronously and in the same direction, in particular as a single magnet carrier arrangement 72.
  • the lifting movement of the lifting device 82 of the lifting mechanism 76 is effected by a lifting drive 84, which in Figure 3 is partially concealed by the guide rail 64 and the belt drive 66.
  • the lifting drive 84 is preferably an electric drive that can be controlled by the control device 40.
  • the movement drives 74a and 74b of the magnetic device 70 and the lifting drive 84 are similar, particularly preferably identical, drives.
  • the useful container device 50 can be moved into its alternative position shown in Figure 3, which is located along the standby movement path RB between its setup position and its standby position.
  • FIG. 3 shows that a plurality of reaction vessel arrangements 86, in this case exactly 12, each comprising 8 reaction vessels 88 are arranged parallel to one another in the reaction vessel carrier 20. This results in an orthogonal arrangement of 96 reaction vessels 88 in a 12 x 8 matrix, which corresponds to that of the reaction vessel receptacles 24, since each reaction vessel 88 is arranged in a reaction vessel receptacle 24.
  • utility liquid containers 90 are also arranged in an orthogonal 12 x 8 matrix, so that in the standby position of the devices 18 and 50 and also in the handling position of the devices 18 and 50, a reaction container receptacle 24 is arranged above each utility liquid container 90, and thus at least one reaction container 88 can be arranged.
  • Figure 3 also shows a contactless container sensor 92, already shown in Figure 2; in the exemplary case shown, this is an ultrasonic sensor, with which the presence of a reaction container arrangement 86 in the reaction container carrier 20 and, if applicable, further information associated with an existing reaction container arrangement 86 can be detected and transmitted to the control device 40.
  • the container sensor 92 is connected to the loading device 62 for joint movement along the loading path BP.
  • the devices 18, 46, 50, 70 and 76 are shown in a perspective sectional view, wherein the sectional plane runs parallel to the handling movement path HB on the one hand and parallel to the standby movement paths RB and NB on the other hand.
  • FIG 4 shows only the magnet carrier 72a of the magnet device 70, but not the magnet carrier 72b, which is also present.
  • the waste container arrangement 44 will be explained in detail below using separate figures.
  • the useful receiving device 50 is moved away from its standby position in the direction of the setup position along its standby movement path NB.
  • the waste liquid container 45 can therefore be brought closer to the reaction containers 88 of the reaction container device 18 by the lifting device 76.
  • An edge 45b of the waste liquid container 45 which projects outward from the receiving volume 45a in the container interior of the waste liquid container 45, rests on a support formation 82a of an arm 82b of the lifting device 82, so that the waste liquid container 45 can be lifted by the lifting device 82 through this positive support engagement.
  • the lifting device 82 encompasses the waste liquid container 45 in a fork-like manner on two opposite sides. The side closer to the viewer in Figure 4, with the arm of the lifting device 82 arranged there, lies in front of the sectional plane of Figure 4 and is therefore not shown.
  • the lifting device 82 also has a projection 82c, here: a vertical projection 82c, on which the useful container assembly 78, optionally with an adapter receiving it in the useful container carrier 52, can engage during a lifting movement along the handling movement path HB of the lifting device 82 for carrying it along against the direction of gravity g.
  • the formations 82a, 82b, and 82c are preferably formed as a single piece and monolithic.
  • the lifting device 76 has a weighing sensor 83, which detects the weight lifted by the lifting device 82 and transmits it to the control device 40. Thus, if the tare weight is known or can be determined, the control device 40 can determine the fill level of the waste container assembly and, when a predetermined fill threshold is reached, issue a warning message on the display and control panel 14.
  • the magnet carrier 72a is in Figure 4 in a maximally lowered position, as is necessary so that the reaction container device 18 with the reaction container assemblies 86 arranged thereon can be moved collision-free along its standby movement path RB from the standby position shown in Figure 4 into the setup position shown in Figure 1.
  • the waste container assembly 44 and/or the useful container assembly 52 can be lifted in their respective standby positions towards the reaction container device 20 in its standby/handling position. This can ensure that an output end 106 of a reaction container container 88 for dispensing liquid into a container containing the liquid consisting of the useful liquid container 90 and the waste liquid container 45, for an immersion distance of approximately 1 to 2 mm.
  • waste container arrangement 44 Since the waste container arrangement 44 would have to be removed from its standby position for the sole lifting movement of the utility container arrangement 78 by the lifting device 76 and its lifting gear 82, which can only be done manually in the illustrated embodiment, either the waste container arrangement 44 alone or the waste container arrangement 44 and the utility container arrangement 78 are lifted together by the lifting device 76.
  • the magnet carrier assembly 72 comprising the magnet carriers 72a and 72b, is raised into the extension area of the reaction containers 88, so that the waste liquid container 45 could be brought closer by the lifting device 86 along the handling movement path HB to the reaction container device 18, which is only movable along the standby movement path RB. Meanwhile, the useful receiving device 50 is in its evasive position, displaced relative to the standby position along its standby movement path NB.
  • Figure 6 shows a rough schematic plan view of the magnet carrier arrangement 72 of the magnetic device 70.
  • Figures 7 and 8 show the magnet carriers 72a and 72b in exploded bottom views, more realistically than in Figure 6.
  • first rows 88a and only four of eight second rows 88b are indicated by dash-dotted lines, starting from the reaction vessel 88 on the upper left in Figure 6.
  • the eight reaction vessels 88 of each reaction vessel arrangement 86 formed in one piece by injection molding run along a first row 88a.
  • the maximum number of reaction vessel arrangements 86 that can be arranged in the reaction vessel carrier 20 corresponds to the maximum number of first rows 88a.
  • first rows 88a and second rows 88b which each run parallel to the plane of the drawing in Figure 6, span a reference plane BE which is also parallel to the plane of the drawing in Figure 6.
  • the magnet carrier arrangement 72 has a plurality of matrix magnets 94, which are arranged distributed among the magnet carriers 72a and 72b.
  • the matrix magnets 94 are physically and magnetically essentially identical permanent magnets, but are arranged with different polarization orientations depending on their location in the magnet carrier arrangement 72. Common to all matrix magnets 94 is that their polarization direction 94a runs parallel to the reference plane BE and non-parallel to both the direction of the first rows 88a and the direction of the second rows 88b.
  • the polarization direction 94a is the shortest direction in which the magnetic south pole of a matrix magnet 94, indicated by the letter “S” in Figure 6, follows the magnetic north pole of the same matrix magnet 94, indicated by the letter “N.”
  • a boundary surface 94b, orthogonal to the polarization direction 94a, between the magnetic north pole and the magnetic south pole of each matrix magnet 94 runs orthogonal to the reference plane BE.
  • all polarization directions 94a of the matrix magnets 94 arranged in the magnet carrier arrangement 72 are offset by an amount of 45° with respect to the direction of the first rows 88a and the direction of the second rows 88b is rotated about an axis of rotation orthogonal to the drawing plane of Figure 6 and thus to the reference plane BE.
  • the number of matrix magnets 94 in the magnet carrier arrangement 72 is less than the number 96 of reaction vessels 88 and is greater than the sum of the first and second rows 88a and 88b, i.e. in the present case greater than 20.
  • the number of matrix magnets is 58. In the illustrated embodiment, it is half the sum of the number (96) of reaction vessels 88, the number (12) of first rows 88a and the number (8) of second rows 88b.
  • the matrix magnets 94 are also arranged in an orthogonal matrix, specifically along mutually parallel third rows 96a and along mutually parallel fourth rows 96b. For clarity, only the left-most first three third rows 96a and only the topmost first three fourth rows 96b are shown in Figure 6 and provided with reference symbols.
  • the third rows 96a are parallel to the first rows 88a, and the fourth rows 96b are parallel to the second rows 88b.
  • the matrix magnets 94 are located at intersections of the third rows 96a and the fourth rows 96b. However, in contrast to the reaction vessels 88, where each intersection between the first rows 88a and the second rows 88b is occupied by a reaction vessel 88, a matrix magnet 94 is not arranged at each intersection of a third row 96a and a fourth row 96b. In the matrix of matrix magnets 94 formed from the third rows 96a and the fourth rows 96b, in each row of the third rows 96a and the fourth rows 96b, an intersection located adjacent to an intersection occupied by a matrix magnet 94 is not occupied by a matrix magnet 94.
  • the polarization directions 94a of all matrix magnets 94 arranged in a common third row 96a are the same, and the polarization directions 94a of all matrix magnets 94 arranged in a common fourth row 96b are the same.
  • the polarization directions 94a of the matrix magnets 94 arranged in adjacent third rows 96a are rotated from row to row by an angular amount of 90° with respect to a rotation axis orthogonal to the reference plane BE.
  • the direction of rotation at the transition from a third row 96a to an adjacent third row 96a is the same for all matrix magnets 94 of a common third row 96a with respect to the matrix magnets in the adjacent third row 96a.
  • the direction of rotation alternates between counterclockwise and clockwise from one third row 96a to the next third row 96a.
  • each reaction vessel 88 is opposite a different polarization section of the two adjacent matrix magnets 94.
  • only one polarization section of one of the matrix magnets 94 i.e. only either the magnetic north pole or only approximately the magnetic south pole, faces the reaction vessel 88, while both polarization sections and the edge emerging from the matrix magnet 94 faces the virtual interface 94b between the two polarization sections of the other of the two matrix magnets 94.
  • the two physically and magnetically essentially identically designed adjacent matrix magnets 94 act with different magnetic field strengths on the magnetic field generated by each of the two matrix magnets 94.
  • the matrix magnets 94 immediately adjacent to one and the same reaction container 88 are arranged on different and separately movable magnet carriers 72a and 72b.
  • all third or fourth rows with odd row numbers are arranged on one and the same magnetic carrier.
  • all third rows 96a with odd numbers are arranged on the magnetic carrier 72a.
  • all third or fourth rows with even numbers are arranged on one and the same other magnetic carrier.
  • all third rows 96a with even row numbers are arranged on the magnetic carrier 72b.
  • All third rows 96a of a magnet carrier 72a or 72a have the same number of matrix magnets 94 in the present case, but the third rows 96a with even numbering, i.e. the third rows 96a of the magnet carrier 72a, in the present case
  • the number of matrix magnets 94 is 1 less than that of the third rows 96a of the magnet carrier 72b.
  • the latter rows have 5 matrix magnets 94.
  • the third rows 96a of the magnet carrier 72a on the other hand, each have only 4 matrix magnets 94.
  • the magnet carriers 72a and 72b are structurally largely identical or similar.
  • Each magnet carrier 72a and 72b comprises a magnet carrier base 72a-1 or 72b-1, from which magnet carrier legs 72a-2 or 72b-2 project orthogonally to the respective magnet carrier base 72a-1 or 72b-1, preferably projecting on one side.
  • the magnet carrier legs 72a-2 run parallel to one another.
  • the magnet carrier legs 72b-2 run parallel to one another.
  • the magnet carrier bases 72a-1 and 72b-1 run parallel to one another. Consequently, the magnet carrier legs 72a-2 and 72b-2 also run parallel to one another.
  • the magnet carrier legs 72a-2 or 72b-2 of one magnet carrier 72a or 72b run towards the magnet carrier base of the other magnet carrier 72b or 72a.
  • the magnet carrier base of a magnet carrier in this case the magnet carrier base 72a-1 of the magnet carrier 72a, is longer than the magnet carrier base 72b-1 of the magnet carrier 72b.
  • the magnet carrier 72a has more magnet carrier legs 72a-1, in this case by exactly one more magnet carrier leg than the magnet carrier 72b has magnet carrier legs 72b-1.
  • the magnet carrier legs 72a-2 and 72b-2 are arranged interlaced, so that each magnet carrier leg 72b-2 of the magnet carrier 72b with the shorter magnet carrier base 72b-1 runs in the spacing space between two immediately adjacent magnet carrier legs 72a-2 of the magnet carrier 72a with the longer magnet carrier base 72a-1.
  • magnet carrier leg 72a-2 or 72b-2 of a magnet carrier 72a or 72b has an adjacent magnet carrier leg on each side along the direction of its magnet carrier base 72a-1 or 72b-1, these two adjacent magnet carrier legs are magnet carrier legs 72b-2 or 72a-2 of the other magnet carrier 72b or 72a, respectively.
  • the magnet support legs 72a-2 and 72b-2 each carry the matrix magnets 94 of a third row 96a.
  • the magnet support legs 72a-2 carry the third Rows 96a with odd row number and the magnet carrier legs 72b-2 the third rows 96a with even row number.
  • those matrix magnets 94 which, in their third row 96a or in their fourth row 96b, in which they are arranged, are not adjacent to an intersection point of a third row 96a with a fourth row 96b in at least one direction are outer matrix magnets 94-1.
  • those matrix magnets 94 which, in both their third row 96a and their fourth row 96b, in which they are arranged, are adjacent to an intersection point of a third row 96a with a fourth row 96b in each row direction are inner matrix magnets 94-2.
  • the inner matrix magnets 94-2 of a magnet support leg 72a-2 or 72b-2 project beyond this magnet support leg on both sides in a direction orthogonal to the direction of extension of the magnet support leg 72a-2 or 72b-2 supporting them. Therefore, sections, preferably equal-sized sections, of one and the same inner matrix magnet 94-2 are exposed on both sides of the magnet support leg 72a-2 or 72b-2 supporting it. The inner matrix magnets 94-2 can thus be brought as close as possible to a container wall 110 of the nearest reaction container 88.
  • reaction vessels 88 which, in their first row 88a or in their second row 88b in which they are arranged, are not adjacent to an intersection point of a first row 88a with a second row 88b in at least one row direction are peripheral reaction vessels 88-1.
  • those reaction vessels 88 which, in both their first row 88a and their second row 88b in which they are arranged, are adjacent to an intersection point of a first row 88a with a second row 88b in each row direction are internal reaction vessels 88-2.
  • Each inner matrix magnet 94-2 is adjacent to four reaction vessels 88, which, due to their orthogonal matrix arrangement, are arranged at the corners of a rectangle containing the respective inner matrix magnet 94-2.
  • the corners of the rectangle are formed by the respective virtual container axes BA (see, for example, Fig. 10A, 11, 15 and 16) of the reaction containers 88 involved.
  • Each outer matrix magnet 94-1 is adjacent to two reaction vessels 88, more precisely two peripheral reaction vessels 88-1.
  • a reaction container 88 is located between each matrix magnet 94 and a matrix magnet 94 of the same rectangle that is adjacent along the edge of the rectangle.
  • the rectangular edges of the virtual rectangles of the matrix magnets 94 thus formed run at an angle of 45° to the third and fourth rows 96a and 96b that the matrix magnets 94 have.
  • each inner matrix magnet 94-2 is arranged face-centered with respect to the rectangle formed by the four reaction vessels 88 closest to and surrounding it in the reference plane BE
  • the reaction vessels 88 are arranged edge-centered with respect to four matrix magnets 94, which span a rectangle with the smallest area in the reference plane BE.
  • Figures 7 and 8 each show a perspective bottom view of the magnet carrier arrangement 72 or its magnet carriers 72a and 72b in a more realistic representation than in Figure 6.
  • the magnet carriers 72a and 72b comprise at least two components, namely a magnet receiving component 73a-1 or 73b-1 and a magnet holding plate 73a-2 or 73b-2.
  • the matrix magnets 94 are inserted from the underside into largely complementary receiving recesses 95a and 95b of the magnet receiving component 73a-1 and 73b-1, respectively, and are secured therein by a form-fitting manner against falling out sideways.
  • the magnets 94 are fixed to the underside of the respective magnet receiving component 73a-1 and 73b-1 with The magnet holding plate 73a-2 or 73b-2, fastened with screws 98, secures the matrix magnets 94 in their receiving recesses 95a or 95b of the magnet receiving component 73a-1 or 73b-1 against falling out in the direction g of gravity.
  • the magnet holding plate 73a-2 or 73b-2 has essentially the same circumferential contour, consisting of the base and the legs projecting therefrom, as the magnet receiving component 73a-1 or 73b-1 to which it is screwed.
  • the matrix magnets 94 can be arranged as close as possible to a dispensing opening of the reaction containers 88, so that a magnetic field emanating from the matrix magnets 94 can effectively act on a liquid held in a reaction container 88 even if the amount of liquid in the reaction container 88 is very small and the liquid is essentially only in the vicinity of the dispensing end or the dispensing opening.
  • a fastening extension 72a-3 or 72b-3 which in the illustrated embodiment is preferably formed in one piece only on the respective magnet receiving component 73a-1 or 73b-1, which in the illustrated embodiment is designed as an extension of the respective magnet carrier base 72a-1 or 72b-1, enables a force-transmitting connection with the respective movement drive 74a or 74b of the magnet carrier 72a or 72b.
  • recesses 100a and 100b are formed in the magnet carrier legs 72a-2 and 72b-2 of the magnet carriers 72a and 72b, respectively, which are complementary to an outer shape of the reaction containers 88, more precisely to an outer shape of an axial section of the reaction containers in which the magnet carriers 72a and 72b are arranged during operation of the device 10.
  • FIG. 9 shows a perspective view obliquely from above of a reaction container arrangement 86, as used on the reaction container device 18.
  • a plurality of reaction containers 88 are arranged successively along a following path FB.
  • Each reaction container 88 extends along a virtual container axis BA.
  • the container axes BA of the reaction containers 88 of a reaction container arrangement 86 which are imagined to pass centrally through the reaction containers 88, lie in a plane spanned by the direction vectors of the container axes BA and the following path FB and, at least when the reaction container arrangement 86 is received in the reaction container carrier 20, run parallel to one another and transversely, preferably orthogonally, to the following path FB.
  • Figure 10A shows a longitudinal sectional view through the reaction container arrangement 86 of Figure 9, wherein the sectional plane contains the virtual container axes BA of the individual reaction containers 88.
  • the viewing direction of the sectional view of Figure 10A is indicated by the arrow XA in Figure 9.
  • Figure 10B shows a roughly schematic side view of the reaction container arrangement 86 of Figure 10A with an exaggerated curvature for improved fixation of the reaction container arrangement 86 in the reaction container carrier 20.
  • Figure 11 shows a longitudinal section through a reaction container 88, more precisely through an edge-mounted reaction container 88-1. The sectional plane of Figure 11 is the same as that of Figure 10A.
  • Figure 12 shows an enlarged view of the output end of the reaction container 88 of Figure 11.
  • Figure 13 shows a roughly schematic detailed view of the input end of a reaction container 88 and the adjoining container section with a radial projection for fixing the reaction container 88 in a reaction container receptacle.
  • Figure 14 shows a cross section with a cutting plane orthogonal to the virtual container axis BA through a reaction container 88, more precisely through an edge-mounted reaction container 88-1, to explain the radial projections arranged equidistantly in the circumferential direction for fixing the reaction container 88 in a reaction container receptacle 24.
  • Figure 15 shows a plan view of the reaction container arrangement of Figures 9 and 10A and Figure 16 shows a cross-sectional view along the cutting plane XVI-XVI of Figure 10A orthogonal to the virtual container axes BA below a band connecting the reaction containers 88 of the reaction container arrangement 86, but in Area of the radial projections and a web connecting a reaction vessel 88 with its adjacent reaction vessel 88 along the following path FB.
  • Each reaction vessel 88 has an input end 102 with, in the illustrated embodiment, a substantially circular input opening 104. At a distance D (see Fig. 11) measured along the virtual vessel axis BA from the input end 102 and the input opening 104, the reaction vessel 88 has an output channel 108 at an output end 106 opposite the input end 102.
  • a receiving volume 112 is formed above the discharge channel 108.
  • a liquid 109 with ferromagnetic particles 109a suspended therein can be received in this receiving volume in the reaction container, which is preferably introduced into the reaction container 88 through the input opening 104.
  • the discharge channel 108 penetrating the container wall 110 is dimensioned such that when the receiving volume 112 is filled with a liquid 109, the liquid 109 is held in the receiving volume 112 by capillary pressure in the discharge channel 108 until the pressure in the receiving volume 112 sufficiently exceeds the capillary pressure in the discharge channel 108 by blowing in gas by means of the pressure-changing device 62b through the inlet opening 104. In this case, the liquid 109 begins to exit the receiving volume 112 through the discharge channel 108. This preferably occurs in a free jet.
  • FIG. 12 A more detailed representation of the shape of the dispensing channel 108 is shown in Figure 12.
  • the dispensing channel 108 On its side facing the receiving volume 112, the dispensing channel 108 has an inlet opening 114, which marks the axial longitudinal end of the dispensing channel 108 closer to the receiving volume 112 along the virtual container axis BA.
  • the dispensing channel 108 ends in a dispensing opening 116.
  • the distance D specified above extends from the input opening 104 to the inlet opening 114 and forms a reference dimension RD of the reaction vessel 88.
  • the input opening 104, the output channel 108 and thus in particular the inlet opening 114 and the output opening 116 are arranged coaxially with respect to the virtual container axis BA.
  • the inlet opening 114 is completely surrounded by an inlet surface 118.
  • the inlet surface 118 is preferably oriented orthogonally to the container axis BA.
  • the outlet opening 116 is completely surrounded by an outlet surface 120, which in the illustrated preferred embodiment is also oriented orthogonally to the virtual container axis BA and is therefore parallel to the inlet surface 118.
  • the surface area of the outlet surface 120 is larger than the surface area of the inlet surface 118.
  • an axial projection 122 extending along the container axis BA preferably extends in a closed manner around the container axis BA in the circumferential direction.
  • the overhang length of the axial projection 122 relative to the dispensing surface 120 is less than the thickness T of the container wall 110.
  • the overhang length L of the axial projection 122 relative to the dispensing surface 120 is also less than the distance d, measured along the container axis BA, between the inlet surface 118 and the dispensing surface 120.
  • the thickness T of the container wall can be 0.5 to 0.8 mm, preferably 0.6 mm.
  • the distance d of the inlet surface 118 from the outlet surface 120 can be 0.3 to 0.6 mm, preferably 0.4 mm. In the illustrated embodiment, this distance d corresponds to the axial length of the outlet channel 108. Due to the formation of the defined surfaces 118 and 120, the distance d of the inlet surface 118 from the outlet surface 120 is preferably smaller than the wall thickness T of the container wall 110, approximately smaller than the wall thickness T of the container wall 110 in the region of its extension along the container axis BA.
  • the projection length L of the axial projection 122 relative to the outlet surface 120 is preferably 0.1 mm or between 20% and 30% of the distance between the inlet surface 118 and the discharge surface 120 or between 40% and 125% of the diameter of the discharge opening 116.
  • the radial width B of the axial projection 122 which preferably extends closed around the container axis BA to protect the discharge opening 116 on all sides, is greater than its projection length L, preferably at least twice as large.
  • the radial width B of the axial projection 122 is between 0.2 and 0.3 mm, particularly preferably between 0.2 mm and 0.24 mm.
  • the input opening 104 is preferably circular and has an opening width OW, in particular a diameter, in the range of 5.7 to 6.3 mm.
  • the diameter of the preferably circular-cylindrical output channel 108 is preferably less than half a millimeter. In the illustrated embodiment, it is in the range of between 0.15 and 0.3 mm.
  • the outer diameter De of the preferably circular inlet surface 118 is preferably 40% to 60% of the outer diameter Da of the preferably circular outlet surface.
  • the diameter De of the inlet surface 118 is approximately 0.5 mm
  • the diameter Da of the outlet surface 120 is approximately 1 mm.
  • An inner wall surface 110a of the container wall 110 which directly delimits the receiving volume 112, is preferably designed in the shape of a rotational body with the virtual container axis BA as the axis of rotation.
  • the inner wall surface 110a is designed such that the receiving volume 112 has a first tapered region 112a, in which the receiving volume 112 tapers as it approaches the discharge channel 108.
  • the tapered angle a1 (see Fig. 11), which is preferably constant over the entire axial length of the first tapered region 112a, is smaller than the tapered angle a2 of a second tapered region 112b following the first tapered region 112a in the direction of the discharge channel 108.
  • the taper angles are drawn on the outer wall surface 110b for better clarity.
  • the taper angles a1 and a2 drawn on the outer wall surface 110b also correctly reflect the taper of the inner wall surface 110a.
  • the taper angles a1 and a2 are half the opening angles within the conical taper regions 112a and 112b of the receiving volume 112, related to the virtual container axis BA, which is also the cone axis of the conical taper regions 112a and 112b.
  • the taper angle a1 is a moderate taper angle in the range of 0.7° to 5°, 1° in the illustrated embodiment.
  • a liquid flow can occur along the container axis BA without generating turbulence in the liquid, and pressure waves can propagate within a liquid 109 held in the reaction container 88 along the container axis BA without generating turbulence.
  • the first tapered region 112a is axially longer than the second tapered region 112b.
  • the second tapered region 112b extends axially to the edge of the inlet surface 118.
  • the first tapered region 112a is at least five times as long as the second tapered region 112b along the container axis BA.
  • two thin parallel lines indicate the axial longitudinal end of the first tapered region 112a, which is closer to the discharge channel 108, and the axial longitudinal end of the second tapered region 112b, which is farther from the discharge channel 108. Between them lies a first transition region 124, in which the inner wall surface 110a transitions seamlessly from the first tapered angle a1 to the second tapered angle a2.
  • the sectional contour of the inner wall surface 110a in the first transition region 124 has a curvature with a radius of curvature in the range from 0.8 mm to 1.1 mm.
  • the taper angle a2 of the second taper region 112b which in the example shown is also preferably constant over its entire axial length, is preferably 45° in the exemplary embodiment shown.
  • the second tapered region 112b whose axial length is only approximately one-twelfth to one-eighth, in this case approximately 2/21, of the axial length of the first tapered region, optimally conditions the liquid in the receiving volume 112 for splash-free discharge in a free jet during discharge of liquid through the discharge channel 108.
  • the entire second tapered section 112b thus forms an inlet section 126, in which the liquid received in the receiving volume 112 is fed to the inlet opening 114 in a laminar or at least substantially laminar manner under appropriate pressure conditions inside the reaction vessel 88.
  • the inlet surface 118 which forms the longitudinal end of the second tapered region 112b closer to the discharge channel 108, can mitigate any shear forces occurring at the inlet opening 114 that could otherwise have a detrimental effect on long-chain molecules contained in the liquid.
  • Nucleic acids in particular, form very long-chain molecules that can be sensitive to shear forces in the liquid containing them and can be destroyed by such shear forces.
  • the dispensing surface 120 can ensure that liquid exiting from the dispensing opening 116 does not wet the outside of the container wall 110. If liquid is nevertheless able to wet the dispensing surface 120, the range of this wetting is limited by the axial projection 122, which also mechanically protects the dispensing opening 116 and the dispensing channel 108, as well as the dispensing surface 120 itself, from impacts and the like.
  • the third taper angle a3 is approximately 30°.
  • the axial length of the funnel region 128 is approximately 3 to 4 times the axial length of the second tapered region 112b and thus of the inlet region 126.
  • the axial length of the first tapered region 112a is in turn approximately 2.5 to 3 times the axial length of the funnel region 128.
  • the funnel region 128 serves to taper the reaction vessel 88 to the shortest possible axial length without jumps or steps in the inner wall surface 110a.
  • a second transition region 130 in which the inner wall surface 110a transitions with a convex curvature from the funnel region 128 into the first tapered region 112a.
  • the curvature of the inner wall surface 110a in the first transition region 124 is concave.
  • the above-mentioned recesses 100a and 100b of the magnet carrier arrangement 72 are designed to accommodate the first tapered region 112a and, with appropriate axial adjustment of the magnet carrier arrangement 72, at least a portion of the funnel region 128. Due to the above-described inclination of the container wall 110 with a substantially constant thickness T, whenever the first tapered region 112a can be accommodated in the recesses 100a and 100b of the magnet carrier arrangement 72, the second tapered section 112b can also be accommodated in the recesses 100a and 100b and exposed to the magnetic field of the matrix magnets 94.
  • immobilization of magnetic particles 109a which may be suspended in a liquid 109 received in the receiving volume 112, takes place in the first tapered section 112a or in at least one of the adjacent transition regions 124 or 130 or in the second tapered section 112b, but preferably in the first tapered section 112a due to the distance from the output channel 108.
  • MA denotes a range of movement along which the magnet carrier arrangement 72 with its two magnet carriers 72a and 72b moves during operation of the Liquid handling device 10 can at least be moved.
  • the magnet carrier assembly 72 can be moved under the dispensing ends 106 of the reaction vessel assemblies 86 to enable the reaction vessel assembly 18 to be moved collision-free between its setup position and its standby position.
  • the mutually facing longitudinal ends of the funnel region 128 and the first tapered region 112a are separated from each other in Figure 11 by thin horizontal lines, between which the second transition region 130 is located.
  • a guide region 132 is located between the inlet opening 104, preferably directly axially adjacent thereto, and the funnel region 128, which guide region also tapers in the direction away from the inlet opening 104 and toward the output channel 108.
  • the fourth taper angle a4 is also constant along the entire guide region 132.
  • the fourth taper angle a4 is smaller than the third taper angle a3 and, in the illustrated embodiment, essentially corresponds to the first taper angle a1 or differs from it by no more than 30% relative to the first taper angle a1.
  • parallel horizontal lines in Figure 11 indicate the mutually facing axial longitudinal ends of the guide region 132 and the funnel region 128, between which a third transition region 134 is located, in which the inner wall surface 110a transitions smoothly and without jumps from the guide region 132 to the funnel region 128 as it approaches the discharge channel 108.
  • reaction vessels 88 of a reaction vessel arrangement 86 are connected to one another at their input ends 112 by a belt 136 running along the follower path FB.
  • the reaction vessel arrangement 86 discussed here is formed in one piece as an injection-molded component made of thermoplastic material.
  • Figure 10A shows a longitudinal sectional view through a reaction vessel assembly 86. The details of the reaction vessels 88 shown therein have already been explained above in connection with Figures 11 and 12.
  • E1 denotes an input-end plane orthogonal to the drawing plane of Figure 10A, in which the input openings 104 of the reaction vessel arrangement 86 shown and of all further reaction vessel arrangements 86 arranged in front of and/or behind the reaction vessel arrangement 86 shown in Figure 10A in the reaction vessel carrier 20 are located.
  • EO denotes a discharge end-side plane orthogonal to the drawing plane of Figure 10A, in which the discharge openings 116 of the reaction container arrangement 86 shown and of all further reaction container arrangements 86 arranged in front of and/or behind the reaction container arrangement 86 shown in Figure 10A in the reaction container carrier 20 are located.
  • the preferably parallel virtual planes E1 and E0 are to be understood as having a certain thickness in order to account for manufacturing tolerances of the reaction vessel arrangements 86 and arrangement tolerances of the reaction vessel arrangements 86 in the reaction vessel carrier 20.
  • the two planes E1 and E0 are parallel to the follow-up path FB and are parallel to the standby movement paths AB, RB, and NB. They are also parallel to the loading path BP.
  • the curvature axis K runs orthogonally to the plane of the drawing in Figure 10B and is actually further away from the belt 136 than shown in Figure 10B.
  • Figure 10B merely serves to qualitatively illustrate the curvature axis K and its position relative to the belt 136.
  • a surface 136a facing away from the reaction vessels 88 is therefore convexly curved.
  • the curvature serves to improve the fixation of the reaction vessel arrangement 86 in the reaction vessel carrier 20.
  • the reaction vessel receptacles 24 in the reaction vessel carrier 20 are also centrally interspersed with virtual receptacle axes, which are aligned parallel to one another.
  • the vessel axes BA of the reaction vessel arrangements 86 curved according to Fig. 10B are oriented divergingly.
  • the reaction vessel arrangement 86 with the diverging vessel axes BA is now arranged in the reaction vessel carrier 20 with the parallel receptacle axes of the reaction vessel receptacles 24, the reaction vessel arrangement 86 is forcibly deformed by the reaction vessel carrier 20 such that the virtual vessel axes BA of the individual reaction vessels 88 of the reaction vessel arrangement 86 are oriented parallel to one another and collinear with the receptacle axes within a certain tolerance range.
  • the resulting deformation is an elastic deformation, which increases the contact force with which a container wall 110 presses against a wall or structure of the reaction container receptacle 24 or the reaction container carrier 20.
  • This increased contact force increases the frictional force acting between the reaction containers 88 and the reaction container carrier 20, so that the resistance of a reaction container arrangement 86, which is deformed due to its curved rest state and arranged in the reaction container carrier 20, to removal from the reaction container carrier 20 is increased compared to the same reaction container arrangement 86 arranged undeformed in the reaction container carrier 20.
  • each reaction container 88 is provided as a fixation reaction container with three radial projections 140 arranged equidistantly around the container axis BA.
  • the radial projections 140 are formed in the guide region 132 and extend parallel to the virtual container axis away from the belt 136 in the direction of the discharge end 106.
  • the axial extension length of the radial projections 140 of a reaction container 88 is the same for each radial projection 140. It is preferably greater than the axial extension length of the webs 138.
  • the radial projections 140 locally increase the outer diameter or the outer dimension of the reaction vessel 88 and in particular of the guide region 132 carrying the radial projections 140. If the guide region 132 with the radial projections 140 is introduced into a reaction vessel receptacle 24 in which no negative counterpart for the radial projections 140 is formed in the receiving cavity, the locally increased outer dimension in the region of the radial projections 140 results in a clamping of the reaction vessel 88 in the reaction vessel receptacles 24 and thus in an improved fixation of the reaction vessel 88 in the reaction vessel carrier 20.
  • this improved fixation of the reaction vessels 88 by the radial projections 140 is based on a similar effect to that resulting from the curved design of the reaction vessel arrangement 86: due to the locally larger external dimensions of the reaction vessels 88 compared to the projection- or recess-free inside width of the reaction vessel receptacles 24, the reaction vessel 88 can only be inserted into the reaction vessel receptacles 24 with elastic deformation of the area carrying the radial projections 140.
  • the essentially identically formed radial projections 140 have lateral flanks that enclose an angle ß1 of between 45 and 55°, preferably 50°.
  • the radially outward-facing end face 140a of the radial projections 140 has a width b, measured in the circumferential direction, of 0.15 mm to 0.3 mm, in the present example 0.2 mm. In the radial direction, the radial projection 140 protrudes 0.4 to 0.7 mm, in the illustrated embodiment 0.5 mm, from the remaining outer wall surface 110b of the container wall 110.
  • the outer dimension of a reaction vessel 88 in the area carrying the radial projections 140, measured across the virtual vessel axis BA, which is thought to pass through centrally, is therefore 0.5 mm larger than the outer diameter of the reaction vessel 88 measured at the same axial position, but across a diameter direction in which no radial projection 140 is present.
  • the radially outward-facing end surface 140a preferably extends parallel to the container axis BA, so that the radial projections 140, with the container axis BA as the cylinder axis, preferably have a cylindrical envelope.
  • An insertion bevel with an inclination of preferably 30° relative to the container axis BA at the longitudinal end of the radial projections 140 closer to the discharge end 106 facilitates their insertion into a cylindrical or conical reaction container receptacle 24.
  • the reaction containers 88 or more precisely the band 136 of the reaction container arrangement 86 connecting them, have or have at a longitudinal end 136b of the band 136 a physical coding formation 142 in the form of a detection surface 142a arranged at a distance from the surface 136a of the band 136 facing away from the output end 106.
  • the container sensor 92 of the device 10 can detect the distance between it and the belt 136, as well as between it and the detection surface 142a, and transmit it to the control device 40. Encoding information by the physical coding formation 142 during manufacture of the reaction container assembly 86 offers the significant advantage of avoiding subsequent erroneous coding by a laboratory technician, as might potentially occur during hectic laboratory work.
  • the detection surface 142a may be raised by a predetermined distance s relative to the surface 136a of the belt 136 or lowered by a predetermined distance s. Even the arrangement of the detection surface 142a at the same surface level as the surface 136a may be an information carrier.
  • the physical coding formation 142 can be arranged at the same longitudinal end, but using the opposite corner of the band 136. Considering only the alternatives of a raised or depressed arrangement of the sensing surface 142a at one of two corner regions of the longitudinal end 136b, four possible different coding states result. Adding the simultaneous formation of a physical coding formation 142 at both corners of the longitudinal end 136b results in six possible different coding states.
  • the coding states are correlated with a physical feature of the reaction container 88 of the reaction container arrangement 86, for example with the design of the dispensing channel 108, more precisely with its diameter and/or length.
  • the coding state of a reaction container arrangement 86 can directly indicate to the control device 40 operating parameters that the control device 40 should set during a handling process on the device 10.
  • One possible such parameter is the specification of an overpressure in the receiving volume 112 in order to be able to ensure a splash-free dispensing of liquid from the receiving volume 112 through the dispensing channel 108.
  • Data assignments can be stored in the data memory 42 of the control device 40, which correspond to a sensor 92, or a coding state associated with this detection, to a pressure value that the control device 40 is intended to achieve during a liquid handling operation for dispensing liquid from a reaction container 88 into its receiving volume 112 by the pressure-changing device 62b.
  • a pressure value for the detection of which the pressure sensor 69a can be used on the device side or a further pressure sensor is to be provided, a duration of an introduction of gas into the receiving volume 112 can also be stored in the data memory 42.
  • the belt 136 can be constricted in regions between two reaction vessels 88 arranged successively along the following path FB (see Fig. 15), preferably forming a seamless and continuous constriction.
  • the reaction vessel arrangement 86 is preferably mirror-symmetrical with respect to a plane containing the vessel axes BA.
  • the container lid 45d covers a filling opening 146 of the bowl- or tub-shaped tub body 45c.
  • the tub body 45c comprises a container bottom 148, which, as shown in Figure 18, can be flat or can have defined support formations to ensure particularly secure support.
  • Side walls 150a to 150d protrude from the container bottom 148, at the edge of which the filling opening 146 is formed, remote from the container bottom 148.
  • the side wall 150a is the side wall which, when the waste liquid container is moved, 45 is oriented transversely to the standby movement path AB from the setup position to the standby position and leads the way.
  • the opposite side wall 150b follows the aforementioned movement of the waste liquid container 45, and the two side walls 150c and 150d connect the first-mentioned side walls 150a and 150b.
  • the container lid 45d has openings 152 arranged in an orthogonal matrix. This is also a 12 x 8 matrix, so that the container lid 45d has as many openings 152 as the maximum number of reaction containers 88 that can be arranged in the reaction container carrier 20. Not only is the number of openings 152 and reaction containers 88 identical, but the distances between the output channels 108 and their output openings 116 of the individual reaction containers 88 are also identical to the distances between the openings 152 in the two orthogonal directions of the 12 x 8 matrix.
  • the portion of the surface 154 of the container lid 45d located between the openings 152 is preferably flat. The same applies to the portion of the surface 154 of the container lid 54c surrounding the waste seal assembly receptacle 27.
  • the waste liquid container 45 can be lifted for the discharge of handling waste from the reaction containers 88, preferably to such an extent that the discharge opening 116 of a reaction container 88 or the discharge openings 116 of all reaction containers 88 are moved through the surface 154 and are located, with respect to the surface 154, on the side of the container lid 45d facing the receiving volume 45a.
  • the longitudinal end sections with the discharge ends 106 of the reaction Containers 88 can protrude 0.2 mm to 5 mm, preferably 0.5 mm to 3 mm, through the surface 154.
  • all dispensing openings 116 of existing reaction containers 88 are preferably located in a common arrangement plane. This arrangement plane can have a thickness of 1 mm, preferably a thickness of 0.5 mm, to account for the manufacturing tolerance of the reaction containers 88.
  • each opening 152 is adjoined by a wall arrangement 156 that tapers from the opening 152 toward the receiving volume 45a and completely encloses an inlet volume 158 in the circumferential direction around inlet axes EA.
  • the wall arrangements 156 of all openings 152 are identical.
  • the wall arrangement 156 forms an inlet funnel for introducing handling waste through the openings 152 into the receiving volume 45a.
  • connecting webs 160 and 162 are formed in both orthogonal directions of the 12 x 8 matrix of the arrangement of openings 152, projecting from the side of the container lid 45d facing the receiving volume 45a and connecting the wall arrangements 156 to one another.
  • the wall arrangements 156 are also preferably formed integrally with the rest of the container lid 45d.
  • the virtual inlet axes EA centrally penetrate the inlet volumes 158 and form, so to speak, cone axes or funnel axes of the wall arrangements 156.
  • the wall arrangements 156 preferably extend smoothly and continuously from the flat surface 154 into the receiving volume 45a.
  • an inlet region 156a of the wall arrangement 156 extends along the inlet axis EA from the container lid 45d towards the container bottom 148.
  • the inlet region 156a is curved, like the remaining wall arrangement 156, around the respective inlet axis EA.
  • the inlet region 156a is also curved around axes of curvature that are orthogonal to the inlet axis EA and spaced apart from it.
  • the infinite number of Inlet axis EA orthogonal axes of curvature extend in the circumferential direction around the inlet axis EA.
  • the wall assemblies 156 In order to prevent the wall assemblies 156 from being wetted by handling waste accumulating in the receiving volume 45a, the wall assemblies 156 preferably extend over less than one-third of the clear height of the receiving volume 45a above the container bottom 148. However, for adequate splash protection, the wall assemblies 156 extend at least over 10% of the clear height of the receiving volume 45a starting from the remaining container lid 45d into the receiving volume 45a.
  • the outlet area 156b is only curved around the inlet axis EA in the illustrated embodiment.
  • the container lid 45d is detachably connected to the tub body 45c. It can be held, for example, frictionally and/or positively to the tub body 45c by retaining tongues 164.
  • Figures 19 and 20 show the loading device 62 with its movement apparatus.
  • the guide rail 64 and the belt drive 66 of the loading device 62 are mounted on a support 166 fixed to the device housing.
  • the belt drive 66 comprises a belt 66a and two deflection pulleys 66b and 66c, of which the deflection pulley 66c is driven by a drive motor 168 also mounted on the support 166.
  • This essentially corresponds to the structure of the belt drives 56 and 60 of the other devices 18 and 50 described above as being driven and displaceable.
  • a guide carriage 170 connected to the belt 66a for common movement is movably arranged along the feed path BP.
  • a mobile support 172 is arranged on the guide carriage 170, which is movable together with the guide carriage 170 along the loading path BP and carries the container sensor 92 and the loading device 62.
  • the mobile support 172 which is rigidly connected to the guide carriage 170, carries a guide rail 174 that, in the example shown, is oriented vertically and thus orthogonally to the guide rail 64 and orthogonally to the parallel guide rails 48, 54, and 58.
  • the loading device 62 is movably guided along a vertical approach path WP on the guide rail 174.
  • the mobile carrier 172 also carries a movement drive 176, by which the loading device 62 can be driven to move along the approach path WP.
  • the loading device 62 can be brought closer to the reaction vessel device 18, and in particular to the input ends 102 with the input openings 104 of the reaction vessels 88, and lifted away from them again.
  • the sealing arrangement 22 shown in Figure 1 when arranged on the loading device 62, can be pressed sealingly against the belt 136 of the reaction vessel assemblies 86 with a predetermined and/or defined contact pressure.
  • the movement drive 176 can move a used seal assembly 22 arranged on the loading device 62 along the approach path WP into the waste seal assembly receptacle 27, from where it can be stripped from the loading device 62, more precisely from the pressure change device 62b, by moving the waste liquid container 45 along its standby movement path AB.
  • the movement drive 176 can move a used seal assembly 22 arranged on the loading device 62 along the approach path WP into the seal assembly receptacle 26, from where it can be stripped from the pressure change device 62b by moving the reaction container carrier 20 along its standby movement path RB.
  • the switching valves 182 switch lines of the metering device 62a between a blocked state and a flow-through state.
  • the switching valves 182 therefore form a metering valve arrangement 183 in the sense of the introduction to the description.
  • the switching valves 184 switch lines of the pressure-changing device 62b between a blocked state and a flow-through state.
  • the switching valves 184 therefore form a gas valve arrangement 185 in the sense of the introduction to the description.
  • Each switching valve 182 and 184 interrupts or connects two line sections formed in the line body 178.
  • Figure 25 shows the loading device 62 in perspective from below, looking at the essentially smooth front side 178c of the line body 78. This view is presented merely as a supplement and conclusion to the previous explanations.

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Abstract

L'invention concerne un appareil de manipulation automatisée de liquide (10) comprenant : i. un dispositif à récipient de réaction (18) pourvu d'un ensemble récipient de réaction (86) doté d'au moins un récipient de réaction (88), le ou les récipients de réaction (88) comportant un orifice d'entrée (104) et, à distance de celui-ci, un orifice de sortie (116) ; ii. un dispositif de réception de liquide utile (50) pour recevoir un liquide distribué par l'orifice de sortie (116) dans le ou les récipients de réaction (86), iii. un dispositif de réception de déchets liquides (46) destiné à recevoir un liquide évacué par l'orifice de sortie (116) dans le ou les récipients de réaction (86), iv. un dispositif magnétique (70) pour générer un champ magnétique dans le ou les récipients de réaction (88), v. un dispositif de modification de pression (62b) pour modifier une pression de gaz dans au moins un récipient de réaction (88), et vi. un dispositif de dosage (62a) pour distribuer un liquide (109) dans au moins un récipient de réaction (88) du dispositif à récipient de réaction (18). Les dispositifs listés aux points i. à v. sont chacun logés dans un boîtier d'appareil (12) de l'appareil de manipulation de liquide (10) de manière à être mobile par rapport à chacun des autres dispositifs listés aux points i. à v., et les dispositifs listés aux points i. à iv. et vi. sont chacun logés dans le boîtier d'appareil (12) de manière à être mobile par rapport à chacun des autres dispositifs listés aux points i. à iv. et vi.
PCT/EP2024/079128 2023-10-19 2024-10-16 Appareil de manipulation automatisée de liquide, dont les composants ont un degré de liberté élevé Pending WO2025083017A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102023128790.7 2023-10-19
DE102023128790.7A DE102023128790A1 (de) 2023-10-19 2023-10-19 Automatisierte Flüssigkeitshandhabungsvorrichtung mit hohem Bewegungsfreiheitsgrad ihrer Komponenten

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WO2025083017A1 true WO2025083017A1 (fr) 2025-04-24

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WO2019096407A1 (fr) 2017-11-17 2019-05-23 Hombrechtikon Systems Engineering Ag Dispositif et procédé d'immobilisation réversible de biomolécules

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