Automated liquid handling device with improved magnet arrangement

Abstract

An automated liquid handling device (10) comprises: i. a reaction vessel arrangement (18) with reaction vessels (88) which are arranged in a matrix-like manner in first rows (88a) and second rows (88b), wherein the first rows (88a) are parallel to each other and wherein the second rows (88b) are parallel to each other and intersect each other, wherein each reaction vessel (88) from the plurality of matrix-like arranged reaction vessels (88) is located at an intersection of a first and a second row (88a, 88b), wherein each reaction vessel (88) has an inlet opening (104) and an outlet opening (116) spaced apart from it, and ii. a magnetic device (70) with a movable magnet support arrangement (72), wherein the number of matrix magnets (94) is less than the number of reaction vessels (88) from the plurality of reaction vessels (88), wherein two matrix magnets (94) are adjacent to each reaction vessel (88) from the plurality of reaction vessels (88). The magnet support arrangement (72) carries a number of matrix magnets (94) which is greater than the sum of first and second rows (88a, 88b), wherein the matrix magnets (94) each have a polarization direction (94a) which is neither parallel to the first rows (88a) nor to the second rows (88b) and which is neither orthogonal to the first rows (88a) nor to the second rows (88b).

Description

[0001] The present invention relates to an automated liquid handling device for handling liquids. Such an automated liquid handling device comprises: i. a reaction vessel device having a plurality of reaction vessels arranged in a matrix-like manner in first rows and second rows, wherein the first rows are parallel to each other and wherein the second rows are parallel to each other, and wherein the first rows and the second rows cross each other, wherein each reaction vessel of the plurality of matrix-arranged reaction vessels is located at an intersection point of a first and a second row, wherein each reaction vessel has an input end with an input opening and an output end spaced from the input end with an output opening, and ii. a magnet device for forming a magnetic field in the plurality of reaction vessels, wherein the magnet device comprises a movable magnet carrier arrangement with a plurality of matrix magnets carried by the magnet carrier arrangement, wherein the matrix magnets are movable outside the plurality of reaction vessels at least in a range of motion between the input ends and the output ends of the reaction vessels, wherein the number of matrix magnets is less than the number of reaction vessels from the plurality of reaction vessels, wherein each reaction vessel from the plurality of reaction vessels has two matrix magnets adjacent to it.

[0002] Such a liquid handling device is used in laboratories, for example, for the purification of nucleic acids.

[0003] A liquid handling device with the features mentioned above is known from WO 2010 / 075199 A2. The liquid handling device known from WO 2010 / 075199 A2 discloses bar magnets arranged in each space between adjacent parallel rows of reaction vessels and extending parallel to the rows of reaction vessels.

[0004] Known automated liquid handling devices, as well as the automated liquid handling device of the present invention in preferred embodiments, also comprise at least one of the following devices: iii. a useful receiving device for receiving liquid dispensed through the dispensing opening of the reaction container as a handling target, iv. a waste receiving device, separate from the useful receiving device, for receiving liquid dispensed as handling waste through the discharge opening of the reaction containers, v. a pressure changing device, wherein the pressure changing device is designed to change a gas pressure difference between an internal gas pressure in the reaction vessels of the reaction vessel device and an external gas pressure outside the reaction vessels, and vi. a dosing device with at least one dosing opening for transferring liquid into the reaction containers of the reaction container device, wherein the dosing device is designed for transferring liquid by means of the dosing opening through the inlet opening of the reaction containers.

[0005] The known liquid handling devices are easier to understand with knowledge of the advantageous refinement provided by the devices according to iii. to vi. Nevertheless, the devices according to iii. to vi. are not absolutely necessary for the automated liquid handling device of the present invention to achieve the purpose of the invention, but rather represent only preferred embodiments. The explanations and refinements given below in the explanation of the prior art for the devices according to iii. to vi. also apply to refinements of the present invention.

[0006] WO 2010 / 075199 A2 does not include a waste collection device as mentioned above under iii. 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.

[0007] Another liquid handling device 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 reaction container. Consequently, there is no reversal of direction of processed liquids, as is known from other prior art liquid handling devices. Thus, a source of potential cross-contamination can be avoided.

[0008] The reaction container device is the device in which a liquid is "processed" in the broadest sense and in which the liquid is handled. This is where, for example, chemical reactions and / or physical processes take place. In the reaction containers of the reaction container device, 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, if necessary waiting for a reaction time, and dispensing a cleaning liquid. The bound and purified nucleic acids can be eluted, i.e. separated from the magnetic particles, by transferring them, if necessary waiting for a reaction time, and dispensing an elution liquid.The resulting eluate can be discharged from the reaction containers as a handling target. In contrast, a portion of the aforementioned starting liquid and the subsequently transferred cleaning liquid can be discharged from the reaction containers as handling waste.

[0009] The principles of binding nucleic acids to magnetic particles specifically prepared for nucleic acid binding are described in US 5705628. The special preparation can be realized, for example, by coating the magnetic particles with functional groups.

[0010] The useful receiving device of the liquid handling device according to the invention serves, as already described above, to receive liquid dispensed from the reaction containers as the desired handling target, typically 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. To receive the handling target, 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.

[0011] Likewise, the waste receiving device of the liquid handling device according to the invention serves to receive liquids that accrue as waste during liquid processing, for example, an original carrier liquid for nucleic acid, in which undesirable impurities, such as residues of cell components of the cells originally containing the nucleic acid and the like, may be present. These impurities, after the nucleic acids have bound to magnetic particles, are to be released with the carrier liquid and washed out by one or more subsequent washing processes. The cleaning liquid used during the washing processes therefore also constitutes 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 for receiving the handling waste.Although the waste container arrangement within the scope of the present invention can also comprise a plurality of waste liquid containers, the waste container arrangement preferably comprises only one waste liquid container as a collecting container for handling waste discharged from the reaction containers, ie preferably one waste liquid container is provided for receiving handling waste from all reaction containers present at the same time.

[0012] The magnetic device serves to temporarily immobilize the magnetic particles in the reaction containers. This ensures that only the liquid suspending the magnetic particles in the reaction containers can be dispensed through the dispensing opening, while the magnetic particles, in particular with attached nucleic acids, can be retained in the reaction container. In order to optionally immobilize or not immobilize the magnetic particles in the reaction containers, the magnetic device is designed to be movable. For example, the magnetic field emanating from the magnetic device can be moved relative to the reaction containers, which, in a coordinate system fixed to the reaction container, leads to a weakening or strengthening of the magnetic field inside the reaction containers.

[0013] The pressure-changing device of the liquid handling device according to the invention serves to create the aforementioned gas pressure difference between a gas inside the reaction vessel and the gas surrounding the reaction vessel. This specifically generated gas pressure difference allows liquid contained in the reaction vessel to be moved through the dispensing opening. Preferably, the pressure-changing device is designed only to generate a positive pressure difference, at which the gas pressure inside the reaction vessel is higher than the gas pressure outside the reaction vessel. According to this preferred embodiment, liquid is exclusively dispensed through the dispensing openings, but not drawn into the reaction vessel.

[0014] The dosing device of the liquid handling device according to the invention serves for the automated addition of liquid into the reaction containers. It is hygienically advantageous that the liquid is poured into the reaction containers through the inlet opening located far from the dispensing openings of the reaction containers.

[0015] 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 then 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 liquids being passed through the reaction container from the inlet opening to the outlet opening. The reason for this is largely that the inlet opening can be designed so large that it does not need to be wetted by the liquid introduced into the reaction container or by a nozzle dispensing it. This is virtually impossible with aspiration and dispensing through one and the same opening.

[0016] The liquid handling device known from EP 1 065 001 A1 comprises a magnetic device comprising two perforated, magnetizable plates, each of which is penetrated by the cannulas of the reaction vessels. Each of the two perforated plates arranged one above the other is in contact with a different one of two magnetic poles of opposite polarity. An air gap completely encircling the cannulas exists between the plates, directly in the area penetrated by the cannulas.

[0017] 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.

[0018] The liquid handling device known from WO 2004 / 113874 A2 discloses bar magnets which are arranged in every second space between adjacent parallel rows of reaction vessels and extend parallel to the rows of reaction vessels over their entire length.

[0019] For further background information on the prior art, reference is made to the documents US 4895706, US 4111754, US 5273718 and US 8877145 B2.

[0020] According to a preferred embodiment of liquid handling by the liquid handling device of the present invention, a liquid is introduced into a reaction vessel and then discharged again at least once, but usually several times, during the liquid handling. Solid components contained in the reaction vessels can be bound in the reaction vessels by different physical principles, depending on the method carried out 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. Bindable orImmobilizable solid components are the aforementioned magnetic particles, which can be immobilized in the reaction vessels 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 vessel, where the liquids can be the same or different liquids. During liquid handling in the reaction vessels, the immobilizable solid components can be suspended once or repeatedly in a liquid contained in the reaction vessels. Other solid components that are undesirable in the reaction vessels can be flushed out with the handling waste.

[0021] The object of the present invention is to further improve the automated liquid handling device mentioned above. The aim is, in particular, to increase the efficiency of the magnetic device and to ensure a uniform magnetic field effect that can be exerted on all reaction vessels of the plurality of reaction vessels.

[0022] According to the present invention, this object is achieved in an automated liquid handling device as described above in that its magnet carrier arrangement carries a number of matrix magnets which is greater than the sum of the first and second rows, wherein the matrix magnets each have a polarization direction which is neither parallel to the first rows nor to the second rows and which is neither orthogonal to the first rows nor to the second rows.

[0023] While in the prior art, as a rule, a bar magnet is arranged in the spaces between rows of reaction vessels and, if appropriate, next to the outermost rows of reaction vessels, and thus the number of magnets for this design is a maximum of 1 greater than the number of parallel rows of reaction vessels along which the bar magnets are arranged, by increasing the number of magnets, their effect on the contents of the reaction vessels can be increased.

[0024] Due to the described orientation, the increased number of magnets can still remain lower than the number of reaction vessels, so that a separate matrix magnet does not have to be provided for each reaction vessel.

[0025] Furthermore, due to the described orientation, each individual matrix magnet with a relatively low mass can be arranged in spaces between reaction containers, so that the total mass of matrix magnets of the liquid handling device of the present invention is at least not higher or even lower than the magnet mass which is installed in the liquid handling device known from WO 2010 / - 075199 A2.

[0026] A higher magnetic field strength inside the reaction vessels with the same or even lower installed magnetic mass represents a significant increase in efficiency compared to the state of the art.

[0027] 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.

[0028] 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 comparable in its flexibility of placement in the laboratory to that of a printer in an office: the device can be set up and operated in almost any location. However, once set up, it often remains at the chosen location until substantial reasons arise for changing the location.

[0029] To clarify the nomenclature used in this application: the term "device" 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.

[0030] The first rows are parallel to each other, and the second rows are parallel to each other, but intersect the first rows. For optimal use of installation space, the first and second rows are preferably orthogonal to each other, although this is not absolutely necessary. The first and second rows, as virtual rows, are determined only by the arrangement of the reaction vessels. However, the first and / or second rows may correspond to physical devices that hold and / or connect reaction vessels along a first and / or a second row.

[0031] To ensure the densest possible arrangement of reaction vessels, it is advantageous to utilize the available installation space if, for at least one of the first and second rows, a reaction vessel is located at each intersection point of a plurality of directly consecutive intersection points along this row. Other intersection points of the first and second rows, however, can be unoccupied by reaction vessels.

[0032] For the intended automation, a uniform arrangement of reaction vessels is also desirable. Again, the available installation space can be utilized particularly intensively by arranging the reaction vessels densely, if there is a reaction vessel at each intersection point of a first and a second row. Therefore, preferably, all first rows each comprise the same number of reaction vessels, and more preferably, all second rows each comprise the same number of reaction vessels.

[0033] Preferably, the reaction vessels are arranged in an orthogonal mx n matrix, where m and n are integers and denote the number of reaction vessels per first and second row, respectively. In the case of a square matrix, m and n can be equal. Typically, m and n are different integers, which in a preferred embodiment result in 96 crossing points. Particularly preferably, one integer of m and n is 12, and the other integer of m and n is 8. However, other matrices are readily conceivable.

[0034] To simplify the automation of processes in the device, the distances between all first rows are preferably the same, and the distances between all second rows are preferably the same. The distances between the first rows, on the one hand, and the second rows, on the other hand, can also be the same, but this does not have to be the case. For the particularly preferred polarization and orientation of the matrix magnets described below, the use of a uniform common row spacing both between the first rows and between the second rows is particularly advantageous. In this case, the four intersection points of two immediately adjacent first rows and two immediately adjacent second rows form the corners of a square.

[0035] The direction vectors of the first and second rows preferably span a plane that is parallel to both the first and second rows. This plane serves as the reference plane in the present application.

[0036] According to a preferred embodiment of the present invention, the inlet openings of the plurality of reaction containers of the reaction container device are arranged in a common surface, in particular in a common plane. In this case, 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 containers, reaction container supports and the like. The inlet openings, arranged ready for handling, are located in this surface. The surface preferably extends parallel to the reference surface. The preferably provided above-mentioned devices: pressure changing device and the dosing device are preferably displaceable parallel to the common surface.

[0037] Particularly preferably, several reaction containers can be arranged detachably in a reaction container carrier as intended.

[0038] Preferably, several reaction containers are combined in one piece in a reaction container arrangement, which is preferably manufactured from plastic by injection molding. In order to be able to equip the reaction container device with only the number of reaction containers actually required for the respective task or with as few excess reaction containers as possible, the reaction container arrangement preferably has a smaller number of containers than the reaction container device. Preferably, a reaction container arrangement has as many reaction containers as the matrix arrangement has containers per first row or per second row. By arranging such reaction container arrangements in the reaction container carrier, the carrier can thus be equipped with reaction containers row by row in a uniform process.If a reaction vessel arrangement comprises as many vessels as are provided in a row of the first and second rows, the number of reaction vessel arrangements in the reaction vessel device is equal to the number of reaction vessels in the other row of the first and second rows.

[0039] The useful container arrangement provided according to a preferred development preferably has a number of useful liquid containers corresponding to the at least number of reaction containers in the reaction container device, 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 each location of liquid dispensing by the reaction container device. The number of useful liquid containers preferably corresponds to the product of the numbers in the first and second rows of the matrix arrangement, so that it is always ensured that a useful liquid container is ready to be received for each possible location of liquid dispensing by the reaction container device.

[0040] Preferably, the discharge opening of a reaction container is arranged along a distance direction from the input opening, wherein the distance direction preferably runs orthogonally to the reference plane. Preferably, the distance direction is the only distance component between the input opening and the discharge opening. Particularly preferably, all reaction containers of the reaction container device are identically designed. To utilize the force of gravity when filling and emptying the reaction containers, the distance direction, when the device is ready for operation, preferably runs along, particularly preferably parallel, the direction of gravity.

[0041] The direction of the first rows, the direction of the second rows and the spacing direction therefore preferably span a Cartesian coordinate system.

[0042] To provide a magnetic field that effectively acts inside an adjacent reaction vessel, a plurality of matrix magnets are preferably polarized and arranged such that an interface between the opposite magnetic poles of each matrix magnet from the plurality of matrix magnets runs transversely to the aforementioned reference plane. Particularly preferably, all matrix magnets are polarized and arranged in the aforementioned manner.

[0043] According to the simplified magnet model underlying this application, a physical magnet has two unlike magnetic poles, each forming a magnetic section of uniform polarity within the magnetic body. The polarization direction of a magnet is the shortest direction in which the magnetic south pole of the physical magnet follows its magnetic north pole. The boundary surface referred to above is located where the two sections of unlike but identical polarity adjoin each other within the magnetic body.

[0044] The force of a magnet is usually lowest near its interface, since magnetic sections of different polarities partially compensate for each other's force due to their proximity. In contrast, the force of a magnet is greater the further a section of the magnet's outer surface is located from the interface, since essentially only the uniformly polarized magnetic section exerts force there.

[0045] According to a preferred embodiment, the matrix magnets comprise a plurality of inner matrix magnets. Each inner matrix magnet is adjacent to exactly four reaction vessels, arranged in two immediately adjacent first rows and two immediately adjacent second rows. In the preferred orthogonal matrix, the four reaction vessels adjacent to an inner matrix magnet thus occupy the corners of a rectangle.

[0046] A matrix magnet can be made relatively small due to its spatial proximity to the adjacent reaction vessels. Matrix magnets can be used that do not extend beyond the adjacent reaction vessels in either the first row or the second row. Preferably, the matrix magnets do not extend beyond the center of the four adjacent reaction vessels along the respective direction in these directions.

[0047] In this way, the magnetic field of an inner matrix magnet can act in four reaction vessels. Due to the preferred orientation and polarization of the matrix magnets described above, and consequently also of the inner matrix magnets, of the four reaction vessels adjacent to an inner matrix magnet, two diagonally opposite reaction vessels are subjected to a stronger force from the inner matrix magnet, while the two remaining diagonally opposite reaction vessels are subjected to a weaker force. The reaction vessels located closer to the interface of an inner matrix magnet experience the weaker force, while the other two reaction vessels experience stronger forces.

[0048] Therefore, a plurality of matrix magnets, particularly preferably all matrix magnets, are polarized and oriented such that the described interface runs along a diagonal between four reaction vessels located at four intersection points formed by two immediately adjacent first rows and by two immediately adjacent second rows.

[0049] To achieve different magnetic force effects of an inner matrix magnet on the four reaction vessels surrounding it, according to a preferred structural embodiment, at least one inner matrix magnet is polarized and arranged such that a first of its four adjacent reaction vessels is opposite a section of the at least one inner matrix magnet with only one of its two magnetic polarities, a second of its four adjacent reaction vessels is opposite a section of the at least one inner matrix magnet with only the other of its magnetic polarities, and a third and a fourth of its four adjacent reaction vessels are each opposite sections of the at least one inner matrix magnet with its two magnetic polarities. Preferably, all inner matrix magnets are polarized and arranged in the manner described.

[0050] If the magnetic device were to have only internal matrix magnets, the magnetic force exerted by the magnetic device on peripheral reaction vessels that have only one adjacent reaction vessel in their first row and / or in their second row could be different from the magnetic force exerted by the magnetic device on internal reaction vessels arranged between the peripheral reaction vessels. Internal reaction vessels are those reaction vessels that have two neighbors in both their first and second rows. The internal reaction vessels are located between their two row neighbors.

[0051] In order to avoid such undesirable different force effects on reaction containers that are essentially physically identical but arranged at different locations in the reaction container device, according to a preferred development of the present invention, the matrix magnets have a plurality of outer matrix magnets, wherein each outer matrix magnet is adjacent to exactly two reaction containers that are arranged either in the same first row or in the same second row.

[0052] Preferably, the magnetic device comprises only inner and outer matrix magnets.

[0053] In order to exert a substantially identical magnetic force on the reaction vessels adjacent to the outer matrix magnet as on the reaction vessels interacting with inner matrix magnets, a preferred development of the present invention provides that at least one outer matrix magnet, preferably a plurality of outer matrix magnets, particularly preferably all outer matrix magnets, is / are polarized and arranged in such a way that a section of the at least one outer matrix magnet with only one of its two magnetic polarities is opposite a first of its two adjacent reaction vessels, and that sections of the at least one outer matrix magnet with its two magnetic polarities are opposite a second of its two adjacent reaction vessels.

[0054] Thus, one of the two adjacent reaction vessels of the outer matrix magnet preferably has its north pole or its south pole opposite it, while the other of the two adjacent reaction vessels has both a north pole section and a south pole section opposite it.

[0055] In an advantageous development of the present invention, to achieve the most uniform possible magnetic force effect on all reaction vessels, the two reaction vessels adjacent to an outer matrix magnet are peripheral reaction vessels. In contrast, an inner matrix magnet can be adjacent to peripheral and internal reaction vessels, or only to internal reaction vessels. Depending on its position relative to the reaction vessels, an inner matrix magnet can be adjacent to no peripheral reaction vessels, two peripheral reaction vessels, or, in individual cases, even three peripheral reaction vessels. The remaining reaction vessels adjacent to the inner matrix magnet are internal reaction vessels.

[0056] Since the reaction vessels are arranged in a matrix, the matrix magnets are also arranged in a matrix to achieve the desired, most uniform possible force effect of the magnetic device on the reaction vessels. However, the matrix of the matrix magnets can differ from the matrix of the reaction vessels. Preferably, the matrix magnets are arranged in third rows parallel to the first rows and in fourth rows parallel to the second rows. The matrix magnets are located at the intersection points of the third and fourth rows.

[0057] Analogous to the peripheral and internal reaction vessels, an outer matrix magnet has only one adjacent matrix magnet in its third and / or fourth row. Inner matrix magnets have two neighbors in both their third and fourth rows. The inner matrix magnets are located between their two row neighbors.

[0058] To exert predetermined magnetic forces on peripheral reaction vessels, the number of third rows is preferably greater than the number of first rows. Further preferably, the number of fourth rows is greater than the number of second rows. Particularly preferably, the number of third rows is exactly 1 greater than the number of first rows. This ensures the possibility of assigning two adjacent matrix magnets to each reaction vessel in a first row, since each first row can then be arranged between two third rows.

[0059] For the same reasoning, the number of fourth rows is preferably exactly 1 greater than the number of second rows, so that every second row can be arranged between two fourth rows.

[0060] In an mx n matrix in which the reaction vessels are arranged, the matrix magnets are therefore preferably arranged in an (m+1) x (n+1) matrix.

[0061] If the number of third rows is 1 higher than the number of first rows, each first row preferably runs between two third rows. Likewise, if the number of fourth rows is 1 higher than the number of second rows, each second row preferably runs between two fourth rows.

[0062] However, according to the definition given above, the number of matrix magnets is lower than the number of reaction vessels to avoid unnecessarily high manufacturing costs. This can be achieved with the matrix-like arrangement of the matrix magnets described above by not occupying all intersections of the magnetic matrix with a matrix magnet. In a preferred embodiment, in both a third row and a fourth row, an intersection occupied by a matrix magnet is adjacent to an intersection not occupied by matrix magnets. This preferably applies to several, particularly preferably to all, matrix magnets of the magnet arrangement.

[0063] Preferably, therefore, between all consecutive matrix magnets along a third row, there is an intersection point between the third row and the fourth row, which is unoccupied by matrix magnets. Likewise, between all consecutive matrix magnets along a fourth row, there is preferably an intersection point between the third row and the fourth row, which is unoccupied by matrix magnets. The preferably orthogonal matrix of matrix magnets thus has more intersection points than matrix magnets. This particularly preferably applies not only to some of the third and fourth rows, but to all third rows and all fourth rows of the magnet matrix.

[0064] In a specific design, directly consecutive third rows of matrix magnets along a fourth row can alternately have a higher and a lower number of matrix magnets. Alternatively, or preferably additionally, directly consecutive fourth rows of matrix magnets along a third row can alternately have a larger and a smaller number of matrix magnets. The larger number of matrix magnets in fourth rows can differ from the higher number of matrix magnets in third rows. Likewise, the smaller number of matrix magnets in fourth rows can differ from the lower number of matrix magnets in third rows.

[0065] Due to the preferably regular arrangement of reaction vessels, the matrix magnets are preferably also arranged with a certain regularity. Therefore, all third rows with a lower number of matrix magnets preferably have the same lower number of matrix magnets. Alternatively, or preferably additionally, all third rows with a higher number of matrix magnets have the same higher number of matrix magnets.

[0066] Preferably, therefore, the number of matrix magnets in successive third rows along a fourth row alternates between the higher and the lower number.

[0067] For the same reason, preferably all fourth rows with a smaller number of matrix magnets have the same smaller number of matrix magnets. Additionally or preferably alternatively, all fourth rows with a larger number of matrix magnets have the same larger number of matrix magnets.

[0068] Preferably, therefore, the number of matrix magnets in fourth rows following one another along a third row alternates between the larger and the smaller number.

[0069] It is particularly preferable for the higher and lower numbers to differ by 1. The same applies to the larger and smaller numbers in the fourth rows.

[0070] For a further description of preferred developments of the magnetic device, all consecutive third rows along a fourth row are considered to be numbered consecutively in ascending order. Likewise, all consecutive fourth rows along a third row are considered to be numbered consecutively in ascending order.

[0071] Although it initially seems logical, due to the regularity discussed so far, to arrange the matrix magnets in the magnetic device with as uniform an orientation as possible, a more uniform magnetic force effect can surprisingly be achieved by a non-uniform but regular orientation of the matrix magnets.

[0072] Thus, the most uniform possible force effect of the matrix magnets on the reaction vessels has been shown in an arrangement in which the matrix magnets of all third rows with even row numbers are identically oriented and in which the matrix magnets of all third rows with odd row numbers are identical, but oriented differently from the matrix magnets in the third rows with even row numbers.

[0073] Alternatively or preferably additionally, the most uniform possible force effect of the matrix magnets on the reaction vessels can also be achieved by orienting the matrix magnets of all fourth rows with even row numbers identically and by orienting the matrix magnets of all fourth rows with odd row numbers identically but differently from the matrix magnets in the fourth rows with even row numbers.

[0074] In a specific design development of the present invention, the matrix magnets of the third rows with even row numbers are preferably arranged rotated by 90° about a rotation axis orthogonal to the reference plane relative to the matrix magnets of the third rows with odd row numbers. The direction of rotation of the matrix magnets in the third rows with even row numbers relative to the matrix magnets in the third rows with odd row numbers is always the same for all affected matrix magnets.

[0075] Alternatively, or preferably additionally, for the same reason, it can be provided that the matrix magnets of the fourth rows with an even row number are arranged rotated by 90° about a rotation axis orthogonal to the reference plane relative to the matrix magnets of the fourth rows with an odd row number. Here, too, the direction of rotation in which the matrix magnets in the fourth rows with an even row number are rotated relative to the matrix magnets in the fourth rows with an odd row number is always the same for all affected matrix magnets.

[0076] Preferably, the axis of rotation is oriented orthogonal to the polarization direction of the matrix magnets.

[0077] In the most preferred embodiment, exactly two matrix magnets are arranged adjacent to each reaction vessel in such a way that each reaction vessel has a section of one matrix magnet with only one magnetic polarity adjacent to or opposite it, and sections of the other matrix magnet with both different magnetic polarities adjacent to or opposite it. Thus, each reaction vessel is influenced by the magnetic fields of two adjacent matrix magnets, with one of the adjacent matrix magnets exerting a stronger magnetic force on the interior of the reaction vessel than the other adjacent matrix magnet. This allows advantageous effects to be achieved. The force effect of matrix magnets located further away is negligible due to the divergence of magnetic fields for the reaction vessel in question.The magnetic field strength decreases proportionally to the square of the distance from a magnet.

[0078] In principle, two particle clusters, also referred to as "pellets" in the field, can be formed by the two adjacent matrix magnets with different forces in the interior of a reaction vessel in which magnetic or magnetizable particles are suspended. The cluster caused by the matrix magnet with the greater magnetic force usually comprises a higher number of particles than the cluster caused by the matrix magnet with the lower magnetic force.

[0079] By moving the two adjacent matrix magnets relative to the reaction vessel, a strongly varying magnetic field can be generated within the reaction vessel. Thus, the movement of the matrix magnets can achieve a stirring effect on the suspension contained in the reaction vessel. The mixing is achieved by the suspended magnetic or magnetizable particles under the influence of the magnetic field, which changes with the movement of the two adjacent matrix magnets.

[0080] The movement can also ensure that the larger particle cluster gradually grows at the expense of the smaller particle cluster until finally only the larger particle cluster remains.

[0081] A particularly good mixing effect and a particularly advantageous cluster formation of magnetic particles suspended in the reaction vessel can be achieved by separate movement of the two matrix magnets adjacent to a reaction vessel.

[0082] For this purpose, in a particularly advantageous development of the present invention, the magnet carrier arrangement has at least two, preferably exactly two, magnet carriers movable relative to one another, each of which is movable with a movement component running along the direction of the distance between the input opening and the output opening.

[0083] Most preferably, one magnet carrier carries only matrix magnets from third rows with even row numbers, while the other magnet carrier carries only matrix magnets from third rows with odd row numbers.

[0084] Additionally or preferably alternatively, one magnet carrier carries only matrix magnets of fourth rows with even row numbers, while another magnet carrier carries only matrix magnets of fourth rows with odd row numbers.

[0085] Preferably, each magnet carrier has its own magnet carrier drive, allowing it to be moved independently of the other magnet carrier. The movement of the magnet carriers or the magnet carrier arrangement is controlled by the aforementioned control device.

[0086] When using suspended magnetic particles, i.e., magnetized or magnetizable particles, in the reaction vessels, it is particularly advantageous if the matrix magnets can be moved out of the reaction vessel's extension area to reduce the effectiveness of a magnetic field in the reaction vessel's receiving volume to a negligible level. This allows the magnetic particles to be surrounded by their carrier fluid without any discernible influence from the external magnetic fields of the matrix magnets, providing nucleic acids with the largest possible surface area and the greatest possible contact probability.

[0087] Since reaction containers are often filled with only a small amount of liquid, it is very advantageous if the matrix magnets can be moved at least into an area closer to the dispensing opening, particularly preferably into a longitudinal end region of the reaction container containing the dispensing opening. To achieve the shortest possible movement paths of the magnetic device or the matrix magnets, the matrix magnets are then moved out of the extension area of ​​the reaction container, usually in the direction of gravity, toward the side of the dispensing opening facing away from the input opening.

[0088] In case of doubt, the longitudinal end region of a reaction container containing the dispensing opening extends from the dispensing opening over no more than one third, preferably no more than one quarter, of the distance between the dispensing opening and the inlet opening in the direction of the inlet opening.

[0089] Preferably, the reference plane in the operational state is oriented orthogonally to the direction of gravity or deviates from the orthogonality by no more than 10°, preferably no more than 5°.

[0090] Preferably, all matrix magnets are identically designed, particularly preferably as cylindrical, generally prismatic or cuboid-shaped magnets.

[0091] The magnet carrier arrangement preferably extends parallel to the first row or parallel to the second row between the reaction vessels arranged in the respective rows, past them. To enable the most dense arrangement of reaction vessels possible, the magnet carrier arrangement preferably has concave recesses in the region of the arrangement of reaction vessels, which, in at least one operating position of the magnet carrier arrangement, surround a peripheral section of the opposing reaction vessels.

[0092] When the matrix magnets are arranged in an operative position in which they exert a magnetic force on the interior spaces of reaction vessels, the matrix magnet extends into the space between two reaction vessels adjacent along the first and / or second rows for a plurality of matrix magnets, preferably for all matrix magnets. This allows the matrix magnet to be moved closer to the reaction vessel, thereby increasing its magnetic force on the interior of the reaction vessel.

[0093] Further preferably, each of the above-mentioned devices according to i. to vi., provided a device according to iii. to vi. is present on the device, is arranged on the device so as to be movable between at least two different operating positions. The mobility of the magnet carrier device has already been described above. This makes it possible, among other things, to avoid collisions between the magnet device and other devices, in particular between the useful receiving device spatially close to the magnet device and the reaction container device during liquid dispensing through the dispensing openings. Furthermore, a handling target can be removed from the device in this way, and devices can thus be set up as operating positions for subsequent handling processes at set-up positions.

[0094] To achieve a defined mobility of the respective device, each of the devices mentioned under i. to vi. 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. As a rule, the guide rails of the guide device are arranged in a fixed location, for example, on at least one device housing component consisting of a side wall, housing base, housing cover, and a structure firmly connected to the device housing.

[0095] Each of the devices mentioned under i. to vi. can be driven for movement 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 movement range of a device. However, the motion drive is preferably effective over the entire movement range of a device. Furthermore, devices can be driven for movement within their movement range by more than one motion drive. This can be advantageous, for example, if the movement path of a device has a bent or angled course, for example a horizontal and a vertical section, so that a different movement drive can be effective in one section of the movement path than in another.

[0096] The above-described separate drives for the two separate magnet carriers are a further development of a very general movement drive of the magnet device, which can be provided according to a further development of the invention.

[0097] The above-mentioned plurality of reaction containers may be a subset of the total reaction containers arranged on the device ready for handling, but is preferably the entirety of the reaction containers arranged on the device ready for handling. The same applies, mutatis mutandis, to the plurality of matrix magnets.

[0098] The present invention will be explained in more detail below with reference to the accompanying drawings. It shows: Fig. 1 is a roughly schematic perspective view of a liquid handling device of the present invention, viewed obliquely from the front and above, Fig. 2 is a schematic perspective view of the liquid handling device of Fig. 1 without housing walls, Fig. 3 an enlarged schematic side view according to Fig. 2 with the reaction vessel device and the useful receiving device in relation to the representation of Fig. 2 different positions, Fig. 4 is an enlarged schematic perspective interior view of the liquid handling device of the Fig. 1 to 3 with partially cut facilities, Fig. 5 is an enlarged schematic perspective interior view, partly sectioned like that of Fig. 4, with the useful receiving device in an alternative position, Fig. 6 a rough schematic representation of the magnet carrier arrangement of the magnetic device of the liquid handling device of Fig. 1 to 5 in top view, Fig. 7 an exploded bottom view of one magnet carrier of the magnet carrier arrangement of the magnet device, Fig. 8 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 vessel assembly for use on the reaction vessel device of the liquid handling device of Fig. 1 to 5, Fig. 10A is a longitudinal sectional view through the reaction vessel assembly of Fig. 9, where the section plane contains the virtual vessel axes of the individual reaction vessels, looking along the arrow XA in Fig. 9, Fig. 10B is a rough schematic side view of the reaction vessel arrangement of Fig. 10A with exaggerated curvature for fixing the reaction vessel arrangement in the reaction vessel carrier, Fig. 11 a longitudinal section through a peripheral reaction vessel, cut along the same cutting plane as that of Fig. 10A, Fig. 12 is an enlarged view of the discharge end of the reaction vessel of Fig. 11, Fig. 13 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 a cross-section through a reaction vessel along a sectional plane orthogonal to its virtual vessel axis, Fig. 15 a plan view of the reaction vessel arrangement of the Fig. 9 and Fig. 10A, Fig. 16 a cross-sectional view of a reaction vessel arrangement along a section plane XVI-XVI oriented orthogonally to the virtual vessel axes of the reaction vessels in Fig. 10A, Fig. 17 is a perspective view of the waste liquid container of the liquid handling device of the Fig. 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 feed device of the liquid handling device of the Fig. 1 to 5 with their musculoskeletal system, when viewed predominantly from below, Fig. 20 another perspective view of the loading device with its movement apparatus of Fig. 19, Fig. 21 Perspective view of the switchable valves carrying the rear of the feeding device of the Fig. 19 and Fig. 20, Fig. 22 a perspective view of the loading device of the Fig. 19 to 21 mainly from below and without switchable valves, Fig. 23 a piping system in the piping body of the feeding device of the Fig. 19 to 22, Fig. 24 a perspective view of the rear of the loading device of Fig. 22, without switchable valves, and Fig. 25 a perspective view of the front of the loading device of the Fig. 19 to 22 and 24, without switchable valves.

[0099] The figures are not to scale, but accurately reflect proportions.

[0100] In Fig. 1 is an embodiment of a liquid handling device according to the present application, generally designated 10. The liquid handling device 10 comprises a device housing 12. The viewer of the Fig. 1 looks at the front 12a with the front wall 13a, the top 12b with the ceiling 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 12a. A display and control panel 14 is arranged on the front 12a, on which information about an ongoing, a prepared and / or a completed liquid handling process of the liquid handling device 10 can be displayed. In the preferred embodiment, the display and control panel 14 is a touch screen and is not only an output device but also 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) must be entered.

[0101] As information about the orientation of the device 10, the direction of gravity g is shown in numerous figures.

[0102] Below the display and control panel 14 there is a Fig. 1 open access opening 16 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 Fig. 1 in its setup position located outside the device housing 12. In the setup position, the reaction vessel device 18 and numerous of its components are accessible to an operator or a service robot.

[0103] The reaction container device 18 comprises a reaction container carrier 20, on which a plurality of reaction container arrangements 86 (see Fig. 3) and a sealing arrangement 22, also explained below, for use in the loading device 62 of the device 10, can be arranged by the operator. The reaction vessel carrier 20 has reaction vessel receptacles 24 arranged in a matrix-like manner in an orthogonal 12 x 8 matrix for receiving reaction vessels 88 (see Fig. 9 to 16) or reaction vessel arrangements 86 and has a sealing arrangement receptacle 26 designed as a recess in which Fig. 1 a new, unused sealing arrangement 22 for a subsequent handling operation.

[0104] 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.

[0105] The access opening 16 is preferably a pre-tensioned in its closed position, in Fig. 1, a flap (not shown) is assigned 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, as it approaches its setup position, against its prestress into its open position, which differs from the closed 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.

[0106] Below the access opening 16 there is a drawer 28 in which a waste receiving device 46 (see Fig. 2 ff.). The drawer 28 is along a straight line of standby movement path AB of the waste receiving device 46, parallel to the standby movement path RB of the reaction container device 18, from the Fig. 1, can be pulled out of the device housing 12 and pushed back into it. 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.

[0107] In Fig. 1 To the left of the drawer 28 there is an on / off button 30 which establishes or interrupts the power supply to the device 10.

[0108] In Fig. 1, to the right of the access opening 16 in a recessed portion of the front side 12a, there is an operating fluid compartment 32, in which, for example, two containers 34 and 36 containing operating fluids are provided for use during fluid handling operations in the device 10. For example, the container 34 may contain a cleaning fluid and the container 36 may contain an elution fluid.

[0109] 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.

[0110] In Fig. 2 shows a part of the interior I of the device 10.

[0111] The control device 40 of the device 10 is only roughly schematically indicated by the representation of some integrated circuit boards, which 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 or writes to a data memory 42 integrated in the control device 40.

[0112] 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 out of the Fig. 1 and Fig. 2 along the standby movement path AB of the waste receiving device 46 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.

[0113] On the floor 13d of the device 10 or its device housing 12, 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.

[0114] Above the Fig. 2 in its standby position is located in Fig. 2, also in its standby position, a useful receiving device 50, from which in Fig. 2 only one useful container carrier 52 can be seen.

[0115] 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.

[0116] In contrast to the waste receiving device 46, which in the present embodiment can only be moved manually, 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, which is also located outside the device housing 12, and the Fig. 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.

[0117] Above the useful receiving device 50 is the already Fig. 1 known reaction vessel device 18. The reaction vessel device 18, more precisely the reaction vessel 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 vessel device 18. The reaction vessel device 18, more precisely the reaction vessel carrier 20, can also be driven by an electric motor-driven belt drive 60 by the control device 40 for movement along the standby movement path RB.

[0118] Due to the arrangement of the reaction vessel device 18 on the one hand and the working receiving device 50 on the other hand, one above the other and one below the other with respect to the direction of gravity g, and their movement guidance by parallel guide rails 54 and 58, the setup positions of the reaction vessel device 18 and the working 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.

[0119] Above the reaction vessel device 18 in its Fig. In the standby position shown in Figure 2, which is identical to the handling position of the reaction container device 18 during liquid handling, a feeding 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 containers 88 and a pressure-changing device 62b for changing the pressure of a gas in one or more reaction containers 88. The metering device 62a and the pressure-changing device 62b are connected or combined for joint movement in the feeding device 62 along a feeding path BP orthogonal to the previously explained standby movement paths AB, NB, and RB.In a similar manner to the reaction vessel device 18 and the useful receiving device 50, the loading device 62 is also guided by a guide rail 64 for movement along the loading path BP and can be driven for movement by means of an electromotive belt drive 66 controllable by the control device 40.

[0120] In Fig. 2, top left, shows a compressor 68 and a pressure accumulator 69 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.

[0121] Gas is always present in a reaction vessel 88 of the reaction vessel device 18. Additionally, the reaction vessel 88 can be filled with a liquid, which can be expelled from a discharge opening of the reaction vessel by increasing the gas pressure in the reaction vessel 88 by the feeding 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 vessel 88 when expelling a liquid, the liquid expelled from the reaction vessel 88 is fed into either the useful liquid container 90 (see Fig. 3) the useful receiving device 50 or into the waste liquid container 45. The present application fundamentally distinguishes between a liquid present in the reaction container 88 as a handling target, in which case the present liquid was desired as an intermediate or final product of a liquid handling operation, and a liquid present in the reaction container 88 as handling waste, in which case the present liquid is no longer required and is disposed of.

[0122] It should be added that by means of a further vertical guide rail 32a, i.e. running along the direction of gravity g, the transparent cover 32b of the operating fluid compartment 32 is removed from the Fig. 1 and Fig. 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 via a framework 32c to a guide carriage 32d which can be displaced along the guide rail 32a. Gravity loads the cover 32b into the position shown in the Fig. 1 and Fig. 2, in which the operating fluid compartment 32 is sealed gas-tight by the cover.

[0123] In the extension area of ​​the reaction vessels 88 of the reaction vessel device 18, a magnetic device 70 is arranged on the device 10, by means of which a magnetic field can act in the interior of the reaction vessels 88. The magnetic device 70 is in the view of Fig. 2 is largely concealed by the reaction vessel device 18. The Fig. However, 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.

[0124] The magnetic device 70 will be discussed in more detail below. It comprises a magnet carrier arrangement 72 in which Fig. 3 insufficiently visible permanent magnets 94 (see Fig. 6) are arranged in a pattern. The magnet carrier arrangement 72 has two magnet carriers 72a and 72b that are movable along the direction of gravity g both relative to one another and relative to the device housing 12. Each of the magnet carriers 72a and 72b has its own movement drive 74a or 74b, by which the respective drivable magnet carrier 72a or 72b can be driven independently of the other magnet carrier by the control device 40 to move along the direction of gravity. Through this relative movement of a magnet carrier 72a and 72b, 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.Of course, the movement drives 74a and 74b can also be controlled by the control device 40 in such a way 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.

[0125] The automated liquid handling device 10 also includes a Fig. 2 to 5, which enables either the waste container arrangement 44 on its own or the waste container arrangement 44 together with a useful container arrangement 78 of the useful receiving device 50 to be raised and lowered along a handling movement path HB defined by a guide rail 80. This allows the waste container arrangement 44 or the useful container arrangement 78 to be brought closer to the reaction container device 18 and removed from it again. In the illustrated embodiment, the useful container arrangement 78 can only be brought closer to the reaction container device 18 together with the waste container arrangement 44, which is then located beneath the useful container arrangement 78 and shielded thereby. When the useful container arrangement 78 is desired to be brought closer to the reaction container device 18, the waste container arrangement 44 is moved along as ballast.However, a single lifting device 76 is sufficient to separately approach and remove both container assemblies 44 and 78 from the reaction container device 18.

[0126] The lifting movement of the lifting device 82 of the lifting device 76 is controlled by a Fig. 3 is effected by the lifting drive 84, which 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. Preferably, the movement drives 74a and 74b of the magnetic device 70 and the lifting drive 84 are similar, particularly preferably identical, drives.

[0127] Then, when an approach of only the waste container arrangement 44 to the reaction container device 18 is desired, the useful container device 50 can be moved into its Fig. 3 shown alternative position, which is located along the standby movement path RB between its setup position and its standby position.

[0128] In 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.

[0129] In the useful container arrangement 78, useful 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 useful liquid container 90, and thus at least one reaction container 88 can be arranged. This ensures that liquid, in this case the handling target, can be dispensed from each reaction container 88 into a useful liquid container 90 in the handling position of the devices 18 and 50. For the sake of clarity, only some of the reaction container arrangements 86, the reaction container 88, and the useful liquid container 90 are provided with reference numerals.

[0130] In Fig. 3 is also already in Fig. 2, an ultrasonic sensor can be seen, with which the presence of a reaction container arrangement 86 in the reaction container carrier 20 and, if appropriate, 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.

[0131] In the Fig. 4 and Fig. 5, 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.

[0132] In 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 assembly 44 will be explained in detail below using separate figures.

[0133] In Fig. 4, 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 outwardly away 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 closer to the viewer of Fig. 4 side with the arm of the lifting device 82 arranged there lies in front of the cutting plane of Fig. 4 and is therefore not shown.

[0134] The lifting device 82 also has a projection 82c, here: a vertical projection 82c, on which the utility container assembly 78, optionally with an adapter receiving it in the utility container carrier 52, can engage during a lifting movement along the handling movement path HB of the lifting device 82 for carrying it against the direction of gravity g. The formations 82a, 82b, and 82c are preferably formed as a single piece and monolithic.

[0135] 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.

[0136] The magnet carrier 72a is located in Fig. 4 in a maximum lowered position, as is necessary so that the reaction vessel device 18 with the reaction vessel arrangements 86 arranged thereon can be moved collision-free along its standby movement path RB from the Fig. 4 shown standby position into the Fig. 1. Thus, with one and the same lifting device 82, the waste container arrangement 44 and / or the useful container arrangement 52 can be lifted in their respective standby positions toward the reaction container device 20 in its standby / handling position. This ensures that a discharge end 106 of a reaction container 88 can be immersed in a container comprising the useful liquid container 90 and the waste liquid container 45 for dispensing liquid, for example, for an immersion distance of 1 to 2 mm.

[0137] Since the waste container arrangement 44 would have to be removed from its standby position for the sole lifting movement of the useful 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 useful container arrangement 78 are lifted together by the lifting device 76.

[0138] In Fig. 5, 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 to the reaction container device 18, which is only movable along the standby movement path RB, by the lifting device 86 along the handling movement path HB. Meanwhile, the useful receiving device 50 is in its evasive position, displaced relative to the standby position along its standby movement path NB.

[0139] In the present case, the useful container arrangement 78 is a known one-piece injection-molded titer plate with the already mentioned 12 x 8 = 96 useful liquid containers 90.

[0140] In Fig. 6 shows a rough schematic plan view of the magnet carrier arrangement 72 of the magnet device 70. In the Fig. 7 and Fig. 8, the magnet carriers 72a and 72b are more realistic than in Fig. 6 shown in exploded subviews.

[0141] In Fig. 6, the reaction vessels 88 of the reaction vessel device 18 are shown in their orthogonal 12 x 8 matrix. The rough schematic view of Fig. 6 is a plan view of the magnet carrier assembly 72 in relation to portions of the reaction vessels 88, which extend with their receiving volume 112 (see, for example, Fig. 11) orthogonal to the plane of Fig. 6. The reaction vessels 88 are arranged along mutually parallel first rows 88a and mutually parallel second rows 88b. The straight first rows 88a and the straight second rows 88b are orthogonal to each other. At each intersection point of each first row 88a with each second row 88b, exactly one reaction vessel 88 is arranged. For the sake of clarity, Fig. 6, starting from the upper left reaction vessel 88, only four of twelve first rows 88a and only four of eight second rows 88b are indicated by dash-dotted lines. The eight reaction vessels 88 of each reaction vessel arrangement 86 formed integrally by injection molding extend 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.

[0142] The intersecting first rows 88a and second rows 88b, which are each parallel to the plane of the Fig. 6, also span the plane of the Fig. 6 parallel reference plane BE.

[0143] The magnet carrier arrangement 72 has a plurality of matrix magnets 94, which are arranged distributed over the magnet carriers 72a and 72b. The matrix magnets 94 are physically and magnetically essentially identical permanent magnets, but are arranged differently oriented with regard to their polarization depending on their location in the magnet carrier arrangement 72. What all matrix magnets 94 have in common 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 Fig. 6, the magnetic south pole of a matrix magnet 94, marked by the letter "S", follows the magnetic north pole of the same matrix magnet 94, marked 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 orthogonally to the reference plane BE.

[0144] In the example shown, 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 by an angle relative to the plane of the drawing of the Fig. 6 and thus rotated to the axis of rotation orthogonal to the reference plane BE.

[0145] 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, respectively, i.e. in the present case greater than 20. In the illustrated embodiment, 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.

[0146] The matrix magnets 94 are also arranged in an orthogonal matrix, namely along mutually parallel third rows 96a and along mutually parallel fourth rows 96b. For reasons of clarity, only the left first three third rows 96a and only the top first three fourth rows 96b are shown in Fig. 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.

[0147] The matrix magnets 94 are located at intersection points of the third rows 96a and the fourth rows 96b. However, in contrast to the reaction vessels 88, where each intersection point 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 point 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 point located next to an intersection point occupied by a matrix magnet 94 is not occupied by a matrix magnet 94.

[0148] In this way, exactly two matrix magnets 94 are adjacent to each reaction vessel 88 in the reference plane BE.

[0149] Furthermore, 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. Furthermore, 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 of the 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. The same applies to the matrix magnets 94 in successive fourth rows 96b.If one imagines the third rows 96a to be consecutively numbered starting with 1, the polarization directions 94a of all matrix magnets 94 arranged in third rows 96a with odd numbers are the same, and the polarization directions 94a of all matrix magnets 94 arranged in third rows 96a with even numbers are the same. If one also imagines the fourth rows 96b to be consecutively numbered starting with 1, the polarization directions 94a of all matrix magnets 94 arranged in fourth rows 96b with odd numbers are the same, and the polarization directions 94a of all matrix magnets 94 arranged in fourth rows 96b with even numbers are the same.

[0150] In this way, each reaction vessel 88 is opposite a different polarization section of the two adjacent matrix magnets 94. Of the two matrix magnets 94 immediately adjacent to a reaction vessel 88, 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 of the other of the two matrix magnets 94, both polarization sections and the edge emerging from the matrix magnet 94 faces the virtual interface 94b between the two polarization sections. As a result, the two adjacent matrix magnets 94, which are physically and magnetically essentially identical, act with different magnetic field strengths on the reaction vessel 88, which is equidistant from each of the two matrix magnets 94.Thus, with an asynchronous relative movement of the two matrix magnets 94 adjacent to the same reaction container 88 relative to each other and relative to the reaction container 88 parallel to the direction of gravity g, or with a synchronous but oppositely directed relative movement of the two matrix magnets 94 adjacent to the same reaction container 88, a very good mixing effect of magnetic particles suspended in a liquid in the reaction container 88 can be achieved. Nevertheless, due to the different magnetic effects of the two adjacent matrix magnets 94 on one and the same reaction container 88, an immobilization of the magnetic particles in the reaction container 88 in the region of the magnetic field of the increasing strength of the matrix magnet 94 can be achieved, thus preventing an undesirable double cluster formation of magnetic particles due to two magnetic fields acting on the interior of the reaction container 48.

[0151] For this purpose of effective utilization of the magnetic fields emanating from the matrix magnets 94 and their effect on the contents of the reaction containers 88, for all reaction containers 88 arranged in the reaction container carrier 20, 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.

[0152] Following the above virtual numbering, all third or fourth rows with odd row numbers are arranged on one and the same magnetic carrier. In this case, all third rows 96a with odd numbers are arranged on the magnetic carrier 72a. Likewise, all third or fourth rows with even numbers are arranged on one and the same other magnetic carrier. In this case, all third rows 96a with even row numbers are arranged on the magnetic carrier 72b.

[0153] All third rows 96a of a magnet carrier 72a or 72a presently have the same number of matrix magnets 94. However, the even-numbered third rows 96a, i.e., the third rows 96a of the magnet carrier 72a, in the present embodiment each have one fewer matrix magnets 94 than the third rows 96a of the magnet carrier 72b. The latter rows have five matrix magnets 94. The third rows 96a of the magnet carrier 72a, in contrast, each have only four matrix magnets 94.

[0154] 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 converge on the magnet carrier base of the other magnet carrier 72b or 72a.

[0155] In the illustrated embodiment, 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. Basically, if a magnet carrier leg 72a-2 or 72b-2 of a magnet carrier 72a or 72b is arranged along the direction of its magnet carrier base 72a-1 or72b-1 has an adjacent magnet carrier leg on each side, these two adjacent magnet carrier legs are magnet carrier legs 72b-2 or 72a-2 of the other magnet carrier 72b or 72a.

[0156] 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 numbers, and the magnet support legs 72b-2 carry the third rows 96a with even row numbers.

[0157] 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. In contrast, 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.

[0158] 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 that supports 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 that supports 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.

[0159] Likewise, those 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 edge-mounted reaction vessels 88-1. In contrast, 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 interior-mounted reaction vessels 88-2.

[0160] 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 defined by the respective virtual vessel axes BA (see, for example, Fig. 10A, Fig. 11, Fig. 15 and Fig. 16) of the reaction vessels 88 involved.

[0161] Each outer matrix magnet 94-1 is adjacent to two reaction vessels 88, more precisely two peripheral reaction vessels 88-1.

[0162] If one considers four matrix magnets 94 arranged closest to one another in a rectangle, two of which are arranged in the same third row 96a and two in the same fourth row 96b, then 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.

[0163] Thus, while 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.

[0164] In the Fig. 7 and Fig. 8 is a perspective bottom view of the magnet carrier arrangement 72 or its magnet carriers 72a and 72b in a more realistic representation than in Fig. 6 shown.

[0165] 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.

[0166] 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 positively secured therein against falling out sideways. The magnet holding plate 73a-2 and 73b-2, respectively, fastened to the underside of the respective magnet receiving component 73a-1 and 73b-1 with screws 98, secures the matrix magnets 94 in their receiving recesses 95a and 95b of the magnet receiving component 73a-1 and 73b-1, respectively, against falling out in the direction g of gravity. The magnet holding plate 73a-2 and 73b-2 essentially has the same circumferential contour, consisting of the base and the legs projecting from it, as the magnet receiving component 73a-1 and 73b-1, respectively, to which it is screwed.In this way, the matrix magnets 94 can be arranged as close as possible to a dispensing opening of the reaction container 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.

[0167] 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.

[0168] In order to be able to bring the matrix magnets 94 as close as possible to the container wall 110 of reaction containers 88, 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.

[0169] In the Fig. 9 to 16, a reaction vessel assembly 86 and reaction vessels 88 of the reaction vessel assembly 86 are shown in different views and with different levels of detail.

[0170] 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, eight in the example shown, are arranged consecutively 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 run parallel to one another and transversely, preferably orthogonally, to the following path FB, at least when the reaction container arrangement 86 is accommodated in the reaction container carrier 20. Fig. Figure 10A shows a longitudinal sectional view through the reaction vessel assembly 86 of Fig. 9, where the section plane contains the virtual vessel axes BA of the individual reaction vessels 88. The viewing direction of the section view of Fig. 10A is indicated by the arrow XA in Fig. 9 is displayed. Fig. Figure 10B shows a rough schematic side view of the reaction vessel assembly 86 of Fig. 10A with exaggerated curvature for improved fixation of the reaction vessel assembly 86 in the reaction vessel carrier 20. Fig. 11 shows a longitudinal section through a reaction vessel 88, more precisely through a peripheral reaction vessel 88-1. The section plane of Fig. 11 is the same as that of Fig. 10A. Fig. Figure 12 shows an enlarged view of the discharge end of the reaction vessel 88 of Fig. 11. Fig. 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. Fig. 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. Fig. 15 shows a plan view of the reaction vessel arrangement of the Fig. 9 and Fig. 10A and Fig. 16 shows a cross-sectional view along the section plane XVI-XVI of Fig. 10A orthogonal to the virtual container axes BA below a band connecting the reaction containers 88 of the reaction container arrangement 86, but in the region of the radial projections and a web connecting a reaction container 88 with its reaction container 88 adjacent along the following path FB.

[0171] Each reaction vessel 88 has an input end 102 with, in the illustrated embodiment, a substantially circular input opening 104. At a distance D measured along the virtual vessel axis BA (see Fig. 11) 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.

[0172] Within the space surrounded by a container wall 110 of the reaction container 88, 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 inlet opening 104.

[0173] 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 gas through the inlet opening 104 by means of the pressure-changing device 62b. 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.

[0174] A more detailed representation of the shape of the output channel 108 shows Fig. 12. On its side facing the receiving volume 112, the output channel 108 has an inlet opening 114, which, along the virtual container axis BA, marks the axial longitudinal end of the output channel 108 closer to the receiving volume 112. At its axial longitudinal end axially opposite the inlet opening 114 and farther from the receiving volume 112, the output channel 108 ends in an output 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 container 88.

[0175] Preferably, 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.

[0176] In the illustrated embodiment, 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.

[0177] To protect the dispensing opening 116 and the dispensing surface 120 surrounding it, an axial projection 122 extending along the container axis BA extends circumferentially around the dispensing surface 120, preferably in a closed configuration. 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.

[0178] For example, 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 discharge surface 120 is preferably 0.1 mm or between 20% and 30% of the distance of the inlet surface 118 from 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 dispensing opening 116 from all sides, is greater than its projection length L, preferably at least twice as large. In the illustrated embodiment, 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.

[0179] 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.

[0180] 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. In the illustrated embodiment, the diameter De of the inlet surface 118 is approximately 0.5 mm, and the diameter Da of the outlet surface 120 is approximately 1 mm.

[0181] 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 taper angle α1 (see Fig. 11), which is preferably constant over the entire axial length of the first tapered region 112a, is smaller than the tapered angle α2 of a second tapered region 112b following the first tapered region 112a in the direction of the output channel 108.

[0182] In Fig. 11, the taper angles are drawn on the outer wall surface 110b for better clarity. Due to the constant thickness T of the container wall 110 along its course along the container axis BA, the taper angles α1 and α2 drawn on the outer wall surface 110b also correctly reflect the taper of the inner wall surface 110a. The taper angles α1 and α2 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.

[0183] The taper angle α1 is a moderate taper angle in the range of 0.7° to 5°, 1° in the illustrated embodiment. In this first taper region 112a, 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.

[0184] In the illustrated embodiment, 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. Preferably, the first tapered region 112a is at least five times as long as the second tapered region 112b along the container axis BA.

[0185] In Fig. 11, 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 α1 to the second tapered angle α2. In longitudinal sectional views containing the virtual container axis BA, 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 of 0.8 mm to 1.1 mm.

[0186] The taper angle α2 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.

[0187] 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. In the illustrated embodiment, 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.

[0188] 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.

[0189] The dispensing surface 120 can ensure that liquid exiting 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 extent 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.

[0190] On the side of the first tapered region 112a closer to the input opening 104, there is a funnel region 128 with a third tapered angle α3, which is greater than the first tapered angle α1 and smaller than the second tapered angle α2. In the illustrated embodiment, the third tapered angle α3 is approximately 30°.

[0191] In the illustrated embodiment, 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. Between the first tapered region 112a and the funnel region 128 there is therefore 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. In contrast, the curvature of the inner wall surface 110a in the first transition region 124 is concave.

[0192] 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. Preferably, 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 transition regions 124 or 126 adjacent thereto.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.

[0193] MA denotes a range of motion along which the magnet carrier assembly 72, with its two magnet carriers 72a and 72b, can at least move during operation of the liquid handling device 10. In fact, the magnet carrier assembly 72 can be moved below the discharge ends 106 of the reaction container assemblies 86 in order to be able to move the reaction container device 18 between its setup position and its standby position without collision.

[0194] The mutually facing longitudinal ends of the funnel region 128 and the first tapered region 112a are in Fig. 11 are separated from each other by thin horizontal lines, between which the second transition region 130 is located.

[0195] To facilitate the introduction of liquid 109 through the inlet opening 104 into the receiving volume 112, 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 outlet channel 108. Preferably, the fourth taper angle α4 is also constant along the entire guide region 132.

[0196] The fourth taper angle α4 is smaller than the third taper angle α3 and, in the illustrated embodiment, essentially corresponds to the first taper angle α1 or differs from it by no more than 30% relative to the first taper angle α1.

[0197] Again, parallel horizontal lines in Fig. 11 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 continuously and without jumps from the guide region 132 as it approaches the discharge channel 108 into the funnel region 128.

[0198] The reaction vessels 88 of a reaction vessel assembly 86 are connected to one another at their input ends 112 by a belt 136 running along the follower path FB. As already explained several times, the reaction vessel assembly 86 discussed here is formed as a single piece as an injection-molded component made of thermoplastic material.

[0199] In Fig. 10A shows a longitudinal sectional view through a reaction vessel assembly 86. The details of the reaction vessels 88 shown therein have already been described above in connection with the Fig. 11 and Fig. 12 explained.

[0200] With EI, Fig. 10A one to the drawing plane of the Fig. 10A orthogonal input end plane, in which the input openings 104 of the reaction vessel arrangement 86 shown and all further ones in front of and / or behind the Fig. 10A shown reaction vessel arrangement 86 arranged in the reaction vessel carrier 20.

[0201] With EO, Fig. 10A one to the drawing plane of the Fig. 10A orthogonal discharge end plane, in which the discharge openings 116 of the reaction vessel arrangement 86 shown and all further ones in front of and / or behind the Fig. 10A shown reaction vessel arrangement 86 arranged in the reaction vessel carrier 20.

[0202] The preferably parallel virtual planes EI and EO are to be understood as having a certain thickness 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 EI and EO 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.

[0203] To stiffen the reaction container arrangement 86, whose belt 136 has approximately the same thickness T as the container wall 110, webs 138 are formed between adjacent reaction containers 88 along the following path FB, more precisely in the illustrated embodiment between adjacent guide regions 132, which connect the adjacent reaction containers 88 to one another. The webs 138 protrude integrally from the belt 136 toward the discharge end. Consequently, with eight consecutive reaction containers 88 along the following path FB, seven webs 138 are formed between adjacent reaction containers 88.

[0204] Fig. 10B shows an unrealistically exaggerated curvature of the reaction vessel arrangement 86 about a curvature axis K orthogonal to the guideway FB and to the vessel axes BA. The curvature axis K runs orthogonally to the plane of the drawing of Fig. 10B and is actually further away from band 136 than in Fig. 10B. The Fig. 10B serves only to qualitatively illustrate the axis of curvature K and its position relative to the belt 136. A surface 136a facing away from the reaction vessels 88 is therefore convexly curved.

[0205] 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 penetrated by virtual receptacle axes, which are aligned parallel to one another. In contrast, the vessel axes BA are Fig. 10B, the curved reaction vessel arrangements 86 are oriented divergingly. If the curved reaction vessel arrangement 86 with the diverging vessel axes BA is now arranged in the reaction vessel carrier 20 with the parallel receiving 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 receiving axes within a certain tolerance range. The resulting deformation is an elastic deformation, which increases the contact force with which a vessel wall 110 presses against a wall or structure of the reaction vessel receptacle 24 or the reaction vessel carrier 20.This increased contact force increases the frictional force acting between the reaction vessels 88 and the reaction vessel carrier 20, so that the resistance of a reaction vessel arrangement 86 arranged deformed in the reaction vessel carrier 20 due to its curved rest state against removal from the reaction vessel carrier 20 is increased compared to the same reaction vessel arrangement 86 arranged undeformed in the reaction vessel carrier 20.

[0206] To further improve the fixation of the reaction container arrangement 86 in the reaction container carrier 20, radial projections 140 are formed on the outer wall surfaces 110b of the container wall 110. In the illustrated embodiment, each reaction container 88 is provided as a fixation reaction container with three radial projections 140 arranged equidistantly around the container axis BA. In the illustrated embodiment, the radial projections 140 are formed in the guide region 132 and extend parallel to the virtual container axis away from the belt 136 toward 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.

[0207] The radial projections 140 are particularly well suited for Fig. 9, Fig. 13, Fig. 14 and Fig. 16 can be seen.

[0208] The radial projections 140 locally increase the outer diameter or outer dimension of the reaction vessel 88 and in particular of the guide region 132 carrying the radial projections 140. Therefore, if the guide region 132 with the radial projections 140 is inserted 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.

[0209] From a technical and physical perspective, 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. Due to the elastic deformation, the contact force with which the radial projections 140 are pressed against a contact surface of the reaction vessel receptacles 24 increases, and as a result of the increased contact force, the frictional force acting between the reaction vessel 88 and the reaction vessel receptacle 24 increases.

[0210] The essentially identically formed radial projections 140 have lateral flanks that enclose an angle β1 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 over a diameter direction in which no radial projection 140 is present.

[0211] While the outer wall surfaces 110b of the guide region 132, which carries the radial projections 140, tapers slightly toward the discharge end 106, the radially outward-facing end surface 140a preferably runs 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.

[0212] 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.

[0213] 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 this distance to the control device 40. Encoding information by the physical coding formation 142 during the manufacture of the reaction container assembly 86 offers the significant advantage of avoiding subsequent incorrect coding by a laboratory technician, as might potentially occur during hectic laboratory work.

[0214] For example, 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.

[0215] Furthermore, 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.

[0216] The coding states are preferably 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, predetermined by the coding formation 142 formed thereon, 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 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 data assignments correspond to a detection area 142a or 142b detected by the container sensor 92.Assign a coding state associated with this detection to a pressure value that the control device 40 is 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. Instead of a pressure value, for the detection of which the pressure sensor 69a can be used on the device side or a further pressure sensor can be provided, a duration of an introduction of gas into the receiving volume 112 can also be stored in the data memory 42.

[0217] The detection surface 142a is preferably a flat surface and is also preferably parallel to the surrounding portion of the surface 136a of the belt 136. This applies at least in a state in which the reaction vessel arrangement 86 is arranged in a reaction vessel carrier 20, since then the above-described curvature about the curvature axis K is eliminated and the reaction vessel arrangement 86 arranged in the reaction vessel carrier 20 is essentially uncurved.

[0218] However, the parallelism of the flat detection surface 142a to at least the section of the surface 136a surrounding it can essentially also apply in the original curved delivery state, since, on the one hand, the curvature about the curvature axis K has a very large radius of curvature, which is significantly greater than the reference length RD, so that the curvature in the area around the coding formation 142 is negligible. Furthermore, the curvature of the reaction vessel arrangement 86 in the delivery state is preferably achieved essentially at the webs 138 by targeted material shrinkage during cooling, so that the longitudinal end region 136b, which is from the edge-positioned reaction vessel 88-1 closest to the coding formation 142 in Fig. 10A projects to the right, can be formed without curvature around the curvature axis K.

[0219] The overall curvature of the reaction vessel arrangement 86 can therefore be composed of flat sections of the reaction vessel arrangement 86 in the region of the inlet openings 104, which, due to the targeted utilization of a material shrinkage in the region of the webs 138, are inclined relative to an adjacent flat region by an angle about an inclination axis parallel to the curvature axis K. Such a reaction vessel arrangement 86 has, when viewed according to the perspective of Fig. 10B is not a continuously curved shape like the one in Fig. 10B, but rather, the band 136 has a polygonal shape with flat regions angled relative to one another in the same direction of inclination at the inlet openings 104 and also at the projecting longitudinal end regions 136b and 136c, resulting in an overall curved shape. In other words, the curved reaction vessel arrangement 86 need not be a continuously curved reaction vessel arrangement 86, but can be a discontinuously curved reaction vessel arrangement 86 formed by a series of flat regions inclined relative to one another.

[0220] To save weight, the belt 136 can be constricted in areas between two reaction vessels 88 following one another along the following path FB (see Fig. 15), wherein a stepless and continuous constriction is preferably formed. With the exception of the physical coding formation 142 and the radial projections 140, the reaction vessel arrangement 86 is preferably mirror-symmetrical with respect to a plane containing the vessel axes BA.

[0221] The waste container assembly 44 with the waste liquid container 45 will be described below.

[0222] In the Fig. 17 and Fig. 18 is the waste liquid container 45 in perspective view ( Fig. 17) and in a cross-sectional view ( Fig. 18).

[0223] The waste liquid container 45 has a tub body 45c, which surrounds a receiving volume 45a of the tub body 45c and thus of the waste liquid container 45. The tub body 45c is covered by a container lid 45d. The container lid 45d does not cover the entire tub body 45c, but rather a spout 144 is formed at each of the longitudinal ends of the tub body 45c. The spouts 144 are recessed in the container lid 45d. In the setup position, an operator or a service robot can lift the waste liquid container 45 from the drawer 28 supporting it and dispose of liquid handling waste, which has accumulated in the receiving volume 45a over several handling operations, through one of the spouts 144 without lifting the lid 45d.In principle, it is also possible to remove the waste liquid container 45 filled with handling waste from its recess 28b in the drawer base 28a and replace it with a similar empty waste liquid container 45. This allows more time for the disposal of the handling waste, and this disposal can be carried out with more care.

[0224] The container lid 45d has an elongated recess serving as a waste seal assembly receptacle 27, into which the loading device 62, or more precisely, the pressure-changing device 62b, can deposit a seal assembly 22. Once the seal assembly 22 arranged on the pressure-changing device 62b is immersed in the waste seal assembly receptacle 27, it can be removed from the loading device 62, or more precisely, from the pressure-changing device 62b, by moving the waste liquid container 45 along the standby movement path AB. An operator or a service robot can then, when the waste liquid container 45 is in its setup position, remove the used seal assembly 22 from the waste seal assembly receptacle 27 in the container lid 45d and dispose of it.

[0225] Both the tub body 45c and the container lid 45d are preferably manufactured as a single piece from a thermoplastic injection-molded component. However, manufacturing from stainless steel is also possible. The tub body 45c and the container lid 45d can be deep-drawn for this purpose. The container lid 45d can also have openings provided by stamping.

[0226] The container lid 45d covers a filling opening 146 of the bowl-shaped or tub-shaped tub body 45c. The tub body 45c comprises a container bottom 148, which, as in Fig. 18, can be flat or can have defined support formations for particularly secure standing. Side walls 150a to 150d protrude from the container bottom 148, and the filling opening 146 is formed on the edge of said walls remote from the container bottom 148. The side wall 150a is the side wall which, during the movement of the waste liquid container 45 from the setup position to the standby position, is oriented transversely to the standby movement path AB and leads the way. The opposite side wall 150b follows during 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.

[0227] 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.In this way, it is ensured that when handling waste is to be dispensed from the reaction containers 88 through the dispensing channels 108, an opening 152 in the container lid 45d of the waste liquid container 45 is opposite each dispensing channel 108 and thus handling waste from any reaction container 88 can safely reach the receiving volume 45a of the waste liquid container 45.

[0228] 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.

[0229] By means of the lifting device 76 described above, the waste liquid container 45 can be raised 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. In the device 10, all discharge 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 take into account the manufacturing tolerance of the reaction vessels 88.

[0230] As a splash guard, 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. Preferably, 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.

[0231] To stiffen the container lid 45d, 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.

[0232] 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.

[0233] Starting from the edge 152a of an opening, an inlet region 156a of the wall arrangement 156 extends along the inlet axis EA from the container lid 45d toward the container bottom 148. The inlet region 156a, like the rest of the wall arrangement 156, is curved around the respective inlet axis EA. The inlet region 156a is also curved around axes of curvature that run orthogonal to the inlet axis EA and spaced apart from it. The infinite number of axes of curvature orthogonal to the inlet axis EA extend circumferentially around the inlet axis EA.

[0234] 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.

[0235] In contrast to the inlet area 156a, the outlet area 156b is only curved around the inlet axis EA in the illustrated embodiment.

[0236] 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.

[0237] In the Fig. 19 and Fig. 20 shows the loading device 62 with its movement apparatus.

[0238] 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.

[0239] On the guide rail 64, a guide carriage 170 connected to the belt 66a for common movement is movably arranged along the feed path BP.

[0240] A mobile support 172 is arranged on the guide carriage 170, which is movable along the loading path BP together with the guide carriage 170 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, which, 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.

[0241] 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. As a result, 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 can be lifted away from them again. Fig. 1 Sealing assembly 22, when arranged on the loading device 62, can be pressed sealingly against the belt 136 of the reaction container assemblies 86 with a predetermined and / or defined contact pressure. Furthermore, the movement drive 176 can move a used sealing assembly 22 arranged on the loading device 62 along the approach path WP into the waste sealing assembly receptacle 27, from where it can be stripped from the loading device 62, more precisely from the pressure-changing device 62b, by moving the waste liquid container 45 along its standby movement path AB.Alternatively, a used sealing arrangement 22 arranged on the loading device 62 can be moved along the approach path WP into the sealing arrangement receptacle 26 by the movement drive 176, from where it can be stripped from the pressure changing device 62b by moving the reaction vessel carrier 20 along its standby movement path RB.

[0242] The feeding device 62 is explained in more detail below, which is shown in the Fig. 19 and Fig. 20 without its switching valves. As can be seen from the Fig. 19 and Fig. 20, the feed device 62 comprises a line body 178 and a discharge component 180. In the line body 178, the switchable valves 182, 184 and 186 (see Fig. 21) are formed with interconnectable and separable lines, which open into metering openings 188 for dispensing liquid and into gas outlet openings 190 for dispensing gas in the dispensing component 180. The metering openings 188 and the gas outlet openings 190 are arranged offset relative to one another along an offset direction VD parallel to the feed path BP. Their distance along the offset direction VD is greater than at least the opening width OW of the inlet openings 104 of the reaction vessels 88, so that if one opening of the metering opening 188 and the gas outlet opening 190 is arranged centrally above an inlet opening 104, the other opening cannot discharge into the inlet opening 104.In order to prevent a simultaneous discharge of a metering opening 188 and a gas outlet opening 190 into the same input opening even when an opening consisting of a metering opening 188 and a gas outlet opening 190 is arranged off-center above an input opening 104, the distance between the metering openings 188 and the gas outlet openings 190 is preferably greater than the opening width OW.

[0243] As in Fig. 22, the metering openings 188 can be formed by simple openings in the dispensing component 180 or as an end opening of a pipe 189 (see in Fig. 22, the rightmost metering opening 188). Preferably, all lines leading to a metering opening 188 are of the same design, i.e., preferably, either all metering openings 188 are openings directly in the dispensing component 180 or all metering openings 188 are openings in a respective pipeline 189. The pipelines 189 preferably protrude beyond a surface 180a of the dispensing component 180 that, during operation, points toward the reaction vessel device 18. The surface 180a, from which the pipelines 189 emerge, can be set back from a further surrounding surface 180b of the dispensing component 180 in order to protect the end sections of the pipelines 189 from external mechanical influences.

[0244] The sealing assembly 22 is received by a receiving projection 22b in a receiving recess 192 in the dispensing component 180, which extends parallel to the standby movement path RB of the reaction container device 18, in a form-fitting manner along an exchange path BB running parallel to the standby movement path RB and orthogonal to the loading path BP. The receiving recess 192 is provided in the dispensing component 180 by a T-slot-shaped seal receiving structure 193.

[0245] Through openings 194 in the sealing arrangement 22, which penetrate the sealing arrangement 22 and its sealing surface 22a designed to engage the surface 136a of the band 136, are arranged in the operative arrangement collinear with the gas outlet openings 190 as a continuation thereof in order to guide gas escaping from the gas outlet openings 190 to the inlet openings 104 of the reaction vessels 88.

[0246] Of the Fig. 21, mounted on the rear side 178a of the line body 178, 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.

[0247] The two switching valves 186 form a switching valve device 187, which allows a liquid from one of the containers 34 and 36 or gas from the gas pressure reservoir 69 to be selectively directed through the metering openings 188 of the metering device 62a. By blowing through the lines and metering openings 188 of the metering device 62a in this way, the lines and metering openings 188 of the metering device 62a can be freed and cleaned of the last liquid passed through between a change of liquids to be metered, for example, between containers 34 and 36. Each switching valve 186 can selectively connect an upper or lower opening to a central opening or separate the openings from each other.

[0248] On the conduit body 178, in the illustrated embodiment on the top side 178b, three conduit connections 196, 198 and 200 are arranged. The conduit connections 196 and 198 are liquid-conducting conduit connections which convey liquids from the containers 34 and 36 to a conduit system 202 (see Fig. 23) of the line body 178. It is assumed that the line connection 196 is connected to the extraction line 38a and the line connection 198 to the extraction line 38b. The line connection 200 is a gas-conducting line connection which supplies pressurized gas from the gas pressure accumulator 69 to the line system 202 of the line body 178. The pressure line 38c in the operating fluid compartment 32 is connected to the gas pressure accumulator 69 and is not routed via the valve arrangements of the charging device 62.

[0249] In Fig. 24 is a perspective view of the feeder 62 looking toward the rear side 178a of the conduit body 178 without the switching valves 182, 184, and 186.

[0250] The large openings 204, arranged in four parallel rows, serve solely for the attachment of the switching valves 182, 184, and 186, with each switching valve being secured to the rear side 178a by two screws screwed into a respective large opening 204. For clarity, not all of the large openings 204 are provided with a reference symbol. There are a total of 36 openings 204 on the rear side 178a of the line body 178, namely two for each of the 18 switching valves.

[0251] A bottom row of small openings 206 leads via line sections 208 directly to the metering openings 188.

[0252] The switching valves 182 are arranged to connect the line sections 208 by means of their small openings 206 with likewise small openings 210 of a line section 212 or to separate the said openings 206 and 210 from each other.

[0253] The line section 212 opens into the rear side 178a of the line body 178 in a small central opening 214, which leads to the Fig. 21 right changeover valve 186 opens.

[0254] From the line connection 198, a short line section 216 extends to a small opening 218, which is an upper one of three small openings 218, 214 and 220 formed by the Fig. 21 right changeover valve 168 can be connected in pairs or separated from each other.

[0255] The lowest small opening 220 opens into a line section 222, which only leads to a middle small opening 224 of the Fig. 21 left changeover valve 186.

[0256] In the Fig. 21 left switching valve 186, in addition to the middle small opening 224, an upper small opening 226 of a line section 228, which leads to the line connection 196, and a lower small opening 230 of a line section 232, which leads to the gas-carrying line connection 200, open.

[0257] Directly connected to the gas-carrying line connection 200 is a further line section 234, which leads to small openings 236 below the switching valves 184 of the gas valve arrangement 185. In addition to the small openings 236, small openings 238 of line sections 240 open toward the switching valves 184, which lead directly into the gas outlet openings 190.

[0258] By switching the switching valves 182, the fluid at the openings 210 and thus the fluid at the opening 214 can be selectively directed to the metering openings 188 or not.

[0259] By switching the switching valves 184, the gas present at the openings 236 via the line section 234 can be selectively directed to the gas outlet openings 190 or not.

[0260] Through the Fig. 21 right switching valve 186 can either direct the fluid present at the line connection 198 via the line section 216 and the opening 218 or the fluid present at the opening 220 to the openings 210.

[0261] Through the Fig. 21 left switching valve 186, the middle opening 224 and thus the line section 222 leading to the opening 220 can be connected either to the line connection 196 and the line section 228 leading to the opening 126 or to the opening 230 and thus to the line section 232 and the gas-carrying line connection 200.

[0262] By appropriately switching the switching valves 186, either liquid from the container 34 or liquid from the container 36 or pressurized gas from the gas pressure accumulator 69 can be supplied to the openings 210 of the metering valve arrangement 183.

[0263] In Fig. 25 shows the loading device 62 in perspective from below, looking at the essentially smooth front side 178c of the conduit body 78. This view is presented merely as a supplement and conclusion to the previous explanations. QUOTES CONTAINED IN THE DESCRIPTION

[0000] This list of documents submitted by the applicant was generated automatically and is included solely for the convenience of the reader. This list is not part of the German patent or utility model application. The DPMA assumes no liability for any errors or omissions. Cited patent literature

[0000] WO 2010 / 075199 A2 [0003, 0006, 0017, 0025] WO 2019 / 096407 A1

[0007] US 5705628

[0009] EP 0 691 541 A2

[0015] EP 1 065 001 A1 [0015, 0016] WO 2004 / 113874 A2 [0017, 0018] US 4895706

[0019] US 4111754

[0019] US 5273718

[0019] US 8877145 B2

[0019]

Claims

[1] Automated liquid handling device (10) for handling liquids (109), comprising: i. a reaction vessel device (18) having a plurality of reaction vessels (88) arranged in a matrix-like manner in first rows (88a) and second rows (88b), wherein the first rows (88a) are parallel to one another and wherein the second rows (88b) are parallel to one another, and wherein the first rows (88a) and the second rows (88b) cross one another, wherein each reaction vessel (88) of the plurality of matrix-arranged reaction vessels (88) is located at an intersection point of a first and a second row (88a, 88b), wherein each reaction vessel (88) has an input end (102) with an input opening (104) and an output end (106) spaced from the input end (102) with an output opening (116), and ii. a magnet device (70) for forming a magnetic field in the plurality of reaction containers (88), wherein the magnet device (70) has a movable magnet carrier arrangement (72) with a plurality of matrix magnets (94) carried by the magnet carrier arrangement (72), which are movable outside the plurality of reaction containers (88) at least in a movement range (MA) between the input ends (102) and the output ends (106) of the reaction containers (88), wherein the number of matrix magnets (94) is less than the number of reaction containers (88) in the plurality of reaction containers (88), wherein each reaction container (88) in the plurality of reaction containers (88) has two matrix magnets (94) adjacent to it, characterized byin that the magnet carrier arrangement (72) carries a number of matrix magnets (94) which is greater than the sum of the first and second rows (88a, 88b), the matrix magnets (94) each having a polarization direction (94a) which is neither parallel to the first rows (88a) nor to the second rows (88b) and which is neither orthogonal to the first rows (88a) nor to the second rows (88b). [2] Automated liquid handling device (10) according to claim 1, characterized by in that a plurality of matrix magnets (94) are polarized and arranged such that an interface (94b) between the unlike magnetic poles of each matrix magnet (94) of the plurality of matrix magnets (94) extends transversely to a reference plane (BE) which extends parallel to both the first and the second rows (88a, 88b). [3] Automated liquid handling device (10) according to claim 1 or 2, characterized byin that the matrix magnets (94) have a plurality of inner matrix magnets (94-2), each inner matrix magnet (94-2) being adjacent to exactly four reaction vessels (88), the four adjacent reaction vessels (88) being arranged in two immediately adjacent first rows (88a) and in two immediately adjacent second rows (88b). [4] Automated liquid handling device (10) according to claim 3, characterized bythat at least one inner matrix magnet (94-2) is polarized and arranged in such a way that a first of its four adjacent reaction vessels (88) is opposite a section of the at least one inner matrix magnet (94-2) with only one of its two magnetic polarities, that a second of its four adjacent reaction vessels (88) is opposite a section of the at least one inner matrix magnet (94-2) with only the other of its magnetic polarities, and that a third and a fourth of its four adjacent reaction vessels (88) are each opposite sections of the at least one inner matrix magnet (94-2) with its two magnetic polarities. [5] Automated liquid handling device (10) according to one of the preceding claims, characterized bythat the matrix magnets (94) have a plurality of outer matrix magnets (94-1), wherein each outer matrix magnet (94) is adjacent to exactly two reaction containers (88) which are arranged either in the same first row (88a) or in the same second row (88b). [6] Automated liquid handling device (10) according to claim 5, characterized by that at least one outer matrix magnet (94-1) is polarized and arranged such that a first of its two adjacent reaction vessels (88) is opposed by a section of the at least one outer matrix magnet (94-1) with only one of its two magnetic polarities, and that a second of its two adjacent reaction vessels (88) is opposed by sections of the at least one outer matrix magnet (94-1) with its two magnetic polarities. [7] Automated liquid handling device (10) according to one of the preceding claims, characterized bythat the matrix magnets (94) are arranged in a matrix-like manner in third rows (96a) parallel to the first rows (88a) and in fourth rows (96b) parallel to the second rows (88b), the matrix magnets (94) being located at intersection points of the third and fourth rows (96a, 96b). [8] Automated liquid handling device (10) according to claim 7, characterized by that the number of third rows (96a) is greater than the number of first rows (88a) and that the number of fourth rows (96b) is greater than the number of second rows (88b). [9] Automated liquid handling device (10) according to claim 7 or 8, characterized by that in a third row (96a) and in a fourth row (96b) an intersection point occupied by a matrix magnet (94) is adjacent to an intersection point unoccupied by matrix magnets (94). [10] Automated liquid handling device (10) according to one of claims 7 to 9, characterized by that along a fourth row (96b) immediately successive third rows (96a) of matrix magnets (94) alternately have a higher and a lower number of matrix magnets (94) and / or that along a third row (96a) immediately successive fourth rows (96b) of matrix magnets (94) alternately have a larger and a smaller number of matrix magnets (94). [11] Automated liquid handling device (10) according to claim 10, characterized by that all third rows (96a) with a lower number of matrix magnets (94) have the same lower number of matrix magnets (94) and that all third rows (96a) with a higher number of matrix magnets (94) have the same higher number of matrix magnets (94), or / and that all fourth rows (96b) with a smaller number of matrix magnets (94) have the same smaller number of matrix magnets (94) and that all fourth rows (96b) with a larger number of matrix magnets (94) have the same larger number of matrix magnets (94). [12] Automated liquid handling device (10) according to one of claims 7 to 11, characterized by that with consecutive ascending numbering of all third rows (96a) following one another along a fourth row (96b), the matrix magnets (94) of all third rows (96a) with even row numbers are identically oriented and that the matrix magnets (94) of all third rows (96a) with odd row numbers are identical but oriented differently from the matrix magnets (94) in the third rows (96a) with even row numbers, or / and that with consecutive ascending numbering of all fourth rows (96b) following one another along a third row (96a), the matrix magnets (94) of all fourth rows (96b) with even row numbers are identically oriented and that the matrix magnets (94) of all fourth rows (96b) with odd row numbers are identical but oriented differently from the matrix magnets (94) in the fourth rows (96b) with even row numbers. [13] Automated liquid handling device (10) according to claim 12, including claim 2, characterized by that the matrix magnets (94) of the third rows (96a) with an even row number are arranged rotated by an angular amount of 90° about an axis of rotation orthogonal to the reference plane (BE) with respect to the matrix magnets (94) of the third rows (96a) with an odd row number, or / and that the matrix magnets (94) of the fourth rows (96b) with an even row number are arranged rotated by an angular amount of 90° about an axis of rotation orthogonal to the reference plane (BE) with respect to the matrix magnets (94) of the fourth rows (96b) with an odd row number. [14] Automated liquid handling device (10) according to one of claims 7 to 13, characterized bythat the magnet carrier arrangement (72) has at least two magnet carriers (72a, 72b) which are movable relative to one another, each of which is movable with a movement component running along the direction of the distance between the input opening (104) and the output opening (116), wherein, with consecutive ascending numbering of all third rows (96a) following one another along a fourth row (96b), one magnet carrier (72a) carries only matrix magnets (94) from third rows (96a) with even row numbers and the other magnet carrier (72b) carries only matrix magnets (94) from third rows (96a) with odd row numbers, or / and wherein, with consecutive ascending numbering of all fourth rows (96b) following one another along a third row (96a), one magnet carrier (72a, 72b) carries only matrix magnets (94) from fourth rows (96b) with even row numbers and the other magnet carrier (72a,72b) carries only matrix magnets (94) of fourth rows (96b) with odd row numbers., [15] Automated liquid handling device (10) according to one of the preceding claims, characterized by that each reaction container (88) is adjacent to exactly two matrix magnets (94) such that each reaction container (88) is adjacent to a section of one matrix magnet (94) with only one magnetic polarity and to sections of the other matrix magnet (94) with different magnetic polarities.

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