Automated liquid-handling device with optimized emptying of its reaction vessel

Abstract

An automated liquid-handling device (10) for handling object liquids (109) comprises: i. at least one reaction vessel (88), wherein the at least one reaction vessel (88) has an output opening (116), wherein on an inner side of the output opening (116) there is an interior space filled at least partially with gas, and wherein on an outer side of the output opening (116) there is a gas atmosphere, ii. a pressure-changing device (62b) for changing a difference in gas pressure between the gases present on the two sides of the outlet opening (116) of the at least one reaction vessel (88), iii. a gas line arrangement (39) for conducting a mass flow of gas produced by the pressure-changing device (62b), and iv. a control device (40) for controlling the operation of the pressure-changing device (62b). The liquid-handling device (10) has at least one flow sensor (242), which detects the mass flow of gas flowing in the gas line arrangement (39) and outputs a flow detection signal (250) to the control device (40), wherein, on the basis of the flow detection signal (250), the control device (40) outputs at least one result signal.

Description

[0001] 68488P WO Hamilton BonaduzAG - 1 -

[0002] Automated liquid handling device with optimized emptying of its reaction vessel

[0003] Description

[0004] The present invention relates to an automated liquid handling device for handling object liquids, in particular for the purification of nucleic acids, comprising:

[0005] i. a reaction vessel arrangement with at least one reaction vessel, wherein the at least one reaction vessel is designed to receive a liquid and a gas, wherein the at least one reaction vessel has an inlet end with an inlet opening and an outlet end with an outlet opening located at a distance from the inlet end, wherein in the operational state of the liquid handling device, an interior space of the at least one reaction vessel, at least partially filled with gas, is present on an inner side of the outlet opening, and wherein a gas atmosphere surrounding the at least one reaction vessel is present on an outer side of the outlet opening opposite the inner side, ii.a pressure changing device, wherein the pressure changing device is designed to change a gas pressure difference between the gases present on both sides of the dispensing opening of the at least one reaction vessel in order to carry out a withdrawal process and thereby, with the participation of the generated gas pressure difference, to withdraw an object liquid taken up in the interior of the at least one reaction vessel through the dispensing opening from the at least one reaction vessel.

[0006] iii. a gas piping arrangement with at least one gas piping arranged to convey a gas flow generated by the pressure changing device for changing the gas pressure difference on both sides of the outlet opening of the at least one reaction vessel in the gas piping arrangement, and68488P WO Hamilton BonaduzAG - 2 -

[0007] iv. a control device which is connected to the pressure changing device for the transmission of signals and / or power in order to control the operation of the pressure changing device.

[0008] Such a liquid handling device is used in laboratories, for example, for the purification of nucleic acids. At the beginning of their purification, the nucleic acids are contained in a carrier liquid.

[0009] A liquid handling device with the aforementioned features is essentially known in abstract form from WO 2019 / 096407 A1. An advantage of this known liquid handling device is that, during processing, the liquid is always moved in the same direction from the inlet opening to the outlet opening of the at least one reaction vessel, and consequently, no reversal of direction of the processed liquid occurs, as is known from other prior art liquid handling devices. Thus, a source of potential cross-contamination can be avoided.

[0010] The well-known automated liquid handling device also includes:

[0011] v. a metering device with at least one metering opening for transferring object liquid into at least one reaction vessel of the reaction vessel arrangement, wherein the metering device for transferring object liquid is formed by means of the metering opening through the inlet opening of the at least one reaction vessel,

[0012] vi. a receiving device for receiving object liquid dispensed as a handling target through the dispensing opening of at least one reaction vessel,

[0013] vii. a waste receiving device separate from the receiving device for receiving object liquid dispensed as handling waste through the dispensing opening of the at least one reaction vessel, and68488P WO Hamilton BonaduzAG - 3 -

[0014] viii. a magnetic device for generating a magnetic field in the at least one reaction vessel.

[0015] In preferred embodiments, the automated liquid handling device of the present invention additionally comprises at least one of the devices v. to viii. In more preferred embodiments, the automated liquid handling device of the present invention comprises a plurality of the devices v. to viii, and in a particularly preferred embodiment, it comprises all devices v. to viii.

[0016] The known liquid handling devices, and also the automated liquid handling device of the present invention, are easier to understand with knowledge of the advantageous further development by the devices according to sections v to viii. Nevertheless, it should be noted that the devices according to sections v to viii are not strictly necessary for achieving the purpose of the invention in the automated liquid handling device of the present invention, but merely represent a preferred embodiment. The explanations and configurations given below in the explanation of the prior art regarding the devices according to sections v to viii also apply to advantageous further developments of the present invention.

[0017] The reaction vessel arrangement is the arrangement in which the object fluid is "processed" in the broadest sense and / or in which the object fluid interacts with the contents of a reaction vessel and in which handling of the object fluid takes place. For example, chemical reactions and / or physical processes take place in the at least one reaction vessel. In the at least one reaction vessel of the reaction vessel arrangement, nucleic acids, in particular DNA or RNA, contained in a starting object fluid introduced 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 purified by passing, optionally waiting for a reaction time, and dispensing a cleaning object fluid. The bound and purified nucleic acids 68488P WO Hamilton BonaduzAG - 4 -

[0018] The magnetic particles can be eluted, i.e., separated from the magnetic particles, by transferring a solution, possibly allowing a reaction time, and dispensing an elution solution. The eluate thus obtained can be dispensed from the at least one reaction vessel as the target solution, i.e., as the target solution. In contrast, a portion of the aforementioned initial solution, as well as the subsequently transferred cleaning solution, can be dispensed from the at least one reaction vessel as handling waste, i.e., as waste solution, unlike the target solution.

[0019] The principles of binding nucleic acids to magnetic particles specifically designed for nucleic acid binding are described in US 5705628. This special design can be achieved, for example, by coating the magnetic particles with functional groups.

[0020] The receiving unit of the automated liquid handling device, as described above, serves to receive the target liquid, typically an eluate containing purified nucleic acid, which is dispensed from at least one reaction vessel. Advantageously, the receiving unit can also transport the received liquid to further processing points or stations. For receiving the target liquid, the receiving unit preferably comprises a liquid container arrangement with at least one liquid container, and more preferably with a plurality of liquid containers.

[0021] Similarly, the waste collection device of the automated liquid handling system serves to collect waste object liquids that arise as waste during liquid processing, for example, an initial carrier liquid of nucleic acid, in which undesirable impurities, such as remnants of cell components from the cells originally containing the nucleic acid, and the like, may be present. These impurities are discharged with the carrier liquid after the binding of nucleic acids to magnetic particles and are washed out by one or more subsequent washing processes. 68488P WO Hamilton BonaduzAG - 5 -

[0022] The cleaning fluid used during the washing processes is also a liquid and, after its use, constitutes handling waste within the meaning of the present application. The waste collection device preferably comprises a waste container arrangement with at least one waste liquid container for receiving the handling waste. Although the waste container arrangement may have a plurality of waste liquid containers within the scope of the present invention, it preferably comprises only one waste liquid container as a collection container for handling waste dispensed from the reaction vessels; that is, preferably one waste liquid container is provided for receiving handling waste from all reaction vessels present simultaneously.

[0023] The magnetic device serves to temporarily immobilize the magnetic particles in the at least one reaction vessel. This ensures that only the respective object liquid suspending the magnetic particles in the at least one reaction vessel can be dispensed through the dispensing opening, while the magnetic particles, especially those with attached nucleic acids, can be retained in the reaction vessel.

[0024] The magnetic device preferably comprises a magnet arrangement configured to provide a magnetic field with variable magnetic field strength in the vicinity of the at least one reaction vessel. For this purpose, the magnet arrangement can, in principle, include electromagnets capable of variable current. However, since an electromagnet can also be a heat source, the magnetic device preferably comprises a plurality of permanent magnets, which are movably arranged relative to the at least one reaction vessel to change the magnetic field strength in the vicinity of the at least one reaction vessel. Particularly preferably, the magnetic device comprises two magnet carrier arrangements, each of which has a plurality of permanent magnets and is movable independently of the other relative to the at least one reaction vessel. 68488P WO Hamilton Bonaduz AG - 6 -

[0025] The at least one reaction vessel preferably extends between the input opening and the output opening along a virtual vessel axis, wherein the magnetic device, in particular each of the two magnetic arrangements independently of the other, is particularly preferably movable along the virtual vessel axis towards and away from a wall section of the at least one reaction vessel.

[0026] The pressure-changing device of the liquid handling apparatus according to the invention serves to generate the aforementioned gas pressure difference between a gas inside the at least one reaction vessel and the gas surrounding the reaction vessel. This precisely generated gas pressure difference on both sides of the discharge opening of a reaction vessel allows the liquid contained in the at least one reaction vessel to be moved through the discharge opening.Since the internal volume of a reaction vessel is typically considerably smaller than the gas volume surrounding it, and since the interior of the reaction vessel is usually much easier to seal for effective gas pressure changes, the pressure-changing device is preferably designed only to generate a positive pressure differential, at which the gas pressure inside the reaction vessel is higher than the gas pressure of the external environment surrounding the at least one reaction vessel. According to this preferred embodiment, the liquid is dispensed exclusively through the dispensing opening, but not drawn into the reaction vessel.

[0027] The dosing device of the liquid handling apparatus according to the invention serves for the automated introduction of object liquid into the at least one reaction vessel. It is hygienically advantageous that the object liquid is filled into the at least one reaction vessel through the inlet opening located away from the outlet opening of the at least one reaction vessel.

[0028] Liquid handling devices are also known, for example from EP 0691 541 A2 or from EP 1 065 001 A1, whose reaction vessels only have a 68488P WO Hamilton Bonaduz AG - 7 -

[0029] The device has an opening through which liquids are aspirated into the reaction vessel and subsequently dispensed. Aspiration and dispensing of different liquids in a single liquid processing operation is considered less hygienic than the liquid processing described above, which involves passing liquids through the reaction vessel from the inlet to the outlet. This is largely because the inlet can be designed to be so large that it does not need to be wetted by the liquid introduced into the reaction vessel or by a nozzle dispensing it. This is virtually impossible when aspiration and dispensing occur through the same opening.

[0030] Another liquid handling device is known from WO 2010 / 075199 A2. The liquid handling device known from WO 2010 / 075199 A2 discloses a similar structure to the one mentioned above. However, WO 2010 / 075199 A2 does not disclose a receiving device. The reaction vessels of the known liquid handling device are connected to a common disposal line, which serves as a waste receiving device. Instead, an eluate produced as the handling target in the liquid handling device known from WO 2010 / 075199 A2 is removed from the device together with the reaction vessels containing the eluate and transported for further processing.

[0031] WO 2004 / 113874 A2 discloses a further 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 vessels. The outlet openings of the reaction vessels of the liquid handling device known from WO 2004 / 113874 A2, located away from the inlet openings, are connected to a common discharge line, as in the liquid handling device of the aforementioned WO 2010 / 075199 A2. The reaction vessels removed from the liquid handling device are therefore, for further processing of the handling target once achieved, together with the material contained therein. 68488P WO Hamilton Bonaduz AG - 8 -

[0032] The handling target is removed from the liquid handling device and transported further.

[0033] For further background information on the state of the art, reference is made to publications US 4895706, US 4111754, US 5273718 and US 8877145 B2.

[0034] According to a preferred embodiment of the liquid handling device of the present invention, during liquid handling, a liquid is introduced into and discharged from the at least one reaction vessel by the metering device at least once, but usually several times. Solid components contained in the at least one reaction vessel can be bound in the at least one reaction vessel by various physical mechanisms, depending on the method and the substances used, such as electrostatic interaction, hydrophobic interaction, or by exploiting a biospecific affinity, such as an antigen-antibody interaction or an enzyme-substrate interaction. Preferably, the substances bound in a reaction vessel are...Immobilizable solid components are the aforementioned magnetic particles, which can be immobilized in the at least one reaction vessel by virtue of an external magnetic field generated by the preferably 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. During liquid handling in the at least one reaction vessel, the immobilizable solid components can be suspended once or several times in a liquid contained in the at least one reaction vessel. Other, non-immobilized solid components, which are undesirable in the reaction vessels, can be flushed out with the handling waste.

[0035] The object of the present invention is to further improve the aforementioned automated liquid handling device. The aim is, in particular, to improve the handling of liquids. (68488P WO Hamilton Bonaduz AG - 9 -)

[0036] dere the reduction of handling times without loss of process quality.

[0037] According to the invention, the aforementioned problem is solved by an automated liquid handling device of the type mentioned at the outset in that the liquid handling device has a flow sensor arrangement with at least one flow sensor which is designed and arranged to detect the gas flow rate flowing to change the gas pressure difference in the gas line arrangement and to output a flow detection signal representing the detected gas flow rate to the control device, wherein the control device is configured to output at least one result signal on the basis of the flow detection signal.

[0038] The gas flow generated by the pressure-changing device, which preferably flows into the interior of a reaction vessel, can alter the gas pressure differential on either side of the outlet. Alternatively or additionally, a gas flow could be drawn from the external environment of the reaction vessel; however, this would require a complex sealing of the external environment, which is simpler with the reaction vessel itself. Furthermore, the gas volume in the external environment of a reaction vessel is usually larger than in the interior, so the same magnitude of the change in the gas pressure differential on either side of the outlet is achieved more quickly by introducing gas into the reaction vessel than by drawing gas from the external environment.

[0039] The pressure-changing device can include a pump and / or at least one valve and / or a pressure accumulator to change the gas flow rate in the gas piping arrangement. The pressure accumulator can be an overpressure accumulator or a vacuum accumulator. Preferably, it is an overpressure accumulator that releases gas into the gas piping arrangement to direct gas from the accumulator into the interior of the at least one reaction vessel. 68488P WO Hamilton Bonaduz AG - 10-

[0040] The pump can be a continuously operating rotary pump, such as a vane pump, or a reciprocating pump, such as a piston pump. The pump, if present, preferably has an electric drive which can be controlled by the control unit, allowing the control unit to regulate the pump's operation. The control unit can be configured to simply switch the pump on and off, and is preferably configured to vary the pump output in stages or, preferably, continuously by controlling the pump's drive.

[0041] Preferably, the pressure-changing device comprises a pump and a pressure vessel connected to the pump, serving as a buffer and pressure reservoir. Preferably, the volume of the pressure vessel is at least 15 times, preferably 20 times, larger than the nominal volume of a reaction vessel, so that the withdrawal of pressurized gas from the pressure vessel into the reaction vessel can significantly increase the gas pressure in the reaction vessel, while the gas pressure in the pressure vessel is only reduced to a negligible extent. The pump can then deliver gas into the pressure vessel as an intermediate or buffer storage, from which the gas is withdrawn via a valve controlled by the control device to change the gas pressure differential on both sides of the outlet opening and is directed through the gas piping arrangement into the interior of a reaction vessel.

[0042] The at least one valve can be adjustable only between a defined open position and a closed position, wherein in the closed position the at least one valve completely blocks the passage of gas through the gas line section comprising the at least one valve. Preferably, the at least one valve comprises or is a valve with a continuously variable or infinitely variable flow cross-section.

[0043] Depending on the operating or functional states of the at least one reaction vessel, the withdrawal process for extracting object liquid from the at least one reaction vessel proceeds differently. Depending on the different operating or functional states of the at least one reaction vessel, the following applies: 68488P WO Hamilton Bonaduz AG - 11 -

[0044] Despite identical operating settings of the pressure-changing device, the reaction vessel exhibits different gas flow rates at the same times during the withdrawal process, which are an indication of the operating or functional state of at least one reaction vessel. Possible different operating or functional states of a reaction vessel include, for example, "proper operating state" and at least one operating or functional state consisting of "empty reaction vessel," "emptied reaction vessel," and "blocked reaction vessel."

[0045] At the beginning of a withdrawal process, a reaction vessel in proper working order contains a quantity of object liquid which can be driven out of the reaction vessel by means of gas through an open or opening dispensing opening by creating a gas pressure difference on both sides of the dispensing opening.

[0046] An empty reaction vessel is fundamentally functional and therefore has an open or openable dispensing opening, but was accidentally not filled with an object liquid or the object liquid was lost before the liquid handling device was loaded with the reaction vessel.

[0047] An emptied reaction vessel was originally a reaction vessel properly filled with object fluid, which was successfully emptied by the dispensing process through the gas pressure differential generated on either side of the dispensing opening. An emptied reaction vessel can be equivalent to an empty reaction vessel. However, due to the initial intake of object fluid, an emptied reaction vessel may differ from an initially empty one by residual wetting of the inner walls of the reaction vessel and / or by a remaining load of magnetic particles that may be present after successful emptying.

[0048] A clogged reaction vessel usually has a non-functional discharge port, i.e., the discharge port is either blocked by solids. 68488P WO Hamilton Bonaduz AG - 12 -

[0049] or a closure of the dispensing opening, such as a lip valve, cannot be opened.

[0050] A reaction vessel in proper working order contains object fluid, which, due to its state of matter and higher viscosity, exhibits a higher flow resistance when passing through the dispensing orifice than the gas expelling the object fluid from the reaction vessel. Therefore, at the beginning of the dispensing process, a relatively small gas flow rate will be observed, which replaces the volume in the reaction vessel that was released by the expelled object fluid.

[0051] An empty reaction vessel allows the gas to flow directly through the dispensing opening without any intervening liquid. Due to the lower flow resistance of the gas compared to the liquid, a higher gas flow rate will be observed from the start of the dispensing process in an empty reaction vessel, assuming the same pressure-changing device settings, than in a properly functioning reaction vessel.

[0052] At the start of the withdrawal process, an empty reaction vessel was in proper working order. Once the liquid has been sufficiently expelled from the interior of the reaction vessel to allow gas to flow directly through the dispensing port, the gas flow rate will increase due to the reduced flow resistance at the dispensing port, assuming the pressure regulator's operating settings remain unchanged. This change in the gas flow rate can be used to indicate a successful withdrawal process.

[0053] The mere possibility of detecting a successfully completed withdrawal process is a significant advantage over the prior art. As far as is known, prior art liquid handling devices that expel liquid with gas from a reaction vessel generally use a fixed withdrawal time, during which a gas flow rate is maintained.

[0054] The gas flows through the gas piping system. This withdrawal time is generally chosen to be long enough to ensure that even known and anticipated difficult withdrawal processes involving a relatively large quantity of a relatively highly viscous liquid are successfully completed by completely removing the liquid from the reaction vessel through the dispensing opening. As a result, while this withdrawal time does lead to reliable emptying of reaction vessels in proper working order, the withdrawal process takes a disproportionately long time for most withdrawal operations.

[0055] To make matters worse, after a complete withdrawal of a target liquid that is usually to be processed further, a gas flow can pass through the gas line assembly and thus through the dispensing opening during the continued gas flow for reasons of process safety, and onto the target liquid collected in a usable liquid container below the dispensing opening, and in the case of air as the most commonly used gas, this can oxidize and / or spray it.

[0056] Here, the measurement of the gas flow rate in the gas piping system by the flow sensor enables more precise extraction of the object liquid from a reaction vessel, which not only reduces the undesirable contamination of the extracted target object liquid, but also significantly reduces the overall process time required in the case of a typical sequential extraction of object liquid from a plurality of reaction vessels.

[0057] The at least one result signal can be any signal or a plurality of signals that are substantively linked to the flow detection signal of the flow sensor arrangement. The term 'result signal' is used here solely to distinguish the signal output by the control unit based on the flow detection signal from other signals within, from, or into the liquid handling device. 68488P WO Hamilton BonaduzAG - 14 -

[0058] The at least one result signal can be output in various ways. It can be humanly perceptible as a warning signal or as information for an operator of the liquid handling device. Additionally or alternatively, the at least one result signal can be output as an information signal and / or control signal to another automated component of the liquid handling device or to another laboratory device cooperating with the liquid handling device. The at least one result signal can therefore be information encoded in a predetermined signal form and / or energy that is transferred to another device or apparatus to activate or maintain its operation.

[0059] Since the primary task of the control device is to control components of the liquid handling device, according to a preferred embodiment of the present invention, the control device is configured to perform control interventions using the at least one result signal.

[0060] In principle, the control unit can be configured to

[0061] a. to terminate a gas flow that is intended to change the gas pressure difference on both sides of the outlet opening of a reaction vessel in the gas piping arrangement.

[0062] Without limiting oneself to the example mentioned above, such termination of a gas flow can occur by referring to the aforementioned functional states of reaction vessels if a reaction vessel is identified at the beginning of a withdrawal process as empty or blocked, rendering withdrawal pointless, or if a reaction vessel initially identified as being in proper working order is identified as empty after the withdrawal process has begun, rendering further withdrawal unnecessary. 68488P WO Hamilton Bonaduz AG - 15-

[0063] Additionally or alternatively, the control unit can be configured to

[0064] b. to generate a gas flow rate to change the gas pressure difference on both sides of the outlet opening of a reaction vessel in the gas piping arrangement.

[0065] Generating a gas flow rate based on at least one result signal can be helpful, for example, in the case of sequentially emptying several reaction vessels in succession, in order to shorten the overall process time required. It is then possible to begin withdrawing liquid from the next reaction vessel without any time loss, after the complete withdrawal of liquid from a previous reaction vessel has been reliably detected.

[0066] Additionally or alternatively, the control unit can be configured to

[0067] c. to mark a section of the liquid handling device for subsequent operations on the liquid handling device and / or on a processing station downstream of the liquid handling device.

[0068] For example, if monitoring or measuring the gas flow rate reveals an initially faulty reaction vessel, either because it contained no object liquid or because its discharge opening is blocked, in both cases a usable liquid container intended to collect the target object liquid will either be empty or contain a different amount than expected.Since a multiple reaction vessels are typically processed in the liquid handling device and these are arranged either in a row or in a matrix, the target liquid vessel associated with the reaction vessel identified as faulty can be marked so that subsequent processing operations on the target liquid vessel do not proceed or proceed without generating an error message, as further processing of the contents of the target liquid vessel can no longer be expected. 68488P WO Hamilton Bonaduz AG - 16-.

[0069] The aforementioned marking is preferably not a physical marking of the usable liquid container or, more generally, of the section of the liquid handling device, but rather an information technology marking by setting a flag or a marker in a database, which identifies the section of the liquid handling device, in particular the usable liquid containers, for further processes.

[0070] Additionally or alternatively, the control unit can be configured to

[0071] d. to output information.

[0072] For example, an operator can be informed visually, audibly, or in some other way about an event in the ongoing dispensing process. However, it is also true that the information does not necessarily have to be displayed in a way that is perceptible to humans, but can be transmitted to another device, such as a smartphone, which in turn displays or stores the received information in a way that is perceptible to humans.

[0073] As explained above, the reaction vessel arrangement can comprise multiple reaction vessels to increase the efficiency of the liquid handling device. The control unit is then preferably configured to use at least one result signal to terminate a gas flow in the gas line arrangement used to change the gas pressure differential on either side of the outlet of a first reaction vessel, and to generate a gas flow in the gas line arrangement used to change the gas pressure differential on either side of the outlet of a second reaction vessel. This significantly reduces the overall process time for withdrawing liquid from the entire reaction vessel arrangement compared to performing withdrawal operations with a fixed process time.The result signal is then the consequence of an evaluation of at least one flow detection signal, indicating that the withdrawal process from the first reaction vessel was successfully completed. For a subsequent withdrawal process, the second 68488P WO Hamilton Bonaduz AG - 17- is then used.

[0074] Reaction vessel of the preceding withdrawal process, the first reaction vessel, etc.

[0075] As also explained above, the liquid handling device comprises a utility liquid container arrangement with a plurality of utility liquid containers, which serve to collect object liquid as the handling target or target object liquid of a handling process.

[0076] In such a further development of the liquid handling device, the control unit can advantageously be configured to generate information assigned to a specific liquid container from among a plurality of liquid containers, and to store this information in a data storage device for retrieval and / or output it as an information signal. This is a general description of the aforementioned information technology-based identification of a liquid container for its further processing after the liquid has been collected by the receiving device. This avoids unnecessary further processing steps and, in particular, saves valuable substances that would otherwise be introduced into a liquid container unsuitable for further processing.

[0077] To evaluate the flow detection signal output by the flow sensor arrangement to the control unit, the control unit can be configured to compare the flow detection signal with at least one predetermined reference signal. To ensure that scientifically meaningful comparisons are made between identical physical quantities or entities, the at least one predetermined reference signal preferably represents a predetermined gas flow rate as a reference value.

[0078] According to a further development of the present invention, the control device can be configured to output at least one result signal based on a comparison between the flow detection signal and the at least one reference signal. 68488P WO Hamilton BonaduzAG - 18 -

[0079] It has been found that at the beginning of a withdrawal process, i.e., in a transient phase at the start of the generation of a gas flow by the pressure-changing device, the flow rate of the compressible gas fluctuates considerably or, at least with numerous flow sensors, leads to unreliable or even erratic readings. To avoid misinterpretations of one or more flow detection signals from the flow sensor arrangement, the control unit is preferably configured to compare the flow detection signal with the at least one predetermined reference signal only after a predetermined time has elapsed since the start of the gas flow generation.

[0080] Due to external influences, which are almost unavoidable, such as signal noise from at least one flow sensor in the flow sensor arrangement or detection artifacts that lead to insufficiently meaningful outlier detection values, so-called 'detection peaks', flow detection signals can be generated that inaccurately reflect the situation of the gas in the gas pipeline arrangement.

[0081] To prevent the output of at least one erroneous result signal based on at least one such inaccurate flow detection signal, the control device can be configured to output the at least one result signal based on the comparison between the flow detection signal and the at least one reference signal only if a predetermined relationship between the flow detection signal and the at least one reference signal is satisfied for at least 80% of the duration of a predetermined comparison time interval. Preferably, the control device outputs the at least one result signal based on the comparison between the flow detection signal and the at least one reference signal only if the predetermined relationship is satisfied for the entire duration of the predetermined comparison time interval.An outlier in the flow detection signal can then, for example, lead to a restart of the comparison time interval, with the condition that the at least one result signal is only output if the condition leading to the output of the at least one result signal is met between the flow detection signal and the 68488P WO Hamilton Bonaduz AG - 19-.

[0082] at least one reference signal is satisfied for at least 80%, preferably 100%, of the newly started comparison time interval.

[0083] To detect as early as possible a reaction vessel accidentally placed empty in the liquid handling device, preferably closer to the beginning of a withdrawal process than to its end, the control device can be configured to compare the flow detection signal with at least one first reference signal only after a predetermined initial period has elapsed since the start of gas flow generation, and to output a first result signal based on the comparison between the flow detection signal and the first reference signal. To detect the proper functioning of the reaction vessel, the first reference signal preferably represents a predetermined first gas flow rate as the first reference value, wherein the first reference value is selected to be greater than a gas flow rate in the gas piping arrangement that would occur during a withdrawal process under normal operating conditions.

[0084] The first reference value can be determined with good statistical reliability in laboratory tests and can be stored in a data memory of the liquid handling device, accessible by the control unit, upon delivery of the liquid handling device.

[0085] Alternatively, or preferably additionally, the control device for the early detection of a blocked reaction vessel can be configured to compare the flow detection signal with at least one second reference signal only after a predetermined second time period has elapsed since the start of the generation of a gas flow, and to output a second result signal based on the comparison between the flow detection signal and the second reference signal. In this case, the second reference signal preferably represents a predetermined second gas flow rate as the second reference value, wherein the second reference value is selected to be smaller than a gas flow rate in the gas piping arrangement that occurs during normal operation.

[0086] The withdrawal process is discontinued. In this case, too, the second reference value can be determined in advance in laboratory tests with good statistical reliability and stored in a data memory of the delivered liquid handling device that can be read by the control device.

[0087] To determine the successful completion of a withdrawal process, the control device can alternatively or preferably additionally be configured to compare the flow detection signal with at least one third reference signal only after a predetermined third time period has elapsed since the start of gas flow generation, and to output a third result signal based on the comparison between the flow detection signal and the third reference signal. In this case, the third reference signal preferably represents a predetermined third gas flow rate as the third reference value of a gas flow rate, wherein the third reference value is selected to be greater than a gas flow rate in the gas pipeline arrangement that would be established during a withdrawal process under normal operating conditions.Again, the third reference value can be determined in advance in laboratory tests with statistical certainty and stored in a data storage device of the liquid handling device that can be accessed by the control device.

[0088] The first, second, or third reference value, or more generally, such a reference value, can be determined in advance in laboratory tests for parameter fields, for example, for different reaction vessels and / or different liquids. Reaction vessels used in the liquid handling device for different handling tasks may differ in their nominal volume, the cross-sectional area of ​​their dispensing opening, and / or the operating principle of their dispensing opening. A dispensing opening can retain the liquid within the capillary volume inside the reaction vessel or may incorporate a valve for this purpose.

[0089] The first and third reference signals both refer to the detection of an empty reaction vessel. Therefore, the first and third reference signals can be the same. For considerations regarding the avoidance of false positives and / or false negatives - 68488P WO Hamilton Bonaduz AG - 21 -

[0090] However, in the assessment results and the resulting result signals, the reference value of the first reference signal may be chosen differently from the reference value of the third reference signal.

[0091] Object fluids can differ in their viscosity. Possible object fluids include nucleic acid carrier fluids, washing fluids, and elution fluids. The elution fluid typically forms a target object fluid. The carrier fluid and washing fluids are usually waste object fluids. Target object fluids and waste object fluids can be handled with different sensitivities.

[0092] The first and second time periods can be the same, since in both cases an unnecessary withdrawal process from a faulty reaction vessel should be avoided as early as possible. However, for the reasons mentioned above, it is preferable that both the first and second time periods are chosen to be long enough so that transient fluctuations at the beginning of the generation of a gas flow in the gas piping system have subsided or at least largely subsided.

[0093] Preferably, the third time period differs from the predetermined first time period and / or the predetermined second time period; particularly preferably, the third time period is longer than both the first and the second time period. This is because the first and second time periods are preferably chosen to be short enough to ensure that a pointless withdrawal process is terminated as early as possible or not even initiated in the first place, while the third time period is chosen to encompass the expected end of a proper withdrawal process.

[0094] In principle, the pressure in the gas piping system can be limited to a maximum pressure, which results from the rated output of a pump or from the maximum storage pressure of a pressure vessel. The maximum pressure in the gas piping system, and thus the maximum gas pressure difference on either side of the outlet, is then the difference between the design-determined maximum pressure described above and the pressure change. 68488P WO Hamilton Bonaduz AG - 22 -

[0095] The device is designed to maintain constant ambient or atmospheric pressure. Such a pressure limitation is possible in a simple design of the liquid handling device, but is not preferred due to its lack of accuracy and reliability.

[0096] Preferably, the liquid handling device includes a pressure limiting device configured to limit the gas pressure in the gas piping arrangement to a predetermined setpoint pressure and / or to limit the gas pressure differential on either side of the outlet opening of the at least one reaction vessel to a predetermined setpoint pressure differential. This pressure limiting device can, for example, include a valve that opens to the environment once a setpoint pressure is reached, so that a gas pressure exceeding the setpoint pressure does not arise in the gas piping arrangement, or exists only extremely briefly and is immediately dissipated.

[0097] Likewise, the pressure changing device can be part of the pressure limiting device, because by controlling the gas flow rate in the gas piping arrangement in terms of magnitude, the gas pressure prevailing in the gas piping arrangement can also be influenced, even influenced relatively precisely.

[0098] Therefore, the liquid handling device preferably includes a pressure limiting device configured to adjust the gas pressure in the gas line assembly to a predetermined target gas pressure range and / or to adjust the gas pressure differential on either side of the outlet opening of the at least one reaction vessel to a predetermined target gas pressure differential range. Thus, not only can an undesirable overpressure or underpressure in the gas line assembly be avoided relative to the ambient pressure, but a gas pressure can also be set within a desired pressure range.

[0099] For the targeted extraction of liquid from a reaction vessel, the pressure limiting device, according to an advantageous embodiment, has at least one pressure sensor. The at least one pressure sensor detects the gas pressure. (68488P WO Hamilton BonaduzAG - 23 -)

[0100] The gas piping assembly is monitored and a pressure sensing signal is sent to the control unit. This pressure sensing signal represents the gas pressure within the gas piping assembly and / or the gas pressure differential on either side of the outlet of the at least one reaction vessel. The pressure limiting device may include an ambient pressure sensor that detects the pressure of the atmosphere surrounding the reaction vessel and / or a differential pressure sensor that detects the pressure differential between the gas pressure inside the gas piping assembly and the gas pressure of the atmosphere surrounding the reaction vessel.

[0101] The control device is then preferably configured to control or regulate the operation of the pressure change device according to the pressure detection signal.

[0102] Preferably, in the preferred sampling process, the flow sensor is arranged downstream of the pressure-limiting device by generating overpressure inside the reaction vessel. Flow detection signals that detect a gas flow rate upstream of the pressure-limiting device are detrimental to the reliability of a resulting signal based on them.

[0103] Preferably, the liquid handling device includes a data storage device. This data storage device preferably contains, among other things, a plurality of different pressure-related target value ranges. For the most precise control of dispensing processes, the different pressure-related target value ranges are preferably assigned to different liquids.

[0104] The control unit is preferably configured to control or regulate the operation of the pressure limiting device according to a pressure-related target value range from the majority of stored pressure-related target value ranges.

[0105] This ensures that different object liquids, especially target object liquids on the one hand and waste object liquid on the other, are separated. - 68488P WO Hamilton BonaduzAG - 24 -

[0106] On the other hand, the properties can be extracted from a reaction vessel using the most suitable operating parameters for each. For the gentlest possible treatment of a target liquid containing nucleic acid, the target gas pressure for such liquids is preferably less than 100 mbar, particularly preferably not greater than 80 mbar, and even more preferably not greater than 50 mbar.

[0107] To shorten the cleaning time of magnetic particles and the nucleic acids adhering to them by washing liquids and / or to shorten the expulsion time of the contaminated initial carrier liquid, a target gas pressure for such waste object liquids is preferably greater than 100 mbar and more preferably greater than 110 mbar.

[0108] The ordinal numbers used in this application merely indicate the order in which the associated features are listed and do not imply any requirement that an identically designated feature with a higher ordinal number presupposes the existence of an identically designated feature with a lower ordinal number. For example, a second reference signal mentioned above may exist without a first reference signal existing, and so on.

[0109] The present invention will be explained in more detail below with reference to the accompanying drawings. It illustrates:

[0110] Fig. 1 shows a rough schematic perspective view of a liquid handling device of the present invention from an oblique front and top view.

[0111] Fig. 2 is a schematic perspective view of the liquid handling device of Figure 1 without housing walls,

[0112] Fig. 3 is an enlarged schematic side view according to Figure 2 with a reaction vessel device and the receiving device in positions differing from the representation of Figure 2, 68488P WO Hamilton BonaduzAG

[0113] Fig. 4 is an enlarged schematic perspective interior view of the liquid handling device of Figures 1 to 3 with partially cut-away components,

[0114] Fig. 5 is an enlarged schematic perspective interior view, partially cut away like that of Figure 4, with the usable recording device in an alternative position,

[0115] Fig. 6 shows a rough schematic representation of the magnet carrier arrangement of the magnetic device of the liquid handling device of Figures 1 to 5 in top view,

[0116] Fig. 7 is an exploded bottom view of one of the magnet carriers of the magnet carrier arrangement of the magnet device,

[0117] Fig. 8 shows an exploded bottom view of the other magnet carrier of the magnet carrier arrangement of the magnet device.

[0118] Fig. 9 shows a perspective view from an oblique angle above of a reaction vessel arrangement for use on the reaction vessel device of the liquid handling device of Figures 1 to 5.

[0119] Fig. 10A is a longitudinal sectional view through the reaction vessel arrangement of Fig. 9, wherein the section plane contains the virtual vessel axes of the individual reaction vessels, with a viewing direction along the arrow XA in Fig. 9.

[0120] Fig. 10B shows a rough schematic side view of the reaction vessel arrangement of Figure 10A with exaggerated curvature for fixing the reaction vessel arrangement in the reaction vessel support.

[0121] Fig. 11 shows a longitudinal section through a peripheral reaction vessel, cut along the same sectional plane as that of Figure 10A,68488P WO Hamilton BonaduzAG

[0122] Fig. 12 shows an enlarged view of the outlet end of the reaction vessel from Figure 11.

[0123] Fig. 13 shows a rough schematic detail view of an inlet 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 support.

[0124] Fig. 14 shows a cross-section through a reaction vessel along a cutting plane orthogonal to its virtual vessel axis,

[0125] Fig. 15 shows a top view of the reaction vessel arrangement of Figures 9 and 10A,

[0126] Fig. 16 shows 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,

[0127] Fig. 17 shows a perspective view of the waste liquid container of the liquid handling device of Figures 1 to 5,

[0128] Fig. 18 shows a perspective cross-sectional view of the waste liquid container from Fig. 17.

[0129] Fig. 19 shows a perspective view of a feeding device of the liquid handling device of Figures 1 to 5 with its movement apparatus, viewed predominantly from below.

[0130] Fig. 20 shows another perspective view of the feeding device with its movement apparatus from Fig. 19, 68488P WO Hamilton Bonaduz AG - 27 -

[0131] Fig. 21 perspective view of the rear side of the feed device of Figures 19 and 20, carrying the switchable valves,

[0132] Fig. 22 shows a perspective view of the feeding device of Figs. 19 to 21, predominantly from below and without switchable valves.

[0133] Fig. 23 shows a piping system in the piping body of the feeding device of Figs. 19 to 22,

[0134] Fig. 24 is a perspective view of the rear of the feeding device of Fig. 22, without switchable valves,

[0135] Fig. 25 shows a perspective view of the front of the feeding device of Figs. 19 to 22 and 24, without switchable valves, and

[0136] Fig. 26 shows a schematic representation of a flow detection signal in the gas pipeline arrangement over time during a withdrawal process.

[0137] The figures are not to scale, but they accurately represent the size relationships.

[0138] Figure 1 shows an embodiment of a liquid handling device according to the present application, generally designated by 10. The liquid handling device 10 comprises a device housing 12. The viewer of Figure 1 sees 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 generally located opposite the front 12a. A display and control panel 14 is arranged on the front 12a, on which information about a running, 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 touchscreen.

[0139] The liquid handling device, or "device" for short, 10, is not only an output device but also an input device. Consequently, data and commands can also be entered into the device 10 or into its control device 40 (see Fig. 2) by an operator via the display and control panel 14.

[0140] The direction of gravity g is shown in numerous figures to indicate the orientation of the device 10.

[0141] Below the display and control panel 14 is an access opening 16, which is open in the operating state shown in Figure 1. A reaction vessel assembly 18 has been moved out of the interior of the device housing 12 through this opening. In Figure 1, the reaction vessel assembly 18 is in its setup position outside the device housing 12. In this setup position, the reaction vessel assembly 18 and many of its components are accessible to an operator or an operating robot.

[0142] The reaction vessel assembly 18 comprises a reaction vessel carrier 20, on which a plurality of reaction vessel assemblies 86 (see Fig. 3), which are described in more detail below, as well as a sealing assembly 22 (also described below) for use in the feeding device 62 of the apparatus 10, can be arranged by the operator. The reaction vessel carrier 20 has reaction vessel receptacles 24 arranged in a matrix-like orthogonal 12-x-8 matrix for receiving reaction vessels 88 (see Figs. 9 to 16) or reaction vessel assemblies 86, and has a sealing assembly receptacle 26 designed as a recess, in which a new, unused sealing assembly 22 for a subsequent handling operation is located in Figure 1.

[0143] The reaction vessel device 18 can be moved along the preferably straight ready movement path RB from the setup position shown to a ready position located inside the device housing 12.

[0144] The access opening 16 is preferably associated with a flap, not shown in Figure 1, which is pre-tensioned in its closed position, in order to open the access opening 16 in Ab-68488P WO Hamilton Bonaduz AG - 29 -

[0145] The flap, not shown, is automatically closed by the means of the devices enforcing it. As the reaction vessel 18 approaches its setup position, it is moved against its preload into an open position (different from the closed position) and is held in the open position for the duration of the reaction vessel 18's projection through the access opening 16 into the external environment U of the device 10.

[0146] Below the access opening 16 is a drawer 28, in which a waste receiving device 46 (see Fig. 2 ff.) is housed, as described below. The drawer 28 can be pulled out of the device housing 12 and pushed back in along a straight ready movement path AB of the waste receiving device 46, which is parallel to the ready movement path RB of the reaction vessel device 18, from the ready position shown in Figure 1. A ready position of the drawer 28 corresponds to a ready position of the waste receiving device 46, which moves together with the drawer 28.

[0147] In Figure 1, to the left of drawer 28, there is an on / off switch 30 which establishes or interrupts the power supply to the device 10.

[0148] In Figure 1, to the right of the access opening 16 in a recessed section of the front 12a, there is an object fluid compartment 32 in which, by way of example, two containers 34 and 36 with object fluids are provided for use during fluid handling operations in the device 10. For example, container 34 can contain a cleaning fluid and container 36 an elution fluid as an object fluid.

[0149] Extraction lines 38a and 38b are inserted into containers 34 and 36, extending almost to the bottom of the respective containers 34 and 36. A pressure line 38c, by introducing gas into the object liquid compartment 32, enables a gas pressure to be increased above the respective liquid level of the object liquid in containers 34 and 36 relative to the ambient atmospheric pressure U, so that the gas pressure in the object liquid compartment 68488P WO Hamilton Bonaduz AG - 30 -

[0150] 32 forces the object fluids in the containers 34 and 36 into the respective extraction lines 38a and 38b. The actual flow of object fluids in a piping system of the device 10, which also includes the extraction lines 38a and 38b, is controlled in the device 10 by switching valves, described in more detail below, which can be switched between a flow-through position and a blocking position. The object fluid compartment 32 is sealed against the outside environment and against the rest of the interior of the device 10 to maintain a higher gas pressure level than the external environment U.

[0151] Figure 2 shows a part of the interior I of the device 10.

[0152] The control unit 40 of the device 10, which acts 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 or writes data to a data storage device 42 integrated into the control unit 40, is only roughly schematically indicated by the representation of some integrated circuit boards.

[0153] The drawer 28 has a drawer base 28a in which a waste container assembly 44, containing in this embodiment only a single waste liquid container 45 as a collection container, is positively engaged in a recess 28b for joint movement with the drawer 28. The waste container assembly 44, and thus the waste liquid container 45, can 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 from the drawer 28, empty it, clean it, and reinsert it into the recess 28b once the drawer 28 has been moved from the ready position shown in Figures 1 and 2 along the ready movement path AB of the waste receiving device 46 to its setup position located outside the device 10. The drawer 28 with its drawer base 28a is a waste container carrier.68488P WO Hamilton Bonaduz AG - 31 -.

[0154] On the base 13d of the device 10 or its device housing 12, a guide rail 48 can be seen as a guide device for the waste receiving device 46, which guides the drawer 28 together with the waste receiving device 46 to movement along the ready movement path AB.

[0155] Above the waste receiving device 46 shown in its ready position in Figure 2, there is a use receiving device 50 in Figure 2, also in its ready position, of which only a use container carrier 52 can be seen in Figure 2.

[0156] The user receiving device 50 is guided by a device housing-fixed guide rail 54 as part of a guide device of the user receiving device 50 for movement along a ready movement path NB of the user receiving device 50.

[0157] In contrast to the waste receiving device 46, which in the present embodiment can only be moved manually, the receiving device 50, more precisely its 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 receiving device 50 between a setup position, also located outside the device housing 12, and the ready position shown in Figure 2. The ready movement path NB of the receiving device 50 is parallel to the ready movement paths AB and RB of the waste receiving device 46 and the reaction container device 18, respectively.

[0158] Above the receiving device 50 is the reaction vessel assembly 18, already known from Figure 1. The reaction vessel assembly 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 ready movement path RB of the reaction vessel assembly 18. The reaction vessel assembly 18, more precisely the reaction vessel carrier 20, is also driven by an electrically operated motor.

[0159] A belt drive 60 can be driven by the control unit 40 for movement along the ready movement path RB.

[0160] Due to the arrangement of the reaction vessel assembly 18 on the one hand and the receiving device 50 on the other, positioned above and below each other with respect to the direction of gravity g and their movement guided by parallel guide rails 54 and 58, the setup positions of the reaction vessel assembly 18 and the receiving device 50 are also located above and below each other outside the device housing 12. The assemblies 18 and 50 can be moved into their setup positions through one and the same access opening 16, provided the access opening 16 is sufficiently large. Otherwise, a separate access opening can be provided for each of the assemblies 18 and 50 on the front 12a of the device housing 12.

[0161] Above the reaction vessel assembly 18 in its ready position shown in Figure 2, which is identical to the handling position of the reaction vessel assembly 18 during liquid handling, a feeding device 62 is arranged. This feeding device, as will be explained in more detail below, comprises a metering device 62a for transferring liquid into one or more reaction vessels 88 and a pressure-changing device 62b for changing the pressure of a gas in one or more reaction vessels 88. The metering device 62a and the pressure-changing device 62b are connected or combined for joint movement within the feeding device 62 along a feeding path BP that is orthogonal to the previously described ready movement paths AB, NB, and RB.In a similar manner to the reaction vessel device 18 and the receiving device 50, the feeding device 62 is also guided for movement along the feeding path BP by a guide rail 64 and can be driven for movement by means of an electromechanical belt drive 66 which can be controlled by the control device 40.

[0162] Figure 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 unit 40, enables the compression of gas, in particular 68488P WO Hamilton BonaduzAG - 33 -

[0163] Air, which is provided as compressed gas, in particular compressed air, in the pressure accumulator 69 and can be withdrawn along selected lines via switchable valves. By way of example only, a pressure limiter 71 with a pressure sensor 71a is provided in the gas line assembly 39 of the liquid handling device 10 between the compressor 68 and the pressure accumulator 69. In the illustrated embodiment, the pressure limiter 71, in conjunction with the compressor 68 and the control unit 40, regulates the gas pressure in the section of the gas line assembly 39 located between the compressor 68 and the feed unit 62 to a pressure specified by the control unit 40. The pressure sensor 71a can detect the gas pressure in the section of the gas line assembly 39 located between the compressor 68 and the feed unit 62, in particular in the pressure accumulator 69, and transmit it to the control unit 40.The control unit 40 reads the target gas pressures to be set in the gas piping arrangement 39 from the data memory 42. Different target gas pressures can be stored in the data memory 42, for example, for different handling tasks depending on the reaction vessels used and / or on at least one of the liquids used in the vessels 34 and 36. For the sake of simplicity, and this is currently preferred, a single target gas pressure can be used. This can also be stored in the data memory 42.

[0164] Thus, preferably for the expulsion of a target object liquid containing nucleic acid, a target gas pressure as an overpressure above the pressure level of the surrounding atmosphere of less than 100 mbar, preferably of no more than 80 mbar, and particularly preferably of no more than 50 mbar, is stored in the data memory 42. Such a target gas pressure ensures gentle extraction of the target object liquid from a reaction vessel 88 in a compact free jet, without splashing losses.

[0165] For the expulsion of a waste object liquid, such as a washing liquid or the initial carrier liquid of nucleic acid, a gas pressure as an overpressure above the pressure level of the surrounding atmosphere of more than 100 mbar, preferably of no less, is preferably used in the data storage 42.

[0166] stored at a pressure of 110 mbar, particularly preferably not less than or exactly 115 mbar.

[0167] Gas is always present in a reaction vessel 88 of the reaction vessel assembly 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 via the feed device 62, more precisely via the pressure-changing device 62b. Depending on whether the receiving device 50 or the waste receiving device 46 is located below the reaction vessel 88 when it is expelled, the liquid is discharged either into the receiving liquid container 90 (see Fig. 3) of the receiving device 50 or into the waste liquid container 45.The present application makes a fundamental distinction between an object liquid present in reaction vessel 88 as a handling target, in which case the object liquid present was desired as an intermediate or end product of liquid handling, and an object liquid present in reaction vessel 88 as handling waste, in which case the object liquid present is no longer needed and is disposed of.

[0168] It should be added that a further vertical guide rail 32a, running along the direction of gravity g, allows the transparent cover 32b of the liquid compartment 32 to be moved upwards from the position shown in Figures 1 and 2, in order to change the containers 34 and 36 in the liquid compartment 32 and, if necessary, to carry out cleaning work in the compartment 32. The cover 32b is connected via a truss 32c to a guide carriage 32d that can be moved along the guide rail 32a. Gravity preloads the cover 32b into the position shown in Figures 1 and 2, in which the liquid compartment 32 is gas-tightly sealed by the cover.

[0169] In the extension area of ​​the reaction vessels 88 of the reaction vessel assembly 18, a magnetic device 70 is arranged on the device 10, by means of which 68488P WO Hamilton BonaduzAG - 35 -

[0170] A magnetic field can act inside the reaction vessel 88. The magnetic device 70 is largely obscured by the reaction vessel 18 in the view shown in Figure 2. However, Figures 3 to 5 show the interior area I of the device housing 12 in further operating situations, which also reveal the magnetic device 70.

[0171] The magnetic assembly 70 will be discussed in more detail below. It comprises a magnetic carrier arrangement 72 in which permanent magnets 94 (see Fig. 6), which are not sufficiently visible in Figure 3, are arranged in a patterned manner. The magnetic carrier arrangement 72 has two magnetic carriers 72a and 72b that are movable along the direction of gravity g, both relative to each other and relative to the device housing 12. Each of the magnetic carriers 72a and 72b has its own drive mechanism 74a or 74b, by which the respective driveable magnetic carrier 72a or 72b can be driven by the control device 40 to a movement along the direction of gravity independently of the other magnetic carrier. This relative movement of a magnetic carrier 72a or 72b allows the magnetic field emanating from the respective magnetic carrier 72a or 72b to be shifted in its spatial position relative to the reaction vessels 88 of the reaction vessel assembly 18.Naturally, the motion drives 74a and 74b can also be controlled by the control unit 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.

[0172] The automated liquid handling device 10 also includes a lifting device 76, shown in Figures 2 to 5, which enables either the waste container arrangement 44 alone or the waste container arrangement 44 together with a working container arrangement 78 of the working receiving device 50 to be raised and lowered along a handling path HB defined by a guide rail 80. This allows the waste container arrangement 44 or the working container arrangement 78 to be moved close to and away from the reaction vessel 18. In the illustrated embodiment, the working container arrangement 78 can only be moved close to the reaction vessel 18 together with the waste container arrangement 44.

[0173] which is then located below the working container arrangement 78 and shielded by it. Although the waste container arrangement 44 is moved along as ballast when the working container arrangement 78 is brought close to the reaction vessel assembly 18, a single lifting device 76 is sufficient to move both container arrangements 44 and 78 separately close to and away from the reaction vessel assembly 18.

[0174] The lifting movement of the lifting device 82 of the lifting assembly 76 is effected by a lifting drive 84, which is partially concealed in Figure 3 by the guide rail 64 and the belt drive 66. The lifting drive 84 is preferably an electric drive, which can be controlled by the control unit 40. Preferably, the motion drives 74a and 74b of the magnetic assembly 70 and the lifting drive 84 are similar, and particularly preferably identical, drives.

[0175] Then, if only the waste container arrangement 44 is desired to approach the reaction vessel assembly 18, the use container assembly 50 can be moved into its escape position shown in Figure 3, which is located along the ready movement path RB between its setup position and its ready position.

[0176] Figure 3 shows that a plurality, in this case exactly 12, of reaction vessel assemblies 86, each containing 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.

[0177] In the working container arrangement 78, working liquid containers 90 are also arranged in an orthogonal 12-x-8 matrix, such that in the ready position of the devices 18 and 50, and likewise in the handling position of the devices 18 and 50, a reaction vessel receptacle 24 is arranged above each working liquid container 90, and thus at least one reaction vessel 88 can be arranged. This ensures that from each reaction vessel 88 in the hand-68488P WO Hamilton Bonaduz AG - 37 -

[0178] The handling position of the devices 18 and 50 allows the object liquid, in this case the handling target, to be dispensed into a usable liquid container 90. For the sake of clarity, only some of the reaction vessel arrangements 86, the reaction vessel 88 and the usable liquid container 90 are marked with reference symbols.

[0179] Figure 3 further shows a non-contact container sensor 92, already depicted in Figure 2. In the illustrated example, this is an ultrasonic sensor, which detects the presence of a reaction vessel assembly 86 in the reaction vessel carrier 20 and, if applicable, other information associated with an existing reaction vessel assembly 86, and transmits this information to the control unit 40. The container sensor 92 is connected to the feeding device 62 for joint movement along the feeding path BP.

[0180] Figures 4 and 5 show the devices 18, 46, 50, 70 and 76 in a perspective sectional view, with the section plane running parallel to the handling movement path HB on the one hand and parallel to the ready movement paths RB and NB on the other.

[0181] Figure 4 shows only the magnet carrier 72a of the magnet assembly 70, but not the also present magnet carrier 72b. The waste container arrangement 44 will be explained in detail below with reference to separate figures.

[0182] In Figure 4, the receiving device 50 is moved away from its ready position along its ready movement path NB in ​​the direction of the setup position. The waste liquid container 45 can therefore be brought close to the reaction vessels 88 of the reaction vessel assembly 18 by the lifting device 76. An edge 45b of the waste liquid container 45, projecting outwards from the receiving volume 45a in the interior of the waste liquid container 45, rests on a support form 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 by this positive-locking support engagement. The lifting device 82 encompasses the waste-68488P WO Hamilton BonaduzAG - 38 -

[0183] Liquid container 45 extends in a fork-like manner on two opposite sides. The side closer to the viewer of Figure 4, with the arm of the lifting device 82 located there, lies in front of the section plane of Figure 4 and is therefore not shown.

[0184] The lifting device 82 also has a projection 82c, here a vertical projection 82c, on which the payload container arrangement 78, optionally with an adapter receiving it in the payload container carrier 52, can engage in a bearing engagement during a lifting movement along the handling path HB of the lifting device 82 for carrying against the direction of gravity g. The formations 82a, 82b and 82c are preferably formed in one piece and monolithically.

[0185] 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 unit 40. Thus, if the tare weight is known or can be determined, the control unit 40 can determine the fill level of the waste container arrangement and issue a warning message on the display and control panel 14 when a predetermined fill threshold is reached.

[0186] The magnetic carrier 72a is shown in Figure 4 in its maximally lowered position, as required to allow the reaction vessel assembly 18, with the reaction vessel assemblies 86 attached to it, to be moved without collision along its ready movement path RB from the ready position shown in Figure 4 to the setup position shown in Figure 1. This allows the waste container assembly 44 and / or the usable container assembly 52 to be lifted in their respective ready positions towards the reaction vessel assembly 20 in its ready / handling position using one and the same lifting device 82. This ensures that a dispensing end 106 of a reaction vessel 88 can be immersed into a container consisting of the usable liquid container 90 and the waste liquid container 45 for the dispensing of object liquid, for example, by an immersion distance of 1 to 2 mm.

[0187] Since the lifting movement of the usable container arrangement 78 by the lifting device 76 and its lifting gear 82 would require the waste container arrangement 44 to be removed from its ready position, which is the case in the illustrated embodiment-68488P WO Hamilton Bonaduz AG - 39 -

[0188] Since the operation can only be carried out manually, either the waste container arrangement 44 alone or the waste container arrangement 44 and the usable container arrangement 78 together are lifted by the lifting device 76.

[0189] In Figure 5, the magnet carrier arrangement 72, comprising the magnet carriers 72a and 72b, is raised into the extension area of ​​the reaction vessels 88, so that the waste liquid container 45 could be brought by the lifting device 86 along the handling path HB to the reaction vessel assembly 18, which is only movable along the ready path RB. The receiving device 50 is meanwhile in its alternative position, shifted relative to the ready position along its ready path NB.

[0190] The usable container arrangement 78 is in the present case a titer plate, known per se, formed in one piece by injection molding, with the already mentioned 12 x 8 = 96 usable liquid containers 90.

[0191] Figure 6 shows a schematic top view of the magnet support arrangement 72 of the magnet device 70. Figures 7 and 8 show the magnet supports 72a and 72b in more realistic exploded bottom views than in Figure 6.

[0192] Figure 6 shows the reaction vessels 88 of the reaction vessel assembly 18 in their orthogonal 12-x-8 matrix. The schematic view in Figure 6 is a top view of the magnet support arrangement 72 in relation to sections of the reaction vessels 88, which have a receiving volume 112 (see, for example, Fig.

[0193] 11) extend orthogonally to the plane of Figure 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 run orthogonally to each other. Exactly one reaction vessel 88 is arranged at each intersection point of each first row 88a with each second row 88b. For clarity, starting from the upper left reaction vessel 88 in Figure 6, only four of the twelve first rows 88a and only four of the eight second rows 88b are indicated by dashed lines. The eight reaction vessels 88 of each reaction vessel, formed in one piece by injection molding, are 68488P WO Hamilton Bonaduz AG - 40 -

[0194] The vessel arrangement 86 runs along a first row 88a. The maximum number of reaction vessel arrangements 86 that can be arranged in the reaction vessel support 20 corresponds to the maximum number of first rows 88a.

[0195] The intersecting first rows 88a and second rows 88b, which each run parallel to the drawing plane of figure 6, span a reference plane BE that is also parallel to the drawing plane of figure 6.

[0196] The magnet carrier arrangement 72 comprises a plurality of matrix magnets 94, which are arranged on the magnet carriers 72a and 72b. The matrix magnets 94 are essentially identical permanent magnets in terms of their physical and magnetic properties, but are oriented differently with respect to their polarization depending on their location within the magnet carrier arrangement 72. All matrix magnets 94 have in common that their polarization direction 94a is parallel to the reference plane BE and non-parallel to both the direction of the first row 88a and the direction of the second row 88b. The polarization direction 94a is the shortest direction in which the magnetic south pole of a matrix magnet 94, designated by the letter "S" in Figure 6, follows the magnetic north pole of the same matrix magnet 94, designated by the letter "N".An interface 94b orthogonal to the polarization direction 94a between the magnetic north pole and the magnetic south pole of each matrix magnet 94 runs orthogonal to the reference plane BE.

[0197] In the example shown, all polarization directions 94a of the matrix magnets 94 arranged in the magnet carrier arrangement 72 are rotated by an amount of 45° with respect to the direction of the first rows 88a and the direction of the second rows 88b about an axis of rotation orthogonal to the plane of the drawing of figure 6 and thus to the reference plane BE.

[0198] The number of matrix magnets 94 in the magnet carrier arrangement 72 is less than the number 96 of reaction vessels 88 and greater than the sum of the first and second rows 88a and 88b respectively, i.e., in this case greater than 20. In the illustrated embodiment, the number of matrix magnets is 58. It is im68488P WO Hamilton Bonaduz AG - 41 -

[0199] In the illustrated embodiment, 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.

[0200] The matrix magnets 94 are also arranged in an orthogonal matrix, along mutually parallel third rows 96a and along mutually parallel fourth rows 96b. For clarity, only the leftmost first three third rows 96a and only the uppermost first three fourth rows 96b are shown in Figure 6 and labeled 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.

[0201] The matrix magnets 94 are located at the intersection points of the third rows 96a and the fourth rows 96b. 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 every 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 adjacent to an intersection point occupied by a matrix magnet 94 is not occupied by a matrix magnet 94.

[0202] In this way, exactly two matrix magnets 94 are adjacent to each reaction vessel 88 in the reference plane BE.

[0203] 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. In addition, the polarization directions 94a of the matrix magnets 94 arranged in adjacent third rows 96a are rotated from row to row by an angle of 90° with respect to a rotation axis orthogonal to the reference plane BE. The direction of rotation at the transition from one third row 96a to an adjacent third row 96a is the same for all matrix magnets 9468488P WO Hamilton BonaduzAG - 42 -

[0204] The polarization directions 94a of all matrix magnets in a common third row 96a are the same 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. The same applies to the matrix magnets 94 in successive fourth rows 96b. If the third rows 96a are numbered consecutively starting with 1, then the polarization directions 94a of all matrix magnets 94 arranged in odd-numbered third rows 96a are the same, and the polarization directions 94a of all matrix magnets 94 arranged in even-numbered third rows 96a are the same.If one also considers the fourth rows 96b to be numbered consecutively 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.

[0205] In this way, each reaction vessel 88 is confronted by 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., either only the magnetic north pole or only approximately the magnetic south pole, faces the reaction vessel 88, while of the other matrix magnet 94, both polarization sections and the edge of the virtual interface 94b protruding from the matrix magnet 94 between the two polarization sections face it. Thus, the two adjacent matrix magnets 94, which are essentially identical in physical and magnetic design, exert different magnetic field strengths on the reaction vessel 88, which is equidistant from each of the two matrix magnets 94.Thus, in the case of an asynchronous relative motion of the two matrix magnets 94 adjacent to the same reaction vessel 88 relative to each other and relative to the reaction vessel 88 parallel to the direction of gravity g, or in the case of a synchronous but oppositely directed relative motion of the two matrix magnets 94 adjacent to the same reaction vessel 88, a very good mixing effect of magnetic particles suspended in a liquid in the reaction vessel 88 can be achieved. Nevertheless, due to the different strengths of the magnets, the mixing effect can be significantly altered.

[0206] The effects of the two adjacent matrix magnets 94 on one and the same reaction vessel 88 result in an immobilization of the magnetic particles in the reaction vessel 88 in the area of ​​the magnetic field of the increasing matrix magnet 94, thus preventing an undesirable double clustering of magnetic particles due to two magnetic fields acting on the interior of the reaction vessel 48.

[0207] For the purpose of effectively utilizing the magnetic fields emanating from the matrix magnets 94 and their effect on the contents of the reaction vessels 88, it is the case for all reaction vessels 88 arranged in the reaction vessel carrier 20 that the matrix magnets 94 immediately adjacent to one and the same reaction vessel 88 are arranged on different and separately movable magnet carriers 72a and 72b.

[0208] Following the virtual numbering above, 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 magnetic carrier 72a. Similarly, 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 magnetic carrier 72b.

[0209] In this embodiment, all third rows 96a of a magnetic carrier 72a or 72b have the same number of matrix magnets 94. However, the third rows 96a with even numbering, i.e., the third rows 96a of the magnetic carrier 72a, each have one fewer matrix magnet 94 than the third rows 96a of the magnetic carrier 72b. The latter rows have 5 matrix magnets 94. In contrast, the third rows 96a of the magnetic carrier 72a each have only 4 matrix magnets 94.

[0210] The magnetic supports 72a and 72b are structurally largely identical or similar. Each magnetic support 72a and 72b comprises a magnetic support base 72a-1 or 72b-1, from which magnetic support legs 72a-268488P WO Hamilton BonaduzAG - 44 - extend.

[0211] The legs 72a-2 and 72b-2 of a magnet support extend orthogonally to the respective magnet support base 72a-1 or 72b-1, preferably extending on one side. The magnet support legs 72a-2 are parallel to each other. The magnet support legs 72b-2 are parallel to each other. The magnet support bases 72a-1 and 72b-1 are parallel to each other. Consequently, the magnet support legs 72a-2 and 72b-2 are also parallel to each other. The magnet support legs 72a-2 and 72b-2 of one magnet support 72a or 72b converge on the magnet support base of the other magnet support 72b or 72a.

[0212] In the illustrated embodiment, the base of a magnet carrier, in this case the base 72a-1 of magnet carrier 72a, is longer than the base 72b-1 of magnet carrier 72b. Magnet carrier 72a has more legs 72a-1, in this case exactly one more leg than magnet carrier 72b has. The legs 72a-2 and 72b-2 are arranged interlocking, such that each leg 72b-2 of magnet carrier 72b with the shorter base 72b-1 runs in the space between two immediately adjacent legs 72a-2 of magnet carrier 72a with the longer base 72a-1. The basic principle is: if a magnetic carrier leg 72a-2 or 72b-2 of a magnetic carrier 72a or 72b is located along the direction of travel of its magnetic carrier base 72a-1 or 72b, respectively.If 72b-1 has an adjacent magnet support leg on each side, these two adjacent magnet support legs are magnet support legs 72b-2 or 72a-2 of the respective other magnet support 72b or 72a.

[0213] 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.

[0214] Those matrix magnets 94 which, in their third row 96a or in their fourth row 96b, in which they are arranged, do not have an intersection point of a third row 96a with a fourth row 96b adjacent 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 in their fourth row 96b, in which they are arranged, have an intersection point of a third row 96a with a fourth row 96b, are 68488P WO Hamilton BonaduzAG - 45 -

[0215] are, in each row direction a crossing point of a third row 96a with a fourth row 96b is adjacent, inner matrix magnets 94-2.

[0216] The inner matrix magnets 94-2 of a magnet support leg 72a-2 or 72b-2 project beyond this support leg on both sides in a direction orthogonal to the direction of extension of the supporting magnet support leg 72a-2 or 72b-2. Therefore, sections, preferably of equal size, of one and the same inner matrix magnet 94-2 are exposed on both sides of the supporting magnet support leg 72a-2 or 72b-2. The inner matrix magnets 94-2 can thus be positioned as close as possible to a container wall 110 of the nearest reaction vessel 88.

[0217] Similarly, those reaction vessels 88 in which, in their first row 88a or in their second row 88b in which they are arranged, no intersection point of a first row 88a with a second row 88b is adjacent in at least one row direction, are marginal reaction vessels 88-1. In contrast, those reaction vessels 88 in which, in both their first row 88a and in their second row 88b in which they are arranged, an intersection point of a first row 88a with a second row 88b is adjacent in each row direction, are inward reaction vessels 88-2.

[0218] Each inner matrix magnet 94-2 is adjacent to four reaction vessels 88, which, due to their orthogonal matrix arrangement, are located at the corners of a rectangle containing the respective inner matrix magnet 94-2. The corners of the rectangle are formed by the respective virtual vessel axes BA (see, for example, Figs. 10A, 11, 15, and 16) of the reaction vessels 88 involved.

[0219] Each outer matrix magnet 94-1 is adjacent to two reaction vessels 88, more precisely two marginal reaction vessels 88-1.

[0220] Considering four matrix magnets 94 arranged in a rectangle that are closest to each other, with two of them arranged in the same third row 96a and two in the same fourth row 96b, then there are between each 68488P WO Hamilton BonaduzAG - 46 -

[0221] Each matrix magnet 94 and a matrix magnet 94 adjacent along the edge of the rectangle of the same rectangle each has a reaction vessel 88. The edges of the virtual rectangles of the matrix magnets 94 thus formed are inclined at an angle of 45° to the third and fourth rows 96a and 96b respectively, which the matrix magnets 94 have.

[0222] Thus, while each inner matrix magnet 94-2 is arranged face-centered with respect to the rectangle formed by the four reaction vessels 88 nearest to it 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 a smallest area in the reference plane BE.

[0223] Figures 7 and 8 each show a perspective bottom view of the magnet carrier arrangement 72 and its magnet carriers 72a and 72b respectively in a more realistic representation than in Figure 6.

[0224] The magnetic carriers 72a and 72b comprise at least two components, namely a magnetic receiving component 73a-1 or 73b-1 and a magnetic holding plate 73a-2 or 73b-1.

[0225] 73b-2.

[0226] 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 73a-1, respectively.

[0227] The magnets 94 are inserted into the magnet holder component 73a-1 or 73b-1 and secured therein by a positive locking mechanism against falling out laterally. The magnet retaining plate 73a-2 or 73b-2, which is attached to the underside of the respective magnet holder component 73a-1 or 73b-1 with screws 98, secures the matrix magnets 94 in their receiving recesses 95a or 95b of the magnet holder component 73a-1 or 73b-1 against falling out in the direction of gravity (g). The magnet retaining plate 73a-2 or 73b-2 has essentially the same circumferential contour, consisting of a base and projecting legs, as the magnet holder component 73a-1 or 73b-1 to which it is screwed. In this way, the matrix magnets 94 can be arranged as close as possible to an outlet opening of the reaction vessels 88, so that a magnetic field emanating from the matrix magnets 94 is directed even when the magnet is located in a reaction vessel 88. - 68488P WO Hamilton BonaduzAG - 47 -

[0228] The object fluid can act effectively if the amount of object fluid in the reaction vessel 88 is very small and the object fluid is essentially only located in the vicinity of the dispensing end or the dispensing opening.

[0229] In the illustrated embodiment, a fastening extension 72a-3 or 72b-3, 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 motion drive 74a or 74b of the magnet carrier 72a or 72b.

[0230] In order 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, 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 in the operation of the device 10.

[0231] Figures 9 to 16 show a reaction vessel arrangement 86 and reaction vessels 88 of the reaction vessel arrangement 86 in different views and with different levels of detail.

[0232] Figure 9 shows a perspective view from an oblique angle of above of a reaction vessel arrangement 86 as used on the reaction vessel device 18. A plurality, in the illustrated example eight, of reaction vessels 88 are arranged successively along a follower track FB. Each reaction vessel 88 extends along a virtual vessel axis BA. The vessel axes BA of the reaction vessels 88 of a reaction vessel arrangement 86, which are imagined to pass centrally through the reaction vessels 88, lie in a plane spanned by the direction vectors of the vessel axes BA and the follower track FB, and run at least when the reaction vessel arrangement 86 is in the reaction-68488P WO Hamilton BonaduzAG - 48 -

[0233] The reaction vessel assembly 86 is mounted in the container carrier 20, parallel to each other and transversely, preferably orthogonally, to the subsequent track FB. Figure 10A shows a longitudinal section through the reaction vessel assembly 86 of Figure 9, the section plane containing the virtual vessel axes BA of the individual reaction vessels 88. The viewing direction to the section view of Figure 10A is indicated by the arrow XA in Figure 9. Figure 10B shows a schematic side view of the reaction vessel assembly 86 of Figure 10A with exaggerated curvature for improved fixation of the reaction vessel assembly 86 in the reaction vessel carrier 20. Figure 11 shows a longitudinal section through a reaction vessel 88, more precisely through an edge-mounted reaction vessel 88-1. The section plane of Figure 11 is the same as that of Figure 10A. Figure 12 shows an enlarged view of the outlet end of the reaction vessel 88 of Figure 11.Figure 13 shows a rough schematic detail view of the inlet end of a reaction vessel 88 and the adjoining vessel section with a radial projection for fixing the reaction vessel 88 in a reaction vessel receptacle. Figure 14 shows a cross-section with a section plane orthogonal to the virtual vessel axis BA through a reaction vessel 88, more precisely through a peripheral reaction vessel 88-1, to illustrate the equidistant circumferentially arranged radial projections for fixing the reaction vessel 88 in a reaction vessel receptacle 24.Figure 15 shows a top view of the reaction vessel arrangement of Figures 9 and 10A and Figure 16 shows a cross-sectional view along the section plane XVI-XVI of Figure 10A orthogonal to the virtual vessel axes BA below a band connecting the reaction vessels 88 of the reaction vessel arrangement 86, but in the area of ​​the radial projections and a web connecting a reaction vessel 88 with its reaction vessel 88 adjacent along the subsequent track FB.

[0234] Each reaction vessel 88 has an input end 102 with an input opening 104 that is substantially circular in the illustrated embodiment. At a distance D (see Fig. 11) from the input end 102 and the input opening 104, measured along the virtual vessel axis BA, the reaction vessel 88 has an output channel 108 at an output end 106.68488P WO Hamilton Bonaduz AG - 49 -

[0235] Within the space enclosed by a vessel wall 110 of the reaction vessel 88, a receiving volume 112 is formed above the output channel 108. This receiving volume can contain a liquid 109 with suspended ferromagnetic particles 109a, which is preferably introduced into the reaction vessel 88 through the inlet opening 104.

[0236] The discharge channel 108, which penetrates 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 injecting gas via the pressure-changing device 62b through the inlet opening 104. In this case, the liquid 109 begins to flow out of the receiving volume 112 through the discharge channel 108. This preferably occurs in a free jet.

[0237] A more detailed representation of the shape of the output channel 108 is shown in Figure 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 that is closer to the receiving volume 112. At its axial longitudinal end, which is axially opposite to the inlet opening 114 and further away from the receiving volume 112, the output channel 108 terminates 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 vessel 88.

[0238] 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.

[0239] 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 surrounded by a 68488P WO Hamilton BonaduzAG - 50 -

[0240] The output surface 120 is completely surrounded by a continuous line, which in the illustrated preferred embodiment is also oriented orthogonally to the virtual container axis BA and consequently parallel to the inlet surface 118. The area of ​​the output surface 120 is larger than the area of ​​the inlet surface 118.

[0241] To protect the dispensing opening 116 and the surrounding dispensing surface 120, an axial projection 122, preferably continuous and extending along the container axis BA, runs circumferentially around the dispensing surface 120. The projection length of the axial projection 122 relative to the dispensing surface 120 is less than the thickness T of the container wall 110. The projection 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.

[0242] 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. Preferably, 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 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 where it runs along the container axis BA. The overhang length L of the axial projection 122 relative to the output surface 120 is preferably 0.1 mm or between 20% and 30% of the distance of the inlet surface 118 from the output surface 120 or between 40% and 125% of the diameter of the output opening 116.The radial width B of the axial projection 122, which preferably surrounds the container axis BA and is enclosed for all-round protection of the dispensing opening 116, is greater than its overhang 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. 68488P WO Hamilton Bonaduz AG - 51 -.

[0243] 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.

[0244] 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.

[0245] An inner wall surface 110a of the container wall 110, directly bounding the receiving volume 112, is preferably designed in the shape of a solid of revolution with the virtual container axis BA as its axis of rotation. The inner wall surface 110a is designed such that the receiving volume 112 has a first tapered section 112a, in which the receiving volume 112 tapers as it approaches the output channel 108. The tapering angle α1 (see Fig. 11), which is preferably constant over the entire axial length of the first tapered section 112a, is smaller than the tapering angle α2 of a second tapered section 112b that follows the first tapered section 112a in the direction of the output channel 108.

[0246] In Figure 11, the taper angles are shown on the outer wall surface 110b for clarity. Due to the constant thickness T of the container wall 110 along its length along the container axis BA, the taper angles a1 and a2 shown on the outer wall surface 110b also correctly represent the taper of the inner wall surface 110a. The taper angles a1 and a2 are defined as half the opening angles within the conical taper sections 112a and 112b of the receiving volume 112, relative to the virtual container axis BA, which is also the cone axis of the conical taper sections 112a and 112b. 68488P WO Hamilton Bonaduz AG - 52 -

[0247] The taper angle a1 is a moderate taper angle in the range of 0.7° to 5°, in the illustrated embodiment of 1°. In this first taper region 112a, a liquid flow along the vessel axis BA can take place without generating turbulence in the object fluid, and pressure waves can propagate within an object fluid 109 contained in the reaction vessel 88 along the vessel axis BA without generating turbulence.

[0248] In the illustrated embodiment, the first tapered section 112a is axially longer than the second tapered section 112b. The second tapered section 112b extends axially to the edge of the inlet surface 118. Preferably, the first tapered section 112a is at least five times as long along the container axis BA as the second tapered section 112b.

[0249] In Figure 11, two thin parallel lines indicate the axial longitudinal end of the first tapered section 112a, which is closer to the output channel 108, and the axial longitudinal end of the second tapered section 112b, which is farther from the output channel 108. Between these lies a first transition section 124, in which the inner wall surface 110a transitions smoothly from the first tapered angle a1 to the second tapered angle a2. In longitudinal section views that include the virtual container axis BA, the section contour of the inner wall surface 110a in the first transition section 124 exhibits a curvature with a radius of curvature in the range of 0.8 mm to 1.1 mm.

[0250] The tapering angle a2 of the second tapering region 112b, which is also preferably constant over its entire axial length in the illustrated example, is preferably 45° in the illustrated embodiment.

[0251] The second tapered section 112b, whose axial length is only about one-twelfth to one-eighth, in this case about 2 / 21, of the axial length of the first tapered section, optimally conditions the object fluid in the receiving volume 112 for splash-free dispensing in a free jet during dispensing through the dispensing channel 108. In the illustrated embodiment, the entire second tapered section 112b thus forms an inlet section 126, in68488P WO Hamilton Bonaduz AG - 53 -

[0252] in which the object fluid taken up in the receiving volume 112 is supplied laminarly or at least substantially laminarly to the inlet opening 114 inside the reaction vessel 88 under appropriate pressure conditions.

[0253] The inlet surface 118, which forms the longitudinal end of the second tapered section 112b closer to the outlet channel 108, can mitigate any shear forces that may occur at the inlet opening 114, which could otherwise have a detrimental effect on long-chain molecules contained in the object fluid. Nucleic acids, in particular, form very long-chain molecules that can be sensitive to shear forces in the object fluid containing them and can be destroyed by such shear forces.

[0254] The dispensing surface 120 ensures that object fluid exiting the dispensing opening 116 does not wet the outside of the container wall 110. If object fluid nevertheless manages 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, the dispensing channel 108, and the dispensing surface 120 itself from impacts and the like.

[0255] On the side of the first tapered section 112a closer to the inlet opening 104, there is a funnel section 128 with a third tapered angle a3, which is larger than the first tapered angle a1 and smaller than the second tapered angle a2. In the illustrated embodiment, the third tapered angle a3 is approximately 30°.

[0256] In the illustrated embodiment, the axial length of the funnel section 128 is approximately 3 to 4 times the axial length of the second tapering section 112b, and thus of the inlet section 126. The axial length of the first tapering section 112a is, in turn, approximately 2.5 to 3 times the axial length of the funnel section 128. The funnel section 128 serves to taper the reaction vessel 88 to the shortest possible axial length without any discontinuities or steps in the inner wall surface 110a. Therefore, a second transition section 130 is located between the first tapering section 112a and the funnel section 128.

[0257] the inner wall surface 110a transitions with convex curvature from the funnel region 128 into the first tapering region 112a. In contrast, the curvature of the inner wall surface 110a in the first transition region 124 is concave.

[0258] The aforementioned recesses 100a and 100b of the magnet carrier assembly 72 are designed to accommodate the first tapered section 112a and, with corresponding axial adjustment of the magnet carrier assembly 72, at least a portion of the funnel section 128. Due to the above-described inclination of the container wall 110 with substantially constant thickness T, whenever the first tapered section 112a can be accommodated in the recesses 100a and 100b of the magnet carrier assembly 72, the second tapered section 112b can also be accommodated in the recesses 100a and 100b, respectively.

[0259] 100b and exposed to the magnetic field of the matrix magnets 94. Preferably, immobilization of magnetic particles 109a, which may be suspended in an object liquid 109 taken up in the receiving volume 112, takes place in the first tapered section 112a or in at least one of the adjacent transition areas 124 or 130 or in the second tapered section 112b, but preferably in the first tapered section 112a because of the distance from the output channel 108.

[0260] MA denotes a range of motion along which the magnet carrier arrangement 72 with its two magnet carriers 72a and 72b can move during operation of the liquid handling device 10. In fact, the magnet carrier arrangement 72 can be moved below the outlet ends 106 of the reaction vessel arrangements 86 in order to move the reaction vessel device 18 between its setup position and its ready position without collision.

[0261] The longitudinal ends of the funnel section 128 and the first tapered section 112a, which face each other, are separated from each other by thin horizontal lines in Figure 11, between which the second transition section 130 is located. 68488P WO Hamilton BonaduzAG - 55 -

[0262] To facilitate the introduction of object fluid 109 through the inlet opening 104 into the receiving volume 112, a guide section 132 is located between the inlet opening 104, preferably directly adjacent to it axially, and the funnel section 128. This guide section also tapers away from the inlet opening 104 and towards the outlet channel 108. Preferably, the fourth taper angle α4 is also constant along the entire guide section 132.

[0263] The fourth taper angle a4 is smaller than the third taper angle a3 and, in the illustrated embodiment, essentially corresponds to the first taper angle a1 or differs from it by no more than 30% with respect to the first taper angle a1.

[0264] Again, parallel horizontal lines in Figure 11 indicate the axial longitudinal ends of the guide area 132 and the funnel area 128 that point towards each other, between which a third transition area 134 is located, in which the inner wall surface 110a transitions from the guide area 132 to the funnel area 128 continuously and without jumps as it approaches the output channel 108.

[0265] The reaction vessels 88 of a reaction vessel arrangement 86 are connected to each other at their inlet ends 112 by a band 136 running along the subsequent track FB. As has already been explained several times, the reaction vessel arrangement 86 discussed here is molded in one piece as an injection-molded component made of thermoplastic material.

[0266] Figure 10A shows a longitudinal sectional view through a reaction vessel arrangement 86. The details of the reaction vessels 88 shown there have already been explained above in connection with Figures 11 and 12.

[0267] In Figure 10A, El denotes an input-end plane orthogonal to the drawing plane of Figure 10A, in which the input openings 104 of the reaction vessel arrangement 86 shown and all further reaction vessel arrangements 86 arranged in front of and / or behind the reaction vessel arrangement 86 shown in Figure 10A in the reaction vessel support 20 are located. 68488P WO Hamilton Bonaduz AG - 56 -

[0268] In Figure 10A, EO denotes an output-end plane orthogonal to the drawing plane of Figure 10A, in which the output openings 116 of the reaction vessel arrangement 86 shown and all further reaction vessel arrangements 86 arranged in front of and / or behind the reaction vessel arrangement 86 shown in Figure 10A in the reaction vessel carrier 20 are located.

[0269] The preferably parallel virtual planes El and EO are to be understood as having a certain thickness in order to accommodate manufacturing tolerances of the reaction vessel assemblies 86 and arrangement tolerances of the reaction vessel assemblies 86 in the reaction vessel carrier 20. The two planes El and EO are parallel to the follower path FB and are parallel to the ready movement paths AB, RB and NB. They are also parallel to the feed path BP.

[0270] To stiffen the reaction vessel arrangement 86, whose strip 136 has approximately the same thickness T as the vessel wall 110, webs 138 are formed between reaction vessels 88 adjacent to each other along the follower track FB, more precisely, in the illustrated embodiment, between adjacent guide areas 132. These webs connect the adjacent reaction vessels 88 to one another. The webs 138 project integrally from the strip 136 towards the output end. Consequently, with eight reaction vessels 88 arranged successively along the follower track FB, seven webs 138 are formed between adjacent reaction vessels 88.

[0271] Figure 10B shows, in an unrealistically exaggerated manner, a curvature of the reaction vessel arrangement 86 around an axis of curvature K orthogonal to the guide track FB and the vessel axes BA. The axis of curvature K runs orthogonal to the plane of Figure 10B and is actually farther from the belt 136 than depicted in Figure 10B. Figure 10B serves only to qualitatively represent the axis of curvature K and its position relative to the belt 136. A surface 136a pointing away from the reaction vessels 88 is therefore convexly curved. 68488P WO Hamilton BonaduzAG - 57 -

[0272] The curvature serves to improve the fixation of the reaction vessel assembly 86 in the reaction vessel support 20. The reaction vessel receptacles 24 in the reaction vessel support 20 are also centrally intersected by virtual receiving axes, which are aligned parallel to each other. In contrast, the vessel axes BA of reaction vessel assemblies 86 curved according to Fig. 10B are oriented divergingly. If the curved reaction vessel assembly 86 with the diverging vessel axes BA is now arranged in the reaction vessel support 20 with the parallel receiving axes of the reaction vessel receptacles 24, then the reaction vessel assembly 86 is forcibly deformed by the reaction vessel support 20 such that the virtual vessel axes BA of the individual reaction vessels 88 of the reaction vessel assembly 86 are oriented parallel to each other and collinear with the receiving axes within a certain tolerance range.The resulting deformation is an elastic deformation that 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 support 20. This increased contact force increases the frictional force acting between the reaction vessels 88 and the reaction vessel support 20, so that the resistance of a reaction vessel assembly 86, which is deformed due to its curved rest state in the reaction vessel support 20, to removal from the reaction vessel support 20 is increased compared to the same reaction vessel assembly 86 in an undeformed state in the reaction vessel support 20.

[0273] To further improve the fixation of the reaction vessel assembly 86 in the reaction vessel support 20, radial projections 140 are formed on the outer wall surfaces 110b of the vessel wall 110. In the illustrated embodiment, each reaction vessel 88 is a fixation reaction vessel provided with three radial projections 140 arranged equidistantly around the vessel axis BA. In the illustrated embodiment, the radial projections 140 are formed in the guide area 132 and extend parallel to the virtual vessel axis away from the belt 136 towards the discharge end 106. The axial extension length of the radial projections 140 of a reaction vessel 88 is the same for each radial projection 140. It is preferably greater than the axial extension length of the webs 138.68488P WO Hamilton Bonaduz AG - 58 -

[0274] The radial projections 140 are particularly easy to see in Figures 9, 13, 14 and 16.

[0275] The radial projections 140 locally increase the outer diameter or outer dimension of the reaction vessel 88 and, in particular, of the guide area 132 supporting the radial projections 140. Therefore, if the guide area 132 with the radial projections 140 is inserted into a reaction vessel receptacle 24 in which no negative corresponding recess for the radial projections 140 is formed in the receiving cavity, then the locally increased outer dimension in the area of ​​the radial projections 140 causes the reaction vessel 88 to be wedged in the reaction vessel receptacles 24, thus improving the fixation of the reaction vessel 88 in the reaction vessel support 20.

[0276] Technically and physically, 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 clear opening of the reaction vessel receptacles 24 without projections or recesses, the reaction vessel 88 can only be inserted into the reaction vessel receptacles 24 by means of elastic deformation of the area supporting the radial projections 140. This elastic deformation increases the contact force with which the radial projections 140 are pressed against a contact surface of the reaction vessel receptacles 24, and consequently, the frictional force acting between the reaction vessel 88 and the reaction vessel receptacle 24 also increases.

[0277] The essentially identical radial projections 140 have lateral flanks enclosing an angle β1 of between 45° and 55°, preferably 50°. The radially outwardly facing end face 140a of the radial projections 140 has a circumferential width b of 0.15 mm to 0.3 mm, 0.2 mm in the present example. The radial projection 1400 extends radially from the 68488P WO Hamilton Bonaduz AG - 59 -

[0278] The remaining outer wall surface 110b of the container wall 110 is given. The outer dimension of a reaction vessel 88 in the area bearing the radial projections 140, measured across the centrally passing virtual container axis BA, 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.

[0279] While the outer wall surfaces 110b of the guide area 132, which carries the radial projections 140, taper slightly towards the outlet end 106, the radially outward-facing end face 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 ramp with an inclination of preferably 30° with respect to the container axis BA at the longitudinal end of the radial projections 140 closer to the outlet end 106 facilitates their insertion into a cylindrical or conical reaction vessel receptacle 24.

[0280] The reaction vessels 88, more precisely the connecting band 136 of the reaction vessel arrangement 86, have a physical coding formation 142 at a longitudinal end 136b of the band 136 in the form of a detection surface 142a arranged at a distance with respect to the surface 136a of the band 136 pointing away from the output end 106.

[0281] 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 information to the control unit 40. The encoding of information by the physical coding formation 142 during the manufacture of the reaction vessel arrangement 86 offers the significant advantage of avoiding subsequent erroneous coding by a laboratory technician, as might occur during hectic laboratory work.

[0282] The detection surface 142a can, for example, be raised above the surface 136a of the band 136 by a predetermined distance s or by a predetermined 68488P WO Hamilton BonaduzAG - 60 -

[0283] The distance s may be lowered. Even the arrangement of the detection area 142a on the same surface level as the surface 136a can be an information carrier.

[0284] Furthermore, the physical coding formation 142 can be arranged at the same longitudinal end, but using the opposite corner of the band 136. If only the alternatives of a raised or recessed arrangement of the detection surface 142a at one of two corner regions of the longitudinal end 136b are considered, then four possible different coding states result. If the simultaneous formation of a physical coding formation 142 at both corners of the longitudinal end 136b is added, six possible different coding states result.

[0285] Preferably, the coding states are correlated with a physical feature of the reaction vessels 88 of the reaction vessel arrangement 86, for example, with the design of the output channel 108, more precisely with its diameter and / or length. The coding state of a reaction vessel arrangement 86, defined by the coding formation 142 formed on it, can directly indicate operating parameters to the control unit 40, which the latter is to set during a handling operation on the device 10. One possible such parameter is the specification of an overpressure in the receiving volume 112 to ensure splash-free dispensing of object liquid from the receiving volume 112 through the output channel 108. Data assignments can be stored in the data memory 42 of the control unit 40, which correspond to a detection area 142a detected by the vessel sensor 92.Assign a coding state associated with this detection to a pressure value that the control device 40 is to achieve during liquid handling for the dispensing of object liquid from a reaction vessel 88 into its receiving volume 112 by means of the pressure changing device 62b. Instead of a pressure value, for the detection of which the pressure sensor 71a can be used on the device side or for which another pressure sensor is to be provided, a duration of the introduction of gas into the receiving volume 112 can also be stored in the data memory 42. 68488P WO Hamilton Bonaduz AG - 61 -.

[0286] The detection surface 142a is preferably a flat surface and is also preferably parallel to the surrounding section of the surface 136a of the strip 136. This applies at least in a state in which the reaction vessel arrangement 86 is arranged in a reaction vessel support 20, since then the curvature about the axis of curvature K described above is eliminated and the reaction vessel arrangement 86 arranged in the reaction vessel support 20 is essentially uncurved.

[0287] The parallelism of the planar detection surface 142a to at least the surrounding section of the surface 136a can, however, essentially also apply in the original curved delivery state, since, firstly, the curvature about the axis of curvature K has a very large radius of curvature, which is significantly larger 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 cantilevers to the right from the peripheral reaction vessel 88-1 nearest to the coding formation 142 in Figure 10A, can be formed without curvature about the axis of curvature K.

[0288] The overall curvature of the reaction vessel assembly 86 can therefore be composed of planar sections of the reaction vessel assembly 86 in the region of the inlet openings 104, which, due to the targeted exploitation of material shrinkage in the region of the webs 138, are inclined relative to an adjacent planar section at an angle about an inclination axis parallel to the curvature axis K. Such a reaction vessel assembly 86, viewed from the perspective of Figure 10B, does not have a continuously curved shape like the reaction vessel assembly 86 shown in Figure 10B, but rather the band 136 exhibits a polygonal shape with planar sections at the inlet openings 104 and also at the projecting longitudinal end sections 136b and 136c that are angled relative to each other in the same direction, resulting in an overall curved shape.In other words, the curved reaction vessel arrangement 86 does not have to be a continuously curved reaction vessel arrangement 86, but can be 68488P WO Hamilton Bonaduz AG - 62 -.

[0289] a curved reaction vessel arrangement 86 formed discontinuously by a series of mutually inclined planar areas.

[0290] To save weight, the strip 136 can be constricted in areas between two successive reaction vessels 88 along the subsequent track FB (see Fig. 15), preferably with a continuous and stepless constriction. 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.

[0291] The waste container arrangement 44 with the waste liquid container 45 will be described below.

[0292] Figures 17 and 18 show the waste liquid container 45 in a perspective view (Figure 17) and in a cross-sectional view (Figure 18).

[0293] The waste liquid container 45 has a trough body 45c, which encloses a receiving volume 45a of the trough body 45c and thus of the waste liquid container 45. The trough body 45c is covered by a container lid 45d. The container lid 45d does not cover the entire trough body 45c; instead, a spout 144 is formed at each of the two longitudinal ends of the trough body 45c. The spouts 144 are recessed in the container lid 45d. In the setup position, an operator or an operating robot can lift the waste liquid container 45 from the drawer 28 that supports 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 removing the lid 45d.It is also possible, in principle, 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, which can then be carried out with greater care. 68488P WO Hamilton BonaduzAG - 63 -.

[0294] The container lid 45d has an elongated recess serving as a waste sealing assembly receptacle 27, into which the feeding device 62, more precisely the pressure changing device 62b, can place a sealing assembly 22. Once the sealing assembly 22, located on the pressure changing device 62b, is immersed in the waste sealing assembly receptacle 27, it can be removed from the feeding device 62, more precisely from the pressure changing device 62b, by moving the waste liquid container 45 along the ready movement path AB. An operator or an operating robot can then, when the waste liquid container 45 is in its setup position, remove the used sealing assembly 22 from the waste sealing assembly receptacle 27 in the container lid 45d and dispose of it.

[0295] Both the tub body 45c and the container lid 45d are preferably manufactured as single-piece injection-molded components from thermoplastic material. However, manufacturing them 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 created by stamping.

[0296] The container lid 45d covers a filling opening 146 of the bowl- or trough-shaped container body 45c. The container body 45c comprises a container base 148, which, as shown in Figure 18, can be flat or have defined support features to ensure stability. Side walls 150a to 150d extend from the container base 148, and the filling opening 146 is formed at the edge of these side walls furthest from the container base 148. Side wall 150a is the side wall that, during the movement of the waste liquid container 45 from the setup position to the ready position, is oriented transversely to the ready movement path AB and leads the way. The opposite side wall 150b follows the aforementioned movement of the waste liquid container 45, and the two side walls 150c and 150d connect the first-mentioned side walls 150a and 150b.

[0297] The container lid 45d has openings 152 arranged in an orthogonal matrix. This is also a 12-x-8 matrix, so that in the container-68488P WO Hamilton BonaduzAG - 64 -

[0298] The lid 45d has as many openings 152 as there are reaction vessels 88 that can be arranged in the reaction vessel carrier 20. Not only is the number of openings 152 and reaction vessels 88 identical, but the distances between the output channels 108 and their output openings 116 of the individual reaction vessels 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 discharged from the reaction vessels 88 through the output channels 108, each output channel 108 has an opening 152 in the lid 45d of the waste-liquid container 45 opposite it, thus allowing handling waste from any reaction vessel 88 to safely enter the receiving volume 45a of the waste-liquid container 45.

[0299] The section of surface 154 of the container lid 45d located between the openings 152 is preferably flat. The same applies to the section of surface 154 of the container lid 54c surrounding the waste sealing arrangement receptacle 27.

[0300] The lifting device 76 described above allows the waste liquid container 45 to be raised for the discharge of handling waste from the reaction vessels 88, preferably to such an extent that the discharge opening 116 of one reaction vessel 88, or the discharge openings 116 of all reaction vessels 88, are moved through the surface 154 and are located on the side of the container lid 45d facing the receiving volume 45a with respect to the surface 154. The longitudinal end sections with the discharge ends 106 of the reaction vessels 88 can project 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 the existing reaction vessels 88 are preferably located in a common plane. This arrangement plane can have a thickness of 1 mm, preferably a thickness of 0.5 mm, to accommodate the manufacturing tolerances of the reaction vessels 88. 68488P WO Hamilton Bonaduz AG - 65 -

[0301] As a splash guard, a wall arrangement 156, tapering from the opening 152 towards the receiving volume 45a, adjoins each opening 152 and completely encloses an inlet volume 158 circumferentially 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.

[0302] 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.

[0303] 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 without discontinuities and continuously from the flat surface 154 into the receiving volume 45a.

[0304] Starting from the edge 152a of an opening, an inlet area 156a of the wall arrangement 156 extends along the inlet axis EA from the container lid 45d towards the container bottom 148. The inlet area 156a is curved about the respective inlet axis EA, like the rest of the wall arrangement 156. The inlet area 156a is also curved about axes of curvature that are orthogonal to the inlet axis EA and spaced apart from it. The infinitely many axes of curvature orthogonal to the inlet axis EA extend circumferentially around the inlet axis EA.

[0305] To prevent the wall arrangements 156 from being wetted by handling waste accumulating in the receiving volume 45a, the wall arrangements 156 preferably extend over less than one-third of the clear height of the receiving volume 45a above the container bottom 148. For adequate splash protection, 68488P WO Hamilton Bonaduz AG - 66 -

[0306] However, the wall arrangements 156 extend at least over 10% of the clear height of the receiving volume 45a from the rest of the container lid 45d into the receiving volume 45a.

[0307] In contrast to the inlet area 156a, the outlet area 156b is curved only around the inlet axis EA in the illustrated embodiment.

[0308] The container lid 45d is detachably connected to the tub body 45c. It can be held, for example, by friction and / or positive locking by retaining tongues 164 on the tub body 45c.

[0309] Figures 19 and 20 show the feeding device 62 with its movement apparatus.

[0310] The guide rail 64 and the belt drive 66 of the feeding 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 design of the belt drives 56 and 60 of the other devices 18 and 50 described above as being movable and driven.

[0311] On the guide rail 64, a guide carriage 170, connected to the belt 66a for common movement, is movably arranged along the feed track BP.

[0312] A mobile support 172, which moves along the feed track BP together with the guide carriage 170, is arranged on the guide carriage 170 and carries the container sensor 92 and the feed device 62. The mobile support 172, which is rigidly connected to the guide carriage 170, carries a guide rail 174, which in the illustrated example is oriented vertically and thus orthogonally to the guide rail 64 and orthogonally to the parallel guide rails 48, 54 and 58. 68488P WO Hamilton BonaduzAG - 67 -

[0313] The feeding device 62 is movably guided along a vertical approach path WP on the guide rail 174. The mobile support 172 also carries a drive unit 176, which drives the feeding device 62 along the approach path WP. This allows the feeding device 62 to approach and then move away from the reaction vessel assembly 18, and in particular from the input ends 102 with the input openings 104 of the reaction vessels 88. This allows the sealing arrangement 22 shown in Figure 1, when attached to the feeding device 62, to be pressed against the belt 136 of the reaction vessel assembly 86 with a predetermined and / or defined contact pressure.Furthermore, the drive mechanism 176 can move a used sealing assembly 22, located on the feeding device 62, along the approach path WP into the waste sealing assembly receptacle 27, from where it can be stripped from the feeding device 62, more precisely from the pressure changing device 62b, by moving the waste liquid container 45 along its ready movement path AB. Alternatively, the drive mechanism 176 can move a used sealing assembly 22, located on the feeding device 62, along the approach path WP into the sealing assembly receptacle 26, from where it can be stripped from the pressure changing device 62b by moving the reaction vessel support 20 along its ready movement path RB.

[0314] The feeding device 62, shown in Figures 19 and 20 without its switching valves, is explained in more detail below. As can be seen from Figures 19 and 20, the feeding device 62 has a conduit body 178 and a dispensing component 180. Connectable and separable conduits are formed in the conduit body 178 by means of the switchable valves 182, 184, and 186 (see Figure 21). These conduits 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 from each other along an offset direction VD parallel to the feeding path BP. Their distance along the offset direction VD is greater than at least the opening width OW of the input openings 104 of the Reak-68488P WO Hamilton BonaduzAG - 68 -

[0315] The container 88 is designed so that if one opening consisting of a metering opening 188 and a gas outlet opening 190 is arranged centrally above an input opening 104, the other opening cannot discharge into the input opening 104. To prevent simultaneous discharge of a metering opening 188 and a gas outlet opening 190 into the same input opening, even if the metering opening 188 and gas outlet opening 190 are not arranged centrally 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.

[0316] As shown in Figure 22, the metering openings 188 can be formed by simple openings in the dispensing component 180 or as the end opening of a pipe 189 (see the rightmost metering opening 188 in Figure 22). Preferably, all pipes leading to a metering opening 188 are of the same design; that is, preferably either all metering openings 188 are openings directly in the dispensing component 180 or all metering openings 188 are openings in a respective pipe 189. The pipes 189 preferably project from a surface 180a of the dispensing component 180 that faces the reaction vessel assembly 18 during operation. The surface 180a, from which the pipes 189 emerge, can be recessed relative to a surrounding surface 180b of the dispensing component 180 in order to protect the end sections of the pipes 189 from external mechanical influences.

[0317] The sealing assembly 22 is positively engaged in a receiving recess 192 in the output component 180, which runs parallel to the ready movement path RB of the reaction vessel device 18, and is slid in and out along an exchange path BB, which runs parallel to the ready movement path RB and orthogonal to the feed path BP, in a receiving recess 192 running parallel to the ready movement path RB and orthogonal to the feed path BP, thus being ready for operation. The receiving recess 192 is provided in the output component 180 by a T-slot-shaped sealing receiving structure 193.

[0318] Through openings 194 in the sealing arrangement 22, which penetrate the sealing arrangement 22 and its sealing surface 22a designed for contact with the surface 136a of the strip 136, are collinear when the arrangement is ready for operation. 68488P WO Hamilton Bonaduz AG - 69 -

[0319] arranged as a continuation of the gas outlet openings 190 in order to direct gas exiting from the gas outlet openings 190 to the input openings 104 of the reaction vessels 88.

[0320] Of the switching valves 182, 184, and 186 shown in Figure 21, mounted on the rear side 178a of the pipe body 178, switching valve 182 switches lines of the metering device 62a between a closed state and a flow state. The switching valves 182 therefore form a metering valve arrangement 183. The switching valves 184 switch lines of the pressure changing device 62b between a closed state and a flow state. The switching valves 184 therefore form a gas valve arrangement 185. Each switching valve 182 and 184 either interrupts or connects two pipe sections formed in the pipe body 178.

[0321] The two switching valves 186 form a changeover valve assembly 187, which allows either a liquid from one of the containers 34 and 36 or gas from the gas pressure accumulator 69 to be selectively directed through the metering openings 188 of the metering device 62a. By purging 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 cleared and cleaned of the last liquid passed through them between changes in the liquids to be metered, for example, between containers 34 and 36. Each switching valve 186 can selectively connect an upper or a lower opening to a middle opening or separate the openings from each other.

[0322] Three line connections 196, 198, and 200 are arranged on the conduit body 178, in the illustrated embodiment on the upper side 178b. Line connections 196 and 198 are liquid-carrying line connections that supply liquids from containers 34 and 36 to a line system 202 (see Figure 23) of the conduit body 178. It is assumed that line connection 196 is connected to the extraction line 38a and line connection 198 to the extraction line 38b. Line connection 200 is a gas-carrying line connection that supplies the line system 202 of the conduit body 178 under pressure.

[0323] The pressure line 38c in the object fluid compartment 32 is connected to the gas pressure reservoir 69 and is not routed via the valve arrangements of the feeding device 62.

[0324] The exclusively gas-carrying pressure line 38c is part of a gas piping arrangement 39, which also includes the components compressor 68, gas pressure storage tank 69, the gas-carrying lines in the piping body 178 and the other gas-carrying lines between the aforementioned components as well as other gas-carrying lines of the liquid handling device 10.

[0325] The line connection 200 has a flow sensor 242, which detects the flow rate of gas flowing through the line connection 200 from the pressure accumulator 69 to the feed device 62 and transmits it to the control unit 40 via signal lines (not shown). The detected flow rate is generally a volumetric flow rate. However, it should not be categorically ruled out that the flow rate could be detected as a mass flow rate, although this is less preferred due to the compressibility of the flowing gas.

[0326] The flow sensor 242 is therefore located in the pipe section between the compressor 68 or pressure accumulator 69 on the one hand and the feed device 62 on the other, in which gas flows only in one direction, namely towards the feed device 62, and is arranged downstream of the pressure limiter 71. However, the flow sensor 242 is arranged upstream of the gas valve assembly 185, so that a single flow sensor 42 is sufficient for the entire feed device 62 and a separate flow sensor is not required for each gas pipe section formed in the pipe body 178. In order to assign the flow detection signal of the flow sensor 242 to a specific reaction vessel 88 via the control unit 40, the reaction vessels 88 of a reaction vessel arrangement 86 are preferably individually and sequentially charged with gas from the pressure accumulator 69 in order to expel any liquid present in the reaction vessel 88 through its discharge opening 116.68488P WO Hamilton Bonaduz AG - 71 -.

[0327] Figure 24 shows a perspective view of the feeding device 62 looking towards the rear 178a of the pipe body 178 without the switching valves 182, 184 and 186.

[0328] The large openings 204, arranged in four parallel rows, serve solely for the installation of the switching valves 182, 184, and 186, each switching valve being secured to the rear 178a by two screws inserted into a large opening 204. For clarity, not all large openings 204 are labeled. A total of 36 openings 204 are present on the rear 178a of the conduit body 178, namely two for each of the 18 switching valves.

[0329] A bottom row of small openings 206 leads via line sections 208 directly to the metering openings 188.

[0330] The switching valves 182 are arranged to connect the pipe sections 208 with similarly small openings 210 of a pipe section 212 by means of their small openings 206 or to separate the said openings 206 and 210 from each other.

[0331] The conduit section 212 terminates in the rear 178a of the conduit body 178 in a small central opening 214, which opens to the switching valve 186 on the right in Figure 21.

[0332] From the line connection 198 a short line section 216 extends to a small opening 218, which is one of three small openings 218, 214 and 220, which are connected or separated in pairs by the switching valve 168 on the right in Figure 21.

[0333] The lowest small opening 220 opens into a pipe section 222, which leads only to a middle small opening 224 of the switching valve 186 on the left in Figure 21. 68488P WO Hamilton Bonaduz AG - 72 -

[0334] In addition to the middle small opening 224, the switching valve 186 on the left in Figure 21 has 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.

[0335] A further pipe section 234 is directly connected to the gas-carrying pipe connection 200, leading to small openings 236 below the switching valves 184 of the gas valve assembly 185. In addition to the small openings 236, small openings 238 of pipe sections 240 open towards the switching valves 184, leading directly into the gas outlet openings 190.

[0336] By switching the switching valves 182, the fluid present at the openings 210 and thus at the opening 214 can be selectively directed to the metering openings 188 or not.

[0337] 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.

[0338] The switching valve 186 on the right in Figure 21 allows either the object fluid present at the line connection 198 to be directed via the line section 216 and the opening 218 or the fluid present at the opening 220 to the openings 210.

[0339] Through the switching valve 186 on the left in Figure 21, 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.

[0340] By appropriately switching the changeover valves 186, either object fluid from the container 3468488P WO Hamilton BonaduzAG - 73 - can be supplied to the openings 210 of the metering valve arrangement 183.

[0341] or object liquid from container 36 or pressurized gas from gas pressure storage tank 69 are supplied.

[0342] Figure 25 shows the feeding device 62 in perspective from a low angle, looking at the essentially smooth front surface 178c of the conductor body 78. This view is presented only as a supplement to and conclusion of the preceding explanations.

[0343] Figure 26 shows a schematic representation of the flow signal 250 detected by the flow sensor 242, which simultaneously forms the flow sensor arrangement of the liquid handling device 10, over time during the withdrawal of liquid from a reaction vessel 88. It is irrelevant whether the liquid is the target liquid or waste liquid. The abscissa represents the time t in milliseconds. The ordinate represents the flow rate f in pl / s.

[0344] The extraction process begins at time to, at which the flow sensor 242 first detects a flow fo of 0 pl / s and transmits a corresponding flow detection signal representing the detected flow f to the control unit 40.

[0345] At time to, the withdrawal process begins at the affected reaction vessel 88, which should be filled with the object liquid at this time. Therefore, at time to, the switching valve 184 associated with the affected reaction vessel 88 is opened.

[0346] Opening the switching valve 184 changes the pressure, and with pressure as the driving factor, the gas flow or gas quantity flow rate in the line branch in the line body 178, which leads to the gas outlet opening 190 associated with the switching valve 184, is caused by a pressure difference. With the opening of the switching valve 184, the pressure and thus the gas quantity flow rate in the gas line assembly 39 increases. Due to its compressibility, the gas used, here: air, is a system prone to strong vibrations. 68488P WO Hamilton Bonaduz AG - 74 -

[0347] At time ts, not only has the gas flow rate stabilized, but a gas flow rate within a narrow range of values ​​is established, which is maintained for a certain period of time until the later time tE. At time ts, a dynamic equilibrium is established in the reaction vessel 88 currently being processed, between the volume of gas introduced per unit time through the inlet opening 104 into the receiving volume 112 and the volume of liquid expelled per unit time from the outlet opening 116 by means of the introduced gas. Due to the upper limit of the gas pressure difference on both sides of the outlet opening 116, or rather,preferably the gas pressure set at a predetermined pressure in the gas line arrangement and consequently a predetermined gas pressure difference on both sides of the dispensing opening 116, determines the quantity flow of gas flowing into the receiving volume 112 in conjunction with the flow resistance acting in the dispensing channel 108.

[0348] In order to reliably exclude the transient behavior of the gas flow rate in the gas piping arrangement 39 and thus also the transient behavior of the flow detection signal from signal processing, the control device 40 only begins to evaluate the flow detection signal after a first time interval Ti has elapsed at time ti.

[0349] At time ti, the control unit 40 compares the flow detection signal 250 with a first reference signal f2, which represents a gas flow rate greater than the gas flow rate that would be established in the dynamic equilibrium state for the known extraction process with the known parameters. If the value of the flow detection signal 250 at time ti were greater than the value of the first reference signal f2, there would at least be a suspicion that the reaction vessel 88 was unexpectedly empty, lacking the required liquid.

[0350] Likewise, from time ti, the control unit 40 can compare the flow detection signal 250 with a second reference signal fi, which is a Gas-68488P WO Hamilton BonaduzAG - 75 -

[0351] The flow rate represents a quantity flow that is lower than the expected gas flow rate established in dynamic equilibrium, approximately 50% or less. If the value of the flow detection signal 250 were to fall below the second reference signal fi at time ti, there would at least be a suspicion that the outlet opening 116 of the reaction vessel 88 currently being processed is not sufficiently clear, and that the reaction vessel 88 should therefore be considered blocked.

[0352] The first time interval Ti is therefore also a second time interval T2 assigned to the second reference signal f2, which must elapse before the control device 40 begins checking for a possible blockage of the output opening 116 of the currently processed reaction vessel 88.

[0353] In principle, it would be possible to recognize a final evaluation concerning an unplanned filling or an unplanned blockage of the currently processed reaction vessel 88 by once exceeding the first reference signal f2 or once falling below the second reference signal fi and to output a meaningful result signal.

[0354] To avoid misjudgments, the control device 40 is designed to continue the flow detection signal 250 for a predetermined first relevance period TRI until time t2 and only then conclude that the reaction vessel 88 is in faulty condition and output a corresponding result signal if the first reference signal f2 is exceeded or the second reference signal fi is undershot for the entire first relevance period TRI.

[0355] If, from time t2 onwards, it is clear by comparing the flow detection signal 250 with the reference signals f2 and fi that the withdrawal process has begun with a properly prepared reaction vessel 88, the control unit 40 continues the withdrawal process and controls the components involved accordingly. This control is the result of one or more result signals. 68488P WO Hamilton BonaduzAG - 76 -

[0356] If, on the other hand, the control unit 40 were to detect an improper condition of the reaction vessel 88 due to a correspondingly deviating course of the flow detection signal, it would abort the withdrawal process and mark the usable liquid container 90 assigned to the current reaction vessel 88 as 'defective' or 'to be discarded' in the data storage 42 for subsequent further processing operations.

[0357] Furthermore, the control unit 40 compares the flow detection signal 250 with a third reference signal fs, the reference value of which is chosen such that the third reference signal fs is only exceeded under the set operating parameters if the gas introduced into the reaction vessel 88 per unit time can flow out of the discharge opening 116 largely undisturbed by the object liquid. This comparison process can, for example, begin after a third time period T3, which in this example corresponds to the sum of the first and second time periods Ti and T2, respectively, and the first relevance period TRI.

[0358] From time tE onwards, the dynamic equilibrium ends because more gas flows into reaction vessel 88 per unit of time than liquid leaves reaction vessel 88. The withdrawal process is nearing its end. Only remnants of the originally present liquid are expelled from reaction vessel 88.

[0359] Due to the lower flow resistance of the gas at the output channel 108 compared to the flow resistance of the object liquid, a larger quantity, i.e., in the present example a larger volume, of gas can pass through the output opening 116 per unit of time than object liquid, given the same gas pressure difference on both sides of the output opening 116.

[0360] If the flow detection signal 250 exceeds the third reference signal fs, there is at least a suspicion that the reaction vessel 88 has been completely emptied. The control unit 40 then checks for a second relevance period TR2 whether the flow detection signal 250 continues to exceed the third reference signal fs. 68488P WO Hamilton BonaduzAG - 77 -

[0361] The exceedance begins at time ts, immediately followed by the second relevance period TR2. If the flow detection signal 250 falls below the third reference signal again during the second relevance period TR2, the second relevance period TR2 is restarted the next time the third reference signal fs is exceeded. This ensures that the reaction vessel 88 is safely emptied. The same applies, mutatis mutandis, to the first relevance period TRI. It is also restarted when the exceedance or fall below the respective reference signal f2 or fi by the flow detection signal 250 ends during the first relevance period TRI.

[0362] If, after the second relevance period TR2, it is clear that the reaction vessel 88 is safely emptied, the control unit 40, via a result signal, initiates a continuation of the gas injection into the reaction vessel 88 for a fourth period T4 and the purging of gas through the outlet opening 116 in order to expel any remaining droplets of liquid from the reaction vessel 88. This continuation of the gas injection into the reaction vessel 88 is optional and not mandatory.

[0363] After the fourth time period T4 has ended, the control unit 40 terminates the withdrawal process at the currently processed reaction vessel 88 by issuing result signals to the components involved and begins a new withdrawal process at another reaction vessel 88.

Claims

1. 68488P WO Hamilton BonaduzAG - 78 - Claims 1. Automated liquid handling device (10) for handling object liquids (109), in particular for purifying nucleic acids, comprising: i. a reaction vessel arrangement (86) with at least one reaction vessel (88), wherein the at least one reaction vessel (88) is designed to receive a liquid (109) and a gas, wherein the at least one reaction vessel (88) has an inlet end (102) with an inlet opening (104) and an outlet end (106) located at a distance from the inlet end (102) with an outlet opening (116), wherein in the operational state of the liquid handling device (10) an interior space of the at least one reaction vessel, at least partially filled with gas, is present on an inner side of the outlet opening (116) and wherein a gas atmosphere surrounding the at least one reaction vessel (88) is present on an outer side of the outlet opening (116) opposite the inner side, ii.a pressure changing device (62b), wherein the pressure changing device (62b) is designed to change a gas pressure difference between the gases present on both sides of the dispensing opening (116) of the at least one reaction vessel (88) in order to carry out a withdrawal process and thereby, with the participation of the generated gas pressure difference, to withdraw an object liquid (109) taken up in the interior (112) of the at least one reaction vessel (88) through the dispensing opening (116) from the at least one reaction vessel (88). iii. a gas conduit arrangement (39) with at least one gas conduit (232) arranged to convey a gas flow generated by the pressure changing device (62b) for changing the gas pressure difference on both sides of the outlet opening (116) of the at least one reaction vessel (88) in the gas conduit arrangement (39), and 68488P WO Hamilton Bonaduz AG - 79 - iv. a control device (40) which is connected to the pressure changing device (62b) for the transmission of signals and / or power in order to control the operation of the pressure changing device (62b), characterized in that the liquid handling device (10) has a flow sensor arrangement (242) with at least one flow sensor (242) which is designed and arranged to detect the gas flow rate flowing to change the gas pressure difference in the gas line arrangement (39) and to output a flow detection signal (250) representing the detected gas flow rate to the control device (40), wherein the control device (40) is configured to output at least one result signal on the basis of the flow detection signal (250).

2. Automated liquid handling device (10) according to claim 1, characterized in that the control device (40) is configured to perform at least one of the following control interventions with the at least one result signal: a. Terminating a gas flow in the gas line arrangement (39) to change the gas pressure difference on both sides of the outlet opening (116) of a reaction vessel (88), b. Generating a gas flow in the gas line arrangement (39) to change the gas pressure difference on both sides of the outlet opening (116) of a reaction vessel (88), c. Identifying a section of the liquid handling device (10) for subsequent operations on the liquid handling device (10) and / or on a processing station downstream of the liquid handling device (10), d. Outputting information.

3. Automated liquid handling device (10) according to claim 2, characterized in that the reaction vessel arrangement (86) comprises a plurality of reaction vessels (88), wherein the control device 68488P WO Hamilton BonaduzAG - 80 - (40) is equipped to terminate a gas flow in the gas piping arrangement (39) for changing the gas pressure difference on both sides of the outlet opening (116) of a first reaction vessel (88) with at least one result signal and to generate a gas flow in the gas piping arrangement (39) for changing the gas pressure difference on both sides of the outlet opening (116) of a second reaction vessel (88).

4. Automated liquid handling device (10) according to claim 2 or 3, characterized in that the liquid handling device (10) comprises a usable liquid container arrangement (78) with a plurality of usable liquid containers (90), wherein the control device (40) is configured to generate information assigned to a usable liquid container (90) from the plurality of usable liquid containers (90) as an identifier for that liquid container (90) and to store this information in a data storage device (42) in a retrievable manner and / or to output it as an information signal.

5. Automated liquid handling device (10) according to any of the preceding claims, characterized in that the control device (40) is configured to compare the flow detection signal (250) with at least one predetermined reference signal (fi, f2, fs), wherein the at least one predetermined reference signal (fi, f2, fs) represents a predetermined gas flow rate as a reference value, and wherein the control device (40) is configured to output the at least one result signal based on the comparison between the flow detection signal (250) and the at least one reference signal (fi, f2, fs).

6. Automated liquid handling device (10) according to claim 5, characterized in that the control device (40) is configured to transmit the flow detection signal (250) only after a predetermined period has elapsed. 68488P WO Hamilton BonaduzAG - 81 - To compare the time period (Ti , T2, T3) from the start of the generation of a gas flow with at least one predetermined reference signal (fi, f2, fs).

7. Automated liquid handling device (10) according to claim 5 or 6, characterized in that the control device (40) is configured to output the at least one result signal based on the comparison between the flow detection signal (250) and the at least one reference signal (f 1 , f2, fs) only if a predetermined relationship between the flow detection signal (250) and the at least one reference signal (f 1 , f2, fs) is satisfied for at least 80% of the duration of a predetermined comparison time interval (TRI, TR2).

8. Automated liquid handling device (10) according to claim 6, or according to claims 6 and 7, characterized in that the control device (40) is configured to compare the flow detection signal (250) with at least one first reference signal (f2) only after a predetermined first time period (Ti) has elapsed since the start of the generation of a gas flow, and to output a first result signal based on the comparison between the flow detection signal (250) and the first reference signal (f2), wherein the first reference signal (f2) represents a predetermined first gas flow as the first reference value, wherein the first reference value is selected to be greater than a gas flow in the gas piping arrangement (39) which occurs during a withdrawal process under normal operating conditions.

9. Automated liquid handling device (10) according to any one of claims 6 to 8, including claim 6, characterized in that the control device (40) is configured to compare the flow detection signal (250) with at least one second reference signal (fi) only after the expiry of a predetermined second time period (T2) from the start of the generation of a gas quantity flow, and a second 68488P WO Hamilton BonaduzAG - 82 - The result signal is to be output based on the comparison between the flow detection signal (250) and the second reference signal (fi), wherein the second reference signal (fi) represents a predetermined second gas flow rate as the second reference value, the second reference value being chosen to be smaller than a gas flow rate in the gas piping arrangement (39) which is established during a withdrawal process under normal operating conditions.

10. Automated liquid handling device (10) according to any one of claims 6 to 9, including claim 6, characterized in that the control device (40) is configured to compare the flow detection signal (250) with at least one third reference signal (fs) only after a predetermined third time period has elapsed since the start of the generation of a gas flow, and to output a third result signal based on the comparison between the flow detection signal (250) and the third reference signal (fs), wherein the third reference signal (fs) represents a predetermined third gas flow as the third reference value of a gas flow, wherein the third reference value is selected such that it is greater than a gas flow in the gas piping arrangement (39) which is established during a withdrawal process under normal operating conditions.

11. Automated liquid handling device (10) according to any of the preceding claims, characterized in that the liquid handling device (10) has a pressure limiting device (71) which is configured to limit the gas pressure in the gas line arrangement (39) to a predetermined target limit gas pressure and / or to limit the gas pressure difference on both sides of the discharge opening (116) of the at least one reaction vessel (88) to a predetermined target limit gas pressure difference. 68488P WO Hamilton Bonaduz AG - 83 - 12. Automated liquid handling device (10) according to any of the preceding claims, characterized in that the liquid handling device (10) has a pressure limiting device (71) which is designed to adjust the gas pressure in the gas line arrangement (39) to a predetermined target gas pressure range and / or to adjust the gas pressure difference on both sides of the dispensing opening (116) of the at least one reaction vessel (88) to a predetermined target gas pressure difference range.

13. Automated liquid handling device (10) according to claim 11 or 12, characterized in that the pressure limiting device (71) has at least one pressure sensor (71a) which detects the gas pressure in the gas line arrangement (39) and outputs a pressure detection signal to the control device (40), wherein the pressure detection signal represents the gas pressure in the gas line arrangement (39) and / or the gas pressure difference on both sides of the output opening (116) of the at least one reaction vessel (88), wherein the control device (40) is configured to control or regulate the operation of the pressure change device (62b) according to the pressure detection signal.

14. Automated liquid handling device (10) according to any one of claims 11 to 13, characterized in that the liquid handling device (10) has a data storage device (42) in which a plurality of different pressure-related setpoint ranges are stored, wherein the different pressure-related setpoint ranges are assigned to different object liquids (109), wherein the control device (40) is configured to control or regulate the operation of the pressure limiting device (71) according to a pressure-related setpoint range from the plurality of stored pressure-related setpoint ranges. 68488P WO Hamilton BonaduzAG - 84 - 15. Automated liquid handling device (10) according to any one of claims 11 to 14, including claim 11 , characterized in that the pressure changing device (62b) forms at least a part of the pressure limiting device (71).

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