Solid phase extraction apparatus with a rotating arm for dispensing reagents

Abstract

A solid phase extraction apparatus has a base plate and a shuttle movable horizontally along the base plate configured to transport a laboratory vessel component. A pressure manifold plate is vertically reciprocally movable defining a hoist well; the shuttle is movable into and out of the hoist well to position the laboratory vessel component below the manifold plate. A reagent dispenser is vertically movable with the manifold plate having a swivel arm and a hinge coupling one end of the swivel arm to the manifold plate. A dispensing tube is located at the other end forming a cavity fluidly coupled to a liquid reagent. A drive mechanism is used to rotate the one end of the swivel arm about the hinge to move the dispensing tube from a position within the hoist well to a position outside the hoist well to dispense the liquid reagent into the laboratory vessel component.

Description

Technical Field

[0001] This invention relates to a positive pressure solid-phase extraction apparatus including a reagent dispenser. Systems comprising solid-phase extraction apparatus and laboratory automation equipment, as well as methods for performing solid-phase extraction using such systems, are part of this invention. Background Technology

[0002] Solid-phase extraction (SPE) is a solid-liquid extraction method that separates, isolates, or purifies compounds dissolved or suspended in a liquid mixture from other compounds in the mixture, based on the compounds' physical and chemical properties in the mixture. The isolated or separated compounds can then be analyzed using methods such as mass spectrometry, gas chromatography, ultraviolet spectroscopy, or infrared spectroscopy.

[0003] Solid-phase extraction requires a filter or column with a solid phase that can be conditioned with a conditioning liquid before the sample liquid is applied to the filter. The filter includes a filter pack that selectively binds certain compounds present in the sample liquid. The conditioning liquid and sample liquid are forced through the filter pack by applying pressure to one side of the filter or applying a vacuum to the opposite side. Alternatively, centrifugation is applied. After the filter has been loaded with the sample liquid, it can be washed with a washing liquid to elute some undesirable compounds, thus purifying the desired compounds in the filter pack. Finally, the filter is treated with an eluent and positive pressure is applied again so that the eluent contains the desired and purified compounds for further analysis.

[0004] Solid-phase extraction (SPE) methods require multiple steps and different reagents, and are laborious when performed manually. Therefore, laboratories use automated equipment to perform SPE methods to improve efficiency and speed, as large volumes of samples often need to be analyzed. SPE methods are performed on dedicated and automated SPE equipment, which can be used as a standalone device or integrated into general laboratory automation systems that include automated pipetting features. Automated pipetting features use a robotic arm to aspirate sample liquid from a sample container and dispense the sample liquid onto filter plates or racks customized for solid-phase extraction. The filter plates include multiple wells and filters arranged in a standardized pattern, such as according to a 96-well plate format with 12 consecutive rows of 8 wells each. The robotic arm of the automated pipetting feature therefore includes adapters for carrying multiple pipette tips, for example, 8 adapters. The pipette tips used can be discarded after a single use to prevent cross-contamination between sample liquids. Pipettes can also be used to aspirate and dispense reagent liquids, i.e., conditioning, washing, or eluting liquids, which increases the consumption of disposable pipette tips. For 96-well plate formats, the automated extraction method is slowed down because the adapter for the eight pipette tips needs to move back and forth between the reagent container and the filter plate 12 times, and the pipette tips need to be changed before switching to another reagent liquid. During the reagent aspiration and dispensing steps, the robotic arm cannot be used for other operations. Furthermore, the need to aspirate large quantities of reagent liquid from open containers that are accessible to the pipette tips can increase the risk of harmful solvent evaporation, and these open containers need to be refilled from larger containers. Therefore, direct dispensing from larger containers may be beneficial.

[0005] US9885732B2 discloses a solid-phase extraction apparatus that uses positive pressure for filtration. A rotating arm can be used to aspirate and dispense reagent or sample liquids. The arm can rotate within the plane of the apparatus stage and precisely aspirate and dispense liquids between two fixed positions on a perimeter defined by the rotating arm.

[0006] US10942193B2 discloses an automated positive pressure solid-phase extraction (SPE) apparatus including a reagent dispenser device. This SPE apparatus includes a vertically raised manifold plate configured to apply pressure to a filter plate located below the manifold plate using a shuttle device. The shuttle allows the filter plate to move horizontally along a shuttle path, and the reagent dispenser uses a dispenser manifold with multiple dispensing heads oriented perpendicular to the shuttle path to dispense reagent liquid into the orifices of the filter plate. Reagent is pumped from a reagent supply through the dispensing heads of the dispenser manifold to dispense liquid into all orifices in a row at once. The manifold is accessed to the row of orifices using a separate lifting device. Summary of the Invention

[0007] When using multiple distributor heads connected to a single distributor manifold, the accuracy of the volume dispensed into each orifice may be compromised. When using different orifice plate formats, the distributor manifold may have to be adjusted, reducing system flexibility, and a single orifice in a row may not be supplied without filling the others. Finally, adding a separate lifting device for the distributor manifold may increase manufacturing costs, and the pump used for the distributor manifold may have to be designed with a greater pumping capacity.

[0008] The purpose of this invention is to overcome the shortcomings of the prior art and to provide a multifunctional solid-phase extraction device and a system including the device, which is flexible in its adaptation to different pore formats and can accurately dispense liquid reagents via a single dispenser. Another purpose is to provide an SPE method using the SPE device.

[0009] The independent claims address these objectives, and further exemplary embodiments will become apparent from the dependent claims and the following description, including the accompanying drawings.

[0010] A first aspect of the invention relates to a solid-phase extraction apparatus, which can assist and accelerate the filtration process by applying pressure or vacuum to a liquid to be filtered through a solid packaging material. The solid-phase extraction apparatus includes a substrate that defines a horizontal plane in the xy direction. A shuttle is mounted on the substrate and configured to carry laboratory glassware components such that the components can be placed on or removed from the shuttle in a vertical direction perpendicular to the horizontal plane. The laboratory glassware components are form-fitted into the shuttle in the xy plane and are immovable. The shuttle, and the laboratory glassware components subsequently positioned on it, are reciprocating along the horizontal length of the substrate, thereby defining a shuttle path along which the shuttle can move back and forth. The shuttle can stop at an end position of the path or at any intermediate position between two end positions to transport or position the laboratory glassware components. The solid-phase extraction apparatus also includes a pressure manifold plate oriented parallel to the substrate and reciprocating in the vertical direction. The manifold has a defined geometry, such as a rectangular shape, and a lift shaft is defined by the manifold that moves vertically up and down. The height of the lift shaft can be variable. The manifold is configured to apply positive pressure to the laboratory glassware component when it contacts the component. The positive pressure can be applied using a compressed gas, such as air or nitrogen. The manifold may include gaskets for forming an hermetically tight fit between the top surface of the laboratory glassware component and the bottom surface of the manifold. The gaskets may surround one or more openings in the manifold. The manifold may include channels for distributing gas to the multiple openings in the manifold, and flow restrictors may be included in the channels to ensure uniform gas pressure distribution on the manifold. The manifold may move downward to contact the laboratory glassware component and provide an hermetically tight fit. Alternatively, the laboratory glassware component may move upward in the lift shaft, or both the manifold and the laboratory glassware component may come close to each other to provide an hermetically tight fit between the manifold and the laboratory glassware component. Positive pressure applied to laboratory glassware components is used to facilitate solid-phase extraction processes by forcing liquid through solid packaging present in the laboratory glassware components.

[0011] A shuttle, including a laboratory glassware component, can move into and out of the lift shaft along a shuttle path. The laboratory glassware component can be aligned with and positioned below the manifold plate. The laboratory glassware component has a shape complementary to the shape of the manifold plate, thus a rectangular manifold plate matches a rectangular laboratory glassware component. The shuttle can move into and out of the lift shaft when the manifold plate is in a vertical position defining an opening available for the shuttle. The height of the opening can vary depending on the position of the manifold plate and can accommodate laboratory glassware components placed on the shuttle or stacks of laboratory glassware components placed on the shuttle. Two movement steps may be required before applying positive pressure to the laboratory glassware component: first, moving the laboratory glassware component into the opening defined by the vertical position of the manifold plate, and then lowering the manifold plate or raising the laboratory glassware component to provide contact and an airtight fit.

[0012] The manifold includes a liquid reagent dispenser. The liquid reagent dispenser is operatively coupled to the manifold, allowing the manifold, including the dispenser, to move vertically relative to a substrate. The liquid reagent dispenser can be releasably coupled to the manifold, making it an add-on to a solid-phase extraction device. Alternatively, the liquid reagent dispenser is permanently coupled and integrated into the manifold. The liquid reagent dispenser can dispense multiple reagent liquids to laboratory glassware components and is configured to automatically switch between different reagent liquids.

[0013] The liquid reagent dispenser may include a start-up station for initiating the dispensing of liquid reagents to laboratory glassware components. The liquid reagent to be dispensed is first initiated into a collection chamber, thereby clearing the tubing and fluid lines from previously dispensed different liquid reagents. The collection chamber of the start-up station may be coupled, for example, releasably coupled to a manifold plate and move vertically together with the plate. The start-up station may include a discharge port for disposing of the initiated liquid from the collection chamber. The discharge port may be a simple tubing, or may include an adjustable-length arrangement depending on the vertical position of the manifold plate. This arrangement may be a constricted arrangement of multiple coaxially arranged sleeves, or alternatively, a flexible tube or corrugated plastic tube.

[0014] The reagent dispenser includes a rotating or pivoting arm defining an axis oriented parallel to the plane of a manifold plate. One end of the arm is hinged to the manifold plate. The hinge may be a joint that allows the rotating arm to rotate, and the joint may include a bearing. A dispensing tube is located at the other end of the arm and provides a cavity oriented vertically toward the substrate. The cavity is an opening that allows for precise dispensing of liquid reagents into a laboratory glassware component. The dispensing tube may include a tapered fluid outlet. The dispensing tube is fluidly connected to or may be connected to a liquid reagent that may be included in a liquid reagent supply unit. When the cavity is flush with the top surface of the laboratory glassware component, the reagent dispenser dispenses liquid reagents into the laboratory glassware component. In an embodiment, the reagent dispenser includes a single dispensing tube providing a single cavity. Alternatively, the dispensing tube terminates in a dispenser manifold that terminates in multiple cavities, such as two, three, or four cavities, up to eight cavities.

[0015] The reagent dispenser also includes a drive mechanism for rotating one end of the rotating arm about a hinge, with the longitudinal axis of the arm parallel to the base plate or parallel to the manifold plate. The drive mechanism can rotate the rotating arm to a predefined angle. The drive mechanism can include an electric drive, pneumatic drive, magnetic drive, or hydraulic drive. An example of an electric drive could be an electric motor, such as a stepper motor, and rotation can be controlled by changing the number of input pulses (steps). The drive mechanism may include a gear mechanism located between the electric drive and the hinge connecting the rotating arm to the manifold plate. When the drive mechanism rotates the rotating arm, the dispensing tube at the other end of the arm moves from a so-called parking position within the lift shaft to a position outside the lift shaft. The dispensing tube of the rotating arm rotates toward the position outside the lift shaft. When the other end of the rotating arm has rotated out of the lift shaft, a cavity, or multiple cavities in an alternative embodiment, can be used to dispense liquid reagents into laboratory glassware components. The rotation of the rotating arm is reversible, allowing the arm to rotate back toward the manifold plate or to the parking position.

[0016] The reagent dispenser may include a gear mechanism or gears for rotating a rotating arm and accelerating or decelerating the speed of an electric motor drive shaft. The gears include a first gear having a first drive shaft and first teeth at the circumference of a first gear. The gears also include a second gear having a hub with an opening for engaging a second drive shaft and second teeth at the circumference of a second gear. When one of the first or second drive shafts is driven to drive one of the first or second gears, the teeth of the second gear are configured to mesh with the teeth present on the circumference of the first gear. The second gear includes one or more elastic elements connecting the hub to the circumference of the second gear. The hub of the second gear may be elastically movable relative to the circumference of the second gear, or the circumference may be radially outwardly offset from the hub.

[0017] The hub of the second gear is surrounded by an inner edge, and one or more elastic elements are connected to the inner edge at one end and to the periphery of the second gear at the other end. The multiple elastic elements are selected from elastic dampers, springs, leg springs, compression springs, torsion springs, elastic spokes or rubber rings that connect the inner edge of the hub to the periphery of the second gear, or O-rings sandwiched between the hub and the periphery of the second gear.

[0018] In a preferred embodiment, the elastic element includes a plurality of spokes between the hub and the circumference of the second gear, and the plurality of spokes are radially oriented between the hub and the circumference, or the plurality of spokes are tangentially oriented between the hub and the circumference.

[0019] The second gear can be configured as a monolithic component manufactured using injection molding. This monolithic component may include both rigid and elastic materials and can be injection molded using two-component injection molding.

[0020] The second gear can be manufactured using three-dimensional (3-D) printing technology, and is preferably made of a single polymer material. The elastic element can be configured as a 3-D printed rib.

[0021] The second gear may be made of a polymer, such as polyamide, for example, polyamide-4,6; polyamide-6; polyamide-12 or polyamide-6,6.

[0022] The hub of the second gear can receive an insert that provides a second drive shaft for direct or indirect connection to the rotating arm. The insert can provide a channel for the distribution pipe.

[0023] The rotating arm can rotate at various angles, thus the dispensing tube can be used in numerous dispensing positions, allowing the rotating arm to adapt to different formats of laboratory glassware components, such as different formats of orifice plates. The rotating arm is coupled to a manifold plate configured to move vertically to contact the laboratory glassware component to apply pressure, and this vertical movement capability is available to the rotating arm when the manifold plate is not in contact with the laboratory glassware component, allowing the reagent dispenser to be precisely positioned above the laboratory glassware component without a separate lifting device. The reagent dispenser in this embodiment has a single chamber, which improves the accuracy of reagent dispensing volume because the liquid is pumped directly from a closed container into a single chamber. Pumping liquid reagents into a dispensing manifold with multiple openings fed by a single inlet can result in uneven liquid distribution among the multiple openings, or the dispensing manifold may require internal flow restrictors, such as precisely manufactured openings, to compensate for differences in the length of the liquid flow path between the openings within the manifold.

[0024] Optionally, the SPE device may include a drip protection device for selectively shielding the bottom surface of the (first) laboratory glassware component, thereby shielding the top surface of another (second) laboratory glassware component located below the (first) laboratory glassware component.

[0025] The reagent dispenser may include a liquid reagent supply unit comprising multiple liquid reagent containers, each containing a different liquid reagent. The liquid reagent supply unit also includes a pump, a pump manifold, valves for switching between liquid reagent containers, and tubing connecting the containers to a dispensing tube via the pump and pump manifold. The dispensing tube may terminate at a start-up station to flush the liquid reagent supply unit before switching to another liquid reagent. When the rotating arm is not rotated out of the manifold plate or is in the parked position, the dispensing tube may terminate at the start-up station before rotating to begin liquid dispensing.

[0026] The liquid reagents used in the liquid reagent supply unit are selected from conditioning liquids, washing liquids, or elution liquids. Each liquid reagent is used during a different stage of the solid-phase extraction process, and each liquid can be started up in the start-up station before being supplied to the laboratory glassware components.

[0027] The lifting well of a solid-phase extraction apparatus includes a first lifting device for vertically reciprocating a manifold plate relative to a substrate. The first lifting device is fixedly connected to the manifold plate such that only the manifold plate can be vertically moved by the first lifting device. The first lifting device may include a belt drive or a lead screw drive. A threaded nut moves up and down on the lead screw via relative rotation between the nut and the lead screw provided by the belt drive. Alternatively, multiple threaded nuts and lead screws are used to vertically move the manifold plate. Multiple nuts (or multiple lead screws) rotate simultaneously and synchronously, for example, via a common belt drive, enabling precise horizontal movement of the manifold plate.

[0028] The second lifting device is located vertically below the first lifting device. The second lifting device is located within a lift shaft defined by a manifold plate and a base plate. The first and second lifting devices may be vertically guided by guide posts, and the first and second lifting devices may have separate guide posts, or they may share the same guide posts. The second lifting device is vertically positioned between the manifold plate and the base plate. The second lifting device includes at least one retainer for receiving and holding laboratory glassware components. The retainer can receive and release the laboratory glassware components, allowing the laboratory glassware components to be temporarily inserted into the second lifting device. The second lifting device is configured to cause the laboratory glassware components to reciprocate vertically between the base plate and the manifold plate. The second lifting device may include a belt drive or a screw drive using a threaded nut, the threaded nut moving up and down on the screw via relative rotation between the nut and the screw. Alternatively, multiple threaded nuts and screws are used to vertically move the retainer for receiving and holding the laboratory glassware components. The multiple nuts (or multiple screws) for the second lifting device rotate simultaneously and synchronously, for example, via a common belt drive. The first and second lifting devices may be driven by two separate electric motors, allowing the two lifting devices to operate independently of each other.

[0029] Optionally, the second lifting device includes a drip protection device comprising a drip protection plate located between a holder for holding the laboratory glassware component and a substrate, the drip protection plate being oriented parallel to the substrate and capable of horizontal reciprocating motion, for selectively shielding the bottom surface of the laboratory glassware component or for selectively covering the top surface of another laboratory glassware component located below or about to move below the laboratory glassware component.

[0030] The solid-phase extraction apparatus includes sensors for detecting the horizontal position of the shuttle along the shuttle path, and sensors for detecting the vertical position of the manifold and / or the vertical position of the retainer of the second lifting device in the lift shaft. The manifold or reagent dispenser includes sensors for detecting the rotation angle of the rotating arm relative to the manifold or relative to the axis defined by the shuttle path.

[0031] The detected horizontal or vertical position and the detected rotation angle are used to control the solid phase extraction (SPE) device using a control unit with control circuitry, which is an integral part of the SPE device. Alternatively, the SPE device includes a transceiver unit, and the sensor data can be transmitted to external devices such as computers, computer networks, or cloud solutions, and commands for controlling the SPE device can be received from external devices.

[0032] Laboratory glassware components can be filter plates or collection plates, comprising multiple openings extending downward from the top surface of the filter plate (or collection plate), the openings being oriented along a pattern on the top surface, and a filter positioned in each opening below a space available for applying liquid reagents on top of the filter. Collection plates or filter plates may also be referred to as collection racks or filter holders. The openings can be arranged according to standardized ANSI / SLAS patterns. Common patterns are, for example, filter plates with 96, 24, 12, or 6 holes. Using a rotating arm with a single cavity, individual openings in the row or column of openings of a filter plate (or collection plate) can be easily filled by rotating the rotating arm and / or moving the shuttle carrying the filter plate before turning to the next row or column in the filter plate. Individual holes can each be filled with a different filling volume, and reagent dispensers with rotating arms provide highly flexible liquid filling options.

[0033] The control unit guides and controls the position of the filter plate (or collection plate) along the shuttle path, the vertical position of the manifold plate, and the rotation of the rotating arm outside the lift shaft, such that the distal end of the distribution tube is centered relative to one of the multiple openings of the filter plate. The filter plate or collection plate may move along the shuttle path and / or the rotating arm may rotate to fill subsequent openings in the filter plate, and this may be repeated until the desired openings, which may be randomly distributed on the filter plate (or collection plate), are filled with reagent liquid.

[0034] The control unit of the solid-phase extraction apparatus guides and controls the liquid reagent supply unit, causing a predetermined volume of reagent liquid to be pumped through the chamber of the rotating arm into the opening of the filter plate. The control unit can guide different filling volumes to different orifices. Once the desired orifice is filled with reagent liquid, the rotating arm rotates back to the parking position, the shuttle with the filter plate moves into the lift shaft, and can raise the filter plate and / or lower the manifold plate to provide contact and airtight fit. Pressure is then applied to the manifold and the orifice, forcing the reagent liquid through the filter.

[0035] Solid-phase extraction apparatus may also include an evaporation unit for evaporating liquid collected from a filter plate. The collected liquid may be eluent collected in a collection plate after pressurizing the filter with eluent. The eluent may require further concentration using the evaporation unit for analytical testing. The evaporation unit may be positioned along a shuttle path, for example, the shuttle may initially move from a position outside the lift shaft into the lift shaft defined by the vertical position of the manifold plate. The shuttle may move further in the same direction, leaving the lift shaft and entering the evaporation unit. Alternatively, the evaporation unit moves toward the position of the shuttle carrying the collection plate. The evaporation unit may include an evaporation manifold having multiple evaporation sleeves extending downward from the evaporation manifold and oriented toward the solid-phase extraction apparatus substrate. The evaporation sleeves may be lowered into openings in the collection plate using a lifting device, and hot air or hot nitrogen may be blown from a gas cylinder through the manifold to each evaporation sleeve. Alternatively, a compressor or nitrogen generator may be used. Eluent present below the opening of each evaporation sleeve evaporates to concentrate the substance for analytical measurement. SPE equipment can also be used to replace a liquid used for elution that is not suitable for certain analytical measurements with another liquid or solvent that is suitable for those measurements. After evaporating the liquid, the sample can be redissolved in another solvent suitable for those analytical measurements, such as in mass spectrometry.

[0036] A second aspect of the invention relates to a system comprising general-purpose laboratory automation equipment and solid-phase extraction (SPE) equipment. The laboratory automation equipment includes a worktable with a working surface and a first transfer mechanism including a gripper configured to grip, transfer, and release laboratory glassware components, such as filter plates or collection plates, to different positions on the worktable. The equipment includes a second transfer mechanism with a pipette tip configured to aspirate sample liquid from a sample laboratory glassware component holding sample liquid and / or dispense sample liquid into another laboratory glassware component, such as a filter plate or collection plate. The sample liquid is a liquid containing a chemical or biological component to be tested. The laboratory automation equipment also includes a microcontroller for controlling the first and second transfer mechanisms and the liquid handling through the pipette tip. Optionally, the microcontroller may assist or replace the control unit of the SPE equipment.

[0037] The substrate of the solid-phase extraction (SPE) device is fixed in a position on the workbench of the laboratory automation equipment, allowing a first transfer mechanism to place the filter plate onto the shuttle, or a second transfer mechanism to dispense sample liquid into one of the multiple openings of the filter plate, located outside the lift shaft. The substrate is oriented parallel to the workbench. The liquid supply unit of the SPE device may not be located on the workbench to achieve a space-saving arrangement within the system, allowing the workbench to be used for other operations or analytical measurement tools such as microplate readers. The liquid supply unit may be located below the workbench of the laboratory automation equipment or next to the external workbench of the laboratory automation equipment.

[0038] Pipette tips in laboratory automation equipment may include multiple pipette tips or adapters for receiving disposable pipette tips, such as adapters for four or eight pipette tips. Alternatively, the adapter may include a fixed pipette tip. Pipette tips in laboratory automation equipment can be dedicated to handling sample liquids, while other reagent liquids can be aspirated and dispensed using the liquid reagent dispenser of a solid-phase extraction device. Using a liquid reagent dispenser provides flexibility for laboratory automation systems because the pipette tip can be used for other operations within the laboratory automation equipment and reduces the need for disposable pipette tips. Furthermore, reagent dispensing speed can be increased using a reagent dispenser because the pipette tip does not need to move back and forth to different positions for dispensing reagents. Reagent liquids do not need to be stored in open containers on the working surface of the laboratory automation equipment, which increases the available space on the working surface and reduces evaporation, as closed containers can be used to store reagents.

[0039] A third aspect of the present invention relates to a solid-phase extraction method using a system comprising laboratory automation equipment and solid-phase extraction equipment, the method comprising the following steps: - At a location outside the elevator shaft of the solid phase extraction (SPE) apparatus, the stack of filter plates and waste trays is presented on the shuttle. Presenting the stack may include sub-steps such as clamping the waste tray from the workbench of the laboratory automation equipment, moving the clamp to the location of the SPE apparatus shuttle using a first transfer mechanism, and releasing the clamp. This process is repeated to place the filter plates on the waste tray. Optionally, spacers are placed between laboratory glassware components or nozzle separators, which will be explained in further detail below. As another option, the shuttle itself includes the waste tray, so it is not necessary to place it on the shuttle in a separate step.

[0040] - Using a pipette tip of the second transfer mechanism of a laboratory automation device, sample liquid is loaded into multiple openings of a filter plate. The pipette tip may include an adapter for gripping multiple disposable pipette tips placed in a storage unit on the worktable. The loading step involves using the second transfer mechanism to move the pipette tip with the pipette tips to the location where the sample liquid is stored in the sample container, and then aspirating the sample liquid. The pipette tip moves to the location of the stack of filter plates and dispenses the sample liquid into the openings of the filter plates.

[0041] The filter plate may need to be conditioned before the sample liquid is dispensed into the opening. Conditioning involves filling the opening of the filter plate with conditioning liquid, followed by applying pressure using a manifold plate. The conditioning liquid can be dispensed into the opening of the filter plate using a pipette tip from a laboratory automation device, or more preferably, using a reagent dispenser from a solid-phase extraction device.

[0042] - The shuttle is moved along its path into the elevator shaft. The shuttle is moved by a shuttle transfer mechanism including an electric drive. The electric drive can use a belt or lead screw mechanism to move the shuttle.

[0043] - The manifold plate of the solid-phase extraction apparatus is lowered using a first lifting device to contact the top surface of the filter plate and create a tight fit between the filter plate and the manifold plate. Pressure is applied to the filter plate via the manifold plate to force the liquid sample through the filter plate into the waste tray. Alternatively, instead of moving the manifold plate vertically, a second lifting device is used to lift the stack of the filter plate and waste tray to contact the manifold plate. Or, as yet another alternative, the manifold plate is lowered and the stack is lifted simultaneously to create an airtight fit between the filter plate and the manifold plate. The waste tray integrated into the shuttle will not be lifted.

[0044] - Subsequently, the manifold plate is lifted using the first lifting device so that there is no contact between the top surface of the filter plate and the bottom surface of the manifold plate. In an alternative embodiment, either the filter plate is lowered, or both the filter plate and the manifold plate are moved using the first and second lifting devices.

[0045] - The stacked shuttle with filter plates and waste trays is moved along the shuttle path from a position inside the elevator shaft toward a position outside the elevator shaft to an intermediate position, where the opening of the filter plates can be covered by a perimeter defined by a rotating arm.

[0046] - Using a reagent dispenser in a solid-phase extraction device, multiple openings in a filter plate are filled or loaded with washing liquid. The dispensing tube is moved out of the lift-up well by rotating the rotating arm, dispensing the washing liquid into the openings in the filter plate. Access to subsequent openings is achieved by moving the shuttle and / or further rotating the rotating arm. The fluid lines of the liquid reagent supply unit are switched to a container filled with washing liquid using a valve system. Before dispensing the washing liquid, even before the rotating arm rotates and pumps fluid into the filter plate, the reagent dispenser can be started at the start-up station because it has previously been used to dispense conditioning liquid. The started liquid is collected from the start-up tray via a discharge port into a waste collector.

[0047] - This causes the stacked shuttle, including the filter plates and waste trays, to move along the shuttle path to the elevator shaft.

[0048] - The manifold plate of the solid-phase extraction apparatus is lowered using a first lifting device to create a tight fit between the filter plate and the manifold plate, and pressure is applied to the manifold plate to force the washing liquid through the filter plate into the waste tray. In an alternative embodiment, either the stack of filter plates is lifted, or both the manifold plate and the stack with filter plates are moved to create an airtight fit.

[0049] - By raising the manifold plate and / or lowering the filter plate, the filter plate is decoupled from the manifold plate.

[0050] - The filter plate is lifted from the waste tray by a second lifting device with a retainer, thereby destabilizing the filter plate from the waste tray. Alternatively, the waste tray is included in the shuttle, and the second lifting device simply lifts the filter plate from the shuttle.

[0051] - As an optional feature, the method may include the step of shielding the bottom surface of the filter plate by moving the anti-drip protection plate below the filter plate. The anti-drip protection plate is part of the anti-drip protection device, which will be explained in further detail below.

[0052] - Move the shuttle with the waste tray along the shuttle path to a position outside the elevator shaft.

[0053] - The collection plate is stacked on top of the waste tray using the gripper of the first transfer mechanism. Alternatively, the collection plate is stacked directly onto the shuttle (which includes the waste tray). The collection plate may be located on the workbench of the laboratory automation equipment, and the gripper of the first transfer mechanism can grip, transfer, and release the collection plate to place it on top of the waste tray.

[0054] - Move the stacked shuttle, including the filter plate and waste tray, along the shuttle path into the lift shaft. When the collection plate is moved into the lift shaft, the drip guard plate may still be positioned below the filter plate, but retract the drip guard plate before starting the next step: lower the second lifting device.

[0055] - Lower the second lifting device that holds the filter plates to stack the filter plates on top of the collection plate.

[0056] - Move the shuttle (or shuttle including the waste tray) with the filter plate, collection plate and waste tray along the shuttle path toward the outside of the elevator shaft to the middle position covered by the rotating arm.

[0057] - The reagent dispenser is used to load the eluent into multiple openings of the filter plate. Rotation moves the dispensing tube out of the lift well and dispenses the eluent into the openings in the filter plate. Access to subsequent openings is achieved by moving the shuttle and / or further rotating the rotating arm. The fluid lines of the liquid reagent supply unit are switched to the container containing the eluent using a valve system. The reagent dispenser can be started at the start-up station before dispensing the eluent into the filter plate, as it has previously been used to apply the washing liquid.

[0058] - This causes the stacked shuttle, including the filter plate, collection plate, and waste tray, to move along the shuttle path into the elevator shaft.

[0059] - The first lifting device lowers the manifold plate of the solid-phase extraction apparatus to form a tight fit between the top surface of the filter plate and the bottom surface of the manifold plate, and applies pressure to the manifold plate to force the eluent through the filter plate into the collection plate. Alternatively, the second lifting device lifts the stack toward the manifold plate, or alternatively, both the first and second lifting devices are moved to bring the stack and the manifold plate closer together. The manifold plate is then lifted, and the shuttle is moved to a position outside the elevator shaft, whereby the clamps of the first transfer mechanism are used to destacking the stack of filter plates, collection plates, and waste trays.

[0060] - Optionally, the collecting plate can be moved to the evaporation unit to concentrate the eluent.

[0061] The concentrated or purified sample collected in the plate can now be used for further processing steps and / or analytical tests.

[0062] Another aspect of the invention relates to a computer program for extracting or concentrating substances from a sample liquid, which, when executed by a processor integrated into a system including a solid-phase extraction device and a laboratory automation device, is adapted to perform the above-described method steps. The computer program may be executed in an embedded computing device, such as a control unit of the solid-phase extraction device or a microcontroller of the laboratory automation device, or in a personal computer (PC) that may be interconnected with the laboratory automation device and / or the solid-phase extraction device.

[0063] On the other hand, it relates to computer-readable media in which such computer programs are stored. Computer-readable media can be floppy disks, hard disks, USB (Universal Serial Bus) storage devices, RAM (Random Access Memory), ROM (Read-Only Memory), EPROM (Erasable Programmable Read-Only Memory), or FLASH memory. Computer-readable media can also be data communication networks, such as the Internet and / or cloud storage, which allow for the download of program code. Typically, computer-readable media can be non-transitory or transient.

[0064] On the other hand, the invention relates to solid-phase extraction (SPE) equipment, which also includes the aforementioned anti-drip protection device. The SPE equipment includes a substrate and a manifold plate oriented parallel to and vertically positioned above the substrate to define a lift shaft. The manifold plate is configured to provide positive pressure to the laboratory glassware component when it contacts the manifold plate. The equipment includes a second lifting device positioned below the manifold plate in the lift shaft, the second lifting device having a retainer for receiving and holding the laboratory glassware component; the second lifting device is configured to allow the laboratory glassware component to reciprocate vertically between the substrate and the manifold plate. The equipment includes an anti-drip protection device having an anti-drip protection plate located between the retainer and the substrate, the anti-drip protection plate being oriented parallel to the substrate and horizontally reciprocating for selectively shielding the bottom surface of the laboratory glassware component placed on the second lifting device. The retainer for receiving and holding the laboratory glassware component includes two horizontally spaced parallel beams oriented parallel to the substrate for receiving the laboratory glassware component between the two parallel beams, the two parallel beams being configured to move up and down simultaneously in the lift shaft. The drip-proof protective plate can be a sheet of metal or a sheet made of polymer material. The drip-proof protective plate may include multiple segments that are retractably movable relative to each other when shielding laboratory glassware components. Alternatively, the drip-proof protective plate may include multiple hinges, such as movable hinges, such that the segments can be stacked when the drip-proof protective plate is retracted. The drip-proof protective plate may be coated with a hydrophobic coating.

[0065] The anti-drip protection device may be an integral part of the second lifting device and may move vertically together with the second lifting device, and the anti-drip protection plate may reciprocate between two parallel beams. Each of the two parallel beams may include a horizontally oriented guide groove for holding and guiding the two parallel edges of the anti-drip protection plate.

[0066] The drip protection device for SPE equipment includes an electrically driven mechanism comprising an electric motor and a linkage system or gear arrangement for reciprocating the drip protection plate between two parallel beams between a shielded position for shielding the bottom surface of laboratory glassware components and an unshielded position for not shielding the bottom surface. The linkage system may include another rotating arm, distinct from the rotating arm used for the liquid dispenser, with one end connected to the rotating shaft of the electric motor and the other end including a guide pin that engages a linear guide groove in the drip protection plate. The guide groove engaging the guide pin is preferably oriented perpendicular to the beams.

[0067] Each of the two parallel beams of the second lifting device includes a first chamfer, and the two first chamfers are oriented along the beam axis of each beam, and the two planes of the two chamfers are divergently oriented relative to the manifold plate, for guiding and centering the laboratory vessel components when the two parallel beams move upward simultaneously in the elevator shaft to collect laboratory vessel components, or when the laboratory vessel components descend between the two beams.

[0068] Each of the two parallel beams of the second lifting device includes a second chamfer, and the two second chamfers are positioned on the front surface of the beams and diverging from each other to provide an inlet section for guiding and aligning the laboratory vessel components between the beams when the laboratory vessel components move horizontally into the second lifting device.

[0069] Laboratory glassware components may be filter plates, and when the collection plate is positioned below the nozzle of the filter plate or moved to the position below the nozzle of the filter plate via a shuttle device, a drip-proof protection device with a drip-proof protective plate selectively shields the bottom surface, including the nozzle opening. The drip-proof protective plate may be placed between the bottom surface of the filter plate and the top surface of the collection plate, thereby shielding the top surface of the collection plate.

[0070] The solid-phase extraction (SPE) apparatus also includes sensors for detecting the horizontal position of the shuttle along the shuttle path, or the horizontal position of the filter plate or collecting plate within the lift shaft. The apparatus may also include sensors for detecting the vertical position of a second lifting device retainer holding the filter plate within the lift shaft, and sensors for detecting the horizontal position of the anti-drip protection plate. The control unit for the SPE apparatus uses the detected horizontal or vertical position, including the position of the anti-drip protection plate of the anti-drip protection device, to control the solid-phase extraction apparatus. The anti-drip protection device can be used in the aforementioned solid-phase extraction method.

[0071] Another aspect of this disclosure (which is not part of this invention) relates to a nozzle separator or a system comprising a nozzle separator and a filter plate. A nozzle separator, also known as a column barrier, provides a liquid protection barrier between columns in a laboratory glassware component. During solid-phase extraction, a sample liquid or reagent liquid is forced through a filter using positive pressure. The liquid exits the filter plate through nozzles and may be ejected from the nozzle openings. Reagent liquids collect in a waste tray and may splash onto the nozzles. Splashes and splashes of liquid may adhere to the nozzle openings and cause cross-contamination of the filtered liquid in subsequent filtration steps. A further object of this disclosure is to provide a system comprising a filter plate and a nozzle separator that provides a solution to reduce the risk of cross-contamination between fluids filtered through different nozzles in a filter plate.

[0072] A system for solid-phase extraction includes an SPE filter plate and a nozzle separator. The SPE filter plate comprises multiple cylinders or columns, each defining a longitudinal axis oriented parallel to each other, and each having an opening as a liquid inlet and a nozzle opposite the opening as a liquid outlet. The cylinders may be formed as multiple syringes. A filter is located between the opening and the nozzle and is configured to extract chemical or biological components from the liquid. The filter is a solid material and may be a porous package. The openings and nozzles are positioned in a plane perpendicular to the longitudinal axis according to a repeating pattern. The repeating pattern may be a standardized pattern according to ANSI / SLAS standards, such as a 24-well plate format. The nozzle separator includes a nozzle separation plate having multiple openings or channels separated from each other, and the centers of the multiple openings are positioned according to the same repeating pattern as the nozzles. The nozzle separation plate is configured to stack below the SPE filter plate, whereby each nozzle is received or may be received in one of the multiple openings to separate each of the multiple nozzles from each other. The SPE filter plate is at least partially protected from fluid contamination, whether from splashes or droplets from other nozzles, by a nozzle protection plate on the bottom surface between the nozzles and / or the nozzle openings.

[0073] The SPE filter plate may also include a frame for holding a plurality of cylinders or columns, and the frame includes a base plate and a top plate oriented parallel to each other. The base plate and the top plate are connected by connecting rods oriented parallel to a longitudinal axis, thereby axially spaced the top plate from the base plate. The cylinders are clamped between the base plate and the top plate of the frame. The frame may have retainers for holding the frame and thus the filter plate. The retainers may be held by a gripper of a first transfer mechanism of a laboratory automation device.

[0074] The cylindrical nozzle extends through the bottom surface of the frame base plate, and the cylindrical opening extends through the top plate of the frame. The opening allows a pipette tip to dispense liquid samples into the opening on top of the filter. When the nozzle separator is not in use, the bottom surface of the base plate and / or the nozzle may be exposed to splash and / or splatter droplets. Each of the plurality of cylinders may include a flange surrounding the opening, and the flange abuts against the top surface of the frame top plate.

[0075] The nozzle separator is configured to be positioned below the bottom surface of the base plate, and the nozzle extends at least partially into an opening or channel in the nozzle separator. The nozzle separator at least partially covers the distal end of the nozzle or the sidewall of the nozzle, and the section of the nozzle separator between the openings protects the bottom surface of the frame base plate from contamination that could affect further processing steps. The channel of the nozzle separator may include a receiving section for receiving the nozzle end and a liquid guiding section away from the receiving section. The receiving section may include a conical or cup-shaped shape. The liquid guiding section is connected to the receiving section and has an internal dimension smaller than that of the receiving section. The liquid guiding section may be directly connected to the conical receiving section. The end of the liquid guiding section is located at the bottom surface of the nozzle separator and may include circular or faceted sections. The surface of the nozzle separator may be coated with a hydrophobic coating.

[0076] Nozzle separation plates can be disposable laboratory glassware products made of metal sheets or polymer materials. Metal sheets can be stamped to provide openings. Nozzle separation plates made of polymer materials can be injection molded from thermoplastic polymers. Polymers can be, for example, polypropylene, polyethylene, polystyrene, and polycarbonate.

[0077] The system may also include a nozzle separator spacer, and the nozzle separator plate is configured to be positioned in a stack between the filter plate and the nozzle separator spacer. The nozzle separator spacer may be a reusable laboratory glassware component. A waste tray may be stacked below the nozzle separator spacer.

[0078] Positive pressure can be applied to the filter plate using a manifold plate through openings in multiple cylinders.

[0079] These and other aspects of the invention will become apparent and will be illustrated with reference to the embodiments described below. Attached Figure Description

[0080] Embodiments of the invention will be described in more detail with reference to the accompanying drawings, in which: Figure 1 : A three-dimensional view of a solid-phase extraction device. Figure 2 The system includes SPE equipment, waste collectors, distributor control boxes, and evaporator control boxes. Figure 3 This system includes laboratory automation equipment, SPE equipment, and liquid reagent supply units located next to the laboratory automation equipment. Figure 4 This includes a system comprising laboratory automation equipment, SPE equipment, and a liquid reagent supply unit located beneath the laboratory automation equipment workbench. Figure 5 A 3D view of an SPE (Self-Purpose Equipment) unit without a cover and showing the lifting device. Figure 6A 3D view of an SPE (Self-Purpose Equipment) unit without a cover and showing the lifting device. Figure 7 A 3D view of the SPE device with the rotating arm of the reagent dispenser in its parked position, without the cap. Figure 8 Details of the reagent dispenser with a rotating arm in the parked position. Figure 9 A 3D view of the SPE device without a cap, showing the rotating arm of the reagent dispenser rotated from the parking position to the dispensing position. Figure 10 Details of a reagent dispenser with a rotating arm that rotates from the parking position to the dispensing position. Figure 11 Cross-sectional view of a reagent dispenser with a rotating arm and starter station. Figure 12 The rotating arm presents a top view showing the range of motion of the distribution tube on the 96-hole plate. Figure 13 Gear mechanism used to drive the rotating arm Figure 14 Top view of the gear mechanism. Figure 15 Alternative embodiment of the second gear, Figure 16 Overview diagram of the anti-drip protection device for the second lifting device. Figure 17 a and 17b: Details of the beam with a second lifting device featuring a drip-proof protective plate. Figure 18 : An SPE device that presents the evaporator unit. Figure 19 : An SPE device that presents the evaporator unit. Figure 20 : Exploded view of the pressure manifold plate Figure 21 : An assembly for nozzle separation plates and spacers in a 96-orifice plate format. Figure 22 Filter plate or filter frame (24-hole plate format) with a nozzle separation plate located below the filter plate. Figure 23 : A cross-sectional view of the filter plates (96-hole plate format) stacked on top of the spacers holding the nozzle separator. Figure 24 The SPE equipment has its filter plate positioned outside the elevator shaft along the shuttle path. Figure 25 The SPE equipment has a filter plate positioned below the manifold plate in the lift shaft. The bottom surface of the filter plate is shielded by an anti-drip protector. The collection plate is located outside the lift shaft along the shuttle path. Figure 26 : A schematic diagram of a system including laboratory automation equipment and SPE equipment, wherein a waste tray is placed on a shuttle located outside the elevator shaft. Figure 27 : Figure 26 A schematic diagram of the system shows that the gripper of the first transfer mechanism stacks the filter plates on top of the waste tray. Figure 28 : Figure 26 A schematic diagram of the system shows that the shuttle moves the stack to the position where the rotary distributor can dispense regulating fluid to the filter plates. Figure 29 : Figure 26 A schematic diagram of the system shows the shuttle moving into the elevator shaft, where the first lifting device lowers the manifold plate; pressure is then applied via the manifold plate. Figure 30 : Figure 26 The system diagram shows the shuttle moving to a position outside the elevator shaft, where a second transfer mechanism draws up the sample liquid and distributes it into the filter plate. Figure 31 : Figure 26 A schematic diagram of the system shows the shuttle moving into the elevator shaft. Figure 32 : Figure 26 A schematic diagram of the system shows the use of a first lifting device to lower the manifold plate and apply pressure via the manifold plate. Figure 33 : Figure 26 A schematic diagram of the system shows the shuttle moving to the central dispensing position to distribute the washing liquid into the filter plates. Figure 34 : Figure 26 A schematic diagram of the system shows the shuttle moving into the elevator shaft, using the first lifting device to lower the manifold plate; pressure is then applied to the filter plate using the manifold plate. Figure 35 : Figure 26 A schematic diagram of the system shows that the second lifting device lifts the filter plate from the waste tray, and an optional anti-drip protective plate shields the bottom surface of the filter plate. Figure 36 : Figure 26 A schematic diagram of the system shows the shuttle moving to a position outside the elevator shaft and collecting the collection plate from the first transfer mechanism. Figure 37 : Figure 26 A schematic diagram of the system shows a shuttle with stacked waste trays and collection plates moving into the elevator shaft. Figure 38 : Figure 26 The system diagram shows stacked shuttles with waste trays and collection plates moving into the lift shaft, and an optional drip-proof protective plate retracting from the bottom surface of the filter plate. Figure 39 : Figure 26 A schematic diagram of the system shows the second lifting device being lowered to stack the filter plates on top of the collection plate. Figure 40 : Figure 26 A schematic diagram of the system shows the shuttle moving to the intermediate distribution position; the first lifting device is lowered and the rotating arm is rotated to distribute the eluent into the filter plates. Figure 41 : Figure 26 A schematic diagram of the system shows the shuttle moving into the elevator shaft, lowering the manifold plate via the first lifting device, and applying pressure to collect the eluent in the collection plate. Figure 42 : Figure 26 A schematic diagram of the system shows the shuttle moving to a position outside the elevator shaft. The first transfer mechanism removes the filter plate from the collection plate, which is now available for further processing. Figure 43 : Figure 26 A schematic diagram of the system shows a stacked shuttle with a waste tray and a filter plate. Optionally, a nozzle protector is positioned between the filter plate and the waste tray. Detailed Implementation

[0081] A three-dimensional view of solid phase extraction device 1 is presented. Figure 1 The SPE device includes a shuttle 2 movable along a shuttle path 4. Laboratory glassware components 3 are positioned on the shuttle, and the shuttle can be electrically driven to move along the shuttle path 4 into an opening 5 in the SPE device. The opening 5 defines an entrance for a lift shaft, which will be explained below. The SPE device includes a base plate 11, which provides a platform for mounting components of the SPE device, which are closed by a cover 19. A system including the SPE device 1, a waste collector 6, a dispenser control box 7, an evaporator control box 8, and a liquid reagent supply unit 10 is shown. Figure 2 The reagent liquid used during solid-phase extraction is collected in waste collector 6 via a pipeline system, and the liquid reagent can be pumped from supply unit 10 to reagent dispenser using dispenser control box 8. The solid-phase extraction apparatus optionally includes an evaporation unit for evaporating and concentrating the extracted sample liquid, and this evaporation unit is controlled by evaporator control box 8.

[0082] The system, including laboratory automation equipment 9, SPE equipment 1, and liquid reagent supply unit 10, is shown in Figure 3The liquid reagent supply unit 10 and waste collector 6 are located adjacent to the laboratory automation equipment 9. The laboratory automation equipment 9 includes a working surface 12, and the base plate 11 of the SPE device 1 is mounted on the working surface 12 of the laboratory automation equipment 9. The laboratory automation equipment 9 includes a first transfer mechanism 13 with a robotic arm for moving a gripper 15 to different positions on the working surface 12 and for controlling the gripper 15 to grip and release laboratory glassware components located on the working surface 12 or on the shuttle 2 of the SPE device 1. The laboratory automation equipment 9 also includes a second transfer mechanism 14 with a robotic arm for moving a pipette tip 16 to different positions on the working surface 12. The pipette tip 16 includes multiple adapters for releasably holding multiple pipette tips 17. The pipette tip 16 is configured to aspirate or dispense liquid using the pipette tips 17.

[0083] Another embodiment of a system including laboratory automation equipment 9 and SPE equipment 1, with liquid reagent supply unit 10 located below the working surface 12 of laboratory automation equipment 9, is shown in Figure 4 Waste collector 6 is located below the working surface 12. The liquid reagent supply unit 10 and waste collector 6 are placed beside the working surface. Figure 3 or below the working surface ( Figure 4 This provides sufficient usable space on the working surface 12 for other laboratory glassware components or analytical measuring equipment. The liquid supply unit 10 includes multiple liquid reagent containers 18, which can be filled with reagents such as conditioning liquids, washing liquids, or elution liquids to supply the SPE extraction process. The containers 18 are fluidly connected to the SPE equipment via tubing and a pump system including valves for switching between different reagent containers.

[0084] The SPE device with cover 19 removed is shown. Figure 5 and Figure 6The diagram presents a basic drive mechanism for a first lifting device 22 configured for vertical movement of a manifold plate and a second lifting device 23 located below the first lifting device 22. The second lifting device 23 is configured to lift laboratory glassware components that can be placed or moved into the second lifting device 23. The SPE device includes four guide posts 20 connecting a top cover plate 21 to a base plate 11. The top cover plate 21 and the base plate 11 are oriented parallel to each other. The first lifting device 22 includes a retaining plate 29 for holding the manifold plate, which applies positive pressure to laboratory glassware components such as filter plates. The first lifting device 22 can move the retaining plate 29 up and down between the top cover plate 21 and the base plate 11, thereby defining a lift shaft 43. The first lifting device 22 includes an electric motor 25 for driving two threaded rods 32. A drive pulley 30 is coupled to the drive shaft of the electric motor 25 and simultaneously drives the two threaded rods 32 via a toothed drive belt 26. The threaded rod 32 engages with a threaded insert 34, which is part of or connected to the retaining plate 29, thereby providing screw drive for the first lifting device 22. The retaining plate 29 includes four sleeve-shaped bushings 36 surrounding four guide posts 20 for guiding the retaining plate 29 during vertical movement, thereby holding the retaining plate horizontally oriented relative to the base plate 11. See [reference needed] Figure 6 .

[0085] The second lifting device 23 includes two beams 38 oriented parallel to each other, and each beam includes a longitudinal groove that provides a guide for the drip-proof protective plate, which will be described in further detail below. Each of the two beams 38 includes two bushings 37 surrounding the guide post 20 for axially guiding the two beams in the vertical direction within the lift shaft 43, see [link to relevant documentation]. Figure 6 The second lifting device 23 includes an electric motor 26 for driving two threaded rods 33. A drive pulley 31 is coupled to the drive shaft of the electric motor 26 and simultaneously drives the two threaded rods 33 via a toothed drive belt 28. The threaded rods 33 engage threaded inserts 35, which are part of or connected to beams 38, thereby providing screw drive for the two beams of the second lifting device 23.

[0086] The shuttle 2 provides a platform for placing laboratory glassware components, and this platform is oriented parallel to the substrate 11. The shuttle 2 includes a top surface designed to engage the laboratory glassware component 3, such that the laboratory glassware component 3 is not movable in the xy plane (parallel to the substrate 11) due to form-fitting engagement. The laboratory glassware component can be lifted from or placed onto the shuttle 2 along a z-axis perpendicular to the substrate 11. The shuttle 2 can move horizontally along its length in the plane of the substrate, defining a shuttle path 4 for entering the elevator shaft 43 from a position 44 outside the elevator shaft. The shuttle is moved by an electric shuttle drive (driver) including an electric motor 24. The first lifting device 22, the second lifting device 23, and the electric shuttle drive include sensors for determining the position of the manifold holder 29, the vertical position of the beam 38, or the position of the shuttle 2 on the shuttle path 4. The sensors may be included in the electric motor, such as an encoder for counting the number of steps of a stepper motor or the number of revolutions of a DC motor. The number of steps or revolutions may correspond to the defined position of the retainer 29 or the beam 38. Alternatively, the sensor is separate from the electric motor, such as a linear position sensor.

[0087] SPE device 1 is controlled by control circuitry 39, which includes a printed circuit board 40 (PCB) that provides a platform for electronic components, switches, or integrated circuits. Figure 6 The control circuitry 39 may include a connector PCB 42 for connection to another microcontroller, such as a personal computer, user interface, or laboratory automation equipment. The connector PCB 42 is connected to the control circuitry 39 using a strip conductor 45. The connector PCB 42 may also include a transmitter / receiver for wireless connection to another device, such as a personal computer or smartphone. Alternatively, the transmitter / receiver may feed or receive data from a cloud solution.

[0088] The SPE equipment includes a steam vent 41 that directs steam from the lift shaft 43 to the outside of the SPE equipment, as the vent 41 is directed through a passage in the cover 19.

[0089] SPE device 1 includes a reagent dispenser 46, which includes a rotating arm 47, an electric motor 48 for rotating the rotating arm 47, and a starter station 49, such as Figure 7As shown. The reagent dispenser 46 may be an integral part of the retaining plate 29, or mounted to the retaining plate 29, thus allowing up-and-down movement in the z-direction using the first lifting device 22. The reagent dispenser 46 may be fixedly mounted to the retaining plate 29 or releasably connected to the retaining plate 29. The reagent dispenser 46 may be configured as an optional additional unit of the retaining plate 29, which is configured to receive the additional unit. The starting station 49 includes a starting tray 51 for receiving liquid to be started, such as elution liquid if washing liquid has been previously dispensed using the reagent dispenser 46. The starting station 49 also includes a discharge port 50 for collecting the started liquid into the waste collector 6. The discharge port 50 is configured as an assembly of coaxially arranged tubes, one end of which is connected to the starting tray 51 and the other end to the base plate 11. The tubes of the discharge port 50 may be stacked relative to each other so that the length of the discharge port 50 adapts to a specific z-position of the retaining plate 29.

[0090] Details of the reagent dispenser 46 with the rotating arm 47 in the parked position are shown. Figure 8 The rotating arm 47 includes a first end 57 and a second end 58, defining an axis parallel to the plane of the retaining plate 29 between the two ends. In the parked position, the axis of the rotating arm is perpendicular to the axis defined by the shuttle path 4. When the rotating arm is in the parked or unrotated position (zero rotation angle), the second end 58 of the rotating arm 47 is located in a cutout 61 in the retaining plate 29. If the retaining plate does not have a cutout 61, the rotating arm will be located within a rectangular profile defined by the retaining plate (including the manifold plate), and thus the second end 58 will be within a lift well defined between the retaining plate 29 and the base plate 11. The first end 57 of the rotating arm 47 is connected to the retaining plate 29 via a hinge 53, allowing the rotating arm or the first end 57 of the rotating arm to rotate about the hinge 53. An electric motor 48 drives and controls the rotation angle of the rotating arm 47. A dispensing tube 52 is guided by the rotating arm to a bushing 56 located at the second end 58 of the rotating arm. The dispensing tube 52 is fluidly connected to or can be connected to the liquid reagent supply unit 10.

[0091] An overview of the SPE equipment, with the rotating arm 47 rotating through a rotation angle to a position outside the elevator shaft (or designated position), is shown below. Figure 9 Detailed views are shown below. Figure 10 The electric motor 48 has rotated the rotating arm 47 out of its parking position. Figure 8 This causes the second end 58 to protrude outward from the retaining plate 29.

[0092] A cross-sectional view of the rotating arm 47 and the starting station 49 is shown in Figure 11A hinge 53 connects an electric motor 48 to a rotating arm 47, and the hinge may include a gear mechanism for accelerating or decelerating the rotational speed of the electric motor drive shaft. The drive shaft of the electric motor may include a pinion that engages with a gear connected to a first end 57 of the rotating arm 47. The first end 57 of the rotating arm 47 is connected to a retaining plate 29 via a bearing 54 and may also include a channel 62 for a dispensing tube 52. The dispensing tube 52 is guided through a bushing 56 located at a second end 58 of the rotating arm, such that the end section of the dispensing tube 52 is oriented along the z-axis. The end of the dispensing tube 52 provides a cavity 55 for dispensing reagent liquid. When the rotating arm is in the parked position, the reagent liquid is dispensed into a starter tray 51 of the starter station 49, such that the started liquid can be collected into a waste collector 6 via a drain port 50. In another embodiment, the dispensing tube 52 terminates in a dispenser manifold, such that multiple cavities are available at the second end 58 of the rotating arm 47. Thus, liquid reagent can be dispensed at once in, for example, two or three holes.

[0093] A schematic diagram of the projection of the rotating arm 47 onto the 96-hole plate 59 is shown below. Figure 12 The orifice plate 59 includes orifices 60, and the rotating arm 47 is rotatable about hinge 53, allowing the second end 58 to rotate above the top surface of the orifice plate to different orifice positions. The cavity 55 of the dispensing tube is movable, providing a range of motion for aligning the cavity 55 with the center of the orifice 60 for dispensing. The cavity can be further moved to another orifice. The orifice plate 59 is movable along shuttle path 4, and the combination of linear and rotational motion ensures that all orifices 60 can subsequently be filled with liquid reagent via the cavity 55. The cavity 55 of the dispensing tube 52 is preferably moved close to the top surface of the orifice plate 59 for precise dispensing. The position of the reagent dispenser 46 along the z-axis is adjustable because the reagent dispenser is coupled to a retaining plate 29, which can be moved in the z-direction using a first lifting device 22. Thus, the first lifting device, used to move the manifold plate to apply positive pressure to the filter plate when the filter plate is inside the lift shaft, is also used to move the reagent dispenser vertically to adjust the gap between the top surface of the filter plate and the cavity when the filter plate is outside the lift shaft. The height of the gap is controlled using a sensor or a separate optical sensing system. In an alternative embodiment, the reagent dispenser uses a separate lifting device for vertical movement.

[0094] Details of the gear mechanism 116 for driving and rotating the rotating arm 47 of the liquid dispenser 46 are shown below. Figure 13 and Figure 14 The gear mechanism includes a first gear or spur gear 110 coupled to the drive shaft of the electric motor 48. The first gear 110 includes teeth 111 on its circumference that mesh with teeth 112 on the circumference 114 of a second gear 109. The second gear 109 includes a hub 113, and a rotating arm 47 is coupled to the hub 113. Bearing 54 ( Figure 11Located between hub 113 and retaining plate 29, it provides hinge 53 for rotating arm 47. Hub 113 is used to retain the rim surrounding insert 108, and insert 108 provides channel 62 for guiding distribution tube 52 into rotating arm. Second gear 109 includes a plurality of spokes 115 that connect the rim of hub 113 to circumferential rim 114. Spokes 115 are tangentially oriented and bias the circumferential rim of second gear 112 toward first gear 110, thereby maintaining contact between the teeth of second gear 109 112 and the teeth of first gear 110 111. Wear of any teeth is compensated by the bias provided by the spokes. The tight fit with controlled clearance between teeth 111, 112 provides precise rotation of rotating arm 47, thereby providing precise positioning of the rotating arm cavity above the orifice opening.

[0095] An alternative embodiment of the second gear is shown in Figure 15 The hub 113 of the second gear 109 is connected to the circumference 114 via an elastic O-ring 117 to provide bias for the meshing engagement of the teeth 111 and 112.

[0096] In this embodiment, the SPE device includes a drip-proof protection device 63, such as... Figure 16 As shown. The anti-drip protection device 63 includes an anti-drip protection plate 64 positioned between the two beams 38 of the second lifting device 23. The anti-drip protection plate 64 is rectangular with edges 72 (see figure). Figure 17 a) The longitudinal grooves 70 on each beam 38 engage, allowing the drip-proof protective plate 64 to slide back and forth between the two beams 38. The two longitudinal grooves 70 are vertically positioned below the retainers 75 on each beam 38. The retainers 75 are configured to hold the laboratory glassware component 3. Therefore, the drip-proof protective plate 64 can slide back and forth below the bottom surface of the laboratory glassware component present on the second lifting device. The drip-proof protective plate 64 may be made of a sheet of metal, a sheet of polymer material, or a sheet of paper. The drip-proof protective plate may comprise multiple sheets that can be arranged in a nested manner and moved over each other. The drip-proof protective plate may be permanently installed in the second lifting device, or it may be an easily replaceable disposable laboratory glassware component. The drip-proof protective plate may be coated with a hydrophobic coating or a coating that changes color when a liquid droplet adheres to the coated surface. The color change may be sensitive to the pH of the liquid droplet adhering to the surface. Alternatively, a change in capacitance is detected when a droplet adheres to the drip-proof protective plate. The change in capacitance or color can be used to determine the lifespan of the drip-proof protective plate 64.

[0097] The drip protection device 63 includes an electric actuator for horizontally moving a drip protection plate 64 between two beams 38. The electric actuator includes an electric motor 65 for driving a linkage system 69. The linkage system 69 includes an arm 66, one end of which is connected to the drive shaft of the electric motor 65, and the other end of which includes a pin 67 engaging a guide slot 68 in the drip protection plate 64. The guide slot 68 in the plate is oriented perpendicular to the axis for moving the plate between the two beams. Rotation of the electric motor 65 activates the linkage system 69, and rotation of the arm 66 ensures axial movement of the drip protection plate 64 as the pin 67 slides through the guide slot 68. The movement of the protection plate can be reversed by reversing the rotation direction of the drive shaft of the electric motor 65. A connecting plate 71 is attached to the electric motor 65 and / or the beams 38 for guiding wiring connecting the electric motor 65 and a control unit with control circuitry. The anti-drip protection device 63 is directly connected to the beam 38 of the second lifting device 23, which moves up and down in the elevator shaft by rotating the threaded rod 33 of the engaging threaded nut 35. During vertical movement, the beam 38 is guided by the guide column 20 (see...). Figure 17 a) In an alternative embodiment, the drip protection device 63 has its own lifting mechanism. The drip protection device 63 can protect the top surface of laboratory glassware components positioned below the second lifting device 23, such as protecting a collection plate positioned or to be positioned below a filter plate between beams 38 on the retainer 75 of the second lifting device 23.

[0098] During solid-phase extraction, different liquids are subsequently loaded and pressed through a filter package containing filter plates, collecting the filtered liquid in a waste tray or ultimately in a collection plate. The filter plates are washed with a wash liquid to leach out undesirable components absorbed by the packaging material within the filter plates. The wash liquid may be ejected from the outlet nozzles of the filter plates, and liquid may splash from the waste tray onto the filter plates. Consequently, droplets may remain attached to the nozzles or the bottom surface of the filter plates, and these droplets may subsequently fall onto the collection plate used in subsequent elution steps. Attached droplets may coalesce and fall onto the collection plate, contaminating the eluent pressed through the filter plates, and thus potentially contaminating the eluent collected in the collection plate. The collection plate must first be moved under the filter plates, remain under the filter plates during the elution steps, and ultimately need to be transported along the shuttle path for further processing. A drip guard 64 is moved under the filter plates before the collection plate is moved under the filter plates, and retracts when the collection plate has been removed from under the filter plates. This ensures that the top surface of the collection plate is protected from droplets from previous processing steps.

[0099] The beam 38 of the second lifting device includes alignment features for horizontally and / or vertically aligning the laboratory glassware component when it is placed between the two beams 38. First alignment feature: Each of the two beams 38 includes a longitudinally extending first chamfer 73 (see...). Figure 17 a) The planes of the two chamfers 75 radiate toward the top cover of the SPE device, and each beam 38 serves to hold the laboratory glassware component vertically below the chamfer 73. The laboratory glassware component, lowered between the two beams (or raised by the second lifting device 23), may first contact the chamfer 75 as it approaches the holder 75. As the chamfer abuts against the bottom surface of the laboratory glassware component during approach, the chamfer 75 allows the laboratory glassware component to self-align until it is placed onto the holder 75 (see [link to product description]). Figure 17 b). Second alignment feature: The front end of each beam 38 includes a second chamfer 74, and the two chamfers 74 are oriented divergently towards each other, providing an entry section for horizontal movement of the laboratory vessel component between the two beams 38. The front end of the laboratory vessel component may abut against one of the two chamfers 74, thereby enabling the laboratory vessel component to self-align when moved horizontally between the two beams.

[0100] SPE equipment 1 may include an evaporation unit 76, such as Figure 18 and Figure 19 The evaporation unit 76, as depicted, can be used to concentrate the sample liquid collected in the collection plate, for example, by evaporating the solvent using hot air or hot nitrogen. The evaporation unit 76 is coupled to a holding plate 29 for holding the manifold plate, which will be described below. The evaporation unit 76 can move vertically together with the holding plate 29 using a first lifting device. The evaporation unit 76 can be releasably coupled to the holding plate 29 for modular arrangement within the SPE apparatus. Thus, the evaporation unit can be coupled to the holding plate when needed. Alternatively, the evaporation unit is an integral part of the SPE apparatus and cannot be easily removed. The evaporation unit 76 includes an evaporation manifold 77 for distributing incoming air or nitrogen to a plurality of hollow evaporation tubes 78 extending axially along the z-axis. Laboratory glassware components, such as the collection plate containing the liquid sample, can be positioned below the evaporation unit using a shuttle 2 that moves horizontally along a shuttle path. Alternatively, the evaporation unit can move horizontally within the holding plate 29 to a position above the laboratory glassware components. In yet another alternative, both the evaporation unit 76 and the laboratory glassware components move toward each other.

[0101] After positioning the evaporation unit 76 above the laboratory glassware assembly, the evaporation tube 78 of the evaporation unit 76 is inserted into the laboratory glassware assembly. A first lifting device can be lowered to lower the holding plate 29 supporting the evaporation unit, and / or a second lifting device can be used to raise the laboratory glassware assembly. Hot air or nitrogen is injected into the evaporation tube 78 through the evaporation manifold 77 to evaporate the solvent, which is ultimately discharged from the SPE equipment via the vapor exhaust port 41.

[0102] Manifold plate 79 for applying positive pressure to the filter plate is shown. Figure 20Manifold 79 is securely attached to retaining plate 29 of the first lifting device, and manifold 79 can be lowered by the first lifting device to contact the top surface of a laboratory glassware component located below the manifold. Manifold 79 can be replaced with a manifold adapted to another orifice plate format using a connector device, thus providing a modular approach to SPE equipment. Manifold 79 includes a top plate 80 with a connector 83 for connecting the manifold to the pressure supply unit. Pressure is distributed across a plurality of outlet openings 84 present in a base plate 81. The top plate 80 and base plate 81 are attached to each other using screws 82. An internal seal 85 is sandwiched between the top and base plates, providing a pressure-resistant seal. An outlet seal 86 is disposed on the bottom surface of the base plate 81, which can be compressed when the manifold 79 is lowered to contact the laboratory glassware component, or alternatively, when the laboratory glassware component is raised toward the manifold. The outlet seal 86 provides a pressure-resistant seal for effectively transferring compressed gas from the inlet of connector 83 to the orifice of the laboratory glassware component aligned with the outlet opening 84 of manifold 79.

[0103] Figure 21 A nozzle separator 91 is presented, which can be placed below a filter plate or filter holder. The nozzle separator 91 includes a nozzle separation plate 92 and a spacer 102. The spacer 102 includes walls surrounding the nozzle separation plate 92, which mechanically support the nozzle separation plate 92. The spacer 102 may include other parts of the nozzle separator, such as a receiving section or fluid guiding section, which will be discussed below. Both the nozzle separation plate 92 and the spacer 102 may be configured as disposable laboratory glassware consumables, or one or both components may be configured as reusable components. A semi-disposable nozzle separator 91 may include a disposable nozzle separation plate 92 and a reusable spacer 102. The nozzle separator may be made of metal or polymer materials. The disposable nozzle separation plate 92 may be made, for example, of an injection-molded polymer selected from polypropylene, polyethylene, polystyrene, polymethyl methacrylate, polycarbonate, etc. The plate may be made of recycled polymers or biopolymers to reduce the carbon footprint of disposable components.

[0104] Figure 22An assembly of a filter plate or filter holder 103 and a nozzle separation plate 92 positioned below the filter plate or filter holder 103 is shown. The filter plate or filter holder 103 includes a plurality of cylinders or columns 87, such as syringes, and each cylinder defines a longitudinal axis oriented parallel to each other. Each cylinder 87 includes a proximal opening 88 serving as a liquid inlet and a nozzle 89 providing a liquid outlet away from the opening. A filter 90 having a solid packaging material is located between the opening 88 and the nozzle 89. The plurality of cylinders are embedded in a frame 95, which includes connecting rods 98 for connecting a top plate 97 to a bottom plate 96. The top and bottom plates are oriented perpendicular to the axis defined by the cylinders 87, and the frame provides mechanical support to the plurality of cylinders such that the plurality of openings 88, and therefore the plurality of nozzles 89, are oriented according to a repeating pattern, such as according to a SLAS or ANSI pattern for orifice plates. The cylinders 87 protrude through the top plate 97, and flanges 99 abut against the top surface of the top plate 97. Nozzle 89 or at least the distal end of the nozzle protrudes through the bottom surface of base plate 96.

[0105] Figure 22 A cross-sectional view of a nozzle separator plate 92, horizontally positioned below the filter plate or filter holder 103, is further shown. The nozzle separator plate 92 includes a plurality of openings 93, the centers of which are oriented to the same repeating pattern for each nozzle 89, such that each nozzle is fitted into an opening 93 and separated from adjacent nozzles by the walls 94 of the nozzle separator plate 92. Each opening 93 includes a receiving section 100 and a fluid guiding section 101. The receiving section 100 may be conical or cup-shaped for receiving the distal tip of the nozzle 89, and the fluid guiding section 101 guides and separates the output of each nozzle into, for example, a waste tray. Nozzle splashes from each nozzle are collected individually in the receiving section of each opening 93, and splashing of liquid from one nozzle to another is prevented because the fluid guiding section 101 separates the nozzles from each other. The nozzle separator plate 92 may include a rim or protrusion 104 at least partially surrounding the nozzle separator plate 92 for guiding and aligning the separator plate when stacked between the filter holder 103 and the spacer 102. The protrusion 104 may have a chamfer to facilitate self-alignment during stacking.

[0106] Figure 23 A cross-sectional view is shown of an assembly of a filter plate or filter holder 103 with a 96-hole plate format stacked on top of a nozzle separator 91. The nozzle separator 91 includes a nozzle separating plate 92 sandwiched between the filter plate 103 and a spacer 102. Each nozzle 89 is received in a receiving section 100 of the nozzle separator, and fluid can be guided through a guide section 101 into a waste tray stacked below the spacer 102.

[0107] Figure 24A stack of filter plates 103 is presented on top of a waste tray 105 positioned on a shuttle 2 located at position 44 outside the lift shaft. Alternatively, the waste tray is part of the shuttle 2. The filter plates 103 are prepared to move along the shuttle path 4 toward the opening 5 to a position that allows the rotating arm of the reagent dispenser 46 to dispense reagents, such as conditioning or washing liquids, into the filter plate orifices. The filter plates 103 can further move along the shuttle path 4 through the lift opening 5 into the lift shaft 43, reaching a position below the manifold plate 79. The manifold plate 79 can be lowered to contact the filter plates 103, and then pressure is applied to the manifold plate, forcing liquid through the filter into the waste tray 2. The waste tray 2 can be connected to a waste collector 6, or, in an alternative embodiment where the waste tray is part of the shuttle: the shuttle can be connected to the waste collector 6. After filtration, the manifold plate 79 is raised, and the filter plates 103 can be used for further processing.

[0108] Figure 25 The SPE device 1 with its cover removed is shown, with the collection plate 106 positioned on the shuttle 2 at position 44 outside the lift shaft. Other components, such as waste trays or nozzle separator stacks, may be located below the collection plate, as this facilitates pre- and post-processing steps in systems that include both SPE equipment and laboratory automation equipment, which will be explained in further detail below. The collection plate 106 is ready to move into the lift shaft 43, positioned below the filter plate 103, which has been lifted by the second lifting device 23. Two beams 38 of the second lifting device support the filter plate 103, creating a gap below the filter plate 103 for the collection plate 106 to use. The bottom surface of the filter plate 103 is shielded by a drip-proof protection plate 64, preventing droplets from falling onto the collection plate 105 during movement into the lift shaft. The drip-proof protection plate 64 retracts from the collection plate 105 once the collection plate 106 has been moved by the shuttle 2 to the position below the filter plate 103. The first lifting device 22 can be lowered to compress the stack of the filter plate and the collection plate, and apply pressure to the manifold plate so that the eluent is forced through the filter and collected in the collection plate 106.

[0109] Methods for using SPE devices in systems that include SPE devices and laboratory automation equipment Figures 26 to 43 The explanation is as follows. Figure 26A side view of a schematic diagram of an SPE device 1 positioned on a work surface 12 of a workbench of a laboratory automation device 9 is presented. The base plate 11 of the SPE device is positioned on the work surface 12. The laboratory automation device 9 includes a first transfer mechanism 13 with a gripper 15 for gripping, moving, and placing laboratory glassware components onto a shuttle 2 of the SPE device. The laboratory automation device also includes a second transfer mechanism 14 configured to hold pipette tips 17 for aspirating and dispensing liquid samples. A waste tray 105 can be placed onto the shuttle 2 using the first transfer mechanism 13, or it can be placed manually onto the shuttle 2. Alternatively, the waste tray is incorporated into the shuttle 2, and a separate waste tray is not used. The shuttle 2 can be moved using a shuttle drive from a position 44 outside the lift shaft along a shuttle path 4 through an opening 5 to a position 107 inside the lift shaft. The SPE device 1 includes a first lifting device 22 for moving a manifold 79, which also holds a rotating arm 47 with a dispensing tube 52. The space between the manifold plates 79 defines the elevator shaft 43, and laboratory equipment components can be moved horizontally into the elevator shaft 43 using the shuttle 2, and can be moved vertically or lifted using the second lifting device 23.

[0110] The first transfer mechanism 13 with clamp 15 has placed the filter plate or filter rack 103 on top of the waste tray 105, as follows: Figure 27 As shown. The shuttle 2 is held at position 44 outside the elevator shaft. Optionally, a spacer may be placed between the waste tray 105 and the filter plate 103, or, as another option, a nozzle separator may be placed between the filter plate and the waste tray, which will be discussed below. Figure 43 The process is further illustrated in the image. Subsequently, shuttle 2 moves along shuttle path 4 to the designated position between position 44 outside the elevator shaft and position 107 inside the elevator shaft, as shown in the image. Figure 28 As depicted. The manifold plate 79 has been lowered to a position just above the top surface of the filter plate 103 using the first lifting device 22, and the dispensing pipe 52 of the rotating arm 47 has been rotated out of the lift well 43, such that the dispensing pipe 52 is aligned with the opening or hole of the filter plate 103. A conditioning liquid is dispensed using the liquid reagent supply unit. Rotating the rotating arm 47 and / or the moving shuttle 2 will approach subsequent openings and thus dispense conditioning liquid until the programmed number of holes are filled with conditioning liquid. Once the programmed openings are filled, the rotating arm rotates back to the parking position, and the shuttle 2 moves into the lift well 43, as... Figure 29 As presented. The manifold plate 79 of the SPE device 1 is lowered using the first lifting device 22, and pressure is applied to the stack of the loaded filter plate 103 and waste tray 105 using the manifold plate 79. The forced conditioning liquid passes through the filter package and is collected in the waste tray 105. The manifold plate 79 with the rotary distributor 47 is raised using the first lifting device 22, so that the shuttle can move from position 107 inside the elevator shaft to position 44 outside the elevator shaft, see [reference]. Figure 30 A second transfer mechanism 14, equipped with a pipette tip 17, draws sample liquid from the sample liquid container or from the sample liquid orifice plate. The second transfer mechanism 14 guides the pipette tip 17 to the opening of the filter plate 103 and distributes the sample liquid onto the adjusted post-filter of the filter plate. The shuttle 2 moves back into the elevator shaft 43, as... Figure 31 As shown, the manifold plate 79 is then lowered to contact the top surface of the stack of waste tray 105 and filter plate 103. Pressure is applied to the manifold plate 79 such that the sample liquid is forced through the packaging of filter plate 103, as... Figure 32 As presented. The manifold plate 79 is raised, and the shuttle 2 moves along the shuttle path 4 to the intermediate position, allowing the rotating arm 47 to rotate and distribute the washing liquid pumped from the liquid reagent supply unit into the opening of the filter plate 103. See [reference needed]. Figure 33 Once the required number of openings have been filled with washing liquid, shuttle 2 moves back into lift shaft 43, and manifold plate contacts the stack with filter plate 103, applying pressure again to manifold plate 79, thereby pushing the washing liquid over the filter plate into waste tray 105, see [link to relevant documentation]. Figure 34 The first lifting device 22 is then raised to move the manifold plate 79 upward, creating space in the elevator shaft 43 so that the second lifting device 23 can lift the filter plate 103 from the waste tray 105. See also... Figure 35 Optionally, the drip-proof protective plate 64 incorporated in the second lifting device 23 moves below the filter plate 103, thereby protecting laboratory glassware components located below the filter plate from droplets that may fall from the filter plate. The shuttle 2 moves along the shuttle path 4 from a position 107 inside the elevator shaft to a position 44 outside the elevator shaft. The first transfer mechanism 13 using the gripper 15 stacks the collection plate 106 on top of the waste tray 105, as... Figure 36 As presented. Optionally, the waste tray 105 is first removed by the first transfer mechanism 13, so that the collection plate is placed directly on the shuttle 2. The stack including the collection plate 106 moves along the shuttle path 4 to position 107 in the elevator shaft, as shown. Figure 37 As shown. During operation, the anti-drip protection plate 64 remains below the filter plate 103, thereby shielding the bottom surface of the filter plate and preventing droplets from contaminating the collection plate 106 moving below the filter plate 103. Once the collection plate 106 is positioned below the filter plate 103, the anti-drip protection plate 64 retracts, see [reference]. Figure 38 Lower the second lifting device 23 to stack the filter plate 103 on top of the collection plate 106, see [link to relevant documentation]. Figure 39The shuttle moves to an intermediate position between position 107 inside the elevator shaft and position 44 outside the elevator shaft, and lowers the manifold plate 79 with the rotating arm 47 via the first lifting device 22 to position the distribution pipe 52 of the rotating arm 47 above the top surface of the filter plate 103. The rotating arm 47 is rotated, and the eluent is distributed into the openings of the filter plate via the distribution pipe 52. See [link to relevant documentation]. Figure 40 Once the required number of openings have been filled with eluent, the rotating arm 47 rotates back to the parking position, the shuttle moves to the lift shaft, and lowers the manifold plate 79 to apply pressure to the eluent in the filter plate, allowing the eluent to be collected in the collection plate 106. Figure 41 The shuttle 2, with a stack including filter plate 103 on top of collection plate 106, moves to a position outside the elevator shaft, and the gripper 15 of the first transfer mechanism of the laboratory automation equipment 9 can destacking the stack, making the collection plate available for further analysis or for another step using the second transfer mechanism, see [link to relevant documentation]. Figure 42 As an option, the collection plate moves below the evaporation unit (see...). Figure 18 and Figure 19 This is to concentrate the filtered sample before further processing.

[0111] As an alternative, the nozzle separator 91 can be placed between the filter plate 103 and the waste tray 105, see [link / reference] Figure 43 .

[0112] The steps for adjusting the filter plate, filling it with sample liquid, washing the filter plate, and collecting the eluent are the same as described above.

[0113] List of reference numerals

[0114] 1 SPE equipment

[0115] 2 shuttles

[0116] 3 Laboratory glassware components

[0117] 4. Shuttle Path

[0118] 5. Lift opening

[0119] 6 Waste Collector

[0120] 7. Distributor Control Box

[0121] 8. Evaporator control box

[0122] 9. Laboratory automation equipment

[0123] 10 Liquid Reagent Supply Unit

[0124] 11 SPE substrate

[0125] 12 Working surfaces

[0126] 13 First Transfer Agency

[0127] 14 Second Transfer Agency

[0128] 15. Clamping device

[0129] 16 pipette tips

[0130] 17. Pipette Tips

[0131] 18. Liquid reagent containers

[0132] 19 Cover

[0133] 20 guide pillars

[0134] 21 Top cover plate

[0135] 22 First lifting device

[0136] 23 Second lifting device

[0137] 24 Electric motor shuttle drive

[0138] 25. Electric motor of the first lifting device

[0139] 26. Electric motor for the second lifting device

[0140] 27 First lifting device drive belt

[0141] 28 Second lifting device drive belt

[0142] 29. Retention Plate

[0143] 30 First lifting device drive pulley

[0144] 31 Second lifting device drive pulley

[0145] 32 First lifting device threaded rod

[0146] 33 Second lifting device threaded rod

[0147] 34 First lifting device threaded insert

[0148] 35 Second lifting device threaded nut

[0149] 36 First lifting device bushing

[0150] 37 Second lifting device bushing

[0151] 38 Second lifting device beam

[0152] 39 Control Unit

[0153] 40 Printed Circuit Boards

[0154] 41 Steam exhaust port

[0155] 42 Connector PCB

[0156] 43. Elevator shaft

[0157] 44. Location outside the elevator shaft

[0158] 45. Strip conductor

[0159] 46. ​​Reagent dispenser

[0160] 47 Rotating Arm

[0161] 48 Electric Motors

[0162] 49 Start-up Station

[0163] 50 Start-up station emission outlet

[0164] 51 Startup Tray

[0165] 52 Distribution pipe

[0166] 53 Hinges

[0167] 54 bearing

[0168] 55 cavities

[0169] 56 Bushing

[0170] 57 First End

[0171] 58 Second End

[0172] 59 96-hole plate

[0173] 60 holes

[0174] 61 Incision

[0175] 62 channels

[0176] 63. Anti-drip protection device

[0177] 64 Anti-drip protection plate

[0178] 65 Electric Motor

[0179] 66 arms

[0180] 67 sales

[0181] 68 guide slots

[0182] 69-link motion system

[0183] 70 Longitudinal groove

[0184] 71 Connecting plate

[0185] 72 Edge

[0186] 73 First chamfer

[0187] 74 Second chamfer

[0188] 75 Retaining parts

[0189] 76 Evaporation Units

[0190] 77 Evaporator Manifold

[0191] 78 Evaporator tube

[0192] 79 Manifold

[0193] 80 top plate

[0194] 81 base plate

[0195] 82 screws

[0196] 83 Connector

[0197] 84 Exit opening

[0198] 85 Internal seals

[0199] 86. Outlet seal

[0200] 87 Cylinder

[0201] 88 Opening

[0202] 89 Nozzles

[0203] 90 Filter

[0204] 91 Nozzle Separator

[0205] 92 Nozzle Separation Plate

[0206] 93 Opening

[0207] 94 wall

[0208] 95 Frame

[0209] 96 base plate

[0210] 97 Top Plate

[0211] 98 Connecting rod

[0212] 99 flange

[0213] 100 Receive Section

[0214] 101 Fluid Guide Section

[0215] 102 Spacer

[0216] 103 Filter plates, filter frames

[0217] 104. Protrusions, rims

[0218] 105 Waste Pallets

[0219] 106 Collection boards, collection racks

[0220] 107 Location inside the elevator shaft

[0221] 108 inserts

[0222] 109 Second Gear

[0223] 110 First gear, spur gear

[0224] 111 First gear teeth

[0225] 112 Second gear teeth

[0226] 113 Wheels

[0227] 114 circumferences

[0228] 115 spokes

[0229] 116 Gear Mechanism

[0230] 117 O-ring

Claims

1. A solid-phase extraction apparatus (1), comprising: - base plate (11), - Shuttle (2), which is mounted on the substrate (11) and can reciprocate along the horizontal length of the substrate, thereby defining the shuttle path (4), which is configured to transport laboratory equipment components (3). - A manifold plate (79), oriented parallel to the base plate (11) and capable of vertical reciprocating motion, thereby defining an elevator shaft (43), the manifold plate (79) being configured to provide positive pressure to the laboratory glassware component (3) when the laboratory glassware component contacts the manifold plate (79); the shuttle (2) being movable into and out of the elevator shaft (43) to position the laboratory glassware component (3) below the manifold plate (79). - A reagent dispenser (46), operably connected to the manifold plate (79) and capable of vertical reciprocating motion with the manifold plate, the reagent dispenser (46) being configured to supply liquid reagents to the laboratory glassware component (3). Its features are, The reagent dispenser (46) includes - Rotating arm (47), the rotating arm being oriented parallel to the substrate (11). - Hinge (53), which connects one end of the rotating arm (47) to the manifold plate (79). - A dispensing tube (52), located at the other end of the rotating arm, forming a cavity (55) oriented vertically toward the substrate and fluidly connected to the liquid reagent. - A drive mechanism for rotating one end of the rotating arm (47) about the hinge (53) in a plane parallel to the base plate (11), thereby moving the other end with the dispensing tube (52) from a position inside the elevator shaft (43) to a position outside the elevator shaft to dispense liquid reagents into the laboratory glassware component (3).

2. The solid-phase extraction apparatus (1) according to claim 1, characterized in that, The reagent dispenser (46) includes a liquid reagent supply unit (10) comprising a plurality of liquid reagent containers (18), a pump, a pump manifold, a valve for switching between the liquid reagent containers (18), and a pipe connecting the liquid reagent containers (18) to the dispensing pipe (52) via the pump and the pump manifold, each liquid reagent container containing a different liquid reagent.

3. The solid-phase extraction apparatus (1) according to claim 1 or 2, characterized in that, The liquid reagent is selected from conditioning liquids, washing liquids, or elution liquids.

4. The solid-phase extraction apparatus (1) according to any one of the preceding claims, characterized in that, The elevator shaft (43) includes - A first lifting device (22) is used to make the manifold plate (79) reciprocate vertically relative to the substrate (11). - A second lifting device (23), located below the first lifting device (22), has a retainer (75) for receiving and holding the laboratory glassware component (3); the second lifting device (23) is configured to cause the laboratory glassware component (3) to reciprocate vertically between the base plate (11) and the manifold plate (79).

5. The solid-phase extraction apparatus (1) according to claim 4, characterized in that, Also includes: - A sensor for detecting the horizontal position of the shuttle (2) on the shuttle path (4). - A sensor for detecting the vertical position of the manifold plate (79) of the first lifting device (22) and / or the vertical position of the retainer (75) of the second lifting device (23) in the elevator shaft (43). - A sensor for detecting the rotation angle of the rotating arm (47) relative to the manifold plate (79).

6. The solid-phase extraction apparatus (1) according to claim 5, characterized in that, It also includes a control unit (39) with control circuitry, wherein the detected horizontal or vertical position and the detected rotation angle are used to control the solid phase extraction device (1).

7. The solid-phase extraction apparatus (1) according to claim 6, characterized in that, The laboratory glassware component (3) is a filter plate (103) including a plurality of openings (88) extending downward from the top surface of the filter plate (106), the plurality of openings (88) being oriented along a pattern on the top surface, and a plurality of filters (90) being positioned in each opening below a space available for applying the liquid reagent to each opening.

8. The solid-phase extraction apparatus (1) according to claim 7, characterized in that, The control unit (39) guides and controls the position of the filter plate (103) along the shuttle path (4), the vertical position of the manifold plate (79), and the rotation of the rotating arm (47) outside the elevator shaft, such that the cavity (55) is centered relative to one of the plurality of openings (88) of the filter plate (103).

9. The solid-phase extraction apparatus (1) according to claim 8, characterized in that, The control unit (39) guides and controls the liquid reagent supply unit (10) such that one of the liquid reagents is pumped into one of the openings (88) of the filter plate (103) via the cavity (55) of the rotating arm (47).

10. The solid-phase extraction apparatus (1) according to any one of the preceding claims, characterized in that, The reagent dispenser (46) includes a starter station (49) for starting the liquid reagent.

11. A system comprising a solid-phase extraction apparatus (1) according to claims 7 to 10 and a laboratory automation apparatus (9), the laboratory automation apparatus (9) comprising: - A worktable with a working surface (12), - A first transfer mechanism (13), comprising a gripper (15) configured to grip, transfer, and release the filter plate (103) to different positions on the worktable. - A second transfer mechanism (14), the second transfer mechanism (14) including a pipette tip (16) configured to draw the sample liquid from a sample laboratory vessel component holding the sample liquid. - A microcontroller for controlling the first transfer mechanism (13) and the second transfer mechanism (14) and the liquid handling via the pipette tip (16), The substrate (11) of the solid phase extraction device is located at a fixed position on the worktable and is oriented parallel to the worktable, such that the position (44) outside the elevator shaft can be used by the first transfer mechanism (13) to place the filter plate (103) on the shuttle (2), or by the second transfer mechanism (14) to distribute the sample liquid into one of the plurality of openings (88) of the filter plate (103).

12. The system according to claim 11, characterized in that, The pipette head (16) includes multiple pipette tips (17).

13. A solid-phase extraction method using the system according to claim 11 or 12, the method comprising the following steps: - At the elevator shaft location (44) of the solid phase extraction device (1), the stack of filter plates (103) and waste trays (105) is presented on the shuttle (2). - Using the pipette tip (17) of the second transfer mechanism (14) of the laboratory automation equipment (9), the sample liquid is loaded into the plurality of openings (88) of the filter plate (103). - To move the shuttle (2) along the shuttle path (4) into the elevator shaft (43), - Using the first lifting device (22), lower the manifold plate (79) of the solid-phase extraction device (1) to form a tight fit between the filter plate (103) and the manifold plate (79), and apply pressure to the manifold plate (79) to force the liquid sample through the filter plate (103) into the waste tray (105). - Use the first lifting device (22) to lift the manifold plate (79). - The shuttle (2) with the filter plate (103) and waste tray (105) stacked together is moved along the shuttle path (4) to the position (44) outside the elevator shaft. - Using the reagent dispenser (46) of the solid phase extraction apparatus, the plurality of openings (88) of the filter plate are loaded with washing liquid. -The stacked shuttle (2), including the filter plate (103) and waste tray (105), moves along the shuttle path (4) into the elevator shaft. - Using the first lifting device (22), lower the manifold plate (79) of the solid-phase extraction device (1) to form a tight fit between the filter plate (103) and the manifold plate (79), and apply pressure to the manifold plate (79) to force the washing liquid through the filter plate (103) into the waste tray (105). - Use the first lifting device (22) to lift the manifold plate. - Lift the second lifting device (23) with the retainer (75) to lift the filter plate (103) from the waste tray (105). - Move the shuttle (2) with the waste tray (105) along the shuttle path (4) to the position (44) outside the elevator shaft. - Using the clamp (15) of the first transfer mechanism (13), the collection plate (106) is stacked on top of the waste tray (105). -The shuttle (2), comprising the stack of the collection plate (106) and the waste tray (105), is moved along the shuttle path (4) into the elevator shaft (43). - Lower the second lifting device (23) to stack the filter plate (103) on top of the collection plate (106). - The shuttle (2) with the filter plate (103), collection plate (106) and waste tray (105) is moved along the shuttle path (4) to the position (44) outside the elevator shaft. - Using the reagent dispenser (46) of the solid phase extraction apparatus (1), the plurality of openings (88) of the filter plate (103) are loaded with elution liquid. -The stacked shuttle (2), including the filter plate (103), the collection plate (106), and the waste tray (105), moves along the shuttle path (4) into the elevator shaft (43). - Using the first lifting device (22), lower the manifold plate (79) of the solid phase extraction device (1) to form a tight fit between the filter plate (103) and the manifold plate (79), and apply pressure to the manifold plate (79) to force the eluent through the filter plate (103) into the collection plate (106).

14. The solid-phase extraction method according to claim 13, characterized in that, It also includes the steps of conditioning the filter plate with conditioning fluid before transferring the sample liquid into the filter plate (103), and / or concentrating the eluent in the collection plate (106) using the evaporation unit (76).

15. A computer program for extracting or concentrating substances from a sample liquid, said computer program, when executed by a processor integrated in a system comprising a solid phase extraction device (1) and a laboratory automation device (9), being adapted to perform the steps of the method of claim 13 or 14 using the control unit of said solid phase extraction device and the microcontroller of said laboratory automation device.

Images