Sample injector with disconnectable injection needle

A sample injector for injecting a fluid into a fluidic path, wherein the sample injector comprises a robot arm configured for moving an injection needle, when being connected to the robot arm, between a fluid container containing the fluid and a seat in fluid communication with the fluidic path, the needle configured for aspirating the fluid from the fluid container, when the needle has been moved to the fluid container, and for injecting aspirated fluid into the fluidic path, when the needle is accommodated in the seat, and the seat configured for accommodating the needle and providing fluid communication with the fluidic path, wherein the robot arm is configured for selectively disconnecting the needle from the robot arm when the needle is accommodated in the seat, and wherein the robot arm is configured for performing a further task while the needle is disconnected from the robot arm.

The present application is a National Stage application under 35 U.S.C. §365 of International Patent Application No. PCT/EP2011/059644 filed on Jun. 9, 2011 naming Hans-Peter Zimmerman, et al. as inventors. Priority is claimed from International Patent Application No. PCT/EP2011/059644 and the entire disclosure of International Patent Application No. PCT/EP2011/059644 is specifically incorporated herein by reference.

BACKGROUND ART

The present invention relates to a sample injector for a sample separation system, in particular for high performance liquid chromatography applications.

In liquid chromatography, a fluidic sample and an eluent (liquid mobile phase) may be pumped through conduits and a column in which separation of sample components takes place. In a sample loop, the sample may be injected into a fluidic path by a mechanically drivable needle. The drivable needle is controllable to be moved out of a seat of the sample loop into a vial or any other fluid container to receive a fluid and back from the vial into the seat. The column may comprise a material which is capable of separating different components of the fluidic analyte. Such a material, so-called beads which may comprise silica gel, may be filled into a column tube which may be connected downstream to other components, such as a detector, a fractioner, a waste, etc., by conduits.

U.S. Pat. No. 7,555,937 discloses a sample injection device, a sample injection method, and a liquid chromatograph that control the flow of a mobile phase using a switching valve. The sample injection device includes a port connected to a separation column, a pump for supplying a mobile phase, first and second sample injection needles, a syringe, and a valve configured to selectively connect the first sample injection needle to the pump or the syringe and to connect the second sample injection needle to the pump. When the first sample injection needle is attached to the port, the first sample injection needle is connected to the pump through operation of the valve. When the second sample injection needle is attached to the port, the first sample injection needle is connected to the syringe and the second sample injection needle is connected to the pump.

U.S. Pat. No. 7,635,326 discloses a tool holder which can be displaced in an x-direction, in a y-direction that is perpendicular thereto, and in a z-direction that is perpendicular to both the x-direction and the y-direction, and which can rotate about the z-direction. A solid matter dosing head, provided as a tool, is automatically attached in a removable manner to the tool holder by means of a permanent magnet. The tool can be easily exchanged for another tool due to this automatic removable attachment of said tool to the tool holder involving the use of a permanent magnet.

The product G1367 of the applicant Agilent Technologies is an example for a commercially available needle assay well plate autosampler.

However, fluid handling and proper operation of movable parts in a sample separation device may still be a challenge.

DISCLOSURE

It is an object of the invention to enable efficient fluid handling in a sample separation system.

According to an exemplary embodiment of a first aspect, a sample injector for injecting a fluid into a fluidic path is provided, wherein the sample injector comprises a robot arm configured for moving an injection needle, when being connected to the robot arm, between a fluid container containing the fluid and a seat in fluid communication with the fluidic path, the injection needle configured for aspirating the fluid from the fluid container, when the injection needle has been moved to the fluid container, and for injecting aspirated fluid into the fluidic path, when the injection needle is accommodated in the seat, and the seat configured for accommodating the injection needle and providing fluid communication with the fluidic path, wherein the robot arm is configured for selectively disconnecting the injection needle from the robot arm when the injection needle is accommodated in the seat, and wherein the robot arm is configured for performing a further task while the injection needle is disconnected from the robot arm.

According to another exemplary embodiment of the first aspect, a method of injecting a fluid into a fluidic path is provided, wherein the method comprises moving an injection needle connected to a robot arm to a fluid container for aspirating the fluid in the injection needle, moving the injection needle connected to the robot arm to a seat in fluid communication with the fluidic path, disconnecting the injection needle from the robot arm when the injection needle is accommodated in the seat, injecting the aspirated fluid from the injection needle into the fluidic path when the injection needle is accommodated in the seat, and performing a further task by the robot arm while the injection needle is disconnected from the robot arm.

According to an exemplary embodiment of a second aspect, a sample injector for injecting a fluid into a fluidic path is provided, wherein the sample injector comprises a robot arm configured for taking out a selected one of a plurality of fluid containers, each containing a fluid, from a fluid container rack and placing the selected fluid container on a fluid container support, wherein the robot arm is further configured for moving an injection needle between the selected fluid container placed on the fluid container support containing the fluid and a seat in fluid communication with the fluidic path, and the injection needle configured for aspirating the fluid from the fluid container, when the injection needle has been moved to the fluid container, and for injecting aspirated fluid into the fluidic path, when the injection needle is accommodated in the seat.

According to another exemplary embodiment of the second aspect, a method of injecting a fluid into a fluidic path is provided, wherein the method comprises taking out a selected one of a plurality of fluid containers, each containing a fluid, from a fluid container rack and placing the selected fluid container on a fluid container support by a robot arm, aspirating the fluid from the selected fluid container placed on the fluid container support by an injection needle supported by the robot arm, moving the injection needle to a seat in fluid communication with the fluidic path by the robot arm, and injecting the aspirated fluid into the fluidic path when the injection needle is accommodated in the seat.

According to an exemplary embodiment of a third aspect, a sample injector for injecting a fluid into a fluidic path is provided, wherein the sample injector comprises a robot arm configured for handling a plurality of fluid containers, each containing a fluid, and an injection needle, configured for aspirating the fluid from one of the plurality of fluid containers and for injecting the aspirated fluid into the fluidic path, wherein the robot arm has a first lift mechanism configured for handling the plurality of fluid containers over a first stroke length along a lift axis, wherein the robot arm has a second lift mechanism configured for handling the injection needle over a second stroke length along the lift axis, and wherein the first stroke length differs from the second stroke length.

According to another exemplary embodiment of the third aspect, a method of injecting a fluid into a fluidic path is provided, wherein the method comprises handling a selected one of a plurality of fluid containers, each containing a fluid, by actuating a first lift mechanism of a robot arm operable over a first stroke length along a lift axis, and handling an injection needle, for aspirating the fluid from one of the plurality of fluid containers and for injecting the aspirated fluid into the fluidic path, by actuating a second lift mechanism of the robot arm operable over a second stroke length along the lift axis, wherein the first stroke length differs from the second stroke length.

According to still another exemplary embodiment (which can be combined with any of the first to third aspects), a fluid separation system for separating compounds of a fluid in a mobile phase is provided, wherein the fluid separation system comprises a mobile phase drive, preferably a pumping system, configured to drive the mobile phase through the fluid separation system, a separation unit, preferably a chromatographic column, configured for separating compounds of the fluid in the mobile phase, and a sample injector having the above mentioned features and being configured for injecting the fluid in the fluidic path between the mobile phase drive and the separation unit.

According to an embodiment of the first aspect, an injection needle may be temporarily disconnected from a robot arm in a parking position while fluid which has previously been aspirated into the injection needle can be injected into a fluidic path coupled with a conduit of the seat. Thus, in the time interval in which the fluid may be further processed from the injection needle placed in a corresponding needle seat to the connected fluidic path and further downstream, the needle disconnection allows the robot to freely perform other tasks which render the management of the robot resources more efficiently. According to this first aspect, the injection of the aspirated fluid from the injection needle via the seat into the fluidic path (particularly a high pressure path between a mobile phase drive unit and a separation unit of a chromatography system) may be performed after having disconnected the injection needle from the robot arm. Hence, after this mechanical and fluidic decoupling of the injection needle from the robot arm, i.e. while the robot arm can perform any other task, the injection needle may rest with one end pressure-tightly connected to the seat and with the other end unconnected but preferably sealed with regard to an environment. Thus, in this operation state, the fluid can be transferred from the disconnected and sealed injection needle through the seat and to the fluidic path, while simultaneously the free capacity of the robot arm may be used for the mentioned other tasks to render operation of the system highly efficiently and the fluid handling very fast.

According to an embodiment of the second aspect, a robot arm can be configured to provide at least two functions, i.e. the handling of fluid containers which may be stored in a fluid container rack, and the handling of an injection needle for aspirating fluid from a fluid container selected out of fluid container rack for later moving the fluid-loaded needle to the seat in order to inject the aspirated fluid into the fluidic path related to this seat. Therefore, one and the same robot may be used very efficiently for two different tasks which usually cannot be performed at the same time, so that a compact system is provided in which a robot can be efficiently used.

According to an embodiment of the third aspect, a robot is provided which comprises two separately operable lift mechanisms with regard to one and the same lifting direction so that different lifting performances can be performed with different stroke heights (i.e. with different distances between an upper and a lower reversal position) using the first and the second lift mechanism. For instance, a larger stroke length and corresponding larger lift mechanism may be needed for handling a plurality of fluid containers accommodated in a fluid container rack vertically stacked above one another. For this task, the robot needs to move over the entire height of the arrangement of the fluid containers. However, for handling an injection needle, a smaller stroke length and correspondingly a smaller lift mechanism may be sufficient, since the needle needs to be lifted only over a smaller range in this scenario.

In the following, further embodiments of any of the above sample injectors (i.e. of any of the above first to third aspects) will be explained. However, these embodiments also apply to any of the above methods (i.e. to any of the above first to third aspects) and to the fluid separation system.

In an embodiment, the robot arm is configured for performing a fluid handling task while the injection needle is disconnected from the robot arm. Thus, an injection task and a fluid handling task may be performed in parallel which renders the operation of the system more efficiently.

In an embodiment, the robot arm is configured for handling at least one selected of a plurality of fluid containers, each containing a fluid, from a fluid container rack while the injection needle is disconnected from the robot arm. Therefore, the robot may have a provision which enables to robot to perform both tasks, i.e. handling a needle and handling a fluid container such as a vial or a well plate.

In an embodiment, the robot arm is configured for being moved, particularly for moving another body along, while the injection needle is disconnected from the robot arm. Such a moving may be a spatial displacement in one, two or three dimensions and allows the robot arm to perform a moving task such as the moving of a connected member like a fluid container while the needle remains disconnected in the seat.

In an embodiment, the robot arm is configured for, while the injection needle is disconnected from the robot arm, serving another injection needle. Therefore, it is not only possible that the robot arm, while the injection needle is disconnected, handles fluid containers, but it is additionally or alternatively possible that a parallel handling of multiple injection needles is performed with one and the same robot arm. Therefore, it is for instance possible in the context of a chromatographic separation, to separate fluidic samples in different fluidic paths simultaneously.

In an embodiment, the robot arm is configured for performing the further task under control of a software program. Therefore, a sequence of automatically performed operation steps can be carried out by a software controlling the robot arm which can further increase the efficiency of the robot resources. Any of the above-described and below-described tasks may be controlled by software.

In an embodiment, the injection needle and the seat are configured to cooperate so that the injection needle is accommodated in the seat in a fluid-tight manner, particularly in a pressure-tight manner. For instance, placing the needle in the seat may activate a mechanism in a self-acting manner which sealingly presses the needle into the seat. This can be advantageous in a chromatographic application in which a pump injects a fluid into a fluidic path at a relatively high pressure. Thus, by configuring the connection between needle and seat pressure-tight, it is possible to perform the injection without a leak and hence without a loss of fluidic sample.

In an embodiment, the sample injector comprises a needle park station configured for retaining the injection needle when the injection needle is accommodated in the seat. Such a needle park station may be a member which is capable of holding the injection needle in the disconnected state and which may also manage, for instance by a mechanical mechanism, the handover or transfer of the needle between robot arm and seat.

In an embodiment, the robot arm and/or the injection needle and/or the seat and/or the needle park station is configured to cooperate for sealing an internal fluid conduit of the injection needle with regard to an environment upon disconnecting the injection needle from the robot arm. Thus, in this advantageous embodiment, it is possible that an upper end of the capillary of the injection needle is sealed with regard to the environment (excluding the seat) making it possible to inject the fluid previously aspired by the injection needle into a connected fluidic conduit of the seat.

In an embodiment, the robot arm and/or the injection needle and/or the seat and/or the needle park station is configured so that, upon inserting the injection needle into the seat by the robot arm, a biasing element (such as a spring, for instance a helical spring), particularly of the injection needle or of the seat, is biased so as to exert a sealing force between the injection needle and the seat, and a mutual locking mechanism of the injection needle and the needle park station is activated. Such a biasing element may be a spring which presses the injection needle against the seat with a certain spring force, thereby supporting or promoting a fluid-tight connection. Moreover, it can then be ensured that the needle is safely stored in the needle park station by simultaneously activating the locking mechanism. Such a locking mechanism may be activated by the engagement of two cooperating engagement elements.

In an embodiment, the robot arm and the injection needle comprise cooperating first retaining elements configured for retaining the injection needle at the robot arm with a first retaining force being operative while the injection needle is outside the seat. The needle park station and the injection needle may comprise cooperating second retaining elements configured for retaining the injection needle at the needle park station with a second retaining force being larger than the first retaining force and being operative when the injection needle is inserted into the seat so that subsequently retracting the robot arm from the seat releases the injection needle from the robot arm and retains the injection needle at the needle park station. By this mechanism of two retaining systems having different retaining forces, it is possible to disconnect the injection needle merely by inserting it into a needle park station and by pulling the robot arm upwardly afterwards. Consequently, the stronger retaining force between needle park station and needle will then force the needle to remain at the needle park station and being in fluid communication with the fluid conduit of the seat.

In an embodiment, the robot arm and the injection needle comprise cooperating retaining elements configured for retaining the injection needle at the robot arm. The robot arm is configured for lowering the injection needle in a lowering direction (particularly in a vertical direction) to place the injection needle in the needle park station and for subsequently performing a motion in a lateral direction (particularly in a horizontal direction) angled relative to the lowering direction to disengage the cooperating retaining elements, thereby disconnecting the injection needle from the robot arm. Hence, the robot arm decouples the needle by a sideward motion and thereby remains in the needle park station.

In an embodiment, the mutual locking mechanism is provided by the second retaining elements. Thus, the second retaining elements do not only result in a disconnection of the needle but may also ensure the mutual locking which renders the device simple and compact and nevertheless reliable in the needle transfer operation.

In an embodiment, the needle park station comprises a latch being actuable by the robot arm to disengage the second retaining elements from one another so that subsequently retracting the robot arm pulls the injection needle along with the robot arm. Therefore, the robot arm may actuate the latch so as to release the connection between the disconnected needle and the needle park station, thereby again connecting the needle to the robot arm by the first retaining elements.

In an embodiment, the injection needle has a lever mechanism operable by the robot arm for reducing a force to be provided by the robot arm required for sealing the fluid conduit by lever action. By such a lever mechanism, it is possible to operate the robot arm with reduced requirements with regard to its force exertion, since a force transfer mechanism may allow actuation with a lower force over a larger actuation length. For this purpose, a leverage effect may be used.

In an embodiment, the robot arm and/or the injection needle and/or the seat is configured to cooperate so that, upon inserting the injection needle into the seat, a locking mechanism is activated for locking the injection needle to the seat and an unlocking mechanism is simultaneously activated for unlocking the injection needle from the robot arm. Thus, two mechanisms may be actuated at the same time or by a single motion of the robot arm, one being activated and the other one being deactivated.

In an embodiment, the locking mechanism and/or the unlocking mechanism is or are configured as a mechanical latching mechanism, a mechanical clamping mechanism and/or a magnetic mechanism. However, other mechanisms such as an electric mechanism or the like may be possible as well.

In an embodiment, the sample injector comprises at least one further seat in fluid communication with at least one further fluidic path, wherein the robot arm is configured for accommodating the injection needle selectively in the seat or in at least one of the at least one further seat. In such an embodiment, the fluidic device may have a plurality of different seats each being capable of receiving a respective needle. This allows to serve multiple seats and hence multiple connected fluid separation systems with the same robot arm.

In an embodiment, the sample injector comprises at least one further needle park station assigned to the at least one further seat and configured for retaining the injection needle when the injection needle is accommodated in a corresponding one of the at least one further seat. Therefore, for each of a plurality of seats, an assigned one of the plurality of needle park stations may be foreseen so that the disconnection of the corresponding needles can be managed by a separate needle park station in each seat. This may allow to further parallelize operation.

In an embodiment, the sample injector comprises at least one further injection needle movable by the robot arm, when being connected thereto, between the fluid container containing the fluid and selectively the seat or one of the at least one further seat. Therefore, also a plurality of injection needles may be implemented so that a highly modular system of multiple injection needles, multiple needle park stations and multiple seats can be implemented. The different seats/needle park stations/needles may be identical or may differ with regard to at least one parameter, for instance may differ in size.

In an embodiment, the robot arm is configured for mounting at least one further tool additionally or alternatively to the injection needle. The at least one further tool may comprise a gripper configured for gripping a vial (or any other fluid container such as a well plate), a reader configured for reading an identification feature of the fluid container or a vial (for instance using a wireless reader technology implementing an RFID tag), a filter for filtering the fluid, a pipette tip, a mixer for mixing the fluid, a punching tool for punching a septum covering a fluid container, and a plate handling tool configured for handling plates having multiple fluid receptacles (such as a well plate). However, other tools are possible as well. The robot arm may therefore be capable of providing more than one task at the same time including needle handling, fluid container handling and at least one additional capability. Therefore, a multiple purpose robot arm may be provided. The gripper may also be configured for gripping SPE (solid phase extraction) cartridges. An SPE is a tube filled with packing material on which sample from a previous processing step can be purified and concentrated. The robot can grip such cartridges and place the cartridge in a special needle park station for sealing it (similar to the sealing of the needle to the hydraulic system). Now the sample can be released from the packing material and can be injected into a liquid chromatography system.

In an embodiment, the robot arm comprises a stripper tool configured for stripping off a fluid container from the injection needle after having aspirated the fluid from the fluid container. Such a stripper tool may allow to apply a force for separating a needle and a fluid container such as a vial from one another. When aspirating a fluid in a vial or other fluid container, it may be necessary that the needle penetrates through a membrane covering the vial. Such a membrane may ensure a sterile storage of the sample in the vial. However, after having penetrated this membrane, it may happen that there remains a connection force between needle and membrane. The robot-bound stripper tool also to release such an undesired connection.

In an embodiment, the robot arm carries a capillary being in fluid communication with a fluid conduit of the injection needle when the injection needle is accommodated in the seat. Such a capillary may be in fluid communication with a metering device of the sample injector, the metering device defining an amount of fluid to be aspirated into the needle.

In an embodiment, the robot arm is configured for taking out a selected one of a plurality of fluid containers, each containing a fluid, from a fluid container rack and placing the selected fluid container on a fluid container support, wherein the robot arm is further configured for moving the injection needle between the selected fluid container placed on the fluid container support containing the fluid and the seat. For example, the fluid containers may be well plates or the like which can be arranged or stacked vertically (and/or horizontally) above one another in the fluid container rack which may be also be denoted as a well plate hotel. Apart from the needle handling task, the robot arm may also be able to handle each individual of the fluid containers, i.e. take a selected one out from the fluid container rack and place it on a support at a defined position.

In an embodiment, the robot arm has a first lift mechanism configured for handling a plurality of fluid containers, particularly when being vertically stacked in a fluid container rack, over a first stroke length along a lift axis, wherein the robot arm has a second lift mechanism configured for handling the injection needle over a second stroke length along the lift axis, wherein the first stroke length differs from, particularly is larger than, the second stroke length. Thus, particularly along a vertical axis, the robot arm may have two separate lift mechanisms (for instance two independently operable raise and lowering equipments) each of which allowing a handling over a certain stroke width which needs to be larger in many cases for handling vertically stacked fluid container racks as compared to a stroke width required for aspirating fluid into an injection needle and injecting this fluid into a fluidic conduit in the seat.

In an embodiment, the fluid container rack comprises a plurality of vertically stacked compartments each configured for accommodating a respective one of the plurality of fluid containers (such as well plates). Each compartment may be capable of receiving a well plate, for instance having 96 or any other plurality of wells with fluidic samples in it. It is also possible that individual vials or groups of vials are stored in the compartments.

In an embodiment, the fluid container rack is operable with a push loading drawer mechanism. Such a mechanism may be actuated by the robot arm for taking fluid containers out of the fluid container rack or for inserting fluid containers into the fluid container rack.

In an embodiment, the robot arm is configured for taking a fluid container from the fluid container support and for moving this fluid container into the fluid container rack. For this purpose, the robot arm may be configured with a certain gripper for gripping fluid containers.

In an embodiment, at least a part of the plurality of fluid containers is a sample plate comprising a plurality of receptacles each configured for accommodating a fluid. Such a sample plate may be a well plate or microtiter plate. A microtiter plate is a flat plate with multiple wells used as small test tubes. The microplate has become a standard tool in analytical research and clinical diagnostic testing laboratories.

In an embodiment, the robot arm is configured so that the injection needle is disconnectably mountable on the robot arm and a provision for handling a fluid container of the robot arm is disconnectably mountable or permanently mounted on the robot arm. Therefore, the robot arm may connect or disconnect with an injection needle and/or a fluid container on demand.

In an embodiment, the sample injector comprises only a single (i.e. exactly one) fluid container support configured for receiving exactly one fluid container, particularly exactly one well plate. Therefore, one specific position for receiving fluid containers from the fluid container rack may be defined. The robot arm will then place any (and only one at a time) fluid container taken from the fluid container rack onto this position so that it is very easy and only involves short moving paths for a needle for moving between a selected fluid container placed on the fluid container support on the one hand and a seat on the other hand. This renders operation of the device very efficient.

In an embodiment, the robot arm is configured for alternatingly handling the plurality of fluid containers and the injection needle. Thus, in a first operation mode, a fluid which has already been aspirated into the needle, the needle being already inserted into a seat, is injected into the fluidic path while the robot arm operates the fluid containers. In another operation mode, the needle is connected to the robot arm and aspirates fluid from a fluid container which has previously been mounted on the fluid container support. This allows to partially parallelize the tasks of fluid injection and fluid aspiration.

In an embodiment, the robot arm is configured for selectively disconnecting the injection needle from the robot arm when the injection needle is accommodated in the seat, wherein the robot arm is configured for handling at least one of the plurality of fluid containers of the fluid container rack while the injection needle is disconnected from the robot arm. This allows to efficiently use the resources of the robot arm.

In an embodiment, the robot arm is movable by a horizontal drive mechanism in a plane perpendicular to the lift axis. Therefore, apart from the lift direction, also movement along one or even two perpendicular horizontal directions is possible.

In an embodiment, the lift axis is a vertical axis. The vertical axis may be defined to be parallel to the direction of gravity force.

In an embodiment, the first lift mechanism and the second lift mechanism are operable independently from one another. This has the advantage that only one lift mechanism which is needed presently needs to be operated, whereas the other lift mechanism which is presently not required can be kept fixed.

A processing element may be filled with a separating material. Such a separating material which may also be denoted as a stationary phase may be any material which allows an adjustable degree of interaction with a sample so as to be capable of separating different components of such a sample. The separating material may be a liquid chromatography column filling material or packing material comprising at least one of the group consisting of polystyrene, zeolite, polyvinylalcohol, polytetrafluorethylene, glass, polymeric powder, silicon dioxide, and silica gel, or any of above with chemically modified (coated, capped etc) surface. However, any packing material can be used which has material properties allowing an analyte passing through this material to be separated into different components, for instance due to different kinds of interactions or affinities between the packing material and fractions of the analyte.

At least a part of the processing element may be filled with a fluid separating material, wherein the fluid separating material may comprise beads having a size in the range of essentially 1 μm to essentially 50 μm. Thus, these beads may be small particles which may be filled inside the separation section of the microfluidic device. The beads may have pores having a size in the range of essentially 0.01 μm to essentially 0.2 μm. The fluidic sample may be passed through the pores, wherein an interaction may occur between the fluidic sample and the pores.

The processing element may be a chromatographic column for separating components of the fluidic sample. Therefore, exemplary embodiments may be particularly implemented in the context of a liquid chromatography apparatus.

The sample separation device may be configured to conduct a liquid mobile phase through the processing element and optionally a further processing element. As an alternative to a liquid mobile phase, a gaseous mobile phase or a mobile phase including solid particles may be processed using the fluidic device. Also materials being mixtures of different phases (solid, liquid, gaseous) may be processed using exemplary embodiments. The sample separation device may be configured to conduct the mobile phase through the system with a high pressure, particularly of at least 600 bar, more particularly of at least 1200 bar.

The sample separation device may be configured as a microfluidic device. The term “microfluidic device” may particularly denote a fluidic device as described herein which allows to convey fluid through microchannels having a dimension in the order of magnitude of less than 500 μm, particularly less than 200 μm, more particularly less than 100 μm or less than 50 μm or less.

Exemplary embodiments may be implemented in a sample injector module of a liquid chromatography apparatus which sample injector module may take up a sample from a fluid container and may inject such a sample in a conduit for supply to a separation column. During this procedure, the sample may be compressed from, for instance, normal pressure to a higher pressure of, for instance several hundred bars or even 1000 bar and more. An autosampler may automatically inject a sample from the vial into a sample loop. A tip or needle of the autosampler may dip into a fluid container, may suck fluid into the capillary and may then drive back into a seat of a sample loop to then, for instance via a switchable fluidic valve, inject the fluid towards a sample separation section of the liquid chromatography apparatus. The sample in the sample loop may be a steel capillary or the like.

The sample separation device may be configured to analyze at least one physical, chemical and/or biological parameter of at least one component of the mobile phase. The term “physical parameter” may particularly denote a size or a temperature of the fluid. The term “chemical parameter” may particularly denote a concentration of a fraction of the analyte, an affinity parameter, or the like. The term “biological parameter” may particularly denote a concentration of a protein, a gene or the like in a biochemical solution, a biological activity of a component, etc.

The sample separation device may be implemented in different technical environments, like a sensor device, a test device, a device for chemical, biological and/or pharmaceutical analysis, a capillary electrophoresis device, a liquid chromatography device, a gas chromatography device, an electronic measurement device, or a mass spectroscopy device. Particularly, the fluidic device may be a High Performance Liquid Chromatography (HPLC) device by which different fractions of an analyte may be separated, examined and analyzed.

An embodiment of the present invention comprises a fluid separation system configured for separating compounds of a sample fluid in a mobile phase. The fluid separation system comprises a mobile phase drive, such as a pumping system, configured to drive the mobile phase through the fluid separation system. A separation unit, which can be a chromatographic column, is provided for separating compounds of the sample fluid in the mobile phase. The fluid separation system may further comprise a sample injector configured to introduce the sample fluid into the mobile phase, a detector configured to detect separated compounds of the sample fluid, a collector configured to collect separated compounds of the sample fluid, a data processing unit configured to process data received from the fluid separation system, and/or a degassing apparatus for degassing the mobile phase.

Embodiments of the present invention might be embodied based on most conventionally available HPLC systems, such as the Agilent 1290 Series Infinity system, Agilent 1200 Series Rapid Resolution LC system, or the Agilent 1100 HPLC series (all provided by the applicant Agilent Technologies—see www.agilent.com—which shall be incorporated herein by reference).

One embodiment comprises a pumping apparatus having a piston for reciprocation in a pump working chamber to compress liquid in the pump working chamber to a high pressure at which compressibility of the liquid becomes noticeable. One embodiment comprises two pumping apparatuses coupled either in a serial (e.g. as disclosed in EP 309596 A1) or parallel manner.

The mobile phase (or eluent) can be either a pure solvent or a mixture of different solvents. It can be chosen e.g. to minimize the retention of the compounds of interest and/or the amount of mobile phase to run the chromatography. The mobile phase can also been chosen so that the different compounds can be separated effectively. The mobile phase might comprise an organic solvent like e.g. methanol or acetonitrile, often diluted with water. For gradient operation water and organic are delivered in separate bottles, from which the gradient pump delivers a programmed blend to the system. Other commonly used solvents may be isopropanol, tetrahydrofuran (THF), hexane, ethanol and/or any combination thereof or any combination of these with aforementioned solvents.

The sample fluid might comprise any type of process liquid, natural sample like juice, body fluids like plasma or it may be the result of a reaction like from a fermentation broth.

The fluid is preferably a liquid but may also be or comprise a gas and/or a supercritical fluid (as e.g. used in supercritical fluid chromatography—SFC—as disclosed e.g. in U.S. Pat. No. 4,982,597 A).

The pressure in the mobile phase might range from 2-200 MPa (20 to 2000 bar), in particular 10-150 MPa (100 to 1500 bar), and more particularly 50-120 MPa (500 to 1200 bar).

The illustration in the drawing is schematic.

Referring now in greater detail to the drawings,FIG. 1depicts a general schematic of a liquid separation system10. A pump20receives a mobile phase from a solvent supply25, typically via a degasser27, which degases and thus reduces the amount of dissolved gases in the mobile phase. The pump20—as a mobile phase drive—drives the mobile phase through a separating device30(such as a chromatographic column) comprising a stationary phase. A sampling unit40(having a needle/seat arrangement depicted inFIG. 1schematically) is provided between the pump20and the separating device30in order to subject or add (often referred to as sample introduction) a sample fluid into the mobile phase. The stationary phase of the separating device30is configured for separating compounds of the sample liquid. A detector50is provided for detecting separated compounds of the sample fluid. A fractionating unit60can be provided for outputting separated compounds of sample fluid.

While the mobile phase can be comprised of one solvent only, it may also be mixed from plural solvents. Such mixing might be a low pressure mixing and provided upstream of the pump20, so that the pump20already receives and pumps the mixed solvents as the mobile phase. Alternatively, the pump20might be comprised of plural individual pumping units, with plural of the pumping units each receiving and pumping a different solvent or mixture, so that the mixing of the mobile phase (as received by the separating device30) occurs at high pressure and downstream of the pump20(or as part thereof). The composition (mixture) of the mobile phase may be kept constant over time, the so called isocratic mode, or varied over time, the so called gradient mode.

A data processing unit70, which can be a conventional PC or workstation, might be coupled (as indicated by the dotted arrows) to one or more of the devices in the liquid separation system10in order to receive information and/or control operation. For example, the data processing unit70might control operation of the pump20(e.g. setting control parameters) and receive therefrom information regarding the actual working conditions (such as output pressure, flow rate, etc. at an outlet of the pump20). The data processing unit70might also control operation of the solvent supply25(e.g. setting the solvent/s or solvent mixture to be supplied) and/or the degasser27(e.g. setting control parameters such as vacuum level) and might receive therefrom information regarding the actual working conditions (such as solvent composition supplied over time, flow rate, vacuum level, etc.). The data processing unit70might further control operation of the sampling unit40(e.g. controlling sample injection or synchronization of sample injection with operating conditions of the pump20). A switchable valve (not shown) can be operated so as to adjust a desired fluidic coupling within the liquid separation system10. The separating device30might also be controlled by the data processing unit70(e.g. selecting a specific flow path or column, setting operation temperature, etc.), and send—in return—information (e.g. operating conditions) to the data processing unit70. Accordingly, the detector50might be controlled by the data processing unit70(e.g. with respect to spectral or wavelength settings, setting time constants, start/stop data acquisition), and send information (e.g. about the detected sample compounds) to the data processing unit70. The data processing unit70might also control operation of the fractionating unit60(e.g. in conjunction with data received from the detector50) and provide data back.

In the following, referring toFIG. 2, a sample injector for use in a fluid separation system10as described inFIG. 1for separating components of a fluidic sample in a mobile phase according to an exemplary embodiment of the invention will be explained.

The sample injector comprises a switchable valve90, a sample loop230in fluid communication with the valve90and contributing to aspirating the fluidic sample from a vial214(or any other fluid container), and a metering pump270in fluid communication with the sample loop230and configured for introducing a metered amount of the fluidic sample into needle202.

The switchable valve90comprises two valve members which are rotatable with respect to one another. By rotating these two valve members along a rotation axis which is perpendicular to the paper plane ofFIG. 2, a plurality of ports262formed in one of the valve members and a plurality of oblong arcuate grooves264formed in the other one of the valve members can be selectively brought in or out of fluid communication with one another. Since the various ports262are connected to dedicated ones of fluidic channels of the fluidic system as shown inFIG. 2, automatically switching the valve90may allow to operate the fluidic system10in different fluid communication configurations. The valve90is configured as a six port high pressure valve in the embodiment ofFIG. 2.

Fluid communication between the high pressure pump20and the separation column30can be accomplished by an according switching state of the valve90. In such a fluidic path, a high pressure of for instance 100 MPa may be present which may be generated by the high pressure pump20. In contrast to this, the pressure state in the sample loop230may be for instance smaller than 0.1 MPa when introducing a sample into the sample loop230. When this sample loaded on sample loop230is to be loaded on column30, the pressure in sample loop230is also high, for instance 100 MPa.

For the purpose of loading the sample, a needle202may be driven out of a correspondingly shaped seat200so that the needle202can be immersed into vial214accommodating a fluidic sample to be loaded onto the needle202.

Hence,FIG. 2shows the movable needle202which can be moved under control of a control unit (not shown, for instance a central processing unit or microprocessor), between vial214and seat200.

Hence, when the needle body with its conically tapering tip is immersed into the vial214, it is possible to suck a fluidic sample accommodated within vial214into the fluidic conduit in the needle body as well as into fluid connected conduits.

Subsequently, the sample may be loaded onto the column30. However, for this purpose, it is required that the needle202be inserted into the seat200. As can be taken from the schematic drawing inFIG. 2, also the seat200has a central bore which allows for fluid communication between the fluidic conduit of the needle202and the fluidic conduit of the seat200. Therefore, the sample which has been previously loaded via the conduit of the needle body204can be conducted through the conduits and finally onto the column30.

Furthermore,FIG. 2illustrates that the sample injector includes a robot arm280which is configured for moving the injection needle202.FIG. 2shows the sample injector in an operation mode in which the injection needle202is connected to the robot arm280. In this operation mode, it is possible for the robot arm280to move the injection needle202between the fluid container214containing the fluid on the one hand and the seat200on the other hand. InFIG. 2, the robot arm280presently moves in such a direction so as to insert the needle202into the seat200for subsequently injecting a fluid which has previously been aspirated by the injection needle202into the fluidic path between pump20and separation column30. In this configuration ofFIG. 2, the injection needle202is mounted temporarily on a needle mounting unit282of the robot arm280.

After having completed the downward motion of the robot arm280(together with mounted needle202) and the needle202has been inserted into the seat200, the needle202is selectively disconnected from the needle mounting unit282and therefore from the robot arm280so that the injection needle202remains accommodated in the seat200and is now separate from the robot arm280, compareFIG. 3.

In the scenario ofFIG. 3, the fluidic switch90can be switched so that the fluid which has previously been injected in the needle202is transferred into a fluidic path between the pump20and the separation column30. During the time interval in which this injection procedure is carried out, the robot arm280is free to be used for any other task.

For instance, as shown inFIG. 4, the robot arm280, now being disconnected from the needle202, can be moved towards the fluid container214so that a fluid container gripping unit284(illustrated inFIG. 2toFIG. 4as some kind of clamping mechanism) is capable to grip the fluid container214for handling it. For instance, the fluid container214may be placed on a specific fluid container support286so as to be located at a defined position so that the needle202can be moved towards the fluid container214for aspirating the fluid (the latter operation mode is not shown in the figures).

In the following, referring toFIG. 5andFIG. 6, a sample injector500for injecting a fluid into a fluidic path according to an exemplary embodiment will be explained.

The sample injector500comprises a robot arm502which is configured for moving an injection needle506. The latter may be attached to an injection needle holder504of the robot arm502for a moving operation. Such a moving operation of an injection needle506which in the operation mode shown inFIG. 5andFIG. 6is presently disconnected from the robot arm502, can be performed between a fluid container containing a fluid to be aspirated into the injection needle506on the one hand and a seat508in fluid communication with the fluidic path (into which the fluid is to be subsequently injected) on the other hand.

Such a motion of the needle506held by the robot arm502can be better seen from the illustrations of a robot arm502of a sample injector500inFIG. 7toFIG. 10(the sample injector500ofFIG. 5toFIG. 6is very similar to the one ofFIG. 7toFIG. 10).

FIG. 7shows needle506attached to the robot arm502so that needle park stations518and seats508are empty.FIG. 8shows how the needle506is disconnected from the robot arm502and inserted in one of the needle park stations518.FIG. 9shows a detail of the scenario ofFIG. 8.FIG. 10shows a scenario similar toFIG. 9in which the needle506is disconnected from the robot arm502.

FIG. 7shows a well plate510having a plurality of fluid containing recesses (also denoted as wells) each configured for receiving a corresponding fluid (such as a biological sample, a solvent, etc.). In the operation modes ofFIG. 5andFIG. 6, the sample plate510is handled by the robot arm502, i.e. a well plate holder of the robot arm502is presently connected to the sample plate510(or well plate). The well plate holder can be brought in engagement with a correspondingly configured connection piece1300of the sample plate510, which can be best seen inFIG. 13, located at a lateral surface of the sample plate510.

Thus, the robot arm502can be used in a first operation mode in which it takes a sample plate510(such as a microtiter plate) out of one of a plurality of sample plates which are presently accommodated in a horizontally and vertically stacked manner in different compartments512of a fluid container rack514which can be best seen inFIG. 5. The well plate rack514is operable with a push loading drawer mechanism. In other words, the robot arm502may be moved along three perpendicular directions to access any desired position in a three-dimensional space, i.e. has a mechanism to move along two horizontal directions520,522and one vertical direction524, so as to able to take a selected one of the well plates510out of a corresponding well plate compartment512of the fluid container rack514and to place it on a correspondingly dimensioned and located well plate support516, i.e. a specifically defined surface area of the sample injector500on which the well plate510may be placed by the robot arm502for further operation.

When the well plate510is placed on the well plate support516, the robot arm502may disconnect from the previously moved well plate510. After this, the robot arm502may then move to a needle506which is presently parked in a seat508and at a needle park station518(compareFIG. 5orFIG. 10). The robot arm502may then take up such a needle506by attaching or connecting it to the injection needle holder504. Subsequently, the robot arm502may take along the needle506and may move it to the well plate support516so that the needle506may be immersed into fluid of a corresponding well of the well plate510for aspirating such a fluid, i.e. for sucking such a fluid into a capillary of the needle506. It is also possible that taking up the needle506by the robot arm502connects the needle506fluidicly to a capillary carried along with the robot arm502. The fluid volume to be aspirated may be defined by a metering device (such as the one shown inFIG. 2toFIG. 4) being in fluid communication with the connected capillary. After having aspirated the fluid, the needle506being still connected to the injection needle holder504of the robot arm502may be then moved back into the seat508so as to be brought in fluid-tight connection with the seat508. This procedure may be supported by foreseeing the seat508with assigned needle park station518.

Hence, the robot arm502may be operable to contribute to the fluid aspiration of the needle506and to its subsequent spatial transfer to the seat508for fluid injection while the well plates510remain spatially fixed. However, the robot arm502may also be operable to contribute to the handling of the well plates510between the fluid container rack514and the well plate support516. Since these two tasks are required alternatingly (i.e. one task is needed while the other one is not needed, and vice versa), the resources of the robot arm502can be used very efficiently basically without inactive time intervals.

In the embodiment ofFIG. 5andFIG. 6, a single seat508with a single assigned needle park station518is shown, whereas in the embodiment ofFIG. 7toFIG. 10, two seats508and two assigned needle park stations518are provided. A skilled person will understand that any desired other number of seats508/needle park stations518may be foreseen so that the robot arm502can serve also multiple seats508, multiple injection needles506and multiple needle park stations518, while simultaneously being capable of serving multiple well plates510being stored in the well plate compartments512of the well plate rack514.

After having taken a dedicated well plate510from a corresponding well plate compartment512of the well plate rack514by the robot arm502using the well plate holder, the robot arm502may move the taken well plate510to the well plate support516. Thereafter the robot arm may move to connect to a needle506(which may be presently stored in a corresponding seat508and fastened by a needle park station518) via the injection needle holder504. Then, the robot arm502having the connected (but disconnectable) injection needle506at the injection needle holder504may move to a dedicated well (shown with reference numeral1302inFIG. 13) which is filled with a fluid such as a sample or a solvent. The injection needle506may then aspire such a fluid from a corresponding well1302of the well plate510. The so aspired fluid may then be injected into a selectable seat508, or more precisely into a fluid conduit connected thereto for injecting the sample or solvent into a fluidic path between a pump20and a separation column30, as shown inFIG. 1. For this purpose, the robot arm502moves the injection needle506connected to the injection needle holder504towards the corresponding seat508/needle park station518. Upon vertically lowering the injection needle506connected to the injection needle holder502by a downward motion of the robot arm502, the injection needle506will insert into a reception hole of the needle park station518, will therefore be brought in fluid-tight engagement with the seat508and will be automatically disconnected from the injection needle holder504and connected to a corresponding supporting element of the needle park station518.

Hence, the injection needle506is configured for aspirating the fluid from the fluid container510, when the injection needle506has been moved to the fluid container510, and is configured for injecting aspirated fluid into the fluidic path when the injection needle506is accommodated in the seat508. The seat508is configured for accommodating the injection needle506and for providing fluid communication with the fluidic path. The robot arm502in turn is configured for selectively disconnecting the injection needle506from the robot arm502when the injection needle506is accommodated in the seat508. While the injection needle506remains accommodated in the seat508held by the needle park station518, the robot arm502is free for performing a further task while the injection needle506remains disconnected from the robot arm502. This further task may for instance be the well plate handling mentioned above in which the robot arm502handles a well plate510, i.e. takes a certain well plate510out of a corresponding well plate compartment512of the well plate rack514, and places the well plate510on the well plate support516. It is also possible that the robot arm502, in this time interval, puts back a well plate510which is presently located on the well plate support516into the corresponding compartment512of the well plate rack514.

In the embodiment ofFIG. 7,FIG. 8,FIG. 9, andFIG. 10, in which multiple seats508/needle park stations518and multiple needles506are present, the robot arm502may also serve another needle506, another seat508and/or another needle park station518while the fluid which has been aspirated into a needle506is presently injected via the seat508into one of fluidic paths.

When the injection needle506is accommodated in the seat508, there is a fluid-tight connection or a pressure-tight connection between the injection needle506and the seat508so that the aspirated fluid may be injected into the fluidic path without leakage.

The needle park station518retains the injection needle506while the injection needle506remains accommodated in the seat508. An advantageous feature of the sample injector500is also that the robot arm502, the injection needle506, the seat508and the needle park station518cooperate for sealing the fluid conduit of the injection needle508with regard to an environment upon disconnecting the injection needle506from the robot arm502. In other words, when the robot arm502moves upwardly after having inserted the still connected injection needle506into the seat508and to the needle park station518, a subsequent upward motion of the robot arm502will not only detach the injection needle506from the injection needle holder504of the robot arm502which is then free for serving other tasks, but at the same time an upper end of the injection needle506will be sealed so that the aspirated fluid may be injected in a downward direction into the seat508by a sucking operation. Furthermore, when the needle506is parked in the needle park station518and is in fluid-tight connection with the seat508, the robot arm502will simply move downwardly again and will operate a locking mechanism so as to unlock the needle506from the needle park station518and the seat508, and will simultaneously connect to the injection needle506by the injection needle holder504.

As can be further taken fromFIG. 5, the robot arm502may be moved along first horizontal direction520, second horizontal direction522(perpendicular to first horizontal direction520) and third vertical direction524. In the vertical direction524, the robot arm502has two separately and independently operable lift mechanisms. A first lift mechanism is configured for handling the well plates510, i.e. for taking out a dedicated well plate510from a corresponding well plate compartment512of the well plate rack514to the well plate support516and/or for putting it back from the well plate support516to a corresponding well plate compartment512of the well plate rack514. Therefore, the first lift mechanism of the robot arm needs to be capable of operating over a first stroke length which is indicated schematically inFIG. 5with reference numeral526and which may basically correspond to the height of the well plate rack514. On the other hand, the robot arm502has a second lift mechanism configured for handling the injection needle506over a second stroke length along the vertical lift axis524. Thus, for operating the needle506between a first operation mode in which it is immersed in a well1302of the well plate510and a second operation mode in which it is placed in the seat508, the needle506may also be lifted for being moved along the arrangement, as can best be seen inFIG. 7. A corresponding second stroke length is indicated schematically with reference numeral702. As can be taken from a comparison ofFIG. 5andFIG. 7, the first stroke length526is larger than the second stroke length702. The robot arm502is hence configured so as to be capable of operating the well plate holder along the first stroke length526and the injection needle holder504along the second stroke length702.

FIG. 11shows a three-dimensional view of a needle park station518together with a corresponding seat508and a cartridge-type injection needle506which has presently been disconnected from the robot arm502, more precisely from the injection needle holder504of the robot arm502.

FIG. 12shows a cross-sectional view corresponding toFIG. 11and will be described in more detail in the following in terms of the combined locking-unlocking mechanism involved in the transfer of the needle506. The robot arm502(only a part thereof is shown schematically inFIG. 12), the seat508and the needle park station518now cooperate so that upon inserting the injection needle506into the seat508by the robot arm502, a biasing spring1200of the injection needle506is biased to as to exert a sealing force between the injection needle506and the seat508. Additionally, a mutual locking mechanism of the injection needle506and the needle park station518is activated. For this purpose, the robot arm502and the injection needle506comprise cooperating first retaining elements configured for retaining the injection needle506at the robot arm502with a first retaining force while the injection needle506is outside the seat508. These first retaining elements can be realized by a latching recess1202of the injection needle506and a corresponding latching ball (or other protrusion)1204configured for engaging the latching recess1202. A further biasing spring1226of the robot arm502may press the latching ball1204into the latching recess1202for exerting the first retaining force.

Furthermore, the needle park station518and the injection needle506comprise cooperating second retaining elements configured for retaining the injection needle506at the needle park station518with the second retaining force being larger than the first retaining force and being operable when the injection needle506is inserted into the seat508so that subsequently retracting the robot arm502from the seat508releases the injection needle506from the robot arm502and retains the injection needle506at the needle park station518. These second retaining elements can be realized by further latching recesses1208of the injection needle506and a pivotable retaining lever1210which can be pivoted in a way as indicated by an arrow inFIG. 12and which has a protrusion1212for engaging one of the one or more latching recesses1208. Thus, the mutual locking mechanism is provided by the second retaining elements1208,1210,1212. Apart from this, a latch may be provided which may be actuated by the robot arm502to disengage the second retaining elements1208,1210,1212from one another so that subsequently retracting the robot arm502pulls the injection needle506along with the robot arm508.

Therefore, the described mechanism results in the fact that when the injection needle506is still connected to an injection needle holder504of the robot arm502and will be placed in the seat508, it will be disconnected from the injection needle holder504upon retracting the robot arm502upwardly. At the same time, the injection needle506will be locked to the needle park station518so as to provide for a secure connection between seat508and needle506. Furthermore, an upper end portion of the needle506is sealed so that aspirated fluid in the capillary of the needle506can subsequently be injected into the fluidic path connected to the seat508.

FIG. 14is a schematic illustration of the combined locking and unlocking mechanism described referring toFIG. 12and specifically shows that the injection needle506is arranged within a package denoted schematically with reference numerals1400,1410. Furthermore,FIG. 14shows that an additional spring1402can be provided for biasing the lever1210so that the protrusion1212will be forced into the recess1208.

FIG. 15shows a part of the schematic arrangement ofFIG. 14and additionally shows a shaft or actuator1500of the injection needle506. Furthermore, as compared to the ball1204and the spring1226, the connection between robot arm502and the injection needle506may in this embodiment be realized by a lever1502having a protrusion1504cooperating with a recess1506in the package of the needle506.

As can furthermore be taken fromFIG. 15schematically, the robot arm502may comprise a stripper tool1508configured for stripping off a fluid container (not shown inFIG. 15) from the injection needle506after having aspirated the fluid from the fluid container. Such a stripper tool1508may be advantageous when the needle506penetrates a septum or a membrane of a vial (for a sterile storage of the fluid), so that after having aspirated fluid from the vial, it may happen that the injection needle506may remain connected to the vial. The stripper tool1508will then allow the needle506to be retracted from the vial.

FIG. 16schematically shows how the shaft1500(such as a camshaft) can cooperate with a curved recess1600via a force transmission lever1602. By taking this measure, the injection needle506having the lever mechanism shown inFIG. 16is operable by the robot arm502with a reduced force exerted by the robot arm502required for sealing the fluid conduit by lever action.

More generally, a force required to be exerted by the robot or robot arm for sealing the needle may be reduced by implementing a force transmission which may use a guide rail, thereby benefiting from a lever action effect.

In the following, referring toFIG. 17toFIG. 22, a sample injector500being very similar to the above-described sample injectors500according to an exemplary embodiment of the invention will be explained.

Generally, the sample injector500provides for a combined plate handler and sample injection robot. The autosampler500shown inFIG. 17has the advantage to increase sample capacity to more than 400 vials or eight or more well plates. Furthermore, it is possible to handle vials but also well plates with the sample injector500. Additionally, the sample injector500has a very low internal volume to allow fast analysis.

In a concept, where the sample needs to be transported to the sampling unit, it would be difficult to handle well plates. In another concept, where the needle moves to the sample, a long connection capillary is required due to the increased amount of sample plates which has to be addressed. The plate handler or sample injector500ofFIG. 17combines the advantages of both systems. It contains a coupling device for pallets. With this coupling mechanism, pallets containing the sample trays can be transported from/to a hotel system (fluid container rack514) to a parking station (fluid container support516) inside the autosampler500. The hotel system contains a plurality of pallets with random access. The plate handler also contains a holding mechanism for the injection needle506. When a pallet with the sample tray is placed on the parking station, the robot (which is also denoted as robot arm502) moves a needle506to the according sample for sample aspiration.

An advantage of such a combined plate/needle movement system is that only one x, y, z robot system is needed for the plate and for the needle movement. The injection needle only has to be moved in the area of one plate (plate on park station). Thus, a short connection capillary between a needle and sampling unit can be achieved. With the x, y movement of only one well plate, the robot is available to reach two stacks of pallets with its coupling mechanism. Thus, in the described embodiment, a sample capacity of 2 stacks each having 6 sample trays can be accessed. Since the sampling needle is movable, the needle can be cleaned in a needle wash port, if desired or required.

The x, y, z robot is denoted with reference numeral1700inFIG. 17.

FIG. 18andFIG. 19show detailed views of the robot arm1700wherein the injection needle is denoted with reference numeral506and the stripper arrangement with reference numeral1508.

FIG. 20shows the sample injector ofFIG. 17in a first operation mode2000in which the robot moves a palette out of a hotel.FIG. 21shows the sample injector ofFIG. 17in a second operation mode2100in which the robot places the palette on the park station.FIG. 22shows the sample injector ofFIG. 17in a third operation mode2200in which the robot moves the needle to the according sample position to aspirate the sample.

In the following, referring toFIG. 23toFIG. 25a sample injector500according to still another slightly modified exemplary embodiment will be explained which can be used as a HPLC sample injector with an automatically disconnectable injection needle506.

A corresponding sample handling robot is able to automatically disconnect the injection needle506in a needle park station518. In this embodiment, the injection needle506is coupled to an x, y, z arm via a needle coupler2300. The needle506can be disconnected from the robot arm by a user for exchange purpose or automatically in the needle park station518. When the needle506is disconnected in the needle park station518, the robot arm is pressing the needle506into the needle seat508and loads a spring. Then, a locking mechanism may be activated which locks the needle506to the needle park station518and at the same time opens the lock to the robot arm. Thus, the needle506now is sealed in the needle seat508by the needle park station518and the robot is decoupled from the needle506. The robot now is able to do other tasks during analysis.

Next, a force amplifying by the needle locking mechanism will be explained. To seal the needle506in the needle seat508, typically a sealing force in the range of 50 to 100 N is needed. Typically, the needle506is pressed into the seat508via the z-axis of the robot. Thus, a minimal force of 50 to 100 N for the z-drive is needed if the needle506is directly coupled to the z-axis of the robot. In an embodiment of a needle coupler, a sealing force amplifying is performed during the decoupling of the needle506from the robot. Therefore, the force for the z-drive can be reduced to for instance 30 to 50 N which is a typical force needed for the z-axis to penetrate the septa of the sample vials.

FIG. 24andFIG. 25schematically illustrate the function of such a force amplification. The arrangement ofFIG. 24has a robot z-arm2400, a camshaft2402and a camplate. Furthermore, a clamp2500, a needle holder2502and a spring2504are shown inFIG. 25.

Inside the needle park station518, a clamp opens the robot end and at the same time another clamp locks the needle holder2502to the needle park station518. Now, the robot z-arm2400is able to move up without a needle506. During the up movement, the camplate2404is activating the camshaft2402inside of the needle holder2502. The camshaft2402rotates during the up movement of the robot and loads spring2504inside the needle holder2502which is pressing the needle506down in the needle seat508.

With this mechanism, a force amplification can be performed. For instance, if the sealing force of 100 N is needed to seal the needle506into the needle seat508, with a camshaft2402only ⅕ of the force is needed to load the spring2504. Of course, a force amplifying during coupling/decoupling the needle506to the robot can also be done by another lever mechanism. The camshaft mechanism is only one example.

Advantages of such embodiments of the invention will be explained in the following. A typical analysis time can be in an order of magnitude of 1 min to 60 min. During this time, the needle has to be sealed if the needle seat is flush-through design. Since the robot arm can be decoupled from the needle, the robot is able to do other tasks during this time without disturbing the analysis.

For example, such other tasks which may be done during analysis include the preparation of a next sample plate. If sample plates are stored in a plate hotel, the robot now can place the current sample plate back in the hotel and can prepare the next sample for sample injection. When the next analysis starts, the correct plate already is in place and prepared, which saves time. Another example for such a task is that a next sample can be injected with a second needle. With a second needle and needle park station, the robot already can prepare the next plate, aspirate the sample and place the second needle back in the needle park station. After the analysis is finished in the first needle/needle seat, a valve switches the second needle/needle seat to the analysis path. During analysis with the second needle, the robot handles and injects with the first needle. Therefore, no additional robotic time is added to the sample analysis time. Furthermore, a force amplifying is possible. With for instance a camshaft mechanism, the z-axis of the robot is able to achieve very high sealing loads on the injection needle. Additionally or alternatively, sample preparation and modification can also be performed as an additional task. Since the robot is decoupled from the needle, it can be used for any sample separation and modification, for instance mixing or shaking samples, operating with additional well plate positions like a heater station, barcode reader station or pipetting station. Furthermore, a vial gripper can be foreseen. It is also possible to identify needles or samples with a barcode or a transponder system (such as an RFID system).

FIG. 26toFIG. 30illustrate different operation modes of a needle handling system2600in which a needle506is decoupled from a robot arm502and coupled to a needle park station518and a seat508. The decoupling is performed by a lateral needle decoupling motion InFIG. 26, the robot arm502holding the needle506approaches the needle park station518. InFIG. 27, the robot arm502has placed the needle506in the seat508and has accommodated the needle506in the needle park station518. A locking mechanism is opened (see reference numeral2700). InFIG. 28, the locking mechanism is again closed. InFIG. 29, a coupling mechanism is opened (see reference numeral2900). InFIG. 30, the robot arm502is laterally removed from the needle506parked in the needle park station518.

It should be noted that the term “comprising” does not exclude other elements or features and the term “a” or “an” does not exclude a plurality. Also elements described in association with different embodiments may be combined. It should also be noted that reference signs in the claims shall not be construed as limiting the scope of the claims.