GB2490148A

GB2490148A - Metering device with cartridge design to safely change metering head

Info

Publication number: GB2490148A
Application number: GB1106651.1A
Authority: GB
Inventors: Hans-Peter Zimmermann
Original assignee: Agilent Technologies Inc
Current assignee: Agilent Technologies Inc
Priority date: 2011-04-20
Filing date: 2011-04-20
Publication date: 2012-10-24
Anticipated expiration: 2031-04-20
Also published as: GB2490148B; GB201106651D0

Abstract

The present invention relates to a metering device for a sample separation system, in particular for high performance liquid chromatography applications. A metering device 270 for a sample injector and for metering a fluid to be injected into a fluidic path 230, wherein the metering device comprises a drive unit 276 configured for providing a driving force for displacing the fluid to be metered, and a metering head 278 mountable to the drive unit 276 and configured for defining an amount of the fluid to be metered, wherein the metering head 278 is configured to be manually detachable from the drive unit so that, upon detaching, a potential residual pressure in the metering device is relieved. The metering head may be configured to be detachable from the drive unit without any tool. At least one further metering head may be provided for defining another amount of fluid to be metered and / or for withstanding another threshold pressure and / or made of another material.

Description

METERING DEVICE WITH CARTRIDGE DESIGN TO SAFELY CHANGE

METERING HEAD

BACKGROUND ART

[0001] The present invention relates to a metering device for a sample separation system, in particular for high performance liquid chromatography applications.

[0002] 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 to receive an amount of fluid defined by a metering device 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.

[0003] In this context, accurately metering a fluid to be injected by an injection needle is a challenge, and handling of a metering device can be complex for a user.

[0004] The product Gi 367 of the applicant Agilent Technologies is an example for a commercially available needle assy well plate autosampler having as well a metering device.

[0005] However, operating a metering device in a sample separation device for an efficient and flexible metering may still be a challenge for a user.

DISCLOSURE

[0006] It is an object of the invention to enable efficient and flexible metering in a sample separation system. The object is solved by the independent claims. Further embodiments are shown by the dependent claims.

[0007] According to an exemplary embodiment, a metering device for a sample injector and for metering a fluid to be injected into a fluidic path is provided, wherein the metering device comprises a drive unit configured for providing a driving force for displacing the fluid to be metered, and a metering head (which may also be denoted as a pump head) mountable to the drive unit and configured for defining an amount of the fluid to be metered, wherein the metering head is configured to be manually detachable from the drive unit so that, upon detaching, a potential residual pressure (i.e. a pressure which may be still present in a fluid chamber of the metering device after having operated the metering device) in the metering device is relieved at least partially.

[0008] According to another exemplary embodiment, a sample injector for injecting a fluid into a fluidic path is provided, wherein the sample injector comprises a metering device having the above mentioned features, and an injection needle being movable between a fluid container containing the fluid and a seat in fluid communication with the fluidic path, wherein the injection needle is configured for receiving the fluid from the fluid container metered by the metering device, when the injection needle has been moved to the fluid container, and for injecting received fluid into the fluidic path, when the injection needle is accommodated in the seat.

[0009] According to another exemplary embodiment, 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, particularly a pumping system, configured to drive the mobile phase through the fluid separation system, a separation unit, particularly a chromatographic column, configured for separating compounds of the fluid in the mobile phase, and a sample injector having the above mentioned features configured for injecting the fluid in the fluidic path between the mobile phase drive and the separation unit.

[0010] According to another exemplary embodiment, a method of operating a metering device for a sample injector and for metering a fluid to be injected into a fluidic path is provided, wherein the method comprises mounting a metering head to a drive unit, the metering head being configured for defining an amount of the fluid to be metered, providing a driving force by the drive unit for displacing the fluid to be metered, and manually detaching the metering head from the drive unit so that, upon detaching, a residual pressure in the metering device is relieved at least partially.

[0011] In an embodiment, a flexibly operable and therefore user-convenient metering device is provided in which it is possible that a user manually disassembles the metering head from the drive unit without the need of using additional tools such as a screwdriver. For example, with a simple turning operation, a certain metering head may be detached from a universal drive unit and may be, if desired, replaced by another metering head which is capable of metering in accordance with another operation parameter, for instance another metering volume. The manual detachability of the metering head is a significant simplification over conventional approaches in which tools such as a screwdriver or the like were required for disassembling a metering head. In addition, the manual detachable configuration of the metering head also implements a safety feature by ensuring that a potential remaining pressure which may still be present in a fluid accommodation volume of the metering device, for example as a result from a previous experiment, may be relieved during the disassembly operation. In other words, the disassembly mechanism may be configured in such a way that disassembling the metering head from the drive unit automatically results in a reduction of such a potential remaining pressure to a safe value before completion of the disassembly procedure (i.e. before the drive unit and the metering head are disassembled into separate bodies).

[0012] Exemplary embodiments of the invention have the advantage that no tooling is needed to exchange a metering head. A simple exchange of the metering head according to a desired application (for instance with regard to a special injection volume and/or pressure) is possible. No canting of the metering head is necessary due to a non-uniform torque of mounting screws. Moreover, a consistent cartridge system for high pressure valve and metering head is made possible.

[0013] In the following, further embodiments of the metering device will be explained.

However, these embodiments also apply to the sample injector, the fluid separation system, and the method.

[0014] In an embodiment, the metering head is configured to be detachable from the drive unit without any tool. Thus, the force required for detaching the metering head from the drive unit may be achievable by the muscle force of an average user, for instance an average adult user.

[0015] In an embodiment, the metering device comprises at least one further metering head mountable to the drive unit, wherein each of the at least one further metering head is configured for defining another amount of fluid to be metered and/or is configured for withstanding another threshold pressure and/or is made of another material. Thus, a set of different metering heads and one common drive unit may be provided, wherein different metering heads may differ regarding at least one property in the context of metering, for instance may differ regarding a volume of a fluid to be metered. For example, metering heads with volumes of 40 p1 injection volume, 100 p1 injection volume and 900 p1 injection volume may be provided. Also the pressure bearable by a respective metering head may differ among different metering heads. For instance, metering heads with a pressure stability of up to 600 bar and of up to 1200 bar may be provided. Depending on the application, it is also possible that different materials for the metering heads are used, for instance a biocompatible metering head and a stainless steel metering head. Hence, a bioinert (for instance titanium) metering head may be provided, as well as a stainless steel metering head.

[0016] In an embodiment, the drive unit comprises a first engagement element and the metering head comprises a cooperating second engagement element, wherein the engagement elements are configured so that upon engaging the first engagement element with the second engagement element the metering head is mounted to the drive unit, and that upon disengaging the first engagement element from the second engagement element the metering head is detached from the drive unit. Such an engagement mechanism provides a form closure locking force when the engagement elements are engaged. Thus, any undesired automatic detachment, for instance due to the presence of a residual pressure in an interior of the metering device is safely prevented by the engagement mechanism. On the other hand, such an engagement mechanism may be manually disengaged by a user so as to change the metering head.

[0017] In an embodiment, the metering device comprises a detachment delay mechanism configured so that when the metering head is manually detached from the drive unit, release of the metering head from the drive unit is delayed until the residual pressure in the metering device is at least partially relieved. Such a delay mechanism allows to delay the detachment of the metering head from their drive unit until the residual pressure is relieved at least down to a threshold value which is considered to be not dangerous for a user. For example, such a delay mechanism can be realized by a locking pin which locks the drive unit to the metering head until a pressure sensor within the metering device releases the locking pin upon detecting that the pressure is relieved to a certain degree.

[0018] In an embodiment, the metering head is configured so that, upon manually detaching the metering head from the drive unit, pressure equilibration between a pressure in the metering device and a pressure in an environment of the metering device is completed before the metering head is released from the drive unit. For example, upon detaching, when the user executes a manual motion for detaching, this detaching mechanism can automatically open certain channels allowing a pressure to be released, for instance fluid channels. These fluid channels can be opened automatically when the user substitutes the metering head.

[0019] In an embodiment, the metering head is configured to be manually mountable, particularly without any tool (such as a screwdriver), to the drive unit. In such an embodiment, it is not only possible to detach the metering head from the drive unit, but also the attachment or mounting procedure can be performed manually without the need to use any separate tool. For example, a turning or a plugging operation may be sufficient for this purpose.

[0020] In an embodiment, the metering head and/or the drive unit comprises a safety mechanism configured for disabling manual detachment of the metering head from the drive unit when the residual pressure exceeds a predetermined threshold value. For example, any mechanical, magnetic, electrical, or other mechanism may be foreseen which ensures that no detachment can be finalized before the residual pressure has been relieved to a non-dangerous degree.

[0021] In an embodiment, the safety mechanism comprises an adaptation of the tribological characteristics of the metering head and the drive unit to one another so that when the residual pressure exceeds the predetermined threshold value, the tribological characteristics generate a frictional force exceeding a muscle force of an operator, particularly exceeding approximately 200 N. Depending on the residual pressure, the friction between the metering head and the drive unit may be influenced by the residual pressure in such a way that a detachment is impossible with a reasonable force until the residual pressure has been reduced to a sufficient degree to enable a muscle force of an operator to perform the disassembly operation. For instance, the metering head and the drive unit may be arranged so that they are pressed to one another by a residual pressure, thereby increasing the frictional force between both components so as to disable manual detachment in the presence of such a force.

[0022] In an embodiment, the metering head is configured to be manually detachable from the drive unit merely by turning a turn-lock fastener, by which the metering head is mounted on the drive unit, by at least two revolutions, particularly by at least five revolutions. By requiring an angle of at least 7200 to be turned by a user, which requires a certain time, it can be ensured that the pressure relief has advanced to a sufficient degree to prevent any danger for a user.

[0023] In an embodiment, the metering head is configured to be manually detachable from the drive unit by actuating a bayonet coupling by which the metering head is mounted on the drive unit. A bayonet coupling is easy to handle by a user and also allows a certain delay of the detaching so that the pressure relief can be achieved.

A bayonet coupling may be a coupling in which two or more pins extend out from a plug and engage in grooves in the side of a socket. One of drive unit and metering head may serve as such a plug, and the other one as such a socket.

[0024] In an embodiment, the metering head is configured to be manually detachable from the drive unit by actuating a knurled head screw by which the metering head is mounted on the drive unit. A knurled head screw allows an attachment or detachment by a simple turning operation of a user which renders the metering device easy to handle and save in use.

[0025] In an embodiment, the metering head comprises a reciprocatable piston reciprocating in a metering volume and being driven by the drive unit. In operation, the drive unit may apply a force which can be transferred to a reciprocating piston which then displaces the fluid from the fluid accommodation volume of the metering device to a flu idic destination such as a capillary.

[0026] In an embodiment, the drive unit comprises a stepper motor driving a spindle which, in turn, is configured for actuating a ball acting on the piston. Thus, an electric motor may drive the spindle which can act on a ball applying a certain force to the drive unit regardless of slight angular misalignments between spindle and piston.

[0027] In an embodiment, the metering head is configured so that the amount of the fluid to be metered is less than approximately 1000 p1, particularly less than approximately 100 p1, more particularly less than approximately 10 p1. In such an embodiment, very small volumes as required by microfluidic applications can be displaced by the metering head as well.

[0028] In an embodiment, the sample injector comprises the seat in fluid communication with the fluidic path and configured for receiving the injection needle in a pressure-tight way. In a sample loop, the sample may be injected into a fluidic path by the mechanically drivable needle. The drivable needle is controllable to be moved out of the seat of the sample loop into a vial or any other sample container (such as a well plate) to receive a fluid and back from the vial into the seat. The seat-needle connection may be pressure tight, for instance up to 600 bar or up to 1200 bar.

[0029] In an embodiment, the drive unit comprises a reader device (such as a contactless reader device like an RFID reader device), and the metering head comprises a transponder (such as an RFID tag or a contactless chip card) storing identification information identifying the metering head, wherein the reader device is configured for reading the information identifying the metering head when the metering head is mounted to the drive unit. This allows an automatic identification of a presently mounted metering head (for instance indicating its metered fluid volume) by the drive unit, wherein this information may be used for controlling operation of the drive unit in correspondence to the used metering head. This may also allow the drive unit to detect the event of the detachment of the metering head, since the readability of the identification information may get lost upon detaching the metering head from the drive unit (due to an increase of a distance between reader device and transponder beyond a readability range).

[0030] The fluidic device may include or cooperate with a processing element 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 or fluid. 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.

[0031] 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 pm to essentially 50 pm. 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 pm to essentially 0.2 pm. The fluidic sample may be passed through the pores, wherein an interaction may occur between the fluidic sample and the pores.

[0032] 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.

[0033] 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 flu idic 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.

[0034] The fluidic 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 pm, particularly less than 200 pm, more particularly less than 100 pm or less than 50 pm or less (for instance down to 15 pm or 12 pm). The analysis system may also be configured as a nanofluidic device. The term "nanofluidic device" may particularly denote a fluidic device as described herein which allows to convey fluid through nanochannels with a flow rate of less than 100 nI/mm, particularly ofless than lOnI/min.

[0035] 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.

[0036] 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. [0037] 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 device (H PLC) device by which different fractions of an analyte may be separated, examined and analyzed.

[0038] 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 fitting element and/or fitting for coupling a tubing (provided the conducting the mobile phase) to a fluidic device in such fluid separation system. 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. The fluidic device to which the tubing is or can be coupled can be any of such devices, and plural of such fittings or fitting elements may be used within such fluid separation system.

[0039] 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.aqilent.com -which shall be incorporated herein by reference).

[0040] 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 is delivered in separate bottles, from which the gradient pump delivers a programmed blend to the system. Other commonly used solvents may be isopropanol, THF, hexane, ethanol and/or any combination thereof or any combination of these with aforementioned solvents.

[0041] 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.

[0042] 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 US 4,982,597 A).

[0043] 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 particular 50-1 20 MPa (500 to 1200 bar).

[0044] The HPLC system might further comprise a sampling unit for introducing the sample fluid into the mobile phase stream, a detector for detecting separated compounds of the sample fluid, a fractionating unit for outputting separated compounds of the sample fluid, or any combination thereof. Further details of HPLC system are disclosed with respect to the aforementioned Agilent HPLC series, provided by the applicant Agilent Technologies, under www.aqilent.com which shall be in cooperated herein by reference.

BRIEF DESCRIPTION OF DRAWINGS

[0045] Other objects and many of the attendant advantages of embodiments of the present invention will be readily appreciated and become better understood by reference to the following more detailed description of embodiments in connection with the accompanied drawing(s). Features that are substantially or functionally equal or similar will be referred to by the same reference sign(s). The illustration in the drawing is schematically.

[0046] Figure 1 shows a liquid sample separation device, in accordance with embodiments of the present invention, e.g. used in high performance liquid chromatography (HPLC).

[0047] Figure 2 shows a sample injector of a liquid separation device in accordance with embodiments of the present invention.

[0048] Figure 3 shows a sample injector having a metering device according to an exemplary embodiment of the invention.

[0049] Figure 4 is another view of the sample injector of Figure 3 however showing a cross-section of the metering device illustrating an interior constitution thereof.

[0050] Figure 5 shows a metering device according to an exemplary embodiment in an assembled state.

[0051] Figure 6 shows a metering head of a metering device according to an exemplary embodiment.

[0052] Figure 7 shows a cross-sectional view of the metering head of Figure 6.

[0053] Figure 8 shows a metering device according to an exemplary embodiment of the invention.

[0054] Figure 9 shows a metering device according to an exemplary embodiment of the invention.

[0055] [0056] The illustration in the drawing is schematically.

[0057] Referring now in greater detail to the drawings, Fig. I depicts a general schematic of a liquid separation system 10. A pump 20 receives a mobile phase from a solvent supply 25, typically via a degasser 27, which degases and thus reduces the amount of dissolved gases in the mobile phase. The pump 20 -as a mobile phase drive -drives the mobile phase through a separating device 30 (such as a chromatographic column) comprising a stationary phase. A sampling unit 40 (having a needle/seat arrangement depicted in Fig. I schematically) is provided between the pump 20 and the separating device 30 in order to subject or add (often referred to as sample introduction) a sample fluid into the mobile phase. The stationary phase of the separating device 30 is configured for separating compounds of the sample liquid. A detector 50 is provided for detecting separated compounds of the sample fluid. A fractionating unit 60 can be provided for outputting separated compounds of sample fluid.

[0058] 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 pump 20, so that the pump 20 already receives and pumps the mixed solvents as the mobile phase. Alternatively, the pump 20 might 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 device 30) occurs at high pressure und downstream of the pump 20 (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.

[0059] A data processing unit 70, 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 system 10 in order to receive information and/or control operation.

For example, the data processing unit 70 might control operation of the pump 20 (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 pump).

The data processing unit 70 might also control operation of the solvent supply 25 (e.g. setting the solvent/s or solvent mixture to be supplied) and/or the degasser 27 (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 unit 70 might further control operation of the sampling unit 40 (e.g. controlling sample injection or -12-synchronization sample injection with operating conditions of the pump 20). A switchable valve 90 can be operated so as to adjust a desired fluidic coupling within the liquid separation system 10. The separating device 30 might also be controlled by the data processing unit 70 (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 unit 70. Accordingly, the detector 50 might be controlled by the data processing unit 70 (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 unit 70. The data processing unit 70 might also control operation of the fractionating unit 60 (e.g. in conjunction with data received from the detector 50) and provides data back.

[0060] In the following, referring to Fig. 2, a sample injector for use in a fluid separation system 10 as described in Fig. I for separating components of a fluidic sample in a mobile phase according to an exemplary embodiment of the invention will be explained.

[0061] The sample injector comprises the switchable valve 90, a sample loop 230 in fluid communication with the valve 90 and configured for receiving the fluidic sample from a vial 214, a metering pump 270 (also denoted as a metering device) in fluid communication with the sample loop 230 and configured for introducing a metered amount of the fluidic sample on the sample loop 230.

[0062] The switchable valve 90 comprises 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 of Fig. 2, a plurality of ports 262 formed in one of the valve members and a plurality of oblong arcuate grooves 264 formed in the other one of the valve members can be selectively brought in or out of fluid communication with one another. Since the various ports 262 are connected to dedicated ones of fluidic channels of the fluidic system as shown in Fig. 2, automatically switching the valve 90 may allow to operate the fluidic system 10 in different fluid communication configurations. The valve 90 is configured as a six port high pressure valve in the embodiment of Fig. 2.

[0063] Fluid communication between the high pressure pump 20 and the separation column 30 can be accomplished by an according switching state of the valve 90. In such a fluidic path, a high pressure of for instance 100 MPa may be present which may be generated by the high pressure pump 20. In contrast to this, the pressure state in the sample loop 230 may be for instance smaller than 0.1 MPa when introducing a sample into the sample loop 230. When this sample loaded on sample loop 230 is to be loaded on column 30, the pressure in sample loop 230 is also high, for instance 100 MPa.

[0064] For the purpose of loading the sample on the sample loop 230, a needle 202 may be driven out of a correspondingly shaped seat 200 so that the needle 202 can be immersed into vial 214 accommodating a fluidic sample to be loaded onto the sample loop 230. A loop capillary 240 is provided in the sample loop 230 for at least partially accommodating the introduced sample.

[0065] More precisely, Fig. 2 shows the movable needle 202 which can be moved under control of a control unit (not shown, for instance a central processing unit or microprocessor), between vial 214 and seat 200. As can be taken from a detailed drawing of needle/seat arrangement 220 in Fig. 2, the needle 202 comprises a needle body 206 having a central lumen acting as a fluid conduit. The needle body 206 is mounted in a fluid tight manner within a fitting 208 which has a central fluidic conduit 210. When the needle body 206 is mounted in the fitting 208, the fluid conduits are in fluid communication to one another.

[0066] Hence, when the needle body 206 with its conically tapering tip is immersed into the vial 214, it is possible to suck a fluidic sample accommodated within vial 214 into the fluidic conduit as well as into fluid connected conduits.

[0067] Subsequently, the sample may be loaded onto the column 30. However, for this purpose, it is required that the needle 202 is inserted into the seat 200. As can be taken from Fig. 2, also the seat 200 has a central bore 252 which allows for fluid communication between the fluidic conduit of the needle 202 and the fluidic conduit of the seat 200. Therefore, the sample which has been previously loaded via the conduit of the needle body 206 can be conducted through the conduits and finally onto the column 30.

[0068] The metering device 270 of the sample injector system of Fig. 2 comprises a drive unit 276 configured for providing a driving force for displacing the fluid to be metered. Furthermore, the metering device 270 comprises a metering head 278 mounted to the drive unit 276 and configured for defining an amount of the fluid to be -14-metered. Fig. 2 shows the metering unit 270 in a mounted state. However, the metering head 278 can be manually detached from the drive unit 276 by a human user so that, upon detaching, a potential residual pressure in the metering device 270 is released.

For this purpose, cooperating engagement means in the form of an external thread 272 of the metering head 278 and an internal thread 274 of the drive unit 276 are provided.

[0069] Fig. 3 shows a sample injector 300 according to an exemplary embodiment of the invention, in which a metering head 302 is manually detachably mounted to a drive unit 304.

[0070] Fig. 4 shows a cross-sectional view of the described components. A stepper motor 400 of the drive unit 304 drives a spindle 402 which, in turn, actuates a ball 404.

In other words, an actuation of the ball 404 is performed from its rear side by the spindle 402. The ball 404 then drives, on its front side, a piston 406 reciprocating within a tubular fluidic channel 408 for metering fluid to be injected through a forward end of the volume 408.

[0071] Fig. 5 shows an embodiment of a metering device 500 in which a manually detachable metering head 504 has been attached onto a drive head 502. By turning a knurled head screw 506 by a user, the metering head 504 can be detached manually, i.e. without the need of any tools, from the drive unit 502. During operating the knurled head screw 506, an operator has to perform a turning operation using her or his hands, wherein during this turning operation any potential residual pressure inside of the metering device 500 can be at least partially relieved so as to prevent a user from injury (resulting from a too high residual pressure) when mounting or disassembling the metering head 504 from the drive unit 502.

[0072] Thus, the autosampler of Fig. 4 when being used with the metering device 500 of Fig. 5 provides for a cartridge system allowing a fast change of the metering head 504 without any tooling. Fig. 5 shows a configuration in which the metering head cartridge 504 is connected to the drive mechanism 502 by the knurled nut 506.

[0073] Fig. 6 shows the metering head 504 in a detached state.

[0074] Fig. 7 shows a cross-sectional view of the metering head 504. The ball 404 at the position where it actuates the metering head 504 is shown schematically as well.

Also the reciprocating piston 700 (made of stainless steel) is shown. Furthermore, an RFID tag 702 is attached at a rear position of the metering head 504. When the metering head 504 is mounted to the drive unit 502, an RFID reader forming part of the drive unit 502 (not shown) is located sufficiently close to the RFID chip 702 so as to read identification information unambiguously identifying the metering head 504 from the RFID tag 702 in a wireless manner. Thus, the corresponding operation of the drive unit 402 can be adjusted to the properties of this identified drive head 504, for instance with regard to a metering volume of the metering head 504, etc. Hence, an RFID tag 702 on each cartridge or metering head 504 allows to detect which metering head is mounted [0075] Fig. 7 furthermore shows a stainless steel holder 704, a ceramic inlet 706, a PEEK guide 708, and an aluminum housing 712. Furthermore, a top seal piston for zero volume metering is shown as well with reference numeral 714.

[0076] Fig. 8 shows a metering device 800 according to another exemplary embodiment of the invention in which a metering head 802 having a bayoneted lock is manually attached to a drive unit 804. Hence, also a bayoneted lock or another fastening mechanisms is possible. Thus, no tooling is necessary to change the metering head 504.

[0077] Fig. 9 shows a metering device 900 according to another exemplary embodiment of the invention in which is similar to the metering device 500. Fig. 9 shows the metering head 504 after being manually detached from the drive head 502. In this embodiment, the attaching is performed by a screw fitting. An external thread 902 of the drive head 502 is brought in engagement with a corresponding internal thread (not shown) of the metering head 504. Since the screw fitting requires a considerable time for disassembly, any remaining pressure in the assembled metering device 900 is released during disassembly.

[0078] It should be noted that the term "comprising" does not exclude other elements or features and the "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.

Claims

CLAIMS1. A metering device (500) for a sample injector (300) and for metering a fluid to be injected into a fluidic path (230), the metering device (500) comprising: a drive unit (502) configured for providing a driving force for displacing the fluid to be metered; a metering head (504) mountable to the drive unit (502) and configured for defining an amount of the fluid to be metered; wherein the metering head (504) is configured to be manually detachable from the drive unit (502) so that, upon detaching, a potential residual pressure in the metering device (500) is relieved.
2. The metering device (500) of the preceding claim, wherein the metering head (504) is configured to be detachable from the drive unit (502) without any tool.
3. The metering device (500) of claim I or any one of the above claims, comprising at least one further metering head mountable to the drive unit (502), wherein each of the at least one further metering head is configured for defining another amount of fluid to be metered and/or is configured for withstanding another threshold pressure than the metering head (504) and/or is made of another material than the metering head (504).
4. The metering device (500) of claim 1 or any one of the above claims, wherein the drive unit (502) comprises a first engagement element (274) and the metering head (504) comprises a cooperating second engagement element (272), wherein the engagement elements (272, 274) are configured so that upon engaging the first engagement element (274) with the second engagement element (272) the metering head (504) is mounted to the drive unit (502), and that upon disengaging the first engagement element (274) from the second engagement element (272) the metering head (504) is detached from the drive unit (502).
5. The metering device (500) of claim I or any one of the above claims, comprising a detachment delay mechanism configured so that when the metering head (504) is manually detached from the drive unit (502), release of the metering head (504) from the drive unit (502) is delayed until the residual pressure in the metering device (500) is at least partially relieved.
6. The metering device (500) of claim I or any one of the above claims, wherein the metering head (504) is configured so that, upon manually detaching the metering head (504) from the drive unit (502), pressure equilibration between a pressure in the metering device (500) and a pressure in an environment of the metering device (500) is completed before the metering head (504) is released from the drive unit (502).
7. The metering device (500) of claim 1 or any one of the above claims, wherein the metering head (504) is configured to be manually mountable, particularly without any tool, to the drive unit (502).
8. The metering device (500) of claim 1 or any one of the above claims, wherein at least one of the metering head (504) and the drive unit (502) comprises a safety mechanism configured for disabling manual detachment of the metering head (504) from the drive unit (502) when the residual pressure exceeds a predetermined threshold value.
9. The metering device (500) of the preceding claim, wherein the safety mechanism comprises an adaptation of the tribological characteristics of contacting surface portions the metering head (504) and the drive unit (502) sO that when the residual pressure exceeds the predetermined threshold value, the tribological characteristics generate a frictional force exceeding a muscle force of an operator, particularly exceeding 200 N.
10. The metering device (500) of claim 1 or any one of the above claims, wherein the metering head (504) is configured to be manually detachable from the drive unit (502) merely by turning a turn-lock fastener, by which the metering head (504) is mounted on the drive unit (502), by at least two revolutions, particularly by at least five revolutions.
11. The metering device (500) of claim 1 or any one of the above claims, wherein the metering head (504) is configured to be manually detachable from the drive unit (502) by actuating a bayonet coupling by which the metering head (504) is mounted on the drive unit (502).
12. The metering device (500) of claim 1 or any one of the above claims, wherein the metering head (504) is configured to be manually detachable from the drive unit (502) by actuating a knurled head screw (506) by which the metering head (504) is mounted on the drive unit (502).
13. The metering device (500) of claim 1 or any one of the above claims, wherein the metering head (504) comprises a reciprocatable piston (700) reciprocating in a metering volume and being driven by the drive unit (502).
14. The metering device (500) of the preceding claim, wherein the drive unit (502) comprises a stepper motor (400) driving a spindle (402) which, in turn, is configured for actuating a ball (404) acting on the piston (400).
15. The metering device (500) of claim 1 or any one of the above claims, wherein the metering head (504) is configured so that the amount of the fluid to be metered is less than 1000 p1, particularly less than 100 p1, more particularly less than 10 p1.
16. The metering device (500) of claim I or any one of the above claims, wherein the drive unit (502) comprises a reader device and the metering head (504) comprises a transponder (702) storing identification information identifying the metering head (504), wherein the reader device (502) is configured for reading the information identifying the metering head (504) when the metering head (504) is mounted to the drive unit (502).
17. A sample injector (300) for injecting a fluid into a fluidic path (230), the sample injector (300) comprising: a metering device (500) of claim 1 or any one of the above claims; an injection needle (202) being movable between a fluid container (214) containing the fluid and a seat (200) in fluid communication with the fluidic path (230); wherein the injection needle (202) is configured for receiving the fluid from the fluid container (214) metered by the metering device (500), when the injection needle (202) has been moved to the fluid container (214), and for injecting received fluid into the fluidic path (230), when the injection needle (202) is accommodated in the seat (200).
18. The sample injector (300) of the preceding claim, comprising the seat (200) in fluid communication with the fluidic path (230) and configured for receiving the injection needle (202) in a pressure-tight way.
19. A fluid separation system (10) for separating compounds of a fluid in a mobile phase, the fluid separation system (10) comprising: a mobile phase drive (20), particularly a pumping system, configured to drive the mobile phase through the fluid separation system (10); a separation unit (30), particularly a chromatographic column, configured for separating compounds of the fluid in the mobile phase; and a sample injector (40, 300) according to claim 17 or any one of the above claims configured for injecting the fluid in the fluidic path (230) between the mobile phase drive (10) and the separation unit (30).
20. The fluid separation system (10) according to the preceding claim, comprising at least one of the following features: the fluid separation system (10) is configured to analyze at least one physical, chemical and/or biological parameter of at least one compound of the fluid; the fluid separation system (10) comprises at least one of the group consisting of a detector device (50), a device for chemical, biological and/or pharmaceutical analysis, a capillary electrophoresis device, a liquid chromatography device, an HPLC device (10), a gas chromatography device, a gel electrophoresis device, and a mass spectroscopy device; the fluid separation system (10) is configured to conduct the fluid with a high pressure; the fluid separation system (10) is configured to conduct the fluid with a pressure of at least 100 bar, particularly of at least 500 bar, more particularly of at least 1000 bar; the fluid separation system (10) is configured as a microfluidic device; the fluid separation system (10) is configured as a nanofluidic device.the separation unit (30) is configured for retaining a part of components of the fluid and for allowing other components of a mobile phase to pass the separation unit (30); at least a part of the separation unit (30) is filled with a separating material; at least a part of the separation unit (30) is filled with a separating material, wherein the separating material comprises beads having a size in the range of I pm to 50 pm; at least a part of the separation unit is filled with a separating material, wherein the separating material comprises beads having pores having a size in the range of 0.01 pm to 0.2 pm.
21. A method of operating a metering device (500) for a sample injector (300) and for metering a fluid to be injected into a fluidic path (230), the method comprising: mounting a metering head (504) to a drive unit (502), the metering head (504) being configured for defining an amount of the fluid to be metered; providing a driving force by the drive unit (502) for displacing the fluid to be metered; manually detaching the metering head (504) from the drive unit (502) 50 that, upon detaching, a residual pressure in the metering device (500) is relieved. -21 -