GB2516027A - Injection needle cartridge with integrated sealing force generator - Google Patents
Injection needle cartridge with integrated sealing force generator Download PDFInfo
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- GB2516027A GB2516027A GB1312181.9A GB201312181A GB2516027A GB 2516027 A GB2516027 A GB 2516027A GB 201312181 A GB201312181 A GB 201312181A GB 2516027 A GB2516027 A GB 2516027A
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- injection needle
- cartridge
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- fluid
- sealing force
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/16—Injection
- G01N30/22—Injection in high pressure liquid systems
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/24—Automatic injection systems
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
- G01N35/1009—Characterised by arrangements for controlling the aspiration or dispense of liquids
- G01N35/1011—Control of the position or alignment of the transfer device
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- Health & Medical Sciences (AREA)
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- Analytical Chemistry (AREA)
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- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Fluid Mechanics (AREA)
- Sampling And Sample Adjustment (AREA)
Abstract
An injection needle cartridge 300 for a sample injector for injecting a sample fluid into a mobile phase in a fluidic path of a fluid separation system between a mobile phase drive and a separation unit comprises, an injection needle 302 configured for aspirating the sample fluid from a fluid container when the injection needle has been moved to the fluid container, and for injecting aspirated sample fluid into the fluidic path when the injection needle is sealingly accommodated in a needle sea. A sealing force generator 304 is configured for applying a sealing force to the injection needle for sealingly accommodating the injection needle in the needle seat. The injection needle cartridge is configured for being substitutably mountable on a handling robot of the sample injector for handling the injection needle cartridge between the fluid container and the needle seat.
Description
INJECTION NEEDLE CARTRIDGE WITH INTEGRATED SEALING
FORCE GENERATOR----
BACKGROUND ART
[0001] The present invention relates to an injection needle cartridge, a needle set, a sample injector for a fluid separation system, a fluid separation system (in particular for high performance liquid chromatography applications), and a method of operating a sample injector.
[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 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.
[0003] WO 2011/085284 discloses techniques for force sensing. A computing device is configured to have a desired force setting. A first vertical position of a needle is, detemiined using the computer device. A control signal is sent from the computing device to a positioning device. In response to the control signal, the needle is positioned *at the first vertical position. When in the first vertical position, surfaces of a tip of the needle are in contact with surfaces of an opening of a sealing member and positioning the needle causes application of a force at surfaces of the opening in contact with surfaces of the tip of the needle. In response to application of the force, a spring is compressed a distance that is proportional to the force. The force is measured using a force sensor.
[0004] US 5,194,226 discloses that, in a dosing device for analyzing apparatus, particularly for liquid chromatography, with a dosing loop, a change-over valve and a dosing needle are provided which can be introduced into a sample inlet of the change-over valve, through which dosing needle sample liquid can be dosed by means of a sample pump into the sample inlet and the dosing loop, the dosing needle has a conical sealing surface at its front end. The sample inlet has a sample inlet passage which forms a conical annular shoulder. The dosing needle with its conical sealing surface engages this annular shoulder with a defined pre-stress.
[0005] The product Gi 329 of the applicant Agilent Technologies, Inc., is an example for a commercially available autosampler with an injection needle and a corresponding needle seat.
[0006] In conventional autosamplers, a robot grips the needle and inserts the needle into the needle seat, wherein the robot applies a sealing force to achieve a high pressure resistant sealing between needle and needle seat. When different kinds of needles are used for different applications, the robot has to apply sealing forces of different values to the needle-seat arrangement. For instance, when a ceramic needle for biological applications is used, another sealing force is required as compared to a scenario in which a stainless steel needle is used. This requires to program or adjust the robot in a way that different needle force values can be applied depending on the used needle. Thus, in conventional systems, the injection needle is mounted to a robot arm and is pressed into the sealing seat with a fixed force. The sealing force is defined by a loading spring inside the robot arm. Hence, the sealing force is defined by the robot system. If an injection needle is a used with different material or sealing geometry (for instance bioinert, 600 bar-resistant, 1200 bar-resistant), the sealing force has to be changed via firmware or software of the needle drive.
[0007] Hence, proper sealing between an injection needle and a needle seat is still a challenge, particularly when a high degree of flexibility is desired to use such a system for different applications.
DISCLOSURE
[oooa It is an object of the invention to enable efficient and flexible fluid handling in a sample separation system. The object is solved by the independent claims. Further embodiments are shown by the dependent claims.
[00091 According to an exemplary embodiment, an injection needle cartridge (such as a separate module) for a sample injector for injecting a sample fluid into a mobile phase in a fluidic path of a fluid separation system between a mobile phase drive and a separation unit is provided, wherein the injection needle cartridge comprises an injection needle configured for aspirating the sample fluid from a fluid container when the injection needle has been moved to the fluid container, and for injecting aspirated sample fluid into the fluidic path when the injection needle is sealingly accommodated in a needle seat, and a sealing force generator configured for generating and applying a sealing force to the injection needle for sealingly accommodating the injection needle in the needle seat, wherein the injection needle cartridge is configured for being substitutably or exchangeably mountable on a handling robot of the sample injector for handling the injection needle cartridge between the fluid container and the needle seat.
[0010] According to another exemplary embodiment, a needle set is provided which comprises a plurality of injection needle cartridges having the above mentioned features, wherein different ones of the injection needle cartridges provide different sealing force values (however, a part of the injection needle cartridges may also provide the same sealing force value).
[0011] According to still another exemplary embodiment, a sample injector for injecting a sample fluid into a mobile phase in a fluidic path of a fluid separation system between a mobile phase drive and a separation unit is provided, wherein the sample injector comprises an injection needle cartridge having the above mentioned features, a needle seat configured for sealingly accommodating the injection needle of the injection needle cartridge and providing fluid communication with the fluidic path, wherein the sealing force generator of the injection needle cartridge provides the sealing force when the injection needle is accommodated in the needle seat, and a handling robot on which the injection needle cartridge is mountable or mounted and being configured for moving the injection needle between a fluid container containing the sample fluid and the needle seat.
[0012] According to still another exemplary embodiment, a fluid separation system (such as a liquid chromatography system) for separating compounds of a sample 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 sample fluid in the mobile phase, and a sample injebtor having the above mentioned features and being configured for injecting the sample fluid in the fluidic path between the mobile phase drive and the separation unit.
[0013] According to yet another exemplary embodiment, a method of operating a sample injector with an injection needle cartridge having the above mentioned features for injecting a sample fluid into a mobile phase in a fluidic path of a fluid separation system between a mobile phase drive and a separation unit is provided, wherein the method comprises substitutably mounting the injection needle cartridge on a handling robot of the sample injector, moving the injection needle cartridge by the handling robot to a fluid container containing the sample fluid, aspirating the sample fluid from the fluid container via the injection needle into a sample loop of the sample injector, moving the injection needle cartridge by the handling robot to the needle seat and sealingly accommodating the injection needle in the needle seat by applying a sealing force generated by the sealing force generator, and injecting the aspirated sample fluid into the fluidic path when the injection needle is sealingly accommodated in the needle seat.
[0014] According to an embodiment, an integral injection needle cartridge is provided as a separate member from robot and needle seat and having integrated therein a sealing force generator for generating a precisely defined value of a sealing force to be applied to the needle cartridge-seat configuration, which value is specifically adapted to the present aplication as well as to the kind of injection needle being integrated as well in the injection needle cartridge. Thus, for each specific application, a user only has to select an appropriate needle cartridge having a needle with desired properties (e.g. ceramic needle or stainless steel needle) to ensure that the correct value of the sealing force is applied to the cartridge-seat configuration. No inconsistencies between robot and needle can occur. Furthermore, any inaccuracies concerning a sealing force being transmitted between robot and needle can be excluded when the sealing force generator forms part of a (for instance inseparable) injection needle cartridge, since no sealing force transmission is necessary between robot and needle according to exemplary embodiments. Thus, a flexible modular needle cartridge is provided in which a predefined, appropriate sealing force is generated which may be adjusted to the individual needle geometry. An exemplary embodiment therefore provides a needle cartridge system, in which a preloaded spring or another appropriate sealing force generator is included in the cartridge which determines the sealing force of the specific needle. If the needle has to be changed in such a system (for instance a liquid chromatography system, in which the injection needle is a consumable), the complete needle cartridge including sealing force generator and housing (e.g. spring and spring cage) may be changed. Therefore, the sealing force can be adapted to the requirements of the needle material, needle geometry and maximum system pressure without changing the algorithm of a needle drive mechanism. Hence, exemplary embodiments have the advantage that the sealing force is an attribute of the needle cartridge rather than of the robot arm. Different types of needle cartridges can thus be handled by the same needle drive mechanism.
[0015] In the following, further embodiments of the injection needle cartridge, the needle set, the sample injector, the fluid separation system, and the method will be explained.
[0016] In an embodiment, the injection needle cartridge comprises a housing accommodating at least part of the injection needle and at least part of the sealing force generator. Such a housing may serve as a mechanical protection of the sealing force generator, guaranteeing its accuracy in terms of the generated sealing force value and direction, as well as of the needle and may ensure a proper cooperation of these components.
[0017] In an embodiment, the sealing force generator comprises an elastic member, particularly one of the group consisting of a sealing force spring and an elastomeric element, configured for applying the sealing force to the injection needle. The term elastic member" may denote a physical structure which intrinsically generates a back driving force proportional to an elongation distance (i.e. a length change in response to a compression or an expansion) thereof upon applying an elongation force. For instance, a spring showing a behavior according to Hooke's law is considered as an elastic member. Another example for an elastic member is a flexible rod made of an elastomeric material. Such a sealing force generator is simple in construction and is capable of applying a precisely defined sealing force between needle and seat.
[0018] In an embodiment, at least part of the sealing force spring (particularly a helical spring) is arranged to circumferentially surround at least part of the injection needle. This allows to manufacture the injection needle cartridge in a compact way since at least part of the injection needle may be accommodated within the interior volume of a helical spring or the like.
[0019] In an embodiment, the elastic member is supported between the injection needle and the housing. For instance, one end of the elastic member may be mounted or supported fixedly on the housing, whereas the opposing other end can be fixed directly or indirectly to-the injection needle so that in response to compressing the elastic member by pressing the needle against the seat, the spring is pressed against the housing and applies a counterforce to the needle with a direction to press the needle apart from the housing and against the seat.
[0020] In an embodiment, the elastic member is mounted in a pre-biased state in the injection needle cartridge. Thus, the elastic member may be pre-compressed or pie-expanded (even in the absence of a pressure applied from the needle to the seat) so that even when the injection needle is presently not pressed into the seat, the elastic member is already under tension. This further strengthens the pressure tight connection between needle and seat because the pre-tensioning of the elastic member further promotes the sealing between needle and seat.
[0021] In an embodiment, the sealing force generator comprises one of the group consisting of a magnetic sealing force generator generating a magnetic sealing force, and an electric sealing force generator generating an electric sealing force. Thus, the sealing force needs not necessarily be generated by a mechanical mechanism or a mechanical mechanism alone. Additionally or alternatively, it is also possible to use the repelling force of two or more spaced magnetic elements (such as permanent magnets), one of which being connected to the housing, and the other one being attached to the needle. When the needle is then pressed into the seat and the needle is consequently moved relative to the housing, the distance between the two magnetic elements is reduced which results in the generation of a back driving counterforce acting on the needle. This sealingly presses the needle in a fluid tight and pressure tight manner into the seat. Additionally or alternatively, even attracting magnetic elements or members generating electric forces can be used for providing the sealing force.
[0022] In an embodiment, the injection needle cartridge comprises a readable marker being indicative of at least one property of the injection needle cartridge (for instance a type of the injection needle cartridge, its needle, its pressure resistance, its size, etc.). Preferably, the marker may be indicative of a sealing force value provided by the sealing force generator.
[0023] In an embodiment, the readable marker comprises a machine-readable marker, particularly one of the group consisting of a barcode and a radio frequency identification tag (RFID tag). Correspondingly, the robot or another member of the sample injector may be equipped with a corresponding reader device such as a barcode reader or an RFID reader. Therefore, it may be made possible for the robot arm or another member of the sample injector to read out the marker to determine which kind of the sealing force and which kind of corresponding injection needle are implemented in the "black box' like injection needle cartridge being configured as a module replaceable as a whole. By equipping the housing of the injection needle cartridge with such a machine-readable marker, the needle drive mechanism of the robot can automatically determine which injection needle cartridge is presently used. If necessary, the needle drive mechanism can then self-adjust its operation in accordance with the presently used injection needle cartridge. Therefore, the sample injector can be synchronized or coordinated so as to prevent an erroneous operation.
10024] In an embodiment, the readable marker comprises a human-readable marker, particularly one of the group consisting of an alphanumeric code and a color marker.
For example, the different types of needle cartridges may be color-coded, wherein different colors may be used for example for the cartridge housing (such as a spring cage when using a spring as sealing force generator) of different injection needLe cartridges. This allows to visualize the type of needle to a user so as to prevent the use of an inappropriate needle for a certain application.
[0025] In an embodiment, the injection needle cartridge comprises a capillary in fluid communication with the injection needle. Such a capillary, which may be at least partially formed within the housing of the cartridge, can then provide for fluid communication of the needle with a sample loop of the sample injector.
[0026] In an embodiment, the injection needle cartridge comprises a fitting member in fluid communication with the injection needle and being configured to form a fluid-tight and fluid communicating fitting upon being connected with a corresponding fitting member counterpart in fluid communication with a mop capillary of the sample injector.
Such a fitting member of the injection needle cartridge may be a male fitting member or a female filling member being connected with a corresponding inverse female filling member or male fitting member, respectively, as the fitting member counterpart. The correspondingly formed filling may be a high pressure resistant fluid tight filling. The connection between the two cooperating fitting members may be performed with a bayonet connection, a snap-in connection, a screwing connection, etc. By such a fitting, the injection needle cartridge may be brought in fluid communication with the rest of the sample injector.
[0027J In an embodiment, the sealing force generator is configured for applying a sealing force with a predefined value and with a predefined direction (preferably along an extension direction of the needle) when the injection needle is accommodated in the needle seat. Therefore, the value and the vector direction of the sealing force may be an intrinsic property of the injection needle cartridge and may be independently of other components such as the robot. Therefore, a very precise adjustment of the sealing force can be ensured.
[0028] In an embodiment, the needle set comprises at least one ceramic needle, and at least one metallic needle. The ceramic needle may for example be used for biological applications. The metallic needle can be used as a standard needle. It can be made of stainless steel, platinum, etc. It is also possible that the set comprises other needles made of other materials, such as plastic.
[0029] It is furthermore possible that the needle set comprises different injection needle cartridges capable to withstand different pressure values. For example, one injection needle cartridge may be made for applications up to 600 bar, another one may be configured for applications of up to 1200 bar. The value of the sealing force may be adjusted correspondingly.
[0030] In an embodiment, the sample injector comprises a cartridge adapter configured for detachably receiving the injection needle cartridge and being configured for being attached to the handling robot. The cartridge adapter forms a mechanic interface between the injection needle cartridge and the robot.
[0031] In an embodiment, the cartridge adapter comprises a needle protection mechanism configured for operating the injection needle selectively in a protected (for instance retracted) state in which at least a tip of the injection needle is accommodated within the cartridge adapter or in an active (for instance expanded) state in which at least the tip of the injection needle protrudes beyond the cartridge adapter. Therefore, a user can be prevented from being injured by the sharp needle when the latter is accommodated fully within the cartridge adapter. Additionally, the needle can be prevented from damage by protecting it within the cartridge adapter. On the other hand, when the needle is in an active operation mode, it may protrude over the cartridge adapter so as to be capable to immerse into a fluid container or to be inserted into the needle seat.
[00321 In an embodiment, the needle protection mechanism is configured for forcing the injection needle into the protected state (automatically or by user operation) upon disassembling the injection needle cartridge from the handling robot and/or for forcing the injection needle into the active state (automatically or by user operation) upon mounting the injection needle cartridge on the handling robot.
[0033] In an embodiment, the cartridge adapter comprises a cartridge locking mechanism configured for detachably locking the injection needle cartridge to the cartridge adapter. For instance, it may be realized by a lever-based clamping mechanism for detachably locking the injection needle cartridge by a latch. Therefore, the injection needle cartridge can be connected by a quick lock system of the cartridge adapter (for instance by merely inserting the injection needle cartridge into the cartridge adapter and by subsequently pivoting a lever) on the needle drive system (particularly on a robot arm thereof). When the cartridge is inserted into a needle holder of the cartridge adapter it can be clamped with a latch so that no tooling is needed for a user to change the needle: [0034] In an embodiment, the injection needle cartridge comprises a robot connection element laterally connected at the housing and configured for attaching the injection needle cartridge to the handling robot by sliding the robot connection element on the handling robot. Thus, the robot connection element may be integrated into the needle cartridge. This provides for very compact configuration.
[00351 In an alternative embodiment, the sample injector comprises a robot connection element laterally connected at the cartridge adapter and configured for attaching the cartridge adapter to the handling robot by sliding the robot connection element on the handFing robot (wherein the robot connection element may be locked to the handling robot upon sliding). Hence, assembling and disassembling the injection needle cartridge (which is necessary regularly in view of the fact that the injection needle cartridge is a consumable) via the robot connection element to the robot can be performed with a very simple procedure.
[0036] In an embodiment, the sample injector comprises a needle set having the above mentioned features, wherein the cartridge adapter may be configured for detachably receiving each of the injection needle cartridges. Therefore, a multi-purpose sample injector can be provided in which only one appropriate of several injection needle cartridge needs to be selected at a time for use with the rest of the sample injector to meet the requirements of a corresponding application.
[0037] In an embodiment, the sealing force generator, the injection needle and the needle seat are configured to cooperate so that the injection needle is accommodatable in the needle seat in a high pressure-tight manner, particularly pressure-tight at a pressure of about 1200 bar. Such an injection needle cartridge meets requirements of modern liquid chromatography applications.
[0038} In an embodiment, the handling robot is free of a sealing force generator for generating a sealing force for sealingly accommodating the injection needle of the injection needle cartridge in the needle seat. Therefore, the handling robot can be formed in a compact way and capable of serving injection needle cartridges for very different applications.
[0039] The separation unit 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 fluid so as to be capable of separating different components of such a sample 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.
[0040] At east a part of the separation unit 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.
[0041] The separation unit 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.
[0042] The fluid separation system may be configured to conduct a liquid mobile phase through the separation unit. As art alternative to a liquid mobile phase, a gaseous mobile phase or a mobile phase including solid particles may be processed using the fluid separation system. Also materials being mixtures of different phases (solid, liquid, gaseous) may be processed using exemplary embodiments. The fluid separation system 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.
[0043] The fluid separation system may be configured as a microfluidic device. The term "microfluidic device' may particularly denote a fluid separation system 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.
[0044] Exemplary embodiments may be implemented in a sample injector of a liquid chromatography apparatus which sample injector may take up a sample fluid from a fluid container and may inject such a sample fluid in a conduit for supply to a separation column. During this procedure, the sample fluid 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 fluid 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 to then, for instance via a switchable fluidic valve, inject the sample fluid towards a sample separation section of the liquid chromatography apparatus.
[0045] The fluid separation system may be configured to analyze at least one physical, chemical and/or biological parameter of at least one component of the sample fluid in 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 -11 -biological parameter" may particularly denote a concentration of a protein, a gene or the like in a biochemicaF solution, a biological activity of a component, etc. [0046J The fluid separation system 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 fluid separation system may be a High Performance Liquid device (HPLC) device by which different fractions of an analyte may be separated, examined and analyzed.
[0047] 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 prbcessing unit configured to process data received from the fluid separation system, and/or a degassing apparatus for degassing the mobile phase.
[0048] 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).
[0049] 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 Al) or parallel manner.
[0050] 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.
[0051] 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.
[0052] The fluid is preferably a liquid but may also be or comprise a gas andlor a supercritical fluid (as e.g. used in supercritical fluid chromatography -SFC -as disclosed e.g. in US 4,982,597 A).
[0053] The pressure in the mobile phase might range from 2-20& MPa (20 to 2000 bar), in particular 10-150 MPa (100 to 1500 bar), and more particular 50-120 MPa (500 to 1200 bar).
BRIEF DESCRIPTION OF DRAWINGS
[0054] Other objects and many of the attendant advantages of embodiments of the present invention will be readily appreciated and become belier understood by reference to the following more detailed description of embodiments in connection with the accompanied drawings. Features that are substantially or functionally equal or similar will be referred to by the same reference signs. The illustration in the drawing is schematically.
[0055] Figure 1 shows a liquid separation device, in accordance with embodiments of the present invention, e.g. used in high performance liquid chromatography (HPLC).
[0056] Figure 2 illustrates a sample injector of the liquid separation device of Figure 1 having a set of injection needle cartridges according to an exemplary embodiment.
[0057] Figure 3 illustrates a cross-sectional view of an injection needle cartridge according to an exemplary embodiment.
[0058] Figure 4 illustrates a cartridge adapter of a sample injector according to an exemplary embodiment receiving the injection needle cartridge of Figure 3 in a locked state.
[0059] Figure 5 illustrates the cartridge adapter of Figure 4 receiving the injection needle cartridge of Figure 3 in an unlocked state.
[0060] Figure 6 illustrates a cartridge adapter for receiving an injection needle cartridge together with a robot connection element according to an exemplary embodiment in an operation mode in which the injection needle is exposed to an environment.
[0061] Figure 7 shows a threedimensional view of the injection needle cartridge implemented in Figure 6.
[0062] Figure 8 illustrates the cartridge adapter of Figure 6 in an operation mode in which the injection needle is retracted into an interior of the cartridge adapter.
[0063] Figure 9 illustrates a robot arm for mounting a cartridge adapter according to an exemplary embodiment.
[0064] The illustration in the drawing is schematically.
[0065] Referring now in greater detail to the drawings, Figure 1 depicts a general schematic of a liquid separation system 10. A pump 20 receives a mobile phase from a solvent supply 26, 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 separation unit 30 (such as a chromatographic column) comprising a stationary phase. A sample injector 40 (compare the detailed description of Figure 2) can be provided between the pump 20 and the separation unit in order to subject or add (often referred to as sample introduction) a sample fluid into the mobile phase. The stationary phase of the separation unit 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.
[0066] 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 separation unit 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.
[0067] 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 (for instance 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 (for instance setting the solvent/s or solvent mixture to be supplied) and/or the degasser 27 (for instance 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 might further control operation of the sample injector 40 (for instance controlling sample injection or synchronization sample injection with operating conditions of the pump 20). The separation unit 30 might also be controlled by the data processing unit (for instance selecting a specific flow path or column, setting operation temperature, etc.), and send -in return -information (for instance operating conditions) to the data processing unit 70. Accordingly, the detector 50 might be controlled by the data processing unit 70 (for instance with respect to spectral or wavelength settings, selling time constants, start/stop data acquisition), and send information (for instance about the detected sample compounds) to the data processing unit 70. The data processing unit might also control operation of the fractionating unit 60 (for instance in conjunction with data received from the detector 50) and provides data back.
[0068] Reference numeral 90 schematically illustrates a switchable valve which is controllable for selectively enabling or disabling specific fluidic paths within liquid separation system 10.
[0069] Figure 2 illustrates constitution of the sample injector 40 of the liquid -15 -separation system 10 of Figure 1 having mounted thereon one injection needle cartridge 300 of a set 280 of injection needle cartridges 300 according to an exemplary embodiment.
[0070] The one injection needle cartridge 300 is presently implemented in the liquid separation system 10 (having particularly the mobile phase drive or pump 20 and the separation unit 30, here a separation column) between a sample loop 204 and a needle seat 208-The injection needle cartridge 300 mOunted between sample loop 204 and needle seat 208 is presently in an active state in terms of sample injecting and belongs to the needle set 280. Additionally, the needle set 280 has (in this embodiment) three other injection needle cartridges 300 which are shown in Figure 2 as well and are presently in an inactive mode and hence located at a waiting position apart from the sample injector 40. The different injection needle cartridges 300 of the needle set 280 differ basically only concerning their capability of providing different values of a sealing force to be applied between an injection needle 302 of the injection needle cartridge 300 and the needle seat 208, when the respective injection needle cartridge 300 is in the active state, i.e. mounted on the sample injector 40. Fig. 2 does not show, how the injection needle cartridges 300 are hydraulically switched from an inactive state to an active state. Further valves (not shown) may be provided to switch an injection needle cartridge 300 from an inactive to an active needle configuration.
[0071] Each of the injection needle cartridges 300 comprises a respective injection needle 302 configured for aspirating sample fluid from a fluid container 230 when immersing therein. Each injection needle 302 has an internal lumen through which the sample fluid can flow. Each of each injection needles 302 is configured for immersing into the fluid container 230 at a tapering end or tip 316 which also contributes to the task of providing a high pressure resistant, fluid tight and sealed connection with the seat 208 and for preventing, inter alla as a result of its tapering shape, an undesired carryover of sample fluid between different sample aspiration and separation cycles.
The sample fluid is aspirated when the injection needle 302 has been moved by a robot arm.250 of a needle drive system to the fluid container 230. The sample fluid is injected into the fluidic path between the mobile phase drive 20 and the separation unit 30 via the injection needle 302 when it is sealingly accommodated in the needle seat 208 and valve 90 is switched correspondingly. In order to ensure proper sealing between needle 302 and needle seat 208, a sealing force generator 304 is integrated in each of the -16-injection needle cartridges 300. Each seating force generator 304 is configured for exerting an assigned, intrinsically-defined value of the sealing force to the injection needle 302 for sealingly accommodating the injection needle 302 when being accommodated in the needle seat 208. Hence, by providing the needle set 280 with injection needle cartridges 300 generating intrinsically different sealing force values, one and the same sample injector 40 can be used for various applications which may require different values of the sealing force. For instance, a 600 bar application requires a lower sealing force than a 1200 bar application. A biological application using a ceramic needle requires a different sealing force than a standard application using a stainless steel needle, etc. Thus, a user may simply select an appropriate one of the injection needle cartridges 300 for implementation into the liquid separation system 10 so as to precisely meet all sealing force related requirements of a certain application.
[00721 The sealing force generator 304 is located completely in an interior of the respective injection needle cartridge 300, more precisely within a sealing force generator cage 300 and a needle holder 306 (holding also the injection needle 302) of the respective injection needle cartridge 300. In the injection needle cartridge 300 being presently in the active mode, the sealing force generator 304 is a helical spring additionally shielded against an environment by the sealing force generator cage 308 within which the sealing force generator 304 is mounted. When that injection needle cartridge 300 being presently in the active mode is driven into the needle seat 208 by the robot arm 250 gripping the injection needle cartridge 300, the helical spring of this injection needle cartridge 300 is compressed so that the helical spring applies a back-driving sealing force to the injection needle-needle seat interface, thereby safely sealing the latter in a fluid tight and pressure resistant way.
[0073] With regard to the injection needle cartridges 300 being presently in the waiting position, the injection needle cartridge 300 of the left hand side and the injection needle cartridge 300 and the middle also comprise a helical spring as sealing force generator 304, wherein the different injection needle cartridges 300 having helical springs as sealing force generator 304 differ concerning the spring constants.
Therefore, each of them provides a different sealing force value. The injection needle cartridge 300 in the waiting position on the right-hand side of Figure 2 uses two repelling ferromagnetic permanent magnets 282 for constituting the sealing force generator of this injection needle cartridge 300. When the latter injection needle cartridge 300 is implemented in the sample injector 40 and its injection needle 302 is inserted into the needle seat 208, the needle 302 is moved relative to the housing 306 which reduces the distance between the repelling permanent magnets 282 (one of which being fixedly connected with sealing force generator cage 308, while the other one is fixedly connected to the needle 302), so that the repellant force between the permanent magnets 282 presses the needle 302 sealingly into the needle seat 208.
[0074] Reference numeral 314 schematically indicates a fitting member (such as a female piece or a male piece) of each injection needle cartridge 300 which mates with a counter fitting member 500 connected to the sample loop 204 so that connection between this fitting member 314 and the counter fitting member 500 forms a fluidic connection between a loop capillary 260 (or directly the sample loop 204) and an internal connection capillary 312 of each injection needle cartridge 300 connecting the fitting piece 314 fluidically to the lumen in the injection needle 302. The cooperating fitting members 314, 500 may be connected to one another by screwing, a bayonet connection or the like.
[0075] As can furthermore be taken from Figure 2. an RFID tag 310 is attached to each of the injection needle cartridges 300 so as to wirelessly communicate with a corresponding RFID reader 299 of the robot arm 250. When a robot connection element 406 of any of the injection needle cartridges 300 is connected to a corresponding cartridge connection element 297 of the robot arm 250, the distance between the respective RFID tag 310 and the REID reader 299 is small enough so that data indicative of the identity of the respective injection needle cartridge 300 (for instance data indicative of a sealing force value of the corresponding injection needle cartridge 300) can be transmitted to the robot arm 250. The color of at least a part of the exterior surface of the injection needle cartridges 300 may be indicative of the value of the internal sealing force value. For instance, the robot connection element 406 may have different colors for the different injection needle cartridges 300 of the set 280.
[0076] The sample loop 204 is in fluid communication with a port of the vave 90 and is configured for receiving the sample fluid via the injection needle 302 which, in turn, receives the sample fluid from the vial or fluid container 230. The needle 302 is in fluid communication with the sample loop 204 via loop capillary 260. The seat 208 is configured for selectively receiving the needle 302 in afluid-tight manner. Furthermore, an optional seat capillary 216 is provided which is in fluid communication with the seat 208 and is in fluid communication with a port 242 of the valve 90. Furthermore, a metering device 210 is shown which is in fluid communication with two ports 242 of the fluidic valve 90. An optional flush pump 212 (such as a 50 bar flush pump) is in fluid communication with a port 242 in a center of the fluidic valve 90. Furthermore, an optional wash port 214 is provided which participates during a needle wash procedure.
[00771 The needle 302 can be moved between the seat 208 and the fluid container 230 by the robot arm 250 (which may be powered by an electric motor or another drive unit, not shown in Figure 2). When the needle 302 is immersed in the fluid container 230, the metering pump 210 can apply an underpressure to the needle 302 so that the sample fluid is sucked via the needle 302 into the ioop capillary 260 and from there into the sample loop 204. Subsequently, the needle 302 is driven back into the seat 208 and the injected fluid is transferred from the sample loop 204 through the seat 208 and the valve 90 into a fluidic path between the mobile phase drive or pump 20 and the separation column 30. All the different operation modes involved during this procedure can be carried out by a corresponding switching operation of the fluidic valve 90. The fluidic valve 90 comprises two cooperating valve members, one of which having the ports 242 and the other one having cooperating grooves 240.
[0078] Figure 3 illustrates a cross-sectional view of an kijection needle cartridge 300 according to an exemplary embodiment. Each of the features of the injection needle cartridge 300 shown in Figure 3 may be implemented in Figure 2 accordingly, and vice versa.
[0079] At the sharp end or tip 316 of the tapering needle 302, lumen 318 extending along the entire injection needle 302 is exposed to an environment for aspirating sample fluid. Figure 3 shows in detail that the casing or housing of the injection needle cartridge 300 comprises two components, i.e. needle holder 306 as inner, first component accommodating a part of the injection needle 302 and a part of the capillary 312, and the sealing force generator cage (here: spring cage) 308 as a second component in which a helical spring as sealing force generator 304 is completely accommodated and shielded with regard to the environment.
[0080] Thus, the sealing force generator 304 is here configured as preloaded spring included in the injection needle cartridge 300 which determines the quantity of the sealing force of the specific injection needle 302. If the injection needle 302 has to be changed in the liquid chromatography system as liquid separation system 10, the complete injection needle cartridge 300 including sealing force generator cage 308 is exchanged. Therefore, the sealing force value and orientation can be adapted to the requirements of the needle material, needle geometry and maximum system pressure without changing the algorithm of the needle drive mechanism, here formed by robot arm 250 and connected drive (not shown in Figure 3).
[0081] The capillary 312 may be welded into the needle 302, for instance by laser welding. To render the welding procedure efficient and successful, the capillary 312 and the needle 302 may be made of the same material. The spring cage 308 may be made for instance of stainless steel, silver or a plastic material. As can be taken from Figure 2, the capillary 312 is hydraulically connected to the loop capillary 260 via the cooperating fitting members 314, 500.
[0082] Figure 4 illustrates a cartridge adapter 400 of a sample injector 40 according to an exemplary embodiment configured for receiving the injection needle cartridge 300 of Figure 3. Figure 4 shows the arrangement of cartridge adapter 400 and injection needle cartridge 300 in a mutually locked state. Figure 5 illustrates the cartridge adapter 400 of Figure 4 receiving the injection needle cartridge 300 of Figure 3 in an unlocked state.
[0083] In the embodiment shown in Figure 4 and Figure 5, the injection needle cartridge 300 is configured to be inserted into the cartridge adapter 400 for connection, in turn, to the robot arm 250 via a robot connection element 406, as described below in more detail. However, as an alternative, the spring cage 308 itself may be used as a component to be gripped by the robot arm 250. For this purpose, an appropriately shaped and dimensioned grip support element (not shown) may be integrally formed with the sealing force generator cage 308. In such an embodiment, the cartridge adapter 404 and the robot connection element 406 can be omitted to obtain a particularly compact device.
[0084] Coming back to the embodiment of Figure 4 and Figure 5, the sample injector comprises the cartridge adapter 400 which is configured for detachably receiving the injection needle cartridge 300 and is configured for being attached, with the injection needle cartridge 300 being mounted, to the handling robot 250. The.cartridge adapter 400 has a needle protection mechanism 402 which is configured for operating the -20 -injection needle 302 selectively in a protected state in which the tip 316 of the injection needle 302 is accommodated within the cartridge adapter 400 (protected state not shown). In such a protected state, a user is protected from injury by the sharp tip 316, and the needle 302 is protected against damage. The needle protection mechanism 402 is also configured for alternatively operating the injection needle 302 in an active state, see Figure 4 and Figure 5, in which the tip 316 of the injection needle 302 protrudes beyond the cartridge adapter 400. In the active state, the injection needle 302 is ready for aspirating sample fluid via tip 316. In the shown embodiment, the needle protection mechanism 402 is formed by a member having two (or more) parallel legs 408 between which the injection needle cartridge 300 can be located and moved upwardly or downwardly. At their lower ends, the legs 408 are connected to one another via an end plate 410. The end plate 410 has a through hole 412 through which the needle 302 can penetrate. In an expanded state of the needle 302, the needle 302 extends through the through hole 412 and is exposed to an environment for aspirating fluid sample or for being inserted into the seat 208. In the retracted state of the needle 302, the needle 302 is completely located between the legs 408 and does not extend through the through hole 412. The legs 402 together with the end plate 410 can be slid relatively to the injection needle 302 (or vice versa) to convert the injection needle 302 between the protected state and the active state. The injection needle 302 can be brought into a stable configuration in both the protected state and the active state.
[0085] Additionally, the cartridge adapter 400 comprises a cartridge locking mechanism 404 in the form of a lever-based clamping mechanism which is configured for detachably locking the injection needle cartridge 300 with the cartridge adapter 400 by a latch 502. Figure 4 shows the lever of the cartridge locking mechanism 404 in a locked state in which the injection needle cartridge 300 is rigidly locked to the cartridge adapter 400. Figure 5 shows the lever of the cartridge locking mechanism 404 in an unlocked state in which the injection needle cartridge 300 is not locked to the cartridge adapter 400, and can be inserted are removed in this state.
10086] A sample injector 40 corresponding to Figure 4 and Figure 5 furthermore comprises a robot connection element 406 which is laterally connected at the cartridge adapter 400 and is configured for attaching the cartridge adapter 400 to the handling robot 250 by sliding the robot connection element 406 on the handling robot 250.
Reference numeral 420 shows a permanent magnet used for simplifying the sliding connection of the arrangement shown in Figure 4 and Figure 5 to the robot arm 250 making use of a supporting, attracting magnetic force. The robot arm 250 has a corresponding permanent magnet (not shown) which attracts the permanent magnet 420 of the cartridge adapter 400 and therefore promotes correct orientation of the cartridge adapter 400 relative to the robot arm 250.
[0087] The arrangement of Figure 4 can further be configured for stripping off a vial or any other fluid container 230 from the injection needle 302 after the injection needle 302 has aspirated sample fluid by immersing into the vial or other fluid container 230.
[00881 Figure 6 illustrates a cartridge adapter 400 presently receiving an injection needle cartridge 300 together with a robot connection element 406 according to an exemplary embodiment in an operation mode in which the injection needle 302 is exposed to an environment. In the shown state, the end tip 316 of the injection needle 302 protrudes over the protection mechanism 402 to thereby enable sample aspiration.
[0089] Figure 7 shows a three-dimensional view of the injection needle cartridge 300 according to an exemplary embodiment implemented in Figure 6. The integrally formed structure of Figure 7 is a consumable which can be, as a whole, connected to or separated from the cartridge adapter 400.
[0090] Figure 8 illustrates the cartridge adapter 406 of Figure 6 in an operation mode in which the injection needle 302 is retracted into an interior of the cartridge adapter 400. Thus, the tip 316 does not protrude over the end plate 410 of the protection mechanism and is therefore prevented from injuring a user and from being damaged by a mechanical impact from the environment.
[0091] Figure 9 illustrates a robot arm 250 for mounting a cartridge adapter 400 according to an exemplary embodiment. The arrangement of Figure 8 can be mounted on the robot arm 250 by sliding the robot connection element 406 onto a corresponding counterpart on the robot arm 250 to a state in which the permanent magnet 420 of the cartridge adapter 400 is in attracting alignment with a permanent magnet 900 of the robot arm 250.
[0092] 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 -22 -reference signs in the claims shall not be construed as limiting the scope of the claims.
-23 -
Claims (29)
- CLAIMS1. An injection needle cartridge (300) for a sample injector (40) for injecting a sample fluid into a mobile phase in a fluidic path of a fluid separation system (10) between a mobile phase drive (20) and a separation unit (30), the injection needle cartridge (300) comprising: an injection needle (302) configured for aspirating the sample fluid from a fluid container (230) when the injection needle (302) has been moved to the fluid container (230), and for injecting aspirated sample fluid into the fluidic path when the injection needle (302) is sealingly accommodated in a needle seat (208); a sealing force generator (304) configured for applying a sealing force to.the injection needle (302) for sealingly accommodating the injection needle (302) in the needle seat (208); wherein the injection needle cartridge (300) is configured for being substitutably mountable on a handling robot (250) of the sample injector (40) for handling the injection needle cartridge (300) between the fluid container (230) and the needle seat (208).
- 2. The injection needle cartridge (300) of claim 1, comprising a housing (306, 308) accommodating at least part of the injection needle (302) and at least part of the sealing force generator (304).
- 3. The injection needle cartridge (300) of claim 1 or 2, wherein the sealing force generator (304) comprises an elastic member, particularly one of the group consisting of a sealing foroe spring and an elastomeric element, configured for applying the sealing force to the injection needle (302).
- 4. The injection needle cartridge (300) of claim 3, wherein at least part of the sealing force spring (304) is arranged to circumferentially surround at east part of the injection needle (302).
- 5. The injection needle cartridge (300) of claims 2 and 3, wherein the elastic member (304) is supported between the injection needle (302) and the housing (306, 308).
- 6. The injection needle cartridge (300) of any of claims 3 to 5, wherein the elastic member (304) is mounted so as to be compressed upon pressing the injection needle (302) against the needle seat (208).
- 7. The injection needle cartridge (300) of any of claims 3 to 6, wherein the elastic member (304) is mounted in a pre-biased state.
- 8. The injection needle cartridge (300) of any of claims 1 to 7, wherein the sealing force generator (304) comprises one of the group consisting of a magnetic sealing force generator (282) generating a magnetic sealing force, and an electric sealing force generator generating an electric sealing force.
- 9. The injection needle cartridge (300) of any of claims I to 8, comprising a readable marker (310) being indicative of at least one property of the injection needle cartridge (300), particularly being indicative of a sealing force value provided by the sealing force generator (304).
- 10. The injection needle cartridge (300) of claim 9, wherein the readable marker (310) comprises a machine-readable marker, particularly one of the group consisting of a barcode and a radio frequency identification tag.
- 11. The injection needle cartridge (300) of claim 9 or 10, wherein the readable marker (310) comprises a human-readable marker, particularly one of the group consisting of an alphanumeric code and a color marker.
- 12. The injection needle cartridge (300) of any of claims ito 11, comprising a capillary (312) in fluid communication with the injection needle (302), particularly a capillary (312) being welded to the injection needle (302) within a housing (306, 308) of the injection needle cartridge (300).
- 13. The injection needle cartridge (300) of any of claims 1 to 12, comprising a fitting member (314) in fluid communication with the injection needle (302) and being configured to provide a fluid-tight fluid communication interface upon being connected with a corresponding fitting member counterpart (500) in fluid communication with a loop capillary (260) of the sample injector (40).
- 14. The injection needle cartridge (300) of any of claims 1 to 13, wherein the sealing force generator (304) is configured for applying a sealing force with a predefined value when the injection needle (302) is accommodated in the needle seat (208).-25 -
- 15. The injection needle cartridge (300) of any of claims 2 to 14, comprising a robot connection element (406) laterally connected at the housing (306, 308) and configured for attaching the injection needle cartridge (300) to the handling robot (250) by sliding the robot connection element (406) on the handling robot (250).
- 16. A needle set (280) comprising a plurality of injection needle cartridges (300) of any of claims 1 to 15, wherein different ones of the injection needle cartridges (300) provide different sealing force values.
- 17. The needle set (280) of claim 16, wherein the injection needle (302) of one of the injection needle cartridges (300) is a ceramic needle, and the injection needle (302) of another one of the injection needle cartridges (300) is a metallic needle.
- 18. A sample injector (40) for injecting a sample fluid into a mobile phase in a fluidic path of a fluid separation system (10) between a mobile phase drive (20) and a separation unit (30), the sample injector (40) comprising: an injection needle cartridge (300) of any of claims 1 to 15; a needle seat (208) configured for sealingly accommodating the injection needle (302) of the injection needle cartridge (300) and providing fluid communication with the fluidic path, wherein the sealing force generator (304) of the injection needle cartridge (300) provides the sealing force when the injection needle (302) is accommodated in the needle seat (208); a handling robot (250) on which the injection needle cartridge (300) is mountable or mounted and being configured for moving the injection needle (302) between a fluid container (230) containing the sample fluid and the needle seat (208).
- 19. The sample injector (40) of claim 18, comprising a cartridge adapter (400) configured for detachably receiving the injection needle cartridge (300) and being configured for being attached to the handling robot (250).
- 20. The sample injector (40) of claim 19, wherein the cartridge adapter (400) comprises a needle protection mechanism (402) configured for operating the injection needle (302) selectively in a protected state in which at least a tip (316) of the injection needle (302) is accommodated within the cartridge adapter (400) or in an active state in which at least the tip (316) of the injection needle (302) protrudes -26 -beyond the cartridge adapter (400).
- 21. The injection needle cartridge (300) of claim 20, wherein the needle protection mechanism (402) is configured* for forcing the injection needle (302) into the protected state upon demounting the injection needle cartridge (300) from the handling robot (250) and/or for forcing the injection needle (302) into the active state upon mounting the injection needle cartridge (300) on the handhng robot (250).
- 22. The sample injector (40) of any of claims 19 to 21, wherein the cartridge adapter (400) comprises a cartridge locking mechanism (404) configured for detachably locking the injection needle cartridge (300) to the cartridge adapter (400), particularly a lever-based clamping mechanism for detachably locking the injection needle cartridge (300) by a latch (502).
- 23. The sample injector (40) of any of claims 19 to 22, comprising a robot connection element (406) laterally connected at the cartridge adapter (400) and configured for affaching the cartridge adapter (400) to the handling robot (250) by fastening, particularly by sliding, the robot connection element (406) on the handling robot (250).
- 24. The sample injector (40) of any of claims 19 to 23, comprising a needle set (280) of claim 15 or 16, wherein the cartridge adapter (400) is configured for detachably receiving each individual of the injection needle cartridges (300).
- 25. The sample injector (40) of any of claims 18 to 24, wherein the sealing force generator (304), *the injection needle (302) and the needle seat (208) are configured to cooperate so that the injection needle (302) is accommodatable in the needle seat (208) in a high pressure-tight manner, particularly pressure-tight at a pressure of 1200 bar.
- 26. The sample injector (40) of any of claims 18 to 25, wherein the handling robot (250) is free of a sealing force generator (304).
- 27. A fluid separation system (10) for separating compounds of a sample fluid in a mobile phase, the fluid separation system (10) comprising: a mobile phase drive (20), particularly a pumping system, configured to drive the -27 -mobile phase through the fluid separation system (10); a separation unit (30), particularly a chromatographic column, configured for separating compounds of the sample fluid in the mobile phase: and a sample injector (40) according to any of claims 18 to 26 configured for injecting the sample fluid in the fluidic path between the mobile phase drive (20) and the separation unit (30).
- 28. The fluid separation system (10) according to claim 27, 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 sample fluid; the fluid separation system (10) comprises at least one of the group consisting of a detector device (50), a device for chemical, biological andlor pharmaceutical analysis, a capillary electrophoresis device, a liquid chromatography device, an HPLC device, a gas chromatography device, a gel electrophoresis device, and a mass spectroscopy device; the fluid separation system (10) is configured to conduct the sample fluid with a high pressure; the fluid separation system (10) is configured to conduct the sample 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 sample 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, -28 -wherein the separating material comprises beads having a size in the range of 1 pm to 50 pm; at least a part of the separation unit (30) 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.
- 29. A method of operating a sample injector (40) with an injection needle cartridge (300) of any of claims 1 to 15 for injecting a sample fluid into a mobile phase in a fluidic path of a fluid separation system (10) between a mobile phase drive (20) and a separation unit (30), the method comprising: substitutably mounting the injection needle cartridge (300) on a handling robot (250) of the sample injector (40); moving the injection needle cartridge (300) by the handling robot (250) to a fluid container (230) containing the sample fluid; aspirating the sample fluid from the fluid container (230) via the injection needle (302) into a sample loop (204) of the sample injector (40); moving the injection needle cartridge (300) by the handling robot (250) to the needle seat (208) and sealingly accommodating the injection needle (302) in the needle seat (208) by applying a sealing force generated by the sealing force generator (304); injecting the aspirated sample fluid from the sample loop (204) via the injection needle (302) into the fluidic path when the injection needle (302) is sealingly accommodated in the needle seat (208). -29 -
Priority Applications (2)
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GB1312181.9A GB2516027B (en) | 2013-07-08 | 2013-07-08 | Injection needle cartridge with integrated sealing force generator |
US14/264,755 US9733221B2 (en) | 2011-06-09 | 2014-04-29 | Injection needle cartridge with integrated sealing force generator |
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GB1312181.9A GB2516027B (en) | 2013-07-08 | 2013-07-08 | Injection needle cartridge with integrated sealing force generator |
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GB201312181D0 GB201312181D0 (en) | 2013-08-21 |
GB2516027A true GB2516027A (en) | 2015-01-14 |
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GB2588635A (en) * | 2019-10-30 | 2021-05-05 | Agilent Technologies Inc | Sample injector with fluidic sample mixing |
CN114113427A (en) * | 2020-08-28 | 2022-03-01 | 豪夫迈·罗氏有限公司 | Sample injector |
Families Citing this family (1)
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CN113109554B (en) * | 2021-03-12 | 2024-07-09 | 天津一安生物技术有限公司 | Meat sampling and chromatography detection integrated device |
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GB2588635B (en) * | 2019-10-30 | 2022-04-20 | Agilent Technologies Inc | Sample injector with fluidic sample mixing |
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GB201312181D0 (en) | 2013-08-21 |
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