Sample injector with catheter tip penetrating into needle opening

Abstract

The present application relates to a sample injector having a catheter tip that penetrates into a needle opening for use in a chromatography system that includes a mobile phase driver that drives a mobile phase through a separation unit that chromatographically separates a complex of a sample fluid in the mobile phase. The sample injector injects the sample fluid into the mobile phase and includes a needle and a catheter. The needle aspirates the sample fluid and includes a needle tip on one end, a needle channel through the needle to direct the aspirated sample fluid, and a needle opening at the needle tip into which the needle channel opens. The catheter is fluidically coupled with the needle and includes a catheter tip on one end and a catheter channel through the catheter to direct fluid, the catheter channel having a catheter opening at the catheter tip. The catheter tip and the needle tip are configured to be pressed against one another to fluidically couple the catheter channel with the needle channel, and at least a portion of the catheter tip penetrates into the needle opening to provide fluidic coupling between the catheter channel and the needle channel.

Description

Technical Field

[0001] This invention relates to sample injection, and in particular to sample injection for chromatographic sample separation. Background Technology

[0002] In liquid separation within a chromatographic system, a mobile phase of a sample fluid (e.g., a chemical or biological mixture) containing complexes to be separated is driven through a stationary phase (e.g., column packing material) to separate the different complexes in the sample fluid, which can then be identified. The term "complex" as used herein should encompass complexes that may contain one or more different components.

[0003] Typically, a mobile phase (e.g., a solvent) is pumped under high pressure through a chromatographic column containing a packed medium (also called the packing material or stationary phase). As the sample is carried through the column by the liquid flow, different complexes (each with a different affinity for the packing medium) move through the column at different speeds. Complexes with a greater affinity for the stationary phase move through the column more slowly than those with a smaller affinity, and this speed difference causes the complexes to separate from each other as they pass through the column. The stationary phase is subjected to mechanical forces, specifically generated by a hydraulic pump that typically pumps the mobile phase from the upstream connection to the downstream connection of the column. Due to the flow, a relatively high pressure drop is generated on the column, depending on the physical properties of the stationary and mobile phases.

[0004] The mobile phase containing the separated complexes exits the column and passes through a detector, which records and / or identifies the molecules, for example, by spectrophotometric absorbance measurements. A two-dimensional curve, called a chromatogram, can be plotted showing the detector measurements relative to elution time or volume, and the complexes can be identified from the chromatogram. For each complex, the chromatogram displays individual curve characteristics, also known as "peaks".

[0005] In preparative chromatography systems, the liquid used as the mobile phase is typically supplied at a controlled flow rate (e.g., from 1 mL / min to several thousand mL / min, such as 1-5 mL / min in preparative LC at the analytical scale and 4-200 mL / min at the preparative scale) and a pressure (e.g., 20-600 bar) in the range of tens to hundreds of bar.

[0006] In high-performance liquid chromatography (HPLC), the liquid as the mobile phase must typically be supplied at very controlled flow rates (e.g., in the range of a few microliters to a few milliliters per minute) and high pressures (typically 20-100 MPa, 200-1000 bar, and currently even higher at 200 MPa, 2000 bar), at which the compressibility of the liquid becomes apparent.

[0007] In preparative chromatography systems used for separating samples with larger volumes of chromatographic fluid, typically in the range of 0.1 mL to tens of mL, it is often necessary to analyze smaller volumes of such samples (e.g., in the sense of an "analytical reconnaissance run") before running larger volumes of separation. For this purpose, analytical chromatography systems can be used to chromatographically separate smaller sample volumes, typically in the range of 10 μL to 50 μL. Such analytical chromatography systems can be HPLC systems.

[0008] The applicant, Agilent Technologies, provides a sampling unit for combined analytical and preparative chromatography systems using its Agilent dual-loop sampler G2258A, which allows for the injection of samples into both analytical and preparative chromatography systems.

[0009] The sample injector in a chromatography system is configured to inject sample fluid into the mobile phase. Such a sample injector typically includes a needle for aspirating sample fluid, for example, from a sample vial. To inject the (aspirated) sample fluid into the mobile phase, the needle can be inserted into a corresponding needle hub, which is fluidly coupled to a chromatographic column for separating the complex of the sample fluid in the mobile phase. Summary of the Invention

[0010] The object of the present invention is, in particular, to provide an improved sample injector by providing improved fluid coupling to the needle, which is preferably used for chromatographic sample separation. This object is achieved by the independent claim. Other embodiments are shown in the dependent claims.

[0011] According to a preferred embodiment of the invention, a sample injector for a chromatographic system includes a mobile phase driver and a separation unit, wherein the mobile phase driver is configured to drive the mobile phase through the separation unit, and the separation unit is configured to chromatographically separate a complex of sample fluids in the mobile phase. The sample injector is configured to inject sample fluid into the mobile phase and includes a needle and a conduit. The needle is configured to aspirate sample fluid and includes a needle tip (which may be conical, flat, or any suitable shape) at one end, a needle channel through the needle to guide the aspirated sample fluid, and a needle opening at the needle tip, wherein the needle channel opens into the needle opening. The conduit is configured to fluidly couple with the needle and includes a conduit tip (which may be conical, flat, or any suitable shape) at one end and a conduit channel through the conduit to guide fluid (e.g., sample fluid), and the conduit channel has a conduit opening at the conduit tip. The conduit tip and the needle tip are configured to press against each other to fluidly couple the conduit channel with the needle channel, and at least a portion of the conduit tip extends into the needle opening to provide fluid coupling between the conduit channel and the needle channel. This allows for improved fluid coupling between the needle and conduit of the sample injector.

[0012] In one embodiment, the surface of the catheter tip (preferably the outer surface) abuts against the surface of the needle opening (preferably the inner surface) to provide fluid coupling between the catheter channel and the needle channel. Preferably, the surface of the catheter tip abuts against the surface of the needle opening in a sealing manner to provide liquid-tight fluid coupling between the catheter channel and the needle channel.

[0013] In one embodiment, at least one of the needle tip and the catheter tip has a tapered shape. The tapered shape preferably comprises an outer cone that extends on the side of the tip and whose diameter decreases toward the end of the tip.

[0014] In one embodiment, the needle includes a tapered shape comprising an outer cone extending on the side of the needle tip and decreasing in diameter toward the end of the needle tip.

[0015] In one embodiment, the catheter includes a tapered shape comprising an outer cone extending on the side of the catheter tip and decreasing in diameter toward the tip. Preferably, the tapered shape of the catheter is configured to match the shape of the needle opening such that when the catheter tip and the needle tip are pressed against each other, the catheter tip seals against the needle opening.

[0016] In one embodiment, the needle includes a conical shape comprising an inner cone extending in the needle opening (preferably from the needle channel) and increasing in diameter toward the end of the needle tip.

[0017] In one embodiment, the catheter includes a tapered shape comprising an inner cone extending in the catheter opening (preferably from the catheter channel) and increasing in diameter toward the end of the catheter.

[0018] In one embodiment, the needle opening includes a first conical shape, which preferably includes an inner cone extending from the needle channel. The diameter of the first conical shape increases towards the end of the needle tip. The catheter tip includes a second conical shape, which preferably includes an outer cone. The second conical shape extends on the side of the catheter tip and its diameter decreases towards the end of the catheter tip. The first conical shape is configured to match the second conical shape such that when the catheter tip and the needle tip are pressed against each other, the catheter tip seals against the needle opening of the needle tip.

[0019] In one embodiment, the needle tip has an asymmetrical shape with a cut-off portion that is angled relative to the elongated shape of the needle. The needle tip may include a tapered inner portion, wherein the diameter of the needle opening increases toward the tip of the needle tip.

[0020] In one embodiment, the needle comprises an elongated shape, preferably a cylindrical shape.

[0021] In one embodiment, the needle channel is configured to at least partially buffer the aspirated sample fluid.

[0022] In one embodiment, the catheter comprises an elongated shape, preferably a cylindrical shape.

[0023] In one embodiment, the conduit is a capillary or includes a capillary.

[0024] In one embodiment, the conduit is a fluid coupling element or includes a fluid coupling element.

[0025] In one embodiment, the catheter is provided with one or more materials selected from the group consisting of glass, ceramic, plastic, polymer, and metal, and the catheter tip may be provided with a different material than the rest of the catheter. The catheter may be presented as a replaceable component, for example, outside the needle hub, and may be inserted into and mechanically fastened and secured by the needle hub.

[0026] In one embodiment, the needle is provided from one or more materials selected from the group consisting of metals, glass, ceramics, plastics, and polymers, and the tip of the needle may be provided from a different material than the rest of the needle. The needle may be presented as a replaceable component that can be inserted into an actuating unit and mechanically fastened and secured by the actuating unit.

[0027] Although all combinations of materials for the catheter and needle can be used as described above (particularly depending on the application), the materials of the catheter and needle, particularly those provided at the catheter tip 370 and needle tip 300 or at the catheter tip 370 and needle tip 300, are preferably chosen to match each other, especially in terms of sealing performance, if they differ from other parts of the catheter 360 and / or needle 200.

[0028] In one embodiment, the sample syringe includes a needle hub configured to receive a needle from one side and a catheter from the other side (preferably opposite the side receiving the needle).

[0029] In one embodiment, the needle hub is configured to press the catheter tip and the needle tip against each other, preferably configured to press the catheter tip and the needle tip against each other elastically.

[0030] In one embodiment, the catheter is fixedly coupled to a first needle hub, preferably providing an axial bias along the catheter when the catheter tip and the needle tip are pressed against each other.

[0031] In one embodiment, the needle hub includes a clamping element configured to clamp and secure the catheter to the needle hub to axially fix the spatial position of the catheter tip relative to the spatial position of the needle tip when the needle tip is received in the needle hub, wherein the clamping element preferably includes a spring element configured to elastically bias the catheter tip relative to the needle tip when the needle tip is received in the needle hub.

[0032] In one embodiment, a separation system is provided for separating complexes of a sample fluid in a mobile phase. The fluid separation system includes a mobile phase driver (preferably a pumping system) adapted to drive the mobile phase through the fluid separation system and a separation unit (preferably a chromatographic column) adapted to separate complexes of the sample fluid in the mobile phase. The separation system also includes a sample injector according to any of the above embodiments, adapted to introduce the sample fluid into the mobile phase.

[0033] In one embodiment, the separation system further includes one or more of the following: a detector adapted to detect the separated complex of the sample fluid; a collection unit adapted to collect the separated complex of the sample fluid; a data processing unit adapted to process data received from the fluid separation system; and a degassing device for degassing the mobile phase.

[0034] In one embodiment, a method of operating a sample injector for a chromatographic system is provided. The chromatographic system includes a mobile phase driver and a separation unit. The mobile phase driver is configured to drive the mobile phase through the separation unit, and the separation unit is configured to chromatographically separate a complex of sample fluids in the mobile phase. The sample injector is configured to inject sample fluid into the mobile phase and includes a needle and a conduit. The needle is configured to aspirate sample fluid. The needle includes a needle tip at one end, a needle channel through the needle to guide the aspirated sample fluid, and a needle opening at the needle tip, wherein the needle channel opens into the needle opening. The conduit is configured to fluidly couple with the needle. The conduit includes a conduit tip at one end and a conduit channel through the conduit to guide fluid, and the conduit channel has a conduit opening at the conduit tip. The method includes inserting at least a portion of the conduit tip into the needle opening, and pressing the conduit tip and the needle tip against each other to fluidly couple the conduit channel with the needle channel.

[0035] In one embodiment of the method, pressing the catheter tip and the needle tip against each other includes: pressing the surface of the catheter tip (preferably the outer surface) against the surface of the needle opening (preferably the inner surface) to provide fluid coupling between the catheter channel and the needle channel. Preferably, the surface of the catheter tip is sealed against the surface of the needle opening to provide liquid-tight fluid coupling between the catheter channel and the needle channel.

[0036] Embodiments of the present invention can be implemented based on the most commonly available HPLC systems, such as the Agilent 1220, 1260 and 1290 Infinity LC series (provided by the applicant, Agilent Technologies).

[0037] One embodiment of an HPLC system includes a pumping device with a piston that reciprocates within a pump working chamber to compress a liquid in the pump working chamber to a high pressure, under which the compressibility of the liquid becomes apparent.

[0038] The separation apparatus preferably includes a chromatographic column providing the stationary phase. This column can be a glass, metal, ceramic, or composite tube (e.g., with a diameter of 50 µm to 5 mm and a length of 1 cm to 1 m) or a microfluidic column (as disclosed in EP 1577012 A1 or in the Agilent 1200 series HPLC-Chip / MS system provided by the applicant, Agilent Technologies). As the components pass through the column at different speeds along with the eluent, they are retained differently by the stationary phase and separated from each other. At the ends of the column, they are eluted at least partially separated from each other. Throughout the chromatography process, the eluent can also be collected in a series of fractions. The stationary phase or adsorbent in column chromatography is typically a solid material. The most commonly used stationary phase in column chromatography is silica gel, followed by alumina. Cellulose powder has been frequently used in the past. Ion exchange chromatography, reversed-phase chromatography (RP), affinity chromatography, or expanded bed adsorption (EBA) are also possible. The stationary phase is typically a finely ground powder or gel and / or microporous for increased surface area, which may be chemically modified, but fluidized beds are used in EBA.

[0039] The mobile phase (or eluent) can be a pure solvent or a mixture of different solvents. It may also contain additives, i.e., a solution of the additives in the solvent or solvent mixture. The retention rate of the target compound and / or the amount of mobile phase used for chromatography can be selected, for example. The mobile phase can also be selected to allow for efficient separation of different compounds. The mobile phase may include an organic solvent typically diluted with water, such as methanol or acetonitrile. For gradient runs, water and the organic solvent are delivered in separate containers, from which a gradient pump delivers the planned mixture to the system. Other commonly used solvents may be isopropanol, THF, hexane, ethanol, and / or any combination thereof, or any combination of these with the aforementioned solvents.

[0040] The sample fluid can include any type of process liquid, natural samples such as fruit juice, bodily fluids such as blood plasma, or it can be the result of a reaction such as that from fermentation broth.

[0041] The fluid is preferably a liquid, but may also be a gas and / or a supercritical fluid (as used in supercritical fluid chromatography-SFC disclosed, for example, in US4,982,597A).

[0042] The pressure in the mobile phase can be 2-200 MPa (20 to 2000 bar), especially 10-150 MPa (100 to 1500 bar), and even more particularly 50-130 MPa (500 to 1300 bar).

[0043] HPLC systems may also include detectors for detecting separated complexes in a sample fluid, fractionation units for discharging the separated complexes from the sample fluid, or any combination thereof. Further details of the HPLC systems described above are disclosed regarding the Agilent HPLC family provided by the applicant, Agilent Technologies.

[0044] Embodiments of the present invention may be embodied or supported, in part or in whole, by one or more suitable software programs or products, which may be stored on or provided by any type of data carrier and may be executed in or by a suitable data processing unit. The software programs or routines may preferably be applied in or by a control unit (e.g., a data processing system such as a computer), and are preferably used to perform any of the methods described herein.

[0045] In the context of this application, the term "fluid sample" can specifically refer to any liquid and / or gaseous medium, and optionally also includes solid particles to be analyzed. Such a fluid sample may include multiple fractions of molecules or particles that should be separated, such as biomolecules like proteins. Since separating a fluid sample into fractions involves specific separation criteria (e.g., mass, volume, chemical properties, etc.), according to which separation is performed, each separated fraction can be further separated by another separation criterion (e.g., mass, volume, chemical properties, etc.), or by a finer separation by the first separation criterion, thereby splitting or separating a single fraction into multiple subfractions.

[0046] In the context of this application, the terms "sample separation apparatus," "fluid separation device," or the like may specifically refer to any apparatus capable of separating different fractions of a fluid sample by applying some separation technique. In particular, when configured for two-dimensional separation, a two-stage separation apparatus may be provided in such a sample separation apparatus. This means that the sample is first separated according to a first separation criterion, and at least one or more fractions obtained from the first separation are subsequently separated according to different second separation criteria, or further separated according to the first separation criterion.

[0047] The terms "separation unit," "separation device," or the like may specifically refer to a fluid component through which a fluid sample is transferred, and which is configured such that, when the fluid sample is guided through the separation unit, it will be separated into different groups of molecules or particles (referred to as fractions or subfractions, respectively). An example of a separation unit is a liquid chromatography column, which is capable of collecting or retaining and selectively releasing different fractions of a fluid sample.

[0048] In the context of this application, the terms “fluid driven,” “mobile phase driven,” or the like may specifically refer to any type of pump configured to force a mobile phase and / or a fluid sample to flow along a fluid path. Attached Figure Description

[0049] Other objects and numerous incidental advantages of the embodiments of the present invention will be readily appreciated and better understood by referring to the following more detailed description of the embodiments in conjunction with the accompanying drawings. Substantially or functionally equivalent or similar features will be referred to by the same reference numerals.

[0050] Figure 1 A liquid chromatography system according to an exemplary embodiment is shown.

[0051] Figure 2 An embodiment of the sample injector 40 is shown in more detail.

[0052] Figure 3 An embodiment of a needle 200 disposed in a needle holder 280 is shown.

[0053] Figure 4 Figure 5 shows another embodiment of the needle 200. Detailed Implementation

[0054] Now refer to the attached diagram for more details. Figure 1 A general schematic diagram of the liquid separation system 10 is shown. A mobile phase driver 20 (e.g., a pump) typically receives the mobile phase from a solvent supply 25 via a degasser 27, which degass the mobile phase and thus reduces the amount of dissolved gas therein. The mobile phase driver 20 drives the mobile phase through a separation device 30 (e.g., a chromatographic column). A sample injector 40 (also called a sample introduction device, sample dispenser, etc.) is disposed between the mobile phase driver 20 and the separation device 30 to apply or add (generally referred to as sample introduction) a portion of one or more sample fluids into the flow of the mobile phase. The separation device 30 is adapted to separate complexes of the sample fluid (e.g., a liquid). A detector 50 is provided for detecting the separated complexes of the sample fluid. A fractionation unit 60 may be provided for discharging the separated complexes of the sample fluid. In one embodiment, at least a portion of the sample injector 40 and the fractionation unit 60 may be combined, for example, in the sense of some common hardware used when both are applied.

[0055] The separation device 30 may include a stationary phase configured to separate the complex of the sample fluid. Alternatively, the separation device 30 may be based on different separation principles (e.g., field flow fractionation).

[0056] While the mobile phase can consist of only one solvent, it can also be a mixture of multiple solvents. Such mixing can be low-pressure mixing and positioned upstream of the mobile phase driver 20, such that the mobile phase driver 20 has already received and pumped the mixed solvents as the mobile phase. Alternatively, the mobile phase driver 20 can be composed of multiple separate pumping units, each receiving and pumping a different solvent or mixture, such that mixing of the mobile phase (received by the separation unit 30) occurs under high pressure and downstream of (or as part of) the mobile phase driver 20. The composition of the mobile phase (mixture) can remain constant over time (so-called isocratic mode) or vary over time (so-called gradient mode).

[0057] A data processing unit 70, which may be a conventional PC or workstation, can be coupled (as indicated by the dashed arrow) to one or more devices in the liquid separation system 10 to receive information and / or control operation. For example, the data processing unit 70 can control the operation of the mobile phase driver 20 (e.g., setting control parameters) and receive information from it about actual operating conditions (e.g., output pressure, flow rate, etc. at the pump outlet). The data processing unit 70 can also control the operation of the solvent supplier 25 (e.g., monitoring the level or amount of available solvent) and / or the degasser 27 (e.g., setting control parameters such as vacuum level), and can receive information from it about actual operating conditions (e.g., solvent composition supplied over time, flow rate, vacuum level, etc.). The data processing unit 70 can further control the operation of the sample injector 40 (e.g., controlling sample introduction or synchronizing sample introduction with the operating conditions of the mobile phase driver 20). The separation device 30 can also be controlled by the data processing unit 70 (e.g., selecting a specific flow path or column, setting the operating temperature, etc.), and in response, sends information (e.g., operating conditions) to the data processing unit 70. Accordingly, detector 50 can be controlled by data processing unit 70 (e.g., regarding spectral or wavelength settings, setting time constants, starting / stopping data acquisition), and information (e.g., regarding detected sample complexes) can be sent to data processing unit 70. Data processing unit 70 can also control the operation of fractionation unit 60 (e.g., combining data received from detector 50) and provide data back. Data processing unit 70 can also process and evaluate data received from the system or a portion thereof to represent the data in an appropriate form for further interpretation.

[0058] Figure 2An embodiment of the sample injector 40 is shown in more detail. The sample injector 40 includes a needle 200 and an actuation unit 210 configured to move and position the needle 200. One or more receivers 220 may be disposed in, for example, a tray 230 (such as a bottle tray or any other container known in the art), wherein the receiver 220 may include, for example, a sample fluid to be injected by the sample injector 40. Figure 2 In the example, only one receiver 220 is shown for the sake of simplicity.

[0059] Positioning of the needle 200 provided by the manipulation unit 210 can be done only in the Z direction, as shown in the axial diagram, allowing the needle 200 to be positioned in height (only) by, for example, lowering or raising it in the Z direction. For this purpose, the manipulation unit 210 may include a slider 240 configured to slide along a guide rail 250 in the Z direction, for example operated by a drive unit 260, where the drive unit 260 may be an electric motor.

[0060] As is known in the art, the manipulation unit 210 can also be configured to move and position the needle 200 in the X and / or Y directions (as shown in the axis diagram).

[0061] As is well known in the art, Figure 2 The tray 230 shown in the embodiment is positioned on a movable slide plate 270, which can be moved in the X and / or Y directions (as shown in the axis diagram) to position one or more receivers 220 relative to the needle 200.

[0062] exist Figure 2 In an exemplary embodiment, the slide 270 is configured to move in the X direction, and the manipulation unit 210 is configured to move the needle 200 in the Z direction as it does in the Y direction. However, it is clear that other (relative) motion mechanisms, including rotational motion and combinations thereof, can be applied accordingly.

[0063] A needle holder 280 is provided, in which a needle 200 can be disposed (e.g., via an operating unit 210) to allow fluid connection of the needle 200 to a high-pressure flow path between the mobile phase driver 20 of the liquid separation system 10 and the separation device 30, for example, to inject sample fluid (drawn from the receiver 220 into the needle 200) into such a high-pressure flow path for chromatographic separation by the separation device 30. Such injection can be performed, for example, by feed injection as described in US 2017343520A1 above and / or by flow-through injection as described in US 20160334031 A1 above.

[0064] Figure 3An embodiment of the needle 200 disposed in the needle holder 280 is shown in more detail and in a two-dimensional sectional view. The needle 200 has an elongated, preferably cylindrical shape, with a needle tip 300. In this embodiment, the needle 200 is physically separated from the needle holder 280. Figure 2 on the contrary, Figure 3 The needle 200 is indicated as being placed in the needle holder 280 such that a portion of the needle 200 (preferably the needle tip 300) passes through the needle holder 280 and is fluidly coupled thereto.

[0065] The needle channel 310 extends through the needle 200 to guide (and preferably also buffer at least a portion) the sample fluid aspirated by the needle 200. The needle channel 310 opens into the needle opening 320 at the needle tip 300. Figure 3 In one embodiment, the needle tip 300 has an outer conical shape 330, wherein the outer diameter of the needle 200 decreases toward the tip 340 of the needle tip 300. Obviously, the outer conical shape 330 can have any suitable form and does not necessarily need to be... Figure 3 The exemplary embodiment of the linear cone is shown.

[0066] The needle tip 300 also has an inner conical shape 350, the diameter of which increases from the needle channel 310 toward the end 340 of the needle tip 300. Again, the inner conical shape 350 can have any suitable form and does not necessarily need to be... Figure 3 The exemplary embodiment of the linear cone is shown.

[0067] The needle hub 280 includes a conduit 360, which has an elongated, preferably cylindrical shape and is configured to be fluidly coupled to the needle 200. The conduit 360 has a conduit tip 370 at one end 372. A conduit channel 375 extends through the conduit 360 to guide fluid (e.g., a sample fluid). The conduit channel 375 opens into a conduit opening 380 at the conduit tip 370.

[0068] The distal end 370 of the catheter has an outer conical shape 382, ​​wherein the outer diameter of the catheter 360 decreases toward the distal end 372 of the needle tip 300. Clearly, the outer conical shape 382 can have any suitable form and does not necessarily need to be... Figure 3 The exemplary embodiment shows a basic straight cone with a rounded outer diameter at end 372 and toward end 372 and toward conduit 360.

[0069] The needle holder 280 also includes a clamping element 385 configured to clamp and secure the catheter 360 to the needle holder 280, preferably fixing the spatial position of the catheter tip 370 relative to the spatial position of the needle tip 300 (e.g., axially) when the needle 200 is received in the needle holder 280. The clamping element 385 is either housed in or part of a housing 387 of the needle holder 280. The housing 387 may include additional components, such as an upper needle holder 390, which is well known in the art and does not need to be described in detail here.

[0070] The clamping element 385 spatially secures the conduit 360 to a defined spatial position within the needle seat 280 in order to ensure and achieve the required sealing force for providing a liquid-tight seal.

[0071] The clamping element 385 may include a retaining element 392, which may be a leaf spring, a disc spring, or any other type of spring, to elastically bias the catheter tip 370 relative to the needle tip 300 when the needle tip 300 is received in the needle holder 280.

[0072] The conduit 360 can be fixedly coupled to the retaining element 392, for example, by welding, clamping, etc.

[0073] When the catheter 360 is held and positioned (e.g., axially) by the clamping element 385, the needle 200 is preferably pressed into the needle holder 280 by the actuation unit 210. Alternative mechanical configurations for holding the needle 200 and pressing it into the needle holder 280 are also possible, and may allow further use of the actuation unit 210 after, for example, the needle 200 has been positioned into the needle holder 280 and the needle 200 has been disengaged from the actuation unit 210.

[0074] The conduit 360 can be a capillary or any other conduit, and can be made of any suitable material, such as glass, ceramic, plastic, polymer, metal, etc. The conduit 360 is preferably presented as a replaceable part outside the needle hub 280, which can be inserted into the needle hub 280 and mechanically fastened and secured by the needle hub 280.

[0075] The needle 200 can be made of any suitable material, such as metal, glass, ceramic, plastic, polymer, etc., and can be presented as a replaceable part that can be inserted into the operating unit 210 and mechanically fastened and fixed by the operating unit 210.

[0076] Although all material combinations of the catheter 360 and needle 200 can be applied as described above (particularly depending on the application), the materials of the catheter 360 and needle 200, particularly those provided at the catheter tip 370 and needle tip 300, are preferably selected to match each other, especially in terms of sealing performance, if they differ from other parts of the catheter 360 and / or needle 200.

[0077] When the needle 200 is received in the needle holder 280, the needle tip 300 and the catheter tip 370 are preferably connected, for example, by applying an application such as... Figure 3 The axial force F is schematically shown in the diagram, pressing against each other. Obviously, this axial force F can be provided by either or both of the needle tip 300 and the catheter tip 370, and represents the resultant force for achieving the fluid tight coupling between the needle 200 and the catheter 360 (and in particular between the needle channel 310 and the catheter channel 375).

[0078] The needle tip 300 and the catheter tip 370 can be elastically pressed against each other, for example by providing an elastic force (e.g. by retaining element 392), in order to avoid damage that may result from hard contact and / or to ensure continuous pressing force F even if the relative positions of the needle tip 300 and the catheter tip 370 relative to each other may change over time.

[0079] When the catheter tip 370 and the needle tip 300 are pressed against each other to fluidly couple the catheter channel 375 with the needle channel 310, at least a portion of the catheter tip 370 extends into the needle opening 320 to provide fluid coupling between the catheter channel 375 and the needle channel 310. With the outer conical shape 382 of the catheter 360 substantially matching the inner conical shape 350 of the needle 200, the catheter tip 370 and the needle tip 300 will provide cone-to-cone coupling, thereby allowing a sealing coupling between the catheter tip 370 and the needle tip 300.

[0080] Obviously, a conical coupling is not required between the catheter tip 370 and the needle tip 300 to provide a liquid-tight and sealing coupling; other types of coupling (particularly shape coupling) can also be provided. As an example, only one of the catheter tip 370 and the needle tip 300 may have a conical shape, while the other may have another suitable shape, such as a flat shape (i.e., a flat front facing the corresponding other component), a circular shape, etc. Alternatively, but less preferably, both the catheter tip 370 and the needle tip 300 may not be provided with a conical shape or a similar shape with varying outer / inner diameters to provide a sealing coupling relative to each other. As an example, the catheter tip 370 may have, for example, a flat shape (i.e., a flat front facing the needle tip 300) and carry an elastic sealing material, such as a sealing ring, etc., and the sealing material elastically deforms when the catheter tip 370 and the needle tip 300 are pressed against each other, thereby providing a sufficient liquid-tight seal.

[0081] It has been found that the coupling of cones with conical shapes provides a reliable sealing surface that is also reasonably tolerant of, for example, misalignment in axial alignment between the guide tip 370 and the needle tip 300. As is known in the art, this can be further improved by appropriately designing corresponding cone angles relative to each other. The cone angles can be designed to be substantially equal (e.g., within manufacturing tolerances) or different. Preferably, the outer “male” cone can be designed to have a smaller cone angle than the corresponding inner “female” cone. As an example, the outer “male” cone can have a cone angle of 58°, while the inner “female” cone has a cone angle of 60°. It goes without saying that the specific angles depend on the specific application and mechanical construction, and are understood only as examples.

[0082] Furthermore, it is clear that the needle 200 does not necessarily need to have an outer conical shape 330, but the needle 200 may also have a substantially constant outer diameter up to the end 340 of the needle 200, or the needle 200 may have any other shape known in the art and as will be shown later. However, the outer conical shape 330 can be very useful in many applications, such as for piercing through the top seal (e.g., a liner) of the receiving seat 220.

[0083] Figure 4 Another embodiment of the needle 200 disposed in the needle holder 280 is shown in a three-dimensional sectional view. Relative to Figure 3 The main difference in the embodiments is the different forming of the needle 200, which is also in Figures 5A-5B It is shown in the three-dimensional diagram. Figure 4 The needle 200 in the embodiment of Figure 5 includes a needle tip 400 having an asymmetrical shape.

[0084] Similar to needle tip 300, needle tip 400 also has an inner conical shape 350, the diameter of which increases from needle channel 310 toward the end of needle tip 400. Again, the inner conical shape 350 can have a suitable form and does not necessarily need to be... Figure 4 The exemplary embodiment of the linear cone is shown.

[0085] and Figure 3 As in the previous embodiment, the needle tip 400 also includes an inner conical shape 350, wherein the diameter of the needle opening 320 increases toward the end 340 of the needle tip 400.

[0086] The needle tip 400 also includes a cut portion 410 that is cut at an angle relative to the elongated shape of the needle 200.

Claims

1. A sample injector for a chromatographic system, the chromatographic system comprising a mobile phase driver and a separation unit, wherein, The mobile phase driver is configured to drive the mobile phase through the separation unit, and the separation unit is configured to chromatographically separate a complex of sample fluid in the mobile phase. The sample injector is configured to inject the sample fluid into the mobile phase and includes: A needle configured to aspirate the sample fluid, wherein the needle includes a needle tip at one end, a needle channel passing through the needle to guide the aspirated sample fluid, and a needle opening at the needle tip, wherein the needle channel leads into the needle opening. A catheter configured to be fluidly coupled to the needle, wherein the catheter includes a catheter tip at one end and a catheter channel passing through the catheter to guide fluid, and the catheter channel has a catheter opening at the catheter tip. The catheter tip and the needle tip are configured to press against each other to fluidly couple the catheter channel with the needle channel, and at least a portion of the catheter tip extends into the needle opening to provide fluid coupling between the catheter channel and the needle channel.

2. The sample injector according to claim 1, wherein: The surface of the catheter tip abuts against the surface of the needle opening to provide fluid coupling between the catheter channel and the needle channel.

3. The sample injector according to claim 2, wherein: The surface of the catheter tip seals against the surface of the needle opening to provide liquid-tight fluid coupling between the catheter channel and the needle channel.

4. The sample injector according to any one of claims 1-3, wherein: At least one of the needle tip and the catheter tip has a tapered shape.

5. The sample injector according to claim 4, comprising at least one of the following: The conical shape includes an outer cone that extends on the side of the needle tip and / or the catheter tip and decreases in diameter toward the end of the needle tip and / or the catheter tip; The needle includes the conical shape, which includes an outer cone extending on the side of the needle tip and decreasing in diameter toward the end of the needle tip; The catheter includes the tapered shape, which comprises an outer cone extending on the side of the catheter tip and decreasing in diameter toward the tip of the catheter tip, wherein... The conical shape of the catheter is configured to match the shape of the needle opening, such that when the catheter tip and the needle tip are pressed against each other, the catheter tip seals against the needle opening; The needle includes the conical shape, which includes an inner cone extending in the needle opening and increasing in diameter toward the end of the needle. The catheter includes the tapered shape, which includes an inner cone extending in the catheter opening and increasing in diameter toward the end of the catheter. The needle opening includes a first conical shape comprising an inner cone extending from the needle channel with a diameter increasing toward the end of the needle tip, and the catheter tip includes a second conical shape comprising an outer cone extending on the side of the catheter tip with a diameter decreasing toward the end of the catheter tip, wherein the first conical shape is configured to match the second conical shape such that when the catheter tip and the needle tip are pressed against each other, the catheter tip seals against the needle opening of the needle tip.

6. The sample injector according to any one of claims 1-3 and 5, wherein: The needle tip has an asymmetrical shape, which includes a tapered inner portion and a cut-off portion cut at an angle relative to the elongated shape of the needle, wherein the diameter of the needle opening increases toward the end of the needle tip.

7. The sample injector according to any one of claims 1-3 and 5, comprising at least one of the following: The needle has an elongated shape; The needle channel is configured to at least partially buffer the aspirated sample fluid; The catheter has an elongated shape; The catheter is a capillary or includes a capillary. The conduit is a fluid coupling element or includes a fluid coupling element.

8. The sample injector according to claim 7, wherein: At least one of the needle and the catheter is cylindrical.

9. The sample injector according to any one of claims 1-3 and 5, comprising: A needle hub configured to receive the needle from one side and the catheter from the other side.

10. The sample injector of claim 9, comprising at least one of the following: The needle hub is configured to press the catheter tip and the needle tip against each other; The catheter is fixedly coupled to the needle hub, providing an elastic bias along the axial direction of the catheter when the catheter tip and the needle tip are pressed against each other. The needle hub includes a clamping element configured to clamp and secure the catheter to the needle hub, such that when the needle tip is received in the needle hub, the spatial position of the catheter tip is axially fixed relative to the spatial position of the needle tip, wherein... The clamping element includes a spring element configured to elastically bias the catheter tip relative to the needle tip when the needle tip is received in the needle seat.

11. The sample injector according to claim 10, wherein: The needle hub is configured to allow the catheter tip and the needle tip to press elastically against each other.

12. A separation system for separating complexes of a sample fluid in a mobile phase, the separation system comprising: A mobile phase actuator adapted to drive the mobile phase through the separation system; A separation unit adapted to separate the complex of the sample fluid in the mobile phase; and The sample injector according to any one of claims 1-11 is adapted to introduce the sample fluid into the mobile phase.

13. The separation system according to claim 12, wherein, The mobile phase driver is a pumping system, and the separation unit is a chromatographic column.

14. The separation system according to claim 12 or 13, further comprising at least one of the following: A detector adapted to detect the separated complexes in the sample fluid; A collection unit adapted to collect the separated complex of the sample fluid; A data processing unit adapted to process data received from the separation system; A degassing device for degassing the mobile phase.

15. A method of operating a sample injector for a chromatographic system, the chromatographic system comprising a mobile phase driver and a separation unit, wherein, The mobile phase driver is configured to drive the mobile phase through the separation unit, and the separation unit is configured to chromatographically separate the complexes of the sample fluid in the mobile phase. The sample injector is configured to inject the sample fluid into the mobile phase and includes... A needle configured to aspirate the sample fluid, wherein the needle includes a needle tip at one end, a needle channel passing through the needle to guide the aspirated sample fluid, and a needle opening at the needle tip, wherein the needle channel leads into the needle opening. A catheter configured to be fluidly coupled to the needle, wherein the catheter includes a catheter tip at one end and a catheter channel passing through the catheter to guide fluid, and the catheter channel has a catheter opening at the catheter tip. The method includes: At least a portion of the distal end of the catheter is inserted into the needle opening, and Press the catheter tip and the needle tip against each other to fluidly couple the catheter channel with the needle channel.

16. The method according to claim 15, wherein, Pressing the catheter tip and the needle tip against each other includes: The surface of the catheter tip is brought into contact with the surface of the needle opening to provide fluid coupling between the catheter channel and the needle channel.

17. A software program product comprising a software program stored on a data carrier and, when run on a data processing system, controlling or performing the method according to any one of claims 15-16.

18. The software program product according to claim 17, wherein the data processing system is a computer.

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