Positioning needles in mass spectrometry systems

Abstract

In one general aspect, the present disclosure relates to a package for a needle component for a mass spectrometry (MS) system. The package includes a container configured to store the needle component in a fixed position within the container. The package further includes an actuator configured to move the needle component from the fixed position within the container to an installation position, in which the needle component protrudes from the container for installation of the needle component to the MS system.

Description

Technical Field

[0001] The present disclosure relates to a packaging for a needle component (such as an electrospray ionization source capillary or nebulizer needle, an atmospheric pressure photoionization source capillary or an atmospheric pressure chemical ionization source electrode) for a mass spectrometry (MS) system. The present disclosure also relates to a method for installing or removing a needle component for an MS system. Background Art

[0002] In clinical laboratories and other laboratory environments, the implementation of mass spectrometry and more specifically the implementation of liquid chromatography (LC) systems or flow injection systems (FIS) connected to mass spectrometers has received increasing attention. Such MS systems typically include an ionization source for converting analyte molecules effluent from the LC system or FIS into the gas phase for further analysis in the mass spectrometer of the MS system (e.g., an MS-based analyzer). In turn, the ionization source may include a needle-like component (e.g., an electrospray ionization source capillary), which is a delicate, fragile element that must be replaced regularly (e.g., once every three months, or even more frequently in some instances) because it is progressively contaminating and corrosive.

[0003] The process of replacing the needle component may include manually removing the component from the box and manually inserting one or more components in the MS system (possibly with the help of special tools). This is not a simple and easy task and may require a certain degree of skill and training due to the fragility and delicacy of the needle component. Therefore, when using some existing solutions, the correct position of the needle component within the ionization source cannot be obtained in some cases. In other cases, the needle component may be bent during the insertion process, which may have a negative impact on the overall performance of the MS system. In addition, if this complex replacement process of the needle component fails, additional maintenance work may be required. In addition, the user may directly contact the sharp and possibly contaminated tip of the needle component during the replacement process, which poses a potential risk. Therefore, replacing the needle component is an important but tedious process that should generally be performed by skilled service technicians rather than by some users who lack experience with prior art MS equipment. Therefore, it is necessary to develop new, effective and simple technologies that can solve the above-mentioned problems. Summary of the invention

[0004] In one general aspect, the present disclosure relates to a package for a needle component for a mass spectrometry (MS) system. The package includes a container for storing the needle component in a fixed position within the container. The package further includes an actuator for moving the needle component from the fixed position within the container to an installation position, in which the needle component protrudes from the container for installation of the needle component to the MS system.

[0005] In a second general aspect, the present disclosure is directed to a method of mounting a needle component to a MS system using the package of the first general aspect.

[0006] In a third general aspect, the present disclosure relates to a method for removing a needle component from a MS system. The method includes engaging a package of the needle component with a needle component mounted to the MS system by activating an actuator of the package. The method also includes retracting the needle component from an installed position to a fixed position within a packaging container by activating an actuator of the package.

[0007] The techniques of the first to third general aspects may have advantageous technical effects.

[0008] First, compared to some prior art techniques, the technology disclosed in the present invention can allow for relatively simple and accurate introduction and positioning of a needle-shaped component (e.g., an electrospray ionization source capillary) in an MS system (e.g., within an ion source of an MS system). Specifically, the needle-shaped component can be easily inserted into the ion source through the packaging of the present invention, which includes an actuator for implementing the insertion. In some instances, the packaging can use a principle similar to that of a safety syringe. In addition, if necessary, it is also easy to remove the needle-shaped component from the ion source using the packaging. Compared to some prior art solutions, this can reduce the risk of the needle-shaped component breaking or bending. When the needle-shaped component is handled manually, the risk of injury to the user is also reduced.

[0009] Second, the current technology may have an advantage in that it does not involve the use of any special complex installation tools. This may make the installation of the needle component easier (e.g., for personnel with little or no training in servicing MS systems) and / or less expensive.

[0010] Third, the disclosed technology can facilitate safe removal and disposal of old, possibly contaminated needle components. In particular, compared to some prior art solutions, the disclosed packaging can minimize the risk of direct user contact with the sharp tip of the needle component. In addition, the current technology packaging can provide safe transportation and storage of the needle component, which is a delicate part of the ionization source of the MS system.

[0011] Fourth, the entire process of inserting / replacing the needle component using the current packaging may not require any special technical skills on the part of the user and, therefore, can be performed by an inexperienced user without having to call in a skilled service technician, as is the case with some prior art MS systems.

[0012] The term "mass spectrometer (MS)" may refer to an analysis module including a mass analyzer that is designed to further separate and / or detect analytes based on the mass-to-charge ratio of the analyte. In some instances, the mass spectrometer is a fast scanning mass spectrometer. However, in some instances, the mass spectrometer is a tandem mass spectrometer that can select parent molecular ions, generate fragments by collision-induced fragmentation, and separate fragments or daughter ions according to their mass-to-charge (m / z) ratios. In yet other instances, the mass spectrometer is a triple quadrupole mass spectrometer known in the art. In addition to a quadrupole mass analyzer, other types of mass analyzers may also be used, including a time-of-flight mass analyzer, an ion trap mass analyzer, or a combination thereof.

[0013] As used herein, the term "ionization source" refers to an interface for connecting a liquid chromatography (LC) system to a liquid chromatography / mass spectrometer LC / MS or a flow injection system to a mass spectrometer (FIS / MS), which is configured to produce charged analyte molecules (molecular ions) and to convert charged analyte molecules from a liquid phase to a gas phase. According to certain embodiments, the ionization source is an electrospray ionization (ESI) source or a heated electrospray ionization (HESI) source or an atmospheric pressure chemical ionization (APCI) source or an atmospheric pressure photoionization (APPI) or an atmospheric pressure laser ionization (APLI) source. However, the LC / MS or FIS / MS interface may include a dual ionization source, for example, both ESI and APCI sources or a modular exchangeable ionization source. Typical components of an ionization source may be a nebulizer and a sampling capillary, which are usually arranged orthogonally or coaxially to each other. The liquid leaving the LC system or FIS is guided through a probe, which includes a needle-like component, such as a nebulizer needle or a capillary or an electrode, depending on the specific ionization source under consideration. In this way, the liquid is atomized in a volume downstream of the spray capillary where ionization occurs and the charged analyte molecules obtained thereby are carried into the gas phase. A sampling device (eg, a sampling capillary or orifice) is provided to collect the ions in the gas phase and direct them into a mass spectrometer.

[0014] The ionization source may further include an assembly for providing a counter gas, also known as a curtain gas, (e.g., N2 or zero air, which is essentially pure, hydrocarbon-free laboratory air) that can shrink droplets and reduce the entry of background ions (e.g., solvent clusters) into the MS. The assembly may have a counter panel and an orifice assembly for providing the counter gas. The ionization source may further include an assembly for providing an auxiliary gas, also known as a heated gas. In order to optimize the ionization conditions, a supplemental flow rate may also be added directly before the ionization source to adjust the solvent composition to adjust the pH, salts, buffers, or organic content. Such ionization sources are known in the art and will not be further described herein.

[0015] The term "liquid" in relation to the FIS effluent refers to the sample or other analyte that is injected directly into the ionization source without subjecting the sample to a preliminary chromatographic separation. In alternative examples, the sample may be chromatographically separated first, and thus the liquid may refer to a liquid commonly used in liquid chromatography (LC) techniques, such as a solvent or solvent mixture used as a mobile phase or LC eluent (elution solvent), and other liquids as known in the art.

[0016] The term "sample" refers to a biological material suspected of containing one or more analytes of interest and whose detection, qualitative and / or quantitative analysis may be associated with a specific condition (e.g., a clinical condition). The sample may be from any biological source, such as a physiological fluid, including blood, saliva, lens fluid, cerebrospinal fluid, sweat, urine, milk, ascites, mucus, synovial fluid, peritoneal fluid, amniotic fluid, tissue, cells, etc. The sample may be pretreated before use, such as preparing plasma from blood, diluting viscous liquids, lysing, etc.; the treatment method may involve filtration, centrifugation, distillation, concentration, inactivation of interfering components, and addition of reagents. In some cases, the sample may be used directly as obtained from the source or may be used following a pretreatment and / or sample preparation workflow to modify the characteristics of the sample (e.g., after adding an internal standard, after diluting with another solution, or after mixing with a reagent), for example: to enable one or more in vitro diagnostic tests, or for enriching (extracting / separating / concentrating) the analyte of interest and / or removing matrix components that may interfere with the detection of the analyte of interest. In general, examples of analytes of interest are vitamin D, drugs of abuse, therapeutic drugs, hormones, and metabolites. However, this list is not exhaustive.

[0017] In some instances, the ionization source can be connected to the LC system or FIS via a valve-detector conduit, and the ionization source is connected to the MS. In some instances, the LC system can be configured as a kind of analysis module, which is designed to prepare samples for mass spectrometry and / or transfer the prepared samples to a mass spectrometer, particularly for separating target analytes before mass spectrometer detection. Specifically, usually, during the LC operation, the mass spectrometer can be set to scan a specific mass range. LC / MS data can be represented by adding the ionization currents in a single mass scan and plotting the "total" ion current as a relationship diagram of intensity points and time.

[0018] The term "liquid chromatography or LC" as used herein may refer to any type of analytical process that subjects a sample injected by an injector to chromatographic separation through an LC column, for example, so as to separate target analytes from one another and thus achieve their individual detection, for example, by mass spectrometry detection. In other examples, the analytical process is also intended to separate the target analyte from matrix components, for example, residual matrix components that may still interfere with subsequent detection after sample preparation. In some examples, such forms of liquid chromatography are used as liquid chromatography performed under pressure, such as "high performance liquid chromatography" or HPLC, "ultra-high performance liquid chromatography" or UHPLC, "micro-liquid chromatography" or μLC, and "small-bore liquid chromatography" or small-bore LC.

[0019] The term "liquid chromatography system or LC system" as used in the present disclosure is an analytical system or a module or unit in an analytical system for performing liquid chromatography analysis. An LC system may be embodied as a single channel system or a multichannel system, which may include one or more LC columns arranged in parallel and / or in series. An LC system may also include elements such as injectors, valves, liquid sources, fluid connections and components (e.g., for mixing liquids, degassing liquids, tempering liquids, etc.), one or more sensors (such as pressure sensors, temperature sensors, etc.), and in particular at least one LC pump. This list is not exhaustive.

[0020] "LC column" may refer to any of a column, cartridge, capillary, etc., used to perform separations of a chromatographic nature. The column is typically filled or loaded with a stationary phase through which a mobile phase is pumped to capture and / or separate and elute and / or transfer target analytes under selected conditions (e.g., based on the polarity or log P value, size or affinity of the target analyte, as is well known). The stationary phase may be particulate or beaded or a porous monolith. However, the term "LC column" may also refer to a capillary or channel that is not filled or loaded with a stationary phase but instead relies on the surface area of ​​the inner capillary wall or geometry to achieve separation. Column array chromatography provides an example in which the separation bed is formed by etching away the interstitial volume on a solid silicon wafer, leaving an array of columns. The resulting channel can be folded onto a smaller footprint by connecting the bed segments in series using optimized flow distributors that limit peak dispersion. This creates a stationary phase support structure that is organized in a reproducible, ordered pattern.

[0021] The composition of the mobile phase (i.e., the concentration of the solvent or solvent mixture that constitutes the mobile phase and is intended to carry the sample through the stationary phase of the LC column) can be a function that varies over time. This chromatographic separation process can be called a gradient elution. In some examples, the desired time dependence of the composition entering the LC column during the gradient elution can be pre-programmed.

[0022] The term "LC eluate" exiting the LC column is used herein to denote the portion of the eluate that contains at least one analyte of interest.

[0023] The term "fluid stream" may refer to a fluid path through which a liquid may flow, in particular through which a sample from a sample injection point may undergo a chromatographic process and may ultimately be transferred to a mass spectrometer.

[0024] The term "MS system" refers to any combination of equipment for performing mass spectrometry. For example, a mass spectrometry system can include one or more mass spectrometers and / or one or more ionization sources, as described above. In some instances, a MS system can include one or more LC systems or FIS as described above. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1a and 1b A needle component of a mass spectrometry (MS) system is schematically shown positioned within a container of a package.

[0026] Figure 2 Schematically shown is an MS system comprising an ionization source, wherein the needle component forms a replaceable part of the ionization source and a mass spectrometer is coupled to the ionization source.

[0027] Figure 3 A needle component is schematically shown protruding from a receptacle for mounting the needle component to a mounting location in an MS system.

[0028] Figure 4 is a flow chart showing a method of packaging a needle component for the MS system of the present disclosure.

[0029] Figure 5 is a flow chart illustrating a method for removing a needle component from the MS system of the present disclosure.

[0030] Figure 6 A MS system comprising a liquid chromatography (LC) system coupled to an electrospray ionization (ESI) source is schematically shown. DETAILED DESCRIPTION

[0031] First, combine Figure 1a and 1b to Figure 3 A general overview of the technology of the present disclosure is given. Then, the following sections will be respectively shown in Figure 4 and 5 Various aspects of the disclosed techniques are summarized in the flowchart in which the techniques relate to packaging of a needle component in a mass spectrometry (MS) system and methods for installing or removing a needle component from an MS system. Finally, when the MS system includes a liquid chromatography (LC) system, the following will be described in detail. Figure 6Some further aspects of the present disclosure are given in the examples of FIG.

[0032] Figure 1a and 1b 1 includes an illustrative example of a package 1 for a needle component 10 of a mass spectrometry (MS) system 100. In one example, the MS system (e.g., an MS-based analyzer) may include a mass spectrometer 30 (e.g., a triple quadrupole mass spectrometer) and an ionization source 20 coupled to the mass spectrometer 30, such as Figure 2 In the present example, the ionization source may be an electrospray ionization (ESI) source configured to provide a flow of ionized gas toward an inlet 31 of a mass spectrometer, such as liquid exiting a liquid chromatography (LC) system containing an eluate of interest. Figure 2 In the examples presented in , the needle-like component can be an ESI capillary or nebulizer needle 10, which can form a replaceable part of an ESI source 20. In some examples, the liquid introduced into the ESI source can be nebulized in a volume downstream of the ESI capillary or nebulizer needle 10, where ionization occurs, resulting in the production of a gas phase of charged molecules constituting the liquid, also referred to as nebulizer gas 23. Figure 2 In the example of , the ionization source 20 can further include a component configured to provide a counter gas 24 (eg, N2). Providing the counter gas 24 can shrink the droplets and reduce the amount of background ions (eg, solvent clusters) entering the mass spectrometer 30.

[0033] In the present technology, the packaging may include a container 11 configured to store the needle component 10 in a fixed position within the container 11. For example, the container 11 may be sealed from the surrounding environment (until the needle component is moved to the installation position). In other examples, the container 11 may include one or more openings, but still shield the needle component 10 from the surrounding environment. Back Figure 1a Or 1b, the container in the example may include a plastic material (e.g., composed of a plastic material). The container may be at least partially transparent (to allow inspection of the interior of the container) or opaque. In other examples, the container may include a glass material or other material. The container may include an opening through which the needle-shaped element may be moved to extend out of the container. In some examples, when the needle-shaped component is in a fixed position in the container, the container (e.g., the opening) may be closed by a cap 15 (e.g., by a nut) to prevent dust or dirt from passing through and accumulating in the container. The cap 15 may be configured to repeatedly close the container or may be a disposable cap. In one example, the closing cap may be a nut including a metal element. In other examples, a plastic cap without screws or other devices known in the art may be used to close the container 11. For example, a removable film may be provided to close the opening of the container (e.g., the removable film may be removed before the actuator is actuated and / or before the package is attached to the MS system).

[0034] In the technology of the present disclosure, the package 1 may further include an actuator 12 configured to move the needle component from a fixed position in the container. When moved, the needle component 10 may protrude from the container 11 for mounting the needle component to the MS system (see, for example, Figure 3 As described above in conjunction with Figure 2 As discussed, the needle component (i.e., the ESI capillary or nebulizer needle 10 shown in this figure) can be a replaceable part of the ESI source 20. In this example, the mounting location can be inside the ESI source of the MS system.

[0035] exist Figure 1a and 3 In the first example presented in , the actuators 12a, 12b may be configured as buttons (e.g., elements configured to be pushed along the side wall of the container to move the needle component from the fixed position to the installed position). Figure 1b In the second example presented in , the actuator 12a, 12b can be a push rod (e.g., an elongated element that can extend from the end of the container and is configured to be pushed to move the needle component from a fixed position to an installed position). In all cases, the actuator (e.g., a push rod or a button) can be coupled to the needle component in the container by a detachable coupling mechanism (i.e., the actuator can be removed from the needle component when the needle component is in the installed position). In one example, the actuator is configured to engage with the needle component by friction.

[0036] Further disclosed and proposed is a method for installing a needle-shaped component for a mass spectrometry (MS) system, continuing to refer to Figures 1 to 3 in Figure 4 The installation method includes: obtaining 101 a package, the package including a needle-like component located in a fixed position within a container of the package. In a further step, the technique includes: by activating an actuator of the package, moving (102) the needle-like component from the fixed position within the container to an installation position, wherein the needle-like component protrudes from the container, to install the needle-like component to the MS system.

[0037] In some examples, the needle-like component is a capillary or an electrode, optionally an electrospray ionization (ESI) capillary or a nebulizer needle, as described above in conjunction with Figure 2 (Other examples of needle-like components are discussed below). The packaging of the present technology may include a needle-like component. In one embodiment, the technology includes: during the initial stage of setting up a new MS system for operation, using a packaging with a needle-like component to install the latter into the MS system, for example, to Figure 2 and 3in an ESI source. In some other instances, when a needle component currently installed in an MS system needs to be replaced with a replacement needle component, the package with the needle component can be used as a spare part for an MS system used by a user. In some instances, the replacement can be performed during scheduled maintenance of the MS system. In still other instances, the replacement must be performed in response to a detection of a failure in the operation of the needle component by the MS system, which failure may be caused, for example, by contamination or aging of the needle component. In an instance, the MS system may automatically trigger a response based on the detected failure. In addition, the response may involve generating an alarm and / or stopping the operation of the MS system to notify the user that the needle element should be replaced. In some instances, before replacing the old needle component, the user may need to remove (e.g., loosen) a corresponding component of the MS system (e.g., a mounting device, such as a mounting nut) to access and remove the old needle component.

[0038] In the technology of the present disclosure, the package 1 may further include a connector element 13, which is configured to connect 103 the package to the MS system. The connector element can be further configured to fix 104 the package relative to the MS system. In a fixed position of the package relative to the MS system, the needle component can be aligned 105 with a tube 21 (e.g., a nebulizer tube) of a housing 22 of the needle component of the MS system (or aligned with another component of the MS system) at a predefined angle. In some instances, the needle component can be aligned parallel to the tube 21 so that the predetermined angle will be substantially zero. In other instances, the needle component can be aligned to form a non-zero inclination angle with the tube 21 (e.g., the inclination angle can be between 0° and 1°, between 0° and 2°, or between 0° and 5°). In some instances, fixing the package relative to the MS system can mean fixing the package relative to an ionization source of the MS system, for example, relative to an ESI source, such as Figure 2 and 3 As shown in the example of . In this case, the housing 22 of the needle-shaped component of the MS system can be the housing of the needle-shaped component of the ESI source. The connector element 13 of the present technology can include a fastening element. In some instances, the fastening element can be a thread, so that the packaging can be fixed to the MS system by screwing the packaging to the corresponding element of the MS system. In other instances, the fastening element can be a pin or a key, so that the packaging can be fixed to the MS system by connecting the packaging to the corresponding recess of the MS system. In other instances, the packaging can include a recess, so that the packaging can be fixed to the MS system by connecting the corresponding pin or key of the MS system to the recess. In some other instances, the fastening element can be an interlocking, a shaped surface or other suitable fastening elements, to be connected to the corresponding corresponding component in the MS system to connect the packaging to the MS system.

[0039] The actuator of the present disclosure may be a pusher configured to push the needle member from a fixed position within the container to an installed position in the MS system (see, e.g., Figure 3 In one example, as discussed above, the pusher may be configured as follows: Figure 1a In other examples, as discussed above, the pusher can be designed as Figure 1b Depicted button 12b. However, the actuator can include any mechanical, electromechanical or other device to realize the movement of the needle-shaped component from a fixed position to an installation position. For example, the actuator can be configured to be actuated by pulling or rotating corresponding parts (for example, buttons or handles) to move the needle-shaped component from a fixed position to an installation position. In these examples, packaging can include suitable elements to convert the motion of corresponding parts (for example, buttons or handles) into translational motion to move the needle-shaped component from a fixed position to an installation position. In an example, the element of the conversion motion can include a gear mechanism. In some examples, the gear mechanism can include a gear with discrete steps and an optional attachment counter triggered by a gear. In addition, the actuator or propeller can be configured to also be used as a puller (for example, to move the needle-shaped component back and forth or to remove the needle-shaped component from the MS system---these two examples are discussed in detail below).

[0040] In the present technology, once the packaging is fixed to the MS system, the packaging is configured to, for example, move the needle-shaped component to the installation position in the MS system by pushing the pusher, so as to facilitate the insertion of the needle-shaped component into 106 of the MS system. In an example, the pusher can be started by the user (for example, manually) to push the needle-shaped component into the installation position from the fixed position. In some examples, the tube 21 of the housing 22 of the needle-shaped component and the needle-shaped component at a predetermined angle can be the same as the installation position at the fixed position of the packaging relative to the MS system. In some examples, moving the needle-shaped component to the installation position can be substantially continuous towards the installation position. In some other examples, moving the needle-shaped component to the installation position can be performed step by step, for example, can be moved at different time points, with different speeds, in a direction towards the installation position, or can be moved back and forth in the forward and backward directions respectively relative to the installation position. Additionally or alternatively, moving the needle component to the installation position may be performed by rotating the pusher about an axis parallel to the needle component or about an axis aligned at a predefined angle as defined above (e.g., in a clockwise or counterclockwise direction during movement of the needle component to the installation position).

[0041] In the technology of the present disclosure, the package 1 may include an elastic element 14 configured to maintain the needle-like component in a fixed position within the container 11. In one example, the elastic element may be a spring element 14, such as in Figure 1a and1b In the embodiment presented in. In other examples, elastic sleeves, tubes or other elastic devices can be used as elastic elements for keeping the needle-shaped component in a fixed position in the container. In some examples, the elastic element can extend between the end of the pusher 12a, 12b and the container, and the end is closed by the closing cap 15 or other devices for closing the opening of the container (for example, the elastic device can be supported and / or fastened to the end of the container closed by the closing cap 15). In some other examples, the elastic element can be shorter than the distance between the pusher and the closing cap (for example, 5%, 10% or 20% shorter). In addition, the elastic element 14 can surround the needle-shaped element in a fixed position so that the latter can be positioned inside the elastic element.

[0042] In some instances, the package 1 may include an indicator configured to indicate one or more states of the needle component (e.g., one or more positions of the needle component before and / or during the placement process). The indicator may indicate the state in various ways (e.g., by presenting a color, a symbol, and / or a text message or a sound). For example, when the needle component 10 is in a fixed position within the container 11, the indicator may indicate a first state. For example, when the needle component 10 is in a fixed position within the container 11, the indicator may light up in a predetermined color (e.g., red). In other instances, the indicator may be a movable mechanical element that presents a predetermined color (e.g., red) when the needle component 10 is in a fixed position within the container. The needle component being in a fixed position may be determined, for example, based on a measured force applied by the elastic element 14 or by a position detection component.

[0043] In some instances, the package 1 can be configured to provide a first resistance, which resists the movement of the actuator 12a; 12b when the actuator is moved to insert the needle-shaped component 10 into the MS system 100. In this case, when the needle-shaped component is inserted into the MS system (e.g., more than 80% or more of the translational movement from the fixed position to the installation position), the user will experience the first resistance. In some instances, this may mean that the speed at which the user inserts the needle-shaped element into the installation position in the MS system may be limited or reduced by the first resistance (e.g., compared to the case where the first resistance does not exist). The first resistance to the movement of the actuator can be provided by an elastic element 14. In one instance, the elastic element capable of providing the first resistance can be different from the elastic element capable of keeping the needle-shaped component in a fixed position in the container. In other instances, the same elastic element can provide a first resistance to resist the movement of the actuator, and the needle-shaped component can be kept in a fixed position in the container. In some instances, the elastic element providing the first resistance can be a spring element, an elastic sleeve, a tube, or other elastic devices known in the art. In some examples, the package 1 may include the above-mentioned indicator, which may indicate the second state when the needle-shaped component 10 is inserted into the MS system. For example, when the needle-shaped component 10 is inserted into the MS system, the indicator may light up in a predetermined color (e.g., orange). In other examples, when the needle-shaped component 10 is inserted into the MS system, the movable mechanical element may present a predetermined color (e.g., orange). The insertion of the needle-shaped component into the MS system can be determined, for example, based on the first resistance provided by the elastic element 14 or by the position detection component.

[0044] The packaging and / or needle-shaped component of the present disclosure may be further configured to provide a second resistance when the needle-shaped component is aligned in the installation position to resist the movement of the actuator. The second resistance may be greater than the first resistance that resists the movement of the above-mentioned actuator. In some instances, when the needle-shaped component is aligned in the installation position, the actuator cannot move beyond a certain limit. In one instance, the second resistance may be provided by a blocking element of the packaging. In addition or alternatively, the second resistance may be provided by a blocking element of the needle-shaped component. In one instance, the blocking element may be a ferrule of the needle-shaped component. In other instances, the blocking element may be a blocking pin or other blocking element of the packaging or MS system. In some instances, when the user reaches the second resistance, she or he may determine that the needle-shaped component is well positioned and has reached the installation position in the MS system. The packaging without the needle-shaped component may then be separated from the MS system. In one instance, the user may eventually use a mounting device (e.g., mounting nut) to fix the needle-shaped component in the MS system.

[0045] Instead of using a resilient element configured to keep the needle-shaped component in a fixed position in the above-mentioned container, the package 1 of the present disclosure may include a thread configured to allow the outside of the package to rotate relative to the inside of the package. In this case, the inside of the package can be configured to keep the needle-shaped component in a fixed position in the container.

[0046] Further disclosed and proposed is a method for removing a needle-shaped component of a mass spectrometry (MS) system, with continued reference to FIGS. 1 to 3 and Figure 6 exist Figure 5 The method for removing the needle component includes: engaging the needle component package with the needle component mounted to the MS system by activating an actuator of the package 201. The technology of the present disclosure further includes: retracting the needle component from the mounted position to a fixed position within the container of the package by activating an actuator of the package 202.

[0047] In some instances, when the old needle-shaped component is removed from the MS system, the engagement and retraction steps can be performed for the old needle-shaped component. In some instances, the above-mentioned packaging can be used for this purpose, and it includes elastic element 14 to keep the needle-shaped component in a fixed position in the container. In other instances, when using a thread to replace the elastic element to keep the needle-shaped component, the packaging can include additional coupling mechanisms. In this case, additional coupling mechanisms (for example, pins or threads) and threads can be configured to provide engagement with the needle-shaped component in the installation position and to retract the needle-shaped component from the installation position to the fixed position in the container. In some instances, using threads and additional coupling mechanisms can be convenient to safely remove old capillaries from MS.

[0048] The retracting step of the present disclosure may include: obtaining 203 a package defined in the present disclosure (e.g., a package that does not include a needle-like component). The present technology can ensure the safe storage of a needle-like component (e.g., an old or new needle-like component) during its transportation. Specifically, the engagement and retracting steps of the present technology can be performed so that the user can avoid direct contact with the sharp tip of the needle-like component, which may have been contaminated with infectious materials or other hazardous materials (if it is removed from the MS system). The present technology may further include: setting 204 the package including the needle-like component in a fixed position within the container of the package. For example, the package can be handled together with the old needle-like component retracted into a fixed position within the container.

[0049] The retraction step of the present technology may further include: pulling the needle-shaped component from the installation position in the MS system to a fixed position in the container. Generally speaking, when the package is connected to the MS system, pulling the needle-shaped component can be performed. In some instances, the pulling step can be performed by the same actuator (e.g., the pusher, push rod, button, rotating rod, etc. disclosed above) used to move the needle-shaped component (e.g., a new needle-shaped component) to the installation position in the MS system. Therefore, when the needle-shaped component is pulled out from the MS system, all previous examples of the movement of the needle-shaped component to the installation position (e.g., continuous or stepwise movement) may also be applicable to the opposite situation. In addition or alternatively, the actuator of the present disclosure may include the additional push / pull device listed above to facilitate pulling the needle-shaped component from the installation position in the MS system. For example, the additional push / pull device may include a mechanism similar to a clip.

[0050] The retracting step of the present disclosure may include separating 206 the package from the MS system. In some instances, separating the package from the MS system may include separating the package from the corresponding corresponding component in the MS system. When the package is connected to the MS system, according to the above discussion about the second overall aspect, the corresponding corresponding component in this context may be a corresponding component to which the package 1 may be connected by a connector 13. Therefore, in some instances, separating the package from the MS system may involve releasing / disconnecting connector 13 (e.g., thread, pin, interlock, key, shaped surface or other suitable fastening elements as described above) from the corresponding corresponding component in the MS system. The separating step of the present disclosure may ultimately include removing 207 the package from a fixed position relative to the MS system.

[0051] In the above examples, the installation of electrospray ionization (ESI) capillary or sprayer needle has been discussed in more detail. However, as also mentioned above, the needle-shaped component can be any needle-shaped component adopted in the MS system, for example, any capillary or needle-shaped electrode. In some instances, the needle-shaped component generally extends in one direction. The needle-shaped component can have an outer diameter lower than 2 mm (for example, lower than 1 mm) within an extension range of at least 1 cm (for example, at least 2 cm).

[0052] In the present technology, the needle-shaped component can be configured to be mounted to the ionization source 20 of the MS system. Figure 2 In one example discussed in detail in the embodiments of the present invention, the ionization source can be an electrospray ionization (ESI) source, in which case the needle-like component can be an ESI capillary or a nebulizer needle. In some other examples, the ionization source can be an atmospheric pressure photoionization (APPI) source. In this case, the needle-like component can be an APPI capillary. In some other examples, the ionization source can be an atmospheric pressure chemical ionization (APCI) source. In these examples, an APCI electrode can be used as the needle-like component.

[0053] In some instances, the needle-shaped component can be automatically moved by using a suitable device. In this case, packaging and actuator can be configured to provide an interface to a motor or an interface for receiving a control signal (to achieve actuation). In other instances, the actuator can be configured to allow automatic and manual (e.g., by a user) actuation. In some instances, one or more magnetic elements can be used in packaging or MS systems to limit the position of the needle-shaped component relative to the MS system or / and relative to packaging. In some instances, the actuator of the present disclosure can be an electromechanically operable actuator (e.g., an actuator configured to convert an electrical signal into the movement of the needle-shaped component). The electromechanically operated actuator can include a motor, which can be a part of packaging or not a part of packaging (e.g., the actuator of packaging can be configured to be connected to a motor). In other instances, the actuator can include a magnetic element configured to translate the needle-shaped component.

[0054] In some examples, the electromechanically operable actuator may be controlled by a measurement signal. The measurement signal may be based on the ionization current of the ionization source. For example, the ionization current may be a function of the distance between the needle-shaped component and the counter plate of the ionization source. Therefore, by measuring the ionization current, the distance between the needle-shaped component and the opposing panel may be accurately determined. In some examples, automatic actuation may be performed immediately after the user manually inserts the needle-shaped component so as to accurately achieve the installation position of the needle-shaped component in the MS system. In one example, after completing the manual insertion of the needle-shaped component 10, the user may receive an indication from the package (for example, the above-mentioned indicator may indicate that the needle-shaped component is still in the second state): the installation position of the needle-shaped element has not yet been fully reached (that is, in the MS system, the position of the needle-shaped component is not accurate enough). In one example, this inaccuracy of the position of the needle-shaped component may be determined based on the measured force applied by the elastic element 14 of the package 1. In other examples, the position inaccuracy may be determined based on the measured ionization current. In some instances, the above-mentioned automatic actuation can be performed in the following manner: correct the position of the needle-shaped component in the MS system, and arrive at the installation position in the MS system. In some instances, when the installation position is accurately reached and the needle-shaped element is well positioned inside the MS system, the aforementioned indicator of the package 1 can indicate the third state. For example, when the needle-shaped element is well positioned inside the MS system, the indicator can light up with a predetermined color (e.g., green). In other instances, when the needle-shaped component is well positioned inside the MS system, the movable mechanical element can present a predetermined color (e.g., green). In this case, the actuator can be separated from the needle-shaped component, and the package without the needle-shaped component can be separated from the MS system. In some instances, the installation position is accurate and can be determined based on the measured force (e.g., based on the second resistance discussed above) applied by the elastic element 14 of the package 1. In other instances, the accuracy of the installation position can be determined based on the ionization current of the measurement. In some instances, when the needle-shaped component is removed from the MS system, the indicator of the package can provide an indication similar to the indication in the above-mentioned opposite case.

[0055] In one example, the ionization source of the MS system can be connected to a liquid chromatography (LC) system 40 of the MS system, which is configured to inject the liquid flowing out of the LC system into the ionization source. In some examples, the liquid leaving the LC system may include one or more target samples, liquid chromatography eluates, etc., which can be directed to the ESI source. Alternatively, the MS system can be connected to a flow injection (FIS) system of the MS system, which is configured to inject the liquid flowing out of the FIS system into the ionization source. In one example, the sample or other analyte of the FIS system can be directly injected into the ionization source without performing a preliminary chromatographic separation on the sample.

[0056] Figure 6A schematic example of an ionization source 20 of an MS system 100 is shown, which is connected to a liquid chromatography (LC) system 40. In some examples, the needle assembly packages of the present disclosure can be used in such MS systems in the context of the above detailed description. Figure 6 In the lower right corner, a mass spectrometer 30 and an ionization source 20 are shown, which are combined with the above Figure 2 The mass spectrometer and ionization source are described. In one example, the LC system can include a plurality of fluid streams 42, 43, 44 (e.g., two or more or three or more fluid streams) that can be alternately connected to the ionization source 20, such that each fluid stream is connected to the ionization source 20 within a predefined time window. Figure 6 In the example shown, the LC system 40 may further include a stream selection valve 50 (e.g., a rotary valve) and a valve-detector conduit 10', which is configured to alternately connect the plurality of fluid streams 42, 43, 44 via the stream selection valve 50 so that the LC eluate flows through the valve-detector conduit 10 to the ionization source 20. The MS system may also include different arrangements for connecting the plurality of fluid streams 42, 43, 44 to the ionization source 20. For example, the MS system may include other stream selection elements in addition to the (rotary) valve.

[0057] Additionally or alternatively, Figure 6 The MS system may include multiple stream selection elements (e.g., stream selection valves). In addition, the LC system may include multiple sets of fluid streams, each set including two or more fluid streams that can be connected to the ESI source. Figure 6 In the depicted example, the stream selection valve 50 includes a plurality of fluid flow ports 51, 52, 53 configured to connect respective fluid flows of the plurality of fluid flows 42, 43, 44 from the LC system to the valve-detector conduit 10 to provide LC eluate 41 flowing out of the respective fluid flows and input into the ionization source. Thus, liquid entering the ionization source from the LC system can be nebulized in a volume downstream of the ESI capillary or nebulizer needle 10, where ionization occurs to produce a gas phase of charged analyte molecules (see Figure 6 ). In this example, the stream selection valve 50 may further include a plurality of waste ports 51', 52', 53' for each fluid stream 42, 43, 44, each of which is derived from a plurality of fluid streams leading to a waste 60. In this example, the ionization source 20 includes an ESI capillary or nebulizer needle 10, which in some examples may form part of the valve-detector conduit 50, such that the mass spectrometer is connected to the valve-detector conduit 10' via the ionization source 20. In other examples, the nebulizer capillary may not necessarily be part of the valve-detector conduit 10 and may be connected to the conduit in a manner known in the art. It should be understood that Figure 6The embodiment presented is only an example, the number of ports and connections can be adjusted in many different ways, in particular depending on the number of fluid flows.

[0058] Further aspects

[0059] Several aspects of the technology relate to packaging for a needle-like component (e.g., an electrospray ionization source capillary or nebulizer needle, an atmospheric pressure photoionization source capillary, or an atmospheric pressure chemical ionization source electrode) for a mass spectrometry system, which have been discussed in the previous sections. In addition, the technology of the present disclosure can also be performed according to the following aspects:

[0060] 1. A package (1) of a needle component (10) for a mass spectrometry (MS) system (100), the package comprising:

[0061] a container (11), the container being configured to store the needle-like component at a fixed position within the container;

[0062] An actuator (12a; 12b) is configured to move the needle component from the fixed position in the container to a mounting position, in which the needle component protrudes from the container for mounting the needle component in the MS system.

[0063] 2. The package according to aspect 1, wherein the needle-shaped component (10) is a capillary, a nebulizer needle or an electrode, optionally an electrospray ionization (ESI) capillary.

[0064] 3. The package according to aspect 1 or 2, further comprising the needle-like member (10).

[0065] 4. The package according to any one of aspects 1 to 3, wherein the package further comprises a connector element (13) configured to couple the package with the MS system (100).

[0066] 5. Package according to aspect 4, wherein the connector (13) element is configured to fix the package (1) relative to the MS system (100).

[0067] 6. A package according to aspect 5, wherein in a fixed position of the package relative to the MS system, the needle component is aligned at a predefined angle with a tube (21) of a housing (22) of the needle component of the MS system.

[0068] 7. A package according to any one of aspects 4 to 6, wherein the connector element includes a fastening element, optionally a thread, a pin, an interlock, a key, a shaped surface or other suitable fastening element, to connect to a corresponding corresponding component in the MS system so as to connect the package to the MS system.

[0069] 8. A package according to any one of aspects 1 to 7, wherein the actuator is a pusher (12) configured to push the needle component (10) from the fixed position within the container (11) to the installed position.

[0070] 9. The package according to aspect 8, wherein once the package is fixed to the MS system, the package is configured to move the needle component (10) to an installation position by pushing the pusher (12), thereby facilitating the insertion of the needle component into the MS system.

[0071] 10. The package according to any one of aspects 1 to 9, wherein the package comprises a resilient element (14), optionally a spring element, configured to maintain the needle member in the fixed position within the container.

[0072] 11. The package of any one of aspects 1 to 10, wherein the package is configured to provide a first resistance force that opposes movement of the actuator when the actuator is moved to insert the needle component into the installation position.

[0073] 12. The package according to aspect 11, wherein the first resistance is provided by an elastic element, optionally a spring element, further optionally provided by the elastic element according to aspect 10.

[0074] 13. A package according to aspect 12, wherein the package and / or the needle-like component is further configured to provide a second resistance, which resists the movement of the actuator when the needle-like component is aligned in the installation position, and wherein the second resistance is greater than the first resistance, optionally wherein when the needle-like component is aligned in the installation position, the actuator cannot move beyond a certain limit.

[0075] 14. A package according to aspect 13, wherein the second resistance is provided by a blocking element of the package and / or the needle member.

[0076] 15. The package according to aspect 14, wherein the blocking element is a collar of the needle element or a blocking pin of the package or MS system.

[0077] 16. The package of any one of aspects 1 to 15, wherein the package is further configured to engage the needle member mounted to the MS system and retract the needle member into the fixed position within the container.

[0078] 17. A package according to any one of aspects 1 to 9, wherein the package includes threads configured to allow the exterior of the package to rotate relative to the interior of the package, wherein the interior of the package is configured to maintain the needle-like component in the fixed position within the container.

[0079] 18. The package of aspect 17, wherein the package comprises an additional coupling mechanism, wherein the additional coupling mechanism and the threads are configured to allow engagement with the needle component mounted to the MS system and retraction of the needle component into the fixed position within the container.

[0080] 19. The package of any one of aspects 1 to 18, wherein the package is configured to transport and store the needle component.

[0081] 20. The package according to any one of aspects 1 to 19, wherein the package is disposable.

[0082] 21. A package according to any one of aspects 1 to 20, wherein the needle-shaped component is configured to be mounted to an ionization source (20) of the MS system, optionally wherein the ionization source is an electrospray ionization (ESI) source or an atmospheric pressure photoionization (APPI) source, wherein the needle-shaped component is an ESI capillary or a sprayer needle or an APPI capillary.

[0083] 22. The package of any one of aspects 1 to 20, wherein the needle-shaped component is configured to be mounted to an ionization source of the MS system, wherein the ionization source is an atmospheric pressure chemical ionization (APCI) source, wherein the needle-shaped component is an APCI electrode.

[0084] 23. The package of any one of aspects 1 to 22, wherein the actuator is an electromechanically operated actuator.

[0085] 24. A package according to aspects 21 to 23 or aspects 22 and 23, wherein the electromechanically operated actuator is configured to be controlled by a measurement signal, optionally wherein the measurement signal is based on an ionization current of the ionization source, wherein the ionization current is a function of the distance between the needle-like component and a facing panel of the ionization source.

[0086] 25. A method for installing a needle component in a mass spectrometry (MS) system, the method comprising:

[0087] obtaining (101) a package, the package comprising a needle-like member located in a fixed position within a container of the package;

[0088] By activating an actuator of the package, the needle member is moved (102) from the fixed position within the container to an installation position in which the needle member protrudes from the container to install the needle member to the MS system.

[0089] 26. The method according to aspect 25, wherein obtaining the needle member in the fixed position comprises maintaining the needle member in the fixed position within the container by means of a resilient element.

[0090] 27. The method according to aspect 25 or 26, further comprising coupling the package with the MS system (103).

[0091] 28. The method according to aspect 27, wherein coupling (103) the package with the MS system comprises coupling (103) the package to a respective corresponding component in the MS system.

[0092] 29. The method of aspect 27 or 28, wherein coupling the package with the MS system comprises securing (104) the package relative to the MS system.

[0093] 30. The method according to aspect 29, wherein fixing the package relative to the MS system comprises aligning (105) the needle component with a tube (21) of a housing (22) of the needle component of the MS system at a predefined angle.

[0094] 31. The method according to any one of aspects 26 to 30, wherein moving the needle member comprises pushing the needle member from the fixed position within the container into the installed position.

[0095] 32. The method of aspect 31, wherein pushing the needle member comprises inserting the needle member into the MS system once the package is secured to the MS system.

[0096] 33. The method according to any one of aspects 26 to 32, wherein moving the needle member comprises controlling the actuator based on a measurement signal.

[0097] 34. The method of aspect 33, wherein the measurement signal is based on an ionization current of the ionization source of the MS system, wherein the ionization current is a function of a distance between the needle member and a counter plate of the ionization source.

[0098] 35. A method for removing a needle from a mass spectrometry (MS) system, the method comprising:

[0099] engaging the package with the needle component mounted to the MS system by activating an actuator of the package for the needle component (201);

[0100] The needle member is retracted (202) from the mounted position to a fixed position within a container of the package by activating the actuator of the package.

[0101] 36. The method of aspect 35, further comprising positioning (204) the package including the needle member in the fixed position within the container of the package.

[0102] 37. The method according to any one of aspects 35 to 36, wherein retracting the needle member comprises pulling (205) the needle member into the fixed position within the container.

[0103] 38. The method of any one of aspects 35 to 37, further comprising separating the package from the MS system (206).

[0104] 39. The method of aspect 38, wherein separating the package from the MS system comprises separating the package from a respective corresponding component in the MS system.

[0105] 40. The method of aspect 38 or 39, wherein separating the package from the MS system comprises removing (207) the package from a fixed position relative to the MS system.

Claims

1. A package (1) of a needle component (10) for a mass spectrometry (MS) system (100), the package comprising: a container (11) configured to store the needle-shaped component at a fixed position within the container, wherein the needle-shaped component is a capillary, a nebulizer needle or an electrode; an actuator (12a; 12b) configured to move the needle-like component from the fixed position in the container to a mounting position in which the needle-like component protrudes from the container for mounting the needle-like component to the MS system, characterised in that the actuator is further configured to be detached from the needle member once the needle member is in the installed position, and the package without the needle member is configured to be separated from the MS system, wherein the actuator is a push rod or a button, the actuator is configured to engage with the needle component by friction, and the actuator is configured to push the needle component from the fixed position in the container to the installed position, Wherein the actuator is an electromechanically operated actuator, wherein the electromechanically operated actuator is configured to be controlled by a measurement signal, wherein the measurement signal is based on an ionization current of an ionization source.

2. The package according to claim 1, further comprising the needle member (10).

3. The package according to claim 1 or 2, wherein the package further comprises a connector element (13) configured to couple the package with the MS system.

4. The package of claim 3, wherein the connector element comprises a fastening element to couple to a corresponding counterpart in the MS system to couple the package to the MS system.

5. The package of claim 4, wherein the fastening element is a thread, a pin, an interlock, a key or a shaped surface.

6. The package according to claim 3, wherein the connector element (13) is configured to fix the package (1) relative to the MS system (100).

7. The package according to claim 6, wherein the package further comprises the needle component (10), wherein in a fixed position of the package relative to the MS system, the needle component is aligned at a predefined angle with a tube (21) of a housing (22) of the needle component of the MS system.

8. The package of claim 1, wherein once the package is secured to the MS system, the package is configured to facilitate insertion of the needle member (10) into the MS system by pushing the actuator (12) to move the needle member (10) to a mounting position.

9. The package according to any one of claims 1 to 2, wherein the package comprises a resilient element (14) configured to retain the needle component in the fixed position within the container.

10. The package of claim 9, wherein the resilient element is a spring element.

11. The package of any one of claims 1 to 2, wherein the package is configured to provide a first resistance force that opposes movement of the actuator when the actuator is moved to insert the needle component into the installation position.

12. The package of claim 11, wherein the first resistance is provided by a resilient element.

13. The package of claim 12, wherein the resilient element is a spring element.

14. The package of claim 11, wherein the first resistance is provided by a resilient element according to claim 9.

15. The package of claim 11, wherein the package and / or the needle component contained therein is further configured to provide a second resistance force that resists movement of the actuator when the needle component is registered in the installed position, and wherein the second resistance force is greater than the first resistance force.

16. The package of claim 11, wherein when the needle member is registered in the installed position, the actuator cannot move beyond a certain limit.

17. The package of claim 15, wherein the second resistance force is provided by a blocking element of the package and / or the needle member.

18. The package of any one of claims 1 to 2, wherein the package is further configured to engage the needle member mounted to the MS system and retract the needle member into the fixed position within the container.

19. The package of any one of claims 1 to 2, wherein the package is configured to transport and store the needle component.

20. The package of any one of claims 1 to 2, wherein the package is disposable.

21. The package according to any one of claims 1 to 2, wherein the package further comprises the needle component (10), wherein the needle component is configured to be mounted to an ionization source (20) of the MS system, wherein the needle component is a capillary, wherein the capillary is an ESI capillary or an APPI capillary, or the needle component is a nebulizer needle.

22. The package of claim 21, wherein the ionization source is an electrospray ionization (ESI) source or an atmospheric pressure photoionization (APPI) source.

23. The package of any one of claims 1 to 2, wherein the ionization current is a function of the distance between the needle member and a facing face plate of the ionization source.

24. A method for installing a needle component in a mass spectrometry (MS) system, the method comprising: obtaining (101) a package comprising a needle-like component located in a fixed position within a container of the package, wherein the needle-like component is a capillary, a nebulizer needle, or an electrode; By activating an actuator of the package, the needle member is moved (102) from the fixed position within the container to an installation position in which the needle member protrudes from the container to install the needle member to the MS system, The method further comprises: removing the actuator from the needle member once the needle member is in the mounted position, separating the package without the needle member from the MS system, wherein the actuator is a push rod or a button, the actuator is configured to engage with the needle component by friction, and the actuator is configured to push the needle component from the fixed position in the container to the installed position, Wherein the actuator is an electromechanically operated actuator, wherein the electromechanically operated actuator is configured to be controlled by a measurement signal, wherein the measurement signal is based on an ionization current of an ionization source.

25. A method for removing a needle from a mass spectrometry (MS) system, the method comprising: engaging the package without the needle component with the needle component mounted to the MS system by activating an actuator of the package for the needle component (201), wherein the needle component is a capillary, a nebulizer needle or an electrode; retracting (202) the needle member from a mounted position to a fixed position within a container of the package by activating the actuator of the package; separating the package from the MS system (206), wherein the actuator is a push rod or a button, the actuator is configured to engage with the needle component by friction, and the actuator is configured to push the needle component from the fixed position in the container to the installed position, Wherein the actuator is an electromechanically operated actuator, wherein the electromechanically operated actuator is configured to be controlled by a measurement signal, wherein the measurement signal is based on an ionization current of an ionization source.

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