CN113341001A

CN113341001A - Sample processing with information detection during sample container transfer

Info

Publication number: CN113341001A
Application number: CN202110224764.9A
Authority: CN
Inventors: 托马斯·欧特曼; 布莱修斯·诺康恩
Original assignee: Agilent Technologies Inc
Current assignee: Agilent Technologies Inc
Priority date: 2020-03-02
Filing date: 2021-03-01
Publication date: 2021-09-03
Also published as: GB202002965D0; GB2592590A; GB2592590B

Abstract

The present invention relates to sample processing utilizing information detection during sample container transfer. The sample processing unit (40) of the present invention comprises: a housing (280), a door (290), a detection unit (300; 420, 430) and a control unit (70). A door (290) is provided for introducing and/or removing sample containers (220, 230) into the housing (280) and/or out of the housing (280), the sample containers (220, 230) including A sample fluid and a detection region (310; 440, 450) containing information related to the sample fluid. The detection unit (300; 420, 430) is configured to provide detection of the detection area (310; 440, 450) of the sample container (220, 230). The control unit (70) is configured to operate the detection units (300; 420, 430) for introducing and/or removing the sample containers (220, 230) into the housing (280) and/or from the housing (280) , 230) during the detection of the detection area (310; 440, 450).

Description

Sample processing with information detection during sample container transfer

Technical Field

The present invention relates to sample processing, in particular for chromatographic sample separation.

Background

For liquid separation in a chromatography system, a mobile phase of a sample fluid (e.g., a chemical or biological mixture) containing the compounds to be separated is driven through a stationary phase (e.g., a chromatography column packing) to separate out different compounds of the sample fluid that can then be identified. The term complex as used herein shall encompass complexes that may comprise one or more different components.

Mobile phases (e.g., solvents) are typically pumped under high pressure through a chromatography column containing packing media (also referred to as packing material or stationary phase). As the sample is carried through the column by the liquid stream, each different complex, having a different affinity for the packing medium, moves through the column at a different velocity. Those complexes with greater affinity for the stationary phase move through the column more slowly than those complexes with lesser affinity, and this difference in velocity causes the complexes to separate from each other as they pass through the column. The stationary phase is subjected to mechanical forces, particularly generated by a hydraulic pump, which pumps the mobile phase, usually from an upstream connection of the column to a downstream connection of the column. Due to the flow, a relatively high pressure drop is generated across the column depending on the physical properties of the stationary and mobile phases.

The mobile phase with the separated complexes leaves the column and passes through a detector which records and/or identifies the molecules, for example by spectrophotometric absorbance measurements. A two-dimensional plot of the detector measurements versus elution time or volume, referred to as a chromatogram, can be drawn and the complex can be identified from the chromatogram. For each complex, the chromatogram shows a separate curve characteristic, also referred to as a "peak".

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

In High Performance Liquid Chromatography (HPLC), it is generally necessary to provide the liquid as a mobile phase at a very controlled flow rate (e.g. in the range of a few microliters to a few milliliters per minute) and at high pressures (typically 20-100MPa, 200-.

In preparative chromatography systems for chromatographically separating samples in fluid form in larger volumes (typically in the range of 0.1mL to tens of mL), it is often necessary to analyze smaller volumes of such samples before running larger volume separations (e.g., in the sense of an "analytical screening run"). For this reason, analytical chromatographic systems can be used for chromatographic separation of relatively small volumes of sample, typically in the range of 10uL to 50 uL. Such an analytical chromatographic system may be an HPLC system.

In many applications, when a sampler is introduced prior to sample injection, it is necessary to reliably track the sample fluid to ensure that such sample fluid will be processed correctly.

Disclosure of Invention

It is an object of the present invention to provide an improved sample transfer, preferably for chromatographic sample separation. This object is solved by the independent claims. Further embodiments are shown in the dependent claims.

In an embodiment according to the invention, a sample processing unit for processing a sample fluid for separation of a complex of the sample fluid is provided. The sample processing unit includes a housing, a door, a detection unit, and a control unit. The door is configured for introducing and/or removing a sample container into and/or from the housing, wherein the sample container includes a sample fluid and a detection zone containing information related to the sample fluid. The detection unit is configured to provide detection of a detection area of the sample container. The control unit is configured to operate the detection unit to provide detection of the detection zone during introduction and/or removal of the sample container into and/or from the housing. This allows information about the respective sample fluid to be reliably tracked and ensures that such sample fluid can be processed correctly and as expected/required. Detection of sample-related information during transfer of sample fluid into or out of the housing allows, for example, following movement of sample fluid transfer and/or extending the detection range beyond static detection.

In one embodiment, the door comprises a detection unit, and the control unit is configured for operating the door and the detection unit to provide detection of the detection area during introduction and/or removal of the sample container into and/or from the housing. This allows combining and/or coordinating the operation and/or movement of the detection unit and the door, for example, because the detection process is performed substantially simultaneously with the process of moving the door.

In one embodiment, the control unit is configured to operate the door to vary the detection angle of the detection unit during introduction and/or removal of the sample container into and/or out of the housing, thereby providing detection of the detection zone at different angles of the detection unit relative to the detection zone. This allows to enlarge the detectable range provided by the detection unit.

In one embodiment, the sample processing unit further comprises a transport mechanism configured for moving the sample container into and/or out of said housing. In such embodiments, the control unit may be configured for operating the transport mechanism, the door and the detection unit to detect the detection area while the transport mechanism moves the sample container into and/or out of the housing through the door. Preferably, the transport mechanism may comprise a drive, preferably a linear drive, configured for moving the sample container into and/or out of the housing.

In one embodiment, the control unit is configured for operating the door from: one or more of the lateral sides of the sample container, the top side of the sample container, and the bottom side of the container provide for detection of the detection zone.

In one embodiment, the detection unit is configured to provide optical detection of a detection area of the sample container, and the detection area is configured for optical detection.

In one embodiment, the detection zone comprises at least one of: any kind of optically detectable symbol, field, etc., such as a bar code, preferably a one-or multi-dimensional bar code, indicia, picture, etc.; a radio frequency detectable tag, preferably an RFID tag; magnetically detectable tags, such as hall sensors, etc.

In one embodiment, the detection unit comprises at least one of: a scanner, a camera, a diode array, an antenna, a hall sensor, or any other type of detection device or method suitable for detecting a corresponding type of detection area.

In an embodiment, the control unit is further configured for determining a loading status of the sample container, wherein the loading status represents information on at least one of: the number of the one or more individual vessels contained in the sample container, the respective spatial locations of the one or more individual vessels contained in the sample container, the respective sample contents contained in the one or more individual vessels contained in the sample container, and the like.

In one embodiment, the housing includes a door, such that the door may represent a portion of the housing.

In one embodiment, the door opens and/or closes relative to the housing by providing a pivoting motion. This may be provided, for example, by one or more hinges. This pivoting movement may be a centering movement or an eccentric movement.

In one embodiment, the sample container comprises a plurality of respective detection zones.

In one embodiment, the sample container comprises one or more individual sample receptacles, each sample receptacle containing a respective sample fluid, and preferably also a respective detection zone containing information about the respective sample fluid.

In one embodiment, the housing includes a plurality of doors, each door containing a respective detection cell configured to provide detection of one or more detection regions of the sample container. This also allows for increasing the detectable angle, e.g. detection from the top and bottom sides, detection from different lateral sides, or any combination thereof.

In one embodiment, the housing includes a plurality of doors, each door opening and/or closing relative to the housing by providing a pivoting motion.

In one embodiment, the housing comprises a first door and a second door, each comprising a respective detection unit configured to provide detection of one or more detection areas of the sample container, wherein the first door and the second door are configured to open and/or close at different angles, preferably opposite angles, and to allow transport of the sample container through the first door and the second door.

In one embodiment, the sample container comprises one or more individual sample receptacles, each configured to comprise a respective sample fluid, and preferably a respective detection zone containing information relating to the respective sample fluid.

In an embodiment, the sample processing unit comprises a data processing unit configured to process the sample fluid based on information derived from the detection of the detection area of the sample container containing the sample fluid.

In one embodiment, the sample processing unit is a sample injector for a chromatography 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, the separation unit is configured for chromatographic separation of a complex of a sample fluid in the mobile phase, and the sample injector is configured for injecting the sample fluid into the mobile phase.

In one embodiment, the sample processing unit is a collection unit for a chromatography 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, the separation unit is for chromatographic separation of a complex of a sample fluid in said mobile phase, and the collection unit is configured for collecting the separated complex of the sample fluid.

In one embodiment, the sample processing unit is configured for a chromatography system comprising a mobile phase driver and a separation unit, wherein the mobile phase driver is configured for driving the mobile phase through the separation unit and the separation unit is configured for performing a chromatographic separation of a complex of the sample fluid in the mobile phase, and the sample processing unit is configured for injecting the sample fluid into the mobile phase and/or for collecting separated compounds of the sample fluid.

In one embodiment, a sample injector for a chromatography system is provided, the chromatography 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 for chromatographic separation of a complex of a sample fluid in the mobile phase. The sample injector is configured for injecting a sample fluid into the mobile phase and comprises: the device comprises a shell, a door, a detection unit and a control unit. The door is configured for introducing and/or removing a sample container into and/or from the housing, wherein the sample container includes a sample fluid and a detection zone containing information related to the sample fluid. A detection unit is comprised in the door and is configured to provide detection, preferably optical detection, of a detection area of the sample container. The control unit is configured to operate the door and the detection unit to provide detection of the detection zone during introduction and/or removal of the sample container into and/or from the housing, and to inject the sample fluid into the mobile phase in dependence on the detected information relating to the sample fluid.

In one embodiment, a separation system for separating a complex of a sample fluid in a mobile phase is provided. A fluid separation system comprising: a mobile phase driver, preferably a pumping system, adapted to drive the mobile phase through the fluid separation system; a separation unit, preferably a chromatography column, adapted for separating complexes of the sample fluid in the mobile phase; and a sample processing unit or sample injector according to any preceding embodiment to introduce a sample fluid into the mobile phase.

The separation system may include: one or more detectors adapted to detect the separated complexes in the sample fluid; a collection unit adapted to collect the separated complexes in the sample fluid; a data processing unit adapted to process data received from the fluid separation system; a degassing apparatus for degassing a mobile phase.

In one embodiment, a method of processing a sample fluid for separation of a complex of the sample fluid is provided. The method comprises the following steps: introducing and/or removing a sample container into and/or from the housing, wherein the sample container contains a sample fluid. The method further comprises detecting a detection region of the sample container during introduction and/or removal of the sample container into and/or from the housing, wherein the detection region contains information about the sample fluid, and processing the sample fluid in accordance with the detected information about the sample fluid.

In one embodiment, processing the sample fluid according to the detected information about the sample fluid may comprise injecting the sample fluid into the mobile phase and chromatographically separating complexes of the sample fluid in the mobile phase.

One embodiment further comprises injecting at least a portion of the aspirated sample fluid into the mobile phase, thereby allowing providing, for example, chromatographic separation of the injected sample fluid. Injection of the sample fluid may be accomplished using a feed injection protocol, such as described in US2017343520a1 by the same applicant. Alternatively or additionally, the injection of the sample fluid may also use a flow-through injection scheme, for example as described in US20160334031a1 of the same applicant. In a feed injection scheme, the sample fluid couples the fluid to a coupling point between the mobile phase driver and the separation unit to combine the flow through the sampling space with the flow of the mobile phase. In a flow-through or loop-injection scheme, the sample fluid couples the fluid between the mobile phase driver and the separation unit.

In an embodiment, the separation system comprises a sampling volume, the sampling volume being or comprising at least one of the group of: sample loop, sample volume, capture column, fluid reservoir, capillary, tube, microfluidic channel structure. The sampling volume may be configured to receive and buffer sample fluid drawn by the needle prior to being injected into the mobile phase.

In one embodiment of the syringe, the needle comprises an elongate shape having an open end for fluid intake and may be or comprise at least one of a conduit and a nozzle. The open end may be coupled to another open end of the fluid path, preferably a needle hub, preferably in a fluid tight manner. The needle may have a sharp end, for example, configured for penetrating a surface (e.g., a cap or other covering the receptacle), but may also be implemented without such a sharp end, e.g., a blunt end. Further, while the needle is preferably implemented using a substantially rigid material such as metal (e.g., stainless steel), ceramic, etc., softer materials may also be used, for example, to allow bending of the needle (e.g., in a sense, a soft (softer) tube).

In one embodiment, at least one of the mobile phase driver and the fluid driver is or comprises at least one of: an injector, an infusion pump, a peristaltic pump or a roller pump, a venturi valve unit coupled with the fluid flow generating unit, a pump and a pump unit comprising a plurality of pumps, a piston pump, preferably a reciprocating piston pump, a double pump comprising two piston pumps connected in parallel or in series with each other, a multi-step piston pump, and a modulating pump.

In one embodiment, the needle is configured for aspirating sample fluid from the receptacle by immersing the needle in the receptacle and actuating the fluid driver.

The sample fluid may be drawn from the containment portion by fluid actuation by the needle. The aspirated sample fluid may be delivered directly to or into the sampling volume, however, any kind of delivery mechanism may be applied accordingly, e.g. a pushing sample fluid or a combined aspiration and pushing scheme, such that the sample fluid or a part thereof is partially aspirated and partially pushed. This may be performed by a fluid driver alone or in conjunction with a fluid delivery device or mechanism.

In one embodiment, the processing unit is configured to control the needle to be immersed in the sample fluid within the receptacle and to operate the fluid driver to draw a portion of the sample fluid from the receptacle into the needle.

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

One embodiment of an HPLC system comprises a pumping device having a piston for reciprocating in a pumping chamber to compress liquid in the pumping chamber to a high pressure at which compressibility of the liquid becomes significant.

The separation device preferably comprises a chromatographic column providing a stationary phase. The column may be a glass, metal, ceramic or composite tube (e.g. 50 μm to 5mm in diameter and 1cm to 1m in length) or a microfluidic column (as disclosed in EP 1577012a1 or the Agilent 1200 series HPLC-Chip/MS system supplied by the applicant Agilent Technologies). The individual components are differently held by the stationary phase and separated from each other as they propagate through the column with the eluent at different rates. At the end of the column, the components elute at least partially separately from each other. The eluent can also be collected in a series of fractions throughout the chromatography. The stationary phase or adsorbent in column chromatography is typically a solid material. The most common stationary phase for column chromatography is silica gel followed by alumina. Cellulose powders have often been used in the past. Ion exchange chromatography, reverse 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 micropores to increase the surface, which may be chemically modified in particular (although a fluidized bed is used in EBA).

The mobile phase (or eluent) may be a pure solvent or a mixture of different solvents. It may also contain additives, i.e. may be a solution of said additives in a solvent or solvent mixture. The mobile phase may be selected, for example, to adjust the retention of the target complex and/or the amount of mobile phase to perform chromatography. The mobile phase may also be chosen such that different complexes can be separated efficiently. The mobile phase may comprise an organic solvent, typically diluted with water, such as methanol or acetonitrile. For gradient operation, water and organic solvent are delivered in separate containers, and a gradient pump delivers the programmed hybrid from the container to the system. Other commonly used solvents may be isopropanol, THF, hexane, ethanol and/or any combination thereof, or any combination of these solvents with the aforementioned solvents.

The sample fluid may comprise any type of processing liquid, a natural sample such as fruit juice, a body fluid such as plasma, or it may be the result of a reaction such as from a fermentation broth or the like.

The fluid is preferably a liquid, but may also be or comprise a gas and/or a supercritical fluid (as used in supercritical fluid chromatography-SFC, for example as disclosed in US 4,982,597 a).

The pressure in the mobile phase may range from 2 to 200MPa (20 to 2000 bar), in particular from 10 to 150MPa (100 to 1500 bar), and more particularly from 50 to 130MPa (500 to 1300 bar).

The HPLC system may further comprise a detector for detecting the separated complexes of the sample fluid, a fractionation unit for outputting the separated complexes of the sample fluid, or any combination thereof. Further details of the HPLC system are disclosed in the above-mentioned Agilent HPLC series provided by the applicant Agilent Technologies.

Embodiments of the invention may be implemented 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 which may be executed in or by any suitable data processing unit. The software program or routine may preferably be applied in or by a control unit (e.g. a computer or other data processing system), preferably for performing any of the methods described herein.

In the context of the present application, the term "fluid sample" may particularly denote any liquid and/or gaseous medium to be analyzed, optionally also comprising solid particles. Such a fluid sample may comprise a plurality of fractions of molecules or particles to be separated, e.g. biomolecules, such as proteins or the like. Since the separation of a fluid sample into fractions involves a particular separation criterion (e.g., mass, volume, chemical properties, etc.) according to which the separation is performed, each separated fraction may be further separated by another separation criterion (e.g., mass, volume, chemical properties, etc.) or more finely separated by a first separation criterion, thereby splitting or separating the separated fraction into a plurality of sub-fractions.

In the context of the present application, the term "sample separation device", "fluid separation device" or similar terms may particularly denote any device capable of separating different fractions of a fluid sample by applying a certain separation technique. In particular, when configured for two-dimensional separation, two separation devices may be provided in such a sample separation device. This means that the sample is first separated according to a first separation criterion and at least one or some of the fractions resulting from the first separation are subsequently separated according to a different second separation criterion, or more finely separated according to the first separation criterion.

The term "separation unit", "separation device" or similar terms may particularly denote a fluidic member through which a fluid sample is transferred and which is configured such that the fluid sample will be separated into different groups of molecules or particles (referred to as fractions or molecular fractions, respectively) when being guided through the separation unit. An example of a separation unit is a liquid chromatography column, which is capable of capturing or retaining and selectively releasing different fractions of a fluid sample.

In the context of the present application, the term "fluid driver", "mobile phase driver" or similar terms may particularly denote any type of pump configured to force a mobile phase and/or a fluid sample to flow along a fluid path.

Drawings

Other objects and many of the attendant advantages of embodiments of this invention will be readily appreciated as the same become better understood by reference to the following more detailed description of the embodiments, when taken in conjunction with the accompanying drawings. Features that are substantially or functionally equivalent or similar will be referred to by the same reference numerals.

FIG. 1 shows a liquid chromatography system according to an exemplary embodiment.

Fig. 2 shows an embodiment of the sample injector 40 in more detail.

Fig. 3A-3B illustrate two different locations for transporting the sample container 230 into the housing 280.

Fig. 4 schematically illustrates another embodiment of the sample injector 40.

Detailed Description

Referring now in more detail to the drawings, FIG. 1 shows a general schematic of a liquid separation system 10. The mobile phase driver 20 (such as a pump or the like) typically receives the mobile phase from the solvent supplier 25 via a degasser 27, which degasser 27 degasses the mobile phase and thus reduces the amount of gas dissolved therein. The mobile phase driver 20 drives the mobile phase through a separation device 30 (such as a chromatography column or the like). A sample injector 40 (also referred to as a sample introduction device, sample distributor, etc.) is provided between the mobile phase drive 20 and the separation apparatus 30 in order to apply or add portions of one or more sample fluids (often referred to as sample introduction) to the flow of mobile phase. The separation device 30 is adapted to separate complexes of a sample fluid (e.g. a liquid). The detector 50 is arranged for detecting the separated complexes of the sample fluid. A fractionation unit 60 may be provided for outputting 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 a sense that certain general purpose hardware is used in common by both the sample injector 40 and the fractionation unit 60.

The separation device 30 may comprise a stationary phase configured for separating a complex of the sample fluid. Alternatively, the separation device 30 may be based on a different separation principle (e.g. field flow fractionation).

Although the mobile phase may consist of only one solvent, it may also be mixed with a plurality of solvents. Such mixing may be low pressure mixing and is disposed upstream of the mobile phase driver 20 such that the mobile phase driver 20 has received and pumped the mixed solvent as a mobile phase. Alternatively, the mobile phase driver 20 may be comprised of a plurality of separate pumping units, wherein the plurality of pumping units each receive and pump a different solvent or mixture such that mixing of the mobile phase (received by the separation device 30) occurs at high pressure and downstream of (or as part of) the mobile phase driver 20. The composition (mixture) of the mobile phase may be kept constant over time (so-called isocratic mode) or may vary over time (so-called gradient mode).

The data processing unit 70, which may be a conventional PC or workstation, may be coupled (as indicated by the dashed arrow) to one or more devices in the liquid separation system 10 in order to receive information and/or control operations. For example, the data processing unit 70 may control the operation of the mobile phase driver 20 (e.g., set control parameters) and receive information therefrom regarding actual operating conditions (e.g., output pressure at the outlet of the pump, flow rate, etc.). The data processing unit 70 may also control the operation of the solvent supply 25 (e.g. monitoring the level or amount of available solvent) and/or the operation of the degasser 27 (e.g. setting control parameters such as vacuum level, etc.) and may receive information from it regarding the actual working conditions (such as solvent composition supplied over time, flow rate, vacuum level, etc.). The data processing unit 70 may further control the operation of the sample injector 40 (e.g., control sample introduction or synchronization of sample introduction with the operating conditions of the mobile phase drive 20). The separation device 30 may also be controlled by the data processing unit 70 (e.g. selecting a particular flow path or column, setting an operating temperature, etc.) and in response send information (e.g. operating conditions) to the data processing unit 70. Accordingly, the detector 50 may be controlled by the data processing unit 70 (e.g. with respect to spectral or wavelength settings, setting time constants, starting/stopping data acquisition) and send information (e.g. with respect to detected sample complexes) to the data processor 70. The data processing unit 70 may also control the operation of the fractionation unit 60 (e.g., in conjunction with data received from the detector 50) and provide data return. The data processing unit 70 may also process data received from the system or a portion thereof and evaluate it in order to represent the data in a suitable form in preparation for further interpretation.

Fig. 2 shows an embodiment of the sample injector 40 in more detail and in three dimensions, which sample injector 40 may also be a combined sample injector and fractionation unit, allowing for providing sample introduction and sample fractionation. The sample injector 40 comprises one or more needles 200 (the exemplary embodiment of fig. 2 shows two

needles

200A and 200B) and a manipulation unit 210 configured for moving and positioning the needles 200. One or more receptacles 220 (which may include, for example, sample fluid to be injected by the sample injector 40) may be provided, for example, in one or more sample containers 230. For simplicity, the exemplary embodiment of fig. 2 shows three sample containers 230A-230C, wherein sample container 230B contains a single receptacle 220. Each sample container 230 may be a tray, vial plate, or the like as known in the art, and/or each receptacle 220 may be a respective vial or the like as known in the art.

The positioning of each needle 200 as provided by the steering unit 210 may be in the Z-direction only, as shown in the axis diagram, allowing to position each needle 200 (only) in height, for example by lowering or lifting the needle 200 in the Z-direction. For this purpose, the handling unit 210 may comprise a respective slider 240 for each needle 200, which slider 240 is configured to be operated, for example, by a drive unit (not illustrated in detail in fig. 2, which may be a motor) to slide in the Z direction. The exemplary embodiment of fig. 2 shows a slider 240A for moving the needle 200A in the Z-direction, and also shows a slider 240B for moving the needle 200B in the Z-direction. Further, in the exemplary embodiment of fig. 2, the sliders 240A-240B may operate independently of each other, thereby allowing each needle 200 to be independently moved and positioned.

The steering unit 210 may also be configured to move and position each needle 200 in the X-direction and/or in the Y-direction (as shown in the axis diagrams), as is well known in the art. In the embodiment of fig. 2, the handling unit 210 comprises a guide 250, which guide 250 allows each slider 240A-240B to move in the Y direction (preferably independently of the respective other slider 240A-240B).

As shown in the embodiment of fig. 2, each sample container 230 may be located on a movable slide 270 that may be moved in the X-direction and/or the Y-direction (as shown in the axis view) as is well known in the art to position one or more receptacles 220 relative to the needle 200.

In the exemplary embodiment of fig. 2, the slider 270 is configured to be movable in the X-direction, while the manipulation unit 210 is configured to move each needle 200A-200B in the Z-direction and the Y-direction independently of each other, thus allowing each needle 200A-200B to be positioned completely independently in the X, Y and Z-directions relative to the respective receptacle 220. Other mechanisms for moving each needle 200 relative to each receptacle 220 as is known in the art may be applied accordingly.

For each needle 200A-200B, a respective needle hub 280A-280B may be provided, in which the respective needle 200A-200B may be placed (by operation of the steering unit 210) allowing the needle 200 to be fluidly coupled with a high pressure flow path between the pump 20 and the separation device 30 of the liquid separation system 10, e.g. to inject sample fluid drawn from the housing 220 into the respective needle 200 into the high pressure flow path for chromatographic separation by the separation device 30. Such injection may be by feed injection as described in the above mentioned US2017343520a1, and/or by flow-through injection as described for example in the above mentioned US20160334031a 1. Instead of a respective hub 280 for each needle 200, a single hub 280 may be provided to accommodate multiple needles 200. Alternatively, combinations may be employed, for example, in a sense that one or more needles 200 may be disposed in any one of one or more hubs 280.

Further in fig. 2, the sample injector 40 includes a housing 280 and a door 290. In the illustration of fig. 2, only the front side 285 is shown, while the other sides are omitted for simplicity and to allow viewing of the inside of the housing 280. The door 290 is hinged to the housing 280 and can pivot to provide an opening 295 in the housing 280 (as shown in fig. 2) or to close the opening 295 (the door 290 is closed by rotating clockwise from the angle shown in fig. 2 by about 90 °). The door 290 is operated by a drive unit (not shown in fig. 2) that allows the door 290 to be automatically opened or closed by automatically pivoting the door 290 relative to the housing 280, as is well known in the art.

When the door 290 is in the open position as shown in fig. 2, the slide 270 may be moved away from the housing 280, thereby allowing one or more sample containers 230 to be placed on the slide 270 or one or more sample containers 230 to be removed from the slide 270. This allows for external loading of one or more receptacles 220 into the sample syringe 40 or removal of one or more receptacles 220 from the sample syringe 40, wherein each receptacle contains a respective sample fluid.

The door 290 includes a detection unit 300, and the detection unit 300 may extend along the entire inside area of the door 290 (facing the inside of the housing when the door 290 is closed) or only a portion thereof. As will be clear from the further description, the detection unit 300 may also be positioned on the door 290 or in any other location within the door 290 depending on the respective detection mechanism provided by the detection unit 300.

The detection unit 300 is provided to detect one or more detection zones 310 that may be disposed on any respective receptacle 220 of a sample container 230. Each detection zone 310 may be, for example, a bar code or label that contains information, for example, regarding the respective sample fluid contained in the respective receptacle 220 within the respective sample container 230. In the exemplary embodiment of fig. 2, such a detection area 310 should be provided below each respective sample container 230, however, this is not directly visible in the illustration of fig. 2.

A control unit (not shown in fig. 2, but may be the data processing unit 70 of fig. 1 or a separate processing unit connected thereto) is provided to operate the door 290in conjunction with the detection unit 300 to detect the detection zone 310 during introduction and/or removal of the sample fluid into and/or from the housing. In other words, the control unit controls the operations of the door 290, the sensing unit 300, and the sliding portion 270 so as to sense the sensing region 310 when the corresponding sample fluid is introduced into the housing 280 through the opening 295 or removed from the housing 280 through the opening 295, i.e., during the movement of the corresponding sample fluid.

By performing the detection of the detection regions 310 during movement of the slider 270 (into the housing 280 or out of the housing 280), different detection angles (i.e., between the detection unit 300 and each detection region 310) may be assumed to allow for more reliable detection, and different detection regions 310 may be assumed, which may be disposed at different locations of the receptacle 220 and/or the sample container 230.

The detection zones 310 may be disposed at any location of the respective receptacles 220 and/or the respective containers 230. For example, as known in the art and applied in different ways, the receptacle 220 may include respective detection areas 310 (e.g., barcodes) on a top side (e.g., on a lid of the receptacle 220, e.g., a bottle lid), a bottom side (e.g., a bottom side of a bottle), and/or lateral sides (e.g., a front side and/or a back side of a bottle). Further, such detection area 310 may be or include any kind of detection mechanism, such as barcodes (e.g., one-dimensional or multi-dimensional barcodes), tags and RFID tags, or any suitable detection mechanism. Thus, the detection unit 300 may include a scanner, a camera, a diode array, an antenna (e.g., for detecting RFID tags), and the like.

Detecting the information provided by the one or more detection zones 310 allows for obtaining information about one or more sample fluids to be introduced into the housing 280 of the sample injector 40 or withdrawn from the housing 280 of the sample injector 40. Such information may be the loading status in the sample container 230, e.g., the number, location, and contents of each receptacle 220 within the respective container 230, etc. The sample injector 40 may use this information to process the respective sample fluid, for example to select the order of injection sequences and/or the respective chromatographic method to perform chromatographic separation on the respective sample fluid.

Fig. 3A-3B illustrate in two-dimensional side views (seen in the direction of arrow a in fig. 2) two different locations for transporting a sample container 230 containing a respective receptacle 220 through an opening 295 into a housing 280 (or vice versa). The position in fig. 3A represents the position in fig. 2, which shows the sample injector 40 in a loading configuration, in which the slides 270 move through the openings 295 and to the outside of the housing 280, thereby allowing the sample containers 230 containing the respective receptacles 220 to be placed onto the slides 270 for loading into the sample injector 40.

In the position of fig. 3B, the slide 270 has moved inside the housing 280, but has not yet reached its final position, which allows the needle 200 to enter the receptacle 220 to aspirate the sample fluid 220 contained therein to inject the mobile phase (see description of fig. 1). The position of the door 290in fig. 3B has been rotated about 45 deg. (clockwise as viewed in fig. 3A) relative to the position in fig. 3A.

During movement of the slide 270, the detection unit 300 (as part of the door 290in the exemplary embodiment of fig. 2 and 3) may detect one or more detection zones 310 on the underside or bottom side of the sample container 230 and/or receptacle 220 (depending on the location of the one or more detection zones 310) as long as in the (horizontal) position shown in fig. 3A. Obviously, the sliding portion 270 needs to have sufficient transparency to allow such detection from below.

When the sliding portion 270 is moved further inward of the housing 280, for example, as shown in the position of fig. 3B, the door 290 follows such movement (by rotating clockwise), allowing the detection unit 300 to detect other detection areas 310 that are otherwise not visible and therefore not detectable, for example, in the position of fig. 3A. Assuming that the door 290 is in the position of fig. 3B, for example, the detection unit 300 can now detect a corresponding detection region 310 located on the back side 320 of the sample container 230, for example.

Fig. 4 schematically illustrates another embodiment of the sample injector 40, wherein the housing 280 includes a first door 400 and a second door 410, each of which is pivotably disposed to open or close an opening 295 of the housing 280. The first door 400 substantially corresponds (e.g., kinematically) to the door 290 of fig. 2-3, while the second door 410 is configured to open/move with opposite rotation with respect to the movement of the first door 400. The first door 400 comprises a first detection unit 420 (corresponding to the detection unit 300 in fig. 2-3) and the second door 410 comprises a second detection unit 430, each

detection unit

420 and 430 facing the inside of the housing 280 (in a closed position not shown in fig. 4), allowing optical detection, for example provided by a respective camera or diode array.

The sample container 230 shows a detection area 440 (denoted by "ABC"), which may be a bar code, label, or the like. The sample container 230 comprises a plurality of receptacles 220, each receptacle carrying a respective detection zone 450. In the exemplary embodiment of fig. 4, each receptacle 220 shows a detection region 450 (indicated by "ABC") on its upper, lower and lateral sides. Obviously,

such detection zones

440 and 450 may also be provided at other locations on the sample container 230 and/or the receptacle 220.

During movement of the sample container 230 as indicated by the arrows in fig. 4, the first door 400 and the second door 410 may be moved so as to follow such movement of the sample container 230 and allow the

respective detection regions

440 and 450 to be detected from different angles. The second door 410 also allows for providing detection of the top side of the sample container 230 and/or receptacle 220 relative to the embodiment of fig. 2-3 having only a single door 290.

Instead of the door 290 (fig. 2-3) and the doors 400, 410 (fig. 4) pivoting about a pivot axis substantially parallel to the Y-axis (in other words with respect to the horizontal direction of the view in fig. 2-4), or in addition thereto, other pivot axes or combinations thereof may be provided accordingly, depending on the respective application and design of the housing 280, for example in a vertical direction substantially parallel to the Z-axis or a pivot axis substantially parallel to the X-axis. Further, instead of the center door rotation, an eccentric rotation may also be applied.

Claims

1. A sample processing unit (40) for processing a sample fluid for separation of complexes of the sample fluid, comprising:

a housing (280) for accommodating the motor,

a door (290) for introducing a sample container (220, 230) into the housing (280) and/or removing the sample container (220, 230) from within the housing (280), wherein the sample container (220, 230) comprises the sample fluid and a detection region (310; 440, 450) comprising information related to the sample fluid,

a detection unit (300; 420, 430) configured to provide detection of the detection area (310; 440, 450) of the sample container (220, 230), and

a control unit (70) configured to operate the detection unit (300; 420, 430) to provide detection of the detection area (310; 440, 450) during introduction of the sample container (220, 230) into the housing (280) and/or removal of the sample container (220, 230) from within the housing (280).

2. The sample processing unit (40) according to the preceding claim, wherein:

the door (290) comprises the detection unit (300; 420, 430), and

the control unit (70) is configured for operating the door (290) and the detection unit (300; 420, 430) to provide detection of the detection area (310; 440, 450) during introduction of the sample container (220, 230) into the housing (280) and/or removal of the sample container (220, 230) from within the housing (280).

3. The sample processing unit (40) according to the preceding claim, wherein:

the control unit (70) is configured to operate the door (290) to vary the detection angle of the detection unit (300; 420, 430) during introduction of the sample container (220, 230) into the housing (280) and/or removal of the sample container (220, 230) from the housing (280), thereby providing detection of the detection area (310; 440, 450) at different angles of the detection unit (300; 420, 430) relative to the detection area (310; 440, 450).

4. The sample processing unit (40) according to any one of the preceding claims, further comprising:

a transport mechanism (270) configured for moving the sample container (220, 230) into the housing (280) and/or moving the sample container (220, 230) out of the housing (280).

5. The sample processing unit (40) according to the preceding claim, wherein:

the control unit (70) is configured for operating the transport mechanism (270), the door (290) and the detection unit (300; 420, 430) for detecting the detection area (310; 440, 450) while the transport mechanism (270) moves the sample container (220, 230) into and/or out of the housing (280) through the door (290),

wherein preferably the transport mechanism (270) comprises a drive, preferably a linear drive, configured for moving the sample container (220, 230) into the housing (280) and/or out of the housing (280).

6. The sample processing unit (40) according to any one of the preceding claims, comprising at least one of:

the control unit (70) is configured for operating the door (290) to operate from: one or more of a lateral side of the sample container (220, 230), a top side of the sample container (220, 230), and a bottom side of the container provides for detection of the detection zone (310; 440, 450);

the detection unit (300; 420, 430) is configured to provide optical detection of the detection area (310; 440, 450) of the sample container (220, 230), and the detection area (310; 440, 450) is configured for optical detection;

the detection area (310; 440, 450) comprises at least one of: any kind of optically detectable symbol, field, etc., such as a bar code, preferably a one-dimensional or multi-dimensional bar code, a label, a picture, etc., a radio frequency detectable tag, preferably an RFID tag, a magnetically detectable tag, such as a hall sensor, etc.;

the detection unit (300; 420, 430) comprises: at least one of a scanner, a camera, a diode array, an antenna, and a hall sensor;

the control unit (70) is further configured for determining a loading status of the sample container (220, 230), wherein the loading status represents information on at least one of: a number of one or more individual vessels contained in the sample container (220, 230), a respective spatial location of one or more individual vessels contained in the sample container (220, 230), a respective sample content contained in one or more individual vessels contained in the sample container (220, 230).

7. The sample processing unit (40) according to any one of the preceding claims, comprising at least one of:

the housing (280) includes the door (290);

the door (290) opens and/or closes relative to the housing (280) by providing a pivoting motion;

the sample container (220, 230) comprises a plurality of respective detection zones (310; 440, 450); and

the sample container (220, 230) comprises one or more individual sample receptacles, each containing a respective sample fluid, and preferably further comprises a respective detection zone (310; 440, 450) containing information relating to the respective sample fluid;

the housing (280) comprises a plurality of doors (290), each door (290) comprising a respective detection unit (300; 420, 430) configured to detect one or more detection zones (310; 440, 450) of the sample container (220, 230);

the housing (280) comprises a plurality of doors (290), each door (290) opening and/or closing relative to the housing (280) by providing a pivoting motion;

the housing (280) comprises a first door (290) and a second door (290) each containing a respective detection unit (300; 420, 430) configured to detect one or more detection areas (310; 440, 450) of the sample container (220, 230), wherein the first door (290) and the second door (290) are configured to open and/or close at different angles, preferably opposite angles, and to allow transport of the sample container (220, 230) through the first door (290) and the second door (290); and

the sample container (220, 230) comprises one or more individual sample receptacles (220), each configured to comprise a respective sample fluid, and preferably a respective detection zone (450) containing information related to the respective sample fluid.

8. The sample processing unit (40) according to any one of the preceding claims, comprising:

a data processing unit (70) configured to process the sample fluid according to information derived from a detection of the detection area (310; 440, 450) of the sample container (220, 230) containing the sample fluid.

9. The sample processing unit (40) according to any one of the preceding claims, comprising at least one of:

the sample processing unit (40) is a sample injector (40) for a chromatography system comprising a mobile phase driver (20) and a separation unit (30), wherein the mobile phase driver (20) is configured to drive a mobile phase through the separation unit (30), the separation unit (30) is configured for chromatographic separation of a complex of a sample fluid in the mobile phase, and the sample injector (40) is configured for injecting the sample fluid into the mobile phase;

the sample processing unit (40) is a collection unit (60) for a chromatography system comprising a mobile phase driver (20) and a separation unit (30), wherein the mobile phase driver (20) is configured to drive a mobile phase through the separation unit (30), the separation unit (30) is configured for chromatographic separation of a complex of a sample fluid in the mobile phase, and the collection unit (60) is configured for collection of the separated complex of the sample fluid; and

the sample processing unit (40; 60) is configured for a chromatography system comprising a mobile phase driver (20) and a separation unit (30), wherein the mobile phase driver (20) is configured for driving a mobile phase (30) through the separation unit (30), and the separation unit (30) is configured for chromatographic separation of a compound of a sample fluid in the mobile phase, and the sample processing unit (40; 60) is configured for injecting the sample fluid into the mobile phase and/or for collecting the separated compound of the sample fluid.

10. A sample injector (40) for a chromatography system comprising a mobile phase driver (20) and a separation unit (30), wherein the mobile phase driver (20) is configured to drive a mobile phase through the separation unit (30), the separation unit (30) is configured for chromatographic separation of a compound of a sample fluid in the mobile phase, and the sample injector (40) is configured for injecting the sample fluid into the mobile phase, and wherein the sample injector (40) comprises:

a housing (280) for accommodating the motor,

a detection unit (300; 420, 430), the door (290) comprising the detection unit (300; 420, 430), and the detection unit (300; 420, 430) being configured to provide detection, preferably optical detection, of the detection area (310; 440, 450) of the sample container (220, 230), and

a control unit (70) configured to operate the door (290) and the detection unit (300; 420, 430) to provide detection of the detection area (310; 440, 450) during introduction of the sample container (220, 230) into the housing (280) and/or removal of the sample container (220, 230) from within the housing (280), and configured for injecting the sample fluid into the mobile phase in dependence on the detected information related to the sample fluid.

11. A separation system (10) for separating a complex of a sample fluid in a mobile phase, the fluid separation system (10) comprising:

a mobile phase driver (20), preferably a pumping system, adapted to drive the mobile phase through the fluid separation system (10);

a separation unit (30), preferably a chromatography column, adapted for separating complexes of the sample fluid in the mobile phase; and

the sample processing unit (40) or sample injector (40) according to any one of the preceding claims, adapted for introducing the sample fluid into the mobile phase.

12. The separation system (10) according to the preceding claim, further comprising at least one of:

a detector (50) adapted to detect the separated complexes in the sample fluid;

a collection unit (60) adapted for collecting the separated complexes in the sample fluid;

a data processing unit (70) adapted to process data received from the fluid separation system (10); and

a degassing device (27) for degassing the mobile phase.

13. A method of processing a sample fluid to separate complexes of the sample fluid, comprising:

introducing a sample container (220, 230) into a housing (280) and/or removing the sample container (220, 230) from within the housing (280), wherein the sample container (220, 230) contains the sample fluid,

detecting a detection region (310; 440, 450) of the sample container (220, 230) during introduction of the sample container (220, 230) into the housing (280) and/or removal of the sample container (220, 230) from within the housing (280), wherein the detection region (310; 440, 450) contains information about the sample fluid, and

processing the sample fluid according to the detected information about the sample fluid.

14. The method according to the preceding claim, wherein:

processing the sample fluid according to the detected information about the sample fluid comprises injecting the sample fluid into a mobile phase and chromatographically separating complexes of the sample fluid in the mobile phase.

15. A software program or product, preferably stored on a data carrier, for controlling or performing the method according to any of the preceding claims when run on a data processing system, such as a computer.