GB2592590A

GB2592590A - Sample processing with information detection during transfer of a sample container

Info

Publication number: GB2592590A
Application number: GB2002965.8A
Authority: GB
Inventors: Ortmann Thomas; Nocon Blasius
Original assignee: Agilent Technologies Inc
Current assignee: Agilent Technologies Inc
Priority date: 2020-03-02
Filing date: 2020-03-02
Publication date: 2021-09-08
Anticipated expiration: 2040-03-02
Also published as: GB2592590B; GB202002965D0; CN113341001A

Abstract

A sample processing unit or sample injector (40) for processing a sample fluid provided for separating compounds of the sample fluid. The sample processing unit comprises a housing (280), a door (290), a detection unit (300; 420, 430), and a control unit (70). The door (290) is provided 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 area (310; 440, 450) such as a barcode or label containing information about the sample fluid. The detection unit (300; 420, 430) is configured for providing a detection of the detection area (310; 440, 450) of the sample container (220, 230). The control unit (70) is configured for operating the detection unit (300; 420, 430) for providing the 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). Detection of sample related information during transfer of sample fluid into or out of the housing allows for example, following a movement of the sample fluid transfer and/or to expand a range of detection beyond a static detection.

Description

DESCRIPTION

SAMPLE PROCESSING WITH INFORMATION DETECTION DURING TRANSFER OF A SAMPLE CONTAINER

BACKGROUND ART

[0001] The present invention relates to sample processing in particular for chromatographic sample separation.

[0002] For liquid separation in a chromatography system, a mobile phase comprising a sample fluid (e.g. a chemical or biological mixture) with compounds to be separated is driven through a stationary phase (such as a chromatographic column packing), thus separating different compounds of the sample fluid which may then be identified. The term compound, as used herein, shall cover compounds which might comprise one or more different components.

[0003] The mobile phase, for example a solvent, is pumped under high-pressure typically through a chromatographic column containing packing medium (also referred to as packing material or stationary phase). As the sample is carried through the column by the liquid flow, the different compounds, each one having a different affinity to the packing medium, move through the column at different speeds. Those compounds having greater affinity for the stationary phase move more slowly through the column than those having less affinity, and this speed differential results in the compounds being separated from one another as they pass through the column. The stationary phase is subject to a mechanical force generated in particular by a hydraulic pump that pumps the mobile phase usually from an upstream connection of the column to a downstream connection of the column. As a result of flow, depending on the physical properties of the stationary phase and the mobile phase, a relatively high-pressure drop is generated across the column.

[0004] The mobile phase with the separated compounds exits the column and passes through a detector, which registers and/or identifies the molecules, for example by spectrophotometric absorbance measurements. A two-dimensional plot of the detector measurements against elution time or volume, known as a 30 chromatogram, may be made, and from the chromatogram the compounds may be -1 -identified. For each compound, the chromatogram displays a separate curve feature also designated as a "peak".

[0005] In preparative chromatography systems, a liquid as the mobile phase is provided usually at a controlled flow rate (e. g. in the range of 1 mL/min to thousands of 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 -200 mL/min) and at pressure in the range of tens to hundreds bar, e.g. 20 -600 bar.

[0006] In high performance liquid chromatography (HPLC), a liquid as the mobile phase has to be provided usually at a very controlled flow rate (e. g. in the range of microliters to milliliters per minute) and at high-pressure (typically 20-100 MPa, 200- 1000 bar, and beyond up to currently 200 MPa, 2000 bar) at which compressibility of the liquid becomes noticeable.

[0007] In preparative chromatography systems used for chromatography fluidically separating samples at a larger volume, typically in the range of 0.1 mL to tens of mL, there often is a need for analysing a smaller volume of such sample prior to running the separation of the larger volume (e.g. in the sense of an "analytical scouting run"). For such purpose, an analytical chromatography system may be used for chromatographically separating smaller sample volumes, typically in the range of 10 uL -50 ul. Such analytical chromatography system may be an HPLC system.

[0008] In many applications, the sample fluid needs to be reliably tracked when introducing into a sampler before sample injection in order to ensure that such sample fluid will be correctly processed.

DISCLOSURE

[0009] It is an object of the invention to provide an improved sample transfer, preferably for chromatographic sample separation. The object is solved by the independent claims. Further embodiments are shown by the dependent claims.

[0010] In an embodiment according to the present invention, a sample processing unit is provided for processing a sample fluid intended for separating compounds of the sample fluid. The sample processing unit comprises a housing, a door, a detection unit, and a control unit. The door is provided for introducing a sample container into -2 -the housing and/or removing the sample container from within the housing, wherein the sample container comprises the sample fluid and a detection area containing information about the sample fluid. The detection unit is configured for providing a detection of the detection area of the sample container. The control unit is configured for operating the detection unit for providing the detection of the detection area during introduction of the sample container into the housing and/or removal of the sample container from within the housing. This allows to reliably track information related to a respective sample fluid and to ensure that such sample fluid can be processed correctly and as intended/required. The detection of the sample related information during the transfer of the sample fluid into or out of the housing allows e.g. following a movement of the sample fluid transfer and/or to expand a range of detection beyond a static detection.

[0011] In one embodiment, the door comprises the detection unit, and the control unit is configured for operating the door and the detection unit for providing the detection of the detection area during introduction of the sample container into the housing and/or removal of the sample container from within the housing. This allows to combine and/or coordination of operation and/or movement of the detection unit and the door, e.g. in that the process of detection is provided substantially simultaneously with the process of moving the door.

[0012] In one embodiment, the control unit is configured for operating the door to a vary, during introduction of the sample container into the housing and/or removal of the sample container from within the housing, an angle of detection of the detection unit, in order to provide the detection of the detection area from different angles of the detection unit with respect to the detection area. This allows expanding the detectable range provided by the detection unit.

[0013] In one embodiment, the sample processing unit further comprises a transport mechanism configured for moving the sample container into the housing and/or removing the sample container from within the housing. In such embodiment, the control unit can be configured for operating the transport mechanism, the door, and the detection unit for providing the detection of the detection area while the transport mechanism moves the sample container through the door into and/or out of the housing. The transport mechanism may preferably comprise a drive, preferably a -3 -linear drive, configured for moving the sample container into the housing and/or out of the housing.

[0014] In one embodiment, the control unit is configured for operating the door to provide the detection of the detection area from one or more of: a lateral side of the sample container, a top side of the sample container, and a bottom side of the container.

[0015] In one embodiment, the detection unit is configured for providing an optical detection of the detection area of the sample container, and the detection area is configured for optical detection.

[0016] In one embodiment, the detection area comprises at least one of: any kind of optically detectable sign, field or the like, such as a barcode, preferably a one-dimensional or plural dimensional barcode, a label, a picture, et cetera, a radio frequency detectable tag, preferably an RFID tag, a magnetically detectable tag such as a Hall sensor, et cetera.

[0017] 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 detecting device or method adequate for detecting a respective type of detection area.

[0018] In one embodiment, the control unit is further configured for determining a state of loading of the sample container, wherein the state of loading represents information about at least one of: a number of one or more individual vessels contained in the sample container, a respective spatial location of one or more individual vessels contained in the sample container, a respective sample content comprised in one or more individual vessels contained in the sample container, et cetera.

[0019] In one embodiment, the housing comprises the door, so that the door may represent a part of the housing.

[0020] In one embodiment, the door is opening and/or closing with respect to the housing by providing a pivoting movement. This may be provided e.g. by one or more hinges. Such pivoting movement may be a centric or eccentric movement. -4 -

[0021] In one embodiment, the sample container comprises a plurality of respective detection areas.

[0022] In one embodiment, the sample container comprises one or more individual sample receptacles each containing a respective sample fluid and preferably a respective detection area containing information about the respective sample fluid.

[0023] In one embodiment, the housing comprises a plurality of doors each containing a respective detection unit configured for providing a respective detection of one or more detection areas of the sample container. This allows also to increase the angle of detectability, e.g. to detect from a top and a bottom side, to detect from different lateral sides, or any kind of combination thereof.

[0024] In one embodiment, the housing comprises a plurality of doors each opening and/or closing with respect to the housing by providing a pivoting movement.

[0025] In one embodiment, the housing comprises a first door and a second door each containing a respective detection unit configured for providing a respective 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 in different, preferably opposing, angles and allowing to transport the sample container through the first door and the second door.

[0026] In one embodiment, the sample container comprises one or more individual sample receptacles each being configured for comprising a respective sample fluid and preferably comprising a respective detection area containing information about the respective sample fluid.

[0027] In one embodiment, the sample processing unit comprises a data processing unit configured for processing the sample fluid in accordance with information derived from the detection of the detection area of the sample container containing the sample fluid.

[0028] In one embodiment, the sample processing unit is a sample injector for a chromatography system comprising a mobile phase drive and a separation unit, wherein the mobile phase drive is configured for driving a mobile phase through the separation unit, and the separation unit is configured for chromatographically -5 -separating compounds of a sample fluid in the mobile phase, and the sample injector is configured for injecting the sample fluid into the mobile phase.

[0029] In one embodiment, the sample processing unit is a collection unit for a chromatography system comprising a mobile phase drive and a separation unit, wherein the mobile phase drive is configured for driving a mobile phase through the separation unit, and the separation unit is configured for chromatographically separating compounds of a sample fluid in the mobile phase, and the collection unit is configured for collecting separated compounds of the sample fluid.

[0030] In one embodiment, the sample processing unit is configured for a chromatography system comprising a mobile phase drive and a separation unit, wherein the mobile phase drive is configured for driving a mobile phase through the separation unit, and the separation unit is configured for chromatographically separating compounds of a 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.

[0031] In one embodiment, a sample injector is provided for a chromatography system comprising a mobile phase drive and a separation unit, wherein the mobile phase drive is configured for driving a mobile phase through the separation unit, and the separation unit is configured for chromatographically separating compounds of a sample fluid in the mobile phase. The sample injector is configured for injecting the sample fluid into the mobile phase and comprises a housing, a door, a detection unit and a control unit. The door is provided for introducing a sample container into the housing and/or removing the sample container from within the housing, wherein the sample container comprises the sample fluid and a detection area containing information about the sample fluid. The detection unit is comprised by the door and configured for providing a detection, preferably an optical detection, of the detection area of the sample container. The control unit is configured for operating the door and the detection unit for providing the detection of the detection area during introduction of the sample container into the housing and/or removal of the sample container from within the housing, and for injecting the sample fluid into the mobile phase in accordance with the detected information about the sample fluid. -6 -

[0032] In one embodiment, a separation system is provided for separating compounds of a sample fluid in a mobile phase. The fluid separation system comprises a mobile phase drive, preferably a pumping system, adapted to drive the mobile phase through the fluid separation system, a separation unit, preferably a chromatographic column, adapted for separating compounds of the sample fluid in the mobile phase, and a sample processing unit or sample injector according to any one of the aforementioned embodiments to introduce the sample fluid into the mobile phase.

[0033] The separation system may comprise one or more of a detector adapted to detect separated compounds of the sample fluid, a collection unit adapted to collect separated compounds of the sample fluid, a data processing unit adapted to process data received from the fluid separation system, and a degassing apparatus for degassing the mobile phase.

[0034] In one embodiment, a method is provided for processing a sample fluid provided for separating compounds of the sample fluid. The method comprises introducing a sample container into a housing and/or removing the sample container from within the housing, wherein the sample container comprises the sample fluid. The method further comprises detecting a detection area of the sample container during introduction of the sample container into the housing and/or removal of the sample container from within the housing, wherein the detection area comprises information about the sample fluid, and processing the sample fluid in accordance with the detected information about the sample fluid.

[0035] In one embodiment, processing the sample fluid in accordance with the detected information about the sample fluid may comprise injecting the sample fluid 25 into a mobile phase and chromatographically separating compounds of the sample fluid in the mobile phase.

[0036] One embodiment further comprises injecting at least a portion of the aspirated sample fluid into the mobile phase, thus allowing to provide e.g. a chromatographic separation of the injected sample fluid. Injection of the sample fluid 30 may be done using a feed injection scheme, as described e.g. in US2017343520A1 by the same applicant Alternatively or in addition, injection of the sample fluid may be -7 -done using flow through injection scheme, as described e.g. in US20160334031A1 by the same applicant. In the feed injection scheme, the sample fluid will be fluidically coupled to a coupling point between the mobile phase drive and the separation unit for combining a flow through the sampling volume with a flow of the mobile phase. In the flow through or loop injection scheme, the sample fluid will be fluidically coupled between the mobile phase drive and the separation unit.

[0037] In one embodiment of the separation system comprises a sampling volume being or comprising at least one of a group of: a sample loop, a sample volume, a trap volume, a trap column, a fluid reservoir, a capillary, a tube, a microfluidic channel structure. The sampling volume may be configured for receiving and buffering the sample fluid aspirated by the needle before being injected into the mobile phase.

[0038] In one embodiment of the injector, the needle comprises an elongated shape with an open end for fluid aspiration, and may be or comprise at least one of a conduit and a nozzle. The open end may be preferably coupled to another open end of a fluid path, preferably a needle seat, in a fluid-tight manner. The needle may have a sharpened end e.g. configured for penetrating through a surface (e.g. a cap or other coverage covering the receptacle), but may also be embodied without such sharpened end, e.g. having a blunt end. Further, while the needle is preferably embodied using a substantially rigid material, such as a metal (e.g. stainless steel), ceramic, et cetera, softer materials may be applied as well e.g. allowing to bend the needle (e.g. in the sense of a soft(er) tubing).

[0039] In one embodiment, at least one of the mobile phase drive and the fluid drive is or comprises at least one of: a syringe, a syringe pump, a peristaltic pump or roller pump, a venturi valve coupled to a fluid flow generating unit, a pump, and a pumping unit comprising a plurality of pumps, a piston pump, preferably a reciprocating piston pump, a dual pump comprising two piston pumps connected in parallel or serial to each other, a multi-stage step-piston pump, and a modulation pump.

[0040] In one embodiment, the needle is configured for aspirating the sample fluid from the receptacle by immersing the needle into the receptacle and driving the fluid drive. -8 -

[0041] The sample fluid can be drawn in by the fluid drive from the receptacle by the needle. The drawn in sample fluid may be transported directly to or into the sampling volume, however, any kind of transport mechanisms may be applied accordingly as well, e.g. pushing the sample fluid or a combined draw and push scheme so that the sample fluid, or parts thereof, is partly drawn and partly pushed.

This may be executed by the fluid drive only or in conjunction with a fluid transport devices or mechanisms.

[0042] In one embodiment, the processing unit is configured to control the needle to immerse into the sample fluid within the receptacle and to operate the fluid drive to aspirate a portion of the sample fluid from the receptacle into the needle.

[0043] Embodiments of the present invention might be embodied based on most conventionally available HPLC systems, such as the Agilent 1220, 1260 and 1290 Infinity LC Series (provided by the applicant Agilent Technologies).

[0044] One embodiment of an HPLC system comprises a pumping apparatus having a piston for reciprocation in a pump working chamber to compress liquid in the pump working chamber to a high pressure at which compressibility of the liquid becomes noticeable.

[0045] The separating device preferably comprises a chromatographic column providing the stationary phase. The column might be a glass, metal, ceramic or a composite material tube (e.g. with a diameter from 50 pm to 5 mm and a length of 1 cm to 1 m) or a microfluidic column (as disclosed e.g. in EP 1577012 Al or the Agilent 1200 Series HPLC-Chip/MS System provided by the applicant Agilent Technologies). The individual components are retained by the stationary phase differently and separate from each other while they are propagating at different speeds through the column with the eluent. At the end of the column they elute at least partly separated from each other. During the entire chromatography process the eluent might be also collected in a series of fractions. The stationary phase or adsorbent in column chromatography usually is a solid material. The most common stationary phase for column chromatography is silica gel, followed by alumina. Cellulose powder has often been used in the past. Also possible are ion exchange chromatography, reversed-phase chromatography (RP), affinity chromatography or expanded bed adsorption -9 - (EBA). The stationary phases are usually finely ground powders or gels and/or are microporous for an increased surface, which can be especially chemically modified, though in EBA a fluidized bed is used.

[0046] The mobile phase (or eluent) can be either a pure solvent or a mixture of different solvents. It can also contain additives, i.e. be a solution of the said additives in a solvent or a mixture of solvents. It can be chosen e.g. to adjust the retention of the compounds of interest and/or the amount of mobile phase to run the chromatography. The mobile phase can also be chosen so that the different compounds can be separated effectively. The mobile phase might comprise an organic solvent like e.g. methanol or acetonitrile, often diluted with water. For gradient operation water and organic solvent is delivered in separate containers, from which the gradient pump delivers a programmed blend to the system. Other commonly used solvents may be isopropanol, THF, hexane, ethanol and/or any combination thereof or any combination of these with aforementioned solvents.

[0047] The sample fluid might comprise any type of process liquid, natural sample like juice, body fluids like plasma or it may be the result of a reaction like from a fermentation broth.

[0048] The fluid is preferably a liquid but may also be or comprise a gas and/or a supercritical fluid (as e.g. used in supercritical fluid chromatography -SFC -as disclosed e.g. in US 4,982,597 A).

[0049] The pressure in the mobile phase might range from 2-200 MPa (20 to 2000 bar), in particular 10-150 MPa (100 to 1500 bar), and more particular 50-130 MPa (500 to 1300 bar).

[0050] The HPLC system might further comprise a detector for detecting separated compounds of the sample fluid, a fractionating unit for outputting separated compounds of the sample fluid, or any combination thereof. Further details of HPLC system are disclosed with respect to the aforementioned Agilent HPLC series, provided by the applicant Agilent Technologies.

[0051] Embodiments of the invention can be partly or entirely embodied or supported by one or more suitable software programs or products, which can be stored on or otherwise provided by any kind of data carrier, and which might be executed in or by any suitable data processing unit. Software programs or routines can be preferably applied in or by the control unit, e.g. a data processing system such as a computer, preferably for executing any of the methods described herein.

[0052] In the context of this application, the term "fluidic sample" may particularly denote any liquid and/or gaseous medium, optionally including also solid particles, which is to be analyzed. Such a fluidic sample may comprise a plurality of fractions of molecules or particles which shall be separated, for instance biomolecules such as proteins. Since separation of a fluidic sample into fractions involves a certain separation criterion (such as mass, volume, chemical properties, etc.) according to which a separation is carried out, each separated fraction may be further separated by another separation criterion (such as mass, volume, chemical properties, etc.) or finer separated by the first separation criterion, thereby splitting up or separating a separate fraction into a plurality of sub-fractions.

[0053] In the context of this application, the term "sample separation apparatus", "fluid separation apparatus" or similar may particularly denote any apparatus which is capable of separating different fractions of a fluidic sample by applying a certain separation technique. Particularly, two separation apparatus may be provided in such a sample separation apparatus when being configured for a two-dimensional separation. This means that the sample is first separated in accordance with a first separation criterion, and at least one or some of the fractions resulting from the first separation are subsequently separated in accordance with a second, different, separation criterion or more finely separated in accordance with the first separation criterion.

[0054] The term "separation unit", "separation device" or similar may particularly denote a fluidic member through which a fluidic sample is transferred, and which is configured so that, upon conducting the fluidic sample through the separation unit, the fluidic sample will be separated into different groups of molecules or particles (called fractions or sub-fractions, respectively). An example for a separation unit is a liquid chromatography column which is capable of trapping or retaining and selectively releasing different fractions of the fluidic sample.

[0055] In the context of this application, the term "fluid drive", "mobile phase drive" or similar may particularly denote any kind of pump which is configured for forcing a flow of mobile phase and/or a fluidic sample along a fluidic path.

BRIEF DESCRIPTION OF DRAWINGS

[0056] Other objects and many of the attendant advantages of embodiments of the present invention will be readily appreciated and become better understood by reference to the following more detailed description of embodiments in connection with the accompanied drawings. Features that are substantially or functionally equal or similar will be referred to by the same reference signs.

[0057] Fig. 1 illustrates a liquid chromatography system according to an exemplary embodiment.

[0058] Figure 2 illustrates in greater detail an embodiment of the sample injector 40.

[0059] Figures 3A-B show two different positions for transporting the sample container 230 into the housing 280.

[0060] Figure 4 schematically illustrates another embodiment of the sample injector 40.

[0061] Referring now in greater detail to the drawings, Fig. 1 depicts a general schematic of a liquid separation system 10. A mobile phase drive 20 (such as a pump) receives a mobile phase from a solvent supply 25, typically via a degasser 27, which degases the mobile phase and thus reduces the amount of dissolved gases in it. The mobile phase drive 20 drives the mobile phase through a separating device 30 (such as a chromatographic column). A sample injector 40 (also referred to as sample introduction apparatus, sample dispatcher, etc.) is provided between the mobile phase drive 20 and the separating device 30 in order to subject or add (often referred to as sample introduction) portions of one or more sample fluids into the flow of a mobile phase. The separating device 30 is adapted for separating compounds of the sample fluid, e.g. a liquid. A detector 50 is provided for detecting separated compounds of the sample fluid. A fractionating unit 60 can be provided for outputting separated compounds of sample fluid. In one embodiment, at least parts of the sample injector 40 and the fractionating unit 60 can be combined, e.g. in the sense that some common hardware is used as applied by both of the sample injector 40 and the fractionating unit 60.

[0062] The separating device 30 may comprise a stationary phase configured for separating compounds of the sample fluid. Alternatively, the separating device 30 may be based on a different separation principle (e.g. field flow fractionation).

[0063] While the mobile phase can be comprised of one solvent only, it may also be mixed of plurality of solvents. Such mixing might be a low pressure mixing and provided upstream of the mobile phase drive 20, so that the mobile phase drive 20 already receives and pumps the mixed solvents as the mobile phase. Alternatively, the mobile phase drive 20 might be comprised of plural individual pumping units, with plural of the pumping units each receiving and pumping a different solvent or mixture, so that the mixing of the mobile phase (as received by the separating device 30) occurs at high pressure and downstream of the mobile phase drive 20 (or as part thereof). The composition (mixture) of the mobile phase may be kept constant over time, the so-called isocratic mode, or varied over time, the so-called gradient mode.

[0064] A data processing unit 70, which can be a conventional PC or workstation, might be coupled (as indicated by the dotted arrows) to one or more of the devices in the liquid separation system 10 in order to receive information and/or control operation. For example, the data processing unit 70 might control operation of the mobile phase drive 20 (e.g. setting control parameters) and receive therefrom information regarding the actual working conditions (such as output pressure, flow rate, etc. at an outlet of the pump). The data processing unit 70 might also control operation of the solvent supply 25 (e.g. monitoring the level or amount of the solvent available) and/or the degasser 27 (e.g. setting control parameters such as vacuum level) and might receive therefrom information regarding the actual working conditions (such as solvent composition supplied over time, flow rate, vacuum level, etc.). The data processing unit 70 might further control operation of the sample injector 40 (e.g. controlling sample introduction or synchronization of the sample introduction with operating conditions of the mobile phase drive 20). The separating device 30 might also be controlled by the data processing unit 70 (e.g. selecting a specific flow path or column, setting operation temperature, etc.), and send -in return -information (e.g. operating conditions) to the data processing unit 70. Accordingly, the detector 50 might be controlled by the data processing unit 70 (e.g. with respect to spectral or wavelength settings, setting time constants, start/stop data acquisition), and send information (e.g. about the detected sample compounds) to the data processing unit 70. The data processing unit 70 might also control operation of the fractionating unit (e.g. in conjunction with data received from the detector 50) and provides data back. The data processing unit 70 might also process the data received from the system or its part and evaluate it in order to represent it in adequate form prepared for further interpretation.

[0065] Figure 2 illustrates in greater detail and in three-dimensional representation an embodiment of the sample injector 40, which may also be a combined sample injector and fractionating unit allowing to provide sample introduction as well as sample fractionating. The sample injector 40 comprises one or more needles 200 (the exemplary embodiment of Figure 2 shows two needles 200A and 200B) and a handling unit 210 configured for moving and positioning the needles 200. One or more receptacles 220, which may comprise e.g. a sample fluid to be injected by the sample injector 40, can be provided e.g. in one or more sample containers 230. The exemplary embodiment of Figure 2 shows three sample containers 230A-C with the sample container 230B containing a single receptacle 220 for the sake of simplicity. Each sample container 230 may be a tray, a vial plate, or similar as known in the art, and/or each receptacle 220 may be a respective vial or similar as known in the art.

[0066] The positioning of each needle 200 as provided by the handling unit 210 may be only in 7-direction, as indicated in the axis diagram, allowing to position each needle 200 in (only) height e.g. by lowering or lifting the needle 200 in 7-direction. For such purpose, the handling unit 210 may comprise for each needle 200 a respective slider 240 configured to slide in Z-direction e.g. operated by a drive unit (not detailed in Figure 2) which may be an electrical motor. The exemplary embodiment of Figure 2 shows a slider 240A for moving the needle 200A in Z-direction and further shows a slider 240B for moving the needle 200B in Z-direction. Further, in the exemplary embodiment of Figure 2 the sliders 240A-B can be operated independently of each other, thus allowing each needle 200 to be independently moved and positioned.

[0067] The handling unit 210 may further be configured to move and position each needle 200 into the X-direction and/or into the Y-direction (as indicated in the axis diagram), as readily known in the art. In the embodiment of Figure 2, the handling unit 210 comprises a rail 250 allowing each slider 240A-B to be moved (preferably independently of the respective other slider 240A-B) in Y-direction.

[0068] Each sample container 230 as shown in the embodiment of Figure 2 can be positioned on a movable sleigh 270, which may be moved into the X-direction and/or into the Y-direction (as indicated in the axis diagram), as readily known in the art, in order to position the one or more receptacles 220 with respect to the needles 10 200.

[0069] In the exemplary embodiment of Figure 2, the sleigh 270 is configured to be movable in X-direction, while the handling unit 210 is configured to move each needle 200A-B independently of each other as well in 7-direction as in Y-direction, thus allowing each needle 200A-B to be fully and independently positioned with respect to a respective receptacle 220 in X-, Y-, and Z-direction. Other mechanisms for moving the respective needles 200 with respect to the respective receptacles 220 can be applied accordingly as readily known in the art.

[0070] For each needle 200A-B, a respective needle seat 280A-B can be provided into which the respective needle 200A-B can be seated (by operation of the handling unit 210) allowing to fluidically couple the needle 200 with the high-pressure flow path between the pump 20 and the separating device 30 of the liquid separation system 10, e.g. in order to inject a sample fluid aspirated into the respective needle 200 from the receptacle 220 into such high pressure flow path for chromatographic separation by the separating device 30. Such injection may be by feed injection, as described e.g. in the aforementioned US2017343520A1, and/or by flow through injection, as described e.g. in the aforementioned US20160334031A1. Instead of a respective needle seat 280 for each needle 200, a single needle seat 280 may be provided in order to receive multiple needles 200. Alternatively, a combination may be applied, e.g. in the sense that one or more needles 200 can be seated into any one of one or more needle seats 280.

[0071] Further in Figure 2, the sample injector 40 comprises a housing 280 and a door 290. In the representation of Figure 2, only a front side 285 is shown while other lateral sides has been omitted for the sake of simplicity and for allowing a view inside of the housing 280. The door 290 is hinged to the housing 280 and can be pivoted to provide an opening 295 into the housing 280 (as shown in Figure 2) or to close such opening 295 (when the door 290 is pivoted by about 90° clockwise from the view shown in Figure 2). The door 290 is operated by a drive unit (not shown in Figure 2) allowing to automatically open or close the door 290 by automatically pivoting the door 290 with respect to the housing 280, as readily known in the art.

[0072] When the door 290 is in an open position as shown in Figure 2, the sleigh 270 can be moved out of the housing 280 allowing to either position one or more sample containers 230 onto the sleigh 270 or to remove one or more sample containers 230 from the sleigh 270. This allows to either load one or more receptacles 220, each containing a respective sample fluid, from external into the sample injector 40 or to remove one or more receptacles 220 out of the sample injector 40.

[0073] The door 290 comprises a detection unit 300 which may extend along the entire inside area (facing into the housing when the door 290 is closed) or only at parts thereof. As will be clear from the further explanations, the detection unit 300 may also be positioned anywhere else at or within the door 290 as dependent on the respective detection mechanism provided by the detection unit 300.

[0074] The detection unit 300 is provided for detecting one or more detection areas 310 which may be provided either on the respective receptacles 220 of sample containers 230. Each detection area 310, which may for example be a barcode or a label, contains information e.g. about a respective sample fluid contained in a respective receptacle 220 within a respective sample container 230. In the exemplary embodiment of Figure 2, such detection area 310 shall be provided underneath each respective sample container 230 which, however, is not directly visible in the representation of Figure 2.

[0075] A control unit (not represented in Figure 2 but which may be the data processing unit 70 of Figure 1 or an individual processing unit thereto) is provided to operate the door 290 together with the detection unit 300 to detect the detection area 310 during introduction and/or removal of sample fluid into/from the housing. In other words, the control unit controls operation of the door 290, the detection unit 300, and the sleigh 270 in order to detect the detection area 310 during movement of the respective sample fluid when being either introduced through the opening 295 into the housing 280 or removed out of the housing 280 through the opening 295.

[0076] With the detection of the detection area 310 being executed during movement of the sleigh 270 (either into or out of the housing 280), different angles of detection (i.e. between the detection unit 300 and the respective detection area 310) can be assumed allowing to provide a more reliable detection as well as different detection areas 310 which may be provided at different positions of the receptacles 220 and/or the sample containers 230.

[0077] The detection area 310 can be provided anywhere at the respective receptacle 220 and/or the respective container 230. For example, the receptacle 220 may comprise a respective detection area 310 (e.g. a barcode) on a top side (e.g. on a cap to the receptacle 220, e.g. a vial cap), a bottom side (e.g. a bottom side of a vial), and/or a lateral side (e.g. a front and/or rear side of a vial), as known and applied differently in the field. Further, such detection area 310 may be or comprise any kind of detection mechanism, such as a barcode (e.g. a one-dimensional or plural dimensional barcode), a label, and RFID tag, or whatever appropriate. Accordingly, the detection unit 300 may comprise a scanner, a camera, a diode array, an antenna (e.g. to detect and RFID tag), et cetera.

[0078] Detecting the information provided by the one or more detection areas 310 allows deriving information about the one or more sample fluids to be introduced into or out of the housing 280 of the sample injector 40. Such information may be a state of loading of the sample container 230, such as the number, position, and content of the individual receptacles 220 within the respective containers 230. Such information can be used by the sample injector 40 for processing the respective sample fluid, for example an order of a sequence of injections and/or a respective chromatographic method to be chosen for chromatographically separating a respective sample fluid.

[0079] Figures 3A-B show in two-dimensional side views (as seen in the direction of arrow A in Figure 2) two different positions for transporting the sample container 230 containing the respective receptacle 220 through the opening 295 into the housing 280 (or vice versa). The position in Figure 3A represents the position of Figure 2 showing the sample injector 40 in a loading configuration, wherein the sleigh 270 is moved through the opening 295 and reaching outside of the housing 280, thus allowing to place the sample container 230 containing a respective receptacle 220 onto the sleigh 270 for loading into the sample injector 40.

[0080] In the position of Figure 3B, the sleigh 270 has already been moved inside the housing 280 but has not yet reached its final position allowing the needle 200 to penetrate into the receptacle 220 in order to aspirate the sample fluid contained within the receptacle 220 for injection into the mobile phase (see the explanations to Figure 1). The door 290 in the position of Figure 3B has been rotated by about 45° (in clockwise direction of the representation in Figures 3) with respect to the position in Figure 3A.

[0081] During movement of the sleigh 270, the detection unit 300 (as part of the door 290 in the exemplary embodiment of Figures 2 and 3) as long as being in the (horizontal) position shown in Figure 3A detects one or more detection areas 310 underneath or at the bottom side of the sample container 230 and/or the receptacle 220, dependent where such one or more detection areas 310 have been provided. It goes without saying that the sleigh 270 needs to be provided with sufficient transparency to allow such detection from underneath.

[0082] When the sleigh 270 further moves inside into the housing 280, e.g. as shown in position of Figure 3B, the door 290 follows such movement (by clockwise rotation) thus allowing the detection unit 300 to detect other detection areas 310 which would otherwise not be visible and thus detectable e.g. in the position of Figure 3A. With the door 290 assuming e.g. the position of Figure 3B, the detection unit 300 may now detect a respective detection area 310 positioned e.g. on a rear side 320 of the sample container 230.

[0083] Figure 4 schematically illustrates another embodiment of the sample injector 40 wherein the housing 280 comprises a first door 400 and a second door 410 each being pivotably provided to either open or close the opening 295 of the housing 280. The first door 400 substantially corresponds (e.g. in movement) to the door 290 of Figures 2-3, while the second door 410 is provided to open/move by 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 Figures 2-3), and the second door 410 comprises a second detection unit 430, each detection unit 420 and 430 being provided facing into the housing 280 (in a closed-door position not shown in Figure 4) allowing for optical detection e.g. provided by a respective camera or diode array.

[0084] The sample container 230 shows a detection area 440 (indicated by "ABC") which may be a barcode, label, et cetera. The sample container 230 contains a plurality of receptacles 220 each bearing respective detection areas 450. In the exemplary embodiment of Figure 4, each receptacle 220 shows detection areas 450 (indicated by "ABC") on its upper, lower and lateral side. It is clear that such detection areas 440 and 450 may also be provided elsewhere on the sample container 230 and/or the receptacle 220.

[0085] During movement of the sample container 230 as indicated by the arrow in Figure 4, the first and second doors 400 and 410 can be moved in order to follow such movement of the sample container 230 and allowing to detect the respective detection areas 440 and 450 from different angles. The second door 410 allows, with respect to the embodiments of Figures 2-3 having only a single door 290, to provide a detection also of the top side of the sample container 230 and/or the receptacle 220.

[0086] Instead of or in addition to the doors 290 (Figures 2-3) and 400,410 (Figure 4) pivoting around pivot axes substantially parallel to the Y-axis (or in other words horizontal with respect to the representations in Figures 2-4), other pivot axes or combinations thereof may be provided accordingly, such as in a vertical direction substantially parallel to the Z-axis or substantially parallel to the X-axis, dependent on the respective application and design of the housing 280. Further, instead of a centric door rotation also an eccentric rotation can be applied.

Claims

CLAIMS1. A sample processing unit (40) for processing a sample fluid provided for separating compounds of the sample fluid, comprising: a housing (280), 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 area (310; 440, 450) containing information about the sample fluid, a detection unit (300; 420, 430) configured for providing a detection of the detection area (310; 440, 450) of the sample container (220, 230), and a control unit (70) configured for operating the detection unit (300; 420, 430) for providing the 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) of 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) for providing the 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 for operating the door (290) to a vary, 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), an angle of detection of the detection unit (300; 420, 430), in order to provide the detection of the detection area (310; 440, 450) from different angles of the detection unit (300; 420, 430) with respect to the detection area (310; 440, 450).
-20 - 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 removing the sample container (220, 230) from within the housing (280).
5. The sample processing unit (40) of 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 providing the detection of the detection area (310; 440, 450) while the transport mechanism (270) moves the sample container (220, 230) through the door (290) into and/or out of the housing (280), 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 provide the detection of the detection area (310; 440, 450) 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; the detection unit (300; 420, 430) is configured for providing an 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 sign, field or the like, such as a barcode, preferably a one-dimensional or plural dimensional barcode, a label, and a picture, a radio frequency detectable tag, preferably an RFID tag, a magnetically detectable tag such as a Hall sensor; the detection unit (300; 420, 430) comprises at least one of: a scanner, a -21 -camera, a diode array, an antenna, a Hall sensor; the control unit (70) is further configured for determining a state of loading of the sample container (220, 230), wherein the state of loading represents information about 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 comprised 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) comprises the door (290); the door (290) is opening and/or closing with respect to the housing (280) by providing a pivoting movement; the sample container (220, 230) comprises a plurality of respective detection areas (310; 440, 450); the sample container (220, 230) comprises one or more individual sample receptacles each containing a respective sample fluid and preferably a respective detection area (310; 440, 450) containing information about the respective sample fluid; the housing (280) comprises a plurality of doors (290) each containing a respective detection unit (300; 420, 430) configured for providing a respective detection of one or more detection areas (310; 440, 450) of the sample container (220, 230); the housing (280) comprises a plurality of doors (290) each opening and/or closing with respect to the housing (280) by providing a pivoting movement; the housing (280) comprises a first door (290) and a second door (290) each containing a respective detection unit (300; 420, 430) configured for providing a respective detection of one or more detection areas (310; 440, 450) of the sample container (220, 230), wherein the first door (290) and the second door -22 - (290) are configured to open and/or close in different, preferably opposing, angles and allowing to transport the sample container (220, 230) through the first door (290) and the second door (290); the sample container (220, 230) comprises one or more individual sample receptacles (220) each being configured for comprising a respective sample fluid and preferably comprising a respective detection area (450) containing information about 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 for processing the sample fluid in accordance with information derived from the 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 drive (20) and a separation unit (30), wherein the mobile phase drive (20) is configured for driving a mobile phase through the separation unit (30), and the separation unit (30) is configured for chromatographically separating compounds 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 drive (20) and a separation unit (30), wherein the mobile phase drive (20) is configured for driving a mobile phase through the separation unit (30), and the separation unit (30) is configured for chromatographically separating compounds of a sample fluid in the mobile phase, and the collection unit (60) is configured for collecting separated compounds of the sample fluid; the sample processing unit (40; 60) is configured for a chromatography system comprising a mobile phase drive (20) and a separation unit (30), wherein the -23 -mobile phase drive (20) is configured for driving a mobile phase through the separation unit (30), and the separation unit (30) is configured for chromatographically separating compounds 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 separated compounds of the sample fluid.
10. A sample injector (40) for a chromatography system comprising a mobile phase drive (20) and a separation unit (30), wherein the mobile phase drive (20) is configured for driving a mobile phase through the separation unit (30), and the separation unit (30) is configured for chromatographically separating compounds of a sample fluid in the mobile phase, the sample injector (40) being configured for injecting the sample fluid into the mobile phase and comprising: a housing (280), 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 area (310; 440, 450) containing information about the sample fluid, a detection unit (300; 420, 430) comprised by the door (290) and being configured for providing a detection, preferably an optical detection, of the detection area (310; 440, 450) of the sample container (220, 230), and a control unit (70) configured for operating the door (290) and the detection unit (300; 420, 430) for providing the 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 for injecting the sample fluid into the mobile phase in accordance with the detected information about the sample fluid.
11. A separation system (10) for separating compounds of a sample fluid in a mobile phase, the fluid separation system (10) comprising: a mobile phase drive (20), preferably a pumping system, adapted to drive the mobile phase through the fluid separation system (10); -24 -a separation unit (30), preferably a chromatographic column, adapted for separating compounds of the sample fluid in the mobile phase; and a sample processing unit (40) or sample injector (40) according to any one of the preceding claims adapted to introduce the sample fluid into the mobile phase.
12. The separation system (10) of the preceding claim, further comprising at least one of: a detector (50) adapted to detect separated compounds of the sample fluid; a collection unit (60) adapted to collect separated compounds of the sample fluid; a data processing unit (70) adapted to process data received from the fluid separation system (10); a degassing apparatus (27) for degassing the mobile phase.
13. A method of processing a sample fluid provided for separating compounds 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) comprises the sample fluid, detecting a detection area (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 area (310; 440, 450) comprises information about the sample fluid, and processing the sample fluid in accordance with the detected information about the sample fluid.
14. The method of the preceding claim, wherein: processing the sample fluid in accordance with the detected information about -25 -the sample fluid comprises injecting the sample fluid into a mobile phase and chromatographically separating compounds of the sample fluid in the mobile phase.
15. A software program or product, preferably stored on a data carrier, for controlling or executing the method of any one of the above claims, when run on a data processing system such as a computer.-26 -