Calibrating object processing device using calibration feature

Abstract

Described is an apparatus (100), preferably a sampling apparatus (100) for an analysis apparatus (10), the apparatus (100) comprising: i) an object processing apparatus (190), in particular a robotic arm, configured to process an object to be processed, in particular a sample such as an analysis sample; ii) a calibration feature (120) configured to at least partially receive a protruding portion (110, 115) of an object handling device (190); and iii) a control device (70) configured to move the protruding portion (110, 115) of the object processing device (190) in the approaching direction (Z) into the calibration feature (120) such that the calibration feature (120) guides the protruding portion (110, 115) into a calibration position in a plane (XY) perpendicular to the approaching direction (Z) during the movement in the approaching direction (Z), therefore, at least one property of the object processing device (190) in a plane (XY) perpendicular to the approaching direction (Z) is defined by the calibration position or relative to the calibration position.

Description

Technical Field

[0001] This disclosure relates to an apparatus, and more particularly, to a sampling device for an analytical apparatus (e.g., a chromatographic apparatus), the apparatus comprising an object processing device and a calibration feature. This disclosure also relates to a method for defining at least one attribute of the object processing device in a plane perpendicular to the approach direction of a protruding portion of the object processing device toward the calibration feature. Background Technology

[0002] Many automation applications use object handling devices (such as robotic arms) to process objects. For example, sample handling devices can be used to automatically process samples for analytical equipment. Analytical equipment is provided to analyze such samples, for example, using sample separation devices.

[0003] For example, in liquid separation in a chromatographic system, a mobile phase containing a sample fluid (e.g., a chemical or biological mixture with compounds to be separated) is driven through a stationary phase (e.g., chromatographic column packing material), thereby separating different compounds from the sample fluid, which can then be identified. As used herein, the term "compound" should cover compounds that may contain one or more different components.

[0004] A mobile phase, typically composed of one or more solvents, is pumped under high pressure and usually passes through a chromatographic column containing a packing medium (also called the packing or stationary phase). As the sample is carried through the column by the liquid flow, different compounds pass through at different rates, each with a different affinity for the packing medium. Compounds with a greater affinity for the stationary phase pass through the column more slowly than those with a lesser affinity, and this rate difference causes the compounds 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 that typically pumps the mobile phase from the upstream connection to the downstream connection of the column. As a result of the flow, a relatively high pressure drop occurs across the column, depending on the physical properties of the stationary and mobile phases.

[0005] The mobile phase containing the compounds to be separated leaves the chromatographic column and passes through a detector, which records and / or identifies the molecules, for example, by spectrophotometric absorbance measurement. A two-dimensional graph, called a chromatogram, is generated, showing the detector measurements relative to elution time or volume, and the compounds can be identified from the chromatogram. For each compound, the chromatogram displays individual curve characteristics, also known as "peaks".

[0006] Today, most analytical devices operate automatically or have automated functions. For example, high-performance liquid chromatographs (HPLC) typically include a sampling device with a robotic arm that performs sample processing in an automated manner. For instance, a sample container (such as a sample vial) containing a fluid sample can be arranged on a sample tray device (especially in a sample carrier tray). The robotic arm can move in the horizontal plane (XY) to position the sample needle above the sample container. The robotic arm can then descend vertically (Z) to move the sample needle into the sample container. The sample needle draws a specific amount of fluid sample into the sample container volume, and then the robotic arm can remove the sample needle vertically from the sample container. Afterward, the robotic arm can move horizontally toward a sample injection port (e.g., a needle holder). Here again, the robotic arm can descend vertically to move the sample needle into the sample injection port and inject the fluid sample into the analytical area. In the case of analyzing a large number of samples, the sampling device can operate day and night and automatically process thousands of samples in the aforementioned manner.

[0007] In many applications, sampling must be highly precise, especially because sample needles and vials are very small. Therefore, the robotic arm must be calibrated so that the system accurately knows the position of the robotic arm, particularly the sample needle. A key attribute here is the precise length of the robotic arm (the extendable arm, one end of which couples to the sample needle, and the other end to the drive unit). Calibration then compensates for variations in the robotic arm length. For example, minute changes in ambient temperature (of the sampling space) can affect the length of the robotic arm, as can manufacturing tolerances (which can affect all relevant components).

[0008] Conventionally, in the field of chromatography, the calibration of robotic arms is accomplished by aligning the sample needle, for example using reference markers / positions combined with an optical camera or electrical contacts. However, conventional methods only calibrate indirectly without physical contact with the sample needle, especially since the needle is a very delicate structure. However, conventional indirect calibration can lead to deficiencies in accuracy and additional costs (such as the provision and maintenance of the camera). Invention Summary

[0009] There may be a need to calibrate object processing devices in an efficient and reliable manner. The independent claims describe a sampling device, an analytical apparatus, a method, and an application. The dependent claims describe further embodiments.

[0010] According to one aspect of this disclosure, an apparatus, preferably a sampling device (e.g., a device for processing, particularly transporting, samples) for analytical equipment (especially sample separation equipment, such as a high-performance liquid chromatograph), is described, the apparatus comprising: i) Object processing devices (especially sample processing devices), particularly robotic arms, are configured to process objects to be processed (e.g., fluid samples), particularly samples (e.g., analytical samples, etc.); ii) Calibration features (e.g., objects with specific geometries, such as tapered shapes) are configured to at least partially accommodate protrusions of the object handling device (e.g., sample needles, simulation needles, push rod devices); and iii) The control device (e.g., the control system of a processor, integrated circuit, or analytical device) is configured as follows: The protruding portion of the object processing device is moved (at least partially) into a calibration feature (the volume of the calibration feature) along the approach direction (particularly the vertical Z direction), such that during the movement along the approach direction, the calibration feature (e.g., mechanically by means of its geometry) guides the protruding portion to a calibration position in a plane perpendicular to the approach direction (particularly the horizontal XY plane), thereby such that at least one attribute of the object processing device in the plane perpendicular to the approach direction (particularly the XY position) is defined by the calibration position (in other words: calibration / alignment) or relative to the calibration position.

[0011] According to one aspect of this disclosure, a method for defining at least one attribute of an object processing device (particularly calibrating an object processing device) is described, the method comprising: i) Move the protruding portion of the object processing device (at least partially) along the approach direction into the calibration feature (configured to accommodate the protruding portion); thereby ii) Guide the protrusion to the calibration position in a plane perpendicular to the approach direction using calibration features; and iii) Define at least one property of the object processing device in a plane perpendicular to the approach direction by means of the calibration position or relative to the calibration position.

[0012] According to one aspect of this disclosure, the use (method of use) of mechanically guiding (with physical contact) an approach portion of a sample processing device to a calibration position using a calibration feature having a tapered shape is described.

[0013] In the context of this document, the term "device" may specifically refer to a machine configured to process objects by means of an object processing device, such as a robotic arm. In a preferred embodiment, the device may be a sampling device configured to process samples by means of a sample processing device. In addition to an object processing device, such a (sampling) device may include calibration features suitable for calibrating the object processing device. Calibration may be performed through direct physical contact between a (protruding) portion of the object processing device and the calibration features.

[0014] In the context of this document, the term "object handling device" may specifically refer to an apparatus suitable for handling objects, such as fluid samples. An object handling device may include a protrusion for interacting with the object. For example, the protrusion may be a sample needle for drawing up a fluid sample. In another example, the protrusion may be a gripper for grasping an object (e.g., a sample vial) or a pusher device for protecting the sample needle. In a preferred embodiment, the object handling device may be configured as a robotic arm, particularly an extendable arm that is rotatable in the XY plane and / or movable vertically in the Z direction.

[0015] In the context of this document, the term "calibration feature" may specifically refer to any structure suitable for guiding a protruding portion of an object processing device, particularly when the object processing device (in a vertical direction) approaches the calibration feature. For example, a calibration feature may include a specific geometry to achieve such guidance. In an illustrative example, the calibration feature includes a tapered shape such that the approaching protrusion is guided along the tapering direction to the center of the calibration feature volume. In the example, the calibration feature protrudes vertically, particularly when arranged on a disk device.

[0016] In the context of this document, the term "calibration position" may specifically refer to a well-defined location, particularly within a calibration feature, such that it can be used as a calibration mark. In a preferred embodiment, the calibration feature may be designed such that an approaching protrusion of the object processing device is (automatically) guided to the calibration position. For example, the object processing device may be moved (under force) along the Z direction while remaining stationary in the XY plane without external force. The protrusion can then be guided to the calibration position, and one or more properties of the object processing device (relative to the plane) can be determined / calculated, such as the length of the extension arm.

[0017] In the context of this document, the term "fluid sample" may specifically refer to any liquid and / or gaseous medium to be analyzed, and optionally also includes solid particles. Such a fluid sample may comprise multiple molecular or particle fractions to be separated, such as small molecules or large biomolecules such as proteins. Separating a fluid sample into fractions involves specific separation criteria (such as mass, volume, chemical properties, etc.) according to which separation is performed.

[0018] In the context of this document, the term "mobile phase" may specifically refer to any liquid and / or gaseous medium that can be used as a fluid carrier for a fluid sample during separation. The mobile phase may be a solvent or a solvent composition (e.g., consisting of water and an organic solvent such as ethanol or acetonitrile). In isocratic separation mode of a liquid chromatography apparatus, the mobile phase may have a constant composition over time. However, in gradient mode, the composition of the mobile phase may vary over time, particularly for fractions of the fluid sample used to desorb previously adsorbed onto the stationary phase of the separation unit.

[0019] In the context of this document, the term "sample separation apparatus" may specifically refer to any apparatus capable of separating different fractions of a fluid sample by applying a particular separation technique, particularly liquid chromatography. The term "separation unit" may specifically refer to a fluid component through which a fluid sample is conveyed, and which is configured such that, upon conveying the fluid sample through the separation unit, the fluid sample is separated into different groups of molecules or particles. An example of a separation unit is a liquid chromatography column capable of capturing or trapping and selectively releasing different fractions of a fluid sample.

[0020] In the context of this application, the term "sample holding volume" may specifically refer to a defined portion or section of a flow path, fluid conduit, or fluid component (such as a fluid valve) in which a predetermined amount of fluid may be held, at least temporarily. In embodiments, the fluid holding volume may be a sample loop (fluidly connected to a port of a modulation valve). The fluid holding volume may be fluidly decoupled, at least temporarily, from the flow path or main path. Through a switching mechanism, the sample holding volume may initially be coupled to a specific location within the sample separation device, and subsequently, alternatively or additionally, coupled to different locations within the sample separation device.

[0021] According to an exemplary embodiment, this disclosure may be based on the concept that when an object processing device moves toward a calibration feature, the object processing device can be calibrated in an efficient and reliable manner, such that the calibration feature guides the object processing device to a calibration position during the movement. Based on the calibration position (directly or indirectly), the properties of the object processing device with respect to a (horizontal) plane perpendicular to the direction of movement can be defined.

[0022] For example, when a protrusion of the object processing device (such as a sample needle) is at least partially moved (lowered) into the receiving volume of a calibration feature, physical contact can be established between the protrusion and the calibration feature. The calibration feature (particularly its geometry) is configured such that the protrusion is mechanically guided to the calibration position during vertical movement. In a preferred embodiment, the object processing device can be kept floating (without external force) in a plane during movement perpendicular to the (horizontal) plane. Thus, the geometry of the calibration feature forces the protrusion of the object processing device to a specific local position in the plane.

[0023] Because the calibration location can be well defined, one or more properties of the object processing device can be defined. These properties may include, for example, the position in the XY plane or the length of the object processing device's extension arm.

[0024] While conventional robotic arm calibration is usually done indirectly without physical contact (e.g., via a camera), it has been found that surprisingly efficient and reliable calibration of robotic arms can be achieved when direct physical contact is established between the object handling device and the calibration feature, allowing the calibration feature to directly guide the object handling device to the calibration position.

[0025] In examples of sample processing apparatus, a sample needle may be used as a protruding part. Such sample needles are typically very fine, thus physical contact with such needles is avoided. However, contrary to conventional teachings, this disclosure utilizes direct physical contact with the sample needle or a substitute for the needle (e.g., a simulated needle or push rod device) to apply efficient calibration.

[0026] Example Implementation In an embodiment, the control device is further configured to maintain the object processing device (substantially) free from external force when the protrusion of the object processing device is at least partially guided (with physical contact) into the calibration feature to the calibration position, particularly in a plane perpendicular to the approach direction. By maintaining the object processing device free from external force in the plane, the calibration feature can directly and mechanically guide the object processing device (its protrusion) to the calibration position (e.g., by its geometry). The object processing device may not be maintained free from external force in the vertical direction, allowing it to be actively moved (lowered) toward the calibration device. Thus, there may be a force acting on the object processing device in the vertical direction toward the calibration device, but no force along the plane, such that the movement of the approaching object processing device is (only) influenced / guided by the calibration feature.

[0027] In this context, the term "no external force" may specifically refer to a situation where the drive unit associated with the object processing device is not in a plane, i.e., provides force in the horizontal direction. Therefore, the associated drive unit may not provide current for achieving movement in the plane. In the example, the (sampling) device includes two drive units: a first drive unit for vertical movement (along the Z-plane) and a second drive unit for horizontal movement (along the XY-plane). Thus, in a preferred example, during calibration, the first drive unit applies a force (provides current) to the object processing device, while the second drive unit does not apply a force (does not provide current) to the object processing device. Further limitations of the term "keeping the object processing device in a plane without external force" may include: keeping the object processing device freely movable, keeping the object processing device floating, or providing the object processing device with (at least) two degrees of freedom.

[0028] In an embodiment, the geometry of the calibration feature is configured such that a protruding portion of the object processing device is at least partially mechanically guided into the calibration feature, particularly into the receiving volume of the calibration feature. This provides the advantage that calibration requires no additional mechanisms or processing. Conversely, the geometry of the calibration feature alone (e.g., shape, size, dimensions) may be sufficient to guide the approaching protruding portion to the calibration position. In particular, the geometry of the receiving volume of the calibration feature may be sufficient to bring the object processing device to the calibration position in the plane when the approaching object processing device is held in place without external force in a plane.

[0029] In one embodiment, the calibration feature includes a tapered shape. In another embodiment, the tapering direction is opposite to the object processing device. In yet another embodiment, the tapered shape is configured to guide a protrusion of the object processing device to the calibration position. Thus, mechanical guidance of the calibration device can be achieved in a simple yet efficient manner. Descriptively, the protrusion can be lowered toward a tapered structure, wherein the wider portion of the tapered structure is closer to the approaching protrusion than the narrower portion. When the protrusion enters the wider portion, there is a large diameter and a high tolerance for position in the plane. However, as the object processing device is further lowered, the diameter of the tapered structure and the tolerance for movement in the plane continuously become smaller. At the final calibration position, there is (substantially) no longer any tolerance for movement in the plane.

[0030] In other words, as the object processing device is lowered, the movement tolerance of the protrusion in the calibration feature (volume) is continuously reduced during the downward movement, so that guidance / correction towards the final calibration position is automatically achieved through the geometry of the calibration feature. The calibration process can be completed when the protrusion is in the calibration position.

[0031] In embodiments, the geometry of the calibration feature, particularly a tapered shape, includes at least one of a cone, truncated cone, pyramid, rectangle, quadrilateral, hemisphere, and polygon. A variety of different geometries are possible to achieve mechanical guidance of the protruding portion of the object handling device within the calibration feature (volume), depending on the desired application. In a preferred example, the geometry tapers away from the approaching protrusion. For example, in the case where a pusher device (see below) with a disc-shaped structure as its lowest part is positioned around the sample needle, the shape of the calibration feature may preferably be a cone / truncated cone.

[0032] In this embodiment, the calibration device includes an elastic material. For example, the calibration feature volume (e.g., conical) includes sidewalls. These sidewalls may (towards the volume) be (at least partially) elastic or include an elastic coating. The elastic material may be a plastic such as rubber. In this way, protruding portions can be protected from damage. For example, the sample needle may be a delicate structure, and it could be damaged or broken when approached by the mechanical structure of the calibration feature. Such a disadvantage can be overcome by the elastic material (sidewalls).

[0033] In an embodiment, the object processing device can be moved along the approach direction (Z) by a first drive unit and in a plane (XY) perpendicular to the approach direction (Z) by a second drive unit. In this embodiment, during movement, the first drive unit is active, specifically powered by current, while the second drive unit is (substantially) inactive, specifically not powered by current. As described above, the object processing device may include at least two drive units, specifically a first drive unit for the approach direction and a second drive unit for the plane. When the first drive unit is kept active (for vertical movement) and the second drive unit is kept inactive (no external force, floating, free movement), the approaching object processing device can be guided to a calibration position (in the plane) efficiently and reliably by means of a calibration feature (shape). In an example, the second drive unit may be an θ-rotation engine.

[0034] In embodiments, the protruding portion of the object processing device includes a sample needle, a simulated sample needle, or a needle replacement device. The object processing device can be coupled to the sample needle such that the protruding portion is already present without any additional measures. Calibration can begin directly by moving the sample needle toward the calibration feature without any additional preparation. However, since the sample needle itself can be very delicate, it can be replaced by a replica, such as a simulated sample needle, during calibration. Other elongated structures are conceivable that can serve as the protruding portion and can replace the actual sample needle during calibration. For example, a robust structure, such as one made of steel, or a flexible structure, such as one made of plastic, can be used. In another example, the protruding portion can be configured to be guided smoothly along the calibration feature, for example, by providing a sliding surface or a structure with one or more rollers.

[0035] In an embodiment, the protruding portion of the object processing device includes a pusher device, particularly wherein the pusher device is configured to at least partially surround the sample needle, and more particularly wherein the pusher device includes a pusher element having an opening through which the sample needle can be guided. In an embodiment, the protruding portion includes a needle guiding device (e.g., a pusher / gripper device), which is coupled to a moving arm, coupled to the needle, and configured to guide the needle toward the needle seat. Thus, the accuracy of needle orientation can be improved. Furthermore, the needle can be protected within the pusher device. Since the pusher device can be significantly more robust than the sample needle, the needle can be protected within the pusher device, and alignment in the calibration feature is performed by using the pusher device as a protruding portion.

[0036] In one embodiment, the pusher device includes a pusher element (perpendicular to the main extension direction of the needle) having an opening through which the needle can be guided, for example, when a sample is drawn from the sample container. When the needle is removed from the sample container, the pusher device (specifically the pusher element) can assist in pushing the sample container back, allowing the needle to be removed from the sample container efficiently and smoothly.

[0037] In an embodiment, the object processing device (protruding portion) includes a gripper device configured to process an object by grasping it. In an example, the gripper includes two or more gripping elements and / or is configured to grip a sample container, such as a sample vial. In an example, the gripper device may be configured to transport a sample container within a sampling space, for example, between two sample carriers.

[0038] In an embodiment, the object processing device includes a processing / transporting / extending arm, specifically having a length to be calibrated, and includes coupling members connected to the arm and configured to couple with a protrusion. Descriptively, the object processing device may include coupling members for connection to the protrusion (e.g., needles and / or push rod devices) and additional coupling members connected to one or more drive units. An extending arm (see, for example, Figure 2) may be arranged between the coupling members. The length of the arm can be a particularly important attribute for reliable automated sampling. Based on the described alignment utilizing the calibration position, the length of the arm can be determined with high precision.

[0039] In embodiments, the apparatus further includes a disk device, particularly a sample disk device, configured to receive at least one object, particularly a sample carrier device and / or at least one sample container and / or at least one sample. While the protruding portion (sample needle) may include one main direction of extension (particularly along the Z), the disk device may include two main directions of extension, particularly in the XY plane. Thus, the disk device can be configured to function as a plate for arranging objects to be processed by the object handling device.

[0040] In this embodiment, the sample tray device is configured to mount sample carriers thereon. Each sample carrier may, for example, hold multiple sample vials in a mounting hole (see, for example, Figure 2). In this way, multiple sets of samples can be arranged on the sample tray device, and the sample processing device can be automatically moved to the sample to be analyzed. For example, while a sample from one sample carrier is being drawn into the sample processing device, another sample carrier can be replaced (manually / automatically) to achieve a continuous sampling process.

[0041] In embodiments, the disk device is configured to be rotatable in a plane (XY) perpendicular to the approach direction (Z), and particularly in said plane (XY). The disk device can be applied in a flexible manner, and sampling (performance, speed) can be highly improved by a movable, and particularly rotatable, disk device. For example, the sample disk device can be rotated such that a sample carrier containing the sample to be analyzed is positioned below the sample processing device, and the sample processing device must only move in the plane above the sample carrier, i.e., above the sample vial to be analyzed.

[0042] In this embodiment, one or more calibration features are arranged at the disk assembly. Thus, the object processing device can be aligned / calibrated relative to the disk assembly. Two or more calibration features can make calibration (especially relative calibration) more efficient and reliable. Furthermore, additional structures may not be required. For example, calibration features can be positioned between two carrier structures.

[0043] In embodiments, the control device is also configured to move, particularly rotate, the object processing device relative to the disk device. In embodiments, the control device is also configured to move, particularly rotate, the disk device relative to the object processing device. In embodiments, the control device is also configured to move, particularly rotate, the object processing device and the disk device relative to each other. In embodiments, the control device is also configured to move the object processing device toward the disk device. In embodiments, the control device is also configured to move the disk device toward the object processing device. In embodiments, the control device is also configured to move the object processing device and the disk device toward each other. Therefore, there are several different movement (proximity) scenarios. Depending on the desired application, one scenario may be particularly suitable.

[0044] In one embodiment, the control device is configured to keep the disk assembly (substantially) free of external force in a plane (XY) perpendicular to the approach direction (Z) during movement. In another embodiment, the disk assembly includes a disk drive unit, and the control device is configured to not activate the disk drive unit (substantially) during movement. In one embodiment, the object processing device may be kept free of external force in the plane; in another embodiment, the disk assembly may be kept free of external force in the plane. In yet another embodiment, both the object processing device and the disk assembly are kept free of external force in the plane (during calibration). This allows for particularly efficient relative alignment, enabling the object processing device and the disk assembly to be moved relative to each other with high precision.

[0045] In embodiments, the calibration feature is configured to be at least one of movable, rotatable, and floating. The flexibility (and efficiency) of the described apparatus can be further improved when the calibration feature itself can be moved (towards the object processing device) for the calibration process. In one example, the calibration feature may be positioned at the disk assembly and thus rotate with it. In another example, the calibration feature may include an associated drive unit to actively move itself. In yet another example, the calibration feature may be arranged in a floating manner. Thus, instead of being held free of external force in a plane during approach, the calibration feature can be held free of external force / floating in a plane, allowing the object processing device to be guided to the calibration position by aligning with the calibration feature.

[0046] According to one aspect of this disclosure, analytical apparatus, particularly sample separation apparatus, including the (sample) apparatus as described above. In embodiments, the analytical apparatus is configured as a fluid chromatography apparatus, more particularly a high-performance liquid chromatography (HPLC) apparatus.

[0047] In an embodiment, the method further includes: rotating the disk device relative to the object processing device, determining the intersection points, particularly two or more intersection points, between the radius of the disk device and the radius of the object processing device as cross-calibration positions, and calibrating the object processing device and / or the disk device based on the cross-calibration positions (see, for example, Figures 7 and 8). Thus, efficient and relative alignment / calibration can be achieved. Rotation of the object processing device and the disk device can be particularly advantageous when not every sample position can be reached by moving only the object processing device.

[0048] In a particular embodiment, the encoders of the object processing device and the disk device are initialized. To determine the offset of the encoders relative to each other, the object processing device and the disk device are aligned such that the object processing device is above the calibration feature of the disk device. Now, the motors of the object processing device and the disk device are turned off, and the object processing device is moved downwards until the object processing device and the disk device are aligned with each other in the calibration feature. The encoder is now set to the value calculated for this position. To achieve a more accurate calculation, another calibration feature is used at the same angular position but a different radius. The measurement of the encoder position is performed as described above. From the obtained angle, the arm length of the object processing device can be determined, for example, as follows: r arm = r2 – r1 (((sin α1 / sin β2)*(sin α1 / sin β1)) / ((sin α2 / sin β2)-(sin α1 / sin β1))); Where r2 > r1 In this embodiment, the sample separation device is configured as a fluid chromatography device, and more particularly as a high-performance liquid chromatography (HPLC) device.

[0049] In preparative chromatography systems, the liquid as the mobile phase is typically supplied at a controlled flow rate (e.g., in the range of 1 mL / min to several thousand mL / min, such as 1–5 mL / min in analytical-scale preparative liquid chromatography and 4–200 mL / min in preparative-scale chromatography) and at a pressure in the range of tens to hundreds of bar (e.g., 20–600 bar).

[0050] In high-performance liquid chromatography (HPLC), the liquid as the mobile phase must typically be supplied 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 currently up to 200 MPa, 2000 bar), where the compressibility of the liquid becomes apparent.

[0051] In analytical equipment, particularly in liquid chromatography (especially HPLC), providing accurate solvent flow can be important, even when the specific properties of the solvent are not known or are not downloaded to the control unit of the analytical equipment.

[0052] Multiple embodiments can be implemented in conventionally available high-performance liquid chromatography (HPLC) systems, such as the analytical Agilent 1290 Infinity II HPLC system or the Agilent 1290 Infinity II preparative HPLC / mass spectrometry detector system (both provided by the applicant, Agilent Technologies – see www.agilent.com – which should be incorporated herein by reference).

[0053] One embodiment of the sample separation device includes a pump having a pump piston for reciprocating within a pump working chamber to compress a liquid in the pump working chamber to a high pressure, under which the compressibility of the liquid becomes apparent. The pump can be configured to know (by means of operator input, notification from another module of the instrument, or similar means) or otherwise extract the properties of the solvent.

[0054] The sample separation unit of the sample separation apparatus preferably includes a chromatographic column providing the stationary phase (see, for example, http: / / en.wikipedia.org / wiki / Column_chromatography). This column can be a glass or steel tube (e.g., with a diameter of 50 micrometers to 5 millimeters and a length of 1 centimeter to 1 meter) or a microfluidic column (such as those disclosed, for example, in EP1577012, or the Agilent 1200 series high-performance liquid chromatography-mass spectrometry system provided by the applicant, Agilent Technologies). The components are retained by the stationary phase in different ways and are at least partially separated from each other as they propagate through the column with the eluent at different speeds. At the end of the column, the components are eluted sequentially, or at least not completely simultaneously. Throughout the chromatography process, the eluent can also be collected as a series of fractions. The stationary phase or adsorbent in column chromatography is typically a solid material. The most commonly used stationary phases in column chromatography are silica gel, surface-modified silica gel, and alumina. Cellulose powder has also been commonly used in the past. Ion exchange chromatography, reversed-phase chromatography (RP), affinity chromatography, or expanded-bed adsorption (EBA) are all viable methods. The stationary phase is typically a finely ground powder or gel, and / or a microporous structure with increased surface area.

[0055] The mobile phase (or eluent) can be a pure solvent or a mixture of different solvents (such as water and organic solvents, such as acetonitrile). The mobile phase can be selected, for example, to adjust the retention time of the target compound and / or to adjust the amount of mobile phase required for chromatographic analysis. The mobile phase can also be selected to enable efficient separation of different compounds or fractions of the fluid sample. The mobile phase may contain an organic solvent, such as methanol or acetonitrile, which is typically diluted with water. For gradient operations, water and organic solvents are stored in separate reservoirs, and a gradient pump delivers a programmed mixture from the reservoirs to the system. Other commonly used solvents include isopropanol, tetrahydrofuran, hexane, ethanol, and / or any combination thereof, or any combination of these solvents with the aforementioned solvents.

[0056] The fluid samples analyzed by the sample separation apparatus according to exemplary embodiments of this disclosure may include, but are not limited to, any type of process liquid, natural sample (e.g., fruit juice), body fluid (e.g., blood plasma), or reaction product (e.g., reaction product of fermentation broth).

[0057] The pressure in the flowing phase generated by the fluid actuator can be in the range of 2-200 MPa (20 to 2000 bar), particularly in the range of 10-150 MPa (150 to 1500 bar), and even more particularly in the range of 50-120 MPa (500 to 1200 bar).

[0058] Sample separation equipment, such as a high-performance liquid chromatography system, may also include a detector, a fractionation collection unit, or any combination thereof; the detector is used to detect the separated compounds in the fluid sample, and the fractionation collection unit is used to output the separated compounds in the fluid sample. For example, a fluorescence detector may be provided.

[0059] In one embodiment, the calibration of the robotic arm is accomplished by moving the arm (along the XY direction) toward a calibration feature, and then lowering the arm (along the Z direction) into the calibration feature, while allowing the arm to move along the XY direction under the influence of the calibration feature. In a particular embodiment, the calibration feature is tapered, thereby providing (fine) movement along the XY direction.

[0060] In one embodiment, the turntable driver may be configured to operate without external force during the alignment process. In another embodiment, the robotic arm driver, the turntable driver, or either of the two drivers may be configured to operate without external force to allow the alignment process to proceed.

[0061] Embodiments of this disclosure may be embodied or supported in part or in whole by one or more suitable software programs, which may be stored on or provided on any kind of data carrier and may be in or executed in any suitable data processing unit. The software programs or routines may preferably be in or applied by a control unit.

[0062] Other objects and numerous accompanying advantages of the embodiments of this disclosure will be readily and better understood by referring to the following more detailed description of embodiments, taken in conjunction with the accompanying drawings. Features that are substantially or functionally identical or similar will be referred to by the same reference numerals. Attached Figure Description

[0063] Figure 1 illustrates a liquid sample separation apparatus specifically for high-performance liquid chromatography (HPLC), which serves as an analytical apparatus including a (sampling) device according to an embodiment of the invention.

[0064] Figure 2 A sampling apparatus of an analytical device according to an embodiment of the present disclosure is shown, which includes an object processing apparatus and a calibration feature.

[0065] Figures 3 and 4 respectively illustrate moving the object processing device toward a calibration feature and guiding the object processing device by the geometry of the calibration feature according to embodiments of the present disclosure.

[0066] Figures 5 and 6 respectively illustrate calibration features for moving an object processing device in a horizontal plane to a disk device according to embodiments of the present disclosure.

[0067] Figure 7 shows the intersection point between the radius of the object processing device and the radius of the disk device according to an embodiment of the present disclosure, while Figure 8 shows two intersection points between the radii of the devices. Detailed Implementation

[0068] The attached diagram is illustrative.

[0069] Figure 1 is a general schematic diagram depicting an analytical apparatus 10 having a (sampling) device 100. A solvent (mobile phase) driver 20 (such as a pump) receives solvent as the mobile phase from a solvent supply unit 25. The solvent driver 20 drives the mobile phase through a separation device 30 (such as a chromatographic column), which can be considered the analytical region of the apparatus. A sample injector 40 (also referred to as a sample introduction device, sample dispenser, etc.) is provided between the solvent driver 20 and the separation device 30 to introduce or add (often referred to as sample introduction) a portion of one or more sample fluids into the flow of the mobile phase at a mixing point 45. The separation device 30 is adapted to separate compounds from the sample fluid (e.g., a liquid). A detector 50 is provided for detecting the separated compounds in the sample fluid. A fractionation collection unit 60 may be provided for discharging the separated compounds from the sample fluid. In one embodiment, at least a portion of the sample injector 40 and the fraction collection unit 60 may be combined, for example, in the sense that some common hardware is used by both the sample injector 40 and the fraction collection unit 60.

[0070] The separation device 30 may include a stationary phase of compounds configured to separate the sample fluid. Alternatively, the separation device 30 may be based on different separation principles (e.g., field flow fractionation).

[0071] While the mobile phase may consist of only one solvent, it may also be a mixture of multiple solvents (solvent supply unit 25). Such mixing may be low-pressure mixing and supplied upstream of the solvent driver 20, such that the solvent driver 20 has received and pumped the mixed solvent as the mobile phase. Alternatively, the solvent driver 20 may include multiple separate pumping units, each of which receives and pumps a different solvent or mixture, such that mixing of the mobile phase (as received by the separation unit 30) occurs at high pressure downstream of (or as part of) the mobile phase driver 20. The composition of the mobile phase (mixture) may remain constant over time, i.e., a so-called isocratic mode, or vary over time, i.e., a so-called gradient mode.

[0072] A data processing device (control device) 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 sample separation device 10 to receive information and / or control operations.

[0073] The fluid sample is injected into the injection path 195 of the analytical device 10 via needle hub 140. Needle hub 140 (via injection path 195) is connected to mixing point 45, where the sample is injected into the high-pressure path. The fluid sample is processed by object processing device 190, which is sample processing device 190 in this case, which takes the sample from sample container 131 (sample vial in this case), transports the sample to needle hub 140, and injects the sample into needle hub 140.

[0074] The object handling device 190 includes an extension arm 178, which is connected at one end to a drive unit 128 having a first drive unit for vertical movement (along the Z) and a second drive unit for horizontal movement (along the XY) (schematically shown by arrows). At the other end, the extension arm 178 is coupled to a protrusion including a sample needle 110. The sample needle 110 is configured to move into a sample container 131 to aspirate a sample and to move into a needle holder 140 for sample injection. A push rod device 115 surrounds the sample needle 110 for protection and for improved sample aspiration (pushing back the sample container after sample aspiration). Furthermore, the sample container 131 is schematically arranged on a disc device 130.

[0075] Figure 2 illustrates a (sampling) device 100 of an analytical apparatus 10 (see Figure 1) according to an embodiment of the present disclosure, having an object processing device 190 and two calibration features 120. The device 100 includes a so-called (automato) sampler, which is a space for preparing (fluid) samples for (chromatographic) analysis. The device 100 includes a disk assembly 130 configured to accommodate a plurality of sample containers 131 in respective sample carriers 132.

[0076] The apparatus 100 also includes a sample handling device 190 for transporting a fluid sample within the needle 110 from the sample tray device 130 to the needle holder 140. The sample handling device 190 includes a moving / extending arm 178, controlled by a drive system 128 to move the arm 178 in both horizontal and vertical directions. The moving arm 178 is coupled to the sample needle 110 and a pusher (or gripper) device 115 surrounding the sample needle 110. The pusher device 115 includes an opening 116 at its bottom portion (here, the tray) through which the needle 110 can be guided (along the Z-direction) during sample aspiration and injection.

[0077] Two calibration features 120 are located on the disk assembly 130 and are configured in a tapered structure to at least partially accommodate the protrusions (sample needle 110 and / or pusher assembly 115) of the object processing device 190. To perform the calibration process, the protrusions 110, 115 of the object processing device 190 move along the approach direction Z into the calibration features 120, such that during movement along the approach direction Z, the calibration features 120 guide the protrusions 110, 115 to a calibration position in a plane XY perpendicular to the approach direction Z. Thus, at least one attribute of the object processing device 190 in the plane perpendicular to the approach direction (particularly the length of the extension arm 178) is defined by or relative to the calibration position.

[0078] Figures 3A to 3C respectively illustrate the movement of the object processing device 190 toward the calibration feature 120 according to embodiments of the present disclosure and the guidance of the object processing device 190 by the geometry of the calibration feature 120. It can be seen that the calibration feature 120 includes a tapered structure that tapers away from the approaching protrusions 110, 115. The object processing device 190 has already moved in the plane to be positioned above the calibration feature 120 and is now moving downwards in the vertical direction z. Thus, the object processing device 190 remains free from external force (floating) in the plane, such that the tapered geometry of the calibration feature 120 mechanically guides (forces) the object processing device 190 (towards the protrusions) toward the calibration position in the lower part of the calibration volume.

[0079] In this example, the sample needle 110 is surrounded and protected by the pusher assembly 115. The disc-shaped pusher element 116 is here the lowest point of the protrusion 115. It can be seen that the pusher element 116 is located on the side wall of the calibration feature 120. Accordingly, there is a misalignment between the object handling device 190 and the disc assembly 130 (which includes the calibration feature 120 here).

[0080] Figures 4A to 4C respectively illustrate guiding the object processing device 190 to the calibration position within the calibration feature (volume) 120 according to embodiments of the present disclosure. The object processing device 190 moves downwards, and it can be seen that the push rod element 116 has moved along the tapered sidewall of the tapered calibration feature 120 toward the center / middle of the volume. This is possible because the object processing device 190 remains free of external force in the plane, and its direction of movement is determined by the geometry of the calibration feature 120. Further downward movement, the push rod element 116, and thus the object processing device 190, reaches the calibration position.

[0081] Figures 5 and 6 respectively show top views of the apparatus 100 according to embodiments of the present disclosure as the object processing device 190 is moved along a horizontal plane to the calibration feature 120 of the disk assembly 130. As can be seen in the top views, the disk assembly 130 includes three trays, each configured to hold a sample carrier 132. In Figure 5, the object processing device 190 is moved toward the calibration feature 120 in the plane. In Figure 6, the object processing device 190 is positioned above the calibration feature 120, and the calibration process begins by moving the protrusions 110, 115 vertically downwards toward the calibration feature 130.

[0082] Figure 7 shows the intersection point 121 between the radius of the object processing device 190 and the radius of the disk device 130, while Figure 8 shows two intersection points 121a and 121b between the radii of the devices 130 and 190 according to an embodiment of the present disclosure. To determine the offset of the respective encoders relative to each other, the object processing device 190 and the disk device 130 are aligned such that the object processing device 190 is above the calibration feature 120 of the disk device 130. The motors of the object processing device 190 and the disk device 130 are now turned off, and the object processing device 190 is moved downwards until the object processing device 190 and the disk device 130 are aligned with each other in the calibration feature 120. The encoder is now set to the value calculated for this position. To achieve a more accurate calculation, another calibration feature is used at the same angular position but with a different radius. The measurement of the encoder position is performed as described above.

[0083] It should be noted that the term "comprising" does not exclude other elements or features, and "a" does not exclude a plurality. Similarly, elements described in conjunction with different embodiments may be combined. It should also be noted that the reference numerals in the claims should not be construed as limiting the scope of the claims.

[0084] List of reference numerals in the attached diagram: 10 Analytical equipment 20 Fluid Drives 25 Solvent Supply Department 30 Sample separation device 40 Sample injector 45 Mixing point 50 detectors 60-level sub-collection unit 70 Data processing device, control device 100 device, sampling device 110 Sample receiving unit, sample needle 115 Push Rod Device 116 Push Rod Component 120 Calibration Features 121 Intersection 128 drive system 130-disc device 131 Sample container 132 Sample carrier device 140 pin hub 178 Conveyor Arm 190 Object processing device 191 Coupling Component 195 Sample Injection Path

Claims

1. An apparatus (100), preferably a sampling device (100) for an analytical apparatus (10), said apparatus (100) comprising: The object processing device (190), in particular a robotic arm, is configured to process objects to be processed, particularly samples such as analytical samples; The calibration feature (120) is configured to at least partially accommodate the protrusions (110, 115) of the object processing device (190); and The control device (70) is configured as follows: The protrusions (110, 115) of the object processing device (190) are moved along the approach direction (Z) into the calibration feature (120) such that, during the movement along the approach direction (Z), the calibration feature (120) guides the protrusions (110, 115) to the calibration position in a plane (XY) perpendicular to the approach direction (Z). This results in at least one attribute of the object processing device (190) in a plane (XY) perpendicular to the approach direction (Z) being defined by or relative to the calibration position.

2. The apparatus (100) according to claim 1, wherein the control device (70) is further configured to: When the protrusions (110, 115) of the object processing device (190) are at least partially guided into the calibration feature (130) to the calibration position, the object processing device (190) is kept substantially free of external force in a plane (XY) perpendicular to the approach direction (Z).

3. The apparatus (100) according to claim 1 or 2. The geometry of the calibration feature (130) is configured such that the protrusions (110, 115) of the object processing device (190) are at least partially mechanically guided into the calibration feature (120), particularly into the receiving volume of the calibration feature (120).

4. The apparatus (100) according to any one of the preceding claims. The calibration feature (120) includes a tapered shape. The tapering direction is away from the object processing device (190), and The tapered shape is configured to guide the protrusions (110, 115) of the object processing device (190) to the calibration position.

5. The apparatus (100) according to claim 4. The tapering shape includes at least one of the following: cone, pyramid, rectangle, quadrilateral, hemisphere, and polygon.

6. The apparatus (100) according to any one of the preceding claims. The object processing device (190) is movable in the approach direction (Z) by a first drive unit and movable in a plane (XY) perpendicular to the approach direction (Z) by a second drive unit. in, During movement, the first drive unit is in an active state, particularly supported by current, while the second drive unit is essentially in an inactive state, particularly not supported by current.

7. The apparatus (100) according to any one of the preceding claims. The protruding portions (110, 115) of the object processing device (190) include a sample needle (110) or a simulated sample needle or a needle replacement device.

8. The apparatus (100) according to any one of the preceding claims. The protruding portion (110, 115) of the object processing device (190) includes a push rod device (115). In particular, the pusher device (115) is configured to at least partially surround the sample needle (110), and more particularly, the pusher device (115) includes a pusher element (116) having an opening through which the sample needle (110) can be guided.

9. The apparatus (100) according to any one of the preceding claims. The object processing device (190) includes a conveying arm (178), particularly a conveying arm with a length L to be calibrated, and includes a coupling member (191) connected to the conveying arm (178) and configured to couple with the protrusions (110, 115).

10. The apparatus (100) according to any one of the preceding claims further comprises: The disk device (130), particularly the sample disk device, is configured to accommodate at least one object, particularly the sample carrier device (132) and / or at least one sample container (131).

11. The apparatus (100) according to claim 10. The disk device (130) is configured to be rotatable in a plane (XY) perpendicular to the approach direction (Z), and particularly rotatable in the plane (XY).

12. The apparatus (100) according to claim 10 or 11. One or more of the calibration features (120) are arranged on the disk device (130).

13. The apparatus (100) according to any one of claims 10 to 12, wherein the control device (70) is further configured to perform at least one of the following steps to define the at least one attribute of the object processing device (190): The object processing device (190) moves, in particular rotates, relative to the disk device (130). The disk device (130) moves relative to the object processing device (190), particularly rotating the disk device (130). The object processing device (190) and the disk device (130) are moved relative to each other, particularly rotated; Move the object processing device (190) toward the disk device (130); Move the disk device (130) toward the object processing device (190); The object processing device (190) and the disk device (130) are moved toward each other.

14. The apparatus (100) according to any one of claims 10 to 13. The control device (70) is configured to keep the disc device (130) substantially free of external force in a plane (XY) perpendicular to the approach direction (Z) during movement, and / or The disk device (130) includes a disk drive unit, and the control device (70) is configured to substantially not activate the disk drive unit during movement.

15. The apparatus (100) according to any one of the preceding claims. The calibration feature (120) is configured to be at least one of being movable, rotatable, or floating.

16. An analytical apparatus (10), particularly a sample separation apparatus, comprising the device (100) according to any of the preceding claims.

17. The analytical apparatus (10) according to claim 16. It is configured as a fluid chromatography device, and more particularly as a high-performance liquid chromatography (HPLC) device.

18. A method for defining at least one attribute of an object processing apparatus (190), the method comprising: The protruding portions (110, 115) of the object processing device (190) are moved along the approach direction (Z) into the calibration feature (120); thereby The protrusions (110, 115) are guided to the calibration position in a plane (XY) perpendicular to the approach direction (Z) by the calibration feature (120); and The object processing device (190) defines at least one attribute in a plane (XY) perpendicular to the approach direction (Z) by means of the calibration position or relative to the calibration position.

19. The method of claim 18, further comprising: Relative to the object processing device (190) and the rotating disk device (130); Determine the intersection points (121), particularly two or more intersection points, between the radius of the disk device (130) and the radius of the object processing device (190) as cross-calibration positions; and The object processing device (190) and / or the disk device (130) are calibrated based on the cross-calibration position.

20. Use a calibration feature (120) with a tapered shape to mechanically guide the approach portion (110, 115) of the sample processing device (190) to the calibration position.

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