Calibrating an object handling device with a calibration feature

Abstract

There is described a device (100), preferably a sampling device (100) for an analytic device (10), the device (100) comprising: i) an object handling device (190), in particular a robotic arm, configured for handling an object to be handled, in particular a sample such as an analytical sample; ii) a calibration feature (120) configured for at least partially accommodating a protruding part (110, 115) of the object handling device (190); and iii) a control device (70), configured to: move the protruding part (110, 115) of the object handling device (190) into the calibration feature (120) in an approaching direction (Z), so that the calibration feature (120) guides the protruding part (110, 115), in a plane (XY) perpendicular to the approaching direction (Z), to a calibration position during movement in the approaching direction (Z), so that at least one property of the object handling device (190) in the plane (XY) perpendicular to the approaching direction (Z) is defined by or relative to the calibration position.

Description

DESCRIPTIONCALIBRATING AN OBJECT HANDLING DEVICE WITH A CALIBRATION FEATUREFIELD OF THE DISCLOSURE

[0001] The present disclosure relates to a device, in particular a sampling device for an analytic device such as a chromatography device, that comprises an object handling device and a calibration feature. The present disclosure further relates to a method of defining at least one property of said object handling device in a plane perpendicular to an approaching direction of a protruding part of the object handling device towards the calibration feature.BACKGROUND ART

[0002] A plurality of automated applications use an object handling device such as a robotic arm to handle objects. For example, a sample handling device can be used to automatically handle samples for an analytic device. Analytical devices are provided for analyzing such a sample, for example using a sample separation device.

[0003] For example, 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.

[0004] The mobile phase, typically comprised of one or more solvents, 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 thecolumn. 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.

[0005] 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 chromatogram, may be made, and from the chromatogram the compounds may be identified. For each compound, the chromatogram displays a separate curve feature also designated as a "peak".

[0006] Nowadays, most analytic devices function automatically or have an automatic functionality. For example, a HPLC normally comprises a sampling device with a robotic arm that performs the sample handling in an automated manner. For example, sample containers (such as vials) with the fluidic sample can be arranged on a sample plater device (in particular within a sample carrier tray). The robotic arm can be movable in the horizontal plane (XY) in order to position a sample needle above a sample container. Then, the robotic arm can be lowered in the vertical direction (Z) to move the sample needle into the sample container. The sample needle can suck a specific amount of fluidic sample into a sample accommodation volume and then, the robotic arm can move the sample needle in the vertical direction out of the sample container. Afterwards, the robotic arm can be moved in the horizontal plane towards a sample injection aperture such as a needle seat. Here again, the robotic arm can be lowered in the vertical direction to move the sample needle into the sample injection aperture and inject the fluidic sample into the analytic domain. In case that many samples are to be analyzed, the sampling device can be active day and night and handle thousands of samples automatically in the described manner.

[0007] In many applications, the sampling has to be very precise, in particular since the sample needle and the sample vials have very small dimensions. For this reason, the robotic arm has to be calibrated, so that the system exactly knows at which position the robotic arm, and in particular the sample needle, is. A main propertymay hereby be the exact length of the robotic arm (extension arm, one extremity may be coupled to the sample needle, while the other extremity may be coupled to a drive unit). Hereby, the calibration compensates for variations in the length of the robotic arm. For example, small variations in the ambient temperature (of the sampling space) may have an influence on the length of the robotic arm as well as manufacturing tolerances (this may refer to all involved components).

[0008] Conventionally, a calibration of the robotic arm in the field of chromatography is done by alignment of the sample needle, for example using reference marks / positions together with an optical camera or an electric contact. However, the conventional approaches calibrate only indirectly without a physical contact to the sample needle, in particular since said needle is a very delicate structure. Yet, the conventional indirect calibration may lead to drawbacks in the precision and additional effort (e.g. providing and maintaining a camera).DISCLOSURE

[0009] There may be a need to calibrate an object handling device in an efficient and reliable manner. A sampler device, an analytic device, a method, and a use are described by the independent claims. Further embodiments are described by the dependent claims.

[0010] According to an aspect of the disclosure, there is described a device, preferably a sampling device (e.g. a device to handle, in particular transport, a sample) for an analytic device (in particular a sample separation device such as an HPLC), the device comprising: i) an object handling device (in particular a sample handling device), in particular a robotic arm, configured for handling an object (e.g. a fluidic sample) to be handled, in particular a sample such as an analytical sample; ii) a calibration feature (for example an object with a specific geometry, e.g. a tapering shape) configured for at least partially accommodating a protruding part (e.g. a sample needle, a needle dummy, a pusher device) of the object handling device; and iii) a control device (e.g. a processor, an integrated circuit, a control system of an analytic device), configured to:move the protruding part of the object handling device (at least partially) into the calibration feature (a volume of the calibration feature) in an approaching direction (in particular in a vertical direction, Z), so that the calibration feature (mechanically, e.g. by its geometry) guides the protruding part, in a plane (in particular the horizontal plane, XY) perpendicular to the approaching direction, to a calibration position during movement in the approaching direction, so that at least one property (in particular the XY position) of the object handling device in the plane perpendicular to the approaching direction is defined (in other words: calibrated / aligned) by or relative to the calibration position.

[0011] According to an aspect of the disclosure, there is described a method of defining at least one property of an object handling device (in particular to calibrate the object handling device), the method comprising: i) moving a protruding part of the object handling device (at least partially) into a calibration feature (configured to accommodate said protruding part) in an approaching direction); thereby ii) guiding, by the calibration feature, the protruding part, in a plane perpendicular to the approaching direction, to a calibration position; and iii) defining the at least one property of the object handling device in the plane perpendicular to the approaching direction by or relative to the calibration position.

[0012] According to an aspect of the disclosure, there is described a use (method of using) of a calibration feature with a tapering shape to mechanically guide (having physical contact) an approaching part of a sample handling device into a calibration position.

[0013] In the context of this document, the term “device” may particularly denote a machine configured to handle an object by means of an object handling device, for example a robotic arm. In a preferred embodiment, the device may be a sampling device, configured to handle samples by means of a sample handling device. Besides the object handling device, such a (sampling) device may comprise a calibration feature suitable to calibrate the object handling device. The calibration may be performed by a direct physical contact between a (protruding) part of the objecthandling device and the calibration feature.

[0014] In the context of this document, the term “object handling device” may particularly denote a device suitable to handle an object such as a fluidic sample. The object handling device may comprise a protruding part for interacting with the object. For example, the protruding part may be a sample needle to intake fluidic sample, In another example, the protruding part may be a gripper to grip an object (e.g. a sample vial) or a pusher device to protect a sample needle. In a preferred embodiment, the object handling device may be configured as a robotic arm, in particular with an extension arm that is rotatable in the XY plane and / or movable up / down in the Z direction.

[0015] In the context of this document, the term “calibration feature” may particularly denote any structure suitable for guiding a protruding part of an object handling device, in particular when the object handling device is approaching the calibration feature (in the vertical direction). For example, the calibration feature may comprise a specific geometry to enable such a guidance. In an illustrative example, the calibration feature comprises a tapering shape, so that an approaching protruding part is guided along the tapering direction to a center of a calibration feature volume. In an example, the calibration feature protrudes in the vertical direction, in particular is arranged on a plater device.

[0016] In the context of this document, the term “calibration position” may particularly denote a position, in particular within a calibration feature, that may be well-defined, so that it may serve as a calibration marker. In a preferred embodiment, the calibration feature may be designed so that an approaching protruding part of an object handling device is (automatically) guided to said calibration position. For example, the object handling device may be moved (under force) in the Z-direction, while it is kept forceless in the XY-plane. Then, the protruding part may be guided to the calibration position and one or more properties (with respect to the plane) of the object handling device can be determined / calculated, e.g. the length of the extension arm.

[0017] In the context of this document, 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 ofmolecules or particles which shall be separated, for instance small mass molecules or large mass biomolecules such as proteins. 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.

[0018] In the context of this document, the term “mobile phase” may particularly denote any liquid and / or gaseous medium which may serve as fluidic carrier of the fluidic sample during separation. A mobile phase may be a solvent or a solvent composition (for instance composed of water and an organic solvent such as ethanol or acetonitrile). In an isocratic separation mode of a liquid chromatography apparatus, the mobile phase may have a constant composition over time. In a gradient mode, however, the composition of the mobile phase may be changed over time, in particular to desorb fractions of the fluidic sample which have previously been adsorbed to a stationary phase of a separation unit.

[0019] In the context of this document, the term “sample separation device” may particularly denote any apparatus which is capable of separating different fractions of a fluidic sample by applying a certain separation technique, in particular liquid chromatography. The term “separation unit” 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. An example for a separation unit is a liquid chromatography column which is capable of trapping or retarding and selectively releasing different fractions of the fluidic sample.

[0020] In the context of this application, the term “sample accommodation volume” may particularly denote a defined portion or section of a flow path, a fluidic conduit or a fluidic member (such as a fluidic valve) in which a predefined amount of fluid may be at least temporarily accommodated. In an embodiment, the fluid accommodation volumes may be sample loops (fluidically connected to ports of a modulator valve). The fluid accommodation volume may be at least temporarily fluidically decoupled from a flow path or main path. By a switching mechanism, the sample accommodation volume may be first coupled to a certain location in a sample separation apparatus, while being later alternatively or additionally coupled to a different location in the sample separation apparatus.

[0021] According to an exemplary embodiment, the disclosure may be based on the idea that an object handling device can be calibrated in an efficient and reliable manner, when said object handling device is moved towards a calibration feature, so that the calibration feature guides the object handling device during moving to a calibration position. Based on said calibration position (directly or indirectly), a property of the object handling device with respect to a (horizontal) plane, being perpendicular to the moving direction, can be defined.

[0022] For example, a physical contact may be established between a protruding part (such as a sample needle) of the object handling device and the calibration feature, when moving (lowering) the protruding part at least partially into an accommodation volume of the calibration feature. The calibration feature (in particular its geometry) is configured so that the protruding part, during moving along the vertical direction, is guided mechanically to the calibration position. In a preferred embodiment, the object handling device may be kept floating (forceless) in the (horizontal) plane during moving along the direction perpendicular to said plane. Thereby, the (geometry of the) calibration feature forces the protruding part of the object handling device to a specific local position in said plane.

[0023] Since the calibration position may be well defined, one or more properties regarding the object handling device may be defined. For example, the position in the XY-plane or the length of an extension arm of the object handling device.

[0024] While conventionally a calibration of a robotic arm is generally done indirectly without a physical contact (e.g. by a camera), it has been found that a surprisingly efficient and reliable calibration of a robotic arm may be done, when a direct physical contact between an object handling device and a calibration feature is established, so that the calibration feature can directly guide the object handling device to the calibration position.

[0025] In the example of a sample handling device, a sample needle may be used as the protruding part. Such a sample needle is generally very delicate and hence physical contact to such a needle is avoided. Yet, in contrast to conventional teachings, the present disclosure applies a highly efficient calibration with direct physical contact to the sample needle or a substitute to the needle, e.g. a dummy needle or a pusher device.EXEMPLARY EMBODIMENTS

[0026] In an embodiment, the control device is further configured to keep the object handling device (substantially) forceless, in particular in the plane perpendicular to the approaching direction, when the protruding part of the object handling device is guided (having physical contact) at least partially into the calibration feature to the calibration position. By keeping the object handling device forceless in the plane, the calibration feature may mechanically guide (e.g. by its geometry) the (protruding part of the) object handling device directly to the calibration position. The object handling device may not be kept forceless in the vertical direction, so that the object handling device can be actively moved (lowered) towards the calibration device. Hence, there may be a force on the object handling device along the vertical direction towards the calibration device, but no force along the plane, so that the movement of the approaching object handling device is (only) influenced / guided by the calibration feature.

[0027] In this context, the term “forceless” may in particular refer to the circumstance that a drive unit associated with the object handling device does not provide a force in the plane, i.e. the horizontal direction. Herefore, the associated drive unit may not provide an electric current to enable a movement in the plane. In an example, the (sampling) device comprises two drive units: a first drive unit for the vertical movement (along Z) and a second drive unit for the horizontal movement (along the plane XY). Thus, in a preferred example, during calibration, the first drive unit puts a force on the object handling device (an electric current is provided), while the second drive unit puts no force on the object handling unit (no electric current is provided). Further definitions for the term “keep the object handling device forceless in the plane” may include: keep the object handling device freely moving, keep the object handling device floating, providing (at least) two degrees of freedom to the object handling device.

[0028] In an embodiment, the geometry of the calibration feature is configured so that the protruding part of the object handling device is guided mechanically at least partially into the calibration feature, in particular into an accommodation volume of the calibration feature. This may provide the advantage that no further mechanism or processing is necessary for the calibration. Instead, merely the geometry (e.g. shape,size, dimension) of the calibration feature may be sufficient to guide the approaching protruding part towards the calibration position. In particular, when the approaching object handling device is kept forceless in the plane, the geometry of the accommodation volume of the calibration feature may be sufficient to bring the object handling device within the plane into the calibration position.

[0029] In an embodiment, the calibration feature comprises a tapering shape. In an embodiment, the tapering direction is facing away from the object handling device. In an embodiment, the tapering shape is configured to guide the protruding part of the object handling device to the calibration position. Thereby, the mechanical guidance by the calibration device may be implement in a simple, but highly efficient manner. Descriptively speaking, the protruding part may be lowered towards a cone-shaped structure, whereby the broad part of the cone is closer to the approaching protruding part than the narrow part of the cone. When the protruding part enters into the broad part, there is a large diameter and a high tolerance for the position in the plane. However, when the object handling device is further lowered, the diameter of the cone and the tolerance for the movement in the plane is getting continuously smaller. In the final calibration position, there may be (essentially) no tolerance for movement in the plane anymore.

[0030] In other words: when lowering the object handling device, the tolerance for movement of the protruding part in the calibration feature (volume) is continuously lowered during moving down, so that a guidance / correction to a final calibration position is automatically achieved by the geometry of the calibration feature. When the protruding part is at the calibration position, the calibration process may already be finished.

[0031] In an embodiment, the geometry of the calibration feature, in particular the tapering shape, comprises at least one of a conical shape, a frustoconical shape, a pyramid, a rectangle, a quadrangle, a hemisphere, a polyangular shape. A plurality of different geometrical shapes are possible to enable a mechanical guidance of the protruding part of the object handling device within the calibration feature (volume), also depending on the desired application. In a preferred example, the geometrical shape is tapering in a direction away from the approaching protruding part. For example, in case a pusher device (see below), with a disk-shaped structure as thelowest part, is provided around a sample needle, the shape of the calibration feature may be preferably conical / frustoconical.

[0032] In an embodiment, the calibration device comprises an elastic material. For example, the calibration feature volume (e.g. cone-shaped) comprises sidewalls. Said sidewalls may be (towards the volume) (at least partially) elastic or comprise an elastic coating. The elastic material may be a plastic such as rubber. In this manner, the protruding part may be protected from damages. For example, a sample needle may be a delicate structure that may be damaged or broken, when approaching the mechanical structure of the calibration feature. Such a drawback may be overcome by the elastic material (sidewalls).

[0033] In an embodiment, the object handling device is movable in the approaching direction (Z) by a first drive unit and in the plane (XY) perpendicular to the approaching direction (Z) by a second drive unit. In an embodiment, during moving, the first drive unit is active, in particular supported by electric current, while the second drive unit is (essentially) inactive, in particular not supported by electric current. As described above, the object handling device may comprise at least two driving units, in particular a first drive unit for the approaching direction, and a second drive unit for the plane. When keeping the second drive unit active (for vertical movement) and keeping the second drive unit inactive (forceless, floating, free moving), the approaching object handling device may be guided to the calibration position (in the plane) by the (shape of the) calibration feature in an efficient and reliable manner. In an example, the second drive unit may be a theta rotation engine.

[0034] In an embodiment, the protruding part of the object handling device comprises a sample needle or a dummy sample needle or a needle substitution device. The object handling device may be coupled with a sample needle, so that the protruding part is already present without further efforts. Without any further preparations, the calibration may be directly started by moving the sample needle towards the calibration feature. Yet, since the sample needle itself may be very delicate, it may be replaced during calibration by a replica, e.g. called a dummy sample needle. One may think of further elongated structures that may be used as the protruding part and that may substitute the actual sample needle during calibration. For example, a robust structure may be used, e.g. made of steel, or aflexible structure, such as a plastic. In a further example, the protruding part may be configured to be guided along the calibration feature in a smooth manner, e.g. by providing a gliding surface or a structure with one or more rolls.

[0035] In an embodiment, the protruding part of the object handling device comprises a pusher device, in particular wherein the pusher device is configured to be arranged at least partially around a sample needle, more in particular wherein the pusher device comprises a pusher element with an opening through which the sample needle can be guided. In an embodiment, the protruding part comprises: a needle guidance device (e.g. a pusher / gripper device), in particular coupled to the moving arm, coupled to the needle, and configured to guide the needle towards a needle seat. Thereby, accuracy of the needle orientation may be improved. Further, the needle may be protected within the pusher device. Since the pusher device may be significantly more robust than the sample needle, the needle may be kept protected within the pusher device, while the alignment in the calibration feature is done by the pusher device as the protruding part.

[0036] In an embodiment, the pusher device comprises a pusher element (perpendicular to the direction of main extension of the needle) with an opening, through which the needle can be guided, e.g. when intaking a sample from a sample container. When the needle is moved out of the sample container, the pusher device (in particular the pusher element) may assist in pushing back the sample container to allow an efficient and smooth movement of the needle out of the sample container.

[0037] In an embodiment, the object handling device (the protruding part) comprises a gripper device, configured to handle an object by gripping said object. In an example, the gripper comprises 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 the sampling space, e.g. between two sample carriers.

[0038] In an embodiment, the object handling device comprises a handling / transport / extension arm, in particular with a length to be calibrated, and a coupling part, connected to the arm, and configured to couple with the protruding part. Descriptively speaking, the object handling device may comprise a coupling part to connect the protruding part (e.g. needle and / or pusher device) and a further couplingpart to be connected to one or more drive units. In between the coupling parts there may be arranged an extension arm (see e.g. Figure 2). The length of said arm may be an especially important property for reliable automated sampling. Based on the described alignment using the calibration position, the length of the arm may be determined with high accuracy.

[0039] In an embodiment, the device further comprises: a plater device, in particular a sample plater device, configured to accommodate at least one object, in particular a sample carrier device and / or at least one sample container and / or at least one sample. While the protruding part (sample needle) may comprise one direction of main extension (in particular along Z), the plater device may comprise two directions of main extension, in particular in the XY plane. Thus, the plater device may be configured to fulfill the function of a plate for arranging thereon objects to be handled by the object handling device.

[0040] In an embodiment, the sample plater device is configured for mounting sample carriers thereon. Each sample carrier may for example carry a plurality of sample vials in mounting holes (see e.g. Figure 2). In this manner, several sets of samples can be arranged on the sample plater device and the sample handling device can be moved automatically to the sample(s) to be analyzed. For example, while the samples of one sample carrier are in-taken by the sample handling device, another sample carrier may be exchanged (manually / automatically) to enable a continuous sampling procedure.

[0041] In an embodiment, the plater device is configured to be rotatable in the plane (XY) perpendicular to the approaching direction (Z), in particular rotatable in said plane (XY). The plater device may be applied in a flexible manner and sampling (performance, speed) may be highly improved by a movable, in particular rotatable plater device. For example, a sample plater device may be rotated such that the sample carrier with the samples to be analyzed is positioned below the sample handling device and the sample handling device only has to be moved in the plane above said sample carrier, i.e. above the sample vial to be analyzed.

[0042] In an embodiment, one or more of the calibration feature(s) is / are arranged at the plater device. Thereby, the object handling device may be aligned / calibrated with respect to the plater device. Two or more calibration features may make thecalibration (in particular the relative calibration) more efficient and reliable. Furthermore, no additional structures may be necessary. For example, a calibration feature may be positioned between two carrier structures.

[0043] In an embodiment, the control device is further configured to move, in particular rotate, the object handling device with respect to the plater device. In an embodiment, the control device is further configured to move, in particular rotate, the plater device with respect to the object handling device. In an embodiment, the control device is further configured to move, in particular rotate, the object handling device and the plater device with respect to each other. In an embodiment, the control device is further configured to move the object handling device towards the plater device. In an embodiment, the control device is further configured to move the plater device towards the object handling device. In an embodiment, the control device is further configured to move the object handling device and the plater device towards each other. Thus, there are a plurality of different moving (approaching) scenarios. Depending on the desired application, one may be especially suitable.

[0044] In an embodiment, the control device is configured to keep the plater device (essentially) forceless in the plane (XY) perpendicular to the approaching direction (Z) during moving. In an embodiment, the plater device comprises a plater drive unit, and wherein the control device is configured to (essentially) inactivate the plater drive unit during moving. While in one embodiment, the object handling device may be kept forceless in the plane, in another embodiment, the plater device may be kept forceless in the plane. In yet another embodiment, both, the object handling device and the plater device, are kept forceless in the plane (during calibration). Thereby, an especially efficient relative alignment may be allowed, so that object handling device and plater device may be moved relative to each other with high precision.

[0045] In an embodiment, the calibration feature is configured to be at least one of movable, rotatable, floating. The flexibility (and efficiency) of the described device may be further increased, when the calibration feature itself can be moved (towards the object handling device) for the calibration process. In an example, the calibration feature may be arranged at the plater device and hence rotate together with said plater device. In another example, the calibration feature may comprise an associated drive unit to actively move the calibration feature itself. In yet another example, thecalibration feature may be arranged in a floating manner. Hereby, the object handling device may not be kept forceless in the plane during approaching, but the calibration feature may be kept forceless / floating in the plane, so that the object handling device is guided to the calibration position by aligning the calibration feature.

[0046] According to an aspect of the disclosure, there is described an analytic device, in particular a sample separation device, comprising the (sample) device as described above. In an embodiment, the analytic device is configured as a fluidic chromatography device, more in particular a high-performance liquid chromatography, HPLC, device.

[0047] In an embodiment, the method further comprises: rotating a plater device with respect to the object handling device, determining a cross-point, in particular two or more cross-points, between a radius of the plater device and a radius of the object handling device as a cross-calibration position, and calibrating the object handling device and / or the plater device based on the cross-calibration position (see e.g. Figures 7 and 8). Thereby, an efficient and relative alignment / calibration may be achieved. A rotation of the object handling device and the plater device may be in particular advantageous, when not every sample position can be reached by moving only the object handling device.

[0048] In a specific embodiment, the encoders of the object handling device and the plater device are initialized. To determine the offset of the encoders relative to each other, the object handling device and the plater device are aligned so that the object handling device is above the calibration feature of the plater device. Now the motors of the object handling device and the plater device are switched off and the object handling device is moved downwards until the object handling device and the plater device align with each other in the calibration feature. The encoders are now set to the value calculated for this position. To enable a more accurate calculation, another calibration feature is used at the same angular position but at a different radius. The measurement of the encoder positions is carried out as described above. From the resulting angles, the arm length of the object handling device can be determined, e.g. as follows: rarm = r2 - r1 (((sin a1 / sin [32)*(sin a1 / sin [31 )) / ((sin a2 / sin |32)-(sin a1 / sin [31))); wherein r2 > r1

[0049] In an embodiment, the sample separation device is configured as a fluidic chromatography device, more in particular a high-performance liquid chromatography, HPLC, device.

[0050] 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.

[0051] 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.

[0052] In analytical devices, specifically in liquid chromatography (in particular HPLC), it may be important to provide an accurate solvent flow, even in the case that specific properties of the solvent are not known or are not downloaded to the control unit of a analytical device.

[0053] Embodiments may be implemented in conventionally available HPLC systems, such as the analytical Agilent 1290 Infinity II LC system or the Agilent 1290 Infinity II Preparative LC / MSD system (both provided by the applicant Agilent Technologies - see www.agilent.com - which shall be incorporated herein by reference).

[0054] One embodiment of a sample separation apparatus comprises a pump having a pump 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. This pump may be configured to know (by means of operator's input, notification from another module of the instrument or similar) or elsewise derive solvent properties.

[0055] The sample separation unit of the sample separation apparatus preferably comprises a chromatographic column (see for instancehttp: / / en.wikipedia.org / wiki / Column_chromatography) providing a stationary phase. The column may be a glass or steel tube (for instance with a diameter from 50 pm to 5 mm and a length of 1 cm to 1 m) or a microfluidic column (as disclosed for instance in EP 1577012 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 at least partly 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 one at a time or at least not entirely simultaneously. During the entire chromatography process the eluent may 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, surface modified 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 (EBA). The stationary phases are usually finely ground powders or gels and / or are microporous for an increased surface.

[0056] The mobile phase (or eluent) can be a pure solvent or a mixture of different solvents (such as water and an organic solvent such as ACN, acetonitrile). It can be chosen for instance 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 or fractions of the fluidic sample can be separated efficiently. The mobile phase may comprise an organic solvent like for instance methanol or acetonitrile, often diluted with water. For gradient operation water and organic is delivered in separate bottles, 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.

[0057] A fluidic sample analyzed by a sample separation apparatus according to an exemplary embodiment of the disclosure may comprise but is not limited to 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.

[0058] The pressure, as generated by the fluid drive, in the mobile phase mayrange from 2-200 MPa (20 to 2000 bar), in particular 10-150 MPa (150 to 1500 bar), and more particular 50-120 MPa (500 to 1200 bar).

[0059] The sample separation apparatus, for instance an HPLC system, may further comprise a detector for detecting separated compounds of the fluidic sample, a fractionating unit for outputting separated compounds of the fluidic sample, or any combination thereof. For example, a fluorescence detector may be implemented.

[0060] In an embodiment, calibration of a robotic arm is done by moving (in XY direction) the arm towards a calibration feature, and then lowering (in Z-direction) the arm into the calibration feature while allowing the arm being moved in XY direction by the calibration feature. In a specific embodiment, the calibration feature is cone shaped thus providing the (fine) movement in XY direction.

[0061] In an embodiment, the turntable drive may be set forceless during the alignment procedure. In an embodiment, either drives of the robotic arm, the drive of the turntable or both drives are set forceless to allow the alignment procedure.

[0062] Embodiments of the disclosure can be partly or entirely embodied or supported by one or more suitable software programs, 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.

[0063] Other objects and many of the attendant advantages of embodiments of the present disclosure 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.BRIEF DESCRIPTION OF DRAWINGS

[0064] Figure 1 shows a liquid sample separation apparatus, particularly used in high performance liquid chromatography (HPLC), as an analytic device that comprises the (sampling) device, in accordance with embodiments of the present disclosure.

[0065] Figure 2 shows a sampling device of an analytic device with the object handling device and the calibration features, in accordance with embodiments of the present disclosure.

[0066] Figures 3 and 4 respectively show moving the object handling device towards the calibration feature and guiding the object handling device by the geometry of the calibration feature, in accordance with embodiments of the present disclosure.

[0067] Figures 5 and 6 respectively show moving the object handling device in a horizontal plane to a calibration feature of a plater device, in accordance with embodiments of the present disclosure.

[0068] Figure 7 shows a cross-point between a radius of the object handling device and a radius of the plater device, while Figure 8 shows two cross-points between the radii of said devices, in accordance with embodiments of the present disclosure.DETAILED DESCRIPTION OF THE DRAWINGS

[0069] The drawings are schematic.

[0070] Figure 1 depicts a general schematic of an analytical device 10 with a (sampling) device 100. A solvent (mobile phase) drive 20 (such as a pump) receives a solvent as the mobile phase from a solvent supply 25. The solvent drive 20 drives the mobile phase through a separating device 30 (such as a chromatographic column), which can be seen here the analytical domain of the device. A sample injector 40 (also referred to as sample introduction apparatus, sample dispatcher, etc.) is provided between the solvent 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 at a mixing point 45. 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.

[0071] The separating device 30 may comprise a stationary phase configured forseparating compounds of the sample fluid. Alternatively, the separating device 30 may be based on a different separation principle (e.g. field flow fractionation).

[0072] While the mobile phase can comprise one solvent only, it may also be mixed of plurality of solvents (solvent supply 25). Such mixing might be a low pressure mixing and provided upstream of the solvent drive 20, so that the solvent drive 20 already receives and pumps the mixed solvents as the mobile phase. Alternatively, the solvent drive 20 might comprise 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.

[0073] A data processing device (control device) 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 sample separation device 10 in order to receive information and / or control operation.

[0074] A fluidic sample is injected into an injection path 195 of the analytic device 10 through a needle seat 140. The needle seat 140 is connected (via the injection path 195) to a mixing point 45, where the sample is injected into a high-pressure path. The fluidic sample is handled by an object handling device 190, here a sample handling device 190, that takes the sample from a sample container 131 (here a sample vial), transports the sample to the needle seat 140, and injects the sample into the needle seat 140.

[0075] The object handling device 190 comprises an extension arm 178 that is connected at one extremity to a driving unit 128 with a first driving unit for the vertical movement (along Z), and a second drive unit for the horizontal movement (along XY). (schematically shown by arrows). At the other extremity, the extension arm 178 is coupled to a protruding part that comprises a sample needle 110. The sample needle 110 is hereby configured to be moved into the sample container 131 , intake the sample, and to be moved into the needle seat 140 for injecting the sample. A pusherdevice 115 surrounds the sample needle 110 for protection and for improved sample intake (pushes back the sample container after sample intake). Further, it isschematically shown, that the sample container 131 is arranged on a plater device 130.

[0076] Figure 2 shows a (sampling) device 100 of an analytic device 10 (see Figure 1 ) with an object handling device 190 and two calibration features 120, in accordance with embodiments of the present disclosure. The device 100 comprises a so-called (auto-) sampler, which is a space for preparing a (fluidic) sample for (chromatographic) analysis. The device 100 comprises a plater device 130 that is configured to accommodate a plurality of sample containers 131 in respective sample carriers 132.

[0077] The device 100 further comprises a sample handling device 190 to transport fluidic sample within the needle 110 from the sample plater device 130 to the needle seat 140. The sample handling device 190 comprises a moving / extension arm 178 that is controlled by drive system 128 to move the arm 178 in the horizontal and vertical direction. The moving arm 178 is coupled to the sample needle 110 and the pusher (or gripper) device 115 that surrounds the sample needle 110. The pusher device 115 comprises at the bottom part (here a disc) an opening 116 through which the needle 110 can be guided (in the Z-direction) during sample intake and sample injection.

[0078] Two calibration features 120 are located on the plater device 130 and are configured as cone-shaped structures for at least partially accommodating a protruding part (the sample needle 110 and / or the pusher device 115) of the object handling device 190. In order to perform a calibration process, said protruding part 110, 115 of the object handling device 190 is moved into the calibration feature 120 in an approaching direction Z, so that the calibration feature 120 guides the protruding part 1 10, 1 15, in a plane XY perpendicular to the approaching direction Z, to a calibration position during movement in the approaching direction Z. Thereby, at least one property (in particular a length of the extension arm 178) of the object handling device 190 in the plane perpendicular to the approaching direction is defined by or relative to the calibration position.

[0079] Figures 3A to 3C respectively show moving the object handling device 190 towards the calibration feature 120 and guiding the object handling device 190 by the geometry of the calibration feature 120, in accordance with embodiments of thepresent disclosure. It can be seen that the calibration feature 120 comprises a tapering structure that tapers in the direction away from the approaching protruding part 110, 115. The object handling device 190 has been moved in the plane to be positioned above the calibration feature 120 and is now moved down in the vertical direction z. Hereby, the object handling device 190 is kept forceless (floating) in the plane, so that the tapering geometry of the calibration feature 120 mechanically guides (forces) the (protruding part of the) object handling device 190 towards a calibration position down in the calibration volume.

[0080] In this example, the sample needle 110 is surrounded and protected by a pusher device 115. A pusher element 116 in form of a disc is here the lowest point of the protruding part 115. It can be seen that the pusher element 116 is located on the sidewall of the calibration feature 120. Accordingly, there is a misalignment between the object handling device 190 and the plater device 130 (that comprises here the calibration feature 120).

[0081] Figures 4A to 4C respectively shows guiding the object handling device 190 in the calibration feature (volume) 120 to a calibration position, in accordance with embodiments of the present disclosure. The object handling device 190 is moved down and it can be seen that the pusher element 116 has been moved along the tapering sidewalls of a cone-shaped calibration feature 120 towards the center / middle of the volume. This is possible, because the object handling device 190 is kept forceless in the plane and its moving direction is determined by the geometry of the calibration feature 120. Moving down further, the pusher element 116, and hence the object handling device 190, reaches the calibration position.

[0082] Figures 5 and 6 respectively show a top view on the device 100 while moving the object handling device 190 in a horizontal plane to a calibration feature 120 of a plater device 130, in accordance with embodiments of the present disclosure. It can be seen in the top view, that the plater device 130 comprises three trays, each configured to accommodate a sample carrier 132. In Figure 5, the object handling device 190 is moved in the plane towards the calibration feature 120. In Figure 6, the object handling device 190 is located above the calibration feature 190 and starts the calibration process by moving the protruding part 110, 115 down to the calibration feature 130 in the vertical direction.

[0083] Figure 7 shows a cross-point 121 between a radius of the object handling device 190 and a radius of the plater device 130, while Figure 8 shows two cross- points 121 a, 121 b between the radii of said devices 130, 190, in accordance with embodiments of the present disclosure. To determine the offset of respective encoders relative to each other, the object handling device 190 and the plater device 130 are aligned so that the object handling device 190 is above the calibration feature 120 of the plater device 130. Now the motors of the object handling device 190 and the plater device 130 are switched off and the object handling device 190 is moved downwards until the object handling device 190 and the plater device 130 align with each other in the calibration feature 120. The encoders are now set to the value calculated for this position. To enable a more accurate calculation, another calibration feature is used at the same angular position but at a different radius. The measurement of the encoder positions is carried out as described above.

[0084] It should be noted that the term “comprising” does not exclude other elements or features and the “a” or “an” does not exclude a plurality. Also elements described in association with different embodiments may be combined. It should also be noted that reference signs in the claims shall not be construed as limiting the scope of the claims.

[0085] Reference signs10 Analytic device20 Fluid drive25 Solvent supply30 Sample separation device40 Sample injector45 Mixing point50 Detector60 Fractionating unit70 Data processing device, control device100 Device, sampling device110 Sample accommodation unit, sample needle115 Pusher device116 Pusher element120 Calibration feature121 Cross-point128 Driving system130 Plater device131 Sample container 132 Sample carrier device140 Needle seat178 Transport arm190 Object handling device191 Coupling part 195 Injection path

Claims

CLAIMS1. A device (100), preferably a sampling device (100) for an analytic device (10), the device (100) comprising: an object handling device (190), in particular a robotic arm, configured for handling an object to be handled, in particular a sample such as an analytical sample; a calibration feature (120) configured for at least partially accommodating a protruding part (110, 115) of the object handling device (190); and a control device (70), configured to: move the protruding part (1 10, 115) of the object handling device (190) into the calibration feature (120) in an approaching direction (Z), so that the calibration feature (120) guides the protruding part (110, 115), in a plane (XY) perpendicular to the approaching direction (Z), to a calibration position during movement in the approaching direction (Z), so that at least one property of the object handling device (190) in the plane (XY) perpendicular to the approaching direction (Z) is defined by or relative to the calibration position.

2. The device (100) according to claim 1 , wherein the control device (70) is further configured to: keep the object handling device (190) substantially forceless in the plane (XY) perpendicular to the approaching direction (Z), when the protruding part (1 10, 115) of the object handling device (190) is guided at least partially into the calibration feature (130) to the calibration position.

3. The device (100) according to claim 1 or 2, wherein the geometry of the calibration feature (130) is configured so that the protruding part (110, 115) of the object handling device (190) is guided mechanically at least partially into the calibration feature (120), in particular into an accommodation volume of the calibration feature (120).

4. The device (100) according to one of the preceding claims, wherein the calibration feature (120) comprises a tapering shape, wherein the tapering direction is facing away from the object handling device (190), and wherein the tapering shape is configured to guide the protruding part (110, 1 15) of the object handling device (190) to the calibration position.

5. The device (100) according to claim 4, wherein the tapering shape comprises at least one of a cone, a pyramid, a rectangle, a quadrangle, a hemisphere, polyangular.

6. The device (100) according to one of the preceding claims, wherein the object handling device (190) is movable in the approaching direction (Z) by a first drive unit and in the plane (XY) perpendicular to the approaching direction (Z) by a second drive unit, and wherein, during moving, the first drive unit is active, in particular supported by electric current, while the second drive unit is essentially inactive, in particular not supported by electric current.

7. The device (100) according to one of the preceding claims, wherein the protruding part (110, 115) of the object handling device (190) comprises a sample needle (110) or a dummy sample needle or a needle substitution device.

8. The device (100) according to one of the preceding claims, wherein the protruding part (110, 115) of the object handling device (190) comprises a pusher device (115), in particular wherein the pusher device (115) is configured to be arranged at least partially around a sample needle (110), more in particular wherein the pusher device (115) comprises a pusher element (116) with an opening throughwhich the sample needle (110) can be guided.

9. The device (100) according to one of the preceding claims, wherein the object handling device (190) comprises a transport arm (178), in particular with a length L to be calibrated, and a coupling part (191 ), connected to the transport arm (178), and configured to couple with the protruding part (110, 115).

10. The device (100) according to one of the preceding claims, further comprising: a plater device (130), in particular a sample plater device, configured to accommodate at least one object, in particular a sample carrier device (132) and / or at least one sample container (131 ).11 . The device (100) according to claim 10, wherein the plater device (130) is configured to be rotatable in the plane (XY) perpendicular to the approaching direction (Z), in particular rotatable in said plane (XY).

12. The device (100) according to claim 10 or 11 , wherein one or more of the calibration feature (120) are arranged at the plater device (130).

13. The device (100) according to one of claims 10 to 12, wherein the control device (70) is further configured to at least one of the following steps to define the at least one property of the object handling device (190): move, in particular rotate, the object handling device (190) with respect to the plater device (130); move, in particular rotate, the plater device (130) with respect to the object handling device (190); move, in particular rotate, the object handling device (190) and the plater device (130) with respect to each other;move the object handling device (190) towards the plater device (130); move the plater device (130) towards the object handling device (190); move the object handling device (190) and the plater device (130) towards each other.

14. The device (100) according to one of claims 10 to 13, wherein the control device (70) is configured to keep the plater device (130) essentially forceless in the plane (XY) perpendicular to the approaching direction (Z) during moving, and / or wherein the plater device (130) comprises a plater drive unit, and wherein the control device (70) is configured to essentially inactivate the plater drive unit during moving.

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

16. An analytic device (10), in particular a sample separation device, comprising the device (100) of one of the preceding claims.

17. The analytic device (100) according to claim 16, configured as a fluidic chromatography device, more in particular a high- performance liquid chromatography, HPLC, device.

18. A method of defining at least one property of an object handling device (190), the method comprising: moving a protruding part (110, 115) of the object handling device (190) into a calibration feature (120) in an approaching direction (Z); thereby guiding, by the calibration feature (120), the protruding part (110, 115), in a plane (XY) perpendicular to the approaching direction (Z), to a calibration position; and defining the at least one property of the object handling device (190) in the plane(XY) perpendicular to the approaching direction (Z) by or relative to the calibration position.

19. The method according to claim 18, further comprising: rotating a plater device (130) with respect to the object handling device (190); determining a cross-point (121 ), in particular two or more cross-points, between a radius of the plater device (130) and a radius of the object handling device (190) as a cross-calibration position; and calibrating the object handling device (190) and / or the plater device (130) based on the cross-calibration position.

20. Using a calibration feature (120) with a tapering shape to mechanically guide an approaching part (110, 115) of a sample handling device (190) into a calibration position.

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