Support and fixing device for chromatography columns

Abstract

The present invention provides a support and fixing device for chromatography columns used or operated by a liquid handling or pipetting robot, and an automated liquid handling system having the same. [Solution] The support fixture 10 for a chromatography column operated by a liquid handling robot includes a frame 14 and lids 22a, 22b. The frame has a base and column stands 16a, 16b extending upward from the base. The frame also includes a hole extending vertically between the base and the top of the column stands. The lids are movably mounted on the top of the column stands and have openings 24a, 24b that are axially aligned with the hole in the frame. The lids are movable between an open position configured to allow a chromatography column to be inserted into the hole and a closed position configured to fix the chromatography column in the hole.

Description

Technical Field

[0001] Cross - Reference to Related Applications This application claims priority to U.S. Provisional Application No. 63 / 147,116, filed on February 8, 2021. The disclosure of this prior application is considered a part of the disclosure of this application and is hereby incorporated by reference in its entirety.

[0002] This disclosure relates to chromatography column supports, such as stands and racks, for holding chromatography columns used by liquid handlers in a laboratory.

Background Art

[0003] Liquid handling or pipetting robots are widely used to run or manipulate chromatography columns, such as in micro - scale biological process development. Liquid handling robots automate tasks in the operation of chromatography columns to reduce the risk of process errors. Generally, liquid handling robots pipette liquid into a set of chromatography columns to enable sample collection below the columns. Chromatography columns are typically held in an array plate supported above a well plate. The well plate is used to collect samples from columns suspended above it. During the execution of pipetting tasks, the pipetting tip or needle is repeatedly inserted into and removed from the chromatography column.

[0004] If the pipetting tip is not aligned, inserting the pipetting tip will Errors may occur. Also, the pipetting tip may come off with a chromatographic color. When removing it from the array, a mechanical error may occur, causing the column to detach from the array plate. Alternatively, the column may shift position within the array plate. More specifically, The frictional force resisting the tip being pulled out from the top of the column causes the column to move away from the array. The friction or other forces holding the column within the array plate may be greater than the column itself. They may detach momentarily or completely. These errors can damage the tip and column. This could potentially spoil the collected samples.

[0005] To avoid errors such as column misalignment or column detachment, liquid handling Program the robot to display a user prompt and indicate if there is a problem or otherwise Confirmation from a human operator before and after the operational steps where such errors tend to occur. In some cases, approval may be required. Human intervention and monitoring may be necessary for tasks performed by robots. Therefore, the liquid handling robot needs to perform these tasks during working hours. Due to these factors, the efficiency of robot systems is significantly reduced, and robots operate outside of human working hours. It becomes impossible to do so. [Overview of the project]

[0006] This disclosure describes how liquid handling or pipetting robots can be used or A support and fixing device for the chromatography column being operated is provided, and such support and fixing Related automated liquid handling systems with fittings are also provided. The support fixtures are rapid Pre-packed chromatography microcavities used for the development of biological processes Designed to mate with a series of chromatography columns such as those from Lamb. The fixture is installed in station structures such as workstations for liquid handling robots. In contrast, to ensure the chromatography column is securely held, the chromatography column is, Maintain precise alignment with the end-effector operated by the robot. In some examples... The support fixture ensures that the chromatography column is fitted in a securely aligned manner. It includes a fitting feature that locks in place, thereby preventing the tip from separating from the chromatography column. When withdrawn, the chromatography column is disengaged from the support fixture. This prevents the mating feature from being detected by a laboratory technician using chromatography without the use of tools or other devices. This snap-fit ​​connector allows for quick unmating and removal of the feed column. Furthermore, some examples of support fixtures may leak from pressurized chromatography columns. By the robot-driven tip, waste liquid may be squeezed out or squeezed out. This allows for the incorporation of a drainage feature to collect excess liquid that is dispensed.

[0007] According to one aspect of this disclosure, a chromatograph operated by a liquid handling robot The support fixture for the feed column includes a frame and a cover. The frame has a base and extends upwards from the base. It has a column stand that extends in the direction. The frame also has a base and the top of the column stand. It includes a hole that extends vertically between them. The lid is movably mounted on top of the column stand. The lid is configured in an open position so that a chromatography column can be inserted into the hole. , and is configured to move between a closed position where a chromatography column is fixed in the hole It can do so. In the closed position, the opening in the lid is axially aligned with the hole in the frame and is configured to receive, for example, a pipetting tip or a needle.

[0008] Embodiments of the present disclosure may include one or more of the following optional features. In some embodiments, the upper part of the column stand includes a surrounding surface adjacent to at least one of the holes, and the surrounding surface is configured to support the color of the chromatography column inserted into the hole. Also, in some embodiments, the frame includes a seat that protrudes into the lower part of the hole to support the bottom of the chromatography column inserted into the hole. In some examples, the hole has a continuous inner surface that extends between the surrounding surface and the seat disposed in the lower part of the hole. In some embodiments, the hole is provided as a set of holes arranged in a row across a column stand, such as at least 8 holes in a row.

[0009] In some examples, the frame has attachment features for attaching the support fixture to the workbench, such as fitting with a locking mechanism on a bridge stand that suspends the support fixture above a well plate. For example, the base of the frame may include a horizontal slot that fits with a locking mechanism on the bridge stand.

[0010] In a further embodiment, the lid includes a lower surface that surrounds at least one of the openings, and in the state where the lid is in the closed position, the lower surface contacts the color of the chromatography column in the It is configured to do so. Also, in some examples, the lid is attached to the top of the column stand. The hinge connection is pivotably coupled and configured to pivot between an open position and a closed position. The lid also snaps onto the column stand when it moves to the closed position. It may include a fitting feature.

[0011] In some examples, each hole has a bottom hole within the base of the frame. The liquid in the chromatography column passes through the bottom hole and is positioned below the support fixture. It is configured to dispense into collection plates such as well plates. Each of them may be configured to receive the leading edge of the chromatography column. In some embodiments, each hole has an enlarged upper portion within the column stand. The enlarged upper portion is positioned above the inserted chromatography column. It is designed to prevent interference with the bell or mark. In some examples, the size of the hole is, It is set to accommodate chromatography columns with a volume of 200 μl or 600 μl. It is being done.

[0012] In a further example, the frame has a second column extending upward from the base and ending at its top. Includes the stand. The second column stand hangs between the base and the top of the second column stand. It includes a second set of holes extending perpendicularly. In some examples, the size of the second set of holes is equal to the volume. Chromatographs with wells of different sizes than the first set, such as 200 μl or 600 μl. It is set to support the column. In some embodiments, the second lid is the The second lid is movably mounted on top of the second column stand. The second lid has a second set of holes. It has an opening that is aligned in the axial direction.

[0013] In further embodiments, the frame is between two separate column stands, for example, the columns This is a drain reservoir located adjacent to the tando. In some examples, the lid is located at the opening. It has a sloping surface that descends toward the drain reservoir, and as a result, the chromatograph inside the hole Liquid leaking from the top opening of one of the rams flows down the slope and into the drain reservoir. In some cases, the top of the column stand also directs the waste liquid to a drain reservoir. It has a channel that extends from the hole towards the drain reservoir.

[0014] According to another aspect of this disclosure, an automated liquid handling system includes a stay equipped with a workbench. It has a structure. The well plate is supported on a workbench, and a liquid handling robot It includes an arm suspended above the workbench, and the arm is configured to dispense liquid. It has a set of tip sections. The liquid handling robot also has an arm that is positioned relative to the workbench. Includes a controller configured to control movement. Support fixtures are located on the well plate. It is fixed to the workbench in an upper position. The support fixture consists of two swivelably connected parts. It consists of two parts and a cylindrical cavity extending within the support and fixing device, which works with the chromatography column. Includes a cylindrical cavity configured to be held perpendicular to the base. Two support fixtures With the parts rotated relative to each other in the open position, the cylindrical cavity is used for inserting the chromatography column. Alternatively, it is exposed for removal. The two parts of the support fixture are rotated relative to each other in the closed position. In this configuration, the upper part of the support fixture fits with the collar of the chromatography column, and the chromatography Secure the feed column within the support fixture. With the support fixture in the closed position, the control Ra moves the tip assembly to a position above the support fixture, and the C is held inside the support fixture. It extends into the chromatography column and dispenses the desired amount of liquid into the chromatography column. Then, the chromatography column is used to deliver the liquid into the well plate, and the support fixture is used. Without unfitting the chromatography column, It is designed to allow the tip assembly to be pulled out.

[0015] In yet another embodiment, a chromatograph operated by a liquid handling robot The support fixture for the fee column consists of a first piece and a second piece that are rotatably connected to each other. This includes a support fixture which is a cylindrical cavity extending within the support fixture, and chromatography - A cylinder configured to hold the column perpendicular to the liquid handling robot. It includes a cavity. With the two parts of the support fixture rotated relative to each other in the open position, the cylindrical cavity is Exposed for insertion or removal of the chromatography column. Two parts of the support fixture. With the pieces rotated relative to each other in the closed position, the upper part of the support fixture is positioned relative to the chromatography column. The color is fitted into the support fixture to secure the chromatography column.

[0016] These embodiments may include one or more of the following optional features: several In some embodiments, the two parts snap together in the closed position. In the example, the two parts of the support fixture are a connecting surface, oriented vertically, and a cylindrical cavity It is mounted along a connecting surface that crosses along the length. In other examples, the first of the support fixtures The part includes a frame, and the second part of the support fixture includes a lid. The frame has a base and a base It may have a column stand extending upward from it, the column stand including a cylindrical cavity The lid may be swivelably mounted on top of the column stand, and the lid is cylindrical. It may include an opening that is aligned with the cavity in the axial direction. Furthermore, the lid may be in the closed position. Under certain conditions, the underside of the lid may come into contact with the color of the chromatography column inside the cylindrical cavity. good.

[0017] In some embodiments, the frame is a seat that protrudes into the lower part of the cylindrical cavity. , including a seat there for supporting the bottom of the chromatography column. Also, several In this example, the top of the column stand includes the surrounding surface adjacent to the cylindrical cavity, and the surrounding surface is made of black. It is configured to support the color of the matrix column. In some examples, circles Each cylindrical cavity has a continuous inner surface that extends between the surrounding surface and the seat.

[0018] In a further embodiment, the first part of the support fixture is a frame, comprising a base and a first A column stand extending upward from the base, and a second column stand spaced apart from the first column stand. It includes a frame having a column stand extending upward from the base. In some examples, The two column stands are designed to support chromatography columns of different sizes. The frame may have different sets of cylindrical cavities of varying sizes. It may include a drainage reservoir positioned between the stands.

[0019] This embodiment may include one or more of the following optional features: several actual In this method of installation, the first part of the support and fixing device comprises a base and a column stand extending upward from the base. The column stand generally includes a frame having such a cylindrical cavity. In the example, the second piece of the support fixture is rotatably mounted on the top of the column stand. It includes a lid, which has an opening aligned axially with the cylindrical cavity.

[0020] Details of one or more embodiments of this disclosure are described in the accompanying drawings and the following description. These aspects and embodiments, as well as other combinations of those described above, are examples of how the subject can be implemented. The present invention demonstrates that all of these methods fall within the scope of the claims. Other aspects, features, and advantages are intended to be described and drawn in the description and drawings, as well as in the claims. This is clear from the scope. [Brief explanation of the drawing]

[0021] [Figure 1] This is a perspective view of a typical station for an automated liquid handling system. [Figure 1A] Figure 1 shows an enlarged perspective view of the area of ​​the automated liquid handling system shown in area A. [Figure 2] A perspective view of an example of a bridge stand for supporting a chromatography column operated by a liquid handling robot. [Figure 3] This is a perspective view of an example of a chromatography column being operated by a liquid handling robot. [Figure 4] This is an overhead perspective view of an example of a support fixture mounted on a bridge stand. [Figure 5] Figure 4 shows another upper perspective view of the support fixture attached to the bridge stand. [Figure 6] This is an upward perspective view of the support fixture shown in Figure 4, removed from the bridge stand, with the lid in the closed position. [Figure 7] Figure 6 is an upward perspective view of the support and fixing device, showing the lid in the open position. [Figure 8] Figure 6 is an overhead perspective view of a support fixture showing a chromatography column inserted into a column stand with the lid open. [Figure 9A] Figure 8 is an upper perspective view of the support and fixing device, showing the column stand with the lid open. [Figure 9B] Figure 9A is an upward perspective view of the support and fixing device, showing the lid in the closed position. [Figure 10] Figure 6 is a plan view of the support fixture, showing a typical chromatography column inserted into a column stand with the lid open. [Figure 11] Figure 6 is a cross-sectional view of the support fixture, showing a chromatography column inserted into the column stand with the lid closed. [Figure 12] This is another cross-sectional view of the support and fixing device shown in Figure 11. [Figure 13] This is an overhead perspective view of another example of a support fixture supported by an array plate suspended above a well plate. [Figure 14] Figure 13 is an enlarged perspective view of the support fixture, showing the chromatography column held within the support fixture. [Modes for carrying out the invention]

[0022] Similar reference symbols in various drawings indicate similar components.

[0023] Next, with reference to the drawings and the exemplary embodiments shown therein, an automated liquid handling system TEM100 (Figure 1) utilizes or manipulates a chromatography column for rapid microscopic analysis. Perform chromatography experiments, such as microcolumns, for the development of simulated biological processes. The automated liquid handling system 100 is a station structure that provides a workbench 104. The workbench 104, including 102, generally supports experimental equipment and apparatus for the purposes of this disclosure. This refers to the work surface for which the work is performed. Therefore, the workbench 104 is an integrated part of the station structure. It may be a surface or platform, or a laboratory table, countertop, etc. P, or other surfaces, which are generally used by station structures. This is also acceptable. As shown in the examples in Figures 1 and 1A, the workbench 104 is used for containers and other laboratory equipment. For example, it is configured to support microplates, well plates, tubes, etc. Furthermore, the workbench is integrated into System 100, along with a shaker, incubator, etc. It may also include other devices. For example, as shown in Figure 3, the well plate 105 is Supported by a workbench 104 below the chromatography column 12, the column 12 Then collect samples.

[0024] The station structure 102 of the automatic liquid handling system 100 is made of different kinds of real Even though they come in various sizes and designs to suit laboratory testing, capacity, and requirements, Good. As shown in Figure 1, the station structure 102 surrounds the workbench 104 and has a transparent cover. - Includes a frame supporting 107. The transparent cover 107 protects dust and contaminants from the work. To prevent interference with the equipment and laboratory instruments located on the table 104 and the workbench 104. Transparent Cover 107 also functions as a safety barrier to prevent injuries during operation. Transparent cover 1 07 or its front part allows the user to prepare the experiment on the workbench 10 before the system is put into operation. To allow access to 4, it may be raised or lowered with the help of a pneumatic cylinder or similar device.

[0025] The liquid handling system 100 also controls the operation of the chromatography column 12. Includes a liquid handling robot 106 that automates the task. The dispensing robot 106 has a liquid handler with means for aspirating and dispensing fluids. Gantry with at least one manipulator, such as the LiHa Arm 108. It may include a re-robot. In further embodiments, the robot arm 108 is multi-related. Supported by various different structures and mechanisms such as joint robot arm assemblies and It may be operated. As shown in Figures 1 and 3, the arm 1 of the liquid handling robot 106 Unit 08 is suspended and operates to move relative to and on the workbench 104. It is possible. Furthermore, the arm 108 has a tip configured to aspirate and dispense liquid. Includes set 109. The liquid handling robot 106 moves the arm 108 relative to the workbench. The program controls the movement and controls the independent or simultaneous movement of the tip portion 109. Includes controllers that are operated in a manner or otherwise.

[0026] Furthermore, as shown in Figures 1 and 3, eight separate tip portions 109 are located at the bottom of the arm 108. It is attached by a tapered nut, and the tip 109 is fixed to the arm 108. Each of the tip sections 109 extends vertically downward from the arm 108 toward the workbench 104. Includes a long, slender tube. The distal end of the tip 109 may be tapered, or In other ways, liquid containers such as the chromatography column 12 illustrated and described herein It may be configured to be inserted into a container or laboratory apparatus. In further embodiments, The robot arm has more than 1, 8, 16, 48, 64, 96, or 384 endpieces. It may have many or a few tip portions 109, and the tip portions 109 may be arranged in various other ways It can also be attached to arm 108.

[0027] As shown in Figures 2 and 3, the chromatography column 12 is connected to the bridge stand 103 It is simply placed within the array plate 101 supported by the bridge stand 10. Below 3, plate carrier 180 is mounted on shuttle 182. L182 collects samples from the collection or from the column in well plate 105. To achieve this, the plate can be moved horizontally along its longitudinal axis. Specifically, The chatter 182 moves the well plate 105 along the column of plate 105. A portion of the liquid dispensed from 12 is collected. As shown in Figure 3, the liquid handling robot... T106 involves transferring the liquid into the chromatography column 12 by pipette or by other means. Dispense the liquid sample into the column, and the liquid sample will flow downwards through the column. It is collected in the plate 105. The support fixture 10 is the workpiece of the liquid handling robot. Reliably maintain the chromatography column for station structures such as chromatograph stations. To ensure accuracy, the chromatography column is precisely controlled by the robot at its tip. Maintain precise alignment.

[0028] To support the chromatography column 12 in an automated liquid handling system Errors and other issues that may arise from directly using the array plate 101 (Figures 2 and 3). To solve the problem (for example, poor alignment between column 12 and tip 109), The chromatography column 12 is arranged as shown in the examples in Figures 4-14, and further as described herein. As disclosed, it is fixed by support fixtures 10 and 110. Support fixtures 10 and 110 are , such as the bridge stand 103 shown in Figures 4 and 5, located above the well plate 105. It is fixed to the workbench 104. As shown in Figure 6, the support fixtures 10 and 110 are generally The first parts 14, 114 and the second parts 22a, 22b are connected to each other so as to be rotatable. Includes 122. Support fixtures 10, 110 also work the chromatography column 12. To fix it vertically to the base 104 and to fully house it, the support fixtures 10 and 110 are Includes an elongated cylindrical cavity 20. First part pieces 14, 114 and second part pieces of the support fixtures 10, 110 With the parts 22a, 22b, and 122 rotated relative to each other to the open position 26, as shown in Figures 7 and 9A. As shown, the cylindrical cavity 20 is for inserting or removing the chromatography column 12. It is exposed. Furthermore, the first parts 14, 114 and the second parts of the support fixtures 10, 110 With 22a, 22b, and 122 rotated relative to each other towards the closed position 28, as shown in Figures 6 and 9B. The chromatography column 12 is fixed within a support fixture.

[0029] Next, referring to Figures 4-12, the support fixture 10 is attached to the frame 14 and the frame 14. It has two removable covers 22a and 22b, and is fitted in the closed position 28 (Figure 6). When combined, the chromatography column 12 is fixed and housed within the support fixture 10. When the lock is released or removed by other means and is in the open position 26 (Figure 7), the chroma The frame 14 allows for the insertion and removal of the tography column 12. The frame 14 has a base 17 and and includes at least one column stand 16a, 16b extending upward from the base 17. The column stand or stand 16a, 16b is injection molded as shown in Figures 4-12. Alternatively, fixings can be manufactured using 3D printing processes (such as fused deposition modeling), etc. The base 17 may be formed integrally as a single piece. Alternatively, stands 16a and 16b can be fixed using fasteners and / or adhesives. Attached to the base 17 by another method, to the frame 14 of the support fixture 10, during system operation A rigid support for fixing the chromatography column 12 to the station structure 102 It is also understood that providing a structural element is acceptable.

[0030] As shown in Figures 6 and 7, the frame 14 is at opposite longitudinal ends of the frame 14 It has two column stands 16a and 16b that extend integrally upward. The dimensions in the hand direction are the longitudinal dimensions of the well plate 105 and the shuttle 182 and corresponding It is referenced to roughly correspond to its longitudinal movement on the track (Figure 3). Stands 16a and 16b are each sized to accommodate the chromatography column 12. It includes a cut hole or cylindrical cavity 20. The cylindrical cavity 20 has eight as shown in Figure 7. The hollow rows are arranged in a single horizontal line across the individual column stands 16a and 16b. The cylindrical cavities 20a and 20b can be grouped together. The lids 22a and 22b are columnar The tops of the arms 16a and 16b are rotatably mounted, and the openings 24a and 24b are respectively It extends through the thickness of each lid 22a, 22b and is aligned with the cylindrical cavity 20. This includes openings 24a and 24b. This is because when the lids 22a and 22b are in the closed position 28 The tip 109 of the liquid handling robot 106 is held inside the cylindrical cavity 20. The rhomography column 12 can be accessed. The openings 24a and 24b are shown in Figure As shown in 6, it is a circular hole aligned in the axial direction with the cylindrical cavity 20. The openings 24a and 24b inside the lids 22a and 22b may be of different shapes, or a single hole may be Alternatively, they could be interconnected as slots.

[0031] Furthermore, as shown in Figures 3-5, the frame 14 of the support fixture 10 is located on the workbench 104. The well plate 10 is supported by a plate carrier mounted on the shuttle. It is attached to a bridge stand 103 that suspends the support fixture 10 above 5. To secure the fastener 10 to the bridge stand 103, the frame 14 supports the fastener. It may have mounting features for attaching to a workbench. As shown in Figures 4-7, The base 17 of the frame 14 is a locking mechanism on the bridge stand 103, as shown in Figure 4. It has a mounting feature 59 configured to engage with mechanism 184. Mounting feature 5 9 is a T-shaped slot extending upward from the bottom surface of the base 17, and the bridge stand 10 Includes a T-shaped slot with a horizontal portion that engages with the locking mechanism 184 on 3.

[0032] As shown in Figures 6 and 7, the column stands 16a and 16b are chromatographs of the corresponding size. The tography columns 12 are of different sizes to accommodate each of them. Specifically, see Figure As shown in 9A, 9B, and 11, one column stand 16a extends vertically from the base 17. In that direction, it extends to a greater height than the other column stand 16b. Therefore, The taller column stand 16a is larger than the other column stand 16b (i.e., longer i) A set of cylindrical cavities 20a sized for a set of chromatography columns 12a The other column stand 16b has a smaller (i.e., shorter) chromatograph. It has a set of shallower cylindrical cavities 20b corresponding to a set of columns 12b. Other examples The cavities 20a and 20b accommodate the chromatography columns 12 having different diameters. To that end, they may have different diameters. Furthermore, as shown in Figure 11, the column stand The sizes of cavity 16a and cylindrical cavity 20a are the same as those of a chromatography column with a volume of 600 μl. It is set to hold 12a, and the size of the column stand 16b and cylindrical cavity 20b is It is set to hold a chromatography column 12b with a volume of 200 μl. In the following example, column stands 16a and 16b are used for chromatography with the same size settings. Columns may be sized to accommodate various different sizes. It is conceivable that any volume would be acceptable.

[0033] As shown in Figure 7, the covers 22a and 22b are located at the opposing longitudinal ends of the support fixture 10. In this case, the hinge between the outer edges of the lids 22a and 22b and the upper edges of the column stands 16a and 16b The hinge connection 50 is pivoted to the open position 26 around the hinge connection 50. 2b is configured to be able to rotate between an open position 26 (Figure 7) and a closed position 28 (Figure 6). As shown in Figure 7, the lids 22a and 22b are used by the experimental technician to access the chromatography column. When inserting or removing, they remain connected to the frame and do not interfere with each other. They rotate so that they move away from each other as they move toward the open position 26. The fastening connection is between the openings 24a, 24b and cylindrical cavities 20a, 20b within the lids 22a, 22b. This helps maintain precise alignment with chromatography, and at the same time, allows experimental technicians to perform chromatography. Assembly or other processes that may reduce the efficiency of loading and unloading column 12 No task is required. Furthermore, the hinge connection part 50 is a living hinge as shown in Figures 6-8. Between frame 14 and lids 22a and 22b, such as at the gap or snap-fit ​​hinge connection. It may be formed integrally with the other, or it may be a different type of hinge such as a pin and barrel hinge. It is also acceptable. Furthermore, in further examples, the hinge connection is on the alternating sides of the lids 22a and 22b. Alternatively, to make the lids 22a and 22b completely removable, snaps may be used. It is conceivable that this could be replaced with a releasable mating connection such as a push-fit connection.

[0034] Furthermore, as shown in Figures 6-11, the lids 22a and 22b are also in the closed position. When moved to 28, the locking mechanism removably fits into column stands 16a and 16b. It may also include element 52. The top of the column stands 16a and 16b is a lid 22a. It may also include a corresponding mating element 54 that mates with the locking element 52 on 22b. In the example shown, the locking element 52 and the mating element 54 work together to form a snap-fit ​​interface. - Provides a face. Snap-fit ​​connection between locking element 52 and mating element 54. Next, the lids 22a and 22b are held in the closed position 28, and the chromatography column 12 is held in the closed position 2 2a and 22b are designed to prevent them from opening by pulling them. Opening in this way is... For example, during the operation of the liquid handling system 100, the chromatography column 12 This is due to the frictional force of the tip portion 109 that is pulled upward from the upper opening 38 (Figure 8).

[0035] As shown in Figures 9A, 9B, and 10, the locking element 52 is located inside the lids 22a and 22b. Tab members 56 positioned on the edge and protruding downward when the lids 22a and 22b are in the closed position 28 The tab members 56 each extend longitudinally from the inner edges of the column stands 16a and 16b. The lower edge of the protruding fitting element 54 is received in a cantilever manner or snapped to it. Includes fasteners 58 designed to fit. Tab members 56 are attached to lids 22a, 22 A narrowed portion 6 at the connection interface with b helps to enable the elastic flexibility of the tab member 56. It may include 0 (Figure 11). In the closed position 28, the tab member 56 extends beyond the fitting element 54. It extends downward and ends at the distal portion 62 of the tab member, which provides access to the user's finger. The user manually pulls the tab member 56, and the fitted column stands 16a, 16b When you separate them and release the snap-fit ​​connection, the tab member 56 elastically It is designed to bend. The tab member 56 also fits with the user's tab member 56. It may also include friction features such as ribs 57, which are used to assist in the fitting process. When the lids 22a and 22b rotate toward the closed position 28, the distal portion 62 of the tab member 56 The tab portion is curved or angled, and a downward force is applied to the lids 22a and 22b. The material 56 bends past the mating element 54, and the fastener 58 snaps into place with the mating element 54. You may do so.

[0036] In addition to or instead of the locking element 52 and / or mating element 54, It may be configured to provide a sliding lock interface. At least one of the locking element 52 and / or mating element 54 is connected to frame 1 It translates along the lateral direction of 4 to selectively engage and disengage. For example, a locking mechanism Element 52 is positioned laterally from the fitting element 54 (i.e., along the longitudinal dimension). Move to the first unlocked position (not aligned) and open the lids 22a and 22b. When moving from position 26 to the closed position 28, the locking element 52 passes alongside the mating element 54. The position may be changed as follows. With the lid in the closed position 28, the locking element 52 is moved to the first position It is translated laterally from the unlocked position to the second locked position. In the locked position, The fitting 58 is positioned directly below the fitting element 54, and the fitting element 54 is adjacent to the constricted portion 60. It is received. To unlock the lids 22a and 22b, move the locking element 52 laterally. By returning to the first unlocked position along the way, the lids 22a and 22b move from the closed position 28 to the open position 26 When moving to the next position, the locking element 52 is allowed to pass alongside the mating element 54. Using another example of a long, ride-type interface, the lids 22a and 22b are fixed in the closed position 28. That's fine. For example, a sliding pin.

[0037] Also, as shown in Figures 11 and 12, with the lids 22a and 22b in the closed position 28, lid 2 The lower surface 63 of 2a is the color of the chromatography column 12 in the cylindrical cavities 20a and 20b. It comes into contact with 44. Similarly, the tops of the column stands 16a and 16b are shown, for example, in Figure 9A. Thus, it includes a surrounding surface 64 adjacent to the upper ends of the cylindrical cavities 20a and 20b. The surrounding surface 64 is The lower surface of the color 44 of the chromatography column 12 may be supported. Specifically, the chromatography column 12 is radially positioned within the lower portions of the cylindrical cavities 20a and 20b. Supported by the seat portion 66 of the base 17 of the frame 14 which protrudes in the direction, the insert is located therein The bottom 32 of the chromatography column 12 may be supported by holes or cylindrical cavities 20a, 2 0b may have a continuous inner surface 68 extending between the surrounding surface 64 and the seat portion 66.

[0038] Furthermore, as shown in Figures 11 and 12, cylindrical cavities 20a and 20b are, respectively, frame 1 The base 17 of 4 has a bottom hole 70, which is surrounded and shown by, for example, a seat 66. The bottom hole 70 allows the liquid in the chromatography column 12 to pass through the support fixture. The device is configured to dispense into a well plate located below the holding and fixing device 10. When the tip of the chromatography column 12 is inserted into the cylindrical cavities 20a and 20b In addition, it may extend through the bottom hole 70. (See Figures 11 and 12 for cylindrical cavities 20a and 20b) Each of these is a label or placed on top of the inserted chromatography column 12. It also has an enlarged upper portion 71 configured to prevent interference with the mark.

[0039] During the operation of the liquid handling system 100, the liquid flows into the chromatography column 12 Leakage may occur from the uppermost opening 38, or from the tip 109 in any other way. It may drip. Frame 14 has a drain reservoir 34 for collecting such waste liquid. It may include. Referring again to Figures 6-10, the drain reservoir 34 is located in column stand 1. It is located adjacent to and between 6a and 16b. The drainage reservoir 34 is a long structure that surrounds the surface of the low basin. Because it includes a containment barrier in the direction of movement, the liquid accumulated on the surface of the low basin is discharged into the drainage reservoir 34. It does not leak out. The drain reservoir 34 collects the fluid, for example, as shown in Figures 4 and 5. Located at the bottom of the drain reservoir 34, configured to dispense into waste tray 188. It may include drains such as openings.

[0040] To guide the fluid to the drain reservoir 34, the lids 22a and 22b are located at the openings 24a and 24b. This includes an inclined surface 36 (Figure 9B) that descends toward the drain reservoir 34 in and around it, As a result, the top of one of the chromatography columns 12 in the cylindrical cavities 20a and 20b The liquid leaking from the opening 38 flows down the inclined surface 36 towards the drain reservoir 34, and there It goes in. The inclined surface 36 of the lid 22a shown in Figure 9B is substantially flat, and the hinge connection part 50 It extends from the outer edge 37a to the inner edge 37b. Also, around the column stands 16a and 16b. The enclosure 64 (Figures 9A, 9B, and 10) has lids 22a and 22b in the closed position 28 (Figure 9B). It connects at least partially to the lower surface. Furthermore, as shown in Figure 9A, channel 40 is surrounding It is positioned on surface 64 and extends from cylindrical cavities 20a and 20b toward the drain reservoir 34 there The channel 40 is configured to guide the fluid into the drain reservoir 34. The lower surfaces of the lids 22a and 22b also have an upper circumference, as shown in Figures 9B and 10, for example. It may include a corresponding channel 41 that interconnects with channel 40 within the enclosure 64.

[0041] With lids 22a and 22b in the closed position, the support and fixing device 10 is positioned on the chromatography column 1 When 2 is housed, the controller positions the tip assembly 109 above the support fixture 10. Move it to the position where it extends into the chromatography column 12 held within the support fixture 10. Dispense the desired amount of liquid into the chromatography column 12, then... The 12 is configured to deliver liquid into the well plate 105, and the chromatograph is connected to the support fixture. Without disengaging the column, the tip assembly can be withdrawn from the chromatography column. It is configured in such a way.

[0042] The controller of the liquid handling robot 106 is data processing hardware and data Memory hardware that communicates with the processing hardware may also be used. When the software runs on data processing hardware, it controls the data processing hardware. It stores commands to perform the action of the robot arm. In some embodiments, the robot arm 108 It connects to the onboard embedded controller running the appropriate firmware. The unit can process machine commands. The liquid handling script is It is written in a rant (PC) application, where it is converted into machine commands. As a result, the controller controls the arm 108 and associated tip to the workbench 104 The controller is configured to control the movement of the 109, and the controller supports the arm 108 of the fixing device. It is configured to move to an upward position. With arm 108 in this raised position... The controller controls the liquid handling robot 106 and holds it within the support fixture 10. The tip 109 is inserted into the chromatography column 12, and liquid is dispensed into the column. And the tip extends upward from the chromatography column 12 held within the support fixture 10. The part 109 can be raised. The support fixing device 10 is positioned relative to the workbench 104, and the chromatograph Holds the fee column 12.

[0043] Next, referring to Figures 13 and 14, the first piece 114 and the second piece 2 are connected to each other so as to be rotatable. The support fixture 110 has a part 122. The support fixture 110 also has a cylindrical cavity 1 20, extending within the support fixture 110, the chromatography column 12 is placed on the workbench 10 Includes a cylindrical cavity 120 that is fixed vertically to 4 and completely accommodates it. Support fixture 110 The two parts 114 and 122 are connecting surfaces, oriented vertically, and the cylindrical cavity 120 It is mounted along the connecting surface that crosses along the length. Two parts of the support fixture 110 114 and 122 rotate relative to each other until they are in the open position, allowing for the insertion of the chromatography column 12. Alternatively, the cylindrical cavity 120 is exposed for removal. Furthermore, the two parts 1 of the support fixture 110 14 and 122 rotate relative to each other until they reach the closed position 128, as shown in Figure 13, for example. The matrix column 12 is fixed within the support fixture 110. The support fixture 10 and related A support fixture 110 and related liquid handling equipment similar to the liquid handling system 100 The features of the ing system will not be explained in detail again, and the same reference numbers will be used. By using this method and increasing it by 100, these similar feature areas are identified.

[0044] For the purposes of this disclosure, the term "combined" (all forms of which it refers to, to combine, to be combined) In general, when two components are joined together, they directly or indirectly interact with each other. It means to join. Such a join may be essentially fixed, or essential They may be movable, and the two components and any further intermediate members may be relative to each other. Alternatively, it can be achieved by forming two components together as a single, unified body. It may be done, and unless otherwise specified, it may be essentially permanent, and essentially It may be removable or detachable.

[0045] For the purposes of this disclosure, the terms "up," "down," "right," "left," "back," "front," and "vertical" are used. "Horizontal" and its derivatives are related to the direction shown in Figure 1. However, it is clear It is understood that various alternative directions may be offered unless otherwise specified. Furthermore, the specific apparatus and processes illustrated in the attached drawings and described herein are This is merely a typical embodiment of the concept of the present invention as defined in the attached claims. Please understand the following. Therefore, the specific dimensions and other details relating to the embodiments disclosed herein are not relevant. The physical properties should be considered limited unless explicitly stated otherwise in the claims. It's not.

[0046] Several embodiments have been described. Nevertheless, the spirit and scope of this disclosure It is understood that various changes may be made without deviating from the boundaries. Therefore, other The embodiments are within the scope of the following claims.

Claims

1. Support and fixation for chromatography columns operated by liquid handling robots The support and fixing device is, A frame, wherein at least one extends upward from the base of the frame and ends at the top. The column stand has a base and at least one of the column stands has a base and The column stand includes at least a number of holes extending vertically between the upper part and the column stand. Frame and, A lid is movably attached to the top of the at least one column stand, Including, The lid is configured so that a chromatography column can be inserted into the plurality of holes. The system is configured to have an open position and to fix the chromatography column within the plurality of holes. It is movable between the closed position and the closed position. The lid is aligned in the axial direction with the plurality of holes when the lid is in the closed position. The support and fixing device includes a plurality of openings.

2. The frame further includes the bottom of the chromatography column inserted into the plurality of holes. The claim 1 includes a seat portion that protrudes into the lower portion of the plurality of holes in order to support the portion. Support fixtures.

3. The plurality of holes are arranged in a row across at least one column stand. A support and fixing device according to claim 1, comprising one set of holes.

4. The frame includes a second column stand extending upward from the base and ending at the top. The second column stand is between the base and the upper part of the second column stand. It includes a second set of holes extending vertically, the size of which is the same as the size of which is the same as the first set The billing is set to support chromatography columns of different sizes than the holes. The support and fixing device described in item 3.

5. The present invention further includes a second lid that is movably attached to the upper part of the second column stand. Furthermore, the second lid, when the second lid is in the closed position, is positioned axially with respect to the second set of holes. The support and fixing device according to claim 4, having a plurality of openings that are aligned and positioned.

6. The frame is a drain reservoir located adjacent to the at least one column stand. The lid includes a lid that allows one of the chromatography columns to enter the plurality of holes. To retain liquid leaking from the uppermost opening, the drain reservoir is provided through the multiple openings. The support and fixing device according to claim 1, including an inclined surface that descends toward.

7. The upper part of the at least one column stand is the drain reservoir through the plurality of holes. The support fixture according to claim 6, comprising a channel extending toward the bar.

8. The frame is on the side of the drain reservoir opposite the at least one column stand. The support and fixing device according to claim 6, comprising a second column stand positioned at [location].

9. The upper part of the at least one column stand is at least of the plurality of holes The surrounding surface includes a periphery adjacent to one hole, and the periphery is the clo inserted into the plurality of holes. It is configured to support at least one color of the matrix columns. The support and fixing device according to claim 1.

10. At least one of the plurality of holes is the surrounding surface and the at least one The support fitting according to claim 9, including a continuous inner surface extending between the lower part of the hole and a seat portion positioned therein. Fixture.

11. The lid includes a lower surface that surrounds at least one of the plurality of openings, and the lid is In the closed position, the lower surface is the cavity of the chromatography column within the plurality of holes. The support according to claim 9, configured to contact at least one of the aforementioned colors. Holding fixture.

12. The lid is hinged to the upper part of the at least one column stand. It is rotatably coupled and configured to pivot between the open position and the closed position, The support and fixing device according to claim 1.

13. The lid, when moved to the closed position, the at least one column stand The support and fixing device according to claim 1, comprising a fitting feature portion that snaps into place.

14. The support and fixing device according to claim 1, wherein the plurality of holes include at least eight holes.

15. The size of the aforementioned plurality of holes is determined by the volume of the chromatography 200 μl or 600 μl. A support fixture according to claim 1, configured to accommodate a ram.

16. Each of the aforementioned multiple holes includes a bottom hole within the base of the frame, and the bottom hole is The liquid in the chromatography column passes through the bottom hole and goes below the support fixture. It is configured to dispense into the well plate, and each of the bottom holes is chrome Support according to claim 1, configured to receive the tip of a matrix column. Fixtures.

17. Each of the aforementioned multiple holes is located in the upper part of the column stand that has been enlarged within the column stand The enlarged upper portion includes the upper part of the inserted chromatography column. The support according to claim 1, configured to prevent interference with labels or marks placed on it. Holding fixture.

18. The frame includes mounting features for attaching the support fixture to the workbench. The support and fixing device according to claim 1.

19. An automated liquid handling system, A station structure having a workbench, A well plate supported on the aforementioned workbench, A liquid handling robot comprising an arm suspended above the workbench and a front Includes a controller configured to control the movement of the arm relative to the workbench, The arm includes a set of tip sections configured to dispense liquid, the liquid handling Grobot and A support fixture fixed to the workbench at a location above the well plate, The support and fixing device is, A first part and a second part connected to each other so as to be rotatable, A plurality of cylindrical cavities extending within the support and fixing device, wherein the chromatography column The plurality of cylindrical cavities are configured to be held vertically with respect to a workbench, With the first and second parts of the support and fixing device rotated relative to each other in the open position, the circle The cylindrical cavity is exposed for insertion or removal of the chromatography column. With the first and second parts of the support fixing device rotated relative to each other in the closed position, The upper part of the fixing device fits into the collar of each of the chromatography columns, and the chromatograph The matrix column is fixed within the support and fixing device. With the support and fixing device in the closed position, the controller moves the set of tip portions forward. Move it to a position above the support and fixing device, and the chromatograph held within the support and fixing device It extends into the roughy column and dispenses a desired amount of liquid into the chromatography column. The chromatography column is configured to deliver liquid into the well plate, and the support Without disengaging the chromatography column from the fixing device, the chromatography The support and fixing device is configured to pull out the set of tip portions from the feed column, The automatic liquid handling system including the following.

20. Claim 1, wherein the first and second parts snap together in the closed position. The automated liquid handling system described in section 9.

21. The first part of the support and fixing device comprises a base and a column stand extending upward from the base. Claim 1 includes a frame having the plurality of cylindrical cavities, wherein the column stand includes the plurality of cylindrical cavities. The automated liquid handling system described in section 9.

22. The second piece of the support and fixing device is rotatably attached to the upper part of the column stand. Including an attached lid, the lid is axially aligned with the plurality of cylindrical cavities. An automatic liquid handling system according to claim 21, having a plurality of openings.

23. The frame further comprises a seat portion that protrudes into the lower portion of the plurality of cylindrical cavities, Claim 21, which includes the seat therefor to support the bottom of the chromatography column. The automated liquid handling system described in [reference].

24. The upper part of the column stand includes the surrounding surface adjacent to the plurality of cylindrical cavities, The surrounding surface is configured to support the color of the chromatography column. An automated liquid handling system as described in item 21.

25. Each of the plurality of cylindrical cavities is arranged on the surrounding surface and the lower portion of the plurality of cylindrical cavities. The automatic liquid handling system according to claim 24, including a continuous inner surface extending between the seat portion and the seat portion. Tem.

26. With the lid in the closed position, the lower surface of the lid is located within the plurality of cylindrical cavities. The self according to claim 22, configured to contact the color of the matrix column. Dynamic fluid handling system.

27. The first part of the support and fixing device is a frame, comprising a base and extending upward from the base An extending first column stand, and the base spaced apart from the first column stand Claim 19 includes the frame having a second column stand extending upward from the above. An automated liquid handling system.

28. The second column stand is between the base and the upper part of the second column stand. The second column stand includes a first set of holes extending vertically, and the base and the The second column stand includes a second set of holes extending vertically between the upper part and the The size of the second set of holes is different from the size of the first set of holes in the chromatography column. An automatic liquid handling system according to claim 27, configured to support the following:

29. The frame includes a drain reservoir positioned between the first and second column stands. The automatic liquid handling system according to claim 28.

30. Support and fixation for chromatography columns operated by liquid handling robots The support and fixing device is, A first part and a second part connected to each other so as to be rotatable, A plurality of cylindrical cavities extending within the support and fixing device, wherein the chromatography column The liquid handling robot is configured to be held vertically relative to the workbench, The plurality of cylindrical cavities include, With the first and second parts of the support and fixing device rotated relative to each other in the open position, The cylindrical cavity is exposed for insertion or removal of the chromatography column. With the first and second parts of the support and fixing device rotated relative to each other in the closed position, The upper part of the support and fixing device fits with the collar of the chromatography column, and the chromatograph A support and fixing device for fixing a graphing column within the support and fixing device.

31. The first part of the support and fixing device comprises a base and a column stand extending upward from the base. Claim 3, which includes a frame having the plurality of cylindrical cavities, wherein the column stand includes the plurality of cylindrical cavities Support and fixing device as described in 0.

32. The second piece of the support and fixing device is rotatably attached to the upper part of the column stand. Including an attached lid, the lid is axially aligned with the plurality of cylindrical cavities. The support and fixing device according to claim 31, having a plurality of openings.

33. The lid snaps into the column stand when the lid is moved to the closed position. The support and fixing device according to claim 32, including a fitting feature portion for securing.

34. The size of the aforementioned plurality of cylindrical cavities is determined by the volume of a chromatograph of 200 μl or 600 μl. A support and fixing device according to claim 33, configured to accommodate a column.

35. Each of the plurality of cylindrical cavities includes a bottom hole within the base of the frame, and the bottom The holes allow the liquid in the chromatography column to pass through the bottom holes to the support and fixing device. The configuration described in claim 34, which is configured to dispense into a well plate located below. Mounting support and fixing device.

36. Each of the aforementioned cylindrical cavities is located at the top of the chromatography column. Claim 35 includes an enlarged upper portion configured to prevent interference with a bell or mark. The support and fixing device described.

37. The frame includes mounting features for attaching the support fixture to the workbench. The support and fixing device according to claim 35.

38. The first and second parts of the support and fixing device are connecting surfaces, which are oriented vertically. Therefore, it is attached along the connecting surface that traverses the height of the plurality of cylindrical cavities, The support and fixing device described in item 30.

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