Robotic liquid handling system

Abstract

A robotic liquid handling system can be provided that includes a robotic arm and a controller configured to control the robotic arm to position and operate the robotic arm in a workspace of the robotic liquid handling system. As part of a liquid handling task, the controller can be configured to control the robotic arm to open a reagent reservoir, where the reagent reservoir has an opening sealed by a foil. The controller can be configured to control the robotic arm to open the foil by controlling the robotic arm to: cut at least two flaps in the foil using a cutting tip (260), and push the at least two flaps down into the reagent reservoir using a blunt protrusion, thereby clearing at least a portion of the opening of the reagent reservoir. Other aspects of the invention relate to a computer-implemented method for controlling a robotic arm and an opening tool (200) including a cutting tip and a blunt protrusion.

Description

Technical Field

[0001] This invention relates to a robotic liquid handling system for performing liquid handling tasks in a laboratory environment, and a computer-implemented method for controlling a robotic arm of the robotic liquid handling system. The invention also relates to a computer-readable medium comprising data representing a computer program for performing the computer-implemented method, and to a tool picked up and used by a robotic arm as part of a liquid handling task. Background Technology

[0002] Robotic liquid handling systems are well-known in the field of laboratory automation. Such systems can be used to automate liquid handling tasks, which may include actions such as handling liquid containers, for example by picking up and placing them on a worktable, and interacting with samples contained within the containers, for example by dispensing liquid into sample containers or by pipetting actions. Various other types of liquid handling tasks and actions are also known that can be at least partially automated by such robotic systems.

[0003] It is also known that robotic liquid handling systems can handle non-liquid samples or other objects in addition to liquid samples. For example, robotic liquid handling systems are typically equipped with a gripper as an end effector to move microplates, for example, from a pipetting position to a vibrator, incubator, thermal cycler or microplate reader for PCR, or to move or sort test tubes.

[0004] One embodiment of a robotic liquid handling system is an automated pipetting system, such as that described in US20150251315. This automated pipetting system, also simply referred to as a "pipette robot," may include at least one pipette for aspirating and dispensing liquid samples. The robotic arm can be positioned at a given location under the control of a controller and can be controlled to perform specific actions at that location. This may, for example, enable the pipette to be lowered into a container to aspirate or dispense liquid therein.

[0005] Various other embodiments of robotic liquid handling systems exist, which typically include a work area for holding samples, such as in the form of a worktable, and at least one robotic arm that can be controllably positioned in a plane above the work area, for example, in the XY direction, and that the at least one robotic arm can be moved toward and away from the work area by positioning along a Z-axis perpendicular to the work area. The robotic arm can be controlled by a controller, thus the robotic arm can be "computer-controlled." For example, the robotic arm can be controlled by a PC, workstation, or server, or by a microprocessor integrated into or connected to the robotic arm. In this way, the robotic arm can be controlled to perform a series of actions, thereby enabling it to perform various liquid handling tasks.

[0006] A known drawback of robotic liquid handling systems is that their ability to automate certain types of actions in liquid handling tasks may be limited. Summary of the Invention

[0007] One object of the present invention is to provide a robotic liquid handling system, and a computer-implemented method for controlling a robotic arm of the robotic liquid handling system so as to perform one or more additional types of actions when performing liquid handling tasks in a laboratory environment.

[0008] A first aspect of the present invention provides a robotic liquid handling system, comprising:

[0009] -At least one robotic arm;

[0010] - A controller configured to control a robotic arm to position and operate the robotic arm within the workspace of the robotic liquid handling system;

[0011] As part of a liquid handling task, the controller can be configured to control a robotic arm to open a reagent reservoir having an opening sealed by a foil, wherein the controller is configured to control the robotic arm to open the foil by controlling the robotic arm to perform the following operations:

[0012] - Use a cutting tip to cut at least two flaps in the foil;

[0013] - Using the blunt protrusion, push the at least two blades downward into the reagent reservoir, thereby clearing at least a portion of the opening of the reagent reservoir.

[0014] Another aspect of the present invention provides a computer-implemented method for controlling a robotic arm of a robotic liquid handling system, the method comprising controlling the robotic arm to open a reagent reservoir, wherein the reagent reservoir has an opening sealed by a foil, wherein the method may include controlling the robotic arm to open the foil by controlling the robotic arm to perform the following operations:

[0015] - Use a cutting tip to cut at least two flaps in the foil;

[0016] - Use the blunt-tipped protrusion to push the at least two blades downward into the reagent reservoir to clear at least a portion of the opening of the reagent reservoir.

[0017] Another aspect of the present invention provides a computer-readable medium comprising transient or non-transient data representing a computer program, said computer program including instructions for causing a processor system to perform a computer-implemented method.

[0018] Another aspect of the present invention provides an opening tool for opening a reagent reservoir, wherein the reagent reservoir has an opening sealed by a foil sheet, the opening tool comprising:

[0019] - A body having an elongated shape, the elongated shape having a surface at each corresponding end of the elongated shape to provide two opposing surfaces at which the tool is laterally clamped and picked up;

[0020] - An elongated surface extending along the length of the body, wherein the elongated surface comprises:

[0021] - At one end of the elongated surface, for piercing and cutting the reagent reservoir

[0022] The cutting tip of the foil in the storage device; and

[0023] - At opposite ends of the elongated surface, a blunt protrusion for pushing the blade into the foil downward into the opening of the reagent reservoir, wherein the blunt protrusion is blunt relative to the cutting tip.

[0024] The foregoing aspects may relate to robotic liquid handling systems that can be used in a workspace to process samples. For example, the workspace may include a workbench, which in some embodiments may be part of the robotic liquid handling system, and liquid containers may be placed on the workbench individually and / or in the form of a stand, plate, or any other assembly. Liquid containers may be, for example, liquid containers for holding samples, such as test tubes, but may also be liquid containers for holding reagents used with the samples, such as in the form of reagent reservoirs.

[0025] The robotic fluid handling system may also include at least one robotic arm that can be positioned within a workspace. For example, the robotic arm may have three degrees of freedom (DoF) within the workspace. In one specific embodiment, the robotic arm may be positionable in a plane parallel to the worktable, thus having two DoFs in that plane, and may be positionable perpendicular to the worktable, thus having another DoF. For ease of reference, this plane may also be referred to as the XY plane when points in the physical space above the worktable are considered to be defined in an XYZ coordinate system with the Z-axis aligned with the direction of gravity. It should be understood that while this plane may be referred to as the XY plane elsewhere, the actual control and movement of the robotic arm may occur in a different coordinate system, such as a cylindrical coordinate system.

[0026] Control and movement of a robotic arm perpendicular to the work area can also be referred to as control and movement along the Z-axis. Thus, the robotic arm can move its end effector toward and away from the worktable. For example, this allows a robotic arm with a gripper as its end effector to pick up samples in the workspace, such as by lowering the gripper, holding a sample container, and then raising the gripper again. It should be understood that, typically, the Z-axis along which the robotic arm can move corresponds to the direction of gravity.

[0027] Generally speaking, this movement within the workspace allows the robotic arm to handle liquid containers and interact with samples within those containers, and to move in the XY plane above any object placed on the surface of the work area.

[0028] Surprisingly, the inventors have devised a method to open reagent reservoirs using a robotic arm. Such reagent reservoirs are liquid containers, typically filled with liquid reagents for use in liquid handling processes, and generally have a top opening through which the reagent can be extracted, for example, by pipetting, and are typically sealed with foil, for example, to prevent contamination and spillage of the liquid reagent before use. A specific, but not limiting, embodiment of the reagent reservoir is a rectangular reservoir, which may also be referred to as a reagent “slot,” and it may be made, for example, of polypropylene and may have standardized dimensions, for example, 79 mm × 16 mm or 78 mm × 17.5 mm. The liquid reagents from the reagent reservoir may be consumed during the liquid handling process. Therefore, the reagent reservoir can be considered a “consumable” and / or “disposable.” Alternatively, the reagent reservoir may be reused after use.

[0029] To prevent damage to the foil during transport, thus preventing reagent contamination or spillage, the foil is typically applied to the reservoir in a manner that will not accidentally open or break, for example, by using a sufficiently thick foil and a sufficiently strong adhesive. Typically, such reagent reservoirs can be opened by hand, for example by a laboratory technician, by grasping a pull tab extending from the foil. The foil can be removed by slowly and firmly pulling laterally across the opening unit, thus completely separating the foil.

[0030] The desired outcome is to enable such reagent storage units to open automatically, i.e., through robotic liquid handling systems, as this can greatly improve efficiency, thereby automating certain liquid handling processes involving the use of reagent storage units using robotic liquid handling systems.

[0031] The inventors anticipated that such reagent reservoirs could not be opened simply by having a robotic arm replicate the manual opening action. That is, these actions might be too complex to reliably reproduce. In particular, the robotic arm might struggle to reliably grip the pull tab, which might not always be easily accessible and in the same position, and it might have difficulty reliably maintaining a grip on the pull tab while pulling the foil away from the reservoir. Furthermore, if such a pulling force is applied to the foil, a reaction force might be required on the reagent reservoir. That is, the reagent reservoir is often not fixed to a worktable but removably placed in a support or similar container. Therefore, any horizontal force applied to the reagent reservoir could cause it to slip or, in some cases, even tip over. To prevent this, two-handed operation might be necessary, as another robotic arm might be needed to apply a reaction force to the reagent reservoir to hold it in place. Such a second robotic arm might not always be available. Moreover, opening the reagent reservoir by pulling the pull tab might require complex control mechanisms, including path planning and collision avoidance, as it might require the robotic arm to perform horizontal movements around the reagent reservoir, risking collisions with other objects on the work surface.

[0032] Therefore, the inventors devised a different method for opening the reagent reservoir that addresses at least one of these drawbacks. Specifically, instead of pulling a tab, a robotic arm can be controlled to open the reagent reservoir using two different tools: a cutting tip sharp enough to pierce the foil and a blunt protrusion used to push a portion of the foil downwards into the reagent reservoir. Here, the term "blunt" can refer to a protrusion that is blunt at least relative to the cutting tip and is not typically intended for cutting the foil. In particular, the robotic arm can be controlled to cut at least two tabs into the foil using the cutting tip. For example, the two tabs could be opposing tabs sharing a common cutting line. The blunt protrusion can then be used to push these two tabs downwards into the reagent reservoir, thereby clearing at least a portion of the opening in the reagent reservoir.

[0033] The method described above for opening reagent reservoirs differs from traditional manual opening; it is tailored for robotic arms. Specifically, by creating two flaps within the foil using a sharp cutting tip, the horizontal force applied to the reagent reservoir can be reduced compared to pulling the flaps. This means a second robotic arm is unnecessary to hold the reservoir or apply a reaction force. Furthermore, clearing the foil by pushing the flaps downwards may involve a downward force, for which a natural reaction force can be provided by the surface where the reagent reservoir is placed or a support. Moreover, opening the reagent reservoir in this manner is independent of the shape, position, and / or orientation of the flaps, and therefore represents a type of opening that can be more easily automated and may even be unnecessary. Additionally, pushing the flaps downwards still adequately clears the opening of the reagent reservoir, thus avoiding the need to completely remove the foil from the reservoir.

[0034] In an advantageous embodiment, the cutting tip and the blunt protrusion can be located at two opposite ends of a single tool. The single tool can be held, for example, by a robotic arm, and then the cutting tip or blunt protrusion is appropriately positioned relative to the reagent reservoir to cut the blade into the foil or push the blade downwards into the opening of the reagent reservoir. This single tool simplifies automated workflows because tool switching is not required when opening the reagent reservoir, which would otherwise require additional time.

[0035] It is conceivable to open a reagent reservoir by simply piercing a foil with the head of a robotic arm, for example, using a pre-installed disposable pipette tip that can also be used to interact with the reagent liquid. Disadvantageously, piercing with such a relatively blunt tool can cause the pressure on the foil to gradually increase until it suddenly tears, potentially causing liquid in the reagent reservoir to splash everywhere. Furthermore, the inventors have considered that such a perforated opening could be difficult to control, meaning that the created opening itself may not have a consistent position and / or size relative to the initial position of the disposable pipette tip. Additionally or alternatively, the contour of the created opening may be worn away due to unpredictable tearing of the foil. This, in turn, could mean that if a disposable pipette tip is inserted into the reagent reservoir through the created opening, for example, to extract a reagent, the unpredictable shape of the created opening could cause the disposable pipette tip to deflect horizontally upon entry or exit, or if the disposable pipette tip becomes stuck in the created opening, it will pull the reagent reservoir upwards along with the disposable pipette tip. Another drawback of the foil opening in this type of sealed reagent reservoir is that if a disposable pipette tip is used to measure the liquid level via capacitance measurement, the measurement may be interfered with if the disposable pipette tip accidentally comes into contact with a worn edge of the metal sealing foil.

[0036] Advantageously, the aforementioned measures can allow for the automation of additional types of actions in liquid handling tasks that previously might have required manual intervention or had to be completely avoided in liquid handling tasks. This can be particularly advantageous in high-throughput applications that may require the use of robotic liquid handling systems to process many samples. Furthermore, while the use of reagents in liquid handling tasks by robotic liquid handling systems is known, this use has previously been limited to manually opened sealed reagents or bulk reagents poured from flasks into reservoirs. The ability to automatically open and use sealed reagents can save time, reduce errors (spills), and avoid misplacement, as sealed reagents typically carry barcodes (reagent type, batch number, expiration date). Another advantage of being able to use sealed reagents is that in open reservoirs, some reagent solution may evaporate, and for example, if too much time has passed since the reagent was poured into the reservoir, this could increase the reagent concentration and affect the assay results.

[0037] In some implementations, the controller can be configured to control the robotic arm to cut an H-shaped or X-shaped pattern in the foil to create at least two flaps. An H-shaped or X-shaped pattern may be an efficient way to cut at least two flaps into the foil because it may require relatively few cuts. Furthermore, such H-shaped or X-shaped flaps may have freely hanging ends adjacent to each other, meaning that multiple flaps can be pushed downwards together into the reagent reservoir using blunt-tipped protrusions. This can reduce the number or length of movements the robotic arm must perform to open the foil, which in turn can lead to increased throughput. Additionally, the flaps may be held fixed to the foil at or near the sidewall of the reagent reservoir, meaning that the flaps do not, or do not significantly obstruct, the opening of the reagent reservoir when pushed downwards.

[0038] In some implementations, the controller is configured to control the robotic arm to cut H-shaped or X-shaped patterns in the foil by controlling the robotic arm to perform the following operations:

[0039] - Cut a central slit in the foil, and

[0040] - Cut from the central slit in two directions, either vertically or diagonally away from the central slit and toward the periphery of the opening, to create at least one winglet on each side of the central slit.

[0041] The above sequence of actions can be an advantageous way for a robotic arm to cut H-shaped or X-shaped patterns in a foil to create a flap. In an alternative embodiment, the robotic arm can be controlled to first cut vertical or diagonal slits toward the periphery of the opening, and then subsequently cut a central slit connecting the peripheral slits in the foil. This embodiment can be advantageous when there are significant variations in the appearance of the foil, for example, even in some cases it is taut, while in others it is concave or has depressions.

[0042] In some embodiments, the opening is a rectangular opening having a width and a length, and the controller is configured to control the robot arm to:

[0043] - Cut the central slit centered along the length of the opening;

[0044] - Cut from each corresponding end of the slit in two directions toward the corner of the opening.

[0045] In the case of a rectangular opening, the robotic arm can cut a central slit along the length of the opening, referring to its longest dimension. This may result in relatively wide and short flaps, as they can only extend at most half the width of the opening. These short flaps do not need to be pushed downwards as far to clear the opening as longer flaps, thus making it easier to clean the reagent reservoir opening for entry. Typically, the cutting pattern can be selected such that the flaps cut into the seal when tilting downwards into the opening due to gravity or by being pushed into the opening have a size and shape that avoids contact with the reagent in the reservoir, thereby minimizing potential contamination. Furthermore, the robotic arm can typically be controlled to prevent the cutting tips and blunt protrusions from contacting the reagent, thereby minimizing potential contamination and spillage.

[0046] In some embodiments, the width of the blunt protrusion spans at least 75% of the width of the opening, and the controller can be configured to control the robotic arm to push two flaps downward, wherein the blunt protrusion is oriented such that its width is aligned parallel to the width of the opening. By using the blunt protrusion, whose width spans a large portion of the reagent reservoir's width, the robotic arm can simultaneously push down multiple flaps formed on opposite sides of the central slit via a downward pushing action, instead of the robotic arm having to push each flap down individually on each opposite side. This reduces the number of pushing actions performed by the robotic arm to open the foil. Furthermore, it eliminates the need to apply lateral forces to the reservoir to clear its opening, which would otherwise require additional reservoir securing.

[0047] In some implementations, as part of cleaning the opening of the reagent reservoir, the controller can be configured to control the robotic arm to individually push the blunt-tipped protrusion downward at multiple locations along the central slit.

[0048] The robotic arm can push downwards at multiple locations along the central slit using blunt-tipped protrusions, which also allows reagent reservoirs with rather elongated openings to be adequately cleaned from the foil. That is, in the case of a rather elongated opening, a single downward push along the length of the opening may result in the fins not being adequately pushed downwards into the reagent reservoir.

[0049] In some implementations, after individually pushing the blunt-tipped protrusion downward at multiple locations along the central slit, the controller is configured to control the robotic arm to:

[0050] - Insert the blunt protrusion into the opening beyond the height of the foil; and

[0051] - Move the blunt-headed protrusion along the length of the central slit.

[0052] After the blade is pushed down, by inserting the blunt protrusion into the opening beyond the original height of the foil (while usually keeping the blunt protrusion above the liquid surface), the blade can be pressed more against the sidewall of the reagent reservoir by subsequently moving the blunt protrusion laterally along the length of the slit, so as to clear the opening from the foil more completely.

[0053] In some implementations, the controller may be configured to cut at least two flaps in the foil by controlling the robotic arm to perform the following operations:

[0054] - Pierce the foil at the entry point with a cutting tip; and

[0055] - Move the cutting tip laterally from the entry position, wherein the cutting tip is inserted into the opening to a first depth exceeding the height of the foil.

[0056] After the cutting tip pierces the foil, the blades can be cut into the foil by the lateral movement of the cutting tip. In particular, the cutting tip can be sharp enough to cut the foil in any direction. This simplifies the cutting action compared to a knife or similar directional tool, as it eliminates the need to reorient the tool according to the cutting direction. Instead, the tool can be held by a robotic arm and then simply moved laterally in any desired manner to cut at least two blades into the foil.

[0057] In some implementations, after the cutting tip has moved laterally along the cutting path to a first depth, the controller can be configured to control the robotic arm to:

[0058] - Move the cutting tip laterally along at least a portion of the cutting path, wherein the cutting tip is inserted into the opening to a second depth exceeding the height of the foil, wherein the second depth exceeds the first depth.

[0059] If the foil is relatively flexible, as a precaution to ensure that the foil has been adequately cut along the cutting path, the cutting tip may be moved repeatedly along at least a portion of the cutting path, for example, once at a first entry depth and a second time at a second depth exceeding the first depth. This ensures that the flap has indeed been cut into the foil before attempting to push the flap downwards.

[0060] In some implementations, the reagent reservoir may be a rectangular reagent tank. For example, the reagent tank may have standardized dimensions such as 79 mm (length) × 16 mm (width) or 78 mm (length) × 17.5 mm (width).

[0061] In some implementations, the controller can be configured to control the robotic arm to:

[0062] - Pick up an opening tool, wherein the opening tool includes a cutting tip and a blunt protrusion;

[0063] - Use the cutting tip of the opening tool to create at least two flaps in the foil; and

[0064] - Use the blunt protrusion of the opening tool to clean at least a portion of the opening of the reagent reservoir.

[0065] The cutting tip and blunt protrusion can be positioned on two opposite ends of a single opening tool. This single tool can be held, for example, by a robotic arm, and then the cutting tip or blunt protrusion is appropriately positioned relative to the reagent reservoir to cut the blade into the foil or push the blade downwards into the opening of the reagent reservoir. This single tool simplifies automated workflows because tool switching is not required when opening the reagent reservoir, which could otherwise take additional time.

[0066] In some embodiments, the opening tool may have two opposing surfaces through which it can be gripped and picked up, wherein a robotic arm may be arranged to mount a pair of grippers for picking up and placing objects in the workspace of a robotic fluid handling system, and wherein a controller may be configured to control the robotic arm to pick up the opening tool by gripping it with the pair of grippers at the two opposing surfaces. The opening tool may have a shape that allows it to be gripped by a robotic arm equipped with a pair of grippers. For this purpose, the two opposing surfaces of the opening tool that can be gripped may be spaced apart in the open position and in the closed “gripping” position of the grippers to match the physical span of the grippers. Furthermore, the opposing surfaces may be large enough to allow the grippers to engage with the surfaces.

[0067] According to another aspect of the invention, a complete set of components including a robotic liquid handling system and an opening tool can be provided.

[0068] In some embodiments of the opening tool, the elongated body includes a corresponding recess at each respective end of the elongated shape, wherein the recess provides opposing surfaces to be clamped.

[0069] In some embodiments of the opening tool, the cutting tip has a pyramidal shape with vertices protruding away from the elongated surface. This type of cutting tip can be multidirectional because it allows cutting the foil in different directions, or even omnidirectionally, which allows cutting to be performed independently of the orientation of the cutting tip around its longitudinal axis relative to the cutting direction.

[0070] In some embodiments of the opening tool, the cutting tip is made of glass fiber reinforced thermoplastic, such as glass fiber reinforced polyetheretherketone (PEEK).

[0071] In some implementations of the opening tool, the opening tool may have external dimensions substantially the same as the reagent reservoir. This allows a robotic arm that can be configured to pick up and place the reagent reservoir to also utilize the same type of end effector (e.g., using the same type of gripper) to pick up and manipulate the opening tool. This avoids the need to change the end effector between picking up and placing the reagent reservoir and opening the foil of the reagent reservoir.

[0072] Those skilled in the art will understand that two or more of the above-described embodiments, implementations, and / or aspects of the present invention can be combined in any manner deemed useful.

[0073] Based on this specification, those skilled in the art can make modifications and variations to any of the robotic liquid handling systems, opening tools, methods, and / or computer programs, which correspond to modifications and variations to the other of the entities described. Attached Figure Description

[0074] These and other aspects of the invention become apparent from the embodiments described below, and will be explained with reference to the embodiments described below. In the accompanying drawings,

[0075] Figure 1 A schematic overview of a robotic liquid handling system is shown, which is configured to create an opening in a foil of a reagent reservoir;

[0076] Figure 2 A clamping module including a pair of grippers is shown, wherein the clamping module can be mounted by a robotic arm so that the robotic arm can pick up an opening tool, which can be used to open the foil of a reagent reservoir;

[0077] Figures 3A-3C An opening tool is shown, comprising a sharp cutting tip at one end for piercing and cutting the foil sealing the reagent reservoir, and a blunt protrusion at the other end for pushing a flap cut into the foil downward into the opening of the reagent reservoir, wherein:

[0078] Figure 3A The main view of the opened tool is shown.

[0079] Figure 3B A bottom view of the tool being opened is shown, and

[0080] Figure 3C A side view of the tool being opened is shown;

[0081] Figure 4 A reagent reservoir sealed with foil is shown;

[0082] Figure 5 An opening tool for cutting a foil sheet of a sealed reagent reservoir is shown, namely by cutting a central slit along the length of the foil sheet;

[0083] Figures 6A-6D This example demonstrates how to use the open tool to cut an H-shaped pattern into a foil to create two flaps within the foil;

[0084] Figure 7 An opening tool is shown for pushing two flaps downward into a reagent reservoir at multiple locations along the length of the opening;

[0085] Figures 8A-8D An example is shown of cleaning the opening of a reagent reservoir by pushing the blade downward using a blunt-tipped protrusion and then moving the blunt-tipped protrusion tool along the length of the opening while partially inserting the blunt-tipped protrusion tool into the opening.

[0086] Figures 9A-9DDifferent embodiments of H-shaped and X-shaped cut patterns are shown.

[0087] It should be noted that items with the same reference numerals in different figures have the same structural features and the same function, or the same signal. Since the function and / or structure of such items have already been explained, it is unnecessary to repeat this explanation in the specific embodiments.

[0088] List of reference numerals

[0089] The following list of references and abbreviations is provided to facilitate the interpretation of the drawings and should not be construed as limiting the claims.

[0090] 100 Robotic Liquid Handling System

[0091] 110 Robotic Liquid Handling Instrument

[0092] 120 workbench

[0093] 140 and 142 robotic arms

[0094] 150 Disposable suction tips mounted on liquid handling heads

[0095] 160 Fixture Module

[0096] 162 Fixture

[0097] 180 controller

[0098] 200 Open tool

[0099] 210, 212 concave part

[0100] 220, 222 surfaces

[0101] 240 Slender face downwards

[0102] 260 Cutting Tip

[0103] 262 Cutting motion

[0104] 280 Blunt-head protrusion

[0105] 282 Width w of the blunt-headed protrusion

[0106] 284 Depth d of the blunt-headed protrusion

[0107] 286 The height h of the blunt-headed protrusion

[0108] 290 Push downwards

[0109] 292 Cleanup Campaign

[0110] 300 Reagent Storage Container

[0111] 310 Opening

[0112] 320 foil

[0113] 340 winglets

[0114] 400 central slit

[0115] 402 The central slit was cut to an increased depth.

[0116] 410 Peripheral slit

[0117] 500 h-shaped cut pattern

[0118] 510 A mixture of H-shaped and X-shaped cut patterns

[0119] 520 X-shaped cut pattern

[0120] 530 Alternative H-shaped cut pattern

[0121] 540 H-shaped cut pattern with additional cross-sectional cuts Detailed Implementation

[0122] The following embodiments relate to a robotic liquid handling system for performing liquid handling tasks in a laboratory environment. A robotic liquid handling system typically includes a robotic arm configured to cut at least two flaps in a foil of a reagent reservoir using a cutting tip and to push the at least two flaps downward into the reagent reservoir using a blunt-tipped protrusion, thereby partially clearing the opening of the reagent reservoir. In some embodiments, the cutting tip and the blunt-tipped protrusion may be part of the same tool, which may be gripped by the robotic arm, for example, using a pair of grippers mounted on the robotic arm.

[0123] Figure 1 A robotic liquid handling system 100 is shown, which may include a robotic liquid handling instrument 110 and a controller 180. Figure 1 A robotic liquid handling instrument 110 is shown, thereby the robotic liquid handling system 100 includes a work area 120 for holding objects such as liquid samples, supports, etc. One embodiment of the work area is a worktable. Figure 1 In one embodiment, the robotic liquid handling instrument 110 and thus the robotic liquid handling system 100 are further shown as comprising two robotic arms 140, 142, but may also have one or more robotic arms. Figure 1In this embodiment, each robotic arm 140, 142 can be controllably positioned in an XY plane parallel to the work area and along the Z-axis perpendicular to the work area. For this purpose, the robotic liquid handling system 100 may include a controller 180, which can be configured to control the robotic arms 140, 142 to position and manipulate the respective robotic arms as part of a liquid handling task. As will be clarified elsewhere in this specification, the controller 180 may be physically integrated into the robotic liquid handling instrument 110, but may also be an external controller (such as...). Figure 1 (as shown), such as a PC or workstation.

[0124] Figure 1 The robotic arms 140 and 142 of the robotic liquid handling instrument 110 are also shown to include various attachments. One robotic arm 142 includes a liquid handling head with a pipette having a connector (not shown separately) to which a disposable pipette tip 150 is mounted. The other robotic arm 140 is shown as including a robotic head in the form of a gripper module to which a pair of grippers 162 are mounted. Figure 2 The latter type of robot head is shown in more detail. Specifically, Figure 2 A clamping module 160 is shown, comprising a pair of grippers 162, which can be mounted to a robotic arm, enabling the robotic arm to pick up and place objects on a worktable 120. For example, a robotic liquid handling system may use the pair of grippers 162 to pick up and place sample containers, such as test tubes or reagent reservoirs. For this purpose, the pair of grippers 162 can move laterally toward each other in "pick-up" or "clamping" type actions and move away from each other in "release" type actions. In some embodiments of the robotic liquid handling system, the pair of grippers 162 may also be used to pick up an opening tool that can be used to open the foil of a reagent reservoir.

[0125] Figures 3A-3C An embodiment of such an opening tool 200 is shown, which can be used to open a reagent reservoir having an opening sealed by a foil sheet. Figure 3A The main view of the opened tool is shown. Figure 3B The image shows a bottom view of the tool being opened. Figure 3C A side view of the opening tool is shown. Here, the term "bottom" can refer to the bottom surface 240 of the opening tool 200, or as... Figure 3B As shown, it faces downwards toward the workbench during the intended use of the opening tool 200.

[0126] like Figures 3A-3CAs can be seen, the exemplary opening tool 200 has an elongated body with recesses 210, 212 at each corresponding end of the elongated shape, so as to provide two opposing and recessed surfaces 220, 222 for the opening tool 200 to be laterally clamped and picked up, for example by the above. Figure 1 and Figure 2 A pair of clamps 162. The opening tool 200 is also shown as including an elongated, downward-facing surface 240 that extends along the length of the body. The elongated surface 240 includes a cutting tip 260 at one end for piercing and cutting the foil of the reagent reservoir, and at the opposite end includes a blunt-tipped protrusion 280 for pushing the blades cut into the foil downward into the opening of the reagent reservoir.

[0127] The blunt-tipped protrusion may be blunt relative to the cutting tip and is generally designed not to cut into the foil. For example, the blunt-tipped protrusion may have a width w 282 at its furthest end, which covers at least 50% of the width of the reagent reservoir, or in some cases at least 75% of the width of the reagent reservoir. In one specific embodiment, in the case of a rectangular reagent reservoir with a 79mm × 16mm opening, the blunt-tipped protrusion may have a width of at least 8mm, or in some embodiments it may have a width of 12mm. In another specific embodiment, in the case of a rectangular reagent reservoir with a 78mm × 17.5mm opening, the blunt-tipped protrusion may have a width of at least 8.75mm, or in some embodiments it may have a width of 13.125mm. Here, "width" w ( Figures 3A-3C Reference numeral 282) in the figure may refer to the dimension of the blunt tip protrusion along the elongated body of the opening tool 200, while "height" h (286) refers to the dimension of the blunt tip protrusion relative to the length of the tool. Figure 3A The width w in the plane is the vertical dimension, and the "depth" d(284) refers to the dimension from the plane. Figure 3A The plane extends vertically / extends vertically into Figure 3A The dimensions of the blunt-headed protrusion in the plane.

[0128] The blunt protrusion 280 can have various shapes, such as generally cuboid, cylindrical, ellipsoidal, or (hemispherical). In other embodiments, the blunt protrusion 280 can be prismatic or wedge-shaped. Typically, the blunt protrusion 280 can have a tapered shape, which can gradually taper along a dimension. Figures 3A-3C In a specific embodiment, the blunt-tipped protrusion 280 is shown to taper gradually at a depth d 284, resulting in the farthest portion of the wide protrusion having a relatively small depth d 284 relative to the width w 282, for example, 3 mm-5 mm compared to 8 mm-12 mm.

[0129] Referring again to the cutting tip 260, the cutting tip 260 may be suitable for cutting by having a pyramidal or conical shape with a single sharp vertex and being made of a material sufficiently rigid relative to the material of the foil. In one particular embodiment, the cutting tip 260 may be made of a glass fiber reinforced thermoplastic, such as glass fiber reinforced polyetheretherketone (PEEK).

[0130] In another specific embodiment, the opening tool 200 can be manufactured using additive manufacturing, such as selective laser sintering (SLS), and can comprise or consist of polyamide powder filled with glass particles. In such an embodiment, the cutting tip can be manufactured using plastic injection molding and can be made of the material PEEK GF30, a glass fiber reinforced PEEK.

[0131] Figure 4 A reagent reservoir 300 with an opening 310, sealed by a foil 320, is shown and can be opened by the robotic liquid handling system described in this specification. The reagent reservoir 300 may also be referred to as a reagent “tank” and may be made of, for example, polypropylene and may have standardized dimensions. Non-limiting embodiments of such dimensions include 79 mm × 16 mm and 78 mm × 17.5 mm, and 50 mm × 74 mm and 77 mm × 113 mm. Liquid reagents from the reagent reservoir may be consumed during the liquid handling process. Therefore, the reagent reservoir can be considered a “consumable” and / or “disposable” item. Alternatively, the reagent reservoir may be reused after use.

[0132] Continue to refer to Figure 1 As part of a liquid handling task, the robotic liquid handling system 100 can be configured to control the robotic arm 140 to open the reagent reservoir 300, i.e., by controlling the robotic arm 140 via the controller 180 to open the foil 320 by using the cutting tip to cut at least two flaps in the foil, and by using the blunt protrusion to push the at least two flaps downward into the reagent reservoir to clear at least a portion of the opening of the reagent reservoir.

[0133] For this purpose, the robotic liquid handling system 100 can pick up or hold in any other way. Figures 3A-3C The opening tool 200. The following example illustrates the opening method by... Figure 2The opening of the opening tool 200 is achieved by a pair of grippers 162 holding it in place. However, this is not a limitation, as the robotic fluid handling system 100 can also use different cutting tips and blunt protrusions, for example, arranged on different tools to be picked up one after another or held simultaneously, or the cutting tips and blunt protrusions can be directly mounted on the robot head that can be mounted by the robotic arm 140. Therefore, the use of the opening tool 200 and the picking up of the opening tool 200 by a pair of grippers 162 are merely exemplary.

[0134] Figure 5 An opening tool 200 for cutting a foil sheet of a sealed reagent reservoir is shown, specifically, the cutting tip 260 of the opening tool 200 is used to cut a central slit 262 along the length of the foil sheet. It should be noted that, to avoid unnecessary confusion, Figure 5 (and what follows) Figure 7 The robotic arm and the pair of grippers themselves are not shown in the diagram. It should also be noted that the depicted operation of opening tool 200 may be a result of the controller of the robotic fluid handling system being programmed to perform these operations. Specifically, Figure 5 Intermediate results from a controller configured to pierce the foil in the entry position and laterally move the cutting tip 262 from the entry position while inserting it into the opening beyond the height of the foil. For example, the foil can be pierced by rapidly moving the cutting tip 260 downwards several millimeters, such as 1.5 mm, 2 mm, or 3 mm, below the plane of the foil, and cutting can be performed with a cutting tip inserted at the same depth as or shallower than the height of the foil. In one specific embodiment, the foil can be pierced by performing a rapid piercing motion up to 3 mm below the foil height, followed by cutting the foil with a cutting tip inserted 1.5 mm below the foil height.

[0135] The cutting of the central slit 262 can be the first step in cutting an H-shaped or X-shaped pattern in the foil, thereby creating at least two fins in the foil.

[0136] Figures 6A-6D This illustrates how an H-shaped pattern is cut into foil 320 using an opening tool. That is, as a first step... Figure 6AThe result is shown in the diagram, where the foil 320 can be pierced and a central slit 400 can be cut into the foil, for example, along the length of the reagent reservoir opening. In a second step, the robotic arm can use a cutting tip to cut at each end of the central slit in two directions, perpendicular (or diagonally in the case of an X-shaped pattern) away from the central slit and towards the corners of the opening, thereby creating four peripheral slits 410, which together with the central slit form an H-shaped cut pattern 500. In some embodiments, the central slit can then be recut at a greater insertion depth, for example, 3 mm below the height of the foil, instead of the original 1.5 mm cutting depth. This is in Figure 6C Example in Figure 6C The central slit 402 is shown after being cut to an increased depth.

[0137] For example Figure 6D As shown, cutting an H-shaped pattern 500 in the foil can result in the creation of two flaps 340 in the foil, which may partially tilt downwards into the opening of the reagent reservoir due to gravity. However, the opening of the reagent reservoir may still not be sufficiently cleared from the foil because the flaps may still cover most of the opening. Similarly, as... Figure 7 As shown, the robotic arm can be controlled to use, for example... Figures 3A-3C The blunt protrusion 280 of the opening tool 200 pushes two flaps downward into the reagent reservoir. For this purpose, the robotic arm can, for example, properly position the blunt protrusion above the reagent reservoir 300 by rotating the opening tool 200. The flaps can then be pushed downward into the opening of the reagent reservoir 300 by at least one downward push 290 of the blunt protrusion 280, and in some embodiments, by multiple downward pushes 290 of the blunt protrusion 280. This pushing can, for example, involve moving the blunt protrusion 280 beyond the height of the foil, but keeping it away from the liquid reagent contained in the reagent reservoir.

[0138] exist Figures 6A-6D In alternatives to the action sequence described, the robotic arm can also be controlled to first cut a vertical or diagonal slit toward the periphery of the opening, for example, as... Figure 6B As illustrated herein, a central slit connecting the outer slits is then cut into the foil, for example, as... Figure 6A and 6C As illustrated by the example itself. In other words, the order of actions can be switched.

[0139] In some embodiments, to further clean the opening of the reagent reservoir 300 from the foil, the controller may be configured to control a robotic arm to push the blades cut into the foil downwards into the reagent reservoir 300 at multiple locations along the length of the opening, as well as... Figure 7As illustrated, these different positions are indicated by different arrows 290, each arrow representing a downward push at one of these positions. For example, the blunt-tipped protrusions 280 can push the flap downward at positions spaced at constant intervals (e.g., every 9 mm) or at varying intervals (e.g., more densely packed near the sidewalls of the reagent reservoir). Also, Figure 7 As shown, the controller can typically be configured to control the robot arm to push two blades downwards, wherein the blunt protrusions are oriented such that the width of the blunt protrusions is aligned parallel to the width of the storage opening.

[0140] Figures 8A-8D A further example illustrates cleaning the opening of a reagent reservoir using a blunt protrusion, which is used to push the foil downwards into the opening and then move the blunt protrusion along the length of the opening while maintaining the blunt protrusion partially inserted into the opening beyond the height of the foil. That is, as... Figure 8A As shown, the robotic arm can use a blunt-tipped protrusion to individually push the wing downwards at multiple locations 290 along the central slit, each location being... Figure 8A The image is visually represented by the dashed outline of the blunt-headed protrusion at the corresponding position. For example... Figure 8B As shown, this can cause the flap to be pushed downwards into the opening of the reagent reservoir, thereby largely clearing the opening of the reagent reservoir from the foil 320. To further clear the opening, the blunt-tipped protrusion can then be inserted again into the opening beyond the height of the foil and moved 292 along the length of the opening. This can further push the flap against the sidewall of the reagent reservoir, thereby further clearing the opening of the reagent reservoir, as well as... Figure 8D The example shown in the middle.

[0141] It should be understood that various notch patterns can be used to create at least two flaps within the foil. For example, a notch pattern may result in more than two flaps being cut into the foil, which can be achieved by referencing a reference. Figures 7-8D The foil is cleaned by pushing the blunt protrusion downwards in a similar manner. For example, Figure 9A A hybrid pattern 510, combining H-shaped and X-shaped cutouts, is shown, which establishes two larger flaps and two smaller flaps within the foil. Figure 9B An X-shaped pattern 520 is shown, which establishes four similarly sized flaps within a foil. As another embodiment, Figure 9C An alternative H-shaped pattern 530 is shown, in which two additional rectangular flaps are created at the corresponding ends of the opening, while Figure 9D An H-shaped pattern 540 is shown, which has a transverse cut in the middle or near the central slit, thereby creating four rectangular flaps of similar size in the foil.

[0142] Generally, a controller can be configured, for example through hardware design or software, to perform the operations related to the control of the robotic arm described in this specification. The controller may be embodied in an external computer, such as a PC, laptop, or workstation, which can be connected to the robotic fluid handling instrument via a communication interface (such as a USB interface or any other serial or parallel interface, local network interface, or personal network interface), to which the robotic arm is connected. Here, the adjective "external" may refer to a controller that is not part of the robotic fluid handling instrument. In some other embodiments, the controller may be embodied in an embedded computer, which may be part of the robotic fluid handling instrument.

[0143] Generally, a controller may include one or more (micro)processors that execute appropriate software, such as one or more x86- or ARM-based processors (CPUs), but may also include combinations or systems of such processors and / or other types of processing units. The software implementing the controller's functionality may already be stored in one or more corresponding memories, for example, in volatile memory such as RAM or non-volatile memory such as flash memory. Alternatively, the controller's functionality may be implemented as programmable logic, such as a field-programmable gate array (FPGA). Typically, a controller can be implemented as a single circuit or a combination of circuits. Typically, a controller can be implemented in a distributed manner, such as distributed across different servers or according to a client-server model. A controller can also be implemented remotely, for example, through control software running on one or more cloud-based servers.

[0144] It should be noted that any computer-implemented method described in this specification, such as any claim, can be implemented as software, dedicated hardware, or a combination of both. Instructions for a computer, such as executable code, can be stored on a computer-readable medium, for example, in the form of a series of machine-readable physical symbols and / or as a series of elements having different electrical (e.g., magnetic) or optical properties or values. Executable code can be stored transiently or non-transiently. Embodiments of computer-readable media include memory devices, optical storage devices, integrated circuits, etc.

[0145] It should be noted that the embodiments mentioned above illustrate the present invention and are not intended to limit the present invention, and those skilled in the art will be able to devise many alternative embodiments.

[0146] In the claims, any reference numerals placed in parentheses should not be construed as limiting the claims. The use of the verb "comprising" and its variations does not exclude the presence of elements or steps other than those stated in the claims. The article "a" or "an" preceding an element does not exclude the presence of a plurality of such elements. Expressions such as "at least one" preceding a list or group of elements indicate the selection of all or any subset of the elements from the list or group. For example, the expression "at least one of A, B, and C" should be understood to include only A, only B, only C, both A and B, both A and C, both B and C, or all A, B, and C. The invention can be implemented by means of hardware comprising several different elements and by means of a suitably programmed computer. In an apparatus claim enumerating several means, several of these means may be embodied by the same item of hardware. The mere fact that certain measures are recited in mutually different dependent claims does not indicate that a combination of these measures cannot be used for benefit.

Claims

1. A liquid handling system (100) for a robot performing liquid handling tasks, comprising: - At least one robotic arm (140); - A controller (180) configured to control a robotic arm to position and operate the robotic arm within the workspace of the robotic liquid handling system; As part of the liquid handling task, the controller is configured to control a robotic arm to open a reagent reservoir (300), wherein the reagent reservoir has an opening sealed by a foil (320), and wherein the controller is configured to control the robotic arm to open the foil by controlling the robotic arm to perform the following operations: - Cut at least two flaps (340) in the foil using a cutting tip held by the robotic arm, wherein cutting the at least two flaps includes piercing the foil at an entry position with the cutting tip and moving the cutting tip laterally from the entry position, wherein the cutting tip is inserted into the opening to a first depth exceeding the height of the foil; - Using the blunt-tipped protrusion held by the robotic arm, the at least two blades are pushed downward into the reagent reservoir, thereby clearing at least a portion of the opening of the reagent reservoir.

2. The robotic liquid handling system (100) according to claim 1, wherein the controller (180) is configured to control the robotic arm (140) to cut an H-shaped pattern or an X-shaped pattern on the foil to create the at least two flaps (340).

3. The robotic liquid handling system (100) according to claim 2, wherein the controller (180) is configured to control the robotic arm (140) to cut H-shaped patterns (500, 510, 530, 540) or X-shaped patterns (520) on the foil by controlling the robotic arm to perform the following operations: - Cut a central slit (400) on the foil, and - Cut from the central slit in two directions, either vertically or diagonally away from the central slit and toward the periphery of the opening, to create at least one winglet on each side of the central slit.

4. The robotic liquid handling system (100) of claim 3, wherein the opening is a rectangular opening having a width and a length, and wherein the controller (180) is configured to control the robotic arm (140) to: - Cut the central slit (400) centered along the length of the opening; - Cut from each corresponding end of the slit in two directions toward the corner of the opening.

5. The robotic liquid handling system (100) of claim 4, wherein the width of the blunt protrusion (280) spans at least 75% of the width of the opening, and wherein the controller (180) is configured to control the robotic arm (140) to push the two flaps (340) downward, wherein the blunt protrusion is oriented such that the width of the blunt protrusion is aligned parallel to the width of the opening.

6. The robotic liquid handling system (100) according to any one of claims 3 to 5, wherein, as part of cleaning the opening of the reagent reservoir, the controller (180) is configured to control the robotic arm (140) to individually push the blunt-tipped protrusion (280) downward at multiple locations along the central slit.

7. The robotic liquid handling system (100) according to claim 6, wherein, After individually pushing the blunt-tipped protrusion (280) downward at multiple locations along the central slit, the controller (180) is configured to control the robotic arm to: - Insert the blunt protrusion into the opening beyond the height of the foil; and - Move the blunt-headed protrusion along the length of the central slit.

8. The robotic liquid handling system (100) according to claim 1, wherein, After the cutting tip (260) is moved laterally along the cutting path to a first depth, the controller (180) is configured to control the robotic arm (140) to: - The cutting tip is moved laterally along at least a portion of the cutting path, wherein the cutting tip is inserted into the opening to a second depth exceeding the height of the foil, wherein the second depth exceeds the first depth.

9. The robotic liquid handling system (100) according to any one of claims 1 to 5, wherein the reagent reservoir is a rectangular reagent tank.

10. The robotic liquid handling system (100) according to any one of claims 1 to 5, wherein the controller (180) is configured to control the robotic arm (140) to: - Pick up an opening tool (200), wherein the opening tool includes a cutting tip (260) and a blunt protrusion (280); - Using the cutting tip of the opening tool, at least two flaps (340) are created in the foil (320); and - Use the blunt protrusion of the opening tool to clean at least a portion of the opening of the reagent reservoir (300).

11. The robotic liquid handling system (100) of claim 10, wherein the opening tool (200) has two opposing surfaces (220, 222) through which the opening tool can be gripped and picked up, wherein the robotic arm (140) is arranged to mount a pair of grippers to pick up and place objects in the workspace (120) of the robotic liquid handling system, and wherein the controller (180) is configured to control the robotic arm to pick up the opening tool by gripping the opening tool with the pair of grippers at the two opposing surfaces.

12. A kit comprising a robotic liquid handling system (100) and an opening tool (200) as claimed in claim 10 or 11.

13. A computer-implemented method for controlling a robotic arm of a robotic liquid handling system according to any one of claims 1 to 5, the method comprising controlling the robotic arm to open a reagent reservoir, wherein the reagent reservoir has an opening sealed by a foil, wherein the method comprises controlling the robotic arm to open the foil by controlling the robotic arm to perform the following actions: - Cut at least two flaps in a foil using a cutting tip held by the robotic arm, wherein cutting the at least two flaps involves piercing the foil with the cutting tip at an entry position and moving the cutting tip laterally from the entry position, wherein the cutting tip is inserted into the opening to a first depth exceeding the height of the foil; - Using the blunt-tipped protrusion held by the robotic arm, the at least two blades are pushed downward into the reagent reservoir to clear at least a portion of the opening of the reagent reservoir.

14. A computer-readable medium comprising transient or non-transient data representing a computer program, said computer program including instructions for causing a processor system to perform the method of claim 13.

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