Pipette operating instrument
Patent Information
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- BECKMAN COULTER INC
- Filing Date
- 2023-06-06
- Publication Date
- 2026-06-08
Smart Images
Figure 00000000_0000_ABST
Abstract
Description
Background Art
[0001] (Cross - reference to related applications) This application claims the benefit and priority of U.S. Provisional Patent Application No. 63 / 349,913, filed on Jun. 7, 2022, and U.S. Provisional Patent Application No. 63 / 383,281, filed on Nov. 11, 2022, which were filed as PCT International Patent Applications on Jun. 6, 2023, the entire disclosures of which are incorporated herein by reference in their entireties.
[0002] Pipetting instruments are often used in laboratory settings to reliably transfer fluids from one container to another. In commercial laboratory settings, automated liquid pipettes are used to reduce labor costs associated with large pipetting projects while potentially increasing the efficiency, accuracy, and precision of the project. Automated liquid pipettes often use disposable pipette tips to reduce cross - contamination of samples by inadvertently mixing residual fluids from one source with another.
[0003] Disposable pipette tips are typically stored in a linear array, such as a pipette tip box, that is accessible to an automated liquid pipette. The automated liquid pipette must load and unload tips from or into these arrays within the pipette tip box. When loading less than the entire array of pipette tips, the automated liquid pipette must load a set of pipette tips from the pipette tip box while the remainder of the pipette tips remain in the pipette tip box.
Summary of the Invention
Means for Solving the Problems
[0004] The present disclosure relates to a pipetting instrument. In some embodiments, by way of non-limiting example, the pipetting instrument performs a loading operation and a pick-and-place operation, and the pipette tip is loaded onto the mandrel of the pipetting instrument from a pipette tip box, or the pipette tip is unloaded from the mandrel into the pipette tip box. In some embodiments, the mandrels are densely packed together to maximize the number of samples per unit area over the loading or unloading space. In some embodiments, the mandrel has a maximum diameter that mates with the maximum pipette tip diameter. Maximizing the pipette tip diameter is desirable because it maximizes the volume of sample that can be taken up in the pipette tip per cycle. Maximizing both the surface area of the mandrel and the number of mandrels per unit area can leave very little space between individual mandrels. Minimizing the space between mandrels can create difficulties when targeting a desired pipette tip using the mandrel. Further, even when a desired pipette tip is loaded or unloaded using the mandrel, an undesired pipette tip can be incidentally loaded from the pipette tip box along with the desired pipette tip. These undesired pipette tips can be loaded due to mechanical or electrostatic coupling to the mandrel or the desired pipette tip. Accordingly, it is desirable to produce a pipetting device and method for loading or unloading a desired pipette tip from a pipette tip box while reliably unloading all undesired pipette tips from the mandrel.
[0005] In one embodiment, an automated liquid pipettor comprising a pipetting instrument for loading and dispensing samples includes a deck for supporting a pipette tip box having a pipette tip, a mandrel that engages the pipette tip and removes at least some of the pipette tips from the pipette tip box, and a controller configured to control the automated liquid pipettor, the controller further configured to perform a pipette tip removal operation to remove any undesired pipette tips removed from the pipette tip box using the mandrel.
[0006] In another embodiment, a method for loading a set of pipette tips onto an automated liquid pipettor includes coupling a desired pipette tip to a mandrel by positioning the mandrel and engaging the pipette tip with the mandrel, lifting the mandrel to partially remove the desired pipette tip from the pipette tip box and lift at least one undesired pipette tip with the desired pipette tip, moving the mandrel to remove the at least one undesired pipette tip from the mandrel and return the at least one undesired pipette tip to the pipette tip box while the desired pipette tip remains coupled to the mandrel, and lifting the mandrel to completely remove the desired pipette tip from the pipette tip box.
[0007] In yet another embodiment, a method for loading one or more pipette tips from an automated liquid pipettor includes positioning a mandrel, engaging the pipette tip, and inserting it into a pipette tip box; activating a plunger set to disengage the pipette tip from the mandrel; dropping the pipette tip into the pipette tip box; positioning the mandrel and partially inserting any pipette tip still attached to the mandrel into the pipette tip box; and moving the mandrel and pipette tip to disengage the pipette tip from the mandrel and drop the pipette tip into the pipette tip box.
[0008] Various additional aspects will be described in the following description. The aspects can relate to individual features and combinations of features. It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the broad inventive concepts on which the embodiments disclosed herein are based.
Brief Description of the Drawings
[0009] The following drawings are illustrative of embodiments of the present disclosure and, therefore, do not limit the scope of the present disclosure. Embodiments of the present disclosure will hereinafter be described in connection with the accompanying drawings, and like numbers indicate like elements.
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[0046] In the accompanying drawings, like components and / or features can have the same reference labels. Further, various components of the same type can be distinguished by following the reference label with a hyphen and a second label that differentiates among the like components. If only the first reference label is used in the specification, the description is applicable to any one of the like components having the same first reference label, regardless of the second reference label.
DETAILED DESCRIPTION OF THE INVENTION
[0047] Detailed Description Various embodiments are described in detail with reference to the drawings, and like reference numbers represent like parts and assemblies throughout several of the figures.
[0048] FIG. 1 is a block diagram of an exemplary pipetting instrument 100. The exemplary pipetting instrument 100 includes an automated liquid pipettor 102, a pipette tip box 104, and a controller 106. In some embodiments, the controller 106 is configured to implement a tip removal program 108.
[0049] The pipetting instrument 100 is an instrument such as a laboratory instrument that performs pipetting operations. An example of the pipetting instrument 100 is a sample preparation instrument. Examples of the sample preparation instrument are illustrated and described in more detail with reference to FIGS. 3A, 3B, 4, 5, 6, 9, 22.
[0050] The automated liquid pipettor 102 is a system that performs an automated pipetting function. Examples of the automated liquid pipettor are illustrated and described in more detail with reference to FIGS. 3A and 3B.
[0051] The pipette tip box 104 is a container configured to store pipette tips 110. In some embodiments, the pipette tip box 104 stores the pipette tips 110 in a linear fashion. The pipette tips 110 can be stored at a uniform distance from each other within the pipette tip box 104. In some embodiments, the pipette tip box 104 can hold 384 pipette tips 110 with a uniform spacing of 4.5 millimeters between each pipette tip 110. In some embodiments, the pipette tip box 104 can hold 96 pipette tips 110 with a uniform spacing of 9 millimeters between each pipette tip 110. In some embodiments, the positioning of the pipette tips 110 within the pipette tip box 104 can conform to industry standards for microplates, such as those developed by the Laboratory Automation and Screening Society (SLAS), the American National Standards Institute (ANSI), or other industry standards. Examples of the pipette tip box 104 are illustrated and described in more detail with reference to FIG. 11.
[0052] Controller 106 is configured to control automated liquid pipettor 102. In some embodiments, automated liquid pipettor 102 receives instructions from controller 106, retrieves and / or returns pipette tip 110 from and to pipette tip box 104, and loads or unloads pipette tip 110 onto automated liquid pipettor 102. Controller 106 is configured to implement tip removal program 108 to remove any undesired pipette tips 132 from automated liquid pipettor 102 as automated liquid pipettor 102 loads or unloads pipette tip 110 from pipette tip box 104.
[0053] FIG. 2A shows a cross-sectional view of pipette operating instrument 100 of FIG. 1, including mandrel 130, pipette tip 110, and pipette tip box 104, with an undesired pipette tip 132 coupled to mandrel 130 and / or another pipette tip 110.
[0054] Mandrel 130 is connected to pipette operating instrument 100 and is configured to engage pipette tip 110 by pressing the mandrel into pipette tip 110. The bottom of the mandrel may be configured to be attached to the top of pipette tip 110 via a friction fit. Thus, pushing mandrel 130 into pipette tip 110 within pipette tip box 104 may push pipette tip 110 onto mandrel 130, providing an airtight connection between pipette tip 110 and mandrel 130. An example of mandrel 130 is shown and described in further detail with reference to FIG. 13.
[0055] An unwanted pipette tip 132 is a pipette tip 110 that remains unintentionally attached to the mandrel 130 or another pipette tip 110 after the mandrel has been lifted out of the pipette tip box 104. The unwanted pipette tip 132 can be inadvertently lifted by the mandrel 130 due to mechanical or electrostatic coupling between the unwanted pipette tip 132 and the mandrel 130, between the unwanted pipette tip 132 and the desired pipette tip 134, or between the unwanted pipette tip 132 and both the mandrel 130 and the desired pipette tip 134. In some embodiments, the controller 106 may control the automated liquid pipettor 102 and provide instructions for loading every other pipette tip 110 from the pipette tip box 104. In these examples, the desired pipette tip 134 is defined by the controller as every other pipette tip 110 within the pipette tip box 104, while the unwanted pipette tip 132 is defined as all pipette tips 110 that are not defined as the desired pipette tip 134. In FIG. 2A, the unwanted pipette tip 132 is located between two desired pipette tips 134 and the unwanted pipette tip 132 has been inadvertently lifted from the pipette tip box 104.
[0056] Figure 2B shows a cross-sectional view of the pipetting instrument 100 of FIG. 1, including the mandrel 130, the pipette tip 110, the tray 111, and the pipette tip box 104. The undesired pipette tip 132 is decoupled from the mandrel 130 and / or another pipette tip 110 and is placed in the pipette tip box 104. The undesired pipette tip 132 can be decoupled from the mandrel 130 by partially inserting the undesired pipette tip 132 into the pipette tip box 104 and completing the coordinated movement 136 of the mandrel 130. The coordinated movement 136 of the mandrel 130 is a movement in which each mandrel 130 moves in synchronization with each other to provide similar movement between each mandrel 130. The tray 111 is positioned above the pipette tip box 104 and guides the pipette tip 110 into the pipette tip box 104 as the mandrel 130 passes through the tray 111. An example of the coordinated movement 136 is illustrated and described in more detail with reference to FIGS. 21 and 27.
[0057] In some embodiments, the pipetting instrument 100 can include at least one sensor for identifying when an undesired pipette tip 132 is coupled to the mandrel 130 or the desired pipette tip 134. If any undesired pipette tip 132 is sensed, the sensor may identify the set of mandrels 130 for performing the coordinated movement 136. If the sensor fails to sense any undesired pipette tip 132, feedback may be provided to the controller 106 to stop the step of performing the coordinated movement 136.
[0058] FIG. 3A shows a front view of an exemplary embodiment of the pipetting instrument 100 of FIG. 1, which may include any combination of the various systems or components shown. For example, the pipetting instrument 100 may include one or more (or none) of each of the pod 150, the mandrel 130, the pipette tip box 104, the deck 152, and the motorized gantry 154. An overview of these various components of the pipetting instrument 100 is provided below.
[0059] In some embodiments, the pipetting instrument 100 may include a motorized gantry 154. In some of such embodiments, the motorized gantry 154 may be movable along one or more axes. For example, the motorized gantry 154 may be slidable laterally along the length of the pipetting instrument 100. In some embodiments, the pipetting instrument 100 may include a pod 150 that is mechanically coupled to the motorized gantry 154. As shown in the figures, the pod 150 may have an elongated housing that is held upright by the motorized gantry 154 about a vertical axis. The bottom of the pod 150, shown in more detail in FIG. 4, may include a mandrel 130 configured to interface with and / or connect to one or more pipette tips 110 within the pipette tip box 104. In certain embodiments, the pod 150 may be movable along the motorized gantry 154 about one or more axes. For example, as shown in the figures, the pod 150 may be slidable laterally along the length of the motorized gantry 154. Further, in some embodiments, the pod 150 may be slidable vertically relative to the motorized gantry 154 such that the bottom of the pod 150 can be positioned higher or lower. Thus, the bottom of the pod 150 can be repositioned using precise 3-axis movement by adjusting a combination of the height of the pod 150 relative to the motorized gantry 154 (e.g., the Z-axis), the lateral position of the pod 150 along the motorized gantry 154 (e.g., the Y-axis 182), and the lateral position of the motorized gantry 154 along the length of the pipetting instrument 100 (e.g., the X-axis 180). In this figure, the lateral movement of the motorized gantry 154 illustrates movement along the Y-axis 182.
[0060] In some embodiments, pod 150 may be a multi-channel pod, which is configured to interface with and connect to a plurality of pipette tips 110 that can be used to perform pipetting operations simultaneously. In some embodiments, pod 150 may contain various components that enable various pipetting operations and fluid handling operations to be performed using the attached pipette tips 110.
[0061] Deck 152 may be located within pipetting instrument 100, and the deck is used to support various laboratory materials associated with pipetting instrument 100. In the figure, deck 152 supports pipette tip box 104, which engages mandrel 130 and is positioned to perform pipetting operations.
[0062] FIG. 3B shows a front view of an exemplary embodiment of pipetting instrument 100 of FIG. 1, which may include any combination of the various systems or components shown. In this figure, the lateral movement of motorized gantry 154 illustrates movement along X-axis 180.
[0063] FIG. 4 shows a front view of pod 150 used in an exemplary embodiment of the pipetting instrument of FIG. 1. In some embodiments, pod 150 may include mandrel 130 at the bottom of pod 150. Each mandrel 130 may be configured to couple to a pipette tip 110, and each mandrel 130 may have an extension channel (not shown) spanning the vertical length of the mandrel 130. This extension channel may enable the performance of pipetting operations on the pipette head to which each mandrel 130 is attached. For example, the extension channel may be used to generate a varying degree of pressure within the attached pipette tip to allow liquid to be drawn into or expelled from the bottom of that pipette tip 110.
[0064] Pod 150 includes pod motor 156. In an exemplary embodiment of pod 150, pod 150 may include three pod motors 156 at the upper part of pod 150. Pod motor 156 may control plunger 190 to remove pipette tip 110 from mandrel 130 along plunger path 312. Examples of plunger 190 and plunger path 312 are illustrated and described in more detail with reference to FIGS. 16 and 25. Further, pod motor 156 may control the position of mandrel 130 along Z-axis 184, which is illustrated and described in more detail with reference to FIGS. 4-6.
[0065] Further, pod 150 may also include arm 158 for gripping an object below pod 150. In some embodiments, arm 158 may extend downward, grip the laboratory instrument below pod 150, stabilize the laboratory instrument, and enable mandrel 130 connected to pod 150 to engage with the laboratory instrument. In some embodiments, arm 158 may be controlled by at least one of pod motors 156, and the pod motor is configured to engage with and disengage from arm 158 to grip or release the laboratory instrument.
[0066] Furthermore, pod 150 includes three pod motors 156A, 156B, and 156C. Pod motors 156A and 156C are mechanically coupled to two lead screws 160A and 160B respectively. Lead screws 160A and 160B are fixed to brackets and coupled to two nuts 162A and 162B respectively, enabling pod 150 to move along Z-axis 184 as pod motors 156A and 156C rotate the two lead screws 160A and 160B. In this figure, pod motor 156B can be used to operate plunger 190 stored within mandrel 130 that is attached to pod 150.
[0067] FIG. 5 shows a top perspective view of the internal components of another embodiment of the pod 150, which is used in the exemplary embodiment of the pipetting instrument 100 of FIG. 1. The pod 150 includes a first feed screw 170, a second feed screw 172, a first Z-axis motor 174, a second Z-axis motor 176, and a mounting plate 178. More specifically, FIG. 5 illustrates how feed screws, such as the first feed screw 170 and the second feed screw 172, can be rotated in various embodiments of the pod 150. It is contemplated that any method and configuration can be used not only through the use of motors mechanically coupled to the feed screws, but also to rotate the feed screws. Further, any number of motors can be mechanically coupled to any number of feed screws. Examples of motors are illustrated and described in more detail with reference to FIGS. 7-9.
[0068] As shown in the figure, each individual feed screw is mechanically coupled to an independent motor. For example, the upper portion of the first feed screw 170 may be mechanically coupled to the first Z-axis motor 174. In some embodiments, the first Z-axis motor 174 may be within the enclosure and both may also be mechanically coupled to the first feed screw 170 by pulleys and belts that can be housed within the pod 150. The operation of the first Z-axis motor 174 may be used to rotate the first feed screw 170 clockwise and counterclockwise. The upper portion of the second feed screw 172 may be mechanically coupled to the second Z-axis motor 176. In some embodiments, the second Z-axis motor 176 may also be mechanically coupled to the second feed screw 172 by pulleys and belts that can both also be housed within the pod 150. The operation of the second Z-axis motor 176 may be used to rotate the second feed screw 172 clockwise and counterclockwise. Both feed screws may span the vertical dimension of the pod 150 and may be tethered to both the top and the bottom of the pod 150.
[0069] Accordingly, in various embodiments, each feed screw may be mechanically coupled to an independent motor that drives it. This configuration may also provide a number of advantages in order to enable partial rack loading of the pipette tips 110, as opposed to loading all of the pipette tips 110 within the pipette tip box 104. In a typical scenario where the entire pipette tip box 104 is loaded, a symmetric downward force can be used. For example, the workstation may reposition the bottom of the pod to be centered over the full tip tray.
[0070] The mounting plate 178 is coupled to the first feed screw 170 and the second feed screw, and is driven along the Z-axis 184 along the feed screw by the first Z-axis motor 174 and the second Z-axis motor 176. In some embodiments, the mounting plate 178 moves the feed screw up and down along the Z-axis 184 to position the mandrel 130 and engage the mandrel 130 with the pipette tip 110 stored within the pipette tip box.
[0071] FIG. 6 shows a side perspective view of the internal components of another embodiment of the pod 150 used in an exemplary embodiment of the pipette operating instrument of FIG. 1. This figure illustrates a diagram of the internal components of the pod 150 utilizing a first feed screw 170 and a second feed screw 172 according to an exemplary embodiment. As described above, the first feed screw 170 is mechanically coupled to the first Z-axis motor 174, and the second feed screw 172 is mechanically coupled to the second motor to provide vertical movement of the mounting plate 178 along the Z-axis 184. This movement enables the pod 150 to engage with the pipette tip box 104 and be positioned to remove the pipette tip 110 from the pipette tip box 104.
[0072] FIG. 7 is a perspective view of the movement of the motorized gantry 154 along the X-axis 180. The pipette operating instrument 100 includes a motorized gantry 154 configured to move the pod 150 along the X-axis 180 and the Y-axis 182. The movement of the motorized gantry 154 along the Y-axis 182 is illustrated and described in more detail with reference to FIGS. 8A and 8B.
[0073] The movement of the motorized gantry 154 along the X-axis 180 is driven by an X-axis motor 186. The X-axis motor 186 is configured to drive a timing pulley and a timing belt, respectively, to move the motorized gantry 154 along the X-axis 180. In some embodiments, the X-axis motor 186 may drive the motorized gantry 154 along a lead screw.
[0074] FIG. 8A shows a perspective view of the movement of the motorized gantry along the Y-axis 182. The pipette operating instrument 100 includes a motorized gantry 154 configured to move the pod 150 along the X-axis 180 and the Y-axis 182. The motorized gantry 154 moves along the Y-axis 182 by sliding along a bridge 191. The bridge 191 serves as a linear guide and guides the motorized gantry along the Y-axis 182.
[0075] FIG. 8B shows a perspective view of the movement of the motorized gantry along the Y-axis, with a portion of the motorized gantry cut away to show the Y-axis motor. In this figure, a portion of the pipette operating instrument 100 is cut away to reveal the Y-axis motor 188. The Y-axis motor 188 drives the motorized gantry 154 along the Y-axis 182 by driving a timing pulley and a timing belt. In some embodiments, the Y-axis motor 188 may drive the motorized gantry 154 along a lead screw.
[0076] FIG. 9 shows a block diagram of the basic hardware components within the pipetting instrument of FIG. 1, illustrating the movement of the motorized gantry along the Z-axis 184. The block diagram includes a controller 106, a first lead screw 170, a second lead screw 172, a first Z-axis motor 174, a second Z-axis motor 176, and a mounting plate 178. Specifically, this block diagram further illustrates the movement of the mounting plate 178 along the Z-axis 184.
[0077] The mounting plate 178 is configured to move along the first and second lead screws as follows. The controller 106 controls the first Z-axis motor 174 and the second Z-axis motor 176 to rotate and drive the lead screws, which in turn move the mounting plate along the Z-axis 184.
[0078] FIG. 10 shows a block diagram of the additional hardware components of the exemplary pipetting instrument of FIG. 1. The block diagram illustrates a pipetting instrument 100 configured to input a sample and output a prepared sample. The pipetting instrument 100 includes a computing device 230 further comprising a system memory 238 and a processing device 232, a display device 268, a sample operation station 200, an automated liquid pipettor 102 including a controller 106 further including a tip removal program, a motorized gantry 154, a pod 150, a deck 152, and a pipette tip box may be stored on the deck within the pipetting instrument 100 as indicated by the dashed outline.
[0079] Examples of the computing device 230, the system memory 238, the processing device 232, and the display device 268 are illustrated and described in further detail with reference to FIG. 17. The computing device 230 can be used to execute an operating system, application programs, and software modules (including software engines) described herein. The display device 268 may communicate with an operator and provide feedback from the computing device 230. The computing device may provide input to, or receive input from, the automated liquid pipettor 102.
[0080] Samples loaded into the automated liquid pipettor 102 may be manipulated at a sample manipulation station 200 configured to manipulate input samples and output prepared samples. The sample manipulation station 200 can complete several different tasks including pipetting, mixing, heating, or otherwise manipulating the sample and preparing an output sample.
[0081] FIG. 11 shows a perspective view of an exemplary embodiment of the pipette tip box 104. As shown in the figure, the pipette tips 110 are held upright within the pipette tip box 104 in a 16×24 configuration for a total of 384 pipette tips. These pipette tips are used in conjunction with a corresponding set of mandrels 130 having the same 16×24 configuration, and will enable pipetting operations to be performed using up to 384 pipette tips. The pipette tip box 104 may be supported by the deck 152 within the pipetting instrument 100. In some embodiments, the pipette tip box 104 may hold the pipette tips 110 upright in an 8×12 configuration for a total of 96 pipette tips. These pipette tips 110 are used in conjunction with a corresponding set of mandrels 130 having the same 8×12 configuration, and will enable pipetting operations to be performed using up to 96 pipette tips 110.
[0082] FIG. 12 shows a perspective view of an exemplary embodiment of the pipette tip box 104, and the spacing between the pipette tips 110 within the pipette tip box 104 can vary slightly. In this figure, the pipette tips 110 are touching in some places or can be further apart than the average spacing between the pipette tips 110. A spacing between the pipette tips 110 that is less than the average spacing between the pipette tips 110 can further contribute to an undesired loading of an undesired pipette tip 132 onto the mandrel 130 or the desired pipette tip 134.
[0083] FIG. 13 shows a perspective view of a mandrel assembly including a mandrel 130 used in an exemplary embodiment of the pipetting instrument of FIG. 1. As shown in the figure, the mandrel 130 is in an 8×12 configuration for a total of 96 mandrels. Thus, the mandrel 130 can be attached to 96 pipette tips 110 simultaneously. In some embodiments, the mandrel 130 may be in a 16×24 configuration for a total of 384 mandrels 130. In some embodiments, each mandrel 130 may be substantially cylindrical with an elongate channel spanning the vertical length of the mandrel. This elongate channel may enable the performance of pipetting operations on the pipette head to which each mandrel 130 is attached. For example, the elongate channel may be used to create a varying degree of pressure within the attached pipette tip 110 to allow liquid to be drawn into or expelled from the bottom of the pipette tip 110. In some embodiments, each mandrel 130 may be tapered towards the bottom end or have features at the bottom end that facilitate an airtight friction fit with the upper portion of the corresponding pipette tip 110.
[0084] FIG. 14A shows a perspective view of an alternative mandrel assembly including a mandrel 130 used in an exemplary embodiment of the pipetting instrument of FIG. 1. As shown in the figure, the mandrel 130 is in a 1×8 configuration for a total of 8 mandrels 130. The mandrel 130 may be coupled to a pod 150.
[0085] FIG. 14B shows a perspective view of an alternative mandrel assembly used in an exemplary embodiment of the pipetting instrument of FIG. 1, where the mandrel is partially inserted into the pipette tip box 104 or the shackle plate. As shown in the figure, the mandrel 130 is in a 1×8 configuration for a total of 8 mandrels 130. The pod 150 may be positioned such that the mandrel 130 is at least partially inserted into the pipette tip box 104 and engaged with the pipette tip 110. The pipette tip box may be stored on the deck 152.
[0086] FIG. 15 shows a segmented mandrel 130 used in an exemplary embodiment of the pipetting instrument of FIG. 1. The mandrel 130 may be segmented to include segments of varying diameter. In some embodiments, the varying diameter may correspond to the diameter of the pipette tip 110 stored within the pipette tip box 104. In some embodiments, the varying diameter may correspond to the diameter of the pipette tip 110 that is standardized by an organization that regulates pipetting microplates. In some embodiments, these standards may be regulated by the Society for Laboratory Automation and Screening (SLAS). In some embodiments, the segments of the mandrel 130 may correspond to the diameter of the pipette tip 110 stored within the pipette tip box 104 that has 384 pipette tips 110 as shown in FIG. 11. In some embodiments, the segments of the mandrel 130 may correspond to the diameter of the pipette tip 110 stored within the pipette tip box 104 that has 96 pipette tips 110 as shown in the pipette tip box 104 having 96 pipette tips 110 as shown in the mandrel assembly of FIG. 13 having 96 mandrels 130. In some embodiments, the mandrel 130 may include stainless steel. In some embodiments, the mandrel 130 may be disposed on the automated liquid pipettor 102 using an interference fit.
[0087] FIG. 16A is a cross-sectional view of a mandrel 130 inserted into a pipette tip 110, the mandrel 130 including a plunger 190 for lowering and raising the pipette tip 110 when the plunger 190 engages a filter 192. In some embodiments, the plunger 190 is driven by a pod motor 156. The plunger 190 lowers and raises the pipette tip 110 by applying a downward force along a plunger path 312 toward the bottom of the mandrel 130. The plunger path 312 is described and illustrated in more detail with reference to FIG. 25. As the plunger 190 is moved along the plunger path 312, the plunger 190 may contact the filter 192, and the filter 192 applies an equal and opposite force on the mandrel 130 in an upward force toward the top of the mandrel 130. These forces remove the pipette tip 110 from the mandrel 130.
[0088] The filter 192 is configured to provide a barrier between the mandrel 130 and fluid drawn from a sample using the pipette tip 110. The filter 192 is configured to allow air to flow through the filter while preventing liquids such as samples from being drawn into the pipette tip 110.
[0089] FIG. 16B is a cross-sectional view of the mandrel 130 inserted into the pipette tip 110 of FIG. 16A, with the plunger 190 engaged with the filter 192. In this figure, the plunger 190 engages the filter 192 and removes the pipette tip 110 from the mandrel 130.
[0090] FIG. 17 illustrates an exemplary architecture of a computing device that may be used to implement aspects of the present disclosure, including any of a plurality of computing devices 230, a controller 106, and the like. The computing device illustrated in FIG. 17 may be used to execute an operating system, application programs, software modules (including software engines and including the tip removal program 108) described herein.
[0091] In some embodiments, the computing device 230 includes at least one processing device 232, such as a central processing unit (CPU). Various processing devices are available from various manufacturers, such as Intel or Advanced Micro Devices. In this example, the computing device 230 also includes a system memory 234 and a system bus 236 that couples various system components including the system memory 234 to the processing device 232. The system bus 236 is one of any number of types of bus structures, including a memory bus or memory controller, a peripheral bus, and a local bus using any of a variety of bus architectures.
[0092] Examples of computing devices suitable for the computing device 230 include server computers, desktop computers, laptop computers, tablet computers, mobile computing devices (such as smartphones, iPod (registered trademark) or iPad (registered trademark) mobile digital devices, or other mobile devices), or other devices configured to process digital instructions.
[0093] The system memory 234 includes a read-only memory 238 and a random access memory 240. The basic input / output system 242, which contains basic routines that act to transfer information within the computing device 230, such as at startup, is typically stored in the read-only memory 238.
[0094] In some embodiments, computing device 230 also includes a secondary storage device 244, such as a hard disk drive, for storing digital data. The secondary storage device 244 is connected to the system bus 236 by a secondary storage interface 246. The secondary storage device 244 and their associated computer-readable media provide a non-volatile storage for computer-readable instructions (including application programs and program modules), data structures, and other data for the computing device 230.
[0095] The exemplary environment described herein employs a hard disk drive as the secondary storage device, but other types of computer-readable storage media may also be used in other embodiments. Examples of these other types of computer-readable storage media include magnetic cassettes, flash memory cards, digital video disks, Bernoulli cartridges, compact disk read-only memory, digital versatile disk read-only memory, random access memory, or read-only memory. Some embodiments include non-transitory media. Additionally, such computer-readable storage media can include local storage devices or cloud-based storage devices.
[0096] Some program modules can be stored in the secondary storage device 244 or the memory 234, including an operating system 248, one or more application programs 250, other program modules 252 (such as software engines described herein), and program data 254. The computing device 230 can utilize any suitable operating system, such as MICROSOFT Windows (registered trademark), Google Chrome TM , Apple OS, and any other suitable operating system for computing devices.
[0097] In some embodiments, a user provides input to computing device 230 through one or more input devices 256. Examples of input devices 256 include keyboard 258, mouse 260, microphone 262, and touch sensor 264 (such as a touch pad or a touch sensor display). Other embodiments include other input devices 256. Input devices are often connected to processing device 232 through an input / output interface 266 that is coupled to system bus 236. These input devices 256 can be connected by any number of input / output interfaces such as parallel ports, serial ports, game ports, or universal serial buses. Wireless communication between the input device and interface 266 is also conceivable, and in some contemplated embodiments, includes infrared, BLUETOOTH® wireless technology, 802.11a / b / g / n, cellular, or other radio frequency communication systems.
[0098] In this exemplary embodiment, a display device 268 such as a monitor, a liquid crystal display device, a projector, or a touch sensor display device is also connected to system bus 236 through an interface such as video adapter 270. In addition to display device 268, computing device 230 can include various other peripheral devices (not shown) such as speakers or printers.
[0099] When used in a local area networking environment or a wide area networking environment (such as the Internet), computing device 230 is typically connected to the network through a network interface 272 such as an Ethernet® interface. Other contemplated embodiments use other communication devices. For example, some embodiments of computing device 230 include a modem for communicating across a network.
[0100] Computing device 230 typically includes at least some form of computer-readable medium. Computer-readable medium includes any available medium that can be accessed by computing device 230. By way of example, computer-readable medium includes computer-readable storage medium and computer-readable communication medium.
[0101] Computer-readable storage medium includes volatile and nonvolatile removable and nonremovable media implemented in any device configured to store information such as computer-readable instructions, data structures, program modules, or other data. Computer-readable storage medium includes, but is not limited to, random access memory, read-only memory, electrically erasable programmable read-only memory, flash memory or other memory technology, compact disc read-only memory, digital versatile disk or other optical storage device, magnetic cassette, magnetic tape, magnetic disk storage device or other magnetic storage device, or any other medium that can be used to store the desired information and can be accessed by computing device 230. Computer-readable storage medium does not include computer-readable communication medium.
[0102] Computer-readable communication medium typically embodies computer-readable instructions, data structures, program modules, or other data in a modulated data signal such as a carrier wave or other transmission mechanism and includes any information delivery medium. The term "modulated data signal" refers to a signal that has one or more of its characteristics set or changed in such a manner as to encode information in the signal. By way of example, computer-readable communication medium includes wired media such as a wired network or direct wired connection, and wireless media such as acoustic, radio frequency, infrared, and other wireless media. Any combination of the above is also included within the scope of computer-readable medium.
[0103] The computing device illustrated in FIG. 17 is also an example of a programmable electronic device, which may include one or more such computing devices, and when multiple computing devices are included, such computing devices can be collectively coupled with a suitable data communication network to implement the various functions, methods, or operations disclosed herein.
[0104] FIG. 18 shows a flowchart depicting the loading of a desired pipette tip 134 according to an exemplary embodiment of the pipette operating instrument of FIG. 1. This figure includes a first step 280 of engaging the pipette tip 110 with the mandrel 130, a second step 282 of partially removing the pipette tip 110 from the pipette tip box 104 by lifting the pipette tip 110 together with the mandrel 130, a third step 284 of moving the pipette tip 110 and the mandrel 130 using a coordinated movement 136 to remove an undesired pipette tip 132, and a fourth step 286 of using the mandrel 130 to completely remove the desired pipette tip 134 from the pipette tip box 104. Examples of each of the first step, the second step, the third step, and the fourth step are illustrated and described in further detail with reference to FIGS. 19, 20, 21, and 22, respectively.
[0105] FIG. 19A shows a cross-sectional view of a pipetting instrument 100 including a mandrel 130, a pipette tip box 104, and a pipette tip 110, depicting the first step 280 of FIG. 18, where the mandrel 130 approaches and enters the pipette tip 110 within the pipette tip box 104. In some embodiments, the mandrel 130 may approach and enter only a partial subset of the pipette tips 110, where the targeted partial subset is the desired pipette tip 134 and any non-targeted subset is the undesired pipette tip 132. In some embodiments, the desired pipette tip 134 may include pipette tips 110 in a patterned arrangement, such as every other pipette tip 110. This would mean that every other pipette tip 110 is the desired pipette tip 134 and the remaining pipette tips 110 are the undesired pipette tips 132. As shown in the figure, the outer pipette tips are the desired pipette tips 134 targeted by the mandrel 130, and the inner pipette tips are the undesired pipette tips 132 not targeted by the mandrel 130. In some embodiments, the mandrel may approach and enter the desired pipette tip 134 by moving the pod 150 along the Z-axis 184. Examples illustrating the movement of the pod 150 along the Z-axis 184 are shown and described in more detail with reference to FIGS. 5, 6, and 9.
[0106] Figure 19B shows a cross-sectional view of the pipetting instrument 100 including the mandrel 130, the pipette tip box 104, and the pipette tip 110, depicting the first step 280 of FIG. 18. The mandrel 130 is coupled to the pipette tip 110 within the pipette tip box 104. In this figure, in some embodiments, the mandrel 130 targets the outer pipette tip 110. Thus, the outer pipette tip 110 is the desired pipette tip 134, and the inner pipette tip 110 is the undesired pipette tip 132. The mandrel 130 is coupled to the desired pipette tip 134 by pressing the mandrel 130 into the desired pipette tip 134 to create an airtight interference fit. An example illustrating the airtight interference fit between the mandrel 130 and the desired pipette tip 134 is shown and described in more detail with reference to FIG. 2.
[0107] Figure 20A shows a cross-sectional view of the mandrel 130, the pipette tip box 104, and the pipette tip 110, depicting the second step 282 of FIG. 18. The mandrel 130 is coupled to the pipette tip 110 within the pipette tip box 104. The step of coupling the mandrel 130 to the pipette tip 110 within the pipette tip box 104 using an airtight friction fit between the mandrel 130 and the desired pipette tip 134 is shown and described in more detail in FIGS. 2, 10, and 13B. In this figure, in some embodiments, the desired pipette tip 134 is the outer pipette tip 110, and the undesired pipette tip 132 is illustrated by the inner pipette tip 110.
[0108] Figure 20B shows a cross-sectional view of the mandrel 130, the pipette tip box 104, and the pipette tip 110, depicting the second step 282 of FIG. 18. The mandrel 130 partially removes the pipette tip 110 from the pipette tip box 104.
[0109] In this figure, in some embodiments, the desired pipette tip 134 is the outer pipette tip 110, and the undesired pipette tip 132 is illustrated by the inner pipette tip 110. In some embodiments, the mandrel 130 can accidentally remove the undesired pipette tip 132 from the pipette tip box 104 as the undesired pipette tip 132 attaches to the mandrel 130, the desired pipette tip 134, or both. In some embodiments, the undesired pipette tip can attach to the mandrel 130, the desired pipette tip 134, or both by mechanical or electrostatic coupling. To remove the undesired pipette tip 132 from the mandrel 130, the mandrel 130 lifts the pipette tip 110 out of the pipette tip box 104 while keeping the pipette tip 110 partially inserted into the pipette tip box 104 prior to performing a coordinated movement 136 to remove any undesired pipette tip 132 from the mandrel 130 and / or the desired pipette tip 134. Examples illustrating the coordinated movement 136 of the mandrel 130 are shown and described in further detail with reference to FIGS. 21 and 27.
[0110] FIG. 21 shows a schematic view depicting a coordinated movement 136 that the mandrel 130 performs to remove any undesired pipette tip 132 from the mandrel 130 or the desired pipette tip 134.
[0111] Coordinated movement 136 includes moving each of the mandrels in a similar motion and removing any undesired pipette tip 132 from the desired pipette tip 134 or the mandrel 130. In some embodiments, the coordinated movement 136 can include moving the mandrel 130 within the pipette tip box 104 in a motion having horizontal and / or vertical components and pressing the pipette tip 110 against the pipette tip box 104. The interference between the undesired pipette tip 132 and the pipette tip box 104 can provide sufficient force to decouple the undesired pipette tip 132 from the desired pipette tip 134 and / or the mandrel 130. It should be understood that the coordinated movement 136 can include any number of movements, including horizontal and vertical components, within the pipette tip box 104 to press the pipette tip 110 against the pipette tip box 104. In some embodiments, the coordinated movement 136 can start from the center of each concave surface within the pipette tip box 104 for storing the pipette tip 110 where the pipette tip 110 is partially inserted into the pipette tip box 104. The mandrel can then move the pipette tip diagonally to one corner of the concave surface within the pipette tip box 104 before moving the pipette tip 110 to each of the other corners of the concave surface within the pipette tip box 104. The mandrel 130 can then return the pipette tip 110 to the center of the concave surface within the pipette tip box 104, enabling the undesired pipette tip to be removed into the pipette tip box 104. In some embodiments, the concave surface within the pipette tip box 104 for receiving the pipette tip 110 can define a cylindrical space. In some embodiments, the coordinated movement 136 can be adjusted to conform to any type of concave surface within the pipette tip box 104 by pressing the pipette tip 110 against the pipette tip box 104. In some embodiments, the coordinated movement 136 can include radial movement having horizontal and vertical components. In some embodiments, the coordinated movement can include only movement in the horizontal direction.In some embodiments, the coordinated movement may include only movement in the vertical direction.
[0112] FIG. 22 shows a cross-sectional view of the mandrel 130, the pipette tip box 104, and the pipette tip 110 depicting the fourth step 286 of FIG. 18 when the desired pipette tip 134 is fully removed from the pipette tip box 104 and any undesired pipette tip 132 is decoupled from the mandrel 130 and is coupled to the mandrel 130. As can be seen from this figure, the desired pipette tip 134 remains coupled to the mandrel 130, while the undesired pipette tip 132 has been removed from the mandrel 130 and returned to the pipette tip box 104.
[0113] FIG. 23 shows a flowchart depicting the loading and unloading of pipette tips from the mandrel into the pipette tip box according to an exemplary embodiment of the pipette operating instrument of FIG. 1.
[0114] This figure includes a first step 302 for positioning the mandrel 130 and engaging and inserting it into the pipette tip 110 within the pipette tip box 104, a second step 304 for activating the plunger set to decouple the pipette tip 110 from the mandrel 130 and load the pipette tip 110 into the pipette tip box 104, a third step 306 for positioning the mandrel 130 such that any pipette tip 110 that remains coupled to the mandrel 130 is partially inserted into the pipette tip box 104, a fourth step 308 for moving the mandrel 130 and the pipette tip 110 to decouple the pipette tip 110 from the mandrel 130 and load the pipette tip 110 into the pipette tip box 104, and a fifth step 310 for removing the mandrel 130 from the pipette tip box 104. Examples of each of the first step, the second step, the third step, the fourth step, and the fifth step are illustrated and described in further detail with reference to FIGS. 24, 25, 26, 27, and 28, respectively.
[0115] Figure 24 shows a cross-sectional view of the mandrel 130, the pipette tip box 104, and the pipette tip 110 depicting the first step 302 of FIG. 23, and the mandrel 130 is positioned to engage and insert into the pipette tip 110 within the pipette tip box 104. In this figure, the mandrel 130 is at least partially inserted into the pipette tip 110. An example for engaging and inserting the mandrel 130 into the pipette tip 110 is illustrated and described in more detail with reference to FIG. 19.
[0116] Figure 25 shows a cross-sectional view of the mandrel 130, the pipette tip box 104, and the pipette tip 110 depicting the second step 304 of FIG. 23, and the plunger is activated along the plunger path 312 on the mandrel 130 to disengage the pipette tip 110 from the mandrel 130 and deposit the pipette tip 110 into the pipette tip box 104.
[0117] The plunger path 312 defines a path for the plunger within each of the mandrels 130 and deposits the desired pipette tip 134 into the pipette tip box 104. The plunger is configured to apply a downward force along the plunger path 312 towards the bottom of the mandrel 130 to remove the desired pipette tip 134. The desired pipette tip 134 is partially inserted into the pipette tip box 104 and guides the desired pipette tip 134 into the pipette tip box 104. In some embodiments, the undesired pipette tip 132 can be mechanically or electrically coupled to the mandrel 130, the desired pipette tip 134, or both. In some embodiments, the desired pipette tip 134 may be defined by a pattern of every other pipette tip 110. In this figure, both pipette tips 110 are the desired pipette tips 134. In some embodiments, the undesired pipette tip 132 can be mechanically or electrostatically coupled to the mandrel 130, the desired pipette tip 134, or both between the desired pipette tips 134. In some embodiments, if the plunger fails to decouple the desired pipette tip 134 from the mandrel 130, the plunger may be reactivated, if necessary, to decouple the desired pipette tip 134 from the mandrel 130 along the plunger path 312.
[0118] Figure 26 shows a cross-sectional view of the mandrel 130, the pipette tip box 104, and the pipette tips 110 depicting the third step 306 of FIG. 23, with any pipette tip 110 that remains coupled to the mandrel 130 positioned such that it is partially inserted into the pipette tip box 104. In this figure, the desired pipette tip 134 has been removed from the mandrel 130 in the second step 304, and only a single undesired pipette tip 132 remains coupled to the mandrel.
[0119] FIG. 27 shows a schematic view depicting a coordinated movement 136 of the mandrel 130 to remove any undesired pipette tip 132 from the mandrel 130, depicting the fourth step 308 of FIG. 23. An example illustrating the coordinated movement 136 of the mandrel 130 is illustrated and described in more detail with reference to FIG. 21.
[0120] FIG. 28 shows a cross-sectional view of the mandrel 130, the pipette tip box 104, and the pipette tip 110, depicting the fifth step 310 of FIG. 23. The mandrel 130 is removed from the pipette tip box 104, and the pipette tips 110 are respectively stacked in the pipette tip box 104.
[0121] FIG. 29 shows a front view of the upper part of the pipette tip 110 having pipette tip features 320 that can affect the process of loading or stacking desired pipette tips. In some embodiments, the pipette tip features 320 can contribute to the loading of the undesired pipette tip 132 onto the mandrel 130 or the desired pipette tip 134. In this figure, the left pipette tip 110 includes filaments that can be coupled to an adjacent pipette tip 110 stored within the pipette tip box 104. In this figure, the right pipette tip 110 includes a protrusion that is not in the same plane as the cylindrical head of the pipette tip 110. The protrusion from the pipette tip 110 can be coupled to an adjacent pipette tip 110 stored within the pipette tip box 104. It is contemplated that many types of pipette tip features on the pipette tip 110 can engage an adjacent pipette tip 110 and affect the process of loading or stacking the desired pipette tip, and the above examples are not limitations of these pipette tip features 320.
[0122] The foregoing description is illustrative, not restrictive. Many variations of the present invention will be apparent to those skilled in the art in light of the above disclosure. The scope of the present invention should therefore be determined not with reference to the above description, but instead with reference to the appended claims in their full scope or equivalents.
[0123] One or more features from any embodiment may be combined with one or more features of any other embodiment without departing from the scope of the invention.
Claims
1. A pipette operating device for loading and dispensing samples, wherein the pipette operating device is An automated liquid pipette comprising a deck for supporting a pipette tip box having pipette tips, and a mandrel for engaging with the pipette tips and for removing at least some of the pipette tips from the pipette tip box, A controller configured to control the automated liquid pipette, the controller further configured to perform a pipette tip removal operation using the mandrel to remove any undesirable pipette tip removed from the pipette tip box, and A pipette operating device equipped with the following features.
2. The pipette manipulator according to claim 1, wherein the mandrel is configured to engage with a pipette tip of varying size.
3. The pipette operating device according to any one of claims 1 to 2, wherein the pipette tip has a spacing of less than 0.30 millimeters between adjacent pipette tips in the pipette tip box.
4. An automated liquid pipette according to any one of claims 1 to 2, further comprising a motor-driven positioning system configured to position the mandrel.
5. The pipette operating device according to claim 4, wherein the motor-driven positioning system comprises at least one motor and is configured to move the mandrel in three dimensions.
6. The motor-driven positioning system according to claim 5, wherein at least one motor is mechanically coupled to drive the mandrel horizontally around its axis.
7. The motorized positioning system according to claim 5, wherein the mandrel is movable along the X-axis and Y-axis by a motorized platform, the mandrel is coupled to the motorized platform, the mandrel is configured to move along the Z-axis by adjusting the height of the pod, and the pod is positioned between the motorized platform and the mandrel.
8. An automated liquid pipette according to any one of claims 1 to 2, further comprising a sensor configured to sense the undesired pipette tip coupled to the mandrel or the desired pipette tip.
9. A method for loading a set of pipette tips onto an automated liquid pipette, the method being: The mandrel is positioned, and the pipette tip is engaged with the mandrel to connect the desired pipette tip to the mandrel. Lift the mandrel, partially remove the desired pipette tip from the pipette tip box, and lift at least one non-desired pipette tip together with the desired pipette tip. Moving the mandrel, removing the at least one unwanted pipette tip from the mandrel, and returning the at least one unwanted pipette tip to the pipette tip box while the desired set of pipette tips remains attached to the mandrel, Lift the mandrel and completely remove the desired pipette tip from the pipette tip box. Methods that include...
10. The method according to claim 9, wherein the mandrel is coupled to the desired pipette tip using friction fitting.
11. The method according to any one of claims 9 to 10, wherein the non-desired pipette tip is coupled to the desired pipette tip and is not coupled to the mandrel.
12. The method according to any one of claims 9 to 10, wherein the mandrel is moved in a motion having a horizontal component, causing the pipette tip to press against the pipette tip box.
13. The method according to any one of claims 9 to 10, wherein the mandrel is moved in motion having a vertical component.
14. The method according to any one of claims 9 to 10, wherein the mandrel is moved in motion having horizontal and vertical components.
15. The method according to any one of claims 9 to 10, wherein the mandrel is moved in a radial motion having horizontal and vertical components.
16. The method according to any one of claims 9 to 10, wherein moving the mandrel and removing the at least one undesired pipette tip from the mandrel may be repeated when any undesired pipette tip remains attached to a desired pipette tip or the mandrel.
17. The method according to any one of claims 9 to 10, further comprising using a sensor to sense whether any undesired pipette tip is coupled to the mandrel or any desired pipette tip, and identifying a set of mandrels and pipette tips to be moved that are coupled to the undesired pipette tip.
18. A method for unloading one or more pipette tips from an automated liquid pipette, wherein the method is: Position the mandrel, engage it with the tip of the pipette, and insert the tip of the pipette into the pipette tip box, Activating the plunger set, detaching one or more pipette tips from the mandrel, and stacking the pipette tips into the pipette tip box, Position the mandrel and partially insert any pipette tip that remains attached to the mandrel into the pipette tip box. The mandrel and the pipette tip are moved, the pipette tip is detached from the mandrel, and the pipette tip is lowered into the pipette tip box. Removing the mandrel from the pipette tip box Methods that include...
19. The method according to claim 18, wherein positioning the mandrel, engaging it with the pipette tip, and inserting the pipette tip into the pipette tip box further includes fully inserting the pipette tip into the pipette tip box.
20. The method according to any one of claims 18 to 19, wherein moving the mandrel and the pipette tip and disengaging the pipette tip from the mandrel further includes moving the mandrel within the pipette tip box and pressing the pipette tip against the pipette tip box in a motion having a horizontal component.
21. The method according to any one of claims 18 to 19, wherein moving the mandrel and the pipette tip and disengaging the pipette tip from the mandrel further includes moving the mandrel within the pipette tip box and pressing the pipette tip against the pipette tip box in a motion having a vertical component.
22. The method according to any one of claims 18 to 19, wherein moving the mandrel and the pipette tip and disengaging the pipette tip from the mandrel further includes moving the mandrel within the pipette tip box and pressing the pipette tip against the pipette tip box in a motion having horizontal and vertical components.
23. The method according to any one of claims 18 to 19, wherein moving the mandrel and the pipette tip and disengaging the pipette tip from the mandrel further includes moving the mandrel within the pipette tip box in a radial motion having horizontal and vertical components and pressing the pipette tip against the pipette tip box.
24. The method according to any one of claims 18 to 19, further comprising using a sensor to sense whether a non-desired pipette tip is coupled to the mandrel or a desired pipette tip, and identifying a set of mandrels and pipette tips to be moved that are coupled to the non-desired pipette tip.